title: Biomarker correlations of urinary 2,4-D levels in foresters: genomic instability and endocrine disruption.
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.
authors.affiliation: Environmental Medicine and Pathology Laboratory, University of Minnesota, Minneapolis, Minnesota 55414-3290, USA. garry001@maroon.tc.umn.edu
authors.forename: V F
authors.initials: VF
authors.lastname: Garry
authors.forename: R E
authors.initials: RE
authors.lastname: Tarone
authors.forename: I R
authors.initials: IR
authors.lastname: Kirsch
authors.forename: J M
authors.initials: JM
authors.lastname: Abdallah
authors.forename: D P
authors.initials: DP
authors.lastname: Lombardi
authors.forename: L K
authors.initials: LK
authors.lastname: Long
authors.forename: B L
authors.initials: BL
authors.lastname: Burroughs
authors.forename: D B
authors.initials: DB
authors.lastname: Barr
authors.forename: J S
authors.initials: JS
authors.lastname: Kesner
mesh_terms: D015084:2,4-Dichlorophenoxyacetic Acid / Q000009:adverse effects / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D004703:Endocrine System / Q000187:drug effects; D016468:Forestry; D015329:Gene Rearrangement, T-Lymphocyte / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000032:analysis / Q000652:urine*; D006540:Herbicides / Q000009:adverse effects / Q000652:urine*; D006801:Humans; D008297:Male; D016296:Mutagenesis / Q000187:drug effects*; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis; D010573:Pesticide Residues / Q000009:adverse effects* / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D015415:Biomarkers; D012739:Gonadal Steroid Hormones; D006540:Herbicides; D010573:Pesticide Residues; D011948:Receptors, Antigen, T-Cell; D015084:2,4-Dichlorophenoxyacetic Acid