1 15 1 https://www.nal.usda.gov/exhibits/speccoll/files/original/705d330b601bd6f010265578c4d03efa.pdf b4e95d1fe9cf25954eae9a55134fb242 PDF Text Text Item ID Number ones Bababunmi, Enitan A. Corporate Author Report/Article TltlB Toxins and Carcinogens in the Environment: An Observation in the Tropics JOUmal/BoOk TltlO Journal of Toxicology and Environmental Health Year Month/Day Color D Number of Images 9 DOSCrlptOn NotOS ^'vin ^- Young filed this item under the category "DDT/Human Toxicology and Environmental Fate" Wednesday, April 11, 2001 Page 1188 of 1242 �TOXINS AND CARCINOGENS IN THE ENVIRONMENT: AN OBSERVATION IN THE TROPICS Department of Biochemistry, School of Medicine, University of Ibadari, Ibadan, Nigeria The incidence of primary liver cancer in the countries of tropical Africa is the highest in the world. There, is a growing belief that the relatively high prevalence of hepatocellular carcinoma in Niyeria may have a multiple chemical factor etiology in such forms as food contaminants, herbal leas, and environmental chemicals. Major chemical toxins and carcinogens that have been identified so far in the tropical environment include supotoxin, cycasin, mushroom toxin, capsaicin, oxalic acid, prussic acid, fluotooleic acid, N-nitroso compounds, aflatoxin, palmotoxin, pyrrolizidine alkaloids, quinine, DOT, and eye/ornate. INTRODUCTION During the past two decades, there has been an increasing awareness of the hazards to human and animal health from various chemical substances Jthat occur in the tropical environment. There is evidence to indicate that azarious health problems, including some forms of cancer, have their origin in the presence of toxic chemicals in medicines, herbal residues, pesticides, foods, and drinks. Some of these problems are common to countries throughout the world, while others are peculiar to Africans who live in the tropics. For example, altogether the incidence of primary liver cancer in adult males is • the highest in the world in African countries such as Nigeria, Uganda, and Mo/ambique (IARC, 1971). The primary objective of the present review is to focus attention on the presence of toxic chemicals in foods and in the environment of tropical African countries, particularly Nigeria, which is the most populous country in Africa. Some of these toxins have been shown to possess carcinogenic (or mutagenic) properties in various biological systems. However; in a large number of cases, adverse effects of some of these toxic substances on human health are not known. It is hoped that this paper will have the important effects of stimulating more research into the special toxicological problems that arc of concern to people living in the tropics. This article was written during the author's tenure as an ICRCTT Fellow of UICC (1977) at the Department of Biochemistry and King's College, University of Cambridge, Cambridge, [England. Requests for reprints should he sent to fcnitan A. Bababunmi, Department of Biochemistry, School'of Medicine, University of Ibadan, Ibadan, Nigeria. 691 journal oi Toxicology and Environmental Health, 4:691-699,1978 Copyright © 1978 by Hemisphere Publishing Corporation 0098-4108/78/040691-09$2.25 �692 E. A. BABABUNMI ENDOGENOUS FOOD TOXINS Endogenous food toxicily is widespread in tropical Africa. Nicholls ct al. (1961) dealt with the various types.of tropical foods that carry toxins. The review of Crampton and Charlcsworth (1975) adequately covers the occurrence of food toxins in the nontropical world. Hypoglycin This toxin is contained in the unripe fruit of the food plant, Blighia sapida. In Nigeria the fruit is called isin, whereas it is commonly known as ak.ee in Jamaica. There are two types of this toxin, A and B. Although both types are biologically active, the A type (/J-mcthylenecyclopropylalaninej is the more toxic. Very little work has been done on the chemistry and the biological function of the B type. Dioscorine This toxic chemical is sometimes referred to simply as dioscorea toxin; it is an alkaloid that is present in Dioscorea hispida. The main toxic species of these tropical yams of West Africa are