Perturbation of lipids and glucose metabolism associated with previous 2,4-D exposure: a cross-sectional study of NHANES III data, 1988-1994.
BACKGROUND
Results from previous population studies showed that mortality rates from acute myocardial infarction and type-2 diabetes during the 1980s and 1990s in rural, agricultural counties of Minnesota, Montana, North and South Dakota, were higher in counties with a higher level of spring wheat farming than in counties with lower levels of this crop. Spring wheat, one of the major field crops in these four states, was treated for 85% or more of its acreage with chlorophenoxy herbicides. In the current study NHANES III data were reviewed for associations of 2,4-dichlorophenoxy acetic acid (2,4-D) exposure, one of the most frequently used chlorophenoxy herbicides, with risk factors that are linked to the pathogenesis of acute myocardial infarction and type-2 diabetes, such as dyslipidemia and impaired glucose metabolism.


METHODS
To investigate the toxicity pattern of chlorophenoxy herbicides, effects of a previous 2,4-D exposure were assessed by comparing levels of lipids, glucose metabolism, and thyroid stimulating hormone in healthy adult NHANES III subjects with urinary 2,4-D above and below the level of detection, using linear regression analysis. The analyses were conducted for all available subjects and for two susceptible subpopulations characterized by high glycosylated hemoglobin (upper 50th percentile) and low thyroxine (lower 50th percentile).


RESULTS
Presence of urinary 2,4-D was associated with a decrease