Department of Production Animal Clinical Science, Norwegian School of Veterinary Science, Oslo, Norway.
J Toxicol Environ Health B Crit Rev. 2009 Apr;12(4):225-49. doi: 10.1080/10937400903094091.
The purposes of this review are to (1) evaluate human and experimental evidence for adverse effects on reproduction and development in humans, produced by exposure to phthalates, and (2) identify knowledge gaps as for future studies. The widespread use of phthalates in consumer products leads to ubiquitous and constant exposure of humans to these chemicals. Phthalates were postulated to produce endocrine-disrupting effects in rodents, where fetal exposure to these compounds was found to induce developmental and reproductive toxicity. The adverse effects observed in rodent models raised concerns as to whether exposure to phthalates represents a potential health risk to humans. At present, di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), and butyl benzyl phthalate (BBP) have been demonstrated to produce reproductive and developmental toxicity; thus, this review focuses on these chemicals. For the general population, DEHP exposure is predominantly via food. The average concentrations of phthalates are highest in children and decrease with age. At present, DEHP exposures in the general population appear to be close to the tolerable daily intake (TDI), suggesting that at least some individuals exceed the TDI. In addition, specific high-risk groups exist with internal levels that are several orders of magnitude above average. Urinary metabolites used as biomarkers for the internal levels provide additional means to determine more specifically phthalate exposure levels in both general and high-risk populations. However, exposure data are not consistent and there are indications that secondary metabolites may be more accurate indicators of the internal exposure compared to primary metabolites. The present human toxicity data are not sufficient for evaluating the occurrence of reproductive effects following phthalate exposure in humans, based on existing relevant animal data. This is especially the case for data on female reproductive toxicity, which are scarce. Therefore, future research needs to focus on developmental and reproductive endpoints in humans. It should be noted that phthalates occur in mixtures but most toxicological information is based on single compounds. Thus, it is concluded that it is important to improve the knowledge of toxic interactions among the different chemicals and to develop measures for combined exposure to various groups of phthalates.
本次综述的目的在于:(1) 评估人类接触邻苯二甲酸酯后对生殖和发育产生的不良影响的人体和实验证据;(2) 确定未来研究的知识空白。由于邻苯二甲酸酯在消费产品中的广泛应用,人类普遍且持续地接触这些化学物质。邻苯二甲酸酯被假设会在啮齿动物中产生内分泌干扰效应,在这些化合物的胎儿暴露中发现了发育和生殖毒性。在啮齿动物模型中观察到的不良影响引发了人们的担忧,即接触邻苯二甲酸酯是否代表了人类潜在的健康风险。目前,已证实二(2-乙基己基)邻苯二甲酸酯(DEHP)、二正丁基邻苯二甲酸酯(DBP)和邻苯二甲酸丁基苄基酯(BBP)可产生生殖和发育毒性;因此,本综述重点关注这些化学物质。对于一般人群,DEHP 的暴露主要通过食物。邻苯二甲酸酯的平均浓度在儿童中最高,并随年龄下降。目前,一般人群中的 DEHP 暴露似乎接近可耐受每日摄入量(TDI),这表明至少有一些个体超过了 TDI。此外,还存在一些特定的高风险群体,其内部水平高出几个数量级。用作内部水平生物标志物的尿液代谢物为确定一般人群和高风险人群中的邻苯二甲酸酯暴露水平提供了额外的手段。然而,暴露数据不一致,并且有迹象表明,次级代谢物可能比初级代谢物更准确地指示内部暴露。基于现有相关动物数据,目前的人类毒性数据不足以评估人类接触邻苯二甲酸酯后生殖效应的发生。这在女性生殖毒性数据方面尤为如此,此类数据稀缺。因此,未来的研究需要专注于人类的发育和生殖终点。需要注意的是,邻苯二甲酸酯存在于混合物中,但大多数毒理学信息基于单一化合物。因此,重要的是要提高对不同化学物质之间毒性相互作用的认识,并制定针对不同邻苯二甲酸酯组的联合暴露的措施。
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