1 15 49 https://www.nal.usda.gov/exhibits/speccoll/files/original/d09e5018355eaded4005465213b014b7.pdf 3a158e8474d3ca4eea02973127471bbd PDF Text Text Item D Number °2287 Author Schecter, Arnold Corporate Author ROpOrt/ArtlGlO TltlB Typescript: Transient Liver Pathology in Patients Consuming Water from a Private Well Contaminated by PCBs from a Submersible Water Pump, [nd] Journal/Book Title Year Month/Day Color D Number of Images 6 DOSCrlPtOll NOtBS Typescript of article published in Chemosphere, 1987, vol. 16, no.1,pp.37-42. Thursday, September 20, 2001 Page 2287 of 2293 �TRANSIENT LIVER PATHOLOGY IN PATIENTS CONSUMING WATER FROM A PRIVATE WELL CONTAMINATED BY PC3s FROM A SUBMERSIBLE WATER PUMP Arnold Schecter Department of Preventive Medicine Upstate Medical Canter Clinical Campus State University of New York Binghamton, New York 13901 ABSTRACT Submersible water pumps in private water wells have in some instances been found to contain PCBs in their oil. When these pumps leak they may release PCSs into the drinking water constituting a potential health hazard. IHTROOUCTIOH Since 1982, in New York State, and in Wisconsin, a number of private water wells, usually in rural areas, have been found to be contaminated with PCBs. The source of this contamination is thought to be submersible water pumps from several manufacturers where PCBs were apparently, found in the oil of the pumps or in their capacitors. Although the manufacturers deny Intentionally putting PCBs in these pumps, the presence of PCSs has been documented by State and County Health Departments from 1982 through 1985 in Broome County and adjacent areas in Upstate New York as well as in Wisconsin. PCB levels in drinking water from these wells has been found to be as high as 57 times greater than State PCB drinking water standards at this time. Whether significant health consequences occur depends on the Ingested dose of specific PCS isomers with their usually coexisting chlorinated dibenzofurans and less frequently coexisting chlorinated dibenzo-p-dioxins. A medical case study with transiently elevated liver enzymes found in three members of a family after ingestion of PCBs 1n their drinking water is presented. FINDINGS A family of three came to the Upstate Medical Center affiliated Faculty Practice Occupational Medicine Clinic in Binghamton, New York, located at Binghamton General �Hospital, with.complaints of feeling sick from documented ingestion of PCBs in their drinking water for at least one week, with accompanying subjective, primarily central nervous system, symptoms of discomfort, a feeling of generalized illness and "dizziness". The family members had noted a chemical odor and a film on the water at times. A Health Department investigation had determined that the source of PCBs and a chemical taste in their water was a submersible water pump of a type shown in Figures 1 and 2, which had been leaking. The pump in question, a Barnes pump from the Barnes Manufacturing Co. of Mansfield, Ohio and Oakland, California, had detectable PCBs when tested by the State Health Depart{12} ment.v ' ' Upon review of Health Department records, it was found that Peabody Barnes Pumps were found to have PCSs which leaked in nine instances between 1982 and 1985. ' ' Some pumps were found to have 2.5% PCBs in their oil, when tested by the State Health Department. In the pump owned by the patients in this case study, there was a finding of 6.6 parts per billion of PCBs in the drinking water. The leaking pump oil was found to have 630,000 parts per billion of PCBs. Analysis for polychlorinated dibenzofurans which so frequently accompany PCBs was not performed. Patients with PCS contaminated water noted bad odors, peculiar taste, a petroleum-like taste, and a disorientation or "spaced out" feeling after drinking the water. Serum PCB levels in the three patients followed by us, a mother, father and 12 year old son, seen one month after the consumption of water contaminated with PCBs were quite low, below 2 ppb; whereas serum PCB values for adults from this part of Upstate New York are usually about 5-10 ppb. The family's diet was somewhat unusual in that they usually ate "natural" foods, usually vegetables, and also Ingested high levels of vitamins. Abnormal (elevated) liver enzymes were found in blood tests performed on all three members of this family who ingested the PCS contaminated water for an estimated one weak. These abnormal values, indicative of liver damage, returned to normal levels within one month after the initial values were documented, or two months after ingestion of water contaminated with PCBs, suggesting that the acute injury was a transient one. No clinical or laboratory evidence of hepatitis or drug induced liver damage was found. The patients recovered from their acute medical problems but are being followed for possible delayed onset pathology. New York State "Safe Drinking Water Guidelines" for PCBs is one part per billion.^ Water from wells contaminated by oil from these pumps, schematically diagramed in Figures 2, 3, and 4, have shown between .26 and 57 parts per billion, according to State records. ' Tests of the oil from the contaminated pumps have shown 630,000 to 24,000,000 parts per billion of PCBs. Tests of the lubricating oil fn these pumps have shown that levels of PCBs have been found in pumps more than 20 years old and as new as a 1982 model. To date the brands of pumps Involved have been Barnes or Peabody Barnes, Reda and Myers, (2^ ' According to the Water Systems Council, Inc,, SOS of private well pumps are above ground units and the remaining 50% are submersible units. Half are oil cooled and half are water cooled. Census figures for 1982 describe 12,000,000 homes connected to private wells in the U.S.A.^ By way of comparison, the U.S. Food and Drug Administration sets a 2 parts per million PCB tolerance level for fish consumption. The P.O.A. recommends eating fish at this level �Check valve Radial bearing Impellers Pump Intake Seal Electric motor Pressure equalizing tube I Thrust and radial bearing Fluid chamber Fig. 2 - This schematic diagrams the internal components of a submersible water pump. Fig. 1 - A Health Department technician is shown holding a PCB contaminated submersible water pump. �\ 150'OF DISCHARGE PIPE WITH 2 - 90° ELBOWS PUMP Fig. 3 - A typical arrangement of a submersible water pump, well, and pipe fixtures leading to a hone Is shown here. �no more than once per week. ' A half pound or eight ounce serving of fish contaminated at this limit would contain 500 nricrograms of PCBs. win. SEAl SlfjDC* V A L V E ' • AI» INTAKE VAIVE !/•;.% :.:•• if NO CHAIN is AVAIIA»U MQTO» \-J Fig. 4 - This schematic depiction details the apparatus immediately related to the pump and well. Also, for comparison, if two liters of water at the New York state Drinking Water PCS Guidelines are consumed for 70 years with a one part per billion PCS level this has been calculated to lead to one additional cancer death per 10,000 persons according to State (a) Health Department calculations. ' Additional concern has been raised by an EPA study performed under contract by Versar, Inc., of Springfield, VA, in 1980 which estimated that 1,100,000 wells may have PC8 capacitors in the well motors. ' This is different from the current findings of PCBs in the oil of the motors or pumps themselves, rather than the capacitors. �SUMMARY AND RECOMMENDATIONS Submersible water pumps in private wells are widespread, especially in rural areas, and may constitute a potential health hazard, especially if they contain PCSs with the usually concomitant chlorinated dlbenzofurans and occasional chlorinated dibenzo-p-diox1ns. These leaking pumps have been demonstrated to contaminate drinking water above levels considered safe for human consumption, PCBs apparently were used in these pumps from at least three known manufacturers at least in the United States without the admitted knowledge of the l&\ presence of PCSs, except in the capacitors, by any party/ ' The extent of these contaminated pumps remain to be documented. To date the only incidents known to us are the nine pumps 1n and around the Broome County, New York area, where the public and health department are especially sensitive to the possible presence of PCBs since the PCS, dloxtn and furan contaminated State Office Building incident of February 1981, ' and In Wisconsin where the Wisconsin Department of Natural Resources (WONR) has also detected PCB contamination in private well water with submersible water pumps as the probable source. It is unclear as to whether only the capacitors contain PCBs or whether the pump oil Itself, usually pharmaceutical grade mineral oil, also contains PCBs. News releases to the public and a notice to well drillers and installers have been issued 1n Wisconsin by the WONR. Further sampling of lubricating oil from additional pumps and water from more wells 1s planned 1n Wisconsin. However, the nationwide distribution of these pumps suggests that other Instances will be documented when the possibility of PCB contamination exists in similar submersible water pumps.elsewhere in the world. Because of the large number of such pumps In the United States and worldwide, it is possible that these may constitute a potential human health hazard. Further chemical testing of suspect pumps and water 1s Indicated and appropriate medical evaluation of patients exposed to PCS contamination is Indicated, including routine blood screening tests as well as blood PCB levels, serially'obtained wherever the possibility of a transient elevation above the patient's baseline exists. REFERENCES 1. 2. 3. 4. 5. 6. 7. Personal communication, Broome County Health Department. Personal communication, Environmental Health Division, New York State Health Department. Mew York State Safe Drinking Water Guidelines, 1984. The Sunday Press, Odato, J.M., July 7, 1985; The Evening Press. OdatO, J.M., July 8, 1985; Press & Sun-Bulletin, Odato, J.M., December 8 & 11, 1985. U.S. Food and Drug Administration Guidelines for Consumption of PCB Contaminated F1sh, 1982. Woodcock, 8. and Powers, P., (Versar, Inc.), PCB Contamination of Well Water: An Engineering Risk assessment, U.S. EPA Document EPA-570/9-SQ-OQ1, January 1982. Schecter, A., Contamination of an Office Building in Blnghamton, New York by PCSs, 01ox1ns, Furans and Biphenylenes after an Electrical Panel and Electrical Transformer Incident, Chemosphere, 12, (4/5), 669-680, Pergamon Press Ltd., London, 1983. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 090 Folder The folder containing the original item. 2287 Series The series number of the original item. Series IV Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Schecter, Arnold Title A name given to the resource Typescript: Transient Liver Pathology in Patients Consuming Water from a Private Well Contaminated by PCBs from a Submersible Water Pump, [nd] Subject The topic of the resource BSOB health studies PCBs water pollution Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 087 Folder The folder containing the original item. 2172 Series The series number of the original item. Series IV Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Date A point or period of time associated with an event in the lifecycle of the resource 1981 Title A name given to the resource Typescript: Summary Statement April 3 Expert Panel Meeting Subject The topic of the resource BSOB building remediation decontamination PCBs https://www.nal.usda.gov/exhibits/speccoll/files/original/e17f3d68c83f49d1cc7bd56951e8f6a8.pdf ce9d5c7d32c1b5eeab80de909dfcce4f PDF Text Text Rom D Number 0227 ° Author Versar New York, Inc., Springfield, Virginia RODOrt/ArtlGlO Title Typescript: Summary Report: Measurement of Residual Contaminants in the Air and on Surfaces in Floors 2 Through 18 of the Binghamton State Office Building Following Completion of the Preliminary Cleanup and Measurement of the Effect of Normal HVAC Operations of the Concentration of Contaminants in the Air Within and Adjacent to the Binghamton State Office Building, August 12, 1985 Journal/Book Title Year Month/Day Color Number of Images D 17 Descriptor! Notes Thursday, September 20, 2001 Page 2270 of 2293 �SUMMARY REPORT: I MEASUREMENT OF RESIDUAL CONTAMINANTS IN THE AIR AND ON SURFACES IN FLOORS 2 THROUGH 18 OF THE BINGHAMTON STATE OFFICE BUILDING FOLLOWING COMPLETION OF THE PRELIMINARY CLEANUP AND MEASUREMENT OF THE EFFECT OF NORMAL HVAC OPERATIONS OF THE CONCENTRATION OF CONTAMINANTS IN THE AIR WITHIN AND ADJACENT TO THE BINGHAMTON STATE OFFICE BUILDING Prepared for: Office of General Services State of Nev York Albany, Nev York 12242 Prepared by: Veraar Nev York Inc. 6850 Veraar Center Springfield, Virginia 221S1 August 12, 1985 �1.0 INTRODUCTION On February 5, 1981, an intense electrical fire in the basement of the Bingharaton State Office Building (BSOB) caused coolant liquid to leak from a transformer into the fire. This coolant liquid consisted of a mixture of polychlorinated biphenyls (PCBs) and chlorinated benzenes. The heat of the fire vaporized the liquid and spread black soot throughout the basement and all 18 floors of the building. Tests of this soot performed shortly after the fire found that it contained several percent PCBs by weight and various polychlorinated dibenzofurans (PCOFs) at a concentration of up to several parts per million. The analysis of the soot also identified low levels of polychlorinated; dibenzo-p-dioxins (PCDDs) and polychlorinated biphenylenea (PCBPs). These chemicals vere apparently created by the pyrolysis of the PCBs and chlorinated benzenes in the transformer liquid. The Nev York State Department of Health determined that the acute toxicity of the soot in guinea pigs vas equivalent to a material containing 58 parts per million 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (2,3,7, 8-TCDD>. The initial cleanup of the BSOB vas halted in late February 1981 vhen it vas learned that TCDDs were present in the work environment. The cleaning was resumed in September 1981 after the necessary procedures and facilities were completed to assure adequate protection of the cleanup workers and the surrounding community during the subsequent extensive decontamination activities. Among the precautions taken was the sealing of existing ventilation openings and installation of an air pollution control system on the roof of the building to clean all air that was exhausted from the building through high efficiency particulate filters and activated carbon. The BSOB consists of three essentially separate ventilation zones (see Figure 1). In September 1984, following completion of the cleaning of all areas above the basement, the stairwells, elevator shafts, ventilating chases, and other openings between floors 1 and 2 were sealed and the roof mounted exhaust fans on the air pollution control equipment were connected to a metal tube that drew air from the basement mechanical room. After these changes were made, entry to the upper portion of the building was possible only through the plaza level entrance on floor 2, and subsequent cleaning has been concentrated on the basement and subbasement. A major test plan, 'Measurement of Residual Contaminants in the Air and on Surfaces in Floors 2 through 18....* dated September 5, 1984, was approved by the State of Hew York C2J. This revision incorporated suggestions made by the Expert Advisory Panel on the BSOB following reviews of previous drafts. Three separate tests were defined with a number of purposes: �PENTHOUSE w N O 14th FLOOR MEC.HANICAL ROOM > N X UJ m Z 3 O O N" 6th FLOOR MECHANICAL ROOM §1 2nd FLOOR - LOBBY PLAZA LEVEL ENTRANCE lit FLOOR - LOBBY, CAFETERIA RAMP STREET LEVEL ENTRANCE BASEMENT - TRANSFORMER ROOM ENTRY TRAILER COUNTY PARKING GARAGE SUB-BASEMENT - STORAGE FIGURE 1. BINGHAMTON STATE OFFICE BUILDING �First Test 1. Determine the normal ambient levels of PCBs, PCDFs, and PCDDs in the air in Binghamton around the BSOB. 2. Determine whether the air in the portion of the building above floor 1 vaa clean enough that a person could safely vork in the upper portion of the building without wearing an air purifying respirator, assuming that protective clothing continued to be worn to prevent skin contact with any remaining surface contaminants. 3. Collect wipe samples from various surfaces within floors 2 through Id for PCB analysis to identify those surfaces which had the highest remaining levels of residual contaminants. I I I Samples were collected from September 14 to September 17, 1984, and the results of the analysis of the samples were summarized in the Versar test report 'Summary of Results of the First Test...* dated January 25, 1985 C71. Second Test It had previously been the consensus of the Expert Advisory Panel that the release of untreated air from the BSOB would not be advisable until such a time that tests demonstrated that breathing the air would not result in a significant risk to a worker in the building. Air dispersion modeling indicated that air released from the building due to normal operations of the HVAC units on floors 6 and 14 would be significantly diluted, and that any potential exposure of people outside the building to contaminants would not be significant. The second test specified measurements of the levels of contaminants in the air around the building at the time normal HVAC operations were resumed as a check on the validity of these calculations. Third Test 1. Teat the quality of the air in the building after several weeks of normal operation of the HVAC system. 2.' Measure the levels of PCDDs and PCDFs on those surfaces in floors 2 through 18 found to have the highest remaining levels of PCBs as necessary to assess the cleanliness of the surfaces in terms of overall toxic exposure potential. The purpose of this summary report is to present the results of the tests in a systematic way to facilitate a decision as to the present cleanliness of floors 2 to 18 of the BSQB, �2.0 AIR QUALITY AROUND THE BINGHAMTON STATE OFFICE BUILDING Air samples vere collected on the roofs of the City Building, County Building, and YMCA adjacent to the BSOB before normal (untreated exhaust) ventilation was resumed using the HVAC units on floors 6 and 14 and at the time normal HVAC operations vere started. The PCDD/PCDF air samples vere collected using the high volume sampler developed by the Nev York State Department of Health which uses silica gel as an adsorbent for these contaminants, and which collects a sample of approximately 75 cubic meters. PCB samples vere collected at the same times and locations using a modified high volume air sampler that used urethane foam as the adsorbant material and collects a sample of approximately 500 cubic meters of air. The First Test air samples vere collected over a period from September 14 to 17, 1984. Duplicate PCDD/PCDF samples were collected on the roof of the county building. The PCDD/PCDF samplers vere extracted by the NYSDOH laboratory, which sent an aliquot of the combined extracts from the County Building sample to Prof. Rappe at the University of Umea (Sweden) for confirmatory analysis. Analysis of the samples by NYSDQH for PCDFs and PCDDs did not detect any of these chemicals [61. Hovever, poor recovery of the internal standard from the samples collected at the City Building and the YMCA resulted in higher than expected limits of detection. Prof. Rappe reported the possible presence of 2,3,7,8-TCDF in the aliquot of extract from the County Building samplers, but at a level near his detection limit and belov the detection limit achieved by NYSDOH. Since the results obtained by Prof. Rappe vere not corrected for the recovery of the internal standard, no accurate estimates could be made of the levels of these contaminants that might have been present in the air. Because of the problems vith the analysis of the ambient PCDD/PCDF air samples from the First Test, it was decided to repeat this ambient sampling before normal HVAC operations vere resumed. This change to the planned test sequence was documented in the Test Plan Modification dated February 14, 1985 C83. This Test Plan Modification also reflected the decision of the Nev York State Department of Health Laboratories to analyze the air samples only for tetra and penta CDFs in an attempt to achieve the detection limit at which Prof. Rappe reported the possible presence of 2,3,7,8-TCDF in the ambient air sample from the First Test. In accordance vith this Test Plan Modification, duplicate PCDD/PCDF air samples and PCB samples vere collected on the roofs of the City Building, the County Building, and the YMCA on February 15 - 18, 1985. Duplicate PCDD/PCDF air samples and PCB samples vere again collected on February 22 - 25, starting vhen the HVAC units on floors 6 and 14 vere returned to normal operating conditions, releasing untreated air from louvers on these floors. The results of the analysis of the ambient air samples for PCBs vere reported in a Test Report dated May 17, 1985 [121. The quantities of PCB1254 (the type of PCB released in the BSOB) found in the ambient air at the three tested locations vere as summarized in Table 1. �TABLE 1 PCBa in Ambient Air (micrograms per cubic meter) Before and After Normal HVAC Operations Started in the BSOB on February 22, 1985. Location September 14-17, 1984 February 15-18,1985 February 22-25,1985 YNCA 003 .0 001 .02 <0.0003 County Bldg. City Bldg. 002 .0 0.002 0.0012 0.0013 000 .09 <O.OQ03 The results of the analysis of the six February ambient,air samples for tetra and penta CDFs vere reported by HYSDOH in their report dated July 17, 1985 Cl71. Ho 2,3,7,8-TCDF vas detected in any of the samples at a maximum detection limit of 0.15 picograms per cubic meter. Ho 2,3,4,7, 8penta CDF or 1,2,3,4,8-penta CDF vas detected at a maximum detection limit of 0.5 picograms per cubic meter. Prof. Rappe verbally reported that his laboratory did not identify the presence of toxic contaminants at a detection limit of one picogram per cubic meter C163. The analysis of samples of ambient air taken before normal HVAC operations vere started and immediately after the HVAC systems on floors 6 and 14 vere returned to normal operating conditions indicates that the release of untreated air from the- Binghamton State Office Building did not result in measurable or significant contamination of the air around the BSOB. 3.0 AIR QUALITY IH FLOORS 2 THROUGH 18 In accordance vith recommendations from the Expert Advisory Panel on the Binghamton State Office Building, release of untreated air from the BSOB vould be advisable only after the quality of the air in the building vas demonstrated to sufficiently clean that it vould be safe for reconstruction vorkers to breath the air in the building. It vas the consensus of the Panel that a dioxin equivalent level of not more than 14 picograms per cubic meter in the air in the building vould be required before entry vithout respirators vould be advisable, assuming that precautions continued to be taken to prevent skin contamination. The Test Plan specified that air samples vould be collected for PCBs and PCDDs/PCDFs in the building during the First Test to determine vhether the air vas sufficiently clean that vorkers could enter the building vithout respirators. PCDD/PCDF and PCB air samples vere collected in the return air plenums of the mechanical rooms on floors 6 and 14. The air entering these plenums returns from all of the areas served by each of the HVAC systems, and so measurements taken at these locations are a good �indication of the average air vithin each HVAC zone. The PCOD/PCDF air samples vere collected over a period of 64 hours. Three PCB samples vere collected at each location during this period, each PCB sample being collected over a period of about 21 hours. In addition, PCB air samples vere taken adjacent to the barriers between floors 1 and 2 to check on the adequacy of the partitions in preventing a spread of contamination from the lover to the upper portions of the building. The results of the analysis of PCB air samples vere summarized in the Versar report dated January 25, 1985 [71. The maximum_PCB concentration in the air in the dead air spaces in the elevator shaft and stairwell betveen floors 1 and 2 on clean side of the partition vas 1 microgram per cubic meter. The PCB levels in the air passing through the HVAC units on floors 6 and 14 ranged from 0.2 to 0.9 micrograms per cubic meter (average » 0.32 on floor 6 and 0.7 on floor 14). The results of the analysis of the PCDD/PCDF air samples by NYSDOH and Prof. Rappe vere summarized in an undated NYSDOH report CS1. The report calculated the average dioxin equivalent air quality based on measured tetra, penta, and hexa CDFs and 2, 3,6,7-TCBP to be 8.5 picograms per cubic meter, and concluded that the average air quality vould be belov 11 picograms per cubic meter even if all of the non-detected dioxins and penta-CBPs vere present at the detection limits achieved in these tests. Based on these results, the Office of General Services submitted to the Nev York State Department of Environmental Conservation a formal Hotice of Determination of Non-significance for the planned resumption of normal operations of the HVAC systems, vith the resultant release of untreated air from the BSOB [93. This action vas taken on February 22, 1985. The Test Plan for the Third Test sampling to determine the quality of the air in the BSOB after the resumption of normal HVAC operations vas modified on March 29, 1985, to add 63 PCB air samples from throughout the building to check on the relative homogeneity of the air vhile PCB and PCDD/PCDF air samples vere being collected -in the return air plenums of the HVAC mechanical rooms on floors 6 and 14 C101. These air samples vere collected over the period March 29 - April 1, 1985. The results of the PCB analysis of these samples is presented in Table 2. The only measurable levels of PCBs at a detection limit of about 0.16 ug/m* vere in the men's restrooms. After the building is renovated, air vill be constantly exhausted from the restrooms by a separate exhaust system in order to control odors. This vill reduce the levels of PCBs in the air. The results of the analysis of these samples for CDFs vas reported by NYSDQH in their report dated July 17, 1985 C43. The samples from the HVAC air return plenums contained measurable amounts of 2,3,7,8-TCDF and 2,3,7,8,X-Penta CDFs, but no hexa CDFs, PCDDs, or PCBPs. The NYSDOH calculated the dioxin equivalent concentration in the air in the building five veeks after normal HVAC operations vere started to be <4.1 picograms per cubic meter vs <11 picograms per cubic meter in November, 1984. �TABLE 2 PCB ANALYSIS OF AIR SAMPLES COLLECTED IN THE BSOB MARCH 29 - APRIL 1, 1985 Floor 2 2 2 2 2 2 2 2 2 Location Elevator Lobby NE Floor 2 fl NE Floor 2 #2 NE Floor 2 #3 West stairwell West elevator shaft East elevator shaft Men's room ' East stairwell PCBs ug/mj. NO ND ND ND HD ND 0.34 ND ND 3 3 3 Elevator lobby Women's room Northeast corner ND ND ND 4 4 4 Elevator lobby Men's room Northeast corner ND 0.43 ND 5 5 5 Elevator lobby Women's room Northeast corner ND ND ND 6 6 Elevator lobby Men's room 6 Northeast corner ND 0.31 ND 7 7 7 Elevator lobby Women's room Northeast corner ND ND ND 8 8 8 Elevator lobby Hen's room Northeast corner ND ND ND 9 9 9 Elevator lobby Women's room Northeast corner ND ND ND 10 10 10 10 10 Elevator lobby Men's room East Stairwell West Stairwell Northeast corner ND ND HD ND ND �11 11 11 Elevator lobby Women's roan Northeast corner NO NO HD 12 12 12 Elevator lobby Hen's roo» Northeast corner NO HD NO 13 13 13 Elevator lobby Women's room Northeast corner ND ND ND 14 14 14 Elevator lobby Hen's room Northeast corner ND 0.37 ND 15 15 15 Elevator lobby Women's room Northeast corner ND ND ND 16 16 16 Elevator lobby Hen's room Northeast corner ND ND ND 17 17 17 Elevator lobby Women's room Northeast corner ND ND ND 18 18 18 18 18 18 18 Elevator lobby Hen's room East atairvell West stairwell Northeast corner tl Northeast corner #2 Northeast corner #3 ND 0.37 ND ND ND ND ND 14 14 14 HVAC HVAC HVAC #A-8 fA-9 fA-10 ND ND ND 6 6 6 6 6 6 HVAC HVAC HVAC HVAC HVAC HVAC fA-1 #A-2 fA-3 *A-4 fA-5 *A-6 ND ND ND ND HD HD . i | . ND: None detected at detection limit of 0.2 ug/tube, approximately 0.16 ug/m*. 