Chemical carcinogens a review and analysis of the literature of selected chemicals and the establishment of the Gene-Tox carcinogen data base. A report of the U.S. environmental protection agency Gene-Tox program

S. Nesnow, M. Argus, H. Bergman, K. Chu, C. Frith, T. Helmes, R. McGaughy, V. Ray, T. J. Slaga, R. Tennant, E. Weisburger

Research output: Contribution to journalReview articlepeer-review

116 Scopus citations

Abstract

The literature on 506 selected chemicals has been evaluated for evidence that these chemicals induce tumors in experimental animals and this assessment comprises the Gene-Tox Carcinogen Data Base. Three major sources of information were used to create this evaluated data base: all 185 chemicals determined by the International Agency for Research on Cancer to have Sufficient evidence of carcinogenic activity in experimental animals, 28 selected chemicals bioassayed for carcinogenic activity by the National Toxicology Program/National Cancer Institute and found to induce tumors in mice and rats, and 293 selected chemicals which had been evaluated in genetic toxicology and related bioassays as determined from previous Gene-Tox reports. The literature data on the 239 chemicals were analyzed by the Gene-Tox Carcinogenesis Panel in an organized, rational and consistent manner. Criteria were established to assess individual studies employing single chemicals and 4 categories of response were developed: Positive, Negative, Inconclusive (Equivocal) and Inconclusive. After evaluating each of the individual studies on the 293 chemicals, the Panel placed each of the 506 chemicals in an overall classification category based on the strength of the evidence indicating the presence or absence of carcinogenic effects. An 8-category decision scheme was established using a modified version of the International Agency for Research on Cancer approach. This scheme included two categories of Positive (Sufficient and Limited), two categories of Negative (Sufficient and Limited), a category of Equivocal (the evidence of carcinogenicity from well-conducted and well-reported lifetime studies had uncertain significance and was neither clearly positive nor negative), and three categories of Inadequate (the evidence of carcinogenicity was insufficient to make a decision, however, the data suggested a positive or negative indication). Of the 506 chemicals in the Gene-Tox Carcinogen Data Base, 252 were evaluated as Sufficient Positive, 99 as Limited Positive, 40 as Sufficient Negative, 21 as Limited Negative, 1 as Equivocal, 13 as Inadequate with the data suggesting a positive indication, 32 as Inadequate with the data suggesting a negative indication, and 48 Inadequate with the data not suggesting any indication of activity. This data base was analyzed and examined according to chemical class, using a 29 chemical class scheme. The major chemical classes represented were: acyl, alkyl and aryl halides (38 chemicals); alcohols and phenols (28 chemicals); alkyl and aryl epoxides (20 chemicals); amines, amides and sulfonamides (70 chemicals); aromatic azo, azide, azoxy, diazo, hydrazo and nitrile chemicals (28 chemicals); aziridines, nitrogen and sulfur mustards (25 chemicals); carbamates, dicarboximides, thioureas and ureas (21 chemicals); metals and organometallics (41 chemicals); nitroalkanes, nitroaromatics, nitrofurans, nitroimidazoles and nitroquinolines (23 chemicals); nitrosamines (19 chemicals); and polycyclic aromatic hydrocarbons and dihydrodiol derivatives (57 chemicals). The Gene-Tox Carcinogen Data Base provides a basis for future in-depth analyses of genetic toxicology bioassay systems with regard to their ability to predict the carcinogenic effects of chemicals.

Original languageEnglish (US)
Pages (from-to)1-195
Number of pages195
JournalMutation Research/Reviews in Genetic Toxicology
Volume185
Issue number1-2
DOIs
StatePublished - 1987
Externally publishedYes

Keywords

  • Carcinogen
  • Chemical carcinogens
  • Data Base
  • Gene-Tox Program.
  • Literature, review and analysis

ASJC Scopus subject areas

  • Toxicology
  • Genetics

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