Reiss_2015_Crit.Rev.Toxicol_45_531

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.