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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.


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 (

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.

Agency for Toxic Substances and Disease Registry.  Toxicological Profile for Pyrethrins and Pyrethroids. Atlanta, GA: US Department of Health and Human Services; 2003.
Bradberry  SM, Cage  SA, Proudfoot  AT, Vale  JA.  Poisoning due to pyrethroids.  Toxicol Rev. 2005;24(2):93-106. doi:10.2165/00139709-200524020-00003PubMedGoogle ScholarCrossref
Wylie  BJ, Hauptman  M, Woolf  AD, Goldman  RH.  Insect repellants during pregnancy in the era of the zika virus.  Obstet Gynecol. 2016;128(5):1111-1115. doi:10.1097/AOG.0000000000001685PubMedGoogle ScholarCrossref
Saillenfait  AM, Ndiaye  D, Sabate  JP.  Pyrethroids: exposure and health effects—an update.  Int J Hyg Environ Health. 2015;218(3):281-292. doi:10.1016/j.ijheh.2015.01.002PubMedGoogle ScholarCrossref
Barr  DB, Olsson  AO, Wong  LY,  et al.  Urinary concentrations of metabolites of pyrethroid insecticides in the general US population: National Health and Nutrition Examination Survey 1999-2002.  Environ Health Perspect. 2010;118(6):742-748. doi:10.1289/ehp.0901275PubMedGoogle ScholarCrossref
Ye  M, Beach  J, Martin  JW, Senthilselvan  A.  Urinary concentrations of pyrethroid metabolites and its association with lung function in a Canadian general population.  Occup Environ Med. 2016;73(2):119-126. doi:10.1136/oemed-2015-102839PubMedGoogle ScholarCrossref
Li  AJ, Kannan  K.  Urinary concentrations and profiles of organophosphate and pyrethroid pesticide metabolites and phenoxyacid herbicides in populations in eight countries.  Environ Int. 2018;121(Pt 2):1148-1154. doi:10.1016/j.envint.2018.10.033PubMedGoogle ScholarCrossref
Leng  G, Kuhn  KH, Idel  H.  Biological monitoring of pyrethroids in blood and pyrethroid metabolites in urine: applications and limitations.  Sci Total Environ. 1997;199(1-2):173-181. doi:10.1016/S0048-9697(97)05493-4PubMedGoogle ScholarCrossref
Zepeda-Arce  R, Rojas-Garcia  AE, Benitez-Trinidad  A,  et al.  Oxidative stress and genetic damage among workers exposed primarily to organophosphate and pyrethroid pesticides.  Environ Toxicol. 2017;32(6):1754-1764. doi:10.1002/tox.22398PubMedGoogle ScholarCrossref
Chrustek  A, Hołynska-Iwan  I, Dziembowska  I,  et al.  Current research on the safety of pyrethroids used as insecticides.  Medicina (Kaunas). 2018;54(4):E61. doi:10.3390/medicina54040061PubMedGoogle Scholar
Wagner-Schuman  M, Richardson  JR, Auinger  P,  et al.  Association of pyrethroid pesticide exposure with attention-deficit/hyperactivity disorder in a nationally representative sample of US children.  Environ Health. 2015;14:44. doi:10.1186/s12940-015-0030-yPubMedGoogle ScholarCrossref
Radwan  M, Jurewicz  J, Wielgomas  B,  et al.  Semen quality and the level of reproductive hormones after environmental exposure to pyrethroids.  J Occup Environ Med. 2014;56(11):1113-1119. doi:10.1097/JOM.0000000000000297PubMedGoogle ScholarCrossref
Meeker  JD, Barr  DB, Hauser  R.  Human semen quality and sperm DNA damage in relation to urinary metabolites of pyrethroid insecticides.  Hum Reprod. 2008;23(8):1932-1940. doi:10.1093/humrep/den242PubMedGoogle ScholarCrossref
Meeker  JD, Barr  DB, Hauser  R.  Pyrethroid insecticide metabolites are associated with serum hormone levels in adult men.  Reprod Toxicol. 2009;27(2):155-160. doi:10.1016/j.reprotox.2008.12.012PubMedGoogle ScholarCrossref
