Reiss Richard, Chang Ellen T, Richardson Rudy J, Goodman Michael
Exponent , Alexandria, VA , USA.
Crit Rev Toxicol. 2015;45(7):531-641. doi: 10.3109/10408444.2015.1043976.
This paper systematically reviews epidemiologic studies related to low-level non-occupational exposures to organophosphorus (OP) insecticides. Many of the studies evaluate levels of maternal OP metabolites and subsequent health outcomes in offspring. The studies focused primarily on birth outcomes (e.g., infant body weight or head circumference) and neurodevelopmental (e.g., mental and psychomotor) testing results. The evidence from these studies was reviewed under the Bradford Hill guidelines. Most of the studies assessing exposure based on urinary levels of OP insecticide metabolites used only one or two measurements during pregnancy. The potential for exposure misclassification with this method is largely due to (1) preformed metabolites that are ingested with food, (2) the short elimination half-life of OP insecticides, and (3) lack of specificity to particular OP insecticides for many of the metabolites. For birth outcomes, the majority of reported results are not statistically significant, and the associations are inconsistent within and across studies. There is more within-study consistency for some of the neurodevelopmental testing results, although few associations were examined across several studies. These associations are generally weak, have been replicated only to a limited extent, and require further confirmation before they can be considered established. The OP insecticide levels measured in the epidemiologic studies are too low to cause biologically meaningful acetylcholinesterase inhibition, the most widely used metric for OP insecticide toxicity. Overall, the available evidence does not establish that low-level exposures to OP insecticides cause adverse birth outcomes or neurodevelopmental problems in humans.
本文系统回顾了与低水平非职业性接触有机磷(OP)杀虫剂相关的流行病学研究。许多研究评估了母体OP代谢物水平及后代随后的健康结局。这些研究主要聚焦于出生结局(如婴儿体重或头围)和神经发育(如智力和精神运动)测试结果。依据布拉德福德·希尔准则对这些研究的证据进行了审查。大多数基于OP杀虫剂代谢物尿液水平评估接触情况的研究在孕期仅进行了一两次测量。用这种方法进行接触错误分类的可能性很大程度上归因于:(1)随食物摄入的预先形成的代谢物;(2)OP杀虫剂较短的消除半衰期;(3)许多代谢物对特定OP杀虫剂缺乏特异性。对于出生结局,大多数报告结果无统计学意义,且各研究内部及之间的关联不一致。对于一些神经发育测试结果,研究内部的一致性更高,尽管很少有研究对多个关联进行检验。这些关联通常较弱,仅在有限程度上得到重复,在被视为确定之前需要进一步证实。流行病学研究中测得的OP杀虫剂水平过低,无法导致具有生物学意义的乙酰胆碱酯酶抑制,而乙酰胆碱酯酶抑制是OP杀虫剂毒性最广泛使用的衡量指标。总体而言,现有证据并未证实低水平接触OP杀虫剂会导致人类出现不良出生结局或神经发育问题。