Hematologic Perturbations among Pesticide Applicators Recently Exposed to Permethrin in the Agricultural Health Study

Abstract

In the Agricultural Health Study (AHS), a large prospective cohort of pesticide applicators, exposure to the pyrethroid insecticide permethrin is associated with an increased risk of multiple myeloma (MM), a hematologic malignancy with an unfavorable prognosis. To gain insight into the biological mechanisms underlying this association, we assessed potential hematotoxic effects of permethrin, in a longitudinal study of 35 permethrin-exposed male pesticide applicators in the AHS. Serial blood samples were collected from each participant in the off-season, the day after permethrin use, and approximately 3 weeks after use. At each time point, we performed a complete blood count with white blood cell differential and measured lymphocyte subsets. We used linear mixed models to assess the relationship between permethrin exposure and cell counts, controlling for season, age, BMI, recent cold/infection (≤7 days), and use of other pesticides (≤30 days). We observed a statistically significant increase in the geometric mean of immature granulocytes (31%, 95% CI=6%, 63%) on the day after permethrin use relative to off-season levels, but not 3 weeks after use. Statistically significant (P<0.05) alterations in several red blood cell parameters were also observed on the day after permethrin use, including decreased red blood cell count, hemoglobin, and hematocrit and increased mean corpuscular volume and red blood cell distribution width-SD. Red blood cell count, hemoglobin, and hematocrit remained significantly decreased 3 weeks after permethrin use. Increased immature granulocytes are indicative of an inflammatory response and enhanced bone marrow activity, and sustained decreases in red blood cell parameters may be a result of increased oxidative stress. Our results suggest inflammatory and hematologic effects of permethrin exposure, and identify targeted cell populations for future mechanistic studies to elucidate the relationship between permethrin use and MM risk.