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Comment & Response
June 1, 2020

Exposure to Pyrethroids and Health Risk

Author Affiliations
  • 1Bayer Crop Science Division, Chesterfield, Missouri
JAMA Intern Med. 2020;180(7):1028. doi:10.1001/jamainternmed.2020.1519

To the Editor We read the article by Bao et al1 with interest. In this study, single spot urine samples from participants in the NHANES survey, collected between 1999 and 2002, were analyzed for pyrethroid metabolites, including 3-phenoxybenzoic acid (3-PBA). Of the 246 participants who died over the next 14 years, 18 of 41 who died of cardiovascular disease had 3-PBA levels measured in the highest tertile (median [range] urinary PBA level, 1.00 [0.50-69.07] ng/mL). For perspective, a higher single trace concentration of this metabolite in urine was associated with an increase in cardiovascular death in 18 of 41 people over the next 14 years, and an additional 90 of 246 people were at increased risk of all-cause mortality.1

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    1 Comment for this article
    Pyrethroid cardiovascular risk
    James Moss, Ph.D | Retired toxicologist
    The article by Bao et al. (1) suggests that pyrethroid exposure may lead to increased mortality, including that caused by cardiovascular disease (CVD). If we only consider pyrethroid action on the sodium channel (main mode of action as an insecticide) then it seems implausible that pyrethroid exposure would lead to increased CVD rate. CVD has increasingly linked to inflammation (2). 3-phenoxybenzoic acid (3-PBA), a pyrethroid metabolite was used as the pyrethroid marker used by Bao et al. (1). Joshi et al. (3) found that this same pyrethroid metabolite (3-PBA) to be associated with adaptive immune system driven inflammation in Gulf War Illness. In addition, Gulf War risk factors (including the pyrethroid insecticide, permethrin) were found to be associated with chronic medical conditions (including cardiovascular ones) at a younger age than expected in Gulf War veterans (4).

    We should assess the findings of Bao et al. (1) based on the whole picture, and not rely on old textbook versions of what a substance is "supposed" to do. Maybe we could generalize this approach to other issues of safety.

    1, Bao W, Liu B, Simonsen DW, Lehmler HJ. Association between exposure to pyrethroid insecticides and risk of all-cause and cause-specific mortality in the general US adult population. JAMA Intern Med. 2020;180(3):367-374 doi:10.1001/jamainternmed.2019.6019

    2. Lorenzatti AJ, Servato ML. New evidence on the role of inflammation in CVD risk. Curr Opin Cardiol. 2019;34(4):418-423. doi:10.1097/HCO.0000000000000625

    3. Joshi U, Pearson A, Evans JE, et al. A permethrin metabolite is associated with adaptive immune responses in Gulf War Illness. Brain Behav Immun. 2019;81:545-559. doi:10.1016/j.bbi.2019.07.015

    4. Zundel CG, Krengel MH, Heeren T, et al. Rates of Chronic Medical Conditions in 1991 Gulf War Veterans Compared to the General Population. Int J Environ Res Public Health. 2019;16(6):949. Published 2019 Mar 16. doi:10.3390/ijerph16060949