Pyrethroid Exposure Increases Risk for Death

Ricki Lewis, PhD

December 31, 2019

Environmental exposure to pyrethroid insecticides was associated with an increased risk for all-cause and cardiovascular disease mortality in an observational study of a nationally representative sample of US adults, according to findings published online December 30 in JAMA Internal Medicine.

Exposure to pyrethroid insecticides has been widespread since the phasing out of organophosphate-containing products, such as DDT, from agricultural fields as well as home gardens. Pyrethoids are synthetic analogues of pyrethin, a naturally occurring insecticide found in some chrysanthemum flowers. More than 1000 synthetic variations of chrysanthemum extract have been made, but only about a dozen are main ingredients of pesticides used in the United States. Thousands of kilograms of pyrethroids have been released to the environment over the years.

The pyrethroid insecticides are popular because they kill bugs and have no acute toxicities in mammals. However, because the compounds can damage DNA and cause oxidative stress and inflammation, effects of long-term chronic exposure are likely. Epidemiologic studies suggest links to diabetes, cardiovascular disease (CVD), Parkinson disease, and interference with reproduction and neurodevelopment.

Wei Bao, MD, PhD, of the University of Iowa, Iowa City, and colleagues investigated a link between pyrethroid exposure and mortality using data from the US National Health and Nutrition Examination Survey of 2116 adults. They assessed levels of 3-phenoxybenzoic acid (3-PBA) in urine samples provided at the time of the survey using analytical chemistry techniques (high-performance liquid chromatography, electrospray chemical ionization, and tandem mass spectrometry).

The survey was conducted from 1999 to 2002. The researchers used mortality data from the time of the survey through December 31, 2015, and analyzed data from May to August 2019. They tracked mortality from all causes, from cardiovascular disease, and from cancer, using the National Death Index database.

During the observation period (median 14.4 years), 246 of the participants died. Of those 246, 41 had cardiovascular disease and 52 had cancer.

Participants with higher levels of 3-PBA were at a higher risk for death during the follow-up period, occurring in 8.5% (unweighted, 75 of 709), 10.2% (unweighted, 81 of 701), and 11.9% (unweighted, 90 of 706) of participants as 3-PBA levels increased.

The researchers adjusted results for age, race/ethnicity, sex, socioeconomic status, dietary and lifestyle factors, body mass index, and urinary creatinine levels. Hazard ratios for all-cause mortality, CVD mortality, and cancer mortality among participants with the highest tertile compared with the lowest tertile of 3-PBA were 1.56, 3.00, and 0.91, respectively.

"Our findings are in line with epidemiologic evidence, which, although limited, indicates a significant association between pyrethroid exposure and CVD," the researchers conclude. The increase in all-cause mortality is likely a result of the insecticides' effect on the cardiovascular system, they add, noting that animal studies also link pyrethroid exposure to cardiovascular damage.

Researchers acknowledge limitations of the study: The study did not address the mechanisms of effects of pyrethroid exposure, and the assessment of a biomarker sampled at one time. The findings might not apply to countries that use different pyrethroids, and exposure to other agents might have contributed to 3-PBA levels. 

In an invited commentary, Steven D. Stellman, PhD, MPH, and Jeanne Mager Stellman, PhD, of the Mailman School of Public Health, Columbia University, New York City, point out another limitation: Average age at the end of follow-up was too young, at approximately 57 years, to fully assess the long-term consequences of chronic exposure to pyrethroids on the cardiovascular system.

The commentators sound an alarm bell. "Given the widespread use of pyrethroids and numerous exposure assessments in the general population, including in children and occupationally exposed individuals, the results of this study warrant immediate further investigation, especially because pyrethroids have long been considered of minimal hazard to humans and play a vital role in public health control of vector-borne illnesses.”

The researchers and commentators have disclosed no relevant financial relationships.

JAMA Int Med. Published online December 30, 2019. Full text, Editorial

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