Correlation of Noncancer Benchmark Doses in Short‐ and Long‐Term Rodent Bioassays

Abstract

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.

The Pebble Remains in the Master's Hand: Two Careers Spent Learning (Still) from John Evans

“…Many of these have been around for a long time and are designed to help provide numbers useful for regulatory decisions (e.g., Layton, Mallon, Rosenblatt, & Small, 1987). Other approaches seek to use short‐term data to predict points of departure for chronic risk assessment (e.g., Kratchman, Wang, Fox, & Gray, 2017; Pennington et al., 2002). These are usually independent of the specific toxic effect, which we know does not predict well across species anyway (Wang & Gray, 2015).…”