8 �4.0 CLEANLINESS OF SURFACES ON FLOORS 2 THROUGH IS First Teat The first teat collected 48 vipe samples that vere analyzed for PCBs In order to identify those surfaces that might have the highest levels of residual PCDDs and PCDFs. Wipe samples vere also collected from Id of the locations for analysis for PCDDs and PCDFs by Battelle. The purpose of these samples vas to establish the ratio of PCBs to total •dioxin equivalent' toxicity so as to determine vhether PCB levels could be used to identify locations having elevated levels of PCDDs and PCDFs. Tvo duplicate vipe samples vere also analyzed for tetra through hexa CDFs by the NYSDOH laboratory. the results of'all of these analyses vere reported in a formal test report 171. The average value of all 48 vipe samples vas 16.6 ug/m*. Wipe samples have been collected by HIOSH from a number of buildings vhich have not had knovn sources of PCBs, and the levels that have been found have usually averaged about 10 ug/m* vith occasional samples as high as 50 ug/m* not being unusual til. Only three vipe samples from the BSQB vere found to have levels above SO ug/m*. These samples vere collected from the top of a ceiling light fixture in the 17th floor elevator lobby vhere the plaster ceiling made access difficult (100 ug/m*), a stair tread in the east stairvell betveen floors 17 and 18 (120 ug/m* >, and a sample from the floor in the 17th floor elevator lobby (150 ug/m*). Since it vas reasonable that these elevated levels vere an indication of possible quality control problems vith the cleaning of the ceiling light fixtures and stair treads, all of the light fixtures in the core area of floors 2 through 18 vere subsequently recleaned, and the stair treads in both stairvells vere also recleaned. The floor sample from the 17th floor elevator lobby vas from a deposit of mastic that remained on floors throughout the building after the vinyl tile vas removed. This tile vill be replaced before the building is occupied, and the mastic vill therefore not be accessible to skin contact. A test application of nev tile has been installed in the building, and is being tested periodically to determine vhether the measured PCB levels increase vith time due to PCBs penetrating through the tile. An analysis of the eighteen samples for PCDDs and PCDFs by Battelle found that the levels of PCDDs vere generally lov to undetected, vith all 2,3,7,8-TCDD levels at or belov one nanogram per square meter. The calculated contamination levels for the 18 PCDD/PCDF vipe samples in terms of "dioxin equivalents' ranged from .01 to 81.7 ng/m*, the highest levels being found in the samples collected from the ceiling lighting fixtures in the core (81.7 ng/m*), and from the stair treads betveen floors 17 and 18 (31 ng/m*) and betveen floors 7 and 3 (30.1 ng/m*). The only other significant level vas found in the sample taken from the coated surface of the men's room exhaust chase on floor 17 (16.6 ng/m*) [41. The surface of this chase vas subsequently painted vith epoxy paint. The tetra and penta CDFs contributed 95X to 98% of the calculated dioxin equivalent levels. �A linear regression analysis of the log transformed PCB and dioxin equivalent data found a correlation coefficient of 0.77. If this relationship were used to predict the expected dioxin equivalent levels from the measured PCB levels, the predicted dioxin equivalent levels vould be within an order of magnitude (from 0.1 to lOx) of the measured levels 92% of the time [53. Third Test Based on information obtained from the First Test samples and suggestions made by members of the Expert Advisory Panel following a review of these results, certain changes vere made to the test plan for the Third Test as documented in the Test Plan Modification - Third Test dated March 29, 1985 C101. These changes specified that the vipe sampling vas to be conducted in tvo phases: the first phase vas to collect 35 wipe samples from types of surfaces found to have high levels of PCBs during the First Test that were subsequently recleaned and from surfaces not previously tested such as the stone floor and walls in the second floor plaza lobby. Aliquots of the extract from eleven of the samples were also to be analyzed by Battelle for PCBs as a check on the analytical methodology. Following analysis of the 85 samples for PCBs, the 10 locations found to have the highest PCB levels were to be wipe sampled to determine the levels of ! PCDFa. The 85 PCB wipe samples specified in the amended test plan and the eleven samples for duplicate analyses were collected on March 29, along with 5 additional samples from areas selected by Mat Gillen who observing the sampling on behalf of the Public Employees Federation. The results of the PCB analysis of all 101 wipe samples were included in the Test Plan Amendment dated May 28 which covered the collection of wipe samples for PCDF analysis C13, attachment A]. The average PCB level of these 101 samples was 7.8 micrograms per square meter. The results of the duplicate analysis of 11 samples by both Versar and Battelle were not significantly different (correlation coefficient = 0.997) CIS]. Only two PCB wipe samples were above 50 ug/m*: stair tread from west stairwell on floor 2, 110 ug/m* as measured by Versar, 106 as measured by Battelle; stone floor from floor 2 plaza lobby, 62 ug/m* measured by Versar, 74 ug/m* measured by Battelle. However, eight of the 10 highest measurements were from stair treads and landings in the stairwells. In order to provide additional assurance as to the cleanliness of the building, 06S had the stairwell treads and landings and the stone floor on floor 2 recleaned, and had the stair treads painted with epoxy paint. (The stair landings, like most of the floors in the building, will be eventually covered by new vinyl tile.) These surfaces were retested for PCBs as specified in the Test Plan Modification dated May 3, 1985 [111. Thirteen wipe samples were collected from landings and stair treads on May 5, and the results from this retest were also included in the May 28 Test Plan 10 �Amendment C13, attachment Bl. 4 ug/m*. None of these samples shoved PCS levels above Based on the results of the March 29 sampling and the Hay 3 resampling of recleaned stairways, it was possible to select surfaces for PCDF sampling which met the criteria of representing the 10 highest PCB levels without having all of the samples being taken in the stairwells. The wipe sampling for PCDFs was defined in the Hay 28 Test Plan Amendment C13], which included 11 locations selected by OGS and an additional 6 locations suggested by Dr. Terry Killer. All samples were to be analyzed by Battelle, for tetra and total penta dibenzofurans, and aliquots of the extract from two wipe samples were to be sent to the Mew York State Department of Health Laboratory for confirmatory analysis. PCB wipe samples from the same locations were analyzed for PCBs by Versar. These samples were collected on Hay 28, and the results of the Battelle analyses were summarized in the Battelle Final Report dated July 19, 1985 [ 8 . 1] The PCDF results, the PCB measurements, and the calculated dioxin equivalent contamination levels based on the levels of 2,3,7, S-TCDF and total penta-CDFs are summarized in Table 3. The highest dioxin equivalent levels were found on the top of ceiling light fixtures from floors 12 and 16 (12.6 and 14 ng/m*), from the concrete floor in the elevator lobby on floor 7 (12.5 ng/m*), and from the stone floor on floor 2 (13.8 and 12.8 ng/m*). The First Test wipe samples, which were analyzed for tetra through hexa CDDs and CDFs, showed that 95X to 98X of the dioxin equivalent level was the result of the presence of tetra and penta CDFs. Assuming that PCBPs might contribute an additional 10% to the toxicity, the contaminant levels calculated from the Test Three data may underestimate the total surface contamination by up to 15%, so the maximum contaminant level might actually be 16.4 ng/m* rather than 14 ng/m*. The two samples that were also analyzed by the Hew York State Department of Health Laboratories were from the stone floor in the floor 2 lobby and from the vinyl wall in the elevator lobby on floor 12. The comparable analytical data from the two laboratories are summarized in Table 4. A linear regression analysis of the log transformed PCB and dioxin equivalent data is shown in Figure 2. The NYSDOH analysis was performed using low resolution mass spectrometry, but did quantify the specific isomers of penta-CDFs that were chlorinated at the 2, 3, 7, and 8 positions. Both laboratories found about the same levels of 2,3,7,8-TCDF. Although HYSDQH found higher levels of total penta CDFs in both samples, the percentage of the penta-CDFa that was chlorinated at the 2, 3, 7, and 8 positions was significantly lower that* the assumed SOX used to calculate the dioxin equivalents from the Battelle data, so the final calculated dioxin equivalent levels were essentially identical for the two laboratories. 11 \ �TflBLE 3 RNflLYTICflL RESULTS FOR PCBS RNO OIOXIN EQUIVALENTS FOR WIPE SAMPLES COLLECTED MAY 29, 1985 IN THE BSOB ng/«2 SAMPLE 2378 ,,,TCDF 2791 29 74 2795 29 76 29 77 20 60 2801 20 82 2810 29/ 723 29/0 723 29/ 789 20 86 20 84 2803 20 88 20 89 20 85 2807 2813 2811 TOTAL PENTACOFs 37 .0 77 .0 13.00 12.00 - 18.70 44 .0 1.70 1.20 03 .0 15.50 11.90 1.00 09 .0 2.50 00 .0 24 .0 07 .0 28 .0 1.10 06 .0 04 .0 11.90 2.0 23 5.0 78 51.70 * 3ft 7 38 .0 4.10 26 .0 00 .0 51.50 5.0 30 1.50 1.00 00 .0 1.40 2.30 00 .0 00 .0 1.90 00 .0 00 .0 ug/oi2 OIOXIN EQUIV 3.22 62 .8 13.97 12.62 12*45__ 2.10 1.25 08 .3 0.10 13.75 12.80 05 .8 04 .7 08 .3 0.23 1.18 02 .3 09 .3 06 .8 02 .0 0.13 PCBs 23 4 5 5 31 16 8 <0.5 <0.5 26 6 2 2 2 4 2 2 <0.5 <0.5 <0.5 STAIR TREAD, FLOOR 2; WEST STAIR WELL STAIR NOSING, FLOOR 18 CEILING LIGHT, FLOOR 16 NE CEILING LIGHT, FLOOR 10 CORE CONCRETE FLOOR, FLOOR 7 CORE INSIDE OF MEN'S ROOM DOOR, FLOOR 3 VINYL WALL, FLOOR 9 CORE INSIDE WOMEN'S ROOM DOOR, FLOOR 15 FIELD BLANK STONE FLOOR, FLOOR 2 CORE DUPLICATE ANALYSIS 2792/3 VINYL WALL, FLOOR 16 CORE STAIRWAY LANDING, FLOOR 12 WEST STAIRWELL STAIR TREAD, FLOOR 14 EAST STAIRWELL COLUMN ENCLOSURE, FLOOR 6 NE PERIMETER STAIRWAY LANDING, FLOOR 8 EAST STAIRWELL STAIRWAY LANDING, FLOOR 5 WEST STAIRWELL STAIR TREAD, FLOOR 13 EAST STAIRWELL STAIR TREAD, FLOOR 11 WEST STAIRWELL LABORATORY BLANK FIELD BLANK �TABLE 4 Comparison of Battelle and NYSDQH analysis of PCDF wipe samples Isomer or Class Vinvl Wall Sample 2,3,7,8-TCDF Total TCDFs 1,2,3,7,8-Penta CDF Total Penta CDFs Stone Floor Sample 2, 3, 7, 8-TCDF Total TCDFa 1,2,3,7,8-Penta CDF Total Penta CDFs 5. HYSDOH Battelle ,\fof 0.9 5.7 0.38 1.3 17. 9. 8 18.8 9. 5 ng/m« ng/m* ng/m* ng/m* ng/ra* ng/m* ng/ra* ng/m* 1.0 8.0 0.39 1.5 ng/m* ng/m* ng/m* ng/m* A//5 15.5 ng/m* 63. ng/m* 16.3 ng/m* ng/m* 52. CONCLUSIONS The release of untreated air from the Binghamton State Office Building when the HVAC units on floors 6 and 14 were returned to normal operating conditions did not cause any measurable contamination of the ambient air around the building. The initial contamination level of the air being vented from the building was <11 picograms dioxin equivalents per cubic meter. The air in floors 2 through 18 of the BSOB on April 1 (five weeks after the HVAC units started normal operations) contained <4.1 picograms dioxin equivalents per cubic meter. The air in floors two through 18 did not contain measurable levels of PC8s at a detection limit of about 0.16 ug/mj, except in one elevator shaft and in the men's restrooms where the levels of PCBs were up to 0.43 ug/m*. Surfaces in the BSOB in late Hay generally had contamination levels of less than one nanogram dioxin equivalents per square meter except for the tops of ceiling lighting fixtures, the concrete floor on floor 7, and the stone floor on the floor 2 plaza entry. The maximum levels of dioxin equivalent contamination calculated from measurements of 2,3,7,8-TCDF and total penta-CDFs did not exceed 14 nanograms per square meter on any of the samples. Adjusting for the possible presence and contribution of PCDDs, hexa-CDFs, and PCBPs, the total dioxin equivalent contaminant level of the highest sample might have been as high as 16.4 nanograms per square meter. 13 �FIGURE 2 RATIO EVALUATION BSOB WIPES or w o »-» n CJ 3 1.2 1.1 1 0.0 O.B 0.7 0.6 0.5 0.40.3 0.2 0.1 0 -0.1 - D -0.2 - D -0.3 -0.4 -0.5 -0.6 -0.7 I I -0.7 -0.5 only furan analysis performed P a a D D D D D T i i r i i i i i i i i i i T i f \ i -0.3 -0.1 0.1 0.3 0.5 0.7 0.0 1.1 1.3 1.5 D LOG PCB MAY 20,1085 �REFERENCES Cll Korainaky, J.R.; J.M. Melius; J.PFlesch. (MIQSH Cincinnati). Assessing PCB Contamination from Electrical Equipment Failures. Paper presented at the American Industrial Hygiene Conference, Philadelphia, Pa. Hay 22-27, 1983. C2J Test Plan: Measurement of Residual Contaminants in the Air and on Surfaces in Floors 2 through Id of the Binghamton State Office Building Following Completion of the Preliminary Cleanup and Measurement of the Effect of Normal HVAC Operations on the Concentration of Contaminants in the Air Within and Adjacent to the Binghamton State Office Building. September 5, 1984. C31 DeRoos, Fred. L. (Battelle Columbus Laboratories). Untitled letter report dated October 26, 1984 to Or. Richard Ronan, Versar Inc. t (Included in C2] as Appendix E) C41 Westin, R.A. (Versar Nev York Inc.) Versar and Battelle Analytical Results from First Test, September 5 Test Plan. Letter to H. Stevens dated November 20, 1 8 . 94 C5] Westin, R.A. (Versar Nev York Inc.) Toxic ratio PCBs/TCDD equivalents in vipe samples from First Test. Letter to H. Stevens dated November 28, 1984. ' C6] Aldous, K.; D. Bilker; P. O'Keefe; R. Smith; 6. Eadon. Chemical Data on Air and Wipe Samples Collected from the Binghamton State Office Building - September 1984. Nev York State Department of Health. Undated. (Included in £23 as Appendix D) C7] Test Report: Summary of Results of the First Test To Determine Residual Contaminants in the Air and on Surfaces in Floors 2 through 18 of the Binghamton State Office Building. Versar Nev York Inc. January 25, 1985. C81 Test Plan - Modification. Second Test: Measurement of the Effect of Normal HVAC Operations on the Concentration of Contaminants in the Air Within and Adjacent to the Binghamton State Office Building. Versar Nev York. February 14, 1985. [9] Egon, J. (Nev York State Office of General Services.) SEQR Negative Declaration: Notice of Determination of Non-Significance: Return to Normal HVAC Operation of Floors 2 to 18 of the Binghamton State Office Building (BSOB). February 20, 1985. CIO] Test Plan - Modification. Third Test: Measurement of the Levels of Toxic Chemicals Remaining in the Air and on Surfaces in the Binghamton State Office Building Following Resumption of Normal HVAC Operations. Versar Nev York Inc. March 29, 1985. �[Ill Test Plan - Modification, Third Test Addendum: Measurement of the Levels of Toxic Chemicals Remaining on Surfaces in the Stairwells in the Binghamton State Office Building. Versar Nev York Inc. May 3, 1965. [12] Test Report - Summary of Results of the Second Test to Determine Ambient Air Concentrations Prior to Venting and During Venting Around Binghamton State Office Building - PCB Measurements. Versar Nev York Inc. May 17, 1985. [13] Test Plan - Amendment to Modification of Third Test Dated March 29, 1985: Measurement of the Levels of Toxic Chemicals Remaining in the Air and on Surfaces in the Binghamton State Office Building Following Resumption of Normal HVAC Operations, Versar New York Inc. May 28, 1985. ' ' * C141 Sampling Report. Amendment to Third Test of the Cleanliness of Floors 2 - 18 of the BSOB: May 28, 1985. Versar New York Inc. June 11, 1985. [153 Hestin, R.A. (Versar Nev York Inc.) PCB results from analyses of split extracts by Battelle and Versar. Letter to H. Stevens dated June 18, 1985. [16] Eadon, G. (Nev York State Department of Health.) Split Sampling Results - BSOB Outdoor Air. Memo dated July 11, 1985. [17] Smith, R.; P. O'Keefe; X. Aldous; D. Milker; G. Eadon. (Nev York State Department of Health.) Chemical Data on Air Samples Collected in and Near the Binghamton State Office Building (February, March 1985) Before and After the HVAC is Returned to Normal. July 17, 1985. [18] DeRoos, F.L.; S.C. Watson. (Battelle Columbus Laboratories.) Final Report on Measurement of Polychlorinated Dibenzofuran Levels in Surface Wipes from the Binghamton State Office Building. July 19, 1985. 16 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 089 Folder The folder containing the original item. 2270 Series The series number of the original item. Series IV Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Description An account of the resource <strong>Corporate Author: </strong>Versar New York, Inc., Springfield, Virginia Title A name given to the resource Typescript: Summary Report: Measurement of Residual Contaminants in the Air and on Surfaces in Floors 2 Through 18 of the Binghamton State Office Building Following Completion of the Preliminary Cleanup and Measurement of the Effect of Normal HVAC Operati Subject The topic of the resource BSOB ambient air sampling PCBs building remediation https://www.nal.usda.gov/exhibits/speccoll/files/original/1e3f63cb354acbe0233bafe147f7d801.pdf 6a26ebc16b4a666030c84735939235d3 PDF Text Text Item D Number 021 si Author Corporate Author RBDOrt/ArtlClB HtlB Typescript: Proposed Worker Surveillance, BSOB, Draft June, 19,1981 Journal/Book Title Year 000 ° Month/Day Color Number of Images D 9 DBSGPlpton Notes Thursday, September 20, 2001 Page 2181 of 2293 �PROPOSED WORKER SURVEILLANCE, BSOB J DATA BASE Ba&ed on data in the possession of the NYS Ueoartment of Health at this tine, partial or complete records exist on 479 persons working for 20 different firms not including a small miscellaneous category. They are shown by employer and leve 1 of exposure categories in Appendix I. It should be pointed out that information on both employer and exposure was obtained from the individuals themselves , either at the time of the blood drawing when a Binqhamton General Hospital medical record questionnaire was completed, or during a personal interview with a nurse. Based on place of exoosure, the 208 persons actually in the BSOB would be the most likely to have sustained genuine exposure. In addition, the qroup in the basement or subbasement (unknown if this was the garage or building) and the 65 with unknown exposure are considered suspect for f building exposure until further information can be obtained on them. The other exposure categories would appear to represent minimal non-exposures to BSOB soot. V ,T u\ 1 4*^ U k \ S. **' tt* ^ wide variation in duration of exposure was indicated as well. At one end of the spectrum, the 33 NEPCO employees worked a minimum of 100 hours in , with many in excess of 700 hours. the The OGS clean-up crew soent between 50 and 100 hours in the building. A few OGS _--.—--•employees have sDent more than, 100 hours in the building. —— The Miske Electric electricians ------ — appear to have spent less than 100 hours in the building. Virtually all other oersons seem to have spent no more than a few minutes to a few hours , in the �Department to their private physicians. Most of the remaining individuals either have no private physician or failed to indicate one at the time of evaluation. «• /"" �on an as needed basis. A telephone answering service is on line to refer health inquiries from individuals in this group to the NYSDH. If the inquiry is in response to a health problem that might reasonably be related to exposure to the BSOB, arrangements will be made, at no expense to the individual, to be seen by a local internist with referral to a dermatolo gist if deemed appropriate. Both of these evaluations are offered for general health screening without regard to etiology and, as such, no attempt will be made to summarize or analyze the data from the group as a whole. SUBSET EVALUATIONS The most intensive surveillance monitoring and analytical efforts will be focused on a small subset of individuals with we11-documented high exposure. High exposure can be defined by both place and duration of exposure. Since contamination is largely an intra-building problem, those persons who have entered the building since the fire are the most likely to have encountered i f significant exposure. Of the groups who have been in the building, duration apparently was greatest for NEPCO cleaners, followed in decreasing order of duration by the OGS clean-up crews, Miske electricians, and National Insulation cleaners. Other groups in the building tended to be small and spend only limited time in the building though individual exceptions exist. guably the most fvp^'if^ riingili n ir V-MS I Ti" • NFP1"" "TtMH"i"rr Unar- Howvftri thn fact that they are more or less continuously involved in toxic 'clean-ups of one sort or another renders any information gleaned fr ^ — ^ ^ * m ^ i i. if not impossible to interpret. While data will be collected on this group, no analysis will be attempted on this information. �*. U V _ •> c -4- The general surveillance scheme is shown graphically in Appendix III. The general health screening which will be provided to persons whose exposure was limited to outside the building has already been described. Persons who have been inside the BSOB but for only a short time will have a similar blood screen with an additional tube of blood saved for potential future reference. Those persons determined to have spent a long time in the BSOB will have a similar blood screen.with sera being saved. A portion of the saved sera will be used to determine a serum PCB level. The long duration BSOB exposures group will also be offered a physical examination. . Because of what is known to occur in animals and humans exposed to PCBs and other compounds in this group, certain a priori hypotheses can be advanced as to health effects one might see amongst the population exposed to the soot from the BSOB. Conclusions on the human health effects of exposure to BSOB » soot wi^l be limited to analytical results which are biologically plausible and have been generated in response to these prestated hypotheses. organ systems of most concern are the liver and integument. The Since a diag- nosis of liver disease is often arrived at only late in the natural course of an illness, we will focus on liver function test abnormalities under the presumption that they are surrogate markers of potential or real future disease, ajj p<=»-gQng '"fr"'"0 v^"" •»p +-v>p Vm-iirHng j=p,pqethe fire for a minimum of 25 hours will be included in t-hir, n m l y n i n i subset may also be analyzed separately. Subsets among this The mean values for several liver function tests drawn while in the building will be compared to the mean values obtained after having terminated exposure for a period of time. The hypothesis, succinctly stated, is that there is an association between exposure to the building and an alteration (either up or down) in liver function tests. The hypothesis must be two-tailed because initial bloods were not �timing then, follc.w-up liver tests might be expected to show a rise or a fall. The liver function tests which will be analyzed include SCOT and GGTP. The physical examinations will give special attention to the skin. Chlor- acne, a condition essentially pathognomonic for exposure to PCBs and related compounds, will be looked for. period before its appearance. Chlgracn_e_.is known to require, a latent It is jalsg^.verv persistent. As such. a single examination approximately six months after initial contact seems a reasonable time to look for such a condition. Since no cases of chloracne are expected, /observation of even a single documented case will be presumptive evidence of an adverse health effect. Skin biopsy of suspect lesions will be required to document chloracne. Dr. Kimbrough of CDC in Atlanta, GA, has agreed to review slides from any biopsied lesions to determine if the changes characteristic of chloracne are present. In an attempt to quantitate exposure to PCBs in the building, a comparison will be made between the initial serum PCS values obtained either before or shortly after entering the building, and the value obtained at follow-up. This evaluation will be performed on values from all persons who were in the BSOB a long time and for, whom an initial sera for PCBs is available. To make data as comparable as possible, several things will be done whenever possible. First, the same laboratory will be used for both initial and follow-up general blood screening. Second, a limited number of physicians familiar with chloracne and other PCB effects will be utilized for physical exams. Finally, serum for PCB levels will be sent to a reputable laboratory �well experienced in PCB analysis. They will be sent both initial and follow-up sera at the same time and asked to analyze them blind as to the time that they were drawn. SUMMARY In summary, the surveillance of persons potentially exposed to contaminants in the BSOB will involve a 3 tiered approach. Those whose only exposure was outside the BSOB will receive a follow-up blood screen while those exposed inside the BSOB may have sera saved for future^ testing, serum PCB determinations and/or a physical examination depending on duration of time spent in the building. Analysis of infnr-mal-irm o n h a a H - h e f f e t e w i l l ho '. in)j,- to selected liver function tests and a search for chloracne. An attempt to quantitate exposure to PCBs will be made by comparing initial and follow-up serum PCB levels. If no health effect or exposure is demonstrated/ no further investigation is expected. Should significant effects or exposure be found, additional investigative steps might be indicated. �APPENDIX I Place of Exposure Total N Firm or Group 1. 