Koureas  M, Tsakalof  A, Tsatsakis  A, Hadjichristodoulou  C.  Systematic review of biomonitoring studies to determine the association between exposure to organophosphorus and pyrethroid insecticides and human health outcomes.  Toxicol Lett. 2012;210(2):155-168. doi:10.1016/j.toxlet.2011.10.007PubMedGoogle ScholarCrossref
Park  J, Park  SK, Choi  YH.  Environmental pyrethroid exposure and diabetes in US adults.  Environ Res. 2019;172:399-407. doi:10.1016/j.envres.2018.12.043PubMedGoogle ScholarCrossref
Han  J, Zhou  L, Luo  M,  et al.  Nonoccupational exposure to pyrethroids and risk of coronary heart disease in the Chinese population.  Environ Sci Technol. 2017;51(1):664-670. doi:10.1021/acs.est.6b05639PubMedGoogle ScholarCrossref
Baltazar  MT, Dinis-Oliveira  RJ, de Lourdes Bastos  M, Tsatsakis  AM, Duarte  JA, Carvalho  F.  Pesticides exposure as etiological factors of Parkinson’s disease and other neurodegenerative diseases—a mechanistic approach.  Toxicol Lett. 2014;230(2):85-103. doi:10.1016/j.toxlet.2014.01.039PubMedGoogle ScholarCrossref
Burns  CJ, Pastoor  TP.  Pyrethroid epidemiology: a quality-based review.  Crit Rev Toxicol. 2018;48(4):297-311. doi:10.1080/10408444.2017.1423463PubMedGoogle ScholarCrossref
National Center for Health Statistics. National health and nutrition examination survey. Centers for Disease Control website. Updated October 30, 2018. Accessed October 8, 2019.
Wielgomas  B.  Variability of urinary excretion of pyrethroid metabolites in seven persons over seven consecutive days—implications for observational studies.  Toxicol Lett. 2013;221(1):15-22. doi:10.1016/j.toxlet.2013.05.009PubMedGoogle ScholarCrossref
Ratelle  M, Cote  J, Bouchard  M.  Toxicokinetics of permethrin biomarkers of exposure in orally exposed volunteers.  Toxicol Lett. 2015;232(2):369-375. doi:10.1016/j.toxlet.2014.12.003PubMedGoogle ScholarCrossref
Ratelle  M, Cote  J, Bouchard  M.  Time profiles and toxicokinetic parameters of key biomarkers of exposure to cypermethrin in orally exposed volunteers compared with previously available kinetic data following permethrin exposure.  J Appl Toxicol. 2015;35(12):1586-1593. doi:10.1002/jat.3124PubMedGoogle ScholarCrossref
Khemiri  R, Cote  J, Fetoui  H, Bouchard  M.  Kinetic time courses of lambda-cyhalothrin metabolites after dermal application of Matador EC 120 in volunteers.  Toxicol Lett. 2018;296:132-138. doi:10.1016/j.toxlet.2018.08.008PubMedGoogle ScholarCrossref
National Center for Health Statistics. The linkage of National Center for Health Statistics survey data to the National Death Index—2015 linked mortality file (LMF): methodology overview and analytic considerations. Published November 6, 2017. Updated April 11, 2019. Accessed August 13, 2019.
Bramer  GR.  International statistical classification of diseases and related health problems. tenth revision.  World Health Stat Q. 1988;41(1):32-36.PubMedGoogle Scholar
Heron  M.  Deaths: leading causes for 2015.  Natl Vital Stat Rep. 2017;66(5):1-76.PubMedGoogle Scholar
Garcia  MC, Bastian  B, Rossen  LM,  et al.  Potentially preventable deaths among the five leading causes of death—United States, 2010 and 2014.  MMWR Morb Mortal Wkly Rep. 2016;65(45):1245-1255. doi:10.15585/mmwr.mm6545a1PubMedGoogle ScholarCrossref
Moy  E, Garcia  MC, Bastian  B,  et al.  Leading causes of death in nonmetropolitan and metropolitan areas—United States, 1999-2014.  MMWR Surveill Summ. 2017;66(1):1-8. doi:10.15585/mmwr.ss6601a1PubMedGoogle ScholarCrossref
Guenther  PM, Casavale  KO, Reedy  J,  et al.  Update of the Healthy Eating Index: HEI–2010.  J Acad Nutr Diet. 2013;113(4):569-580. doi:10.1016/j.jand.2012.12.016PubMedGoogle ScholarCrossref
