Thiazopyr and thyroid disruption: case study within the context of the 2006 IPCS Human Relevance Framework for analysis of a cancer mode of action.

Abstract

Thiazopyr increases the incidence of male rat thyroid follicular-cell tumors; however, it is not carcinogenic in mice. Thiazopyr is not genotoxic. Thiazopyr exerts its carcinogenic effect on the rat thyroid gland secondary to enhanced metabolism of thyroxin leading to hormone imbalance. The relevance of these rat tumors to human health was assessed by using the 2006 IPCS Human Relevance Framework. The postulated rodent tumor mode of action was tested against the Bradford Hill criteria and was found to satisfy the conditions of dose and temporal concordance, biological plausibility, coherence, strength, consistency, and specificity that fits with a well-established mode of action for thyroid follicular-cell tumors. Although the postulated mode of action could theoretically operate in humans, marked quantitative differences in the inherent susceptibility for neoplasia to thyroid hormone imbalance in rats allows for the conclusion that thiazopyr does not pose a carcinogenic hazard to humans.

• Authors: Vicki L Dellarco, Douglas McGregor, Sir Colin Berry, Samuel M Cohen, Alan R Boobis
• Journal: Critical reviews in toxicology (Crit Rev Toxicol) 2006 Nov-Dec Vol. 36 Issue 10 Pg. 793-801 ISSN: 1040-8444 [Print] England
• PMID: 17118729 (Publication Type: Journal Article, Review)

Chemical References

• Carcinogens
• Thiazoles
• Niacin
• thiazopyr

Topics

• Animals
• Carcinogenicity Tests
• Carcinogens (toxicity)
• Disease Models, Animal
• Humans
• Male
• Mice
• Niacin (analogs & derivatives, toxicity)
• Rats
• Research Design
• Risk Assessment
• Species Specificity
• Thiazoles (toxicity)
• Thyroid Neoplasms (chemically induced, metabolism)