A longitudinal study of atrazine and 2,4‐D exposure and oxidative stress markers among iowa corn farmers

Abstract

Reactive oxygen species, potentially formed through environmental exposures, can overwhelm an organism’s antioxidant capabilities resulting in oxidative stress. Long-term oxidative stress is linked with chronic diseases. Pesticide exposures have been shown to cause oxidative stress in vivo. We utilized a longitudinal study of corn farmers and non-farming controls in Iowa to examine the impact of exposure to the widely used herbicides atrazine and 2,4-dichlorophenoxyacetic acid (2,4-D) on markers of oxidative stress. 225 urine samples were collected during five agricultural time periods (pre-planting, planting, growing, harvest, off-season) for 30 farmers who applied pesticides occupationally and 10 controls who did not; all were non-smoking men ages 40–60. Atrazine mercapturate (atrazine metabolite), 2,4-D, and oxidative stress markers (malondialdehyde [MDA], 8-hydroxy-2′-deoxyguanosine [8-OHdG], and 8-isoprostaglandin-F2α [8-isoPGF]) were measured in urine. We calculated β estimates and 95% confidence intervals (95%CI) for each pesticide-oxidative stress marker combination using multivariate linear mixed-effect models for repeated measures. Farmers had higher urinary atrazine mercapturate and 2,4-D levels compared to controls. In regression models, after natural log transformation, 2,4-D was associated with elevated levels of 8-OHdG (β=0.066, 95%CI=0.008–0.124) and 8-isoPGF (β=0.088, 95%CI=0.004–0.172). 2,4-D may be associated with oxidative stress because of modest increases in 8-OHdG, a marker of oxidative DNA damage, and 8-isoPGF, a product of lipoprotein peroxidation, with recent 2,4-D exposure. Future studies should investigate the role of 2,4-D-induced oxidative stress in the pathogenesis of human diseases.

2,4-D exposure and urinary markers of oxidative DNA damage and lipid peroxidation: a longitudinal study

“…Here in KS applicators, we observed increased 8-isoprostane (third quartile of 2,4-D exposure), but not in the fourth quartile and no evidence of a monotonic trend. Our findings did not replicate the earlier study, despite evaluating the same urinary oxidative stress markers in applicators with measured urinary levels of 2,4-D much higher than those reported in Iowa corn farmers 13. For example, the lowest quartile of exposure in the KS weed applicators encompassed the entire range of 2,4-D exposures reported in the Iowa corn farmers.…”

“…For example, the lowest quartile of exposure in the KS weed applicators encompassed the entire range of 2,4-D exposures reported in the Iowa corn farmers. One reason for the difference in the results could be the age difference in the two study populations; the mean age in the Iowa study is 51 years, almost 20 years older than this analysis 13. In the present study, 2,4-D was not measured at baseline for controls or applicators.…”

“…2,4-D exposure has been demonstrated to cause oxidative tissue damage in vivo 12. Additionally, a longitudinal epidemiologic study of 30 Iowa corn farmers and 10 non-farming controls found that urinary 2,4-D (modelled continuously) was associated with modest elevations in 8-OHdG and 8-isoprostane 13. Here in KS applicators, we observed increased 8-isoprostane (third quartile of 2,4-D exposure), but not in the fourth quartile and no evidence of a monotonic trend.…”

“…The International Agency for Research on Cancer recently classified 2,4-D as a possible human carcinogen (2B), based on limited epidemiologic evidence and animal models that demonstrated consistent and strong associations between 2,4-D and increased oxidative stress 12. A recent longitudinal study of pesticide applicators and non-applicator controls noted modest elevations in urinary markers of oxidative stress shortly after 2,4-D exposure 13. Oxidative stress occurs when the presence of free radicals overwhelm an organism’s antioxidants and DNA repair mechanisms 14.…”

Oxidative stress in triazine pesticide toxicity: a review of the main biomarker findings

“…Several studies in humans reported an imbalance between oxidative stress markers and the antioxidant defences in farmers/pesticide applicators or agricultural workers (7,(100)(101)(102). However, a thorough search of relevant literature yielded only one epidemiological study of the association between the biomarkers of atrazine exposure and biomarkers of oxidative stress (103), and none about terbuthylazine. In that one study, no association was found between atrazine mercapturate (AM) and MDA, 8-hydroxy-2'-deoxyguanosine (8-OHdG), or 8-isoprostaglandin-F2 (8-isoPGF) in urine samples collected from 30 farmers over five time points of atrazine application.…”