Biomarker Correlations of Urinary 2,4-D Levels in Foresters: Genomic Instability and Endocrine Disruption Vincent F. Garry,1 Robert E. Tarone,2 Ilan R. Kirsch,3 Jorge M. Abdallah,3 Donald P. Lombardi,3 Leslie K. Long,1 Barbara L. Burroughs,1 Dana B. Barr,4 and James S. Kesner5 1Environmental Medicine and Pathology Laboratory, University of Minnesota, Minneapolis, Minnesota, USA 2Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA 3Genetics Department, Medicine Branch, National Cancer Institute, Bethesda, Maryland, USA 4Centers for Disease Control and Prevention, Atlanta, Georgia, USA 5Reproductive Health Assessment Section, National Institute for Occupational Safety and Health, Cincinnati, Ohio, USA Abstract Forest pesticide applicators constitute a unique pesticide use group. Aerial, mechanical-ground, and focal weed control by application of herbicides, in particular chlorophenoxy herbicides, yield diverse exposure scenarios. In the present work, we analyzed aberrations in G-banded chromosomes, reproductive hormone levels, and polymerase chain reaction-based V(D) J rearrangement frequencies in applicators whose exposures were mostly limited to chlorophenoxy herbicides. Data from appliers where chlorophenoxy use was less frequent were also examined. The biomarker outcome data were compared to urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D) obtained at the time of maximum 2,4-D use. Further comparisons of outcome data were made to the total volume of herbicides applied during the entire pesticide-use season.Twenty-four applicators and 15 minimally exposed foresters (control) subjects were studied. Categorized by applicator method, men who used a hand-held, backpack sprayer in their applications showed the highest average level (453.6 ppb) of 2,4-D in urine. Serum luteinizing hormone (LH) values were correlated with urinary 2,4-D levels, but follicle-stimulating hormone and free and total testosterone were not. At the height of the application season ; 6/7 backpack sprayers, 3/4 applicators who used multinozzle mechanical (boom) sprayers, 4/8 aerial applicators, and 2/5 skidder-radiarc (closed cab) appliers had two or more V(D) J region rearrangements per microgram of DNA. Only 5 of 15 minimally exposed (control) foresters had two or more rearrangements, and 3 of these 5 subjects demonstrated detectable levels of 2,4-D in the urine. Only 8/24 DNA samples obtained from the exposed group 10 months or more after their last chlorophenoxy use had two rearrangements per microgram of DNA, suggesting that the exposure-related effects observed were reversible and temporary. Although urinary 2,4-D levels were not correlated with chromosome aberration frequency, chromosome aberration frequencies were correlated with the total volume of herbicides applied, including products other than 2,4-D. In summary, herbicide applicators with high urinary levels of 2,4-D (backpack and boom spray applications) exhibited elevated LH levels. They also exhibited altered genomic stability as measured by V(D) J rearrangement frequency, which appears reversible months after peak exposure. Though highly detailed, the limited sample size warrants cautious interpretation of the data. Key words: 2, 4-D, foresters, reproductive hormones, V(D) J rearrangements. Environ Health Perspect 109:495-500 (2001) . [Online 9 May 2001] http://ehpnet1.niehs.nih.gov/docs/2001/109p495-500garry/ abstract.html Address correspondence to V.F. Garry, Environmental Medicine and Pathology Laboratory, University of Minnesota, 421 29th Avenue SE, Minneapolis, MN 55414-3290 USA. Telephone: (612) 627-4235. Fax: (612) 627-4241. E-mail: garry001@maroon.tc.umn.edu We thank the foresters of the state of Minnesota who gave of their time and effort to make this study possible. Special thanks to M. Harkins, B. Coleman, and E.A. Knecht for their technical assistance. This work was supported in part by U.S. Department of Agriculture research agreement 23-94-19 (forestry) , and National Institute of Environmental Health Sciences grant 5RO1-ESO 8161. Received 17 July 2000 ; accepted 22 November, 2000. The full version of this article is available for free in HTML or PDF formats. |