2. New York Telephone Press 3. Firemen 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. Police AJ Cerasaro Talent Search NIOSH Broome County City of Binghamton Bldg. Services Aides BGH Staff NEPCO New York Gas & Electric Valley Welding Fanta Sea Central Steel OGS Miske Electric S NYS, Miscellaneous Security Miscellaneous TOTALS In SOB Bldg. 3 In Garage Only 0 1 0 4 0 0 0 9 0 In City or In Cars County From Bldg. Garage 1 6 6 32 39 14 4 1 60 54 3 4 48 21 1 2 6 66 33 39 20 20 6 2 0 0 34 19 0 0 4 48 29 22 1 2 0 0 0 0 0 2 0 0 0 1 0 0 0 0 17 0 0 0 19 48 0 4 0 0 0 0 0 8 0 1 0 1 479 208 17 99 4 27 4 2 0 I 0 0 0 7 0 0 0 14 0 Exposed to Bldg. Materials In B Outside of or SB Bldg. or Definite Bldg. or Near NonGarage Bldg . Exposure 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 12 0 0 7 0 0 0 0 0 0 0 0 2 0 2 2 0 0 0 1 0 0 4 0 0 0 0 0 0 0 1 0 0 2 0 4 13 3 21 26 28 0 0 0 0 0 0 0 1 0 3 0 8 0 0 0 0 0 0 i i Unknown i 2 1 3 : 7 . F 0 0 0 4 4 0 0 6 2 0 0 2 6 2 0 4 8 2 14 15 65 1 ;• ; , ! : �Bjochem is try 5c reen Glucose BUN Creatim'ne Total bflirubin Direct bilirubin Total protein Albumin Uric acid Alkaline phosphatase SCOT LDH SGPT GGPT Cholesterol' Triglycerides Calcium Phosphorus Acid phosphatase Serum iron Total iron binding capacity ootainea, �APPKNDiX III Possible Exposure Initial Blood Screen (CBC, SMAC 20, Saved Sera) Exposure Outside BSOB Exposure Inside BSOB Short Duration Follow-up Blood Screen (CBC, SMAC 20) Follow-up Blood Screen (CBC, SMAC 20, Saved Sera) Long Duration Follow-up Blood Screen (CBC, SMAC 20, Serum PCB, Saved Sera) Physical Exam � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 087 Folder The folder containing the original item. 2181 Series The series number of the original item. Series IV Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Typescript: Proposed Worker Surveillance, BSOB, Draft June, 19, 1981 Subject The topic of the resource exposure assessment PCBs health monitoring https://www.nal.usda.gov/exhibits/speccoll/files/original/6e557b4dd98341b1aa4143c1bdf9bdca.pdf f94d8d48acca10e633409bc4d569daf9 PDF Text Text Rom D Number 02239 Author Tumasonis, Casimir Corporate Author Report/Article Title Typescript: Preliminary Report: Chick Embryos as a Probe of the Relative Toxicities of Soot Samples from a Polychlorinated Biphenyl-Containing Transformer, [nd] Journal/Book Title Year Month/Day Color Number of unaoes n 14 Descriptor) Notes Thursday, September 20,2001 Page 2289 of 2293 �PRELIMINARY REPORT CHICK EMBRYOS AS A PROBE OF THE RELATIVE TOXICITIES OF SOOT SAMPLES FROM A POLYCHLORINATED BIPHENYL-CONTAINING TRANSFORMER Casimir Tumasonis and Laurence Kaminsky Division of Laboratories and Research New York State Department of Health Albany, New York 12201 �Chick Embryos as a Probe of the Relative Toxicities of Soot Samples from a Polychlorinated Biphenyl-Containing Transformer. Tumasonis, C. and Kaminsky, L. The involvement of a polychlorinated biphenyl (PCB)-containing transformer in a fire resulted in widespread contamination of the State Office Building in Binghamton, New York with a soot-like material containing 1 ppm 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), 50 ppm 2,3,7,8-tetrachlorodibenzofuran (2,3,7,8-TCDF), and relatively high concentrations of PCBs and other polychlorinated dibenzofurans and dibenzodioxins. The chick embryo system has been investigated as a rapid and inexpensive method for assessing the relative toxicities of large numbers of soot samples derived from different sites in the building, and as a means of assessing effectiveness of the clean up procedures. Samples were administered to the embryos in an aqueous 0.75% methyl cellulose vehicle via a hole drilled into the shell over the air sac. Soot exhibited the greatest embryo lethality when administered on day 4 of incubation. There was a non-linear dose related embryo lethal response with a marked saturation of embryo lethality between the 0.2 and 2.0 mg soot/egg doses. At 2.0 mg soot/egg administered in 0.1 ml aqueous vehicle approximately 50% of the embryos were dead by day 18 of incubation. No deaths were observed with the same quantities of active carbon or fireplace soot. Increasing volumes of vehicle increased the embryo lethal effects of the soot probably indicating that the non-linear dose response was partially due to a lack of availability of all the administered soot to the' inner air sac membrane. At doses of 2.0 mg Binghamton soot/egg some teratological effects were observed in �embryos surviving to day 18 of incubation. The effects included curled toes, anophthalmia, exencephaly and edema and occurred at low frequency and non-reproducibly. 2,3,7,8~TCDD when administered into the eggs at doses of up to 500 ng/egg in the aqueous vehicle and up to 800 ng/egg in corn oil killed 3 out 15 embryos at the highest dose and all embryos above 10 ng/egg in the two vehicles respectively. Further studies are underway to develop the chick embryo system for use in investigating the relative toxicities of different soot samples. �A fire which involved a transformer in the State Office Building in Binghamton, New York resulted in extensive contamination of the building with a soot-like material. The transformer contained a dielectric fluid (pyranol) which comprised 65% Arochlor 1254 (a polychlorinated biphenyl (PCB) mixture), 35% chlorinated benzenes and trace additives. Soot samples collected from two sites in the building were • contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and 2,3,7,8-tetrachlorodibenzofuran (2,3,7,8-TCDF)(Smith et al., 1981a). Based on pyrolysis studies with PCBs it was predicted that the soot would also have relatively large contamination by other isomers and congeners of the polychlorinated dibenzo dioxins and dibenzofurans (Buser _et al., 1978). Predictions of the toxicity of the soot based on the known concentrations and toxicities of 2,3,7,8-TCDD and 2,3,7,8-TCDF are suspect for a number of reasons: Not all contaminating components of the soot can be determined, the toxicities of all polychlorinated dibenzodioxins and dibenzofurans is not known, the role of the soot matrix was not known (Silkworth et al., 1981) and the potential for synergistic or antagonistic effects of the pollutants on the toxicity of other pollutants is unknown. Thus there was a requirement for a toxicological assessment of the soot where it would be treated as a single compound. As part of the clean-up procedures in the building, assessments of the variations in toxicity of soot from different sites and at different times as the clean-up proceeds will require toxicologic analysis of numerous samples. A method was required which would provide a rapid analysis of large numbers of samples without enormous �resources of personnel and equipment. using chick embryos. These criteria could be met by In 1966 a group meeting under the auspices of the World Health Organization recommended that the chick embryo not be used for screening drugs for teratogenicity since it is "too sensitive to a wide range of agents and affords no parallel with the anatomical and physiological relationship existing between a pregnant mammal and her conceptus" (World Health Organization, 1967). Subsequently argu- ments have been raised in favor of the introduction of the use of chick embryos in teratology most notably by Gebhardt (1972) in the Netherlands and Wilson (1978) in the USA. A number of reports have appeared recently in which the chick embryo method has been used to investigate the teratogenicity of methylene chloride, trichlorethane, trichloroethylene, tetrachloroethylene and toluene (Elovaara et al. 1979), DDT (Swartz, 1980), cholinergic insecticides (Misawa et al., 1981) and Lambda-Carrageenan (Monis and Ravasio, 1981). The chick embryo has also recently been used to evaluate the cardiovascular teratogenicity of 2,3,7,8-TCDD (Cheung et jal., 1981). In this paper we report our preliminary investigations on the use of the chick embryo to investigate the relative toxicities of samples of soot collected in the state office building. The main criterion which will be used is embryo lethality rather than teratogenicity in view of the controversy associated with interpretation of teratological effects and the relative ease in assessing embryo lethality. �METHODS Fertile White-Leghorn chicken eggs (50-60 g) were obtained from a farm maintained by this Division. After collection the eggs were placed into a humidified (65-67% humidity), forced-draft incubator (Humidaire) and were incubated at 37.5° ±0.32°C to initiate embryo development. Contaminated soot was obtained with a vacuum cleaner fitted with clean collection bags from the stairwells of the third and fourth floors of the State Office Building in Binghamton, New York. It was filtered through a wire gauze to remove gross inert contamination. Extracts of the soot were prepared by Soxhlet extraction with benzene for 16 hr. Benzene was removed by heating the solution. 2,3,7,8-TCDD was obtained from Dow, Midland, MI as a solution in toluene. The soot was analyzed as previously reported (Smith _et al., 1981b). For administration of samples a small hole was drilled into the egg shell in the center of the airspace (determined by candling) and samples injected by a syringe (fitted with an 18g needle) onto the inner membrane. The hole was then immediately sealed with paraffin and the eggs incubated. At the end of the incubation period eggs were cracked open and the embryos were removed and evaluated for lethality, gross malformation, and subcutaneous edema. Surviving and non-auto- lized embryos were individually preserved in 10% neutral buffered formalin. Studies were performed to determine the optimal day of administration and day of termination, dose response-curve, effect of volume of vehicle, effect of polarity of vehicle and effect of the soot matrix on the toxicity of contaminants. The last study will be per- formed by comparing the embryo lethality of the soot itself with that �of the benzene extract of the soot. Effect of vehicle polarity was tested using 2,3,7,8-TCDD as the test compound. The vehicle chosen for most of the studies is 0.75% aqueous methyl cellulose. A similar system has recently been demonstrated to be a safe vehicle in teratological studies (Fritz and Decker, 1981). This vehicle has also been used in extensive studies of the toxicity of the soot in guinea pigs (Silkworth et al., 1981). �RESULTS AND DISCUSSION Thirty eggs were randomized into three groups of 10 each. On each of days 0, 3 or 4 of incubation one of the groups was inoculated with 2.0 mg spot/egg in 0.75% aqueous methyl cellulose (0.1 ml/egg). One half of each group was opened on day 14 and the remainder on day 18, and the embryos examined for viability. Administration on days 0, 3 and 4 resulted in a total of 17, 38 and 78% embryo deaths respectively. It was thus apparent that administration on day 4 was the most effective for the expression of soot toxicity in this system and all subsequent studies incorporate administration on day 4. In a series of studies designed to determine the dose response and reproducibility of embryo lethality, eggs were administered 0.02, 0.2 or 2.0 mg soot/egg in aqueous methyl cellulose into the air sac on day 4 of incubation. In each study 15 eggs/group were used. Two control articles, fireplace soot and active carbon, were also inoculated separately on day 4 into the air sac at doses of 2 mg/egg in the aqueous vehicle. lethality. In no case did the control articles result in embryo In two separate experiments 2 mg soot/egg led to 53 and 56% dead embryos indicative of the reproducibility of the system. However, studies repeated at periods over several months showed much greater variability. In one of these experiments only one of the soot-exposed embryo which survived the 18-day incubation exhibited anophthalmia, exencephaly, toe curl and a short upper beak while four other embryos exhibited edema. Toe curl was found for the majority of the chicks surviving up to the 18th day. In the duplicate experiment the only gross teratological effect observed was toe curl. In Fig. 1 the dose response curve for embryo lethality is shown. There was a marked saturation in embryo lethality between the 0.2 8 �mg/egg and 2.0 rag/egg close levels. To explain this we hypothesized that the aqueous soot-containing vehicle would form droplets on the inner membrane and that some' of the soot, distant from the droplet surface exposed to the membrane, would not be available for xenobiotic release to the embryo. To test this hypothesis we administered to groups of 15 eggs, doses of soot in differing volumes of vehicle. Doses of 1 mg/egg and 0.1 mg/egg were administered in 0.05, 0.10, 0.50 and 1.00 ml aqueous vehicle. No volume effect was noted at the low dose but at the high dose lethality increased with increasing volume until the highest volume where embryo lethality was diminished. Mor- talities were 13% at 0.05 ml, 20% at 0.1 ml, 40% at 0.50 ml and 27% at 1.00 ml. It is thus possible that low vehicle volume prevents com- plete exposure of the soot to the membrane. In a recent study (Cheung et al.f 1981) 2,3,7,8-TCDD was administered into the egg white of fertile chicken eggs in a vehicle of acetone/corn oil at doses of 0.003 to 25 ng/egg on day 0 of incubation. At no dose was there more than 45% lethality. The soot sample used in the current study has been reported to contain approximately 1 ppm of 2,3,7,8-TCDD and 50 ppm 2,3,7,8-TCDF (Smith et al., 1981b). At a dose of 2 mg soot/egg there was thus approximately 2 ng 2,3,7,8-TCDD/egg and 100 ng 2,3 ,7 ,8-TCDF/egg. In an effort to compare the soot embryo lethality with that of one of its similarly administered components, and to determine the effect of the aqueous vehicle relative to a more hydrophobic vehicle 2,3,7,8-TCDD was administered to the eggs in aqueous methyl cellulose or corn oil vehicles. Groups of 15 eggs received 0.1, 1.0, 5.0, 10.0, 100, 250 or 500 ng TCDD/egg in 0.1 ml aqueous methyl cellulose, or 10, �50, 100, 250 or 800 ng TCDD/egg in 0.10 ml corn oil, or 0.1 ml of the vehicles on day 4 of incubation, into the air sac. With the aqueous vehicle only the two highest doses were embryo lethal producing 1 and 3 deaths respectively. In contrast all doses above 10 ng/egg in corn oil killed all the embryos. The corn oil vehicle killed 4 embryos. While this study has not been completed it is apparent that the embryo lethality of the soot probably does not arise from the bound 2,3,7,8TCDD. The effect of corn oil itself in killing 27% of the embryos is consistent with a previous report that olive oil (25 yI/egg) injected into the air sac on day 3 of incubation killed 27% of the embryos by day 14 of incubation (Elovaara et al./ 1979). However, in another study (Kitos et al., 1981), corn oil when injected into the yolks of eggs at 50 yl/egg on day 6 of incubation produced no deaths of embryos by day 18. In conclusion we have demonstrated that the Binghamton soot produces embryo lethal effects when administered into the air sacs of fertile eggs under conditions where active carbon and fireplace soot have no effect. The lethal effects are dose dependent and also dependent on the volume of administration vehicle. One of the components of the soot, 2,3,7,8-TCDD, is markedly more toxic when administered in corn oil-than in an aqueous vehicle and it is possible that the apparent toxicity of the soot is similarly dependent on vehicle polarity. Further studies are underway to develop the chick embryo method for evaluation of relative toxicities of Binghamton soot samples. 10 �REFERENCES BUSER, H. R., BOSSHART, H.-P., and RAPPE, C. (1978). Formation of polychlorinated dibenzofurans from the pyrolysis of PCBs. Chemosphere 7, 109. CHEUNG, M. 0., GILBERT, E. P., and PETERSON, R. E. (1981). Cardiovas- cular teratogenicity of 2,3,7,8-tetrachlorodi-benzo-p-dioxin in the chick embryo. Toxicol. App1. P h armaco1. 61, 197-204. ELOVAARA, E., HEMMINKI, K., and VAINIO, H. (1979). Effects of methylene chloride, trichloroethane, tetrachloroethylene and toluene on the development of chick embryos. Toxicology 12, 111- 119. FRITZ, H., and BECKER, H. (1981). The suitability of carboxymethyl- cellulose as a vehicle in reproductive studies. Arzn.-Forsch. Drug Res. 31, 813-815. GEBHARDT, D. O. E. (1972). teratology. The use of the chick embryo in applied Adv. in Teratology 5_, 97-111. KITOS, P. A., WYTTENBACH, C. R., OLSON, K., and UYEKI, E. M. (1981). Precision delivery of small volumes of liquids to very young avian embryos. Toxicol. Appl. Pharmacol. 59, 49-53. MISAWA, M., DOULL, J., KITOS, P. A., and UYEKI, E. M. (1981). Teratogenic effects of cholinergic insecticides in chick embryos Toxicol. Appl. Pharmacol. 57, 20-29. MONIS, B., and RAVASIO, R. A. (1981). Teratogenic effect of lambdaCarrageenan on the chick embryo. Teratology 23, 273-278. SILKWORTH, J., MCMARTIN, D., DE CAPRIO, A., REJ, R., KUMAR, S., and KAMINSKY, L. (1982). Acute toxicity of soot from a polychlori- nated biphenyl-containing transformer fire, (in preparation). 11 �SMITH, R. M. , O'KEEFE, P. W., HILKER, D. L. , JELUS-TYROR, B. L. , and ALDOUS, K. (1981a). Chemical analysis of 2,3,7,8-tetrachlorodi- benzo-p-dioxin and 2,3,7,8-tetrachlorodibenzofuran in a soot sample from the transformer explosion in Binghamton, New York. N.Y. State Dept. of Health Report. Feb. 20, 1981. SMITH, R. M., HILKER, D. L., O'KEEFE, P. W., KUMAR, S. , O'BRIEN, J., JELUS-TYROR, B. L., and ALDOUS, K. (1981b). Analysis of a Binghamton soot sample for tetrachlorodibenzofurans and tetrachlorodibenzo-p-dioxins. N.Y. State Dept. of Health Report/ October 1, 1981. SWARTZ, W. J. (1980). Dissimilarities in the toxic responses of early chick embryos to DDT administered in different vehicles. Bull. Environ. Contam. Toxicol. 25, 898-901. WILSON, J. G. (1978). Review of in vitro systems with potential for use in teratogenicity screening. J. Environ. Path. Toxicol. 2, 149-167. WORLD HEALTH ORGANIZATION, Techn. Rep. Ser. (1967) No. 364. 12 �Figure Legend Fig. 1. The embryo lethality of Binghamton soot as a function of dose. Soot was administered to fertile chicken eggs in 0.1 ml 0.75% aqueous methyl cellulose through a hole into the air sac on day 4 of incubation. The viability of the embryos was assessed on day 18 of incubation. 13 �PERCENT LETHALITY f>0 O CO a a ^-s b O � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 090 Folder The folder containing the original item. 2289 Series The series number of the original item. Series IV Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Tumasonis, Casimir Laurence Kaminsky Title A name given to the resource Typescript: Preliminary Report: Chick Embryos as a Probe of the Relative Toxicities of Soot Samples from a Polychlorinated Biphenyl-Containing Transformer, [nd] Subject The topic of the resource BSOB PCBs animal studies https://www.nal.usda.gov/exhibits/speccoll/files/original/8e00b3c2c828a8548f18e5c8175df198.pdf e8943709ce3308fea7c257872cd8a80a PDF Text Text Item D Number 0219 Author Turner, J.N. ° Corporate Author RepOrt/ArtlOlB TltlB Typescript: Binghamton State Office Building SootInduced Morphologic Alterations in the Liver of Guinea Pigs, Preliminary Report Submitted to Dr. D.O. Carpenter, Januarys, 1982 Journal/Book Title Year 000 ° Month/Day Color Number of Images D 31 Thursday, September 20, 2001 Page 2190 of 2293 �BINGHAMTON STATE OFFICE BUILDING SOOT-INDUCED MORPHOLOGIC ALTERATIONS IN THE LIVERS OF GUINEA PIGS Preliminary Report submitted to Dr. D«0« Carpenter on 1/6/82 by J«,N. Turner, PtuD,, and D«>Ne Collins, M.D. Division of Laboratories and Research New York State Department of Health Albany, New York �ABSTRACT A fire in an office building transformer cooled with Pyranol which is composed of 65% Aroclor 1254 (containing tri, tetra, penta and hexachlorobiphenyls) and 35% chlorinated benzenes, resulted in contamination of the building with a fine sooto Due to the pyrolysis of the fluid mixture, the soot contains a number of polychlorinated organics, including biphenyls, dioxins, and dibenzofurans. As part of the evaluation of the soot's toxicity, it was dispersed in 0.75% methyl cellulose and administered by gavage to Hartley guinea pigs in a single dose* Animals were sacrificed after forty-two days and liver tissue was examined by light and electron microscopy. Hypertrophy of hepatocytes, fat infiltration, focal piecemeal necrosis, bile duct proliferation with fibrosclerosis, and hyaline-like bodies were observed by light microscopy. Proliferation of the smooth endoplasmic reticulum (SER), concentric membrane arrays (CMA), mitochondrial alterations, decreased rough endoplasmic reticulum (RER), and autophagolysosomes were observed by electron microscopy,, The CMAs frequently surrounded lipid droplets, but also encircled areas of the cytoplasm including mitochondria and degenerating organelles. These CMAs corresponded to the hyaline-like bodies observed by light microscopy. �On February 5, 1981 a fire occurred in the electric service transformer of the New York State Office Building in Binghamton, New York (henceforth referred to as the BSOB)0 The transformer was cooled and in- sulated with Pyranol-65% Aroclor 1254 (a mixture of polychlorinated biphenyls-PCBs) and 357= chlorinated benzenes. The building was contaminated with a fine soot subsequently shown to contain a number of PCB, dioxin, and dibenzofuran isomers including the highly toxic 2, 3, 7, 8 - tetrachlorodibenzo-p-dioxin (Schwetz, et al., 1973)» Chemical analysis was done and will be reported elsexvfhere by P. O'Keeffe and co-workers, Division of Laboratories and Researchj New York State Department of Health, The dioxin and dibenzofuran isomers x?ere formed by pyroloysis of the Pyranol (Butnb, et al., 1980; Buser, et al., 1978). A series of animal tests were designed and performed by Dr« L» Kaminsky and co-workers of the Division of Laboratories and Research, New York State Department of Health, to test the soot's toxicity. In one of these experiments, guinea pigs were fed a single dose of BSOB soot, and the morphologic alterations of their livers are reported here. Other experimental data and results will be presented elsewhere by Kaminsky and co-workers. Guinea pigs were selected as the experimental animal because they are more sensitive to dioxin and dibenzofuran intoxication than other laboratory animals including rats, mice, Rhesus monkeys, rabbits, and dogs (Gupta, et al», 1973; Harris, et al., 1973; Schwetz, et al., 1973; McConnell, et al., 1978; Moore, et al., 1979). The liver was of particular interest because it is a target organ for PCBs, dioxin, and dibenzofuran (Litterst, et al., 1972; Harris, et al,, 1973; Piper, et al,, 1973; Rose, et al., 1976; Gasiewicz and Neal, 1979)0 PCBs, and chlorinated dioxins and dibenzofurans all produce similar morphological alterations in the liver (Kimbrough, 1974), At the light microscopic �level the changes are: liver necrosis, fat infiltration, hypertrophy of hepatocytes, proliferation of bile ducts, and hyaline bodies in the cytoplasm of the hepatocytes. These observations have been reported in a number of species - rats (Bennett, et al., 1938; Miller, 1944; Jones and Butler, 1974; Gupta, et al., 1973; Greig and Osborne, 1978; Norback and Allen, 1973; Kasza, et al., 1976; Jonsson, et al., 1981), mice (Nishizumi, 1970; Gupta, et al., 1973), monkeys (Nishizumi, 1970; Norback and Allen, 1973; McConnell, et al., 1978), rabbits (Miller, 1944; Vos and Beems, 1971), and guinea pigs (Miller, 1944; Gupta, et al., 1973). The presence of a yellow- brown or brown pigment sometimes weakly staining for hemosiderin is reported for PCB intoxication, but not for purified dioxins or dibenzofurans (Nishizumi, 1970; Vos and Beems, 1971; Kimbrough, et al., 1972; Buse, et al., 1974; Jonsson, et al., 1981). The pigment is not, however, a consistent finding, and Kimbrough, et al., 1972, reported its presence in rats fed Aroclor 1242, but not in those fed Aroclor 1016. The presence of necrosis is frequently reported as single cell, focal, or piecemeal (Vos and Beems, 1971; Gupta, et al., 1973; Jones