Correlations between chemically related site-specific carcinogenic effects in long-term studies in rats and mice.

Abstract

We examined a database of 379 long-term carcinogenicity studies in rats and mice to evaluate sex and species correlations in site-specific carcinogenic responses. Within a species, most target sites showed a strong correlation between males and females. For example, chemicals producing forestomach or liver tumors in males were likely to produce these same types of tumors in females. There was also a significant correlation between species for certain site-specific carcinogenic effects, most notably tumors of the forestomach, liver, and thyroid gland. In contrast, adrenal pheochromocytoma, preputial/clitoral gland neoplasms, and lung tumors showed no significant interspecies correlation. Many chemicals produced a syndrome of carcinogenic effects involving tumors of the skin, Zymbal gland, preputial/clitoral gland, mammary gland, and/or oral cavity. Regarding different target sites, there appeared to be a correlation between thyroid and liver tumors both within and between species. Further, all chemicals producing mesotheliomas in male rats also produced mammary gland neoplasms in female rats. In contrast, kidney and urinary bladder tumors showed no significant association with any other tumor type in rats or mice. If a chemical produced a site-specific carcinogenic effect in female rats or mice, there was approximately a 65% probability that the chemical would also be carcinogenic at that same site in males. The interspecies correlation was somewhat lower: approximately 36% of the site-specific carcinogenic effects observed in one species (rats or mice) were also observed in the other species.(ABSTRACT TRUNCATED AT 250 WORDS)Imagesp50-a

Tumor profiles and carcinogenic potency in rodents and humans: Value for cancer risk assessment

“…Moreover, the species specificity was remarkably higher than the sex specificity among different species. This result is in agreement with evidence found by other investigators in different subsets of the database(17,18).A similar check was performed on the potency data. For this preliminary analysis, we used the TD50 values listed by species/sex group in a compilation byNesnow (19).…”

Are tumor incidence rates from chronic bioassays telling us what we need to know about carcinogens?

“…Thus, based on the results from testing a chemical with 50 animals per group, the probability of at least one tissue site with a statistically dose-response trend can be estimated for a chemical with a specified larger sample size, e.g., 200 animals per group. Haseman and Lockhart (1993) indicate relatively few correlations between chemically related site-specific carcinogenic effects.…”

Mortality Patterns Among Workers Exposed to Acrylamide: Updated Follow Up

“…[15][16][17][18][19] Only two epidemiology studies of AMD-exposed workers have been conducted to date. Recognizing the limitations of extrapolating findings of carcinogenicity bioassays across animal species or from animals to humans, 20 these studies were prompted by experimental animal studies that suggested AMD's carcinogenic potential based on an increased incidence of cancers, including those of the brain and other central nervous system (CNS), thyroid gland, other endocrine glands, reproductive organs, and mesotheliomas. [3][4][5][6] The first epidemiology study, a small historical cohort study of 371 Dow Chemical Company employees assigned to AMD monomer and polymerization operations, found no statistically significant mortality excesses in the total cohort and no deaths for the implicated cancer sites.…”