D. hispida, D. dumctorum, D. sansibarensis, and D. bulbifem. Since the isolation and identification of the related alkaloid dehydrodioscorine by Bevan and H.rst (1958), scientists have not looked into the existence of these or other structures in the other species of the wild yams. Sapotoxin Some tropical foodstuffs such as soybean, breadfruit, tomato, melon, orange, and groundnut contain some sapotoxin, which, at high concentrations, has drastic effects on humans. The toxin can cause gastroenteritis and produce paralysis of the nerve centers. Sapotoxin is a nitrogen-free glycosidc. Cycasin Cycasin occurs in plants of the family Cycadaceae, which are indigenous to tropical and subtropical regions (IARC, 1972). The biologically active moiety of cycasin is the aglycone melhyla/oxymelhanol. Cycad seeds are used as medicine in some parts of Africa, Indochina, and India. Feeding of a cycad diet has been shown to induce malignant tumors of the liver in the rat, mouse, hamster, fish, and guinea pig (IARC, 1972). Mushroom Toxin A large number of mushroom species are edible, but certain species that arc eaten in the tropics are poisonous. Examples of toxins elaborated by these species are agaritine (Ayaric'us bisporus toxin) and champigeon (A. hortemis toxin). Muscarine and Amanita phalloictes toxin have been reported to be toxic by Nicholls el al. (1961). �TOXINS AND CARCINOGENS IN THE TROPICS 693 Names for different species of mushrooms are descriptive in many pails of I he tropics. In the western state of Nigeria, these names give an indication either of the habitat, morphology, and texture or of the growth habitat of the fungi (Oso, 1975). Corprinus ephemerus, a fungus that grows on dunghills, appears at night or early in the morning, and within a very short time the pilcus is fully expanded. However, it deliquesces in the sun. It is considered poisonous by the Yoruba people of Nigeria, and local doctors use it in the preparation of some (harms. (Extracts of the fungus should be tested for mutagenicity. Capsaicin (Red Pepper Toxin) The substance is the active principle of the plants Capsicum annum and C. frutescens. It is a powerful irritant and a skin blister. Although these plants are rich in vitamin C, excessive feeding on them can be dangerous. Species of pepper such as Piper nigrum contain alkaloids and volatile oils that are toxic to both animals and humans. Halogeton Toxin (Oxalic Acid) Plant species such as Halogelon ylomeritus, Celosia argentae, Amaranthus candatus, Celosia laxa, and Talinum are used as food in tropical Africa, especially on the west coast. These vegetables contain significant levels of oxalic acid (Oke, 1967). There are conflicting data on the lethal dose for humans. However, Oke showed that an average healthy Nigerian would consume about 6 g of oxalic acid daily, on the basis that 50 g of fresh vegetables could be consumed at a meal. Cyanogen (Prussic Acid) Tropical plants, cassava, mai/ie, and sugar cane are good sources of cyanogenetic glycosides such as linamarin and dhurrin. Cassava (manioc; Man/hot ulilissima} is the most widely grown of all tropical root crops. It is mainly a carbohydrate food with a very low protein content. In West Africa, manioc flour (gari). has become a major diet. In the West Indies the dried flour is called farina. All over the tropics it is used as food for the young and adults in one form or another. The en/yme linasc liberates prussic acid (HCN) from linamarin. HCN is toxic to many species of animals, including humans. The production of HCN varies with the variety of the plant and the conditions of cultivation (Osuntokun et a!., 1969). Although significant amounts of HCN arc said to occur only in the bitter variety of cassava, there is in fact no clear differentiation between the sweet and hitler strains. The fact that the cortex of the root contains the highest concentrations of the toxin provides biological protection for the plant against invading insects. Chronic cyanide intoxication by laboratory animals has resulted in neural damage in the guinea pig, rabbit, sheep, and cat. �694 E. A. BABABUNMI Fluoruoleic Acid The seeds of the West