1 15 3 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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. 104 Folder The folder containing the original item. 2823 Series The series number of the original item. Series 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/. Creator An entity primarily responsible for making the resource Rizzardini, M. M. Romano F. Tursi M. Salmona A. Vecchi M. Sironi F. Gizzi E. Benfenati S. Garattini R. Fanelli Source A related resource from which the described resource is derived Chemospere 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 Toxicological Evaluation of Urban Waste Incinerator Emissions 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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. 097 Folder The folder containing the original item. 2484 Series The series number of the original item. Series 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/. Creator An entity primarily responsible for making the resource Cantoni, Lavinia M. Salmona M. Rizzardini Source A related resource from which the described resource is derived Toxicology and Applied Pharmacology 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 Porphyrogenic Effect of Chronic Treatment with 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Female Rats. Dose-Effect Relationship Following Urinary Excretion of Porphyrins https://www.nal.usda.gov/exhibits/speccoll/files/original/eb3a0f653bc6c863caddf5bc819dbdbc.pdf d0a6a8d81b69aefc041ddd6b323097b2 PDF Text Text Item D Number 02331 Author Rizzardini, M. Corporate Author Report/ArticleTltlO Typescript: Toxicological Evaluation of Urban Waste Incinerator Emissions Journal/Book Title Year 1982 Month/Day November Color D Number of Images 6 DBSCriptOn NOtBS Chemosphere, submitted November '82 Monday, September 24,2001 Page 2331 of 2337 �Chemosphere Submitted, Novemberr82 TOXICOLOGICAL EVALUATION OF URBAN WASTE INCINERATOR . ' - ., ; EMISSIONS :.M« Rizzardini, M. Romano, F. Tursi, M. Salmona, A. Vecchi, M. Sironi, F. Gizzi, E, Benfenati, S. Garattini and R. Fanelli Istituto di Ricerche Farmacologiche "Marie Negri" Via Eritrea 62, 20157 MILAN, Italy ft.EGIONE L O M B A R ' DI A • . • Ufficso Specials di Sevesp' • Servizio Documentazibns Seie Via S. Carlo, 4 . - , 20030 SEVESO (Ml) INTRODUCTION •'"_". .The- incineration of solid urban waste raises- serious problems related to the presence of highly toxic micropollutants in the emissions of incinerating plants. In particular polychlorinated dibenzo-p-dioxins(PCDD) and polychlorinated dibenzofurans (PCDF) mixtures have been found in these emissions (1-5). Assessment of the toxicological risk associated with these mixtures is a major, still unsolved problem. In fact only a few of the 75 PCDD isomers and 135 PCDr isomers have been studied as regards toxicological properties (6,7), and even scarcer are the data on the toxicological effects of their mixtures, most of them artificially built by joining some individual isomers (8-13). In a first attempt to study the potential toxicological properties of a PCDD/PCDF mixture released from an urban incinerator, we carried out an experiment to characterize its immunodepressive and enzyme-inducing properties. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDi) has been shown to. be a very potent immunosuppressant in animals (14), single doses of 1 jig/kg depressing antibody production for more than 40 days ( 5 . Little information is 1) available on the immunosuppressive effects of 2,3,7,8-tetrachlorodibenzofuran (TCDF) in laboratory animals ( 6 . .Very recently TCDF was compared with TCDD for its toxicity on the 1) immune system of mice ( 7 . It is generally believed that these two compounds induce 1) similar toxic effects (18) when 10-30 times more TCDF is given. We reported (17) that the humoral response is more sensitive than cell-mediated reactions (Graft versus Host reactionmitogenic responsiveness) to single TCDF exposure and that the immunosuppression induced by TCDF recovers faster than that induced by TCDD, antibody induction being totally restored by day 40. We thus chose to investigate the effects of extracts from an incinerator on humoral antibody