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Pyrethroid pesticides (PYRs) are synthetic insecticides widely used in crops and consumer products, such as residential insecticides, pet sprays and shampoos, lice treatments, and mosquito repellents. A 2025 study published in Ecotoxicology and Environmental Safety reported on the relationship between exposure to PYRs and neurodevelopment between the ages of 1 and 2. The final analysis included 305 children from a rural area in China participating in a prospective birth cohort study who underwent neurodevelopmental testing, primarily the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III), and provided urine samples to measure PYR metabolites at ages 1 and 2, including 3PBA, 4F3PBA, and DBCA. 3PBA is a general metabolite of multiple PYRs, while 4F3PBA is a specific metabolite of cyfluthrin, and DBCA is a specific metabolite of deltamethrin. Notably, 3PBA and 4F3PBA were detected in over 87% of 1-year-olds, and at least one metabolite was detected in 98.7% by age 1. By age 2, the frequency and detection levels of each metabolite had increased, with 100% of 2-year-olds having detectable levels of at least one PYR.
After adjusting for family and sociodemographic variables, higher levels of DBCA were associated with lower scores in language and adaptive behavior, and high levels of 3PBA with lower motor development scores (OR of 1.9 comparing high vs. low). Two-year-olds with higher DBCA levels had over a 2-fold increase (OR = 2.259) in risk for a decline in language development, as well as adaptive behavior development (OR = 2.032). Urinary levels of 4F3PBA were associated with a negative effect on the improvement of cognitive and language development; this aligns with a previous study, which suggests a sensitive window of exposure between 6-8 months that may interfere with language development.
In 2020, the journal Environmental Pollution published an estimate of the exposure of U.S. adults and children to PYRs, which is considered to be widespread if not ubiquitous. Urinary analysis of 2,295 U.S. children and 5,233 adults participating in the NHANES 2007-2012 study was performed for the same three analytes (note F-PBA = 4F3PBA = 4-fluoro-3-phenoxybenzoic acid). Over 78% of samples contained 3PBA, and 79.3% of children aged 6-19 years, with a trend toward increasing exposure between 2007 and 2012. Detection rates of the more specific analytes were much lower, with 4F3PBA detected in 8.6% and DBCA in 1.27% of all participants. Keep in mind that 3PBA is a common metabolite of many PYRs, and between 12-18 PYRs are in use in the U.S., while 4F3PBA and DBCA reflect only exposure to 2 specific PYRs. In this sample, the median creatinine-adjusted levels among children (between 6-11) were 0.75 μg/g creatinine, as compared to median levels of 0.752 μg/g creatinine among 1-year-olds in the more recent study in rural China.
This recent report is not the first to suggest PYRs may adversely impact neurodevelopment. For example, data from the 2000-2001 NHANES assessed urinary 3PBA levels in U.S. children between the ages of 8 and 15. This study (published in 2015), found that children with detectable levels had a more than 2-fold (2.42) risk for attention-deficit/hyperactivity disorder (ADHD). For every 10-fold increase in 3PBA levels, a 50% risk for ADHD was observed, with the association stronger in boys than girls. A 2022 review published in Critical Reviews in Toxicology submits that while more data is needed, “the majority of studies… suggest a relatively small, but potentially significant, increase in risk in some populations for neurodevelopmental delay, lower cognitive capabilities, and rates of adverse behavioral outcomes following both prenatal and childhood pyrethroid exposures.” The use of pyrethroids is also increasing, comprising more than 80% of public health insecticides and 17% of the agricultural insecticide market in 2015, per this review.
It's also worth noting that in 2020, JAMA Internal Medicine published an analysis of NHANES cohort data, and after multivariate adjustment, adults in the highest vs. lowest tertile of 3PBA urinary levels had a 56% higher all-cause mortality risk and a 200% higher cardiovascular mortality risk. Additionally, a dose-dependent association with type 2 diabetes has been observed, with over a 2-fold increase in risk when comparing the highest vs. the lowest quartile of 3PBA urinary levels.
While diet has typically been the largest source of PYR exposure, this may be changing as they are increasingly used residentially, and can be absorbed by skin contact, inhalation, or ingestion. PYRs are likely to have neurotoxicity mediated via modification of voltage-gated sodium channels, their primary mechanism of action is as insecticides, but they can also affect chloride channels, including GABA-dependent ones, and they do pass through the blood-brain barrier. Animal studies suggest they increase DNA damage, lipid oxidation, and inflammation, and some have been associated with mitochondrial dysfunction and dopaminergic degeneration.
In addition to avoiding their use in products, consuming an organic diet can also reduce exposure. In a small 24-week study, women in their first trimester of pregnancy were randomly assigned to an organic diet (approximately 66% of all fruits/veggies) vs. a conventional diet (<3%). An average of 23 spot urine samples per participant were collected, and 3PBA levels were significantly lower on the organic diet (0.27 μg/L) compared to the conventional one (0.95 ug/L).
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