African plant Dichapctalum toxicarum contain fluoroeleic acid and some minute amounts of shorter-chained fluoro acids. These fluoro compounds arc toxic.'Local, doctors in the countries of West: Africa often administer the seed extracts in an attempt to produce loss of motor activity, loss of sensation, and sometimes death (Peters el al., I960). Free oleic acid uncouples oxidative phosphorylation (Pressman and Lardy, 1956). /V-Nitroso Compounds .Dimclhylnilrosaminc (DMN) and diethylnilrosamine (DEN) have been detected in measurable quantities in several alcoholic beverages in Nigeria (joaquim, 1973). Bababunmi et al. (1977) reviewed the extent of contamination of these drinks by the two carcinogens. There is some evidence that the formation of these nil.rosamines involves bacterial action. FUNGAL TOXIC CONTAMINANTS Fungus-infected foodstuffs are the cause of many types of food poisoning (see Kadis et al., 1972). In the tropics, a Variety of fungal species have been reported to be involved in some toxicity syndromes. Notable examples are Asperyi/lus, Penicil/ium, Stachybotrys, Trichoderma, f-'usarium, Pseudomonas, and .Helminthosporiurn species. The most ubiquitous in Nigeria are Aspergillus and Pcnicillium. Many strains of each of these fungi are toxigenic. Among the common toxic metabolites of the aspergilli arc aspergillic acid, flavacol, j3-nilropropionic acid, kojic acid, sterigrnatocystin, ochratoxin, aspet toxin, aflaloxin, and palmotoxin. Penicillium elaborates the mycotoxins patulin, islandiloxjn, lutcoskyrin, rugulosin, cifrinin, frcquentic acid (citreomycctin), gliotoxin, costaclavine, and citreviridin. Of these, aflatoxin has been studied most extensively, mainly because of its potent carcinogenic properties. A comctabolile of aflaloxin, palmotoxin, has been the subject of investigation for some years in this laboratory. Many other naturally occurring toxins (Table 1) that are known should be tested for carcinogenictty. Aflatoxin The literature on the biochemistry, toxicity, carcinogenicity, and mutagenicity of aflatoxin is enormous (Goldblatt, 1969; Wogan, 1975a, 1975b; IRAC, 1976), The discovery of aflatoxin in the tropics (Asplin and Carnagnan, 1961) as a contaminant of human and animal foodstuffs (groundnuts) aroused the interest of scientists all over the world because of i t . health ha/aids and possible economic effects on the producers of these foods. Nigeria is one .of the world's major exporters of groundnuts. Other tropical foods that arc vectors of aflatoxin are beans, corn, rice, cocoa, and wheat. �TOXINS AND CARCINQGtNS IN lilt. TROPICS 695 TABLE 1. Sonic Known Naturally Occurring Toxins Toxic sulislance Occurrence in l-'usaric acid Fiisariuni oxysp oiium Pcriconin T toxin llclminthosporo'sidc Tabtoxin Javanicin Pcriconia circ'inatu 1 lei min tli ospvrium may dis Hvlniitithosporium sqcchari Pseudomonus coronal aciens f-'usarium solan! Possible human exposure through Tomato, sorghum, maize Sorghum Maize Sugarcane Tobacco Maize Aspergillus flavus, the main source of aflatoxin, is common in air and soil, It will grow on agricultural products and food materials in a favorable environment with a relative humidity of 70-90% and a minimum temperature of about 10°C. In general, the growth of A. flavus can be correlated with the production of aflatoxin except at high temperatures, 40-50°C. !n different regions of Muranga in Kenya (Hast Africa), mean aflaloxin levels of about 0.25 ppm in food and 0.1 mg/l in beer have been detected (IARC, 1972). When common food preparations of Nigeria's principal food crops were sampled from local market stalls and assessed for aflatoxin contamination by conventional techniques, the aflatoxin content was not less than 0.5 ppm in any of the foods (Bababunmi, 1976). Several industrialized countries such as the United States, Denmark, Britain, and Italy consider a level of aflatoxin of the order of 0.25 ppm as dangerous and the contaminated food as unconsumable. Although the proportional contribution of agriculture to the Nigerian economy continues to fall, it will continue to be the single most important sector in the economy for a