Rodent species are commonly used in traditional toxicology testing guidelines to predict human health toxicity outcomes. The use of a consistent species in test guidelines is important for maintaining consistency and comparability between tests and testing guidelines. This recommendation was operationalized for this study as the implicit assumption of uniform species and species-sex sensitivities. This investigation analyzed the uniformity assumption using data from National Toxicology Program Technical Reports (and where applicable Toxicity Reports), which provide data from both short-term and chronic rodent toxicity tests. These data were extracted and modeled using the Environmental Protection Agency's Benchmark Dose Software. Minimum best-fit benchmark doses (BMD) and benchmark dose lower limits (BMDL) were determined and a minimum best-fit BMD10 and BMDL10 estimated for every chemical and study duration. Endpoints of interest included non-neoplastic lesions, final mean body weights, and mean organ weights. The distribution of findings was then assessed to determine the most sensitive species and species-sex combinations associated with the minimum best-fit BMDL10. Data indicated that species and species-sex sensitivity for this group of chemicals is not uniform and that rats are significantly more sensitive than mice for non-cancerous outcomes observed, depending upon study duration. There are also indications that male rats may be more sensitive than other species-sex groups in certain situations.

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This study investigated whether, in the absence of chronic noncancer toxicity data, short-term noncancer toxicity data can be used to predict chronic toxicity effect levels by focusing on the dose-response relationship instead of a critical effect. Data from National Toxicology Program (NTP) technical reports have been extracted and modeled using the Environmental Protection Agency's Benchmark Dose Software. Best-fit, minimum benchmark dose (BMD), and benchmark dose lower limits (BMDLs) have been modeled for all NTP pathologist identified significant nonneoplastic lesions, final mean body weight, and mean organ weight of 41 chemicals tested by NTP between 2000 and 2012. Models were then developed at the chemical level using orthogonal regression techniques to predict chronic (two years) noncancer health effect levels using the results of the short-term (three months) toxicity data. The findings indicate that short-term animal studies may reasonably provide a quantitative estimate of a chronic BMD or BMDL. This can allow for faster development of human health toxicity values for risk assessment for chemicals that lack chronic toxicity data.