Association Between Exposure to Pyrethroid Insecticides and Risk of All-Cause and Cause-Specific Mortality in the General US Adult Population

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Abstract

<p class="first" id="d551789e263">This cohort study uses data from the National Health and Nutrition Examination Survey conducted from 1999 to 2002 to investigate whether exposure to pyrethroid insecticides is associated with the risk of all-cause, cardiovascular, and cancer mortality in the general US adult population. </p><div class="section"> <a class="named-anchor" id="ab-ioi190101-1">  </a> <h5 class="title" id="d551789e269">Question</h5> <p id="d551789e271">Is pyrethroid exposure associated with long-term mortality in the general US adult population? </p> </div><div class="section"> <a class="named-anchor" id="ab-ioi190101-2">  </a> <h5 class="title" id="d551789e274">Findings</h5> <p id="d551789e276">In this cohort study of a nationally representative sample of 2116 adults in the United States, higher exposure to pyrethroid insecticides, indicated by higher levels of general pyrethroid metabolite 3-phenoxybenzoic acid in urine samples, was associated with a higher risk of death from all causes or cardiovascular disease over 14 years of observation. </p> </div><div class="section"> <a class="named-anchor" id="ab-ioi190101-3">  </a> <h5 class="title" id="d551789e279">Meaning</h5> <p id="d551789e281">Environmental exposure to pyrethroid insecticides appears to be associated with an increased risk of long-term all-cause mortality and cardiovascular mortality in the US general adult population. </p> </div><div class="section"> <a class="named-anchor" id="ab-ioi190101-4">  </a> <h5 class="title" id="d551789e285">Importance</h5> <p id="d551789e287">Widespread exposure to pyrethroid insecticides has been reported among the general population in the United States and worldwide. However, little is known about the association of pyrethroid exposure with long-term health outcomes in adults. </p> </div><div class="section"> <a class="named-anchor" id="ab-ioi190101-5">  </a> <h5 class="title" id="d551789e290">Objective</h5> <p id="d551789e292">To examine the association of pyrethroid exposure with all-cause and cause-specific mortality among adults in the United States. </p> </div><div class="section"> <a class="named-anchor" id="ab-ioi190101-6">  </a> <h5 class="title" id="d551789e295">Design, Setting, and Participants</h5> <p id="d551789e297">The nationally representative cohort included 2116 adults aged 20 years and older who participated in the US National Health and Nutrition Examination Survey conducted from 1999 to 2002 and provided urine samples for pyrethroid metabolite measurements. Participants were linked to mortality data from the survey date through December 31, 2015. Data were analyzed from May to August 2019. </p> </div><div class="section"> <a class="named-anchor" id="ab-ioi190101-7">  </a> <h5 class="title" id="d551789e300">Exposures</h5> <p id="d551789e302">Urinary levels of 3-phenoxybenzoic acid, a general pyrethroid metabolite and commonly used biomarker for pyrethroid exposure, were determined by using high-performance liquid chromatography coupled with electrospray chemical ionization and tandem mass spectrometry. </p> </div><div class="section"> <a class="named-anchor" id="ab-ioi190101-8">  </a> <h5 class="title" id="d551789e305">Main Outcomes and Measures</h5> <p id="d551789e307">Mortality from all causes, cardiovascular disease, and cancer.</p> </div><div class="section"> <a class="named-anchor" id="ab-ioi190101-9">  </a> <h5 class="title" id="d551789e310">Results</h5> <p id="d551789e312">This cohort study of 2116 adults comprised 1145 women (weighted proportion, 51.6%) and 971 men (weighted, 48.4%), with a weighted mean (SE) age of 42.6 (0.5) years; 958 participants (weighted, 68.4%) were of non-Hispanic white ancestry, 646 (weighted, 14.7%) of Hispanic ancestry, 419 (weighted, 11.3%) of non-Hispanic black ancestry, and 93 (weighted, 5.6%) of other ancestry. During a median of 14.4 years (range, 0.1-16.8 years) of observation, 246 deaths occurred, including 41 associated with cardiovascular disease and 52 associated with cancer. Participants with higher urinary 3-phenoxybenzoic acid levels were at a higher risk of death during the follow-up period, with death occurring in 8.5% (unweighted, 75 of 709), 10.2% (unweighted, 81 of 701), and 11.9% (unweighted, 90 of 706) of participants across increasing tertiles of urinary 3-phenoxybenzoic acid levels. After adjustment for age, sex, race/ethnicity, socioeconomic status, dietary and lifestyle factors, body mass index, and urinary creatinine levels, the hazard ratios for all-cause mortality, cardiovascular disease mortality, and cancer mortality among participants with the highest tertile compared with those with the lowest tertile of urinary 3-phenoxybenzoic acid levels were 1.56 (95% CI, 1.08-2.26), 3.00 (95% CI, 1.02-8.80), and 0.91 (95% CI, 0.31-2.72), respectively. </p> </div><div class="section"> <a class="named-anchor" id="ab-ioi190101-10">  </a> <h5 class="title" id="d551789e315">Conclusions and Relevance</h5> <p id="d551789e317">In this nationally representative sample of US adults, environmental exposure to pyrethroid insecticides was associated with an increased risk of all-cause and cardiovascular disease mortality. Further studies are needed to replicate the findings and determine the underlying mechanisms. </p> </div>