and Butler, 1974; McConnell, et al., 1978; Jonsson, et al., 1 8 ) 91, and altered hepatocytes were predominantly in the centrilobular region. Bile duct proliferation has been reported as a result of feeding both purified dioxin (Norback and Allen, 1973) and PCBs (Kimbrough, et al., 1972; Norback and Allen, 1972; Kasza, et al., 1976; Jonsson, et al., 1981). Adenofibrosis, generally taken to be the result of bile duct proliferation, has also been reported (Kimbrough, et al., 1972, and 1973; Kimbrough and Linder, 1974; Wassermann, et al., 1978). Kimbrough, et al., 1972, reported a higher in- cidence of adenofibrosis in female rats than in males. Kimbrough, 1973, re- ported extensive adenofibrosis and the development of pancreatic-type cells in rats chronically fed high levels of Aroclor 1254. �Animals fed purified dioxin have been frequently reported to have multinucleated hepatocytes (Jones and Butler, 1974; Gupta, et -al., 1973; Norback and Allen, 1973; Greig and Osborne, 1978; McConnell, et al., 1978). Jones and Butler claim these cells arise by cell fusion as opposed to mitosis. This is supported by the fact that none of the other authors report mitosis of bi or multinucleated cells. Similar cells have not been reported in PCB fed animals* Ultrastructurally, the livers of animals fed PCS or purified chlorinated dioxins and dibenzenofurans have similar alterations. These changes include proliferation of SER, decreased RER, large numbers of lipid droplets, concentric membrane arrays (CMAs), and mitochondrial alterations. For a review of these changes, see Kimbrough, 1974. Most workers report large numbers of lipid droplets,proliferated SER,and decreased RER (Nishizumi, 1970; Norback and Allen, 1972; Kimbrough, et al., 1972; Allen and Abrahamson, 1973; Jones and Butler, 1974; Kasza, et al., 1976; Jonsson, et alc, 1981). CMAs are also frequently reported in hepatocytes (Norback and Allen, 1972 and 1973; Kimbrough, et al., 1973; Allen and Abrahamson, 1973; Jonsson, et al., 1981). Mitochondrial alterations are occasionally reported and range from shape changes,to parallel arranged cristae,to severe deterioration and dense granulation in the matrix (Burse, et al., 1974; Jonsson, et al,, 1981). Jones and Butler, 1974 demonstrated multinucleated cells,and Greig and Osborne, 1978 demonstrated areas of lateral plasma membrane fusion. The morphological alterations of the liver of a wide variety of species fed PCBs,and chlorinated dioxins and dibeiizofurans are usually reported as similar to each other and a number of other toxic organic molecules (Kimbrough, 1974). The reports are not, however, completely consistent and may vary with respect to the mixture of compounds, dose,or method of administration. �Cockerham, et al,, 1980, for example, reported no liver alterations in beach mice exposed to dioxin. �METHOD Soot collected from the BSOB was suspended in 0.75% aqueous methyl cellulose, and administered in a single gavage at 1, 10, 100, and SOOmgm soot/kgm body weight to Hartley guinea pigs. of six males and six females. Each dose group was composed A fifth group was fed SOOmgm activated carbon/kgm body v/eight in 0.75% methyl cellulose as a control. An additional control group of six males was fed 0.75% methyl cellulose, while a second group of six males served as an untreated control. Female animals were eleven weeks old at the start of the test and the males were eight weeks old. All animals were sacrificed by suffocation in CC^ 42 days after administration of the single dose, and complete necropsy performed. free access to food and water during the test. Animals had This animal experiment was designed and carried out by L.S. Kamlnsky, J. Silkworth and D. McMartin of the Toxicology Institute, Division of Laboratories and Research, New York State Department of Health, and results, other than the liver morphology presented here, will be reported elsewhere. Two other untreated control groups, both composed of ten animals - five males and five females - were used for comparison to the experimental groups. One group was randomly selected from the New York State Department of Health's guinea pig colony. (Charles Rivers). The other group was from an outside commercial supplier These animals were sacrificed and necropsied in the same way as the experimental animals. Specimens from the liver of 91 guinea pigs (one female in the SOOmgm soot/kgm group died during the test) were processed for light microscopy. Samples from all livers were fixed in buffered formalin and embedded in paraffin. Sections were stained with hematoxylin and eosin ( & ) periodic HE, acid - Schiff (PAS), PAS after diastase,and phosphotungstic acid hematoxylin �;:t V- r> 'j _...:. i .•;;-! I.:1-.-1 • ' • L ^ ' . n i l r;:..;; J, S ; i • • ."_i 'i f. :• ~ o '• .•• !. o c1 c r o t : ; • d c r o s c o p / r,v -; r .- t : i '<. ^ a ( r OTI r a nci o m, L y r, ,-• L * o t a d i b y a.t;.''iu- ' f ". r.ir.ricim na::be': '<•.•'•> ] -) ,':-!Laci'A p > . 23 t r> - each doaa f.;roup, to a ace Lvct^u';! c'irbon C') p i::rc'i ,u : ;T'.p T aiid •'t'hfr ^ ^ i r r e a t ^ d c o n t r o l grc".sp» I~-."^ males r.ud t ;.;.-» f r f p ^ l . i s :-;er3 os'!dcc- o 'i fr-om o^oh losa l e v e l "nd iron tT"i« Two ^ - - ' ' - - ^ ?" ; -o 3 w^"^ d-lecced From i;'>.a ::a- acti vaf'eti c a r b o n eoi'crol... (.""Gti-ed n i l ma' 1 ^ 3 r o u p > ^?.i?.nl-3 ;/^re a]';o caken. _\'om one fenale pig f r o n tbs 'rrv^Vib-jt d w s ^ j j'.rox.p -/b'.ch wan ;.:or '.'r)'.".id ;.nd sacrificed aC Jay 17 into the I:-?:-.1:-, '"'tie l l v ^ ^ - j "-''" 2'3 ^ u i n ^ n ? ' - g a v?ra e--c -.nla-d by e l * c t r - > n aicr:\-;^ A cb ',:•>. ol t-.'e >~>'~ I ' , . ' - : - : :MJ r^-inov^d f-utn ca^ •jai-i.di-; ay so>;n a f c e r deacn .-.13 -i i un b u f f e r .'•,': ph 7u ; 't f 1 '^ one h n u r '.t- j.'^oja hydr\i"prl L-T.-e .- c^ t con: v.-ic'.': w 11 LrM i - -i t'">c"i n . o i: ?!j? ""'•-".••"^ -,;a."i ucaivyi. a c ^ f t c i �RESULTS Gross Observations and Light Microscopy At necropsy, single and occasionally multiple focal pale areas were observed on the surface of the livers of guinea pigs from all groups0 Microscopically, morphologic alterations in the hepatocytes were observed in the experimental .guinea pigs and in one guinea pig in the activated carbon control group (guinea pig No. 37), These alterations were: hypertrophy of hepatocytes, fat infiltration, focal piecemeal necrosis, bile duct proliferation with fibrosclerosis, and hyaline-like cytoplasmic inclusion bodies. Figo 1 is representative of the widespread fat infiltration It is a micrograph of a frozen section stained with oil red 0, observed. The fat droplets vary from cytoplasmic microdroplets to confluent globules larger than the nucleus. With the exception of No. 37, the control guinea pigs exhibited fat droplets of normal size, number and distribution. Fig. 2 sclerosis. illustrates proliferation of bile ductulea and fibroSeveral small duct-like structures intermingled with collagenous proliferation are evident. This alteration was observed in six female guinea pigs, two in the 1 mgm soot/kgm group, three in the 100 mgm soot/kgm group and one in the 500 mgm soot/kgm group, as well as in one male in the 500 mgm/kgm group, Fig. 3 shows a paraffin section stained with PTAH. Cytoplasmic alteration is reflected in the numerous discrete spherical hyaline-like bodies which stain an intense dark blue. These hyaline-like bodies shoxtf greater contrast and detail in PTAH stained than in H&E stained sections. of these hyaline-like bodies. Fig. 4 is a higher magnification They exhibit a wide range of sizes and shapes - some minute, others as large or larger than the nucleus„ Single round bodies ranging in size from 1.9 to 5.7/im are observed, some with clear centers (small �arrows), others of solid density (large arrows)0 Individual cells may contain several bodies or & confluent group. These groups may'be as large as lOum (double arrows). Figo 5 illustrates a l^im toludine blue stained plastic section. Hexa- gonally shaped hepatocytes appear enlarged and contain round appearing nuclei with prominant nucleoli. Binucleated cells, such as the one in the center of the field, are not uncommon. The hyaline-like bodies present in the cytoplasm display a wide range of sizes, and most have a light center with a dark peripheral annulus consisting of as much as 2/3's the diameter of the body. Multiple bodies are frequently seen in a single cell, and confluent groups as large as 14um are present. Many small bodies appear uniformly dense« The PAS and PAS/diastase stained sections showed normal amounts of glycogen in all animals. Electron Microscopy Electron microscopic examination of ultrathin sections show the following hepatocyte alterations: proliferated SER, CMAs, mitochondrial degeneration, decreased RER,and margination of organelles. All experimental anJmals and No« 37 show proliferated SER, frequently causing margination of mitochondria by increasing the cytoplasmic matrix. CMAs were most frequently observed surrounding fat droplets, and occasionally encompassing volumes of cytoplasm, mitochondria and degenerating organelles0 CMAs were, on occasion, found in the sinusoidal lumen. The mitochondrial alterations appeared to be of two types, changes in shape and lamination of cristae. All experimental animals and No. 37 showed variations in shape but variations in cristae were observed only in the two highest dose groups. Fig. 6 is a low magnification electron micrograph of 5 hepatocytes showing nuclei, lipid droplets, proliferated SER and margination of mitochondria. �Two large CMAs surround lipid droplets. Figo 7 shows details of two CMAs in which regularly spaced smooth membranes are arranged concentrically about lipid droplets* The outer membranes appear to be continuous with portions of the SER, Fig« 8 more clearly demonstrates this association of the membranes to a large lipid droplet^ The membrane layers nearest the lipid droplet are regularly and closely spaced, appearing to continuously surround the droplet. The outer layers are less evenly spaced and are irregularly organized with large protruding areas. The outermost membranes are continuous with portions of the SER as indicated by the arrows, and are present as discrete leaflets that appear to cover only part of the circumference of the CMA«, The sinusoid and associated perisinusoidal space of Disse occasionally contained cellular debris and CMAs as in Fig0 9. Fig* 10 shows three lipid droplets which are confluent and contain internal membrane fragments. The droplets are membrane bound, but lack concentric arrays as illustrated in Figs« 6, 7,and 8. Fig. 11 shows two lipid droplets with fragmented membranes internally, with concentric membranes associated with part of their circumference. Random condensations of SER associated with islands of proliferated SER are illustrated in Fig. 12. Alterations in the shape of mitochondria were occasionally noted. Fig» 13 shows many normal mitochondria, and one irregularly shaped one0 A pseudo-inclusioi composed of cytoplasmic components is evident in the large central mitochondria. The two highest dose groups show motochondria with parallel cristae. Fig. 14 is an illustration of this alteration. 10 �DISCUSSION The pale areas on the liver surface observed at necropsy in all groups have been shown to be manifested microscopically as coagulative necrosis, and to be present in otherwise normal guinea pig populations (Wagner and Manning, 1976). All of the control animals with the exception of guinea pig No, 37 in the activated carbon group showed morphologically normal livers at both the light and electron microscopic levels. The experimental animals in all dose groups exhibited alterations at both microscopic levels, demonstrating a toxic reaction to the ingestion of BSOB soot. Since guinea pig No» 37 was only one of fortyfour control animals and only one of twelve in the activated carbon group, the observation of morphologic alterations in its liver was not taken to be significant. An adequate control is., therefore, established and differences between control and experimental guinea pigs have been demonstrated. Comparison of the four dose groups did not produce differences, and to date the only alteration that is a function of the dose level is the parallel raitochondrial cristae observed in the 100 and 500 mgm soot/kgm groups. The morphologic alterations observed are consistent with those found by other workers in the liver of animals fed either PCBs or purified chlorinated dioxins (see Kimbrough, 1974 for a review). However, the current experiment did not exhibit the multinucleated hepatocytes observed by workers who fed purified dioxins (Gupta, et al,, 1973; Norback and Allen, 1973; Jones and Butler, 1974; Greig and Osborne, 1978), nor did other studies of PCB fed animals (Nishizumi, 1970; Kimbrough, et al., 1972; Norback and Allen, 1972; Allen and Abrahamson, 1973; Kasza, et al,, 1976; Jonsson, et al., 1981), Since PCBs, dioxins and dibenzofurans are present in the BSOB soot and the PCBs of the other studies were probably contaminated with 11 �dioxins, it appears that multinucleated cells are not formed when a mixture is present. The observation of bile duct proliferation with fibrosclerosis in seven of forty-seven experimental animals is consistent with a number of other reports in which animals were fed PCBs or dioxins (see introduction for references). It is difficult, however, to compare the various studies since the dose levels, number of doses, and time course of the experiments are different, Kimbrough, et al0, 1972 and 1973 report a large percentage of animals with this alteration, but their experiment involved multiple doses over longer time periods. Differences in toxicity of the particular compounds used may also be a variable as Kimbrough, et al», 1972 reported a difference between Aroclor 1254 and 1260» The possibility and extent of dioxin contamination in various PCB mixtures is also an unknown parameter. Kimbrough, et ale, 1972 reported an increased incidence in females as opposed to males, and six of the seven animals exhibiting the alteration in this study were females . Hyaline-like bodies in the cytoplasm of the hepatocytes have been observed in a number of studies for a variety of toxic organic molecules including PCBs, dioxins, and dibenzofurans (Kimbrough, 1974)D The CMAs at the ultrastructural level undoubtedly correspond to these bodies at the light microscopic level* This is also suggested by Kimbrough, 1974. The observation of the CMAs is consistent with many other studies in which a variety of species were fed PCBs or dioxins (Kimbrough, 1974, Jonsson, et al., 1981)0 Jonsson, et al0, 1981 suggested that the ejection of CMAs into the sinusoids and bile canaliculi was a mechanism to rid the hepatocyte of toxic materials. The ejection of CMAs and other cell debris into the sinusoids was also observed in this study. The ultrastructural alterations reported here are in general consistent with other reports, but some variation is also observed. For example, Jonsson, et al«, 1981 reported severe degeneration of mitochondria, but we observed few de12 �generated mitochondria,, The observation of parallel cristae in a small number of mitochondria in the two highest dose groups is in agreement with the results of Burse, et al,, 19740 The increased SER and decreased RER is in agreement with all previous studies of PCB, dioxin and dibenzofuran intoxication except Fowler, et al., 1973 who reported an increase in RER in rat hepatocytes following a single oral dose of dioxin. The condensed, laminated SER of Fig. 12 has not been previously reported, but was occasionally observed in some experimental animals, The morphological differences between control and treated guinea pigs demonstrate a toxic effect due to the ingestion of BSOB soot, but dose level related effects have not been documentede The alterations reported here and in the literature vary in some details, but are generally consistent. The explanation of the variation in morphological alterations cannot be determined at this time, but is probably a complex function of sampling, ingested moleculeSjdose level, number of doses, time course of the experiment, and animal species. 1,3 �REFERENCES l e "Allen, J.R., Abrahamson, L.J, Morphological and biochemical changes in the liver of rats fed polychlorinated biphenyls0 Arch, Environ, Contam. Tox. 1., 265-280, 1973. 2. Bumb, R.R., Cruramett, W.B., Gutie, S.Se, Gledhill, J0R0, Hummel, R,H., Kagel, R.O., Lamparski, L.L., Luoma, E0V., Miller, D0Le, Nestrick, T.J., Shadoff, L.A., Stehl, R.H., Woods, J.S. Trace chemistries of fire: a source of chlorinated 'dioxins. Science 210, 385-390, 1980, 3. Burse, V.W., Kimbrough, R.D., Villanueva, E.G., Jennings, R.W., Linder, R.E., Sovocool, G»W» Polychlorinated biphenyls. Arch. Environ, Health 29., 301-307, 1974. 4» Buser, H.R., Bosshardt, H.P«, Rappe, C» Formation of polychlorinated dibenzofurans (PCDFs) from the pyrolysis of PCBs, Cheraosphere !_, 109-119, 1978. 5. Cockerham, L.G., Young, A.L., Thalken, C.E. Histopathological and ultrastructural studies of liver tissue from TCDD-exposed beach mice FJSRL. Technical Report 80-0008, United States Air Force, 1980. 6» Fowler, B,A«, Lucien, GeW«, Brown, H.W., McDaniel, 0 S , . Ultrastructural changes in rat liver cells following a single oral dose of TCDD» Environ. Health Perspectives 5_, 141-148, 1973, 7. Gasiewicz, T.A., Neal, R,A« 2,3,7,8-tetrachlorodibenzo-p-dioxin tissue distribution, excretion and effects on clinical chemical parameters in guinea pigs. Tox. Appl. Pharmacol. 51, 329-339, 1979. 8. Greig, J.B., Osborne, G. Changes in rat hepatic cell membranes during 2,3,7,8 tetrachlorodibenzo-p-dioxin intoxication. In: Dioxin (edc F, Cattabeni, A. Cavallaro and G« Galli), SP Medical, and Sci3ntific Books, a division of John Wiley, New York, 1978. 9. Gupta, B.N., Vos, J.G., Moore, J.A», Zinkl, JaG., Bullock, B.C, Pathologic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in laboratory animals. Enriron. Health Perspectives 5_, 125-140, 1973. 10. Harris, M.W., Moore, J.A., Vos, J.G», Gupta, BeN, General biological effects of TCDD in laboratory animals. Environ. Health Perspectives 5_, 101, 1973. 11. Jones, G., Butler, W0H. A morphological study of the liver lesion induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. J. Pathol0 112, 93-97, 1974. 14 �12. Kasza, L., Weinberger, M.A., Carter, C0, Hinton, D.E., Trump, B.F., Brouwer, EoA. Acute,subacute and residual effects of polychlorinated biphenyl (PCB) in rats II Pathology and electron microscopy of liver . and serum enzyme study. J 0 Tox» and Environ, Health !_, 689-703, 1976. 13. Kimbrough, R.D. The toxicity of polychlorinated polycyclic compounds and related chemicalsdn: Critical Reviews in Toxicology (ed. L. Goldberg). The Chemical Rubber Co,, West Palm Beach, Fla., 1974. 14. Kimbrough, R.D., Linder, R.E., Gaines, T.B. Morphological changes in livers of rats fed polychlorinated biphenyls. Arch, Environ» Health 25., 354-364, 1972. 15. Kimbrough, R.D., Linder, R.E., Burse, V.W., Jennings, R0W. Adenofibrosis in the rat liver. Arch. Environ. Health 27, 390-395, 1973. 16. Kimbrough, R.D., Linder, R.E, Induction of adenofibrosis and hepatomas of the liver in Balb/cJ mice by polychlorinated biphenyls (Aroclor 1254)» J. Nat. Cancer Inst. 53., 547-552, 1974. 17. Litterst, C.L., Farber, T.M., Baken, A.M. van Loon, E»JC Effect of polychlorinated biphenyls on hepatic microsomal enzymes in the rate Tox. Appl. Pharmacol. 23, 112-122, 1972. 18. McConnell, E.E., Moore, J«A0, Dalgard, D.W. Toxicity of 2,3,7,8tetrachlorodibenzo-p-dioxin in Rhesus monkeys (Macaca mulatta) following a single oral dose. Tox* Appl* Pharmacol. 43, 175-187, 1978a, 19. McConnell, E0E., Moore, J 0 A 0 , Hoseman, J.K», Harris, M.W» The comparative toxicity of chlorinated dibenzo-p-dioxins in mice and guinea pigs. Tox. Appl, Pharmacolc 44, 335-356, 1978b. 20. Miller, J.W. Pathologic changes in animals exposed to a commercial chlorinated biphenyl. Public Health Rep. 59., 1085-1093, 1944. 21m Moore, J.A., McConnell, EeE., Dalgard, D.W., Harris, M»W. Comparative toxicity of three halogenated dibenzofurans in guinea pigs, mice, and Rhesus monkeys. Ann. N.Y. Acad. Sci. 320. 151-163, 1979. 22. Nishizumi, M., Fukuoka, M.D. Light and electron microscope study of chlorobiphenyl poisoning. Arch. Environ, Health 27, 16-21, 19700 23» Norback, D.H., Allen, J.R, Chlorinated aromatic hydrocarbon induced modifications of the hepatic endoplasmic reticulum: concentric membrane arrays. Environ. Health Perspectives 1., 137-143, 1972, 24. Norback, D»H., Allen, J,Ri> Biological responses of the nonhuman primate, chicken, and rat to chlorinated dibenzo-p-dioxin ingestions Environ, Health Perspectives 5_, 233-240, 1973. 15 �25. Piper, W.N., Rose, J.G., Gehring, P.J. Excretion and tissue distribution of 2,3,7,8~tetrachlorodibenzo-p-dloxin in the rat. Environ. Health Perspectives 5_, 241-244, 1973. 26. Rose, J.Q., Ramsey, J.C., Wentzler, T.H., Hummel, R.A., Gehring, P.J. The fate of 2,3,7,8-tetrachlorodibenzo-p-dioxin following single and repeated oral doses to the rat. Tox. Appl. Pharmacol. 36, 209-226, 1976. 27. Schwetz, B.A., Norris, J.M., Sparschu, G.K., Rowe, V.K., Gehring, P.J., Emerson, J.L., Gerbig, G.C, Toxicology of chlorinated dibenzo-p-dioxins, Environ. Health Perspectives 5_, 87-99, 1973. 28. Vos, J. G., Beems, R.B. Dermal toxicity studies of technical polychlorinated biphenyls and fractions thereof in rabbits. Tox. Appl. Pharmacol. 19., 617, 1971. 29. Wagner, J.E., Manning, P.J. Press, New York, 1976. Biology of the Guinea Pig. Academic 30. Wassermann, D», Miller, H.J., Wassermann, M. Polychlorinated biphenyls induced rat liver adenomas. Tox. European Res. 1^, 159-172, 1978. 16 �FIGURE LEGENDS Fig. 1 is a photomicrograph of a frozen liver section stained with oil red 0 Magnification is 500X, . Figo 2 is a photomicrograph of an H&E stained paraffin section of liver from an area of bile duct proliferation with fibrosclerosis. Magnification is 800X. Fig. 3 is a photomicrograph of a PTAH stained paraffin section of the liver. The magnification is 320X. Fig, 4 is a photomicrograph of a PTAH stained paraffin section of the liver. The hyaline-like bodies are indicated by the arrows: clear centers by the small arrows, dense bodies by the large arrows, and a confluent group by the double arrow. The magnification is 800X. Fig. 5 is a photomicrograph of a lura plastic section of the liver stained with toludine blue. The magnification is 800X. Fig, 6 is an electron micrograph of an ultrathin section at 5,100 times magnification. The nuclei (N), lipid droplets (Li), concentric membrane arrays (CMA), and mitochondria (Mi) are readily observed. Fig, 7 is an electron micrograph of three CMAs viewed at 26,192X magnification. Fig, 8 is an electron micrograph of a portion of a CMA around a lipid droplet (Li). The arrows indicate areas of continuity between the outer CMA membrane and the SER. Magnification is 18,OOOX» Fig. 9 is an electron micrograph of a CMA in a liver sinus. A red blood cell (RBC) and Disse space (DS) are seen. Magnification is 18,OOOX. Fig. 10 is an electron micrograph of three lipid droplets and their associated membrane systems in a hepatocyte. Magnification is 18,OOOX. Fig. 11 is an electron micrograph of two lipid droplets x^ith associated 17 �membrane systems, and some areas of parallel aligned SER in a hepatocyte. Magnification is 18,OOOX. Fig« 1.2 is an electron micrograph of areas of condensed SER in a hepatocyte. Magnification is 18,OOOX0 Fig, 13 is an electron micrograph of several mitochondria in a hepatocyte. Magnification is 18,OOOX. Fige 14 is an electron micrograph of several mitochondria, two of which have parallel arranged cristae. Magnification is 51,000x. �• « \{'«s*' T&M?**^ ^.'''^Vkv'V ^'5-5r E _ rs-*J«*S«Sr ^ r If!nxr-* tte,™!". •» A* S ^ ^; .^^rr * ' .s-tW t.fiSzi.te&t^-J' j • *•* f •* �^^^srar$ • f/^Q3^v^i : ^n>'n:V; X>V;>V,V;- A^r^w. -.^''/V^- •*&•<"*>, c/- c,. i^ 4\^ - Jj "T^Z^T^^ -' "V^Wr.,e£ ; i"^^ • - ^^?^^^v^. fr^^x A-3 .iy % 20 �5«'**^^.*3ti^:^^*7^->>*^S"^JSl - •.' *''-:#*?'** 1--.S'•'•' , ^-^ VrfV^A^.l^'^^irr^-V'iW^v^V^ ' >- j, . • - • , •* V ... l ' ' • '' ' ' . - • - . • • ;'-.• .- »/•• ' • " ' * ' v '«•••• • ' • - • "•'.. 22 ' , ."' ; ' • ri* . '• - \ ^ f* . .. ' '. ' j '.'•.*"'.-- • ts^ti. •* / ' . ' " • ' ''•',-\:'";"'" "ii* •• • • �ft?^*** _._^^^Jij4—XcAv.^;-.tw-^^:l;.,-.,.; .i.g>.ciA.^> rt, ,n',i,A Jt'^.fA,-j..J. 21 �23 �24 �V 25 �WvV^lSfl : •j£f' ^iS" Jy^ll^^ 26 �27 �28 �/ �r -1.V'».'-«?-«2.T:Sl'vii v! ;W '*'«k1~V5 ^^^a^m^£vM> N 30 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 087 Folder The folder containing the original item. 2190 Series The series number of the original item. Series IV Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Turner, J.N. D.N. Collins Title A name given to the resource Typescript: Binghamton State Office Building Soot-Induced Morphologic Alterations in the Liver of Guinea Pigs, Preliminary Report Submitted to Dr. D.O. Carpenter, January 6, 1982 Subject The topic of the resource BSOB animal testing PCBs Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 087 Folder The folder containing the original item. 2171 Series The series number of the original item. Series IV Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Date A point or period of time associated with an event in the lifecycle of the resource April 3 1981 Title A name given to the resource Typescript: Binghamton State Office Building Panel Meeting Presentation Subject The topic of the resource BSOB building remediation decontamination PCBs https://www.nal.usda.gov/exhibits/speccoll/files/original/853b047330bd474a0bc02eb0ee2e5c84.pdf 73689b98be00e93815db3d804a567c57 PDF Text Text Item D Number 02133 Author Smith, P.M. Corporate Author ROport/APtlClO HUB Typescript: Analysis of a Binghamton Soot Sample for Tetrachlorodibenzofurans and Tetrachlorodibenzo-pdioxins, October 1, 1981 Journal/Book Title Year Month/Day Color Number of Images D 21 Descrfyton Notes Thursday, September 20, 2001 Page 2183 of 2293 �Analysis of a Binghamtcm Soot Sample for Tetrachlorodibetizafurans and ;" --Tetrachlorodibenzo-p-dloxins R.M. Smith., D.L. Hilker, P.W. O'Keefe, S. Kumar, J. O'Brien, B.L. Jelus-Tyror, K. Aldous October 1, 1981 �INTRODUCTION A fire caused by a malfunctioning PCB-filled transformer in the Binghamton state office building on February 6, 1981 released an unknown amount of incomplete combustion products into the 18-story building. A sample of soot (Tox. No. 811711965) was collected from an unspecified area * u of the building using a vacuum cleaner. " A portion of the homogenized soot, intended to be used for animal toxicology studies, was soxhlet extracted for 16 hrs in benzene and analyzed for TCDF's and TCDD's by capillary GC/High resolution mass spectrometry (HUMS). PROCEDURE Fifty yl of the benzene extract (corresponding to 46 mg soot) was spiked with 6 ng of 13 C labelled 2,3,7,8-TCDD and cleaned-up prior to GC/HRMS injection using sequential liquid chromatographic columns containing PX-21 adsorptive carbon, 2% deactivated silica gel, and activated Florisil. An .