title: Overlooking relevant confounders in the assessment of pesticides and human health: a reply to Mostafalou and Abdollahi.
abstract: Mostafalou and Abdollahi (Arch Toxicol, 2016. doi: 10.1007/s00204-016-1849-x ) have recently conducted a review exploring human exposure to pesticides and systematically highlighting known toxic mechanisms from these exposures. Their review is extensive and appraises the literature on pesticide toxicity in a number of domains, including neurotoxicity and developmental toxicity. However, as important as it may be to understand the toxicological potential of these chemicals in humans and other species, the role of these chemicals as proxies for other environmental exposures should not be excluded. Recently, we published evidence suggesting use of the herbicide, glyphosate, may predict health care utilization for attention-deficit hyperactivity disorder (ADHD), a neurodevelopmental disorder that is characterized by cognitive impairments leading to attention deficits, impulsivity, and hyperactivity. Given that the finding appeared to be land-dependent, we concluded that glyphosate may be an instrumental variable that predicts severe ADHD mostly through its inseparableness from nitrogen fertilizers at a county level and increasing agricultural air emissions of the compound, nitrous oxide (N2O). Since the WHO designates N2O as an important modern health medicine, its environmental imprint is largely thought to be inconsequential in a human health context and, unfortunately, not worthy of further consideration. Our findings and subsequent review on the topic are not amenable to this complacency. We argue that future pesticide risk assessments be made more comprehensive insofar as identifying not only critical, direct routes of toxicity, as extensively reviewed by Mostafalou and Abdollahi (2016), but also indirect toxicological mechanisms such as the one presented in this correspondence.
authors.affiliation: Institute of Health and Environmental Research, Cleveland, OH, 44118, USA. keithfluegge@gmail.com.
authors.forename: Keith
authors.identifier: 0000-0003-3866-9781
authors.initials: K
authors.lastname: Fluegge
mesh_terms: D004781:Environmental Exposure; D006540:Herbicides / Q000633:toxicity; D006801:Humans; D010575:Pesticides / Q000633:toxicity*; D018570:Risk Assessment
chemical_list: D006540:Herbicides; D010575:Pesticides
keywords: ADHD; Developmental toxicity; Glyphosate; Human health; Nitrous oxide; Pesticides