Phthalate Exposure and Male Reproductive Outcomes: A Systematic Review of the Human Epidemiological Evidence

Details

• Personal Author:
  Braun, Joseph M. ; Cooper, Glinda S. ; Meeker, John D. ; Radke, Elizabeth G.
• 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), dibutyl phthalate (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, studies were evaluated using criteria defined a priori for risk of bias and sensitivity by two reviewers using a 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 BBP. 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 key findings: Overall, despite some inconsistencies across phthalates in the specific outcomes associated with exposure, these results support 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. Corrigendum - Environ Int 2019 Apr; 125:606-607: The authors regret that a transposition error was made in Table 5. The results listed for Jurewicz et al. (2013) for motility and morphology were switched. This error does not change the overall conclusion regarding the association between DINP and semen parameters or male reproductive effects, but the evidence for an inverse association is stronger for motility than for morphology, which differs from the original text. The authors would like to apologise for any inconvenience caused. [Description provided by NIOSH]
• Subjects:
  Epidemiology Men Occupational Health Phthalic Acids Safety Urogenital System
• Keywords:
  Epidemiology; Reproductive effects; Reproductive hazards; Humans; Men; Phthalates; Systematic reviews; Exposure assessment; Di(2-ethylhexyl) phthalate; Dibutyl phthalate; Diethyl phthalate
• ISSN:
  0160-4120
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  District of Columbia ; Illinois ; Michigan ; OSHA Region 1 ; OSHA Region 3 ; OSHA Region 5 ; Rhode Island
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  30 pdf pages
• Volume:
  121
• NIOSHTIC Number:
  nn:20055249
• Citation:
  Environ Int 2018 Dec; 121(Pt 1):764-793
• Contact Point Address:
  Elizabeth G. Radke, U.S. Environmental Protection Agency, National Center for Environmental Assessment, Washington, DC, United States
• Email:
  radke-farabaugh.elizabeth@epa.gov
• CAS Registry Number:
  Butyl benzyl phthalate (CAS RN 85-68-7) ; Dibutyl phthalate (CAS RN 84-74-2) ; Diethyl phthalate (CAS RN 84-66-2) ; Diisobutyl phthalate (CAS RN 84-69-5) ; Diisononyl phthalate (CAS RN 28553-12-0) ; Dioctyl phthalate (CAS RN 117-81-7)
• Federal Fiscal Year:
  2019
• Performing Organization:
  University of Michigan, Ann Arbor
• Peer Reviewed:
  True
• Part Number:
  1
• Start Date:
  20050701
• Source Full Name:
  Environment International
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:473bb920443ad0a21d102a758efc23e1f15f64722830f304071a2f8f4519cbf034ec764dffe97ed124b45073c55d95ced609420420b88299959a36d3097066b4
• Download URL:
  https://stacks.cdc.gov/view/cdc/231608/cdc_231608_DS1.pdf
• File Type:
  [PDF - 6.16 MB ]