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Saccharin and tryptophan metabolism
174
Reviews of recent publications--Fd Chem. Toxic. Vol. 22, no. 2
identification of the actual compounds (including impurities) involved. In considering the pesticides individually, the Group concluded that there was sufficient evidence for the carcinogenicity of nitrofen and sulfallate in animals. Although no data were available on the carcinogenecity of chlordimeform in animals there was sufficient evidence that p-chloro-otoluene, a chlordimeform metabolite, was carcinogenic in animals. Limited evidence was available for the carcinogenicity of chlorobenzilate, dicofol, tetrachlorvinphos, diallate, captan, chlorothalonil and sodium o-phenylphenate in animals. The data from animal studies were inadequate for evaluating the carcinogenicity of parathion, fluometuron, (4-chloro-2-methylphenoxy) acetic acid, o-phenylphenol, l-naphthylthiourea and trichlorfon, but further work with trichlorfon was recommended because of its demonstrated mutagenicity. The available data did not provide any evidence that malathion (or its metabolite malaoxon), methylparathion or piperonyl butoxide were carcinogenic in animals. Although there were no relevant human data, it was concluded that there was no evidence to suggest that these substances were likely to represent a carcinogenic risk for man. There were inadequate or insufficient human data for evaluation of the risk posed to man by diallate, l-naphthylthiourea, fluometuron, (4-chloro-2-methylphenoxy) acetic acid, chlordimeform, chlorobenzilate, dicofol, parathion, tetrachlorvinphos, trichlorfon, nitrofen, sulfallate, captan, chlorothalonil, o-phenylphenol and sodium o-phenylphenate, but in view of the animal findings on nitrofen and sulfallate, the Group considered that these two pesticides should be treated in practice as human carcinogens. Since pesticides containing secondary or tertiary amino groups can be nitrosated, the possibility exists that N-nitroso compounds could be formed from pesticide residues in vivo or during the manufacture or storage of the commerical product. The Appendix to this volume discusses pesticide nitrosation, lists the N-nitroso compounds that are reported to have been formed by this mechanism and names the pesticides in which N-nitroso compounds may be found. Brief details of the studies that have been performed with N-nitrosatable pesticides (with and without nitrite) and N-nitroso derivatives of pesticides are also tabulated, along with information on the genotoxicity of non-nitrosated and nitrosated products of selected pesticides. Volume 31, the most recent issue in this series, covers a number of food additives, naturally occurring substances and veterinary drugs that are added to animal feeds. The Working Group concluded that 3-amino- 1,4-dimethyl-5H-pyrido[4,3-b]indole (TrpP-l) and its acetate, 3-amino-l-methyl-5Hpyrido(4,3-b]indole (Trp-P-2) and its acetate, 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2), degraded carrageenan and gyromitrin had all yielded sufficient evidence of carcinogenicity in animal studies. Limited evidence for carcinogenicity was obtained from animal studies with 2-amino5-nitrothiazole, nithiazide, cinnamyl anthranilate, ochratoxin A, petasitenine, quercetin, senkirkine, zearalenone and two fungal metabolites of agaritine (although not the compound itself), but only inade-
quate data were yielded by animal studies on cholesterol, furazolidone, fusarenon X, kaempferol, nitrovin, symphytine and T2-tricothecene. The available data did not provide evidence that native (undegraded) carrageenan is carcinogenic in exl~erimental animals. The data were insufficient or inadequate for evaluation of the risks for man posed by AF-2, agaritine, 2-amino-5-nitrothiazole, degraded and undegraded carrageenan, T2-tricothecene, gyromitrin, cinnamyl anthranilate, furazolidone, fusarenon X, zearalenone, kaempferol, nithiazide, nitrovin, ochratoxin A, TrpP-l, Trp-P-2, petasitenine, quercetin, senkirkine and symphytine, but again it was felt that in view of the results of animal studies it would be reasonable, in practice, to treat Trp-P-l, Trp-P-2, gyromitrin, AF-2 and undegraded carrageenan as if they presented a carcinogenic risk. Animal data for cholesterol were sparse. Although human data revealed limited evidence that a raised dietary intake of cholesterol was associated with an increased risk of breast and colorectal cancer, the data were inadequate to assess the carcinogenicity of cholesterol per se for man. There was, in addition, strong evidence that a low serum-cholesterol level was not in itself related to an increased risk of cancer but there was limited evidence that, within the populations studied, male individuals with relatively low serum-cholesterol levels had an increased risk of colon cancer. The data pertaining to women were inadequate for evaluation. The evidence that a low serum cholesterol increases the risk of cancer at sites other than the colon was considered inadequate. Interest in the potential carcinogenicity of flavonoids, stemming from their presence as glycosides in food and beverages, led the Group to tabulate information on the genotoxicity of various plant flavonoids for which long-term test data have not been published. In addition, to complement the full-scale monographs on the two pyrolysis products of tryptophan (Trp-P-1 and Trp-P-2), details of Ames tests with other pyrolysates isolated from foods were reviewed briefly. Thus the IARC has once again demonstrated its capacity for reviewing and, to some extent, interpreting published data on chemicals to which man is exposed. As an added bonus, sensible and down-toearth comments on related topics of a more general nature, such as quantitative risk assessment and evaluation of risks in specific occupations, have been incorporated. This series deserves a place on most technical bookshelves and, more to the point, deserves to be regularly consulted. BOOKS RECEIVED FOR REVIEW Residue Reviews. Residues of Pesticides and Other Contaminants in the Total Environment. Vol. 87. Edited by
F. A. Gunther. Springer Verlag, Berlin, 1983. pp. viii+ 108. DM 58.00. Pesticide Chemistry: Human Welfare and the Environment: Vol. 1. Synthesis and Structure-Activity Relationships; Vol. 2. Natural Products; Vol. 3. Mode of Action, Metabolism and Toxicology; Vol. 4. Pesticide Residues and Formulation Chemistry. Editors-in-Chief J.