-.-!. ;. aliquot of the concentrated sample was then injected onto a 40 m x 3 mm OV275 coated soda glass GC capillary which is interfaced to the MS-50 HRMS through a jet separator. The temperature was appropriately programmed and mass profile data was accumulated for the m/e 306 CTCDF), 322,320 (TCDD) and 334 (13C TCDD) ions. 13 Standards ( C 2,3,78-TCDD and unlabelled 2S3,7,8-TCDF) were run. prior to sample injection. A control sample of Fisher activated coconut charcoal was similarly spiked and analyzed. RESULTS AND DISCUSSION The sample was found to contain a complex mixture of TCDFs as shown in the chromatogram in Figure 1. present. At lea'st twelve distinct TCDF peaks are 2,3,7,8-TCDF eluted as peak No. 12 as determined by comparison with an injection of authentic 2,3,7,8-TCDF. Trie presence of amounts of tetrachloroclibenzo-p-dioxicis in the sample are indicated by the M3 chroma tog ram �—3- in. Figure 2. Closer inspection of the data revealed the presence of an interferent. However the data system allowed consideration of -the intensity due to tetrachlorodioxin ions which were partially resolved from the interferents (Figure 3 . ) The interferent appears at an m/e value very similar to that of the [M ~C1] fragment of heptachlorobiphenyl. Signal detected in the dioxin ion position in the m/e 321.8936 mass region, which occurred at the same time in the chromatogram as the being due to native 2,3,7,8-TCDD. C-2,3,7,8-TCDD were taken as This implies a relative retention tine of 1.00 for native 2,3,7,8-TCDD. The quantitative results of the analysis of the. samples are summarized in Table I. and TCDD. The figures given in the table denote only "detectable" TCDF The sample cleati-up procedure that was used requires the use of isotypically labelled standards to correct for low recovery. Presently, no labelled TCDF is available and the assumption was made that the recovery of all TCDF and TCDD isomers was the same as that of the 13 C labelled 2,3,7,8- TCDD internal standard based on preliminary TCDF recovery experiments. Although the capillary GC column gives a high degree of isomer separation, the analysis should not be considered completely 2,3,7,8-TCDD or TCDF isomer specific as other isomers may co-elute. The unexpectedly large amounts of TCDFs found in the sample exceeded the linear range of the HEMS, making a second injection using less sample necessary (Fig. 4) for proper quantitation (All calculations and several important mass profiles are included in the appendix). No TCDDs or TCDFs were found in the control carbon. The results show that concentrations of TCDDs and TCDFs in this soot appear to be similar to those found in soot TOX No. 811710280 and air particulate sample Tox No. 811710977 previously taken from the Binghamton state office building. �u TIME: Ml 166 �B-S55 HIGH RESOLUTION MPM .» • RUNNRME FDHM3 DOTE 7/10/81 TT-H TIME G9:30 L 05:30 1 1 10:30 1 TIME 21 :11 20:30 1 ,* ?5:30 ric Ml 12 13 14 . 105 1 209 313 41? *DL * DRTE 7/10/81 TIME 21:11 RUNHRME FDHM8 SWEEP 300 (PPM) SCRNTIME 0.3 (SECS) MRSS 305.8936 SCflNS 194-205 100'-S INTENSITY 143676 100 75 305.8527 305,8986 395.9445 �R U N N f l M E FTJHM9 •MBSS 321.893B SC.RNS 149-433 IIRTE 7/1D/81 TlM'E 21 i l l SWEEP 389 ( P P M ) S C f l N T I M E 0.3 I N T E N S I T Y 442547 CSECS) 109 25 321.8452 *BL HOU KRNY RRERS73* 321.8935 DSSS HIGH RESOLUTION MP« PERK SUtlilRTION REPORT RUNNflJIE FBHM8 DOTE 7/10/81 TIME 21 i l l MOSS 321.8935 389 PPM SCflN WIDTH SCRN TIME 6.3 SECS SCRN NUMBERS 149- 438 STRNDflRD FflCTOR 0.6899 0 KflMINSKY'S BING. SOOT 2.S5 OF 9.0UL MPSS ITEM CENTROID ' 321.8789 TOTRL 321.8733 1 321.9021 2 321.9331 3 RREfl - 'BRSELIHE BRSELINE SUBTRflCTED SKIMflED 32772100. YES NO 27343790. YES NO 5367326. YES NO 61077. YES NO •<TOTfiL RELATIVE RRER TO STflNBRRB 95.17 0.00 79.41 0.00 IS.59 0.G0 Q.18 0.00 �bfcC0JUft • 720 SCITSS6A HIGH RESOLUTION MPM •„• RUNNflJlE TDHM4 DflTE 7/16x81 "I vit -*- *>/ ** TINE 12i28 RETN TltlE ,60:39 , ,03:39 ^16:39 n- .* 2 : 3 a . f t20130 TIC 305.8986 '^l 060255 Ml M2 ?=Ty^y2^?" 1 • ~T r- 105 1 1 209 *DL * DS55 HIGH RESOLUTION MPM RUNNflJIE TDHM4 DfiTE 7/16/81 RETN TIME 69:39 rw r"' •™""r"—r* 313 r 417 TIME 12:28 04 ;39 20! 38 . 313 *DL * 180'-S» 1869255 '4 1 ? �Table I. Results for Sample 811711965* TotalVpuran Concentration - 597 ppm (Detection Limit = 2.3 ppm) 2,3,7,8-Furan Concentration - 48 ppm (D.L. - .45 ppm) Total Dioxin - 1.8 ppm (D.L. = .04 ppm) Ratio 320/322 = 0»87 2,3,7,8-Dioxin - 1.2 ppm (D.L. =.008 ppm.) Ratio 320/322 = 0.86 Recovery - 4% Amt. of 13 C-2,3,7,8-TCDD spike - 6000 pg Weight of Sample - 46 ing Cone, of Spike - .13 ppm Relative Retention Times: 2,3,7,8-tetrachlorofuran - Standard: .1.264 Sample: 1.269 2,3,7,8-tetrachlorodioxin - Sample: 1.00 No TCDF or TCDD was found in the control carbon sample �_APPENDIX: Supplementary Data 1. Carbon blank 2. External standards 3. Mass profiles 1st injection-Runname FDHM8 4. Second injection data-Runnarae TDHM4 5. Calculations �DS55 HIGH RESOLUTION MPM RUNNRME: FBHM? DRTE RFTH TIME 60; 30 t • 85; 39 r1"" TINE 20»26 15i39 . f 25:38 'TIC Ml M2 «3 N4 101 **> 201 301 T" �BS55 HIGH RESOLUTION MPM •RUMNRME FBHMb DOTE 7/18/81 RETt) TIME 03:39 J TIC M2 M3 M4 03:39 j i 06:30 J TIME 19:43 L 89:38 j L. 12:39 15 �-T<rr>1L linear ravine m » sT RUNNflME FDHN8 DflTE 7/10/81 TIME 21jll MflSS 395.8986 SUEEP 300 (PPM) SCRNTIME 8.3 CSECS) SCRNS 149-438 188'< INTENSITY ?9?1778 108 305.8986 395.8527 *SK OREO IBt2 DS55 HIGH RESOLUTION MPtt PERK SUMMRTION REPORT RUNNflUE FDHM8 DflTE 7/10/81 TIME 21 ill MOSS 3D5.8987 SCRN UIDTH 300 PPM SCflH TIME 0.3 SECS SCflN NUMBERS 149- 438 STflNDflRD 6.0000 FRCTOR 0 KRMIHSKY'S BING. SOOT 2.55 OF 9.8UL MRSS CEHTROID 305.9972 3Q5.8716 385.9972 305 .9333 ITEM TOTRL 1 2 3 RREfl 585240398. 1871699. 551408180. 1415924. BRSELINE BRSELINE SUBTRRCTED SKIMMED YES HO YES NO YES YES YES NO '•iTOTRL RELRTIVE RRER TO STflNDRRD 98.97 6.00 0.32 0.0Q 93.25 0.60 0.24 0.C0 �FHHK§ DATE! 7/10/81 TIME: 21111 MOSS 333.9335 SUEEP 399 (PPM) SCRNS 279-307 10ET-S INTENSITY 4589 SCRHTIME 0.3 CSECS) 333.9335 333V8835 333.983^ BS55 HIGH RESOLUTIOH MPJ1 PEflK SUMMflTION REPORT RUNNfiME FDHM8 DflTE '7/10/81 TIME 2It'll MflSS 333.9336 SCflH U1TJTH 309 PPM SCflN TIME 8.3 SECS SCRN NUMBERS 279- 307 STRNBflRD 0.0000 FflCTOR 0 KflMIHSKY'S BIHG. SOOT 2.SS OF 9.0UL MfiSS CENTROID 333.9351 333.8982 333 .9402 333.9746 ITEM TOTOL 1 2 RREfl 319029. 44037. 223488. 17729. BRSELINE BflSELINE SLIBTRRCTED SKItlMED HO YES NO YES YES YES NO YES •<TOTPL RELRTIVE RRER TO STRHDRRB 66.S4 e.ea 9.19 0.00 46.61 0.08 3.70 0.08 �U.3 ISECS) •SCRNS 279-397 188** INTENSITY 83676 109 25 321.8935 321.84S2 321.9418 DSB5 HIGH RESOLUTION MPW PEflK SUMMRTIOH REPORT RUNHRME: FDHMS DRTE TIME MflSS 321.8935 SCflN WIDTH 308 PPM SCffN TIME 8.3 SECS SCflN NUMBERS 279- 307 STBMDflRD 0.8008 FflCTOR 0 KRMINSKY'S BIHG. SOOT 2.55 OF 9.8UL MflSS CEHTROID 321 .8323 321 .8748 321 .9023 321 .9319 ITEM TOTflL 1 2 7275879. 5220057. 2050417. 5485. BRSELINE BRSELINE SUBTRfiCTEET S K I M M E D HO YES YES YES YES HO NO NO RELfiTIVE flREfl TO STRNBflRD 97.33 8.00 69.83 0.QO 27.43 0.08 0.07 0.00 v.TOTOL �•RUNNRME FDHMB J3RTE 7x10x81 TIME 21 11 MRSS 319.8964 SUEEP 300 (PPM) SCflNTIME 0.3 (SECS) SCflNS 149-438 1.00*4 INTENSITY 89622 180 25 319.8483 *SK RREfl JD:2 319.94?S ~3T9.89~S"4" DSB5 HIGH RESOLUTION MPM PERK SUMMATION REPORT RUNNRtlE FDHM8 BflTE 7/10x81 TIMESltll HflSS 319.8965 SCflN UIBTH 300 PPM SCRN TIME 0.3 SECS SCON NUMBERS 149- 438 STflNDflRB 0.8009 FfiCTOR 8 KflMINSKY'S BING. SOOT 2.55 OF 9.0UL MflSS CENTROID 319.8972 319.8596 319.8930 319.9319 ITEM TOTRL 1 2 E364537. 79597. 46853S7. 66501 . 3RSELINE BRSELINE SUBTRflCTED SKIMMED HO YES NO YES YES YES NO YES "sTOTflL RELPT1VE RRER TO STRNDflRD 72.82 6.00 1.98 C.B0 63.60 0.B8 8.99 0.0B �.MOSS 305.8936 SWEEP 390 (PPMl SCPHS 338-406 109'-: INTENSITY 31138 SCFWTINE 0.3 (SECS) 1,39 305.852? 305.8986' DS55 HIGH RESOLUTION MPM PERK SUMMflTION REPORT RUHNflME TDHM4 BRTE TIME 12»28 MOSS 305.8987 SCOH UIDTH 309 PPM SCON TIME 0.3 SECS SCflH HUMBERS 388- 406 STflNBPRD 0.0009 FflCTOR 0 l.PUL D-ILUTIOH OF KflMINSKY'S SOOT MPSS ITEM CEHTROID 395.8933 305 .8613 305.8938 335.9392 TOTflL 1 2 3 flRER 2859185. 14863, 1917649. 11737. BflSELIHE BRSELIHE •SUBTRflCTED SKIMMED HO YES HO YES YES YES NO YES VTOTflL RELfiTIVE RREfl TO STRHDP.RB 6.00 95.36 0.00 0.69 89.20 0.00 0.55 0.00 �I 1 1 t n I I !_ i JJ I 1 1 > I •MOSS 305.8986 SUEEP 300 (PPtli SCRHS 214-478 189V: INTENSITY 379262 SCflNTIME 8.3 (SECS) TcD'f Joe 306.8527 30'6.8986 80S. 9445 DS65 HIGH RESOLUTION MPtt PERK SUMMflTION REPORT RUNNflME TBHM4 DflTE .7/16x81 T I M E 12$28 MflSS 385.8987 SCflN W I D T H 300 PPM SCPH TIME 8.3 SECS SCflN NUMBERS 214- 478 STflHDBRB 8.0080 FflCTOR 8 1.0UL B'lLUTIOH OF KRMIHSKY'S SOOT MRSS CENTROID 305.8948 305.8611 305.8948 385.9309 ITEM TQTflL 1 2 3 flREfl 25127260. 64216. 24077639. 73307. BRSELINE EflSELINE 'SUBTRflCTED SKI TIMED YES NO YES HO YES YES YES HO '-iJOTRL RELRTIVE RRER TO STRNDR.RB 92.56 0.08 0.24 0.08 88.70 8.08 0.27 8.00 �Calculation of Response Factor of Furau to Dioxia Asit of TCDF injected = 1.2 yL of 150 pg/uL Int of TCDF con = 677482 Sensitivity = 677482/180 = 3764 counts/pg Amt of 13 C TCDD injected ~ 1.0 uL of 600 pg/^L Int. of TCDD ion = 1949179 Sensitivity = 1949179/600 = 3249 counts/pg. Response Factor of Furan is 3764/3249 « 1.16 For equal amounts of material, the response of TCDF is 1.16 times 13 C TCDD, �Calculation, of Furan in peak number 1 (this peak was used as internal furan standard for the second injection) Amt Furan = X305 x <Amt 13c I / 334> *R -F- 1305 = intensity of m/z 305 ion for peak no. 1 (the small peak delimited which has not saturated the amplifier) = 8596844 Anit|, = Amt of 1J C = 6 ng C-TCDD spike (internal std.) added to sample I334 = intensity of m/z 334 ion (int. std.) = 223480 R.F. = response of 2,3,7,8-TCDF compared to 13C 2,3,7,8-TCDD =1.16 Amt Furan = 8'597x ^6 ng/.223480) x 1.15 - 268 ng �Calculation of 2 , 3 , 7 , 8-TCDF ^ 3 8 = J2378X 2 7 Amt2378 = amt of 2, 3 ,7, 8-TCDF I 2378 = intensity of 2,3,7,8-TCDF ions = 1917649 , « amt of furan in peak 1 = 268 ng I = intensity of furan in peak 1 = 235188 = 1.918 x (268/235) - 2187 ng Conc2378 = 2187 ng/46 mg «= 48 ppm Calculation of Total TCDF - ITOT = 24. -78 x (268/.23S) *= 27459 ng Cone = (27459 ng/46 mg) = 597 ppm �Calculation, of 2,3,7,8-TCDD (scans 279-307) 1 2378 X -^Vj » 2.050417 x (6/.223480) =* 55.04 ng Conc___ — 55.0 ng/46 mg Z3/O =1.2 ppm CalcualtiQn of Total TCDD (scans 149-438) Ant TOT =1 x (Ant 13 C/Io ) = 5.367 x (6/. 395528) = 80.4 ng ac23 - = 80.4 ng/46 mg — 1 . 8 pptn � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 087 Folder The folder containing the original item. 2183 Series The series number of the original item. Series IV Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Smith, R.M. D.L. Hilker P.W. O'Keefe S. Kumar J. O'Brien B.L. Jelus-Tyror K. Aldous Title A name given to the resource Typescript: Analysis of a Binghamton Soot Sample for Tetrachlorodibenzofurans and Tetrachlorodibenzo-p-dioxins, October 1, 1981 Subject The topic of the resource BSOB PCBs analytical studies https://www.nal.usda.gov/exhibits/speccoll/files/original/d18c92ba1c7b5858ce473a3255575d2e.pdf fc5119254c705b4269445699dfd21b7f PDF Text Text Item D Number °2212 Author Gierthy, John F. Corporate Author RODOrt/APtlClO TItiB Typescript: A Preliminary Report on the Evaluation of an In Vitro Assay for the Detection of "Dioxin-Like" Activity Using Extracts of Soot from the Binghamton State Office Building, 1982 Journal/Book Title Year Month/Day Color Number of Images D 28 Thursday, September 20, 2001 Page 2212 of 2293 �A Preliminary Report on the Evaluation of an In Vitro Assay for the Detection of "Dioxin-Like" Activity Using Extracts of Soot from the Binghamton State Office Building ~? "by John F. Gierthy and Gerald D. Frenkel New York State Department of Health Division of Laboratories and Research �.V " ' Abstract. As a result of the involvement of an electrical transformer containing polychlorinated biphenyls (PCBs) and chlorinated "benzenes in a fire in the Binghamton State Office Building (BSOB), the structure was contaminated vith soot ladened with dioxin congeners and isomers, which included 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8 TCDD) and 2,3,7,8-tetrachlorodibenzofuran (2,3,7,8 TCDF). A panel of experts, which was convened to examine decontamination procedurestrecommended the development of a short term assay for these compounds, based on an in vitro model of the in vivo chloracne response to dioxin exposure. This assay uses the dioxininduced keratinization of epithelial cell cultures as an endpoint. This endpoint is evaluated by eye, using intensity of the keratin specific stain, Rhodamine B, as a marker. This report describes the evaluation of the potential utility of such an assay as a rapid, semiquantitative screen for monitoring the BSOB decontamination process. Initial experiments using a 2,3,7,8 TCDD standard established that the kera.tinization model could be duplicated in this laboratory. A soot sample from the building for which levels of 2,3,7,8 TCDD and 2,3,7,8 TCDF had been determined by mass spectrometry, was tested in this in vitro system. The resulting activity was of the same order of magnitude as expected from the content of TCDD and TCDF as determined in the mass spectrometry analysis. Twelve extracts of soot from various floors of the building were tested for their activity in the assay. Activity of soot extracts from the various floors ranged over three orders of magnitude with samples from the lower floors generally having lower activity. These studies have also lead to the observation that after exposure to 2,3,7,8 TCDD, cells in the assay undergo a change in morphology characterized by the appearance of flat, apparently nonproliferating cells. This change in morphology, when used as an endpoint, correlated well with the keratinization endpoint and thus �ii may form the basis of an alternative and possibly better in vitro assay for dioxin congeners and isomers. A possible correlation between the keratinization activity and the PCB content of these soot extracts was observed. Preliminary assays on a PCB mixture (Aroclor 125H), which utilized the flat cell morphology as an endpoint, have indicated that this correlation was probably not due to a direct effect of the PCBs on this assay. The effect of a proposed decontamination agent, Triton X-100, was also tested using this endpoint. A concentration of 0.1 vil/ml was toxic while lower levels had no activity in this assay, nor did they affect the sensitivity of the assay to 2,3,7,8 TCDD. The keratinization assay exhibited a decrease,with time, in the magnitude of the response to the point that keratinization was characterized by the appearance of colonies of keratinizing cells on a background of nonkeratinizing cells. These cultures could be evaluated microscopically and there was no loss of sensitivity to 2,3S7»8 TCDD associated with the decline of the response magnitude. Efforts to determine the cause of the decline, and to reverse it, are discussed. �The occurrence of polychlorinated di"benzo-p-dioxins (PCDD) and dibenzofurans (PCDP) in the environment poses a serious potential threat to human health. These compounds are among the most toxic and teratogenic low molecular weight compounds known (Poland et_ al_. , 1976). • Chlorinated dibenzo-p-dioxins are formed from the condensation of two orthochlorophenates under conditions of high alkalinity, pressure and temperature. The combustion, chemical nature and combustion chamber residence time can also lead to the production of PCDDs and PCDFs. This has been verified by the analysis of flue gas emission and fly ash of some municipal incinerators in the Netherlands (Hutzinger et_ al_. , 198l). (Langer et_ al_. , 1973). This process has also been observed in laboratory models The pyrolysis of organohalogens such as chlorinated phenols and PCBs lead to the formation of PCDDs and PCDPs. This observation was evidenced under field conditions recently in New York State. On February 5, 1983., as a result of fire, the Binghamton State Office Building (BSOB) was heavily contaminated with soot; subsequent cleanup efforts were halted when chemical analysis indicated the presence of high levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,3,7,8tetrachlorodibenzofuran (TCDF) as well as other possibly toxic congeners (Smith et al., 198l). This contamination was traced to the involvement by fire of an electrical transformer which contained the dielectric fluid Pyranol, a mixture of PCBs composed of Aroclor 125^ and chlorinated benzenes. A number of human exposures to dioxin congeners and isomers have been reported. An acne outbreak in Germany in 195^ was traced to trichlorophenol con- taminated with TCDD and TCDF (.Poland et_ aJU , 1976). Similar outbreaks of chloracne, the most common manifestation of dioxin exposure in humans, were noted in 2,^,5-T production plants in France, Germany and the United States in the 1950"s and 1960's. In 1971 the use of waste oil contaminated with TCDD for dust control in a riding arena lead to the death of a large number of horses and other small animals, as well as some cases of chloracne in children who played in the area (Kimbrough _et_ al_. , 1977). The contamination of rice oil with dibenzofuran analogs lead to many cases of chloracne in Japan (Bradlaw et al., 1979). The explosion of a chemical plant in Seveso, Italy �2 in 1976 lead to exposure of the population to TCDD which was thought to be responsible for the occurrence of chloracne in humans and a number of livestock losses (Hay, 1980; Pocchiari et_ al_. , 1979; Reggiani, 1978). The use of Agent Orange ( a mixture of n-butyl esters of 2,^-D and 2,^,5-T), a defolient, in Vietnam between 1962 and 1969 lead to the contamination of large areas by TCDD (.Poland et_ al_. , 1976). Recent work by Knutson and Poland has demonstrated that the hyperkeratinization response to TCDD exposure which occurs upon exposure to TCDD in vivo could be reproduced in an in vitro model system (Knutson et_ al_. , 1980). The induction of keratinization is thought to be responsible for the in vivo induction of chloracne. They found that although TCDD did not produce an acute toxic response in various cell types in culture (Knutson et_ al_. , 1980a), XB cells, a cloned epithelial line of mouse teratoma cells (Rheinwald et_ al_. , 1975) when co-cultured at high density with irradiated 3T3 mouse fibrablast cells exhibited a keratinization response when exposed to TCDD. Spontaneous keratinization occurs in these cells when they are seeded at low density (.Rheinwald et_ al_. , 1975). High density XB/3T3 cultures not treated with TCDD did not show this response. Other halogenated aromatic hydrocarbon congeners including dibenzo-pdioxins, dibenzofurans, biphenyls and azp(xy)benzenes also induced keratinization in the XB/3T3 system although to a lesser extent than 2,3,7,8 TCDD. Keratinization could also be induced by some non halogenated aromatic hydrocarbons such as benz(a) anthracene and 5,6-benzoflavone (Knutson et_ al_. , 1980). Since 2,3,7,8 TCDD is the most potent, but not the only inducer of this hyperkeratinization response, this effect will be referred to here as "dioxin-like" activity. Unrelated toxins were studied to determine if the keratinization response was due to nonspecific cell damage. The direct acting alkylating agents W-acetoxy-2-acetylaminofluorene and Mi-methyl-N'-nitrosoguanidine; inhibitors of nucleic acid synthesis, actinomycin D, bleomycin and cordycepin; the spindle microtubule inhibitor, colchicine; kepone, a chlorinated hydrocarbon producing a toxic syndrome distinct from that of TCDD; and 2,6-dichlorobenzo-nitrile, and acnegen considered to have a different mechanism �1 * than TCDD all failed to produce keratinization in the XB/3T3 culture system (Knutson et_ aJL , 1980). 3 Furthermore, a correlation has "been demonstrated between the degree of toxicity of various TCDD isomers and congeners and the extent of enzyme induction, receptor landing and hyperkeratinization response (Knutson et al., 1980; Poland et_ al. , 197T; Poland et_ al. , 1976a; Kende et_ al_. , 1971*). The XB/3T3 system is extremely sensitive, giving an induction of keratinization with as little as 3.2 pg of TCDD (Knutson et_al., 1980). In addition, this system is particularly relevant as a model since it deals with an induced differentiation of the intact cell using an endpoint (hyperkeratinization) known to "be relevant to human exposure (i.e., chloracne). This report describes studies which have been carried out to determine the feasibility of using the in vitro XB/3T3 keratinization model as a mass screen of environmental samples for "dioxin-like" activity, i.e., the ability to induce a hyperkeratinization response. Such an assay could be applied to the detection of "dioxin-like" activity in extracts of samples collected at the Binghamton State Office Building. The evaluation and verification of this assay system is being done by the testing of 12 specific soot samples from various floors of the BSOB building and comparing the results with those obtained from high resolution mass spectroscopy of the same samples when they become available. �METHODS Sample Preparation A soxhlet extract of the soot sample in "benzene (Smith et_ al. , 1981) at a volume of 0.5 - 2.0 ml was mixed with 100 yl of dimethylsulfoxide (DMSO) and evaporated at room temperature for 2k- hours in darkness to allow for solvent exchange from benzene to DMSO with a final volume of 100 yl. A solvent exchange was also done with the positive controls (2,3,7,8 TCDD in DMSO) and solvent controls (DM50). The extract, now in DMSO, was diluted 1:1000 in tissue culture medium (Dulbecco's modified Eagles medium supplemented with 20$ fetal calf serum) and four more 10-fold dilutions were made in this medium for application to the cell cultures. This di- lution series was freshly made for each of the twice weekly refeedings. Cells The XB-2 cell line and the 3T3 feeder cells were obtained from H. Green (M.I.T. ) (.Rheinwald et. al_. , 1975). The cultures were grown in Dulbecco's modified Eagles medium with 100 TJ/ml penicillin and 100 yg/ml streptomycin. The XB line was cultured in medium conditioned "by a 2U hour exposure to confluent 3T3 cells (25 ml/ 75 cm2). The medium was supplemented with 20$ fetal calf serum for the XB cells and 10$ for the 3T3 cells. No contamination with mycoplasma was detected by the Hoechst fluorescence staining method (Chen, 197^). Keratinization screen assay for "dioxin-like" activity Initial screening was done essentially as described by Knutson and Poland (.Knutson. _et_ al_. , 1980) for the in vitro keratinization model. Target cells were the XB epithelial clone derived from mouse teratoma cells by Rheinwald and Green (Rheinwald et. al., 1975). When these cells are plated at low cell density (250 cells per 60 mm dish) along with lethally irradiated 3T3 cells (3 X 105 cells per 60 mm dish), the XB cells form epithelial colonies which stain red with Rhodanile blue. Rhodanile blue stains most mammalian tissue blue but keratinized tissues are stained red (MacConaill et al., 196^). When XB cells are plated at high density (lO5 cells/dish) in the pre- �5 sence of irradiated 3T3 cells (3 X 10 cells per dish), the XB cells replicate but 5 keratinization is not seen and therefore the red staining component of Rhodanile blue (Rhodamine B) is absent. Addition of TCDD to cultures of XB cells at high cell density which are refactory to spontaneous keratinization, produces a dose-related keratinization with the associated red staining with Rhodanile blue. TCDD was shown to pro- duce maximal red staining at concentrations of 5 X 10"11 to 1CT7M; 1 X lO'^M TCDD produces an intermediate response while cultures treated with 5 X 10~12M TCDD and untreated control cultures do not keratinize. This response reaches a maximum by day 10-13. When XB/3T3 cells were plated in l6 mm wells containing 1 ml of medium, as little as 3.2 pg of TCDD produced observable keratinization (Knutson et_ aJL., 1980). Confluent cultures of 3T3 cells were lethally irradiated with IfOOO rads by a cesium source and both the irradiated 3T3 and XB cells were seeded together in Costar Multiwell dishes (15 mm) at 5 X 104 XB cells and 5 X 10U irradiated 3T3 cells per ml per well. These dishes were incubated at 37°C in a humidified of 5% COa in air. atmosphere The medium was replaced twice weekly. The dilution series of the sample was added to the assay cultures 2U hr post seeding and with each medium change. Appropriate solvent controls were run as well as 2,3,7,8 TCDD reference samples. After 12 days, the cultures were rinsed with phosplate buffered saline (PBS) fixed for 30 min. in 10% formalin-PBS and stained with 1% Rhodanile blue or 1% Rhodamine B (.Knutson et_ al_, , 1980). The cultures were then observed for the occurrence of red staining material indicative of the keratinization response. The highest dilution of sample capable of inducing keratinization greater than background levels was taken as the endpoint. The endpoint of the 2,3,7,8 TCDD standard was compared to the endpoints derived from the extracts in order to determine the TCDD equivalency of the sample. The range of activity of a sample was calculated from, the endpoint as follows: It has been shown (Knutson et_ al_., 1980) that 10-11M TCDD produces only a moderate keratinization response, (compared to that produced by 10~10M and higher). �6 >•; Furthermore, one half this amount, i.e. 5 X 10~~12M TCDD produces no response at all. Therefore, in all cases production of such a moderate endpoint was taken to indicate the presence of "between 5 X 10~12 and 1 X 10-nM TCDD equivalent. The assumption was made that one fifth the amount of sample which gave the moderate response would give a negative response. Thus the amount of sample which contains "between 5 X 10~12 and 1 X 10~1:1M dioxin-like activity was taken to "be "between 2Q% and 100$ of the actual amount of sample which gave the moderate response. Safety Considerations It is recognized that the safe handling, containment, and disposal of the substances to "be used in this study are essential. Some of the precautions include prohibition of mouth pipetting, subtraction weighting, use of glove box storage cabinets vented with HEPA and charcoal filters, restriction of traffic in hazard-area, no food, smoking or drinking in hazard area, accurate record keeping of hazardous materials from r-eceipt to disposal, use of filter vented biohazard hoods (BioGard Type II B) f°r medium changes and use of commercial hazardous waste disposal facilities. �RESULTS Assay of BSOB Extracts Preliminary studies were performed to attempt to duplicate the in vitro keratinization model in tMs laboratory. XB/3T3 cultures vere exposed to 10~9M TCDD in DMSO or to DMSO alone at 0.01% final concentration to correspond to the level in the TCDD solution. After 12 days of incubation, with refeeding every 3 to h days, these cultures were fixed and stained. Cultures exposed to 10~9M TCDD showed a marked increase in keratin deposition, as shown by intense Ehodamine B staining, as compared to the DMSO negative control [Fig. l). A 10-fold dilution series of authentic 2,3,7,8 TCDD from 10~8 to 10~12M was tested. The minimal concentration capable of inducing a keratinization response greater than background levels was found to be IQ-^M (Fig. 2b). This is equivalent to 3.2pg/ml and is in general agreement with published results for this compound (Knutson et_ al_. , 1980). A BSOB soot extract which had been analyzed by mass spectroscopy for TCDD and TCDF CSmith et_ al., 198la) was also tested in this experiment for its ability to induce a hyperkeratinization response. A dilution series of this extract was applied to the XB/3T3 cell cultures as described in methods. Figure 2a shows that the DMSO solvent control dilution series induced no keratinization. The highest concentration of the DMSO soot extract (l ul/ml, equivalent to 820 ug soot/ml) caused cytotoxicity. The lowest concentration of extract which induced keratinization was 10~3 ul/ml, which is equivalent to 0.82 yg of soot CFig. 2c). From this result the concentration of .dioxin-like activity in the extract vas calculated (as described in Methods)" to be in the range of 2-20 ppm. Analysis of this sample by mass spectrometry (Smith et_al. , 198lb) indicated the presence of 1.2 ppm 2,3,7,8 TCDD and U8 ppm 2,3,7,8 TCDF. 