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

Educational Objective
To examine the association of pyrethroid exposure with all-cause and cause-specific mortality among adults in the United States.
1 Credit CME
Key Points

Question  Is pyrethroid exposure associated with long-term mortality in the general US adult population?

Findings  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.

Meaning  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.

Abstract

Importance  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.

Objective  To examine the association of pyrethroid exposure with all-cause and cause-specific mortality among adults in the United States.

Design, Setting, and Participants  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.

Exposures  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.

Main Outcomes and Measures  Mortality from all causes, cardiovascular disease, and cancer.

Results  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.

Conclusions and Relevance  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.

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Article Information

Accepted for Publication: October 14, 2019.

Corresponding Author: Wei Bao, MD, PhD, Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242 (wei-bao@uiowa.edu).

Published Online: December 30, 2019. doi:10.1001/jamainternmed.2019.6019

Author Contributions: Dr Bao had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Bao.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Bao, Simonsen, Lehmler.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Bao, Liu.

Obtained funding: Bao.

Administrative, technical, or material support: Bao, Lehmler.

Supervision: Bao, Lehmler.

Conflict of Interest Disclosures: Dr Lehmler reported receiving grants from the National Institute of Environmental Health Sciences and the National Institutes of Health during the conduct of the study. No other disclosures were reported.

Funding/Support: This work was supported in part by grant NIEHS/NIH P30 ES005605 from the National Institutes of Health through the University of Iowa Environmental Health Sciences Research Center.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: The authors thank all the participants and staff of the National Health and Nutrition Examination Survey and the National Center for Environmental Health for their valuable contributions.

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