Hypothesis-Driven Weight of Evidence Evaluation Indicates Ethylbenzene Lacks Endocrine Disruption Potential by EATS Pathways
by:
Borgert, CJ
Borgert, CJ
Summary:
Results of toxicology studies on Ethylbenzene (EB) were used to evaluate estrogen, androgen, thyroid, and steroidogenic (EATS) endpoints by an established Weight of Evidence (WoE) methodology, as required by U.S. EPA and OECD guidelines for evaluating a chemical’s endocrine disruptive potential. Data on EB were sufficient to assess its effects on endpoints that would be expected to respond to chemicals that operate via EATS modes of action (MoAs) in various screening assays (Tier 1) and toxicity tests (Tier 2) that evaluate reproduction, development, and sub-chronic and chronic toxicity. In those studies, EB produced a pattern of responses inconsistent with the responses that would be expected for hormones and chemicals known to operate via EATS MoAs. Endocrine-sensitive endpoints that respond to EB administration generally do so only at dose levels above its kinetic maximum dose (KMD) indicating a lack of relevance to potential effects at lower dose levels in either the test species or humans. Thus, EB lacks the potential to exhibit endocrine disruptive properties and cannot be deemed an endocrine disruptor or potential endocrine disruptor.
Results of toxicology studies on Ethylbenzene (EB) were used to evaluate estrogen, androgen, thyroid, and steroidogenic (EATS) endpoints by an established Weight of Evidence (WoE) methodology, as required by U.S. EPA and OECD guidelines for evaluating a chemical’s endocrine disruptive potential. Data on EB were sufficient to assess its effects on endpoints that would be expected to respond to chemicals that operate via EATS modes of action (MoAs) in various screening assays (Tier 1) and toxicity tests (Tier 2) that evaluate reproduction, development, and sub-chronic and chronic toxicity. In those studies, EB produced a pattern of responses inconsistent with the responses that would be expected for hormones and chemicals known to operate via EATS MoAs. Endocrine-sensitive endpoints that respond to EB administration generally do so only at dose levels above its kinetic maximum dose (KMD) indicating a lack of relevance to potential effects at lower dose levels in either the test species or humans. Thus, EB lacks the potential to exhibit endocrine disruptive properties and cannot be deemed an endocrine disruptor or potential endocrine disruptor.