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• Long-term carcinogenesis bioassays in animals are poor predictors of cancer risk to humans
  Joseph Manuppello
  Published on: 27 April 2016

• Published on: 27 April 2016

  Long-term carcinogenesis bioassays in animals are poor predictors of cancer risk to humans

  • Joseph Manuppello , Research Associate

  In his letter, Predicting chemicals causing cancer in animals as human carcinogens (Occup Environ Med 2010;67:720), Huff surprisingly finds opportunity to promote long-term carcinogenesis bioassays using animals in response to an editorial by Suarthana et al (Occup Environ Med 2009;66:713e14), Predicting occupational diseases. In their editorial, Suarthana et al generalize from the development of diagnostic models to pred...

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  In his letter, Predicting chemicals causing cancer in animals as human carcinogens (Occup Environ Med 2010;67:720), Huff surprisingly finds opportunity to promote long-term carcinogenesis bioassays using animals in response to an editorial by Suarthana et al (Occup Environ Med 2009;66:713e14), Predicting occupational diseases. In their editorial, Suarthana et al generalize from the development of diagnostic models to predict sensitisation to occupational allergens. Suarthana et al mention no animal studies and conclude that "[t]here is now an opportunity to develop prediction models for diverse occupational diseases, especially given the existing large epidemiological studies."

  Huff asserts that "findings from independently conducted bioassays on the same chemicals are consistent[.]" In fact, a comparison of 121 bioassays from the U.S. National Toxicology Program (NTP) database with those in the published scientific literature found that the studies produced consistent results only 57 percent of the time.[1] Huff also claims that "less than10% of all chemicals if evaluated in bioassays would be predicted to be carcinogenic." In our analysis of more than 500 NTP bioassays, we show that more than half of the substances evaluated produced evidence of carcinogenicity in at least one group of animals.[2] The high false positive rate is thought to be an indirect effect of increased cell proliferation in response to cell injury and death caused by the near toxic doses of test substances used.[3] Huff observes that there are more similarities than differences between rodents and humans. However, well-characterized species-specific modes of action not operating in humans also contribute to the high rate of false positives.[4]

  The time has come for antiquated animal tests like the bioassay to be abandoned in favor of modern, human-relevant methods such as the epidemiological studies recommended in Suarthana et al's editorial, high- throughput in vitro methods, and computational toxicology.

  [1] Gottmann E, Kramer S, Pfahringer B, et al. Data quality in predictive toxicology: reproducibility of rodent carcinogenicity experiments. Environ Health Perspect 2001;109:509-14.

  [2] PETA. Wasted money, wasted lives: A layperson's guide to the problems with rodent cancer studies and the National Toxicology Program. Norfolk, VA: People for the Ethical Treatment of Animals. 2006. http://www.mediapeta.com/peta/pdf/Wasted-money-PDF.pdf (accessed 17 Sept 2010).

  [3] Gaylor DW. Are tumor incidence rates from chronic bioassays telling us what we need to know about carcinogens? Regul Toxicol Pharmacol 2005;41:128-33.

  [4] Cohen SM. Human carcinogenic risk evaluation: an alternative approach to the two-year rodent bioassay. Toxicol Sci 2004;80:225-9.

  Conflict of Interest:

  Conflict of Interest: The author is employed by People for the Ethical Treatment of Animals.

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  Conflict of Interest:
  None declared.

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