Male reproductive alterations found in animals and humans following in utero phthalate exposure include decreased anogenital distance (AGD) and other reproductive-tract malformations. The aim of this investigation was to conduct systematic reviews of human and animal evidence of the effect of in utero exposure to diethylhexyl phthalate (DEHP) on anogenital distance (AGD) in males. PubMed, Embase, and Toxline were searched for relevant human and experimental animal studies on August 15, 2016. Search results were screened for relevance, and studies that met the inclusion criteria were evaluated for quality and data extracted for analysis. Confidence in the human and animal bodies of evidence was assessed and hazard conclusions reached by integrating evidence streams. The search yielded 6 relevant human studies and 19 animal studies. Meta-analysis of 5 human observational prospective cohort studies showed that increased maternal urinary concentrations of DEHP metabolites were associated with decreased AGD in boys (−4.07 [CI, −6.49 to −1.66] % decrease per log₁₀ rise in DEHP metabolites). Meta-analysis and meta-regression of the 19 experimental animal studies found reduced AGD with DEHP treatment, with a dose-response gradient, and with heterogeneity explained by species and strain. There is a moderate level of evidence from human investigations and a high level of data from animal studies that in utero exposure to DEHP decreases AGD. Based upon the available human and animal evidence, and consideration of mechanistic data, DEHP is presumed to be a reproductive hazard to humans on the basis of effects on AGD.

中文翻译：

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对人和动物的产前邻苯二甲酸二乙基己酯接触以及男性肛门生殖器距离变化的证据进行系统的回顾和荟萃分析

在子宫和邻苯二甲酸酯暴露后在动物和人类中发现的男性生殖变化包括肛门生殖器距离（AGD）减少和其他生殖道畸形。这项调查的目的是对人和动物在子宫内的影响的证据进行系统的审查男性在肛门生殖器距离（AGD）上接触邻苯二甲酸二乙基己酯（DEHP）。在2016年8月15日对PubMed，Embase和Toxline进行了相关的人类和实验动物研究。筛选搜索结果的相关性，并对符合纳入标准的研究进行质量评估，并提取数据进行分析。通过整合证据流，评估了人类和动物证据的自信心，并得出了危害结论。该搜索产生了6项相关的人体研究和19项动物研究。对5项人类观察性前瞻性队列研究的荟萃分析显示，男孩中DEHP代谢产物的母亲尿液浓度升高与男孩的AGD降低有关（每log ₁₀降低−4.07 [CI，−6.49至-1.66]％DEHP代谢产物的增加）。对19项实验动物研究的荟萃分析和荟萃回归发现，DEHP处理，剂量反应梯度和异质性（通过物种和菌株来解释）可降低AGD。来自人体研究的证据水平适中，来自动物研究的数据水平较高，表明子宫内暴露于DEHP会降低AGD。根据现有的人类和动物证据，并考虑到机械数据，基于对AGD的影响，DEHP被认为对人类具有生殖危害。