'The latter is 20-fold less potent then 2,3,7,8 TCDD (.Knutson et_ aiU , 1980); therefore, W ppm of this compound is equivalent in keratinization activity to 2.1* ppm of 2,3,7,8 TCDD. Thus, the total keratinization activity,.based on the mass spectrometry data for these two compounds, should be that of 3.6 ppm 2,3,7,8 TCDD. This is within the concentration limits actually ob- tained in the keratinization assay. �• ; 8 In order to further test the ability of the assay to predict the results of mass spectrometric analysis, benzene extracts of 12 soot samples from different floors of the BSOB vere tested for their ability to induce keratinization. Cells were seeded and exposed to dilutions of the extracts in culture medium. The cultures vere refed every 3-^ days with fresh dilutions of the extract. After 21 days, the cultures were fixed and stained with Rhodamine B. It became obvious, however, that a decrease in the magnitude of the hyperkeratinization effect in response to TCBB exposure had occurred, apparently with time, such that induced keratinization could be seen clearly only under microscopic observation. Colonies of keratinizing cells, similar to those described by Rheinwald and Green (1975) could be seen on a background of non-keratinizing cells. (Attempts to determine the reason for this decrease and to regain the earlier level of responsiveness seen in Figure 1 will be described later.) This decrease in magnitude of the keratinization response did not however, decrease the sensitivity of the assay as seen in studies with authentic TCDD. Accordingly, blind microscopic evaluation was carried out on each of three replicates for each sample by two observers for the occurrence of keratinizing colonies. The results, shown in Table 1, are an average of 6 values per sample and showed good reproducibility with variation rarely being greater than one dilution for any of the replicates of any single sample. The solvent controls and blanks showed no false positive response. Calculations for dioxin-like activity were made as described in Methods. The results show a variation of about 3 orders of magnitude in the ^dioxin-like" activity of the various samples. There appears to be something of a trend in that the samples from the lower floors seem in general to have less activity than those from the higher floors. The results of this study will be compared to the mass spectrometric analysis of these samples when this becomes available. The average keratinization results in terms of dioxin-like activity in ppm were plotted against the available PCB analysis data for these samples generated by gas chromatography (Pause, 1981). Figure 3 shows a double log plot of these two sets of data. There appears to be a possible correlation between the PCB content �9 and the keratinization inducing activity of these soot extracts. Possible reasons for this correlation are examined in the discussion section. AttemptG Made to Reverse the Decrease in the Magnitude of the Hyperkeratinization Effect A personal communication from Dr. A. Poland confirmed that a decline in magnitude was also experienced in his laboratory and was alleviated by the use of reconstituted frozen stocks of early passage XB cells. However, such a strategy in this laboratory failed to increase the magnitude of the keratinization endpoint. It has also been shown that the ratio of XB cells to the irradiated 3T3 feeder cells can affect the magnitude of the response (Rheinwald et_ al_. , 1975). Experiments done to optimize this ratio also failed to restore the response to the early levels, as did changing the irradiation time of the feeder cells, changing the refeeding schedule, using culture vessels of different manufacture and lot numbers, changing incubators, altering the pH of the cultures, using stain from various sources or using medium conditioned by unirradiated 3T3 cells rather than co-cultivation of XB cells with irradiated 3T3 cells. Current attempts to increase the magnitude of the keratinization response will be addressed in the discussion section. Morphological Alteration - A Possible Alternative Endpoint The appearance of an altered cell morphology was observed with those cells which had been exposed to TCDD as well as the various soot extracts in the experiment described in table 1. This change was first seen after 7 days of exposure to the samples and was characterized by a flat cell morphology as compared to the more fibroblastoid cells in the unexposed cultures or those exposed to less than 10""11!/! TCDD CFigure U). An apparent cessation in cell growth was also seen in these flat cells, while the unexposed cells continued to proliferate, resulting in more dense cultures. The minimal concentration of each sample capable of inducing the flat cell response was recorded on the 13th day of exposure of the cultures to the extracts. Replicate dilution series were evaluated by phase microscopy of the living cells by two observers generating 10 values for each sample. The agreement between replicates was excellent with variation rarely being greater than one dilution �••; lo for any one sample. One half of the replicates were fixed and stained for a record, while the remaining cultures were later evaluated for the previously described keratinization (table l). The high correlation between the induction of the keratinization response and that of the flat cell morphology'(Figure 5) indicates that it may by possible to use this flat cell morphological change as an alternative and perhaps improved endpoint in the assay for dioxin-like activity. Preliminary experiments suggest that the induction of the flat cell appearence by TCDD is not dependent upon the irradiated 3T3 feeder layer, thus simplifying any proposed assay procedure using this endpoint. The induced flat cell morphology has been found to be apparent after only 6-7 days of exposure to authentic 2,3,7,8 TCDD, thereby allowing the assay to be run without the necessary refeeding needed in the keratinization assay. Effects of Triton X 100 on the Assay Triton 30.00 (TX) has been proposed for use in the decontamination of the BSOB. Since TX is soluble in benzene which is currently used in the soxhlet ex- traction of the samples and could therefore be encountered in samples to be assayed, a preliminary experiment was carried out to deterimine whether TX has any effect on the assay. A concentration range of TX from 10~* - 10~^yl/ml was tested with the standard concentration series of the TCDD standard (10~8 - 10~12M). It was found that TX at 10"1 yl/ml is cytotoxic while levels of 10~2 and 10~3 yl/ml are not. No synergistic or antagonistic effect of TX in regard to the TCDD induced flat cell endpoint was observed. There was also no induction of a false positive result by TX alone at any concentration tested. Experiments to determine the effect of TX on the keratinization endpoint are in progress. �11 DISCUSSION: The fire at the Binghamton State Office Building and involvement of an electrical transformer containing a mixture of PCBs (Araclor 125^-) and chlorinated "benzenes lead to subsequent contamination of the structure with dioxin and dibenzofuran laden soot. A need was established for a rapid semiquantitative assay for "dioxin-like" activity. This would allow prioritization of samples for high resolution quantitative and qualitative analysis in order to monitor the progress, of decontamination. This preliminary report has dealt with the evaluation and verification of such an assay which is based on an in vitro model of the in vivo keratinization response to dioxin exposure. Preliminary studies demonstrated that the published in vitro model was reproducible in this laboratory and that this model was sensitive to levels of dioxin (2,3,758-TCDD) which corresponds to that in the literature (Rnutson et al, 1980) (approximately 10 M). Assay results of a single soot extract for which mass spectrometry data were available indicated a good correlation between these data and the data resulting from the keratinization mo'del. This initial verification lead to the application of this assay to 12 soot extracts for comparison with results of mass spectrometry of the same samples as they become available. However, the decrease in the magnitude of the TCDD induced keratinization effect may reduce the usefulness of this particular endpoint in spite of the readily apparent, microscopically observable, induction of keratinizing colonies. Attempts are currently being made to redone the XB cell line for the desired characteristics of hyperkeratinization upon TCDD exposure/ Successful monitoring of the cell line, cell storage and recloning would insure a stable cell population upon which the keratinization assay could be based. Cloning is being done by identification and isolation of spontaneously keratinizing colonies of XB cells in sparse culture, as well as keratinizing colonies of XB cells induced by TCDD �12 exposure in dense cultures. New XB and 3T3 feeder cell starter cultures will be obtained, since the reconstitution and use of our early passage frozen stocks has failed to increase the magnitude of the keratinization response to that seen in the initial assays. The subjective reading of the endpoint by visual estimation of the minimal concentration of extract capable of keratin induction based on the intensity of Rhodamine B staining or identification of keratinizing cell colonies limits the degree of quantitation possible. Therefore, several other methods of achieving better quantitation of the induced keratin production are being considered and evaluated. One involves extraction of the Rhodamine B stain from the cells and quantitation by fluorometric measurement. Another involves a quantitative radio- immunoassay method for mammalian epidermal keratin protein which has recently been published (Yuspa et_ al, I960). Another possible method for detection of increased keratin production to be explored is based upon the observation (Steinert et al_, 19T8) that in keratinizing cells, keratin represents 20% of the total urea extractable cellular protein. synthesized. Thus, keratin may represent the predominent protein being Furthermore, keratin has been shown to be relatively rich in histidine, methionine and cysteine (Belanger, 1956; Clark, 1968; Hambrick, 1966). Thus, it may be possible to quantitate keratin production by measurement of incorporation of these (radiolabeled) amino acids into cellular protein. The verification of the flat cell morphological change as an indicator of "dioxin-like" activity would allow a second and perhaps improved biological endpoint to be used in a routine screen assay in addition to or in place of the keratinization assay. The Endpoint is apparent after only 6-7 days and can be readily assessed by microscopic observation of living cultures'. Another advantage of the short development time of this endpoint is the lack of the necessity to refeed the cultures, thus reducing both the sample requirement and handling of the cultures. The homo- geneity of these cells may allow use of smaller culture vessels, reducing even further �13 the amount of sample needed. In addition recent experiments have suggested i that the irradiated 3T3 cell feeder layer may not "be needed for the development of this endpoint. Further studies vill be carried out to establish whether the induction of the flat cell morphology is a valid endpoint for the detection of dioxin-like activity. These will include a double blind study to test the ability of the endpoint to quantitate various concentrations of authentic 2,3,798-TCDD and a test of the relative activities of other halogenated polycyclic compounds, e.g. TCDF, biphenylene, PCB, azo(xy)benzenes, as well as nonhalogenated aromatic hydrocarbons. Compounds that inhibit cell proliferation by acting on macromolecular synthesis vill also be tested to determine if the flat cell response in these cells is simply due to the coincidental inhibition of cell growth. Attempts to establish cloned cell lines exhibiting the flat cell characteristic to insure homogeneity are currently underway. The possible correlation which we have observed between the in vitro assay results and the PCB content of the soot samples (Figure 3) lead to concern that the PCBs were responsible for the induction of keratinization. In fact, it has been reported that 2,3,^,2' ,3' ,^' polybrominated biphenyl can induce keratinization in the XB/3T3 system at a concentration 2,000 fold higher than 2,3,7,8TCDD (Knutson et al, I960). To examine this possibility, Araclor 125U, the PCB mixture present in the transformer coolant and thus the presumed source of PCBs in the soot samples, was tested for .the induction of the flat cell morphology. The lowest concentration of Araclor 125^ for which the flat cell induction was observed vas 10 yg/ml. The highest concentration of PCBs found in any of the soot samples tested was 23,000 yg/gm (Pause, 1981}> The lowest amount of this sample which gave an endpoint was 1.5 yg of soot per ml which contains 0.035 Pg of PCBs per ml. Based upon the results with Araclor 125U, this is insufficient to induce the flat cell response. Thus, the observed induction of the flat cell morphology by the soot extracts is unlikely to have been caused by the PCBs contained in the �lit samples. Experiments are in progress to determine if similar results are obtained for PCB induced keratinization. Another explanation for the correspondence "between the PCB data and the in vitro assay results may be a synergistic or additive interaction between PCBs and low levels of TCDD or some other substance in the soot samples. Studies designed to detect such interaction between Araclor 125^ and 2,3,7,8-TCDD are being carried out and studies using PCBs to spike actual soot extracts are planned. The correspondence could also be the result of a similar deposition pattern of the PCBs and the dioxin congeners and isomers in the building. Triton X-100, the proposed decontamination agent for the BSOB, was found to be toxic to the in vitro system at 0.10 yl/ml but not at 0.01 yl/ml. TX is soluble in benzene, and a relatively low, non toxic, concentration in a sample could be concentrated by a benzene extraction procedure to toxic levels and preclude use of the in vitro assay. This possibility should be considered in the development of decontamination and sample collection procedures. The lack, of effect of TX on the induction of the flat cell response does however, decrease the concern of a false positive result from low levels of this compound. In summary, the in vitro keratinization model developed by Knutson and Poland (Knutson et al, 1980) has been examined for use as a screen assay for the detection of "dioxin-like" activity in extracts of BSOB soot samples. After initial verification with authentic TCDD, a preliminary assay was done on the one sample for which TCDD and TCDF data from mass spectrometry'were available. The results of this in vitro assay compared well with the quantitative analysis data. Based on this result, a screen for keratinization induction was carried out on 12 extracts of soot from various floors in the BSOB. These results will be compared to the mass spectrometry data on the same samples, thus allowing a more rigorous validation. A high correlation would indicate that this model may be �-.; 15 used as a semiquantitative mass screen assay for "dioxin-like" activity. The decrease in the magnitude of the keratinization response which we have observed with time gives reason for concern, as the cause for this decline has not been determined. The problem may be solved by the acquisition of new starter cultures, or stabilized for a time by recloning the line for the desired characteristics and/or using reconstituted frozen stocks of those cultures which currently exhibit TCDD induced keratinizing colonies. Alternatively, the TCDD- • induced change in morphology (which is characterized by the appearance of flat, non proliferating cells) which seems to correlate very well with the keratinization endpoint may have the potential for use as an additional or alternative (and possibly better) endpoint for use in mass screening for "dioxin-like" activity. �16 REFERENCES Belanger, L.F. (1956) Autoradiographic Visualization of the Entry and Transit of 6^5 Methionine and Cystine in the Soft and Hard Tissues of the Growing Rat. Anat. Rec_., 12^:555-563 Bradlaw, J.A., and Casterline, J.L. (1979) Induction of Enzyme Activity in Cell Culture: A Rapid Screen for Detection of Planar Polychlorinated Organic Compounds. J_. Asspc. Off. Anal. Chem., 62:90^-915 Chen, T.R. (197*0 Utilization of Fluorescent Hoechst Stain to Effectively Detect Mycoplasma Contamination. In Vitro 10:390 Clark, S.L. (1968) Incorporation of Sulfate by the Mouse Thymus: Its Relation to Secretion "by Medullary Epithelial Cells and to Thymic Lymphopoiesis. J_. Exp. Med. , 128, 927-957Fukuyama, K. and Epstein, W.L. (1966) Epidermal Keratinization: Localization of Isotopically Labeled Amino Acids. J_. Inves. Derm., kj, 551-559. Hambrick, G.W., Lamberg, S.I. and Bloomberg, R. (1966) Observations on Keratinization of Human Skin In Vitro. £. Inves.Derm., Vr, 5^1-550. Hay, A. (i960) Health monitoring endangered at Sev&so. Nature, 283, 237. Hutzinger, 0., Olie, K., Lustenhouver, J.W.A., Okey, A.B., Bandiera, S., and Safe, S. (1981) Polychlorinated Dibenzo-P-Diozins and Dibenzofurans: A Bioanalytical Approach. Chemosphere 10, 19-25. Kende, A.S., Wade, J.J., Ridge, D. and Poland, A. (197*0 Synthesis and Fourier Transform Carbon-13 Nuclear Magnetic Resonance Spectroscopy of New Polyhalodibenzo-p-dioxins. J_. Org. Chem., 39, 931-937. Kimbrough, R.D., Coleman, D.C., Liddle, J.A., Cline, R.E. (1977) Epidemiology and Pathology of a Tetrachlorodibenzodioxin Poisoning Episode. Arch. Environ. Health, March-April, 77-85. Knutson, J.C., and Poland, A. (1980) Keratinization of Mouse Teratoma Cell Line XB Produced by 2,3,7,8-Tetrachlorodibenzo-p-dioxin: an in vitro model of toxicity. Cell, 22, 27-36. Knutson, J.C. and Poland, A. ( 9 0 2,3,7,8-Tetrachlorodibenzo-p-dioxin: 18) Failure to Demonstrate Toxicity in Twenty-three Cultured Cell Types. Toxicol. and Applied Pharmacol., 5^, 377-383. Langer, H.G., Brady, T.P. and Briggs, P.R. (1973) Formation of Dibenzodioxins and other Condensation Products from Chlorinated Phenols and Derivatives. Environ. Health Perspect., 5, 3-7. Lowery, O.K., Rosebrough, N.J., Farr, A.L. and Randall, R.J. (1951) Protein Measurement with the Folin Phenol Reagent. J_. Biol_. Chem., 193, 265-275. �17 MacConaill, M.A. , and Gurr, E. (19610 The Histological Properties of Rhodanile Blue. Ir_. J_. Med. Sci . , June, 2^3-250. Pause, R. ( 1981 ) Personal Communication, N.Y. State Department of Health. Pocchiari, F., Silano, V. and Zampieri , A. (1979) Human Health Effects from Accidental Release of TCDD at Seveso, Italy. Ann. N.Y. Ac ad. Sci. 320, 311-320. Poland, A. and Kende, A. (1976) 2,3,7»8-Tetrachlorodibenzo-p-dioxin: environmental contaminant and molecular probe. Fed. Proc., 35 , Poland, A., Glover, E., Kende, A.S., DeCamp, M. , and Giandomenico, C.M. (I976a) 3,^,3' jV-tetrachloroazoxybenzene and azobenzene: Potent Inducers of Aryl Hydrocarbon Hydroxylase. Science , 19^, 627-630. Poland, A. and Glover, E, (1977) Chlorinated Biphenyl Induction of Aryl Hydrocarbon Hydroxylase Activity: A Study of the Structure -Activity Relationship. (1977) Mol. Pharmacol., 13, 921+-938. Reggiani, G. (1978) Medical Problems Raised by the TCDD Contamination in Seveso, Italy. Arch. Toxicol. , UO, l6l-l88. Rheinwald, J.G. and Green, H. (1975) Formation of a Keratinizing Epithelium in Culture by a Cloned Cell Line Derived from a Teratoma. Cell* 6, 317-330. Smith, R.M., O'Keefe, P.¥., Hilker, D.L., Jelus-Tyror, B.L., and Aldous, K. ( 9 l Chemical analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,3,7,8I8) tetrachlorodibenzofuran in a soot sample from the transformer explosion in Binghamton, New York. N.Y. State Department of Health Report. February 20, 198l. Smith, R.M., Hilker, D.L., O'Keefe, P.W., Kumar, S., O'Brien, J., Jelus-Tyror, B.L., and Aldous, K. (I98la) Analysis of a Binghamton soot sample for tetrachlorodibenzofurans and tetrachlorodibenzo-p-dioxins . N.Y. State Department of Health Report, October 1, 1981. Steinert, P. and Yuspa, S.H. (1978) Biochemical Evidence for Keratinization by Mouse Epidermal Cells in Culture. Science , 200, Yuspa, S.H., Poirier, M.C., Harness, J.R., Olsom, D.R. and Steinert, P.M. (1980) Specific Quantification of Mouse and Human Keratin Proteins by Radioimmunoassay. Bio_chem. J_. , 187 » 281-28U. �18 Table I Keratinization Assay of BSOB Soot Samples Floor number Lowest active c o n c e n r a o n owes a c v e concentration of extract (pg soot equivalent/ma)a 3 k 6 1.3 llt.O 15.9 7 8 0.3 1.0 9 10 12 Ik 15 17 1.5 0.5 0.7 12.9 O.It. O.k TCDD , v equivalent ,(ppm) 0.01 1.2 0.11 0.10 - 0.10 - 12 - 1.1 - 1.0 5.3 - 53 1.6 - 16 l.l 3.2 2.3 0.12 k.O k.O - 11 - 32 - 23 - 1.2 - kO - kO a) Activity was determined by the appearance of keratinizing colonies. This result is the average of values from 3 replicates evaluated by two observers. b) .Calculated as described in Methods. �Figure Legends Figure 1 Effect of 2,3,7,8 TCDD on XB/3T3 Cell Cultures Cultures were seeded and cultivated as described in methods. Figure la is representative of an XB/3T3 culture exposed to 10r* M 2,3,7,8 TCDD in the presence of 0.01$ DMSO. Figure Ib is representative of a replicate culture exposed to 0.01$ DMSO alone. The bright red rhodamine B stain, indicative of keratin deposition} shows as dark grey in these photos. Figure^ 2 Keratinization assay of a BSOB soot extract Figure 2a shows the negative response of the DMSO control. Figure 2b shows the effect of 2,3,Tj8 TCDD on this system with keratinization first evident with 10"1:LM. Figure 2c shows the toxic effect of a BSOB soot extract at the highest concentration (l yl/ml) and the induction of keratinization at lower concentrations, with the effect first detected at the fourth highest dilution (10~3 ul/ml), equivalent to 0.82 yg soot/ml. Figure 3 Log-log plot of the amount of PCBs detected in BSOB soot extracts from various floors by gas chromatography (abscissa) and the calculated values of "dioxin-like" activity generated by the keratinization assay of the same samples (ordinate). The values for "dioxin-like" activity were derived by dividing the amount of soot per ml in the lowest soot extract concentration capable of inducing keratinization into 3.2 pg/ml which is the lowest concentration of 2,3,7>8 TCDD found to induce keratinization. Figure k TCDD induced flat cell morphology Figure Ua: XB/3T3 culture after 12 days of incubation with 0.1$ DMSO, showing high density and fibroblast-like organization. Figure li-b: a similar culture exposed to 10~°M TCDD in 0.1$ DMSO, showing flat morphology and relative low density. Phase, l^OOX magnif ifcation. Figure 5 Log-log plot of calculated values of "dioxin-like" activity of BSOB soot extracts from various floors generated by the keratinization assay (ordinate) and by the induction of the flat cell response (abscissa) calculated as in Figure 3. �20 Figure la Figure Ib �21 X .