a IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Milan , Italy.
b ICPS-International Centre for Pesticides and Health Risk Prevention , ASST Fatebenefratelli Sacco , Milan , Italy.
Crit Rev Toxicol. 2017 Jul;47(6):482-508. doi: 10.1080/10408444.2016.1271972. Epub 2017 Feb 15.
Toxicological and epidemiological evidence on the association between perfluorooctanoic acid (PFOA) or perfluorooctane sulfonic acid (PFOS) and birth/fetal weight was assessed. An extensive search for toxicological information in rats and mice, and a systematic search for epidemiological evidence were conducted. The linear regression coefficient (LRC) of birth weight (BrthW) on PFOA/PFOS was considered, and separate random effects meta-analyses for untransformed (i.e. not mathematically transformed) and log-transformed values were performed. Toxicological evidence: PFOA: 12 studies (21 datasets) in mice showed statistically significant lower birth/fetal weights from 5 mg/kg body weight per day. PFOS: most of the 13 studies (19 datasets) showed lower birth/fetal weights following in utero exposure. Epidemiological evidence: Sixteen articles were considered. The pooled LRC for a 1 ng/mL increase in untransformed PFOA (12 studies) in maternal plasma/serum was -12.8 g (95% CI -23.2; 2.4), and -27.1 g (95% CI -50.6; -3.6) for an increase of 1 log ng/mL PFOA (nine studies). The pooled LRC for untransformed PFOS (eight studies) was -0.92 g (95%CI -3.4; 1.6), and for an increase of 1 log ng/mL was -46.1(95% CI -80.3; -11.9). No consistent pattern emerged for study location or timing of blood sampling.
Epidemiological and toxicological evidence suggests that PFOA and PFOS elicit a decrease in BrthW both in humans and rodents. However, the effective animal extrapolated serum concentrations are 10-10 times higher than those in humans. Thus, there is no quantitative toxicological evidence to support the epidemiological association, thus reducing the biological plausibility of a causal relationship.
评估了全氟辛酸(PFOA)或全氟辛烷磺酸(PFOS)与出生体重/胎儿体重之间关联的毒理学和流行病学证据。对大鼠和小鼠的毒理学信息进行了广泛搜索,并对流行病学证据进行了系统搜索。考虑了出生体重(BrthW)与 PFOA/PFOS 的线性回归系数(LRC),并对未经转换(即未进行数学转换)和对数转换值分别进行了随机效应荟萃分析。毒理学证据:PFOA:12 项研究(21 个数据集)在小鼠中表明,每天 5mg/kg 体重的 PFOA 会导致出生体重/胎儿体重显著降低。PFOS:大多数 13 项研究(19 个数据集)表明,宫内暴露后出生体重/胎儿体重降低。流行病学证据:考虑了 16 篇文章。母体血浆/血清中未转换 PFOA 增加 1ng/mL 时的汇总 LRC 为-12.8g(95%CI-23.2;2.4),而 PFOA 增加 1logng/mL 时为-27.1g(95%CI-50.6;-3.6)(9 项研究)。未转换 PFOS(8 项研究)的汇总 LRC 为-0.92g(95%CI-3.4;1.6),而增加 1logng/mL 时为-46.1(95%CI-80.3;-11.9)。血液采样的研究地点或时间没有出现一致的模式。
毒理学和流行病学证据表明,PFOA 和 PFOS 均会导致人类和啮齿动物的 BrthW 降低。然而,有效动物外推的血清浓度比人类高 10-10 倍。因此,没有定量毒理学证据支持流行病学关联,从而降低了因果关系的生物学可能性。