Johnson  CL, Paulose-Ram  R, Ogden  CL,  et al.  National health and nutrition examination survey: analytic guidelines, 1999-2010.  Vital Health Stat 2. 2013;(161):1-24.PubMedGoogle Scholar
Barr  DB, Wilder  LC, Caudill  SP, Gonzalez  AJ, Needham  LL, Pirkle  JL.  Urinary creatinine concentrations in the US population: implications for urinary biologic monitoring measurements.  Environ Health Perspect. 2005;113(2):192-200. doi:10.1289/ehp.7337PubMedGoogle ScholarCrossref
Singh  H, Luni  FK, Marwaha  B, Ali  SS, Alo  M.  Transient complete heart block secondary to bed bug insecticide: a case of pyrethroid cardiac toxicity.  Cardiology. 2016;135(3):160-163. doi:10.1159/000446574PubMedGoogle ScholarCrossref
Bhaskar  EM, Moorthy  S, Ganeshwala  G, Abraham  G.  Cardiac conduction disturbance due to prallethrin (pyrethroid) poisoning.  J Med Toxicol. 2010;6(1):27-30. doi:10.1007/s13181-010-0032-7PubMedGoogle ScholarCrossref
Rusiecki  JA, Patel  R, Koutros  S,  et al.  Cancer incidence among pesticide applicators exposed to permethrin in the Agricultural Health Study.  Environ Health Perspect. 2009;117(4):581-586. doi:10.1289/ehp.11318PubMedGoogle ScholarCrossref
Georgiadis  N, Tsarouhas  K, Tsitsimpikou  C,  et al.  Pesticides and cardiotoxicity. where do we stand?  Toxicol Appl Pharmacol. 2018;353:1-14. doi:10.1016/j.taap.2018.06.004PubMedGoogle ScholarCrossref
Vadhana  MS, Carloni  M, Nasuti  C, Fedeli  D, Gabbianelli  R.  Early life permethrin insecticide treatment leads to heart damage in adult rats.  Exp Gerontol. 2011;46(9):731-738. doi:10.1016/j.exger.2011.05.005PubMedGoogle ScholarCrossref
Dhivya Vadhana  MS, Siva Arumugam  S, Carloni  M, Nasuti  C, Gabbianelli  R.  Early life permethrin treatment leads to long-term cardiotoxicity.  Chemosphere. 2013;93(6):1029-1034. doi:10.1016/j.chemosphere.2013.05.073PubMedGoogle ScholarCrossref
Haverinen  J, Vornanen  M.  Deltamethrin is toxic to the fish (crucian carp, Carassius carassius) heart.  Pestic Biochem Physiol. 2016;129:36-42. doi:10.1016/j.pestbp.2015.10.014PubMedGoogle ScholarCrossref
Richardson  JR, Fitsanakis  V, Westerink  RHS, Kanthasamy  AG.  Neurotoxicity of pesticides.  Acta Neuropathol. 2019;138(3):343-362. doi:10.1007/s00401-019-02033-9PubMedGoogle ScholarCrossref
Zhang  C, Jia  L, Wang  S,  et al.  Biodegradation of beta-cypermethrin by two Serratia spp. with different cell surface hydrophobicity.  Bioresour Technol. 2010;101(10):3423-3429. doi:10.1016/j.biortech.2009.12.083PubMedGoogle ScholarCrossref
Liu  P, Liu  Y, Liu  Q, Liu  J.  Photodegradation mechanism of deltamethrin and fenvalerate.  J Environ Sci (China). 2010;22(7):1123-1128. doi:10.1016/S1001-0742(09)60227-8PubMedGoogle ScholarCrossref
Chen  L, Zhao  T, Pan  C, Ross  JH, Krieger  RI.  Preformed biomarkers including dialkylphosphates (DAPs) in produce may confound biomonitoring in pesticide exposure and risk assessment.  J Agric Food Chem. 2012;60(36):9342-9351. doi:10.1021/jf303116pPubMedGoogle ScholarCrossref
Starr  J, Graham  S, Stout  D  II, Andrews  K, Nishioka  M.  Pyrethroid pesticides and their metabolites in vacuum cleaner dust collected from homes and day-care centers.  Environ Res. 2008;108(3):271-279. doi:10.1016/j.envres.2008.07.022PubMedGoogle ScholarCrossref
Morgan  MK, MacMillan  DK, Zehr  D, Sobus  JR.  Pyrethroid insecticides and their environmental degradates in repeated duplicate-diet solid food samples of 50 adults.  J Expo Sci Environ Epidemiol. 2018;28(1):40-45. doi:10.1038/jes.2016.69PubMedGoogle ScholarCrossref
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