Abstract

BackgroundNeonicotinoids, which are novel pesticides, have entered into usage around the world because they are selectively toxic to arthropods and relatively non-toxic to vertebrates. It has been suggested that several neonicotinoids cause neurodevelopmental toxicity in mammals. The aim was to establish the relationship between oral intake and urinary excretion of neonicotinoids by humans to facilitate biological monitoring, and to estimate dietary neonicotinoid intakes by Japanese adults.Methodology/Principal FindingsDeuterium-labeled neonicotinoid (acetamiprid, clothianidin, dinotefuran, and imidacloprid) microdoses were orally ingested by nine healthy adults, and 24 h pooled urine samples were collected for 4 consecutive days after dosing. The excretion kinetics were modeled using one- and two-compartment models, then validated in a non-deuterium-labeled neonicotinoid microdose study involving 12 healthy adults. Increased urinary concentrations of labeled neonicotinoids were observed after dosing. Clothianidin was recovered unchanged within 3 days, and most dinotefuran was recovered unchanged within 1 day. Around 10% of the imidacloprid dose was excreted unchanged. Most of the acetamiprid was metabolized to desmethyl-acetamiprid. Spot urine samples from 373 Japanese adults were analyzed for neonicotinoids, and daily intakes were estimated. The estimated average daily intake of these neonicotinoids was 0.53–3.66 μg/day. The highest intake of any of the neonicotinoids in the study population was 64.5 μg/day for dinotefuran, and this was <1% of the acceptable daily intake.

Highlights

  • Neonicotinoid pesticides have been widely used to protect vegetables, rice, and fruit trees because they are effective at controlling a range of pests, shield bugs and aphids

  • We developed a one-compartment pharmacokinetic model for clothianidin, dinotefuran, and imidacloprid and a two-compartment pharmacokinetic model for acetamiprid to describe the metabolic fates of these pesticides in urine (S1 Fig)

  • We identified the statistical characteristics of acetamiprid, clothianidin, dinotefuran, and imidacloprid assuming that the pharmacokinetic behaviors of these compounds followed pharmacokinetic models that have previously been described.[17]

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Summary

Introduction

Neonicotinoid pesticides have been widely used to protect vegetables, rice, and fruit trees because they are effective at controlling a range of pests, shield bugs and aphids. The ecological impacts of neonicotinoid pesticides on invertebrates and their predators have recently been causing concern.[1, 2] Seven neonicotinoid pesticides are used in many of the Japanese prefectures because they are not very toxic to humans.[3] the European Food Safety Authority (EFSA) reviewed the data available for three neonicotinoid pesticides (clothianidin, imidacloprid, and thiamethoxam) and evaluated their impacts on bees in January 2013. A method for assessing human exposure to neonicotinoid pesticides using actual measurements is urgently required. It is necessary to identify convenient biomarkers for neonicotinoid exposure so that the biological monitoring method can be fully established. The aim was to establish the relationship between oral intake and urinary excretion of neonicotinoids by humans to facilitate biological monitoring, and to estimate dietary neonicotinoid intakes by Japanese adults

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