Miyamoto & P. C. Kearney. Pergamon Press Ltd,
Reviews of recent publications--Fd Chem. Toxic. Vol. 22, no. 2 Oxford, 1983. pp. ix+383, ix+372, xi+569 and xi + 429. £195.00 for 4-volume set. Alcohols Toxicology. By W. W. Wimer, J. A. Russell & H. L. Kaplan. Noyes Data Corp., Park Ridge, NJ, 1983. pp. x + 278. $36.00. Dermatological Formulations: Percutaneous Absorption. By B. W. Barry. Marcel Dekker, New York, 1983. pp. viii + 480. Sw,fr. 149.00.
Environmental Carcinogens--Selected Methods of Analysis. Vol. 6. N-Nitroso Compounds. Edited by R. Preussmann, I. K. O'Neill, G. Eisenbrand, B. Spiegelhalder & H.
175
Bartsch. IARC Scient. Publ. no. 45. International Agency for Research on Cancer, Lyon, 1983. pp. xxiv + 508. Sw.fr 80.00 (available in the UK through HMSO). Progress in Drug Metabolism. Edited by J. W. Bridges & L. F. Chasseaud. John Wiley & Sons Ltd, Chichester, 1983. pp. ix + 446. £45.00.
Unconventional Sources of Dietary Fiber: Physiological and In Vitro Functional Properties, Edited by I. Furda. American Chemical Society, Washington, 1983. pp. x + 315. $70.95 (US/Canada $58.95).
Reviews of recent publications--Fd Chem. Toxic. Vol. 22, no. 2
identification of the actual compounds (including impurities) involved. In considering the pesticides individually, the Group concluded that there was sufficient evidence for the carcinogenicity of nitrofen and sulfallate in animals. Although no data were available on the carcinogenecity of chlordimeform in animals there was sufficient evidence that p-chloro-otoluene, a chlordimeform metabolite, was carcinogenic in animals. Limited evidence was available for the carcinogenicity of chlorobenzilate, dicofol, tetrachlorvinphos, diallate, captan, chlorothalonil and sodium o-phenylphenate in animals. The data from animal studies were inadequate for evaluating the carcinogenicity of parathion, fluometuron, (4-chloro-2-methylphenoxy) acetic acid, o-phenylphenol, l-naphthylthiourea and trichlorfon, but further work with trichlorfon was recommended because of its demonstrated mutagenicity. The available data did not provide any evidence that malathion (or its metabolite malaoxon), methylparathion or piperonyl butoxide were carcinogenic in animals. Although there were no relevant human data, it was concluded that there was no evidence to suggest that these substances were likely to represent a carcinogenic risk for man. There were inadequate or insufficient human data for evaluation of the risk posed to man by diallate, l-naphthylthiourea, fluometuron, (4-chloro-2-methylphenoxy) acetic acid, chlordimeform, chlorobenzilate, dicofol, parathion, tetrachlorvinphos, trichlorfon, nitrofen, sulfallate, captan, chlorothalonil, o-phenylphenol and sodium o-phenylphenate, but in view of the animal findings on nitrofen and sulfallate, the Group considered that these two pesticides should be treated in practice as human carcinogens. Since pesticides containing secondary or tertiary amino groups can be nitrosated, the possibility exists that N-nitroso compounds could be formed from pesticide residues in vivo or during the manufacture or storage of the commerical product. The Appendix to this volume discusses pesticide nitrosation, lists the N-nitroso compounds that are reported to have been formed by this mechanism and names the pesticides in which N-nitroso compounds may be found. Brief details of the studies that have been performed with N-nitrosatable pesticides (with and without nitrite) and N-nitroso derivatives of pesticides are also tabulated, along with information on the genotoxicity of non-nitrosated and nitrosated products of selected pesticides. Volume 31, the most recent issue in this series, covers a number of food additives, naturally occurring substances and veterinary drugs that are added to animal feeds. The Working Group concluded that 3-amino- 1,4-dimethyl-5H-pyrido[4,3-b]indole (TrpP-l) and its acetate, 3-amino-l-methyl-5Hpyrido(4,3-b]indole (Trp-P-2) and its acetate, 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2), degraded carrageenan and gyromitrin had all yielded sufficient evidence of carcinogenicity in animal studies. Limited evidence for carcinogenicity was obtained from animal studies with 2-amino5-nitrothiazole, nithiazide, cinnamyl anthranilate, ochratoxin A, petasitenine, quercetin, senkirkine, zearalenone and two fungal metabolites of agaritine (although not the compound itself), but only inade-
