Background

Semen quality in men continues to decline in Western countries, but the contours of the issue remain obscure, in relation to contributing chemicals.

Objectives

To obtain more clarity about the chemicals that drive the deterioration of semen quality, we conducted a mixture risk assessment based on European exposures.

Methods

We included chemicals capable of affecting semen quality after prenatal exposures, among them androgen receptor antagonists, substances that disrupt prostaglandin signalling, suppress testosterone synthesis, inhibit steroidogenic enzymes or activate the aryl hydrocarbon receptor. We employed the Hazard Index approach (HI), based on risk quotients of exposures in Europe and reference doses for reductions in semen quality. By summing up the risk quotients of the 29 chemicals included in the assessment we examined fold-exceedances of “acceptable” mixture exposures relative to an index value of 1. For bisphenols A, F, S, phthalates DEHP, DnBP, BBzP, DiNP, n-butyl paraben and paracetamol we relied on biomonitoring studies in which these 9 chemicals were measured together in the same subjects. This allowed us to construct personalised Hazard Indices.

Results

Highly exposed subjects experienced combined exposures to the 9 chemicals that exceeded the index value of 1 by more than 100-fold; the median was a 17-fold exceedance. Accounting for median background exposures to the remaining 20 chemicals added a Hazard Index of 1.39. Bisphenol A made the largest contribution to the HI, followed by polychlorinated dioxins, bisphenols S and F and DEHP. Eliminating bisphenol A alone would still leave unacceptably high mixture risks. Paracetamol is also a driver of mixture risks among subjects using the drug.

Conclusions

Tolerable exposures to substances associated with deteriorations of semen quality are exceeded by a large margin. Bisphenols, polychlorinated dioxins, phthalates and analgesics drive these risks. Dedicated efforts towards lowering exposures to these substances are necessary to mitigate risks.

中文翻译：

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双酚、多氯二恶英、扑热息痛和邻苯二甲酸酯的综合暴露是精液质量恶化的驱动因素

背景

在西方国家，男性精液质量继续下降，但与化学物质有关的问题的轮廓仍然模糊不清。

目标

为了更清楚地了解导致精液质量恶化的化学物质，我们根据欧洲暴露情况进行了混合物风险评估。

方法

我们纳入了能够在产前暴露后影响精液质量的化学物质，其中包括雄激素受体拮抗剂、破坏前列腺素信号传导、抑制睾酮合成、抑制类固醇生成酶或激活芳烃受体的物质。我们采用危害指数方法 (HI)，基于欧洲暴露的风险商数和降低精液质量的参考剂量。通过总结评估中包含的 29 种化学品的风险商，我们检查了相对于指数值 1 的“可接受”混合物暴露的倍数。对于双酚 A、F、S、邻苯二甲酸盐 DEHP、DnBP、BBzP、DiNP，对羟基苯甲酸正丁酯和对乙酰氨基酚我们依赖于生物监测研究，其中这 9 种化学物质在同一受试者中一起测量。这使我们能够构建个性化的危险指数。

结果

高度暴露的受试者经历了超过指数值 1 100 倍以上的 9 种化学品的联合暴露；中位数超过 17 倍。考虑到其余 20 种化学品的背景暴露中值，危险指数增加了 1.39。双酚 A 对 HI 的贡献最大，其次是多氯二恶英、双酚 S 和 F 以及 DEHP。单独消除双酚 A 仍然会留下不可接受的高混合风险。对乙酰氨基酚也是使用该药物的受试者之间混合风险的驱动因素。

结论

与精液质量恶化有关的物质的可容忍暴露量大大超过了。双酚、多氯二恶英、邻苯二甲酸酯和镇痛剂会导致这些风险。为了降低风险，必须努力降低对这些物质的接触。