We contributed to several rodent studies that investigated sources of variability in response to genetics and environmental agents. The NTP was considering including environmental enrichment materials (e.g., nesting materials, polycarbonate shelters) in rodent cages within its testing program. We designed a study and analyzed data to confirm that these materials will not affect toxicity endpoints in short-term rat and mouse studies. In the past, the NTP has used genetically identical mice in its testing program. While these provide for a homogeneous response to chemical toxins, they do not reliably represent the potential range of responses of genetically diverse humans. The NTP conducted a large study of benzene using Diversity Outbred (DO) mice to examine the range of responses that could be obtained using mice that were approximately as genetically diverse as the human population. The primary endpoint in this study was micronucleus formation in response to DNA damage. We analyzed the data and contributed to NTP showing that there were regions within two genes associated with resistance to the DNA damaging effects of benzene. We also performed low dose extrapolation to determine the benchmark doses for this damage, suggesting that allowable human exposure levels should probably be reduced. Also in a demonstration of the effects of genetic diversity, we tested the effects of ozone exposure on clinical and histopathological indicators of cardiovascular disease in eight rat strains. We helped design this study and analyzed the data. The study showed distinct differences among the strains in susceptibility to cardiovascular disease following ozone exposure. In a mouse study of perfluorooctanoic acid (PFOA), mice were fed either a regular or high-fat diet while exposed to PFOA or control. Although mice on the high fat diet had higher body weights and blood lipid values than those on the regular diet, diet did not appear to affect their response to PFOA. Similarly, histopathological changes in the liver were associated with a high fat diet, but the diet did not affect liver changes seen with exposure to PFOA. Thus, the effects of diet appeared to be independent of the effects of PFOA.
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