long time (Aboyadc, 1971). The export value of cocoa ranks second to that of oil in Nigeria. In 1974, Nigeria's foreign trade was $3.462 billion. If oil accounted for 80% of the export value in the 1974-1975 fiscal year, other export products such as cocoa, groundnuts, and palm products should account for about $700 million. Therefore, if aflatoxin contamination in this class of export commodities is not eliminated, Nigeria's foreign reserves may diminish continuously. Palmotoxin Isolation of two additional fluorescent toxins from cultures of A. flavus on unfcrmcnled palm sap (a common West African wine) obtained from a variety of Elacis yuineensis was reported by Bassir and Adekunle (1968). Toxicity titrations of pal rnolox iris B 0 and G0 on 6-d-old White Rock chick embryos indicated that B 0 is as toxic as aflatoxin B t . Recent results of Uwaifo ct al. (1977) suggest that the structures of the palmotoxins could be hetetocyclic and may be similar to those of the aflatoxin family (Asao et al., 1965). Comparative mulagenicily studies by �696 E. A. BABABUNMI Uwaifo el v.al. (1978) show that palrnotoxin B() induces microlesions thai consist of point mutations, in Ames' tester strains of Salmonella typhimurium. However, the ratio of the mutagcnicity of aflatoxin fi, to that of palmotoxin B0 is about 6:1. In Nigeria and several developing African countries, several facilities and preservation techniques for agricultural products are quite inadequate. The combination of this unfortunate situation, the natural warm and moist weather, a dirty environment, human error, and ignorance is conducive to the growth of A. f/avus and consequently to the elaboration of mycotoxins (such as aflatoxin and palrnotoxin) on agricultural commodities. It seems to me, therefore, that the problems associated with mycotoxin contamination of food and agricultural products will remain in the developing tropical regions of the world for some time, at least.in the foreseeable future, unless very drastic control measures a' - c initialed. HERBAL RESIDUES For years, herbalists and local doctors in tropical Africa have used herbs and their concoctions to treat various human diseases (Dal/.iel, 1948). In modern times, countries such as Nigeria and Ghana have intensified their search for authentic medicinal plants ;ind their active principles. Apart from their use as local medicines, many toxic plant species are used as food in many parts of West Africa. Many chemical compounds have been isolated from useful plants of West Africa and characteri/cd in their pure forms. In this respect, scientists in the Department of Chemistry of the University of Ibadan have contributed immensely to the knowledge of the chemistry of active principles in plants. Toxicological and other biological studies of these chemicals are, however, scanty. Miller and Miller (1976) staled that the plant genera Crotolaria, Senecio, Laburnum, and Heliotropium have long been known to contain carcinogenic substances (IARC, 1976), some of which arc pyrroli/idine alkaloids. •; • FOREIGN TOXIC CHEMICALS Environmental toxins of this class exist in such forms as medicines, pesticides, and food additives. With the gradual emergence of some tropical African countries (for example, Nigeria) from the underdeveloped to the developing slate, environmental pollution and the presence of industrial materials such as those used in the processing and packaging of foods are potential sources of toxins. Common examples in this calegory are ioni/ing radiation, plastici/ers, adhesives, paraffins, printing inks, and irea'cd papers. Well-rccogni/.cd environmental toxic (or carcinogenic) chei lical substances in this tropical area of the world include quinine (antirnalarial drug), DDT (insecticide), and cyclarnate (food additive). �TOXINS AND CARCINOGENS IN THt TROPICS 697 Quinine Malaria is a disease that occurs throughout the tropical and subtropical countries. It is actually a group of diseases characterized by recurrent attacks of fever, anemia, and enlargement of the spleen. Malaria can also occur in temperate climates if the environmental temperature is right for