quate data were yielded by animal studies on cholesterol, furazolidone, fusarenon X, kaempferol, nitrovin, symphytine and T2-tricothecene. The available data did not provide evidence that native (undegraded) carrageenan is carcinogenic in exl~erimental animals. The data were insufficient or inadequate for evaluation of the risks for man posed by AF-2, agaritine, 2-amino-5-nitrothiazole, degraded and undegraded carrageenan, T2-tricothecene, gyromitrin, cinnamyl anthranilate, furazolidone, fusarenon X, zearalenone, kaempferol, nithiazide, nitrovin, ochratoxin A, TrpP-l, Trp-P-2, petasitenine, quercetin, senkirkine and symphytine, but again it was felt that in view of the results of animal studies it would be reasonable, in practice, to treat Trp-P-l, Trp-P-2, gyromitrin, AF-2 and undegraded carrageenan as if they presented a carcinogenic risk. Animal data for cholesterol were sparse. Although human data revealed limited evidence that a raised dietary intake of cholesterol was associated with an increased risk of breast and colorectal cancer, the data were inadequate to assess the carcinogenicity of cholesterol per se for man. There was, in addition, strong evidence that a low serum-cholesterol level was not in itself related to an increased risk of cancer but there was limited evidence that, within the populations studied, male individuals with relatively low serum-cholesterol levels had an increased risk of colon cancer. The data pertaining to women were inadequate for evaluation. The evidence that a low serum cholesterol increases the risk of cancer at sites other than the colon was considered inadequate. Interest in the potential carcinogenicity of flavonoids, stemming from their presence as glycosides in food and beverages, led the Group to tabulate information on the genotoxicity of various plant flavonoids for which long-term test data have not been published. In addition, to complement the full-scale monographs on the two pyrolysis products of tryptophan (Trp-P-1 and Trp-P-2), details of Ames tests with other pyrolysates isolated from foods were reviewed briefly. Thus the IARC has once again demonstrated its capacity for reviewing and, to some extent, interpreting published data on chemicals to which man is exposed. As an added bonus, sensible and down-toearth comments on related topics of a more general nature, such as quantitative risk assessment and evaluation of risks in specific occupations, have been incorporated. This series deserves a place on most technical bookshelves and, more to the point, deserves to be regularly consulted. BOOKS RECEIVED FOR REVIEW Residue Reviews. Residues of Pesticides and Other Contaminants in the Total Environment. Vol. 87. Edited by
F. A. Gunther. Springer Verlag, Berlin, 1983. pp. viii+ 108. DM 58.00. Pesticide Chemistry: Human Welfare and the Environment: Vol. 1. Synthesis and Structure-Activity Relationships; Vol. 2. Natural Products; Vol. 3. Mode of Action, Metabolism and Toxicology; Vol. 4. Pesticide Residues and Formulation Chemistry. Editors-in-Chief J.
Miyamoto & P. C. Kearney. Pergamon Press Ltd,
Reviews of recent publications--Fd Chem. Toxic. Vol. 22, no. 2 Oxford, 1983. pp. ix+383, ix+372, xi+569 and xi + 429. £195.00 for 4-volume set. Alcohols Toxicology. By W. W. Wimer, J. A. Russell & H. L. Kaplan. Noyes Data Corp., Park Ridge, NJ, 1983. pp. x + 278. $36.00. Dermatological Formulations: Percutaneous Absorption. By B. W. Barry. Marcel Dekker, New York, 1983. pp. viii + 480. Sw,fr. 149.00.
Environmental Carcinogens--Selected Methods of Analysis. Vol. 6. N-Nitroso Compounds. Edited by R. Preussmann, I. K. O'Neill, G. Eisenbrand, B. Spiegelhalder & H.
175
Bartsch. IARC Scient. Publ. no. 45. International Agency for Research on Cancer, Lyon, 1983. pp. xxiv + 508. Sw.fr 80.00 (available in the UK through HMSO). Progress in Drug Metabolism. Edited by J. W. Bridges & L. F. Chasseaud. John Wiley & Sons Ltd, Chichester, 1983. pp. ix + 446. £45.00.
Unconventional Sources of Dietary Fiber: Physiological and In Vitro Functional Properties, Edited by I. Furda. American Chemical Society, Washington, 1983. pp. x + 315. $70.95 (US/Canada $58.95).