production, using heterologous erythrocytes as antigen. An artificial mixture containing known amounts of TCDD and TCDF was prepared as reference control, to evaluate the interaction of the two toxic agents or their possible synergism. TCDD is among the most potent mixed-function oxidase (MFO) inducing agents yet demonstrated in mammalian liver. Low dose studies in the rat gave an ED5Q of TCDD induction .of benzo(oO pyrene-hydroxylase of 0.63 ug/kg and the smallest dose of TCDD which significantly increased enzyme activity was 0.002 ug/kg (19). In mice (C57B1/6J) an £050 of 0.29 ug/kg TCDD for hepatic AHH induction was estimated (20). �4' * TCDF is closely related to TCDD in structure and acute toxicity ( 8 . Its bio1) logical activity (ED5Q for AHH induction) is almost equivalent to TCDD in the chick embryo (21). In mice (C57B1/6J) and ED50 of 7 ug/kg TCDF was found (20) (AHH induction). An important observation was that there is an excellent correlation between AHH induction and the toxic potency of certain PCDD and PCDF isomers ( 2 . Despite the large 2) amount of information about the single compounds none is yet available on the effect of a mixture of TCDD and TCDF on these parameters (P-450 content and hepatic MFO enzyme system). It was therefore deemed interesting to investigate the inducing properties of a mixture of the two compounds and of extracts from an urban waste incinerator, containing complex mixtures of PCDD and PCDF. " - ' - - - . . / - ' .; MATERIALS Animals ' • , - . , • ' " . • • C57B1/6J male mice where obtaine from Charles River, Calco. (Italy) and used when 10 weeks old* Chemicals ' ' . . • All chemicals involved in the extraction, purification and analysis of the PCDD and PCDF micture have been reported ( ) TCDF was a kind gift from Dr. C. Rappa, University 5. of Umea, Sweden. ' • " ' ' • "^ ' EXPERIMENTAL The PCDD and PCDF mixture was drawn from a modern municipal incinerator in Italy, equipped with electrostatic precipitators. Gas condensate collection and the methods of extraction with n-hexane and of purification were as previously described ( ) An LKB 2091 5. GC-MS equipped with an LKB 2130 computer was used for GC-MS analysis, in the reported conditions (5). An imal_t r eatment After analysis, the sample (mixture 1) was dissolved in 10 ml of acetone-corn oil (1:6 v/v) and given as a single i.p. injection to mice (7-8 per group) as such or diluted 10 times (mixture 1/10), at a dose of 10 ml/kg. TCDD (1.2 ug/kg), TCDF (10 ug/kg) and the mixture of TCDD and TCDF (respectively 1.2 ug/kg and 10 ug/kg) were dissolved and given as described for mixture 1. '~~~' groduction assay_ Q 4- 10° sheep red blood cells were injected i.p. 7 days after treatment with the different toxic agents and plaque forming cells (PFC) in the spleen were counted 5 days later by the Yeme's technique (23). �1 statistical analysis -r- _ - Results are presentad as means +_ s.e.; the statistical significance was evaluated by Duncan's test* Enzyme indue tion_ass ay Mice were killed by cervical dislocation and livers were immediately removed, rinsed in saline and blotted dry. The tissues were homogenized with an Ultra-Turrax apparatus in 0.05M phosphate buffer pH 7.4 (1:4 v/v) and centrifuged at 9000xg for 20 min in a refrigerated centrifuge. The supernatant fractions were stored at -70°C until used for cy to chrome P-450, 7-ECD and protein assay. Cytochrome P-450 was determined according to Omura and Sato (24) . 7-Ethoxycoumarin 0-deethylase activity was assayed according to Greenlee and Poland. ( 5 . Proteins were measured according to Lowry et al. (26). 2) ' ' • ' * . - . . , RESULTS The amounts of individual classes of PCDD and PCDF employed for the experiment are listed in Table 1. They correspond approximately to the amount of micropollutants •released in about . . seconds or the amount obtained from about 0.5 kg of waste ( 7 . 05 2) Table 1 - PCDD-PCDF dose administered (ng/kg) , corresponding to mixture 1 PCDD PCDF a Tetra Penta Hexa Hepta Octa a 3688 (17.5) 4816 (22.9) 7152 (34.0) 4332 (20.6) 1064 (5.0) 8800 (35.3) 7696 (30.9) 4540 (18.2) 3004 (12.1) 880 (3.5) Total 21052 . 