Ivan Rusyn, M.D., Ph.D.
Texas A&M University
NIEHS grantees found that the Collaborative Cross (CC) mouse model — which uses genetically diverse mice to capture over 90% of the known mouse genetic variations — can account for individual differences in susceptibility to environmental chemicals. Using the CC mouse model, researchers measured individual variability in kidney toxicity after exposure to tetrachloroethylene (PERC), a solvent frequently used in dry cleaning solutions, adhesives, and metal degreasers.
Overall, mice exposed to PERC had lower kidney weight and more markers of kidney injury, supporting previous findings that the kidney is a target of PERC toxicity. Among the 45 CC strains tested, the team found variation in PERC metabolism and toxicity, with greater variability observed in levels of toxicity than in metabolism. They also found that inbred mice used in previous studies generally exhibited metabolism of PERC at the lower end of the overall distribution. Because differences in metabolism can affect how quickly toxicants leave the body, lower metabolism of PERC may indicate that those inbred strains may underestimate effects in a more general population.
According to the authors, when comparing the results of this study to the default values that are generally used by the U.S. Environmental Protection Agency in human health risk assessments to adjust for population variation, the default values may protect 95% of the population but not the most sensitive individuals. This study illustrates how the CC mouse population can be used to fine-tune protective adjustment factors for population variability in risk assessments.
Citation: Luo YS, Cichocki JA, Hsieh NH, Lewis L, Wright FA, Threadgill DW, Chiu WA, Rusyn I. 2019. Using collaborative cross mouse population to fill data gaps in risk assessment: a case study of population-based analysis of toxicokinetics and kidney toxicodynamics of tetrachloroethylene. Environ Health Perspect 127(6):67011.