Intra-individual variations of organophosphate pesticide metabolite concentrations in repeatedly collected urine samples from pregnant women in Japan

Keisuke Hioki,Mayumi Sugiura-Ogasawara,Takeshi Ebara,Tomohiko Isobe,Shoji F Nakayama,Kanemitsu Shibata,Yuki Ito,Jun Ueyama,Naomi Nishikawa,Tomota Kamida,Kunihiko Nakai,Naoko Oya,Michihiro Kamijima

doi:10.1186/s12199-019-0761-4

Abstract

BackgroundLow-dose exposure to organophosphate (OP) insecticides during pregnancy may adversely affect neurodevelopment in children. To evaluate the OP exposure levels, single urine sampling is commonly adopted to measure the levels of dialkylphosphates (DAPs), common OP metabolites. However, the inter-day variations of urinary DAP concentrations within subjects are supposed to be large due to the short biological half-lives of the metabolites, and it is thus considered difficult to accurately assess OP exposure during pregnancy with single sampling. This study aimed to assess intra-individual variations of DAP concentrations and the reproducibility of the exposure dose categorization of OPs according to DAP concentration ranges in pregnant women in Japan.MethodsUrine samples were collected from 62 non-smoking pregnant women (12–22 weeks of gestation) living in Aichi Prefecture, Japan. First morning void (FMV) and spot urine samples taken between lunch and dinner on the same day were collected on five different days during 2 weeks. The concentrations of DAP and creatinine in urine samples were measured using an ultra performance liquid chromatography with tandem mass spectrometry. Creatinine-adjusted and unadjusted concentrations were used for the intraclass correlation coefficient (ICC) calculations and surrogate category analyses.ResultsFor all DAP metabolites, the creatinine-adjusted single ICCs exceeded 0.4, indicating moderate reliability. Overall, ICCs of spot urine samples taken in the afternoon were better than those taken as FMV. Surrogate category analyses showed that participants were categorized accurately into four exposure dose groups according to the quartile points.ConclusionThis study indicated that a single urine sample taken in the afternoon may be useful in assessing OP exposure as long as the exposure is categorized into quartiles when conducting epidemiological studies in early to mid-pregnant women in Japan.

Highlights

Low-dose exposure to organophosphate (OP) insecticides during pregnancy may adversely affect neurodevelopment in children
It has been reported that low-dose exposure to OP pesticides may adversely affect human neurodevelopment, if the exposure occurs during the prenatal period when the fetal brain is undergoing rapid development and the ability to detoxify OPs has not yet matured [5]
The distribution of unadjusted and Cr-adjusted urinary DAP concentrations among pregnant women is summarized in Table 1 and Additional file 1: Table S1, respectively

Summary

Introduction

Low-dose exposure to organophosphate (OP) insecticides during pregnancy may adversely affect neurodevelopment in children. To evaluate the OP exposure levels, single urine sampling is commonly adopted to measure the levels of dialkylphosphates (DAPs), common OP metabolites. The inter-day variations of urinary DAP concentrations within subjects are supposed to be large due to the short biological half-lives of the metabolites, and it is considered difficult to accurately assess OP exposure during pregnancy with single sampling. It has been reported that low-dose exposure to OP pesticides may adversely affect human neurodevelopment, if the exposure occurs during the prenatal period when the fetal brain is undergoing rapid development and the ability to detoxify OPs has not yet matured [5]. Potential positive associations have been reported for prenatal OP exposures with lower intelligence quotient [6], increases in attention problems and attention deficit hyperactivity disorder [7], and an increase in abnormal reflexes [8]

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