Carcinogen testing

In additional EPA studies, subchronic inhalation was evaluated ia the rat for 4 and 13 weeks, respectively, and no adverse effects other than nasal irritation were noted. In the above-mentioned NTP chronic toxicity study ia mice, no chronic toxic effects other than those resulting from bronchial irritation were noted. There was no treatment-related increase ia tumors ia male mice, but female mice had a slight increase in bronchial tumors. Neither species had an increase in cancer. Naphthalene showed no biological activity in other chemical carcinogen tests, indicating Htde cancer risk (44). No incidents of chronic effects have been reported as a result of industrial exposure to naphthalene (28,41). 

Table 3 Hsts the U.S. producers of methylene chloride and their rated yearly capacities. Since the product mix of a typical chloromethanes process is very flexible, production may be adjusted according to the demand for methylene chloride and chloroform. The demand for methylene chloride has taken a broad downturn as a result of the 1985 NTP carcinogenicity tests (Table 4). The 1988 and 1989 demands were 227,000 t and 216,000 t, respectively, with a forecast 1993 demand of 186,000 t. The historical growth rate (1979—1988) was —2.7% pet year. In the future this should decrease even further to —3 to...

GL28 Safety carcinogenicity Studies to evaluate the safety of residues of veterinary drug in human food carcinogenicity testing... 

Longer-term carcinogenicity tests are undertaken, particularly if (a) the product s likely therapeutic indication will necessitate its administration over prolonged periods (a few weeks or more) or (b) if there is any reason to suspect that the active ingredient or other constituents could be carcinogenic. These tests normally entail ongoing administration of the product to rodents at various dosage levels for periods of up to (or above) 2 years. 

Hendricks, J.D. 1984. Use of Small Fish Species in Carcinogenicity Testing. Pages 397-404 in K.L. Hoover (ed.). National Cancer Institute Monograph 65, Washington, D.C. 

Two rodent species are routinely used for carcinogenicity testing in the pharmaceutical industry, the mouse and the rat. Sprague-Dawley derived rats are most commonly used in American pharmaceutical toxicology laboratories. However, the Wistar and Fischer 344 strains are favored by some companies, while the Long Evans and CFE (Carworth) strains are rarely used [Pharmaceutical Manufacturers Association (PMA), 1988]. 

A review of data from 250 chemicals found an 82% concordance between results of carcinogenicity testing in the mouse and the rat (Purchase, 1980). Haseman et al. (1984a) reported a concordance of 73% for 60 compounds studies in both species. However, 30 to 40% of 186 National Cancer Institute (NCI) chemicals were found to be positive in one species and negative in the other (Gold et al., 1984). It is reasonable to conclude that neither rodent species will always predict the results in the other rodent species or in humans, and that the use of two species will continue until we have a much better understanding of the mechanisms of carcinogenesis. 

Haseman, J.K. (1985). Issues in carcinogenicity testing Dose selection. Fundam. Appl. Toxicol. 5 66-78. 

McAnulty, PA. (2000). Transgenic Mouse models in carcinogenicity testing, European Pharmaceutical Contractor, July, 2000, pp. 84-90. 

Spindler, P, Loan, J., Ceuppens, P., Harling, R., Eittlin, R. and Lima, B.S. (2000). Carcinogenicity testing of pharmaceuticals in the European Union a workshop report, Drug Information J. 34 821-828. 

McQueen, C.A. and Williams, G.M. (1985). Methods and modifications of the hepatocyte primary culture/DNA repair test. In Handbook of Carcinogenic Testing (Milman, H.A. and Weisburger, E.K., Eds.). Noyes Publications, Park Ridge, NJ, pp. 116-129. 

Kluwe WM, McConnell EE, Huff JE, et al. 1982. Carcinogenicity testing of phthalate esters and related compounds by the National Toxicology Program and the National Cancer Institute. Environ Health Perspect 45 129-133. 

A review of carcinogenicity testing procedures addresses the many factors that should be considered in a carcinogenicity program.27... 

The relevance of carcinogenicity testing is a continuing source of differing opinions, and some thoughtful insights have been proposed.28,29... 

Mihnan, H. A., and Weisburger, E. K. 1994. Handbook of Carcinogen Testing, 2nd ed. Noyes Data Corp., Park Ridge, NJ. 

Maronpot RR, Shimkin MB, Witschi HP, et al. 1986. Strain A mouse pulmonary tumor test results for chemical previously tested in the National Cancer Institute carcinogenicity tests. J Natl Cancer Inst 76 1101-1112. 

Brusick D. 1983. Evaluation of chronic rodent bioassays and Ames assay tests as accurate models for predicting human carcinogens. In Milman HA, ed. Application of biological markers for carcinogen testing, 153-163. 

Kurokawa Y, Takayama S, Konishi Y (1986) Long-term in vivo carcinogenicity tests of potassium bromate, sodium hypochlorite, and sodium chlorite conducted in Japan. Environ... 

MOREAU, P. and DEVORET, R. Potential Carcinogens Tested by Inductions and Mutageneisis of Prophage X in Escherichia coli K12 , in HIATT, H. H., WATSON, J. D. and WINSTEN, J. A. (eds.). Origins of Human Cancer, p. 1451, Cold Springs Harbor Laboratory Publ., Cold Springs Harbor, NY, 1977. 

Combined chronic toxicity/carcinogenicity testing of respirable fibrous particles (July 2001)... 

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