the protozoan species (e.g., Plasmodium falciparum) to complete their life cycle in the female Anopheles mosquitoes. The parasite lives in the red blood cells. There are three forms of the malaria parasite in humans corresponding to malignant tertian, benign tertian, and quartan malaria. In the tropics the most common malaria is the malignant tertian, although the other two varieties have been identified in a very few cases. Chloroquinc, mcpacrine, and quinine arc drugs that are very effective in rapidly destroying the parasite in the blood. Chloroquinc (Nivaquine) is the most widely used antimalarial drug and has been reported to be the safest. Mcpacrine (Atebrin) can be given only intramuscularly and is not often used. Quinine is the oldest of all the antimalarial medicines. It is also the quickest acting. For many years quinine was the only drug available for the treatment of malaria. Although quinine has some toxic side effects, it is still used, especially for cases that are resistant to other drugs. Quinine was the first alkaloid isolated from the bark of the Cinchona tree. A single oral dose of about 8 g is regarded as fatal for an adult man. Quinine poisoning usually results in nausea, headache, visual disturbances, nervous system and cardiovascular system disorders, and respiratory arrest. DDT The insecticidal properties of DDT are well known (IARC, 1974). This compound has been extensively used as an insecticide and produced commercially for this purpose since 1943, when a low-cost production technique was developed. It has been widely used for the control of numerous insect pests—for example, as a mosquito larvicide and as a residual spray for eradicating malaria in the tropics. DDT is distributed by the World Health Organi/ation throughout the world for the prevention of yellow fever, sleeping sickness, and malaria. Apart from these uses, quantities of DDT are used for the treatment of peppers, onions, soybeans, groundnuts, cowpeas, and sweet potatoes, in storage. Tropical countries such as the Upper Volta and Ghana use at least 500 kg of DDT annually for agricultural purposes. In 1973, research on the environmental effects of pesticides in the tropics was carried out at the International Institute for Tropical Agriculture (IITA), Ibadan. The study was concerned with the effects of DDT (used as a crop protector) on the fertility of agricultural soil. Cowpca (Vigna unyuiculata var. Prima), which is a high-yielding legume, was selected in the IITA study because it requires regular pesticide applications and also because of its growing �698 C. A. BABABUNMI importance in tropical agriculture. Since 1970, DDT has been restricted to uses other than on human and animal foodstuffs in the more advanced countries. The hepatocarcinogenicity of DDT on oral administration has been amply demonstrated in several strains of mice. Liver cell tumors were produced in both male and female mice, and an increased tumor incidence was reported in some other organs. The most frequent tumor types were leukemia, rcticulum cell sarcoma, carcinoma of the lungs, and hemangioendothclioma (IARC, 1974). Cyclamate Calcium cyclamate (cyclohexylsulfamic acid calcium salt) is still used as a nonnutritivc sweetener in a large number of soft drinks in many African countries. The use of cyclamic acid as a sweetener has been banned in several industrialized' countries because the compound was suspected of being a bladder carcinogen in the rat. CONCLUSION Apart from foods, beverages, and medicines, there are other sources of potential toxins and carcinogens that are introduced by humans into the tropical environment, especially in the cities, in such forms as narcotics and atmospheric pollutants. With the arrival of various industries in big African cities, inhalation of dust, vapors, and exhausts presents a new form of danger. Epidemiologic appraisal of these factors is lacking. There is a need to estimate the total load of toxins and carcinogens in the tropical environment. REFERENCES Aboyadc, O. 1971. Nigeria's economy. In Africa South of the Sahara, 1st ed., pp. 558-563. London: