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Phthalate exposure and male reproductive outcomes: A systematic review of human epidemiological evidence
Citation:
Radke-Farabaugh, E., J. Braun, J. Meeker, AND G. Cooper. Phthalate exposure and male reproductive outcomes: A systematic review of human epidemiological evidence. ENVIRONMENT INTERNATIONAL. Elsevier B.V., Amsterdam, Netherlands, 121(Part 1):764-793, (2018). https://doi.org/10.1016/j.envint.2018.07.029
Impact/Purpose:
Phthalates have well documented anti-androgenic activity in rodent studies resulting in reduced circulating testosterone and male reproductive tract abnormalities (Johnson et al., 2012; Howdeshell et al., 2008). Individual studies and reviews in humans and animals, including a recent report from the National Academies of Science (NAS 2017), have investigated male reproductive effects of phthalate exposure, but have not looked across the full spectrum of male reproductive effects (i.e., from exposures and outcomes during different lifestages, including fetal development, infancy, childhood, puberty, and sexually mature lifestages) in epidemiological studies for DEHP, DINP, DBP, DIBP, BBP, and DEP. We performed a systematic review of the epidemiology literature on the male reproductive effects associated with phthalate exposure. This included review of the following outcomes: anogenital distance, semen parameters, time to pregnancy (male exposure), testosterone, timing of pubertal development, and hypospadias/cryptorchidism.
Description:
Objective: We performed a systematic review of the epidemiology literature to identify the male reproductive effects associated with phthalate exposure. Data sources and study eligibility criteria: Six phthalates were included in the review: di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), dibutylphthalate (DBP), diisobutyl phthalate (DIBP), butyl benzyl phthalate (BBP), and diethyl phthalate (DEP). The initial literature search (of PubMed, Web of Science,and Toxline) included all studies of male reproductive effects in humans, and outcomes were selected for full systematic review based on data availability. Study evaluation and synthesis methods: For each outcome, domain-based approach. Evidence was synthesized by outcome and phthalate and strength of evidence was summarized using a structured framework. Results:The primary outcomes reviewed here are (number of included/excluded studies in parentheses):anogenital distance(6/1), semen parameters(15/9),time to pregnancy (3/5), testosterone (13/8), timing of pubertal development (5/15), and hypospadias/cryptorchidism (4/10). Looking at the overall hazard, there was robust evidence of an association between DEHP and DBP exposure and male reproductive outcomes; this was based primarily on studies of anogenital distance,semen parameters, and testosterone for DEHP and semen parameters and time to pregnancy for DBP. There was moderate evidence of an association between DINP and BBP exposure and male reproductive outcomes based on testosterone and semen parameters for DINP and semen parameters and time to pregnancy for BP.DIBP and DEP were considered to have slight evidence of an association. For DIBP, the less conclusive evidence was attributed to a more limited literature base(i.e.,fewer studies)and lower exposure levels in the population,decreasing the ability to observe an effect. For DEP, the findings were consistent with experimental animal data that suggest DEP does not haves as strong an anti-androgenic effect as other phthalates. Conclusions and implications of keyfindings:Overall, despite some inconsistencies across phthalates in the specific outcomes associated with exposure, these resultssupport that phthalate exposure at levels seen in human populations may have male reproductive effects, particularly DEHP and DBP. The relative strength of the evidence reflects differing levels of toxicity as well as differences in the range of exposures studied and the number of available studies.
URLs/Downloads:
DOI: Phthalate exposure and male reproductive outcomes: A systematic review of human epidemiological evidence