Concurrent urinary organophosphate metabolites and acetylcholinesterase activity in Ecuadorian adolescents

Abstract

Background: Organophosphates are insecticides that inhibit the enzymatic activity of acetylcholinesterase (AChE). Because of this, AChE is considered a physiological marker of organophosphate exposure in agricultural settings. However, limited research exists on the associations between urinary organophosphate metabolites and AChE activity in children.

Methods: This study included 526 participants from 2 exams (April and July-October 2016) of ages 12-17 years living in agricultural communities in Ecuador. AChE activity was measured at both examinations, and organophosphate metabolites, including para-nitrophenol (PNP), 3,5,6-trichloro-2-pyridinol (TCPy), and malathion dicarboxylic acid (MDA) were measured in urine collected in July-October. We used generalized estimating equation generalized linear model (GEEGLM), adjusting for hemoglobin, creatinine, and other demographic and anthropometric covariates, to estimate associations of urinary metabolite concentrations with AChE activity (July-October) and AChE% change between April and July-October.

Results: The mean (SD) of AChE and AChE% change (April vs July-October) were 3.67 U/mL (0.54) and -2.5% (15.4%), respectively. AChE activity was inversely associated with PNP concentration, whereas AChE% change was inversely associated with PNP and MDA. There was evidence of a threshold: difference was only significant above the 80th percentile of PNP concentration (AChE difference per SD increase of metabolite = -0.12 U/mL [95%CI: 0.20, -0.04]). Likewise, associations with AChE% change were significant only above the 80th percentile of TCPy (AChE % change per SD increase of metabolite = -1.38% [95%CI: 2.43%, -0.32%]) and PNP -2.47% [95%CI: 4.45%, -0.50%]). PNP concentration at ≥80th percentile was associated with elevated ORs for low AChE activity of 2.9 (95% CI: 1.5, 5.7) and for AChE inhibition of ≤ -10% of 3.7 (95% CI: 1.4, 9.8).

Conclusions: Urinary organophosphate metabolites, including PNP, TCPy and MDA, particularly at concentrations above the 80th percentile, were associated with lower AChE activity among adolescents. These findings bring attention to the value of using multiple constructs of pesticide exposure in epidemiologic studies.

Keywords: Adolescent; Agriculture; Exposure; Organophosphates; Pesticides.