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Neurotoxicity of Pesticides

Jason R. Richardson, Vanessa Fitsanakis, Remco Westerink … (2019)

Pesticides are unique environmental contaminants in that they are specifically introduced into the environment to control pests, often by killing them. Although pesticide application serves many important purposes, including protection against crop loss and against vector borne diseases, there are significant concerns over the potential toxic effects of pesticides to non-target organisms, including humans. In many cases, the molecular target of a pesticide is shared by non-target species, leading to the potential for untoward effects. Here, we review the history of pesticide usage and the neurotoxicity of selected classes of pesticides, including insecticides, herbicides and fungicides, to humans and experimental animals. Specific emphasis is given to linkages between exposure to pesticides and risk of neurological disease and dysfunction in humans coupled with mechanistic findings in humans and animal models. Finally, we discuss emerging techniques and strategies to improve translation from animal models to humans.

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Pyrethroids: exposure and health effects--an update.

Anne Saillenfait, Dieynaba Ndiaye, Jean Philippe Sabaté (2015)

Synthetic pyrethroids are present in numerous commercial insecticide formulations and have extensive indoor and outdoor applications worldwide, including agricultural, public, residential, and veterinary usages for pest control. Pyrethroid use has increased continuously in recent years. The aim of this review is to provide updated and comprehensive information on human exposure and potential hazards associated with this class of pesticides. An initial keyword search in the PubMed database was conducted to identify relevant articles. Were taken into considerations only the studies published in the last decade that have assessed exposure and health effects of pyrethroids in human populations. Literature review shows that exposure evaluations increasingly focus on biomonitoring and that a large number of recent epidemiological studies pertain to the effects of pyrethroids on male fertility and prenatal development. The main metabolites of pyrethroids have frequently been detected in urine samples from the general population, confirming widespread exposure of children and adults to one or more pyrethroids. Non-occupational exposure to pyrethroids mainly occurs through ingestion of residues in food, or ingestion of or dermal contact with contaminated house dust or surface-adhering particles, following domestic use. Although clinical features resulting from acute accidental exposure to pyrethroids are well described (e.g., paraesthesiae, and respiratory, eye and skin irritation), information regarding their chronic effects at low concentrations is both limited and controversial. Several recent epidemiological studies have raised concerns about potentially adverse effects on sperm quality and sperm DNA, reproductive hormones, and pregnancy outcomes. Early neurobehavioural development after in utero exposure is discussed. Further research is needed to clarify the possible risks associated with long-term environmental exposure to pyrethroids.

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Urinary Concentrations of Metabolites of Pyrethroid Insecticides in the General U.S. Population: National Health and Nutrition Examination Survey 1999–2002

Dana Barr, Anders O Olsson, Lee-Yang Wong … (2010)

Background Pyrethroid insecticides are the most commonly used residential insecticides in the United States. Objectives Our objective was to assess human exposure via biomonitoring to pyrethroid insecticides in a representative sample of the general U.S. population ≥ 6 years of age. Methods By using isotope-dilution high-performance liquid chromatography/electrospray chemical ionization/tandem mass spectrometry, we measured five urinary metabolites of pyrethroid insecticides in 5,046 samples collected as a part of the 1999–2002 National Health and Nutrition Examination Survey (NHANES). Univariate, multivariate, and Pearson correlation analyses were performed using SUDAAN and SAS software, incorporating the appropriate sample weights into the analyses. Multivariate analyses included age, sex, race/ethnicity, creatinine, fasting status, and urine collection time as covariates. Results We detected 3-phenoxybenzoic acid (3PBA), a metabolite common to many pyrethroid insecticides, in more than 70% of the samples. The least-squares geometric mean (LSGM) concentration (corrected for covariates) of 3PBA and the frequency of detection increased from 1999–2000 (0.292 ng/mL) to 2001–2002 (0.318 ng/mL) but not significantly. Non-Hispanic blacks had significantly higher LSGM 3PBA concentrations than did non-Hispanic whites and Mexican Americans in the 2001–2002 survey period and in the combined 4-year survey periods but not in the 1999–2000 survey period. Children had significantly higher LSGM concentrations of 3PBA than did adolescents in both NHANES periods and than adults in NHANES 1999–2000. Cis- and trans-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid were highly correlated with each other and with 3PBA, suggesting that urinary 3PBA was derived primarily from exposure to permethrin, cypermethrin, or their degradates. Conclusions Pyrethroid insecticide exposure in the U.S. population is widespread, and the presence of its metabolites in the urine of U.S. residents indicates that children may have higher exposures than adolescents and adults.