* • •! - o •-- - o' = • Figure 2a Figure 2b �22 Figure 2c �23 4-J •H n •u o «j rt O cd -H OT ?*! a8 p< to ,3 I 1 2 i 3 log ppm PCB in soot samples Figure 3 t 4 JE �Figure 4a Figure 4b �.3 4J 0 I 4J 3 ctf »H W I <U 0 log ppm "dloxin-like" flat cell induction in soot samples Figure 5 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 088 Folder The folder containing the original item. 2212 Series The series number of the original item. Series IV Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Gierthy, John F. Gerald D. Frenkel Title A name given to the resource Typescript: A Preliminary Report on the Evaluation of an In Vitro Assay for the Detection of "Dioxin-Like" Activity Using Extracts of Soot from the Binghamton State Office Building, 1982 Subject The topic of the resource BSOB PCBs analytical studies Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 087 Folder The folder containing the original item. 2170 Series The series number of the original item. Series IV Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Description An account of the resource <strong>Corporate Author: </strong>State of New York, Department of Health, Office of Public Health Date A point or period of time associated with an event in the lifecycle of the resource March 25 1981 Title A name given to the resource Typescript with cover letter: Letter from Glenn E. Haugie to Alvin L. Young with agenda packet for Expert Panel for the Binghamton State Office Building for April 3, 1981 Subject The topic of the resource BSOB building remediation decontamination PCBs Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 052 Folder The folder containing the original item. 1369 Series The series number of the original item. Series III Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Miller, Stanton Source A related resource from which the described resource is derived Environmental Science and Technology Date A point or period of time associated with an event in the lifecycle of the resource 1983 Title A name given to the resource The PCB Imbroglio Subject The topic of the resource PCBs industrial exposure agricultural exposure EPA ao_seriesIII Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 052 Folder The folder containing the original item. 1363 Series The series number of the original item. Series III Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Stara, J.F. D. Mukerjee R. McGaughy P. Durkin M.L. Dourson Source A related resource from which the described resource is derived Environmental Health Perspectives Date A point or period of time associated with an event in the lifecycle of the resource 1983 Title A name given to the resource The Current Use of Studies on Promoters and Cocarcinogens in Quantitative Risk Assessment Subject The topic of the resource dioxin PCBs water pollution EPA ao_seriesIII Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 087 Folder The folder containing the original item. 2184 Series The series number of the original item. Series IV Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Roberts, Gail Source A related resource from which the described resource is derived The Sun-Bulletin Date A point or period of time associated with an event in the lifecycle of the resource October 14 1981 Title A name given to the resource Tainted Air Leaked Daily from Tower Subject The topic of the resource BSOB popular press PCBs https://www.nal.usda.gov/exhibits/speccoll/files/original/3ab6ff3c3a89f8b1ae106112fb5a6e9f.pdf 04e173994a1e0cd7c504385460fdda6c PDF Text Text Item D Number °2202 Author DeCaprio, Anthony P. Corporate Author Center for Laboratories and Research, New York State Report/Article Title Subchronic Oral Toxicity in Guinea Pigs of Soot from a Polychlorinated Biphenyl-Containing Transformer Fire Journal/Book Title Year Month/Day Color Number of Images October 13 D 34 Descrlpton Notes Thursday, September 20, 2001 Page 2202 of 2293 �Subchronic Oral Toxicity in Guinea Pigs of Soot from a Polychlorinated Biphenyl-Containing Transformer Fire Anthony P. DeCaprio , Donald M. McMartin, Jay B. Silkworth, Robert Rej, Ronald Pause, and Laurence S. Karainsky Center for Laboratories and Research, New York State Dept. of Health, Albany, New York 12201. Running Title: TOXICITY OF A PCS-BASED PYROLYSATE D To whom correspondence should be addressed. *** OCT 1 3 1932 -iHEALTH �Subchroaic Oral Toxicity in Guinea Pigs of Soot From a Polychlorinated BiphenylContaining Transformer Fire. DeCaprio, A.P., Silkworth, J.B., McMartin, D.M., Rej3 R., Pause R., and Kaminsky, L.S. (1982). 00, 000-000. Toxicol. Appl. Pharmacol. We have previously described the acute oral toxicity in guinea pigs of soot from a transformer fire at the State Office Building in Binghamtoa, New York. The soot was determined to contain high ppm concentrations of poly- chlorinated biphenyls, biphenylenes, dibenzodioxins, and dibenzofurans. The pre- sent study evaluates soot toxicity in guinea pigs receiving 0, 0.2, 1.9, 9.3, or 46.3 ppm soot in the feed for 90 days or 231.5 ppm for 32 days. At 231.5 ppm, body weight loss, thymic atrophy, bone marrow depletion, skeletal muscle and gastrointestinal tract epithelial degeneration, and fatty infiltration of hepatocytes were observed. Mortality had reached 35% by day 32 when survivors were * killed, with total soot consumption of approximately 400 mg/kg. At 46.3 or 9.3 ppm soot a reduced rate of body weight gain was observed, with 30% mortality by day 90 at 46.3 ppm. Relative (to body) thymus weights were decreased in both groups, while relative spleen weights were increased at 46.3 ppm soot only. Salivary gland interlobular duct squamous metaplasia and focal lacrimal gland adenitis were detected histopathologically, while bone marrow depletion was noted only in females at the higher dose. Diminished serum alanine aminotrans- ferase (ALT) activity in both sexes and decreased serum sodium levels in male and potassium levels in female animals were detected at both dose levels. Decreased ^-glutarayl transferase activity and red blood cell count, and elevated serum creatinine and triglycerides were observed only in animals- fed 46.3 ppm soot. At 1.9 ppm soot, salivary gland duct metaplasia was observed in both sexes, along with decreased relative thymus weights, ALT activity, and serum sodium levels in male animals only. No effects attributable to soot exposure -2- �were noted in animals receiving 0.2 ppm soot for 90 days. Total soot consumption in the 0.2, 1.9, 9.3, and 46.3 ppm dosage groups was 1.2, 12, 55, and 275 rag/kg, respectively. Although many of the observed effects were typical of acute exposure of guinea pigs to the Binghamton soot or to polychlorinated aromatic hydrocarbons in general, salivary gland duct metaplasia has not been previously reported. The results suggest a possiblw increased toxicity of the soot in guinea pigs during prolonged as opposed to acute exposure, although variations in absorption due to effects of different vehicles (aqueous in the acute study versus the feed in this study) could account for some or all of this difference. -3- �On February 5, 1981, a transformer fire in the State Office Building in Bingharaton, New York resulted in the dispersal of a soot-like combustion product throughout the building. The dielectric and coolant fluid within the transformer was composed of the polychlorinated biphenyl (PCS) mixture Aroclor 1254 (65%), chlorinated benzenes (35%), and other trace additives. The building was subsequently closed and extensive hazard assessment and clean-up operations were begun. Chemical analysis of the soot revealed the presence of numerous con- geners and isomers of polychlorinated biphenyls, naphthalenes, biphenylenes, dibenzofurans (PCDFs), and dibenzodioxins (PCDDs) (Stalling, 1981; Smith ejt al., 1982a). Based on an estimated PCDF content of 5 ppm in a sample of Aroclor 1254 similar to that present in the transformer fluid (Stalling, 1981), and on the analyzed PCDF and PCB contents of 320 and 5000 ppm, respectively, in an average soot sample (Smith e£ al_., 1982b; Eadon et^ £l., 1982), the pyrolysis of the fluid apparently resulted in a very substantial concentration increase of highly toxic PCDFs in the soot. This incident is an example of what could be a significant public health problem since such PCB-filled transformers are widely utilized. Although PCDFs and PCDDs are among the compounds formed during combustion of PCBs (Buser et al., 1978), electrical capacitor fires (jansson and Sundstrom, 1982), and incineration of municipal waste (Olie e£ al^., 1977), there are few reports on the toxicological effects of such complex pyrolysates. Animal toxicity studies with the Binghamton soot were therefore initiated with the ultimate aim of developing risk assessment data for subsequent clean-up operations and reoccupation of the contaminated building. The complex chemical nature of the soot pre- cluded hazard estimation based on the known toxicity of individual components, since not all components could be detected and quantitated, and because of the potential for synergistic or antagonistic effects. Acute toxicity studies of -4- �the soot in guinea pigs, the species most sensitive to toxic effects of PCDFs and PCDDs (Kociba and Schwetz, 1982), indicated an oral LD50 of 410 mg/kg (Silkworth et^ a_K, 1982). A similar value was obtained with aa organic extract of the soot, suggesting that the soot matrix did not affect the toxicity of the bound toxic components. A variety of dose-related pathological changes were observed, including pancreatic duct hyperplasia, salivary gland metaplasia, thymic atrophy, elevated serum triglycerides, and body weight loss. Similar effects have been reported during exposure to purified PCDDs (McConell e_£ al., 1978) and PCDFs (Moore e_£ _al., 1979). These acute studies indicated that the toxicity of the soot could not be ascribed solely to effects of the extremely toxic 2,3,7,8-TCDD and 2,3,7,8-TCDF isomers, but that other soot contaminants were major contributors to its overall toxicity. The present investigation was designed to evaluate the subchronic oral toxicity of the soot in guinea pigs in order to establish a no-effect level and to determine target organs for risk assessment. An additional aim was to compare the effects of low-level, cumulative exposure to the soot with those produced by single acute exposures. The lack of data on subchronic exposure of guinea pigs to chlorinated-aromatic hydrocarbons made dose selection difficult. Metabolism and excretion of 2,3,7,8-TCDD and 2,3,7,8-TCDF in the guinea pig are very slow, indicating that the toxicity of these compounds may be cumulative (Gasiewicz and Neal, 1979; Decad £t al_., 1981). LD50 values of 2,3,7,8-TCDD in this spe- cies were similar when the compound was given in either a single oral dose (McConnell e_t_ al., 1978), or in 4 weekly oral doses (Harris et al., 1973). These results suggested that cumulative mortality in guinea pigs fed soot might approach 50% after approximately 410 mg/kg had been ingested. on these considerations soot was incorporated into the feed in five dosage groups ranging from 0.2 to 231.5 ppm. -5- Based �METHODS Animals and dosing. Male (250-350 g) and female (200-350 g) Hartley guinea piga were obtained from a colony maintained in this center. Animals were randomly assigned to six dosage groups of 10 males and 10 females each, and were acclimated to a 12-hr on 12-hr off light cycle for 1 week. maintained at 22-24°C and relative humidity at 40-60%. Room temperature was Animals were housed individually in plastic cages (19 X 10.5 X 8 in.) on hardwood chips and were identified by numbered ear tags. Cages were equipped with polyester filter cage covers (Hazleton Systems, Inc., Aberdeen, Md.) to prevent cross-contamination. Samples of soot were collected from stairwells of the third and fourth floors of the Binghamton, New York State Office Building and sieved through No. 40 copper wire mesh to remove inert debris. Sieved soot was incorporated into certified guinea pig chow (NIH-34) by a commercial feed processor (Zeigler Bros,, Inc., Gardners, Pa), at concentrations of 0.2, 1.9, 9.3, 46.3, and 231.5 ppm. Groups received formulated or control feed and municipal tap water ad libitum for 90 days. Observation and necropsy. signs of toxicity. Animals were evaluated daily for clinical Food consumption and body weights were measured weekly and the cumulative soot consumption was calculated. All surviving animals were killed at 90 days by CO. asphyxiation and subjected to complete necropsy. Major organs were weighed, and samples from 32 tissues were fixed in 10% neutral phosphate buffered formalin. Tissues were processed by standard paraffin tech- niques and sections stained with hematoxylin and eosin. Samples'of blood and bladder urine were taken for clinical chemistry and hematological analysis. Clinical chemistry. Serum enzymes (except sorbitol dehydrogenase) and triglycerides were determined using methods previously cited (Silkworth et al., 1982). Sorbitol dehydrogenase was determined by the method of Rose -6- �and Henderson (1975). Bilirubin, total protein, albumin, creatinine, blood urea nitrogen (BUN), and glucose were determined with methods routinely used at this center. Sodium and potassium levels were determined by flame emission spectro- scopy and calcium with atomic absorption spectroscopy. Serum chloride was mea- sured with a Buchler Chloridometer. Urine pH, protein, glucose, ketones, and occult blood cell contents content were determined using Chemstrip 5 (BioDynamics, Inc., Indianapolis, IN) reagent sticks. Urine specific gravity was measured by refractometry. Chemical analysis of PCS concentrations in formulated feed. Assessment of actual concentrations of soot and of the homogeneity of its incorporation into guinea pig feed was performed using Aroclor 1254 concentration as an indicator for the soot. Samples (5 g) of feed were subjected to exhaustive soxhlet extraction in 1:1 acetone:hexane for 24 hr. Extracts were analyzed for PCS using packed column gas chromatography with electron capture detection (New York State Dept. of Health, 1982). Levels of incorporation were calculated based on an Aroclor 1254 concentration of 5000 ppra in the original soot (Eadon ej: al., 1982). -7- �RESULTS Soot incorporation into feed. Aroclor-1254 concentrations in the 231.5 and 46.3 ppm soot formulated feed levels were 1.10 and 0.27 ug/g feed, respectively, compared with calculated values of 1.16 and 0.23.ug/g. Interfering extractants precluded the estimation of Aroclor concentrations in the 0.2, 1.9, and 9.3 ppm formulated feeds. Five samples from different regions of a barrel containing the 46.3 ppm feed were individually analyzed to determine homogeneity of soot incorporation. The mean and standard error for Aroclor concentration was 0.28 jf 0.02 ug/g feed, with a range of 0.24 to 0.34 ug/g feed. ?ig. 1 Clinical signs of toxicity. Both male (Fig. la) and female (Fig. Ib) animals displayed dose-related diminished body weight gain as compared to control animals. This effect was statistically significant (p < 0.05) in the 46.3 and 9.3 ppm dosage groups. : Animals receiving 231.5 ppm soot in the feed exhibited a severe net body weight loss probably due to both decreased food consumption and toxic effects of the soot. Seven animals in this group died between days 28 and 31 of the study, and the surviving animals were killed and necropsied at 32 days. Food consumption (g/kg/day) in all other dose groups was not significant- ly different from that of the control group. Animals receiving food with 46.3 ppm soot began to show net body weight loss in the final week of the study. Three male and three female animals from this group died during the course of the study with gross pathology reflecting emaciation. Of these animals, two males and one female exhibited moderate to severe pneumonia. Deaths of one male control animal at 76 days and one male animal in the 9.3 ppm group at 32 days were due to pneumonia. Body weights and estimated total soot consumption for each treatment group Table 1 are shown in Table 1. Soot consumption in the 231.5 ppm dosage group had -8- �approached the acute LD50 value of 410 mg/kg. The cumulative mortality of this group had reached 35% at the time of necropsy and all remaining animals were moribound. Total soot consumption in the 46.3, 9.3, 1.9, and 0.2 ppm groups represented approximately 67, 13, 3, and 0.3% of the acute oral LD50 dose, respectively, at termination. On day 30, mold was detected in several barrels of the commerciallyformulated control and soot-containing feeds. This mold was identified as several non-pathogenic strains of Aspergillus glaucus. Measures taken to eli- minate the mold included the removal of contaminated feed from the metal feeders, cleaning and sterilization of these feeders, reduction of room humidity, and refrigeration of remaining feed stocks. No alterations in general health or food consumption in animals exposed to the mold were noted. Gross pathology. Gross pathology in animals administered 231.5 ppm soot for 32 days or 46.3 ppm soot for 90 days consisted of varying degrees of emaciation and thymic atrophy. Gross observations in animals receiving 0.2, 1.9, or 9.3 ppm soot for 90 days were normal with the exception of thymic atrophy in males at 1.9 and in both sexes at 9.3 ppm. No grossly observable effects were noted in animals receiving 0.2 ppm soot. Organ weights. Table 2 Absolute organ weights of treated and control animals are summarized in Table 2. Organ weights in the 231.5 ppm dose group were not deter- mined due to lack of suitable controls for comparison. Significant dose-related decreases were observed in absolute brain, liver, thymus, kidney, adrenal, and testes weights in males, and absolute thymus, kidney, and adrenal weights in females as compared to control weights. Thymus weight was a sensitive indicator of toxicity in male animals, with a significant decrease present at the 1.9 ppm level as compared to controls. Since absolute organ weights frequently reflect �body weight changes rather than specific target organ toxicity (Feron et al., 1973; Scharer, 1977), relative (to body weight) organ weights were also Table 3 calculated (Table 3). Significant increases in the organ/body weight ratio were observed for brain, spleen, and testes. In contrast, decreases were observed in thymus/body weight ratios at the two highest dose levels in females and the three highest levels in males. No alterations in absolute or relative organ weights were observed in animals receiving 0.2 ppm soot. Hematology. Table 4 Dose-related hematological alterations relative to controls were observed only in animals at the 46.3 ppm dose level (Table 4). Erythrocyte counts were decreased in animals from both sexes in this dosage group and white cell counts and packed cell volume were lowered in females. Although these values were significantly different from control, they were generally within published normal ranges (Mitruka and Rawnsley, 1981). No alterations in white blood cell differential counts were noted. Serum Chemistry. Table 5 Serum alanine aminotransferase and ^"glutamyl trans- ferase activities were decreased by soot exposure (Table 5). Activity of ala- nine aminotransferase decreased in a dose-related manner in male animals receiving 1.9, 9.3, -and 46.3 ppm and in female animals at 9.3 and 46.3 ppm. Activity of Y~glutamyl transferase was depressed in male and female animals at the 46.3 ppm dose level. The decreases in serum enzyme levels observed at the higher doses are in contrast to effects expected from organ damage, and probably instead reflect decreases in organ and muscle mass. Table 6 Results of other serum chemistry determinations are summarized in Table 6. Serum sodium levels were significantly lowered in male animals at the 1.9, 9.3,and 46.3 ppm dose levels, and potassium levels were decreased in female animals at 9.3 and 46.3 ppm. Serum triglyceride levels were significantly increased in animals receiving 46.3 ppm soot. -10- �A relatively high triglyceride level in female control animals probably contributed to an apparently significant decrease in this component in serum from females receiving 0.2, 1.9, and 9.3 ppra soot. This decrease was not dose related and is thus unlikely to reflect soot exposure. Serum creatinine was significantly elevated in male and female guinea pigs at the 46.3 ppm dose level. Urinalysis did not reveal any alterations in pH or specific gravity attributable to soot exposure. No abnormal levels of protein, glucose, ketones, or red blood cells were detected in the urine of animals treated for 90 days. Microscopic pathology. All tissues were examined for pathological altera- tions in the control, 9.3, 46.3, and 231.5 ppm dosage groups. The only tissues examined in the 0.2 and 1.9 ppm dosage groups were those identified as target tissues in the acute studies (Silkworth e_t ^a_l., 1982), or which exhibited lesions at the three upper dose levels in the present study. A variety of doserelated pathological changes were observed in guinea pigs receiving Binghamton Table 7 soot in the feed (Tables 7 and 8). Metaplasia of salivary gland interlobular Table 8 duct epithelium was present in animals receiving 1.9, 9.3, or 46.3 ppm soot for Fig. 2 90 days or 231.5 ppm for 32 days (Fig. 2). All female animals at the 46.3 ppm dose level exhibited this lesion after 90 days. Epithelium having a severity grade of +1 was thickened by proliferating cells similar to those of the stratum spinosum of the skin. The lesion had progressed to squamous metaplasia in the 46.3 ppm group, with flattening and occasional keratinization of superficial epithelial cells (severity grade +2). Pancreatic duct goblet cell hyperplasia was frequently observed in male animals fed 46.3 ppm soot for 90 days and 231.5 ppm soot for 32 days. Goblet cells were considered hyperplastic when they occupied more than one-half of the circumference of the duct epithelium. Hyperplastic epithelium contained excessive numbers of goblet cells and was 25 to 35 um high -11- �in contrast to the normal height of 10 to 17 jam. Although this lesion was also observed in female animals, its significance is questionable, since it was observed in 20% of female controls but not in male controls. Focal lacrimal gland adenitis was found in male animals at the 9.3, 46.3, and 231.5 ppm dose levels, and in female animals at the upper two dose levels. This was in con- trast to the results of acute dosing, where the lesion was also observed in control animals (Silkworth e_t a_l., 1982). Fig. 3 Depletion of hematopoietic cells from bone marrow (Fig. 3) was noted in 29% of female animals receiving 46.3 ppm soot for 90 days. Such depletion was also observed and was more severe in male and female animals receiving 231.5 ppm soot for 32 days. nephritis was present in all groups after 90 days. Focal interstitial This lesion was not observed in animals at the high dose level of 231.5 ppm after 32 days. Solid or ring-shaped hyaline-like hepatocellular cytoplasmic inclusions were present primarily in animals receiving 9.3 and 46.3 ppm soot, but not in animals at the highest dose level. The number of inclusions ranged from approxi- mately 4 to 10 per liver section (severity grade +1) to at least 10 per 250X microscopic field (severity grade +3). Focal hepatic necrosis similar to that described in normal guinea pigs by Cuba-Caparo and Myers (1977) was noted in animals from every group, including the control group. These lesions were also observed in previous acute studies (Silkworth e_t^ al^., 1982) and were considered of no toxicological significance. Degenerative changes of skeletal muscle were present in two female animals in the 46.3 ppm group which died two weeks prior to completion of the study and in a male animal in the 231.5 ppm group. These lesions displayed shrunken fibers with the occasional loss of striations, proliferation of myoblasts, and foci of mineralization. -12- �A variety of other pathological alterations were noted only in animals receiving 231.5 ppm soot for 32 days. Fatty infiltration was observed in liver from 57% of the male and 51% of the female animals at this dose level. Hepatocytes with fatty infiltration were scattered throughout the lobule and comprised 10 to 50% of the cells contained in a section. Degenerative changes of the stomach and intestine were occasionally seen in males from this group. These lesions consisted of mildly dilated crypts and a moderate number of pyknotic cells in the mucosa. Thinning of the thymic cortex was apparent in several animals receiving 231.5 ppm soot. -13- �DISCUSSION We have previously reported a spectrum of clinical and pathological effects in guinea pigs exposed to acute, oral doses of transformer-fire soot from the Binghamton State Office Building (Silkworth et al^., 1982). Generally the effects were typical of those observed after acute exposure to chlorinated aromatic hydrocarbons (McConnell e£ ail., 1978; Moore et_ al_., 1979). The pre- sent report describes findings in guinea pigs receiving soot in the feed for 90 days. Toxic effects were seen at lower total dose levels of soot as compared with effects of acute exposure. These effects, which included thymic atrophy and salivary gland duct metaplasia, were observed in male animals receiving a total of 12 mg soot/kg, or 0.13 mg soot/kg/day. Salivary gland metaplasia was also noted in female guinea pigs at this dose. In contrast, an acute oral dose i of 10 mg soot/kg produced no detectable