Carcinogenicity In Experimental Animals Research Articles

International activities in the field of food additives, with particular reference to carcinogenicity

In recent years, a number of food additives, the use of which had been generally recognized as safe, have been prohibited or restricted following reports of their carcinogenicity in experimental animals. These regulatory actions have created much controversy; notable examples are those related to cyclamates, amaranth, and saccharin. The U.S. decisions in these cases are more stringent than those of other major countries. This paper provides a brief review of the events leading to these decisions, and outline of the “Regulations” in certain major countries, as well as the recommendations of the WHO/FAO Expert Committee on Food Additives. It would appear that the general principle of not permitting the use of proved carcinogens as food additives has been adopted by all regulatory agencies. However, in cases where the benefits to the consumer are unequivocal and the risks are minimal, there is virtual unanimity in decisions regarding their acceptability. On the other hand, where this is not true, differing assessment of the risks and benefits appears to be the main reason for the variance in regulatory decisions.

Hepatic lesions in patients treated with synthetic anabolic steriods.

Hepatic abnormalities are described in three patients who received synthetic anabolic steroids. A child with Franconi's anaemia was treated for four years and at necropsy the liver showed generalized hyperplasia, hyperplastic nodules, and a benign hepatoma. Two adults received only three months' therapy with synthetic androgens; in one there was generalized hepatic hyperplasia and in the other widespread nodular hyperplasia. It is suggested that anabolic steroids may induce tumours through intermediate hyperplastic lesions, a sequence similar to that seen during tumour induction by carcinogens in experimental animals.

The IARC program on the evaluation of the carcinogenic risk of chemicals to man.

The International Agency for Research on Cancer has initiated a program to evaluate the carcinogenic risk of chemicals to man. This program is centered on the production of monographs on individual chemicals, consisting of data on use and production, carcinogenicity in experimental animals, epidemiological studies and case reports, and other biological data such as metabolism and mutagenicity, and ending with a balanced evaluation of all the data made by an international group of experts. Chemicals to be surveyed for the preparation of monographs have so far been selected among those for which some evidence or suspicion of carcinogenicity in experimental animals and/or man exists and for which human exposure is known to occur. Of the 196 compounds already evaluated, 17 have been found to be associated with cancer in man. Ninety-four compounds were definitely carcinogenic in experimental animals, and 41 were shown to have a limited carcinogenic effect in experimental animals. A number of the chemicals found to be carcinogenic in experimental animals are produced in very large quantities. The type of exposure to the 17 chemicals found carcinogenic to man was occupational for fourteen, medicinal for two, and dietary for one.

The carcinogenicity of anticancer drugs: a hazard in man.

The carcinogenic potential of anticancer drugs is discussed in the light of selected basic principles of chemical carcinogenesis. Anticancer drugs which act by alkylation and/or by binding tightly to DNA frequently cause cancer in experimental animals and may be carcinogenic in man. In addition, certain anticancer drugs act as cocarcinogens in experimental systems and augment the tumorigenicity of chemical carcinogens. Host determinants are important in chemical carcinogenesis. Many chemical carcinogens and anticancer drugs require metabolic activation by microsomal enzymes. Studies in twins have shown interindividual variation of drug metabolism in man is greater than intraindividual variation caused by exogenous factors. Therefore, certain individuals may be unusually susceptible to the carcinogenicity of anticancer drugs on a pharmacogenetic basis. Age is also a host determinant. At a given total dose level, age at first exposure to chemical carcinogens has been shown to be an important risk factor in experimental studies and in some epidemiologic investigations in man. Therefore, children may be especially susceptible to the carcinogenicity of anticancer drugs. These treated children have the potential of a normal lifespan; the latency period between initial exposure to a carcinogen and clinical evidence of cancer in man is long, usually 2-5 decades. The problems involved in extrapolating data of carcinogenicity in experimental animals to man are discussed. A single drug may have multiple consequences in experimental studies; for example, actinomycin D can act as an anticancer drug, an anticarcinogen, and a carcinogen. These uncertainities and the clinical results concerning second neoplasms following cancer therapy in both children and adults clearly indicate the need to follow carefully long-term survivors who have received cancer therapy.

