Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 1 No. 1 August 06, 2014 p.1-6
Letter
Investigation of organ-specific assessment factors related to sub-acute and sub-chronic toxicity studies
  • Jun-ichi Takeshita (Research Institute of Science for Safety and Sustainability, National Institute of Advanced Industrial Science and Technology (AIST) / jun-takeshita@aist.go.jp)
Jun-ichi Takeshita 1) , Atsuo Kishimoto 2) , Masashi Gamo 1)
1) Research Institute of Science for Safety and Sustainability, National Institute of Advanced Industrial Science and Technology (AIST) , 2) Graduate School of Public Policy, The University of Tokyo
Keywords: Risk assessment, Assessment factor, Exposure duration, Sub-acute toxicity study, Sub-chronic toxicity study, Chemical-specific factor
Abstracts

In risk assessment of chemicals, we often use default assessment factors to compensate for lack of knowledge. Such assessment factors can be especially useful for regulatory decisions. The present study focuses on assessment factors related to exposure duration, especially under sub-acute and sub-chronic conditions; and discussions attempt to utilize chemical-specific toxicological data. Most previous studies have not focused on target organs, but recent reports such as Malkiewicz et al. (2009) suggest that assessment factors may be target organ-dependent. Therefore, we addressed selected target organs (liver, kidney, blood, and body weight) by investigating assessment factors for these target organs. Using existing data, we calculated the ratio of the no-observed-effect level (NOEL) derived from sub-acute studies to the NOEL derived from sub-chronic studies, to assess for effects involving individual target organs (liver, kidney, blood, or body weight). Then, we compared these ratios with the ratio derived from the substances’ sub-acute and sub-chronic NOELs (the minimum values among all four target organs’ NOELs) by using the Dunnett’s multiple comparison test. Our analysis indicates that effects involving liver, kidney, and body weight need not be treated independently, although the effect on blood should be treated separately. Based on our results, we discuss potential refinement of assessment factors to reflect exposure duration.