Increased lymphocyte replicative index following 2,4-dichlorophenoxyacetic acid herbicide exposure

Cancer Causes Control. 2000 Apr;11(4):373-80. doi: 10.1023/a:1008925824242.


Objective: Evaluate peripheral blood lymphocyte proliferation (replicative index:RI) and micronuclei frequency (MF) among 2,4-D herbicide applicators.

Methods: Twelve applicators spraying only 2,4-D provided a blood and urine specimen upon enrollment, several urine samples during the spraying season, and a blood specimen at the study's end. Nine controls provided blood and urine specimens upon enrollment and at the study's end. Gas chromatography/tandem mass spectroscopy determined urinary 2,4-D levels and standard in-vitro assays determined RI and MF scores. Applicator RI and MF were compared before and after spraying and with controls.

Results: Applicators contributed 45 urine specimens with concentrations ranging from 1.0 to 1700 (microg 2,4-D/g creatinine/L urine) that logarithmically (In) increased as spraying time increased. Applicator RI increased after spraying (p = 0.016), independent of tobacco and alcohol use, and demonstrated a weak dose-response with increasing urinary 2,4-D levels (p = 0.15). Among 2,4-D applicators, pre-exposure complete blood counts and lymphocyte immunophenotypes were not significantly different from post-exposure measurements.

Conclusion: Urinary 2,4-D concentration, an exposure biomarker, may be associated with lymphocyte replicative index, a cell proliferation biomarker.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2,4-Dichlorophenoxyacetic Acid / adverse effects*
  • 2,4-Dichlorophenoxyacetic Acid / blood
  • 2,4-Dichlorophenoxyacetic Acid / urine*
  • Adolescent
  • Adult
  • Alcohol Drinking
  • Biomarkers / urine
  • Case-Control Studies
  • Gas Chromatography-Mass Spectrometry
  • Herbicides / adverse effects*
  • Herbicides / blood
  • Herbicides / urine*
  • Humans
  • Lymphocyte Activation / drug effects*
  • Male
  • Micronuclei, Chromosome-Defective / drug effects
  • Middle Aged
  • Occupational Exposure / adverse effects*
  • Occupational Exposure / analysis
  • Pilot Projects
  • Smoking
  • Surveys and Questionnaires


  • Biomarkers
  • Herbicides
  • 2,4-Dichlorophenoxyacetic Acid