24920 In brackets the percentage of the individual classes of isomers. Effect_on_antibody_groduction The effect of an artificial mixture of TCDD and TCDF at a ratio of ' about 1:8 was first investigated. As shown in Fig. 1, TCDD inhibited antibody production by 80% while TCDF at the dose used was not depressive. However, when the two toxic agents were administered together in the same solution, the degree of inhibition (50%) was significantly lower than that induced by TCDD alone (80%) when results are expressed either as PFC/10° splenocytes or as PFC/spleen. Thus, the presence of TCDF can modify the immunosuppressive capacity of TCDD. The simultaneous administration of 3.688 ;ug/kg tetrachlorodibenzodioxin and 8.8 jug/kg tetrachlorodibenzofuran (mixture 1) or of a dose 10 times lower (mix I/ 1C) did not significantly modify the immune response, antibody production being only 15% inhibited. �EFFECT OF SIMULTANEOUS ADMINISTRATION OF TCOD AND TCDF AND OF MIXTURES FROM INCINERATOR ON ANTIBODY PRODUCTION. PFC/10 6 splenocytes r? RFC /spleen 100- o cc H~ z o u u. 50O ** TCDD TCDF TCDO TCDF Mix. Mix. 1/10 1 TCOO TCOF TCDD TCOF Mix. Mix. 1/10 1 •FIG. 1 TCDD (1.2 ug/kg), TCDF (10 ug/kg) and extracts from an incinerator were dissolved in acetone:corn oil (1:6 v/v) and given i.p. on day -7. 4-108 SRBC were given i.p. on day 0 and the test was done 5 days later. Mix 1 = extract containing 3.7 and 8.8 ug/kg of tetrachloro-dibenzodioxin and -dibenzofuran respectively; see Table 1. • Mix. 1/10 » dose one-tenth Mix 1 Effect_on_CYtochrome_P-450_content_and_on_7-etox2Coumarin-0-deeth2lase activity Twelve days after a single dose of 1.2 pg/kg TCDD, cytochrome P-450 content was still about 3 times higher than, in control mice. As expected, there was a shift of 2 nm in.-the peak absorption maximum (from 450 nm to 448 nm; see,Table 2). This shift was also observed when TCDD was administered simultaneously with TCDF. No effect on maximum peak absorption was observed with TCDF alone. In this respect, no clear-cut response was seen when incinerator extracts were given. Parallel to cytochrome P-450 induction, a ten-fold increase was observed in the activity of 7-etoxycoumarin-O-deethylase. TCDF at 10 ug/kg had no inducing effect. When the same doses of chlorinated compounds were given in combination, an induction pattern similar to that caused by TCDD alone was observed; however the content of cytochrome P450 was only doubled in comparison to controls and was significantly lower (p^O.05) than in mice treated with TCDD alone. In the same treatment groups the activity of 7-ECD was 8 times higher than in control mice, but somewhat lower (1179 pmol/min/mg prot. versus 1315) than in TCDD treated animals. The effect of an extract from urban incinerator smoke containing 3.3 and 8.8 ,ug/kg of tetrachloro-dibenzodioxins and dibenzofurans was then evaluated: cytochrome P-450 content �», significantly raised and this inductive effect was more evident on 7-ECD activity. — ten times lower dose of incinerator extract had no effect on cytochrome P-450 or 7-ECD, ' Table 2 - Effect of simultaneous administration of TCDD, TCDF and incinerator mixtures on cytochrome P-450 levels and 7-ethoxycoumarin-O-deethylase activity. Treatment Cytochrome P-450 or P-448a (nmol/mg prot) Vehicle 0.63 +:0.028b ( ) 6c 2,3,7,8 TCDD 2,3,7,8 TCDF 1.87 0.75 1.57 0.97 0.82 TCDD +• TCDF Mix 1 Mix 1/10 + 0.07** (6) £0.04- (6) +_ 0.18**+(5) ^ 0.06* (5) -t- 0.017 ' 6 () 7-Ethoxycoumarin-O-deethylase (pmol/min/mg prot) 143 + 6 (5) 1315 +_ 62 (6)" 173 1179 352 234 ^ 15 (6) +_ 98 ( ) 5' +_ 40 ( ) 6' + 16 (6) +•* p^O.Ol from control group (Duncan's test) *- p^O.05 + pjgO.05 from mice treated with TCDD alone (Duncan's test) 3 . Cytochrome P-450 indicates the microsomal co-binding pigment found in control mice, b Mean + S.E. c In. parentheses the number of observations. For treatment schedule refer to Fig. 1 I CONCLUSIONS Our preliminary results indicate that microsomal enzyme induction is a prompt, sensitive biological parameter of exposure to PCDD and PCDF, even when these compounds are in mixtures whose composition is not completely known. The observation that the administration of a dose of TCDF inactive per se simultaneously with an active dose of TCDD reduced the