Chlorinated dibenzodioxins and dibenzofurans.

Research ArticleOpen AccessChlorinated dibenzodioxins and dibenzofurans.is corrected byErratum J E Huff, and J S Wassom J E Huff Search for more papers by this author and J S Wassom Search for more papers by this author Published:1 September 1973https://doi.org/10.1289/ehp.7305283Cited by:7AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited ByHuff J, Weisburger E and Fung V (2018) Multicomponent criteria for predicting carcinogenicity: dataset of 30 NTP chemicals., Environmental Health Perspectives, 104:suppl 5, (1105-1112), Online publication date: 1-Oct-1996. Huff J (1992) 2,3,7,8-TCDD: A potent & complete carcinogen in experimental animals, Chemosphere, 10.1016/0045-6535(92)90506-M, 25:1-2, (173-176), Online publication date: 1-Jul-1992. Van Den Berg M, Olie K and Hutzinger O (2008) Polychlorinated dibenzofurans (PCDFs), Toxicological & Environmental Chemistry, 10.1080/02772248509357079, 9:3, (171-217), Online publication date: 1-Feb-1985. Veerkamp W, Wever J and Hutzinger O (1981) The metabolism of some chlorinated dibenzofurans by rats, Chemosphere, 10.1016/0045-6535(81)90235-6, 10:4, (397-403), Online publication date: 1-Jan-1981. Huff J, Moore J, Saracci R and Tomatis L (2018) Long-term hazards of polychlorinated dibenzodioxins and polychlorinated dibenzofurans., Environmental Health Perspectives, 36, (221-240), Online publication date: 1-Jun-1980. Wassom J, Huff J and Loprieno N (1977) A review of the genetic toxicology of chlorinated dibenzo-p-dioxins, Mutation Research/Reviews in Genetic Toxicology, 10.1016/0165-1110(77)90001-X, 47:3-4, (141-160), Online publication date: 1-Jan-1977. Madge D (1977) Effects of trichlorophenoxyacetic acid and chlorodioxins on small intestinal function, General Pharmacology: The Vascular System, 10.1016/0306-3623(77)90007-6, 8:5-6, (319-324), Online publication date: 1-Jan-1977. Related articlesErratumDec 1, 1973, 12:00:00 AMEnvironmental Health Perspectives Vol. 5September 1973Metrics About Article Metrics Publication History Originally published1 September 1973Published in print1 September 1973 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact ehponline@niehs.nih.gov. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

888. Nitrosamines in food? Action needed now!: Sakshaug, J., Sögnen, E., Hansen, M. A. & Koppang, N. (1965). Dimethylnitrosamine; its hepatotoxic effect in sheep and its occurrence in toxic batches of herring meal. Nature, Lond.206, 1261

Five therapeutic drugs which are secondary and tertiary amines were investigated by reaction mechanisms for the derivation of nitrosamines in the human environments. These drugs are chlorpromazine (tranquilizer), methadone (analgesic), chloroquine (antimalarial), primaquine (antimalarial), and phenacetin (analgesic). Phenacetin is an N-acetylated secondary amine; chloroquine and primaquine are secondary amines; methadone and chlorpromazine are tertiary amines; and chloroquine is also a tertiary amine. In the human environments of the gastrointestinal tract, stomach, and bladder which generate the nitrosating agent, the derivation of various nitrosamines from these drugs has been presented. Dimethyl nitrosamine has been derived from methadone and diethylnitrosamine has been generated from chlorpromazine and chloroquine, respectively. Chlorpromazine, methadone, chloroquine, primaquine, and phenacetin have also produced by reaction mechanisms various nitrosamines of hitherto unknown carcinogenicity. The dimethylnitrosamine and diethylnitrosamine derived from methadone, chlorpromazine, and chloroquine are of proven carcinogenicity in experimental animals and they therefore constitute a hazard to humans.