Luropa. Asao, T., Buchi, G., Abdel-Kader, M. M., Chang, S. 13., Wick, E. I . and Wogan, G. N. 1965. The ., structures of aflaloxins B and G,. ]. Am. Chum. Soi: 87:882-886. Asplin, [-". D. and Carnaghan, K. 13. A. 1961. The toxicity o\ certain groundnut meals for poultry with special reference to their effect on ducklings and chickens. Vet. Kec. 73:1215-1219. Bababunrni, Li. A. 1976. Excretion of af'latoxin in the urine of normal individuals and patients with liver diseases in Ibadan (Nigeria). In Di'tuclifin and 1'revcnt/on of Cancer, ed. H. E. Nieburgs. New York: Ueker. Babdbunni, L:. A., Uwaifo, A. O., and Bassir, O. 1977. Hepatocarcinogeris in Nigerian foodstuffs. World Rev. Nutr. Did 28: article 44. Bassir, O. and Adckunle, A. A. 1968. Two new metabolites of Aspcnjillus lluvus (Link). FF.BS Lett. 2:23-25. Bevan, C, W. 1.. and Hirst, ). 1958. A convulsuil alkaloid of Dioscoreu dunu'torurn.' Chcm. Ind, 4: 103. . Crampton, K. l:. and Charlesworlh, I . A. 1975. Occurrence of natural toxins in food. Or. Mvd. B II. 31:209-213. Dal/:iel J. M. 1948. Useful plants of west tropical Africa. In i-loia of West Tropical Africa, cds. J. hutchinson and J. M. Dal/iel. London: Crown Agents for the Colonies. �TOXINS AND CARCINOGENS IN Tilt TROPICS 699 Goldblalt, L A. 1969. Allatoxln. New Yoik: Academic Press. IARC. 1971. Liver Cancer. Sci. I'ubl. no. I. l.yon: International Agency for Research on Cancer. IARC. 1972. Evaluation of Carcinogenic Risk of Chemicals to Man, vol. 1. Lyon: International Agency for Research on Cancer. IARC. 1974. Chemical Carcinogencsis l.'ssays. Sci. Publ, no. 10. Lyon; International Agency for Research on Cancer. IARC. 1976. Evaluation of Carcinogenic Risk of Chemical* to Man, vol. 10. Lyon: International Agency lor Research on Cancer. Joaquim, K. .1973. Nilrosamine contamination of some Nigerian beverages. Ph.D. thesis, Ibadan University. Kadis, $., Ciegler, A., and Ajl, S. J. 1972. In Microbkil Toxins: A Comprehensive Treatise, vol. 8, Fungal Toxins. New York: Academic Press. Miller, j. A. and Miller, !"..• C. 1976. Carcinogens occurring naturally in foods. Fed. Proc. 35:1316-1321. Nicholls, L., Sinclair, H. M., and Jelliffe, D. B. 1961. Tropical Nutrition and Dietetics. London: Bailliere, Tindall & Cox. Oke, O. L. 1967. Oxalic acid in plants and in nutrition. World Rev. Nutr. Diet. 8:262-303. Oso, B. A. 1975. Mushrooms and the Yoruba people of Nigeria. Mycologia 67:311-319. Osuntokun, B. O., Monekosso, G. L., and Wilson, J. 1969. Cassava diet and a chronic degenerative neuropathy. An epidemiological study. Niger, j. Sci. 3:3-15. Peters, R. A., Hall, R. J., Ward, P. l:. V., and Sheppard, N. 1960. The chemical nature of the toxic compounds containing fluorine in the seeds of Dkhapelalum toxicarium. Biochcm. J. 77:17-23, Pressman, B. C. and Lardy, II. A. 1956. Effect of surface active agents on the latent ATP-asc of mitochondria. Biochim. B/ophys. Ada 21:458-466. Uwaifo, A. O., Emcrolu, C. O., and Bassir, O. 1977. Comparative study of the fluorescent characteristics ol solutions of aflatoxins and palmotoxins in chloroform. /. Agric. Food Chem. 25:1218-1220. Uwaifo, A. O., Emcrolc, G. O., Bababunrni, E. A., and Bassir, O. 1978. Comparative rnutagcnicity of palmotoxin U0 and aflatoxin B,. In press. Wogan, G. N. I975a. Mycotoxins. Annii. Rev. Pliarmacol. 15:437-451. Wogan, G. N. 1975b. Dietary lactors and special epidemiological situations of. liver cancer in Thailand and Africa. Cancer Rex. 35:3499-3502. Received March 12, 1978 Accepted April 3, 1978 � 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. 047 Folder The folder containing the original item. 1188 Series The series number of the original item. Series III Subseries I 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 Bababunmi, Enitan A. Source A related resource from which the described resource is derived Journal of Toxicology and Environmental Health Date A point or period of time associated with an event in the lifecycle of the resource 1978 Title A name given to the resource Toxins and Carcinogens in the Environment: An Observation in the Tropics Subject The topic of the resource heath effects pesticide toxicology ao_seriesIII