toxicological effects, and a dose of 100 mg soot/kg resulted only in elevated serum triglycerides in male animals and thymic atrophy in female animals. Although these comparisons suggest an increased toxicity of soot components with prolonged exposure, variations in absorption due to the effects of the different vehicles (aqueous in the acute study versus the feed in this study) could account for some or all of this difference. Higher dose levels of soot produced toxic effects not predicted from the acute dosing studies. Spleen to body weight ratios were significantly increased in animals receiving 46.3 ppm soot. This increase probably represents a direct toxic effect and was not secondary to body weight changes, since spleen/body weight ratios usually decrease during restricted weight gain (Feron et al., 1973; Scharer, 1977). Bone marrow depletion and decreased erythrocyte counts were noted in animals at this dose level and thus the increased relative spleen weight might represent an adaptive response by the organ to provide an alternate -14- �heraatopoietic center. Similar changes have been reported in rats receiving oral doses of 2,3,7,8-TCDD for 90 days (Kociba et a_l., 1976). Brain/body and testes/body relative organ weight changes most likely reflect decreased body weight gain rather than specific organ toxicity. There are no reports concerning subchronic or chronic toxicity of PCDDs or PCDFs in guinea pigs. It is therefore difficult to compare the subchronic toxi- city of the Binghamton soot with known effects of its components and comparisons can only be based on the well-characterized effects of acute exposure (McConnell et. al_., 1978; Gasiewicz and Neal, 1979; Huf f et al^., 1980). Thymic atro- phy, bone marrow hypoplasia, and decreased body weight gain are typically encountered during acute PCDD and PCDF exposure in guinea pigs, and such effects were prominent in animals receiving Binghamton soot for 90 days. Elevated serum tri- glycerides are also indicative of acute polychlorinated aromatic hydrocarbon exposure in guinea pigs, and may reflect altered utilization of 'exogenous nutrients. Such increased levels were observed during acute exposure to the Binghamton soot and in animals fed 46.3 ppm soot for 90 days. Body weight gain was significantly lower in the 9.3 and 46.3 ppm groups as compared to control rates. Feed consumption in animals administered soot was not different from that of control animals, indicating that the decreased weight gain was a toxic effect rather than a reflection of reduced nutrient intake. Thymic atrophy was probably the most reliable indicator of soot toxicity, since it was apparent at a low dose level (1.9 ppm in male animals) and was highly correlated with total soot exposure. Decreased thymus weights indicate the potential, for diminished immune response as a result of exposure to these compounds (McConnell et al., 1978). Although cellular depletion was not marked in the thymus of treated animals, thinning of thyraic cortex was confirmed in several animals -15- �receiving 231.5 ppm soot for 32 days. Alterations in the immune response and thyraic atrophy have been reported in experimental animals after exposure to 2,3,7,8-TCDD (Vos et a_l., 1973) and 2,3,7,8-TCDF (Luster £t a_l., 1979). Guinea pigs receiving 231.5 ppm Binghamton soot in the feed for 32 days exhibited additional lesions characteristic of acute exposure to these compounds, including skeletal muscle degeneration, fatty change in hepatocytes, and degeneration of gastrointestinal tract epithelium. In contrast, other commonly repor- ted effects (e.g., renal pelvis hyperplasia, adrenal hemorrhage, and testicular atrophy) were not marked in guinea pigs fed Binghamton soot. Other clinical and pathological effects observed in the present study have not previously been reported in guinea pigs exposed acutely to purified PCDD or PCDF congeners. The elevated serum creatinine levels observed in animals receiv- ing 46.3 pptn soot suggests an impairment of glomerular filtration, although indicators of glomerular pathology (e.g., elevated BUN and serum sodium) were not observed. Lowered serum sodium levels in male and potassium levels in female animals are also not characteristic of PCDD or PCDF exposure in guinea pigs. significance and mechanism of these serum alterations remains obscure. The Salivary gland duct epithelium metaplasia was also highly correlated with soot exposure. This lesion may be species-specific, since it was not reported in rats fed pure 2,3, 7,8-TCDD for 90 days (Kociba ejt al., 1976) or two years (Kociba e£ £l., 1978). Lethality due to soot exposure was encountered in the 46.3 and 231.5 ppm dosage groups. Animals in the highest dosage group exhibited a~progressive body weight loss similar to that observed during acute dosing regimens. Seven ani- mals (35%) in this group died after consuming approximately 400 mg soot/kg, although it is likely that all the remaining animals would have died within a -16- �short time thereafter. In addition, the rapid weight loss observed in this group suggests that the total dose required for lethality had actually been consumed much earlier in the study. In the 46.3 ppra dose group, lethality reached 30% after consumption of approximately 225 mg soot/kg. pared with the acute LD50 value of 410 mg soot/kg. These results can be com- Based on chemical analyses of the soot (Smith ejt a_l., 1982fa), the amount of soot consumed by animals at the 46.3 ppm dose level would result in a dose of 0.27 ug 2,3,7,8-TCDD/kg and 11 lag 2,3,7,8-TCDF/kg, while total exposure to these compounds at the 1.9 ppm dose level would be 14 and 580 ng/kg, respectively. As a basis for comparison, LD50 values in guinea pigs have been reported as 0.6-2.5 ug/kg for 2,3,7,8-TCDD (Schwetz e_t al., 1973; Silkworth e_t _al., 1982) and 5-10 ug/kg for 2,3,7,8-TCDF (Huff e£ £l•, 1980). It is apparent that many of the other soot components must have contributed to the observed toxicity at low dose lavels. Chemical analysis of the soot has revealed the presence of many addi- tional PCDD and PCDF congeners along with potentially toxic polychlorinated biphenyls, biphenylenes, and naphthalenes (Stalling, 1981; Smith ejt al_., 1982b). Results from the present investigation have indicated a possible enhanced toxicity of Binghamton State Office Building soot in guinea pigs during prolonged versus acute exposure. A total dose of 1.2 mg soot/kg (0.013 mg/kg/ day) was determined to produce no toxic effects. Higher doses produced effects gener- ally attributable to exposure to polychlorinated aromatic hydrocarbons, although some observed changes have not been previously reported as effects of these compounds. A comparison of the acute oral LD50 value of the soot in guinea pigs with that of pure 2,3,7,8-TCDD indicated that the acute toxicity of the soot was -17- �equivalent to that which would be produced by a dose of soot containing 58 ppm 2,3,7,8-TCDD (Eadon et_ al., 1982). Based on this calculation, soot consumption at the no-effect level in this study resulted in a total intake of toxic components equivalent to a dose of 70 ng 2,3,7,8-TCDD/kg (0.78 ng/kg/day). Thus, the toxic dose of soot at the lowest effect level was equivalent to 700 ng 2,3,7,8-TCDD/kg (7.8 ng/kg/day). This contrasts with data from rats, where a total dose of 650 ng 2,3,7,8-TCDD/kg given over 90 days produced no toxic effects (Kociba et £l., 1976). A preliminary study has revealed no overt toxicity in rats fed 231.5 ppm Binghamton soot for 35 days, confirming the lower sensitivity of this species to toxic soot components. The guinea pig has proved extremely sensitive to toxicity induced by exposure to the Binghamton soot, and may therefore be useful in providing further data for hazard assessment. -18- �ACKNOWLEDGMENTS The authors would like to thank Dr. Ira Salkin, New York State Department of Health, for his identification and characterization of fungal contamination in guinea pig feed. The expert technical assistance of Ms. Andrea Kelly, Mr. Brian Linton, and Ms. Deborah Dunbar is also gratefully acknowledged. -19- �REFERENCES Buser, H.R., Bosshart, H.P., and Rappe, C. (1978). dibenzofurans from the pyrolysis of PCBs. Cuba-Caparo, A. and Myers, D.M. (1977). Formation of polychlorinated Chemosphere 7, 109-119. Focal hepatic necrosis in clinically-normal guinea pigs: Bacteriological studies. J. Comp. Pathol. 87, 441-450. Decad, G.M., Birnbaum, L.S., and Matthews, H.B. (1981). 2,3,7,8-Tetrachloro- dibenzofuran tissue distribution and excretion in guinea pigs. Toxicol. Appl. Pharmacol. 57, 231-240. Eadon, G., Aldous, K,, Frenkel, G., Gierthy, J., Hilker, D., Kaminsky, L., O'Keefe, P., Silkworth, J., and Smith, R. (1982). Comparisons of Chemical and Biological Data on Soot Samples From the Binghamton State Office Building. N.Y. State Department of Health Report; March, 1982. Feron, V.J., DeGroot, A.P., Spanjers, M.T., and Til, H.P. (1978). An evaluation of the criterion "organ weight" under conditions of growth retardation. Food Cosmet. Toxicol. 11, 85-94. Gasiewicz, T.A. and Neal, R.A. (1979). 2,3,7,8-Tetrachlorodibenzo-p-dioxin tissue distribution, excretion, and effects on clinical chemical parameters in guinea pigs. Toxicol. Appl. Pharmacol. 51, 329-339. Harris, M.W., Moore, J.A., Vox, J.G., and Gupta, B.N. (1973). biological effects of TCDD in laboratory animals. General Environ. Health Perspect. 5, 101-109. Huff, J.E., Moore, J.A., Saracci, R., and Tomatis, L. (1980). Long-term hazards of polychlorinated dibenzodioxins and polychlorinated dibenzofurans. Environ. Health Perspect. 36, 221-240. -20- �Jansson, B. and Sundstrora, G. (1982). Formation of polychlorinated dibenzofurans (PCDF) during a fire accident in capacitors containing polychlorinated biphenyls (PCS). Compounds: In Chlorinated Dioxins and Related Impact on the Environment (0. Hutzinger, R.W. Frei, E. Merian, and F. Pocchiari, eds.). pp. 201-213. Pergamon Press, New York, N.Y. Kociba, R.J., Keyes, D.G., Beyer, J.E., Carreon, R.M., Wade, C.E., Dittenber, D.A., Kalnins, R.P., Frauson, L.ee,, Pank, C.N., Barnard, S.D., Hummel, R.A., and Humiston, C.G. (1978). Results of a two-year chronic toxicity and oacogenicity study of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. Toxicol. Appl. Pharmacol. 46, 279-303. Kociba, R.J., Keeler, P.A., Park, C.N., and Gehring, P.J. (1976). chlorodibenzo-p-dioxin (TCDD): rats. 2,3,7,8-Tetra- Results of a 13-week oral toxicity study in Toxicol. Appl. Pharmacol. 35, 553-574. Kociba, R.J. and Schwetz, B.A. (1982). dibenzo-p-dioxin (TCDD). Toxicity of 2,3,7,8-tetrachloro- Drug Metab. Rev. 13, 387-406. Luster, M.I., Faith, R.E., and Lawson, L.D. (1979). Effects of 2,3,7,8-tetrachlorodibenzofuran (TCDF) on the immune system in guinea pigs. Drug Chem. Toxico^. 2, 49-60. McConnell, E.E., Moore, J.A., Haseman, J.K., and Harris, M.W. (1978). The comparative toxicity of chlorinated dibenzo-p-dioxitis in mice and guinea pigs. Toxicol. Appl. Pharmacol. 44, 335-356. Mitruka, M.M. and Rawnsley, H.M. (1981). Clinical Biochemical and Hematolo- gical Reference Values in Normal Experimental Animals and Normal Humans. Masson Publishing USA, Inc., New York. Moore, J.A., McConnell, E.E., Dalgard, D.W., and Harris, M.W. (1979). Comparative toxicity of three halogenated dibenzofurans in guinea pigs, mice and rhesus monkeys. Ann. New York Acad. Sci. 320, 151-163. -21- �New York State Dept. of Health, Center for Laboratories and Research (1982). Analytical Handbook - Toxicology Institute.) Section 312.1. Olie, K., Vermuelen, P.L., and Hutzinger, 0. (1977). Chlorodibenzo-p-dioxins and chlorodibenzofurans are trace components of fly ash and flue gas of some municipal incinerators in the Netherlands. Chemosphere 6, 445-459. Rose, C.I. and Henderson, A.R. (1975). dehydrogenase activity at 37°C. Reaction-rate assay of serum sorbitol Clin. Chem. 21, 1619-1626. Scharer, K. (1977). The effects of chronic underfeeding on organ weight of i rats. How to interpret organ weight changes in cases of marked growth retardation in toxicity tests? Toxicology 7, 45-56. Schwetz, B.A., Norris, J.M., Sparschu, G.L., Rowe, V.K., Gehring, P.J., Emerson, J.L., and Gerbig, C.G. (1973). dibenzo-p-dioxins. Toxicology of chlorinated Environ. Health Perspect. 5, 87-99. Silkworth, J., McMartin, D., DeCaprio, A., Rej, R., O'Keefe, P., and Kaminsky, L. (1982). Acute toxicity in guinea pigs and rabbits of soot from a polychlorinated biphenyl-containing transformer fire. Toxicol. Appl. Pharmacol., in press. Smith, R.M., O'Keefe, P.W., Bilker, D.R., Jelus-Tyror, B.L., and Aldous, K.M. (1982a). Analysis for 2,3,7,8-tetrachlorodibenzofuran and 2,3,7,8-tetrachlorodibenzo-p-dioxin in a soot sample from a transformer explosion in Binghamton, New York. Chemosphere 11, 715-720. Smith, R.M., Hilker, D., O'Keefe, P.W., Kumar, S., Aldous, K., and Jelus-Tryor, B. (1982b). Determination of Polychlorinated Dibenzofurans and Poly- chlorinated Dibenzodioxins in Soot Samples From a Contaminated Office Building. New York State Department of Health Report; March, 1982. -22- �Stalling, D.L., (1981). Chlorinated Dibenzofurans and Related Compounds in Soot Formed in a Transformer Fire in Binghamton, New York, Preliminary Report, Columbia National Fisheries Research Laboratory, U.S. Fish and Wildlife Service, March 31, 1982. Vos, J.G., Moore, J.A., and Zinkl, J.G. (1973). Effects of 2,3,7,8-tetrachloro- dibenzo—p—dioxin on the immune system of laboratory animals. Health Perspect. 5, 149-162. -23- Environ. �Table 1 Body Weights and Soot Consumption in Guinea Pigs After 90-Day Administration of BinRhamton Soot in the Feed Dose Sex Body weight— (g) % of initial body weight Daily soot consumption (rag/kg/day) Total soot consumption (mg/kg) ._. M F 712 ± 27 ( ) 9 594 ± 15 (10) 209 183 0.2 ppm M F 734 ± 17 (10) 591 ± 19 (10) 204 185 0.013 0.013 — 1 .2 1 .2 1.9 ppm M F 663 ± 29 (10) 605 ± 23 (10) 181 177 0.13 0.13 11 .7 11 .9 9.3 ppm M F 9 596 ± 30 ( ) 551 ± 23 (10) 157f 161^ 0.62 0.59 56 .1 0 53 . 46.3 ppm M F 7 498 ± 25 ( ) ± 37 ( ) 7 423 10 3| 128^- 2 .76 3.33 248 .6 299 .6 M F 6 288 ± 17 ( ) ± 14 ( ) 7 235 7 7 Control 231.5 ppn£ I 71^ P B * » • X "12 .9 ~12 .9 — Values expressed ^as x ± standard error ( ) n. — Significantly different from control (Student's t-test), p < 0.05. - p < 0.01 - p < 0.001 £ Necropsy at 32 days. weights at day 32. ~400 ~400 Statistical comparisons made using control animal �Table 2 Absolute Organ Weights in Guinea Pigs Fed Binghamton Soot for 90 Days Absolute Organ Weights Spleen Thyraus Kidney Adrenal Testes 35.936^5.681 0.601+0.023 0.455+0.039 4.588+0.170 0.267+0.011 4.523+0.159 3.761 +_ 0.050 27.609^1.530 0.587^0.055 0.480 + 0.032 4.737 +_ 0.218 0.299+0.015 4.549+0.189 1.9 ppm 3.757 + 0.054 31.081+2.660 0.596 + 0.037 0.351 +_ 0.026^- 4.246 +_ 0.176 0.276 + 0.016 4.505 + 0.169 9.3 ppm 3.570^0.053-31.230 + 2.269 0.598 +_ 0.046 0.254 +_ 0.021- 3.910 + 0.125s- 0.237 + 0.012 3.741 + 0.22(£ 46.3 ppm 3.531 + 0.032-2-23.058 + 1.70(£ 0.601 + 0.034 0.212 + 0.015^- 3.375 + 0.134^ 0.206 + 0.0l£ 3.575 + 0.163^ 3.598 +_ 0.060 24.221 + 2.922 0.737 + 0.047 0.674 + 0.028 4.017 +_ 0.171 0.239 jf 0.011 0.2 ppm 3.708 + 0.076 24.145 + 2.766 0.696 _+ 0.046 0.624 +_ 0.050 3.911 + 0.138 0.240 + 0.011 1,9 ppm 3.619 + 0.037 25.706 ^ 1.806 0.708 + 0.042 0.645 + 0.053 4.063 + 0.199 9.3 ppm 3.600 +_ 0.046 26.410 + 2.115 0,582 + 0.025^- 0.535 +_ 0.032- 3.560 +_ 0.111- 0.197 + 0.007^ 46.3 ppm 3.398 + 0.076 21.849 + 1.138 0.674 + 0.044 3.116 + 0.183^- Sex Brain Male 3.721+0.047 0.2 ppm Dose Control Control Female Liver 0.261 + 0.040^- — Values expressed as x ± standard arror. — Significantly different from control (Student's t-test), p < 0.05 - p < 0.01. - p < 0.001. 0.253 + 0.015 0.173 + 0.010^ �Table 3 Relative Organ Weights in Guinea Pigs Fed Binghamton Soot for 90 Days Relative Organ Weights (g/g body weight X 100)— Dose Sex Brain Th ymus Spleen Kidney Adrenal Testes 5.156 + 0.897 0.085 + 0.005 0.064 + 0.004 0.647 i 0.019 0.038 JH 0.002 0.640 + 0.026 0.2 ppm 0.515 + 0.015 3.749 + 0.151 0.080 +_ 0.007 0.065 + 0.004 0.644 + 0.020 0.041 + 0.002 0.619 _+ 0.017 1.9 ppm 0.575 + 0.022 4.899 i 0.662 0.090 jf 0.005 0.052 + 0.002^- 0.643 jf 0.011 0.042 Hr 0 0 2 . 0 0.683 +_ 0.016 9.3 ppm 0.611 HH 0.030^- 5.370 + 0.550 0.102 +_ 0.009 0.043 i 0.002^ 0.662 + 0.019 0.040 +_ 0.002 0.628 +_ 0.020 46.3 ppm 0.723 + 0.044-S- 4.630 + 0.240 0.122 + 0.007-5- 0.041 + 0.003^- 0.681 Jh 0.014 0.041 j* 0.002 0.721 + 0.019^- 0.609 i 0.016 4.076 + 0.503 0.124 + 0.007 0.114 + 0.004 0.676 +_ 0.020 0.040 + 0.001 0.2 ppm 0.635 + 0.027 4.138 + 0.619 0.118 +_ 0.007 0.105 +_ 0.006 0.664 + 0.017 0.041 _+ 0.002 1 . ppm 9 6.605 + 0.021 4,227 + 0.184 0.119 + 0.011 0.106 +_ 0.007 0.672 ^ 0.020 0.042 + 0.002 9.3 ppm 0.662 + 0.027 4.853 + 0.445 0.106 + 0 0 4 . 0.097 ± 0.003^- 0.650 + 0.015 .0^ 0.036 i 0.001^- 46.3 ppm 0.841 + 0 0 4 5.496 + 0.687 :7^ 0.162 + 0. 007- 0.060 i 0.006^- 0.752 + 0.031 0.042 + 0.003 Control Control Male Female 0.529 _+ 0.020 Liver — Values expressed as x ± standard error. — Significantly different from control (Student's t-test), p < 0.05 - p < 0.01. d - p < 0.001 . �Table 4 Heraatological Values in Guinea Pigs Fed Binghamton Soot for 90 Days— Sex Red Cell Count (X 10 /nun ) White Cell Count (X 10 J /mm J ) Platelet Count (X 10 /nun ) Male 5 .95 ± °- 20 5.67 + 0.80 25.00 + 2.43 0.2 ppm 5 .24 ± °- 13^ 6.90 + 0.81 -n.d 1.9 ppm 5 .90 ± °- 18 7.48 i 1.42 19.83 + 2.74 47.7 ± ° .8 9.3 ppm 5 .34 ± °- 21 7.31 + 1.09 23.00 + 4.64 44.0 + 1 .0^ 46.3 ppm 5 .17 ± °- is* 3.79 ± °-41 17.57 + 2.51 43.9 ± 5 .50 ± °- 14 7.80 ± i- 08 29.78 ^ 5.07 43.9 ± ° .8 0 , 2 ppm 4 .83 ± °- 15* 6.93 i 0.89 -n.d. i .9 ppm 5 .31 ± °- 12 6.53 + 1.09 18.40 ± 1.63^ 45.2 + 1 .2 9.3 ppm 5 .17 ± °- 13 5.18 + 0.65 27.10 + 2.77 43.8 ± ° .7 46.3 ppm 5 .04 ± °- 15* 4.57 + 0.67^- 26.00 + 1.76 39.1 ± ° .71 Dose Control Control Female * - Values expressed as x ± standard error. — Significantly different from control (Student's t-test), p < 0.05. - p < 0.01. - p < 0.001. — not determined. Packed Cell Volume ("/) \**j 48.0 ± l .1 47,7 ± ° .7 3 .2 46.1 ± ° .6^ �Table 5 a^ Serum Enzyme Values from Guinea Pigs Receiving Binghamton Soot for 90 Days Sex Lactate Dehydrogenase (uM/min/L) Aspartate Aminotransf erase (uM/min/L) Alanine Aminotransf erase (uM/min/L) y-Glutamyl Transf erase (uM/min/L) Alkaline Phosphatase (uM/min/L) Sorbitol Dehydrogenase (uM/min/L) Male 250 + 42 60 + 11 65 + 11 11.4 + 1.2 103.2 + 7.3 93 + 19 0.2 ppm 237 + 29 62 + 9 41+4 10.8+0.2 112.0+12.2 70+17 1.9 ppm 289 + 39 69 + 12 39 + 2^ 10.7+1.0 92.0+10.1 80+21 9.3 ppm 309 + 60 74 + 18 27 + 3- 9.0+0.5 105.2+6.8 68+17 46.3 ppm 251 + 37 47 + 6 25 + 3^" 8.2 + 0 3 .k 107.6+11.1. 56+7 226 + 24 49 + 8 33 + 2 0.2 ppm 174 + 22 48 + 6 1.9 ppm 157 + 7~ 9.3 ppm 46.3 ppm Dose Control Control Female 10.5 + 0.7 106.7 + 5.0 23 + 1- 8.9 + 0.8 101.1 + 3.3 49+9 40 + 3 27 + 3 8.2 + 0 4 105.1 + 8.1 .- 57 + 7 221 + 55 58 + 16 22 + 1- 9.1 + 0.3 99 + 34 189 + 15 53 + 15 20 + 2^- 8.4 + 0 5 103.4 + 6.9 .- a — Data expressed as 3c ± standard error, n - 5 to 10 per group. b — Significantly different from control (Student's t-test), p < 0.05. — p < 00. .1 - p < 001 .0. 117.2 + 9.1 • 84 + 17 51+7 �Table 6 Serum Chemistry Values^- from Guinea Pigs Receiving Binghamton Soot for 90 Days Bilirubin (mg/dl) Glucose (mg/dl) BUN (mg/dl) Total protein (g/dl) Albumin (g/dl) Globulin (g/dl) Na+ (mEq/1) K+ (mEq/1) •HCa (mg/dl) 0.2 ± 0.0 175 ± 19 26 ± 1 5.4 ± 0.1 3.5 ± 0.1 1.9 ± 0.1 147 ± 1 10.4 ± 0.3 13.2 ± 0.2 107 ± 1 94 ± 8 0.5 ± 0.0 0.3 ± 0.0 250 ± 13 22 ± 1 5.4 ± 0.1 3.6 ± 0.1 2.0 ± 0.1 143 ± 2 10.3 ± 0.4 13.5 ± 0.1 106 ± 1 98 ± 23 0.5 ± 0.0 1.9 ppm 0.0 t 0 0 203 ± 11 .^ 25 ± 1 6.4 ± 0.4s- 3.6 ± 0.3 2.8 ± 0 4 141 ± l£ 10.4 ± 0.2 .^ 13.6 ± 0.1 105 ± 1 93 ± 7 0.6 ± 0.0 9.3 ppm 0.2 ± 0.0 192 ± 12 23 ± 1 5.3 ± 0.1 3.4 ± 0.1 1.9 ± 0.1 139 ± 2 . S 9.7 ± 0.3 13.0 ± 0.1 104 ± 1^ 127 ± 16 0.5 ± 0.0 46.3 ppm 0.2 ± 0.0 223 ± 14 26 ± 1 5.2 ± 0.1 3.5 ± 0.1 1.9 ± 0.1 140 ± 2^ 9.4 ± 0.5 13.1 ± 0.2 105 ± 1 176 ± 22^ 0.7 0.2 ±.0.0 221 ±16 23 ± 1 5.5 ± 0.1 3.5 ± 0.1 1.9 ± 0.1 148 ± 1 10.9 ± 0.3 13.2 ± 0.2 106 ± 1 0,2 ppm 0.3 ± 0.0 200 ±12 26 ± 1 5.5 ± 0.1 3.5 ± 0.1 2.0 ± 0.1 146 ± 1 10.2 ± 0.3 13.3 ± 0.1 106 ± 1 91 ± 6 ^ 0.5 ± 0.0 1.9 ppm 0.0 ± 0 0 208 ± 8 .^ 24 ± 1 5.6 ± 0.2 3.6 ± 0.1 2.1 ± 0.2 145 ± 1 10.3 ± 0.3 13.2 ± 0.2 104 ± 1 73 ± 8 ^ 0.4 ± 0.0 9.3 ppm 0.3 ± 0.<£ 204 ± 8 24 ± 1 5.7 ± 0.1 3.8 ± 0.1 2.0 ± 0.0 147 ± 1 9.7 ± 0 3 13.1 ± 0.1 106 ± 1 .^ 101 ± 14- 0.5 ± 0.0 0.2 ± 0.0 26 i 2 5.3 ± 0.1 3.5 ± 0.1 147 ± 2 9.0 ± 0.4- 164 ± 23^ 0.6 ± Dose Sex Control 0.2 ppm Control Male Female 46.3 ppm 173 ±18 a —• — Data expressed as x t standard error, n - 5 to 10 per group. i . Significantly different form .control (Student's t-test), p < 0.05. - p < 0.01. — p < 001 .0. 1.9 ± 0.1 Cl Triglycerides Creatinine (mEq/1) (mg triolein (mg/dl) equivalent/dl) 13.2 ± 0.2 107 ± 2 144 ± 6 t o.os. 0.5 ± 0.0 �Table 7 Frequency of Microscopic Lesions in Male Guinea Pigs Dose Control No.— % Grade5- 1.9 ppm 0.2 ppm 46.3 ppm 9.3 ppm No. X Grade No. X Grade No. % Grade No. 0 0/10 0 2/10 20 1± 0 4/9 44 1± 0 0/9 0 0/10 0 2/10 20 1/9 11 Lancrimal gland, focal adenitis 0/9 0 0/10 0 0/10 0 4/9 44 Bone marrow, cellular depletion 0/9 0 0/9 0 Skeletal muscle, degeneration 0/9 0 0/9 0 Liver, focal necrosis 5/9 55 5/10 50 3/10 30 1/9 11 Liver, fatty infiltration 0/9 0 0/10 0 0/10 0 0/9 Liver, bile duct hyperplasia 1/9 11 1 ± 0 0/10 0 3/10 30 0/9 Liver, hepatocellular cytoplasmic inclusion bodies 0/9 0 0/10 0 0/10 Kidney, focal Interstitial nephritis 3/9 33 Thymus, thinning of cortex 0/9 Stomach, degeneration Salivary gland, metaplasia of duct epithelium 0/9 Pancreas, goblet cell hyperplasia of duct epithelium , 0 1± 0 231.5 ppm No. % Grade 4/7 57 2 ± 1 3/7 43 1 ± 0 4/7 57 3/7 43 4/7 57 1 ± 0 3/7 43 1 ± 1 0/7 0 4/7 57 2 ± 1 0/7 0 1/7 14 5/7 71 2/7 29 0 0/7 0 4/7 57 0 2/7 29 1 ± 0 0/7 0 5/7 71 2 ± 1 0/7 0 5/7 71 0/7 0 4/10 40 1± 0 2±0 z Grade 5/9 55 0 0/9 0 0/7 0 1/6 17 0/9 0 0/9 0 0/7 0 2/5 40 Small intestine, degeneration 0/9 0 0/9 0 0/7 0 1/7 14 Large Intestine, degeneration 0/9 0 0/9 0 0/7 0 1/7 14 Testis, unilateral degeneration 0/9 0 2/9 22 0/7 0 0/7 0 5/10 50 — Animals surviving for 90 days, except 32 days for 231.5 ppm group. b — Data expressed as no. of positive findings/no, of animals examined. £ _ Data expressed as x ± standard deviation. 4/10 40 2 ± 1 �Table B Frequency of Microscopic Lesions in Female Guinea Figa Dose Control b No.- % Grade" 0.2 ppm 9.3 ppm 1.9 ppm No. 2 Grade No. % Grade No. % Grade No. 0/10 0 2/10 20 1± 0 3/10 30 1± 0 7/7 100 Salivary gland, metaplasia of duct epithelium 0/10 Pancreas, goblet cell hyperplasia of duct epithelium 2/10 20 1/10 10 3/10 30 Lacrimal gland, focal adenitis 0/10 0 1/10 10 0/10 Bone marrow, cellular depletion 0 46.3 ppm % 231.5 ppm Grade No. z Grade 1/7 14 1 ± 0 2±0 3/10 30 3/7 43 0/7 0 0/10 0 5/7 57 1 ± 0 3/7 43 1 ± 0 0/10 0 0/10 0 2/7 29 1 ± 0 5/7 57 2 ± 1 Skeletal muscle, degeneration 0/10 0 0/10 0 0/7 0 0/7 0 Liver, focal necrosis 4/10 40 1/10 10 2/7 29 1/7 14 Liver, fatty infiltration 0/10 0/10 0/7 0 4/7 51 Liver, bile duct hyperplasia 0/10 0 1/7 14 2 ± 0 0/7 0 Liver, hepatocellular cytoplasmic inclusion bodies 0/10 5/7 57 1± 1 0/7 0 Kidney, focal interstitial nephritis 6/10 60 3/7 43 0/7 0 Thymus, thinning of cortex 0/10 0 0/10 0 0/7 0 3/7 43 Stomach, degeneration 0/10 0 0/10 0 0/7 0 0/7 0 Small intestine, degeneration 0/10 0 0/10 0 0/7 0 0/7 0 Large intestine, degeneration 0/10 0 0/10 0 0/7 0 0/7 0 0 0 1/10 10 1/10 10 0 0/10 0 1/10 10 2/10 20 0/10 0 0/10 0 1/10 10 7/10 70 6/10 60 0/10 — Animals surviving for 90 days, except 32 days for 231.5 ppm group, — Data expressed as no. of positive findings/no, of animals examined. — Data expressed as 3c ± standard deviation. 0 3±0 1± 0 0 8/10 80 7/10 70 2t1 I ± 0 �LEGENDS Fig. 1: Body weight changes in (a) male and (b) female guinea pigs receiving soot from the Binghamton. State Office Building transformer fire in the feed. Asterisks indicate individual mortalities during the observa- tion period. Values significantly different from control (p < 0.05) at 46.3 and 231.5 ppm soot dose levels from day 6 onward, and at 1.9 ppm soot from day 14 onward. Fig. 2: Interlobular duct of salivary gland from (a) control guinea pig and (b) guinea pig receiving 46.3 ppm Binghamton soot in the feed for 90 days. Stratified squamous epithelium has replaced the normal columnar cells of this duct. Fig. 3: Bone marrow of sternum from (a) control guinea pig and (b) guinea pig receiving 231.5 ppm Binghamton soot in the feed for 32 days. Heraatopoietic cells are markedly reduced in number in marrow from treated animals. -24- �CONTROL 200 150 46.3 X CD 100 UJ 231.5 50 CD E 200 o B CONTROL- o 150 xp • * •• 46.3 100 231.5 500 20 40 60 DAY OF STUDY 80 �f l V, � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 088 Folder The folder containing the original item. 2202 Series The series number of the original item. Series IV Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource DeCaprio, Anthony P. Donald M. McMartin Jay B. Silkworth Robert Rej Ronald Pause Laurence S. Kaminsky Description An account of the resource <strong>Corporate Author: </strong>Center for Laboratories and Research, New York State Department of Health, Albany, New York Date A point or period of time associated with an event in the lifecycle of the resource October 13 1982 Title A name given to the resource Subchronic Oral Toxicity in Guinea Pigs of Soot from a Polychlorinated Biphenyl-Containing Transformer Fire Subject The topic of the resource BSOB animal testing PCBs risk assessment Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 092 Folder The folder containing the original item. 2312 Series The series number of the original item. Series IV Subseries IV Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Wander Tumiatti, P. I. Description An account of the resource <strong>Corporate Author: </strong>Sea Marconi Decontamination Date A point or period of time associated with an event in the lifecycle of the resource October 1 1979 Title A name given to the resource Sea Decontamination Codet-PCB system Subject The topic of the resource PCBs decontamination