Biomarker correlations of urinary 2,4-d levels in foresters: Genomic instability and endocrine disruption

Forest pesticide applicators constitute a unique pesticide use group. Aeria l, mechanical-ground, and focal weed control by application of herbicides, in particular chlorophenoxy herbicides, yield diverse exposure scenarios. I n the present work, we analyzed aberrations in G-banded chromosomes, reprod uctive hormone levels, and polymerase chain reaction-based V(D)J rearrangem ent frequencies in applicators whose exposures were mostly limited to chlor ophenoxy herbicides. Data from appliers where chlorophenoxy use was less fr equent were also examined. The biomarker outcome data were compared to urin ary levels of 2,4-dichlorophenoxyacetic acid (2,4-D) obtained at the time o f maximum 2,4-D use. Further comparisons of outcome data were made to the t otal volume of herbicides applied during the entire pesticide-use season. T wenty-four applicators and 15 minimally exposed foresters (control) subject s were studied. Categorized by applicator method, men who used a hand-held, backpack sprayer in their applications showed the highest average level (4 53.6 ppb) of 2,4-D in urine. Serum luteinizing hormone (LH) values were cor related with urinary 2,4-D levels, but follicle-stimulating hormone and fre e and total testosterone were not. At the height of the application season; 6/7 backpack sprayers, 3/4 applicators who used multinozzle mechanical (bo om) 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 rearrang ements, and 3 of these 5 subjects demonstrated detectable levels of 2,4-D i n the urine. Only 8/24 DNA samples obtained from the exposed group 10 month s or more after their last chlorophenoxy use had two rearrangements per mic rogram of DNA, suggesting that the exposure-related effects observed were r eversible and temporary. Although urinary 2,4-D levels were not correlated with chromosome aberration frequency, chromosome aberration frequencies wer e correlated with the total volume of herbicides applied, including product s other than 2,4-D. In summary, herbicide applicators with high urinary lev els of 2,4-D (backpack and boom spray applications) exhibited elevated LH l evels. They also exhibited altered genomic stability as measured by V(D)J r earrangement frequency, which appears reversible months after peak exposure . Though highly detailed, the limited sample size warrants cautious interpr etation of the data.