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2,4-D exposure and urinary markers of oxidative DNA damage and lipid peroxidation: a longitudinal study
  1. Catherine Chase Lerro,
  2. Gabriella Andreotti,
  3. Jason YY Wong,
  4. Aaron Blair,
  5. Nathaniel Rothman,
  6. Laura E Beane Freeman
  1. Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA
  1. Correspondence to Dr Catherine Chase Lerro, Division of Cancer Epidemiology and Genetics, Occupational and Environmental Epidemiology Branch, National Cancer Institute, Rockville, MD 20892-2590, USA; catherine.lerro{at}


Objective 2,4-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.

Methods We used multivariable generalised linear mixed-effect models to evaluate the association between urinary 2,4-D and natural log-transformed 8-iso prostaglandin F (8-isoprostane) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), adjusting for urinary creatinine, age, tobacco use and concomitant use of the herbicide picloram.

Results Compared 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).

Conclusions We 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.

  • cancer
  • free radicals
  • longitudinal studies
  • pesticides
  • environment

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  • Contributors AB and NR conceived and designed the original study. CCL performed the data analysis and prepared draft figures and tables. CCL prepared the manuscript draft with important intellectual input from LEBF. All authors were involved in writing and editing the manuscript and approved the submitted version. CCL is the guarantor for this work. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding This work was supported by the Intramural Research Program of the National Institutes of Health.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. Contact the study principal investigator (;