title: Hypothesis-driven weight of evidence analysis to determine potential endocrine activity of MTBE.
abstract: Endocrine-related endpoints in animals have been reported to respond to high doses of methyl tertiary-butyl ether (MTBE), however, a systematic and transparent evaluation of endocrine potential has not been published. Resolving whether MTBE exhibits endocrine activity is important given regulatory and public interest in endocrine disrupting substances and their potential for causing adverse effects in humans or wildlife. A weight-of-evidence (WoE) analysis was conducted, focusing on hypotheses related to the potential for MTBE to interact with estrogen, androgen, and thyroid pathways, and steroidogenesis. To reach scientifically justified conclusions based on the totality of evidence, this WoE procedure involved a semi-quantitative relevance weighting of each endpoint for each hypothesis and systematic consideration of each endpoint in various study designs. This procedure maximized use of an extensive body of relevant and reliable literature on MTBE with evidence supporting or opposing a given mode of action hypothesis. Evaluating the strength and consistency of observations from many MTBE studies also provided a way to assess whether high doses used in experiments with MTBE confound identification of direct endocrine system responses. Based on results of studies using mammalian and fish models and in vitro screening assays, this WoE assessment reveals that MTBE lacks direct endocrine activity.
authors.affiliation: Graduate School of Public Health, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182, United States. Electronic address: adepeyst@mail.sdsu.edu.
authors.forename: Ann
authors.initials: A
authors.lastname: de Peyster
authors.affiliation: Environmental and Regulatory Resources, LLC, 6807 Lipscomb Drive, Durham, NC 27712, United States. Electronic address: emihaich@nc.rr.com.
authors.forename: Ellen
authors.initials: E
authors.lastname: Mihaich
mesh_terms: D000728:Androgens / Q000378:metabolism; D000818:Animals; D052244:Endocrine Disruptors / Q000009:adverse effects*; D004703:Endocrine System / Q000187:drug effects*; D004967:Estrogens / Q000378:metabolism; D006801:Humans; D008738:Methyl Ethers / Q000009:adverse effects*; D013961:Thyroid Gland / Q000187:drug effects
chemical_list: D000728:Androgens; D052244:Endocrine Disruptors; D004967:Estrogens; D008738:Methyl Ethers; C043243:methyl tert-butyl ether
keywords: Androgen; Endocrine; Estrogen; Hypothesis; MTBE; Methyl t-butyl ether; Steroidogenesis; Thyroid; Weight-of-evidence