Use of genomic data in risk assessment case study: I. Evaluation of the dibutyl phthalate male reproductive development toxicity data set

作者：Makris Susan L^*; Euling Susan Y; Gray L Earl Jr; Benson Robert; Foster Paul M D

来源：Toxicology and Applied Pharmacology, 2013, 271(3): 336-348.

DOI：10.1016/j.taap.2010.09.006

• Dibutyl phthalate
• Risk assessment
• Toxicogenomic

A case study was conducted, using dibutyl phthalate (DBP), to explore an approach to using toxicogenomic data in risk assessment. The toxicity and toxicogenomic data sets relative to DBP-related male reproductive developmental outcomes were considered conjointly to derive information about mode and mechanism of action. In this manuscript, we describe the case study evaluation of the toxicological database for DBP, focusing on identifying the full spectrum of male reproductive developmental effects. The data were assessed to 1) evaluate low dose and low incidence findings and 2) identify male reproductive toxicity endpoints without well-established modes of action (MOAs). These efforts led to the characterization of data gaps and research needs for the toxicity and toxicogenomic studies in a risk assessment context. Further, the identification of endpoints with unexplained MOAs in the toxicity data set was useful in the subsequent evaluation of the mechanistic information that the toxicogenomic data set evaluation could provide. The extensive analysis of the toxicology data set within the MOA context provided a resource of information for DBP in attempts to hypothesize MOAs (for endpoints without a well-established MOA) and to phenotypically anchor toxicogenomic and other mechanistic data both to toxicity endpoints and to available toxicogenomic data. This case study serves as an example of the steps that can be taken to develop a toxicological data source for a risk assessment, both in general and especially for risk assessments that include toxicogenomic data. Published by Elsevier Inc.

• 出版日期2013-9-15