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Cited by 439Effects and risks of endocrine disrupting chemicalsSperm and Testicular FunctionPesticide Exposure and Toxicity

Phthalate exposure and male reproductive outcomes: A systematic review of the human epidemiological evidence

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Radke, Elizabeth G., Braun, Joseph M., Meeker, John D., Cooper, Glinda S.·2018·Environment International
DOI 10.1016/j.envint.2018.07.029PMC PMC10825890
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Abstract

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. The views expressed are those of the authors and do not necessarily represent the views or policies of the U.S. EPA.

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  • Moderate to strong evidence of male reproductive effects have been demonstrated in the literature.

    “Whereas some inconsistencies exist across phthalates for specific health outcomes associated with exposures, moderate to strong evidence of male reproductive effects have been demonstrated in the literature [208].”

    From A Review of Biomonitoring of Phthalate Exposures (2019) · cites this paper as [208]

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Cited by

Sorted by citations

Authors
Radke, E. G., Braun, J. M., Meeker, J. D., & Cooper, G. S.
Affiliations
  • Environmental Protection Agency (US)
  • Brown University (US)
  • University of Michigan (US)
Corresponding author
Radke, Elizabeth G.
ORCID
Venue
Environment International
Publisher
Elsevier BV
Published
2018-12
Volume
121
Issue
Pt 1
Pages
764-793
ISSN
0160-4120 (ISSN-L)
DOI
10.1016/j.envint.2018.07.029
PMC
PMC10825890
OpenAlex
W2897158557
Cited by
439
References
2
Citations by year
2026: 35 · 2025: 65 · 2024: 46 · 2023: 67 · 2022: 81 · 2021: 71 · 2020: 48 · 2019: 22 · 2018: 4
FWCI
3.80
Type
journal article
Language
en
Update notices
erratum (2019-04-01)
Open access
Licence
Locations
  • Environment International (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute for Occupational Safety and Health (T42-OH008455))
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
Keywords
phthalate exposure, DEHP, dibutyl phthalate, diisononyl phthalate, diisobutyl phthalate, butyl benzyl phthalate, diethyl phthalate, anogenital distance, semen parameters, time to pregnancy, testosterone, pubertal development, hypospadias, cryptorchidism, endocrine disruptors, antiandrogenic effects, risk of bias
MeSH terms
Environmental Exposure, Humans, Male, Phthalic Acids, Reproduction, Semen, Testosterone

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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