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

Abstract

Objective2,4-Dichlorophenoxyacetic acid (2,4-D) is a herbicide that is commonly used commercially, agriculturally and residentially worldwide. There is concern about its potential for carcinogenicity based on studies in laboratory animals demonstrating the potential for induction of oxidative stress. We conducted a longitudinal biomarker study of 31 pesticide applicators in Kansas who heavily applied 2,4-D and 34 non-applicator controls.MethodsWe used multivariable generalised linear mixed-effect models to evaluate the association between urinary 2,4-D and natural log-transformed 8-iso prostaglandin F2α (8-isoprostane) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), adjusting for urinary creatinine, age, tobacco use and concomitant use of the herbicide picloram.ResultsCompared with non-applicator controls, urinary 2,4-D in the third quartile of exposure was associated with elevated 8-isoprostane (eβ=1.38, 95% CI 1.03 to 1.84). There was no association among the highest exposed and no exposure-response trend. 2,4-D exposure was not associated with 8-OHdG. Results were unchanged when restricted to participants who only applied 2,4-D (no picloram use).ConclusionsWe did not find evidence that increasing 2,4-D exposure was associated with 8-isoprostane or 8-OHdG. Future work should carefully evaluate potential confounders of this association, such as diet and physical activity, as well as additional biological markers of oxidative stress and damage.

Prostaglandin Metabolome Profiles in Zebrafish (Danio rerio) Exposed to Acetochlor and Butachlor

“…The present study indicated that iPGs could be novel biomarker candidates for assessing chloroacetanilide herbicides. Several molecular epidemiological studies had provided us with evidence that iPGs showed a significant positive correlation to pesticide exposure [ 36 , 37 , 38 ]. For example, the level of 8-iPGF2a was significantly related to urinary organophosphorus metabolites in South Korean male farmers [ 36 ], to urinary 2,4-Dichlorophenoxyacetic acid (2,4-D) in pesticide applicators in Kansas, USA [ 37 ], and to urinary glyphosate in agricultural workers in Brazil [ 38 ].…”

“…Several molecular epidemiological studies had provided us with evidence that iPGs showed a significant positive correlation to pesticide exposure [ 36 , 37 , 38 ]. For example, the level of 8-iPGF2a was significantly related to urinary organophosphorus metabolites in South Korean male farmers [ 36 ], to urinary 2,4-Dichlorophenoxyacetic acid (2,4-D) in pesticide applicators in Kansas, USA [ 37 ], and to urinary glyphosate in agricultural workers in Brazil [ 38 ]. Our metabolomic data showed the 8-iPGF2a level in zebrafish was not affected by AC and BC exposure; however, three iPGs, 8-iso PGF1α, 5-iPF2α-VI, and 8-iso-16-cyclohexyl-tetranor PGE2, were induced by AC and BC.…”

Association between increasing agricultural use of 2,4-D and population biomarkers of exposure: findings from the National Health and Nutrition Examination Survey, 2001–2014

“…While the carcinogenicity of 2,4-D has been intensively studied and long debated [31,32], new studies have heightened concern. A 2020 longitudinal biomarker study linked 2,4-D with increased systemic markers of oxidative stress [33]. Association between 2,4-D exposures and non-Hodgkin lymphoma (NHL) have been reported, with a recent meta-analysis showing that highly exposed groups experience an elevated relative risk of NHL (RR = 1.73, CI: 1.10-2.72) [34].…”

Decreased Antioxidant Capacity in Corn Farmers Occupationally Exposed to the Mixture of Herbicides

“…Previous studies demonstrated that the increase of lipid peroxidation by-product (8-isoprostane) was induced in corn farmers exposed with mixtures of herbicide usage between atrazine and 2-(2,4-dichlorophenoxy) acetic acid (2,4-D) 9,10 . Available studies about antioxidant defense has been reported that superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) level was significantly decreased in herbicide-exposed workers 11,12 .…”