immunosuppfessive and enzyme inducing capacity of TCDD suggest a competitive effect at the receptor level. From this finding with a given TCDD:TCDF ratio, however, it* is impossible to extrapolate the effects of different ratios or of higher active doses of TCDF. These unexpected biological effects illustrate the complexity of problems to be tackled in order to improve the prediction of toxic effects of mixtures of chemicals released simultaneously in the environment. For the time being, statements on the harmlessness to humans of urban waste incinerator emissions appear untimely (28). / ACKNOWLEDGEMENTS The authors express their gratitude to M. Lodi and R. Tagliaferri (ECOLAB s.r.l. Coop., Vignate, Milano, Italy) for sampling and to Dr. C. Rappe (Department of Organic Chemistry, University of Umea, Sweden), for .supplying the TCDF standard. �'•-.. ^1. K..;.01ie, P.L.. Vermeulen and 0..Hutzinger, Chemosphere, £, 455-459 (1977).* t 2. H.R. Buser, H-P. Bosshardt and C. Rappe, Chemosphere, 7_, 165-172 (1978). 3. G.A. Eiceman, R.E. Clement and F..W. Karasek, Anal. Chem., 51, 2343-2350 (1979). f j 4. J.W.A. Lustenhouwer, K. Olie and 0. Hutzinger, Chemosphere, 9, 501-522 (1980). . ' i c ~~ 5. F. Gizzi, R. Reginato, E. Benfenati and R. Fanelli, Chemosphere, 11, 577-583 (1982). [ 6. M.P. Esposito, T.O. Tiernan and F.E. Dryden, "Dioxins" tJ.S. EPA ; Cincinnati, Ohio (1980). 7. J.A. Goldstein. Halogenated Biphenyls, Terphenyls, Naphthalenes, Dibenzodioxins and Related Products, Elsevier, Amsterdam, R.D. Kimbrough (ed.), 151-190 (1980). ; 8. M. Nishizumi, Toxicol. Appl. Pharmacol., 45, 209-212 (1978). —*—* 9. S.. Oishi, M. Morita and H. Fukuda., Toxicol. Appl. Pharmacol., 43, 13-22 (1978). i i ] 10. H. Bauer, K.H. Schulz and U.Spiegelberg,Arch.iGewerbepathol.Gewerbehyg. 1_8_,538-555( 1961). ! 11. 5. Kawano and. K. Hiraga,, Jpn. J. Pharmacol.,, 28, 305-315 (1978). "" ' 12. S^ Oishi and K. Hiraga, Food Cosmet. Toxicol., 16» 47-48 (1978). 13. K.D. Courtney, Bull. Environ. Contain. Toxicol., 16, 674-681 (1976). 14. J.G. Vos, R.E. Faith and M.I. Luster. Halogenated Biphenyls, Terphenyls, Naphthalenes, Dibenzodioxins and Related Products, Elsevier, Amsterdam, R.D. Kimbrough (ed.), 241-266 (1980). 15* A. Vecchi, A. Mantovani, M., Sironi, W. Luini, M. Cairo and S. Garattini, Chem. Biol. Interact., 20, 337-342 (1980). 16. M.I. Luster, R.E. Faith and L.D. Lawson, Drug Chem. Toxicol., 2_, 49-60 (1979). 17. A. Vecchi, M. Sironi, M.A. Canegrati and S. Garattini, Symposium on Chlorinated Dioxins and Dibenzofurans in the Total Environment, Ann Arbor, Science Publishers, L.H. Keith, G. Chondhary and C. Rappe (eds.), 1983, in press. 18. E.E. McConnell and J.A. Moore, Ann. N.Y. Acad. Sci., 320, 138-150 (1979). 19. K.T. Kitchin and J.S. Woods, Toxicol. Appl. Pharmacol., 47, 537-546 (1979). S'. *"" """ 20. A. Poland, E. Glover, M. DeCamp, C.M. Giandomenico and A.S. Kende, Science, 194, 627-630 (1976). 21. A. Poland, E. Glover and A.S. Kende, J. Biol. Chem., 251, 4936-4946 (1976). 22. A. Poland, W.F. Greenlee and A.S. Kende, Ann. N.Y. Acad. Sci., 320, 214-230 (1979). 23. N.K. Jerne and A.A. Nordin, Science, 140, 405 (1963). 24. T. Omura and R. Sato,'J. Biol. Chem., 239, 2370-2378 (1964). 25. W.F. Greenlee and A. Poland, J. Pharmacol. Exp. Ther., 205, 596-605 (1978). 26. O.H. Lowry, N.J. Rosebrough, A.L. Farr and R.J. Randall, J. Biol. Chem., 193, 265-275 (1951). 27. E. Benfenati, F. Gizzi, R. Reginato, R. Fanelli, M. Lodi and R. Tagliaferri, Chemosphere, in press. i / "28. U.S. Environmental Protection Agency, Environmental News, Nov.19 (1981). _, } � 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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. 093 Folder The folder containing the original item. 2331 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 Rizzardini, M. M. Romano F. Tursi M. Salmona A. Vecchi M. Sironi F. Gizzi E. Benfenati S. Garattini R. Fanelli Date A point or period of time associated with an event in the lifecycle of the resource 1982-11-01 Title A name given to the resource Typescript: Toxicological Evaluation of Urban Waste Incinerator Emissions Subject The topic of the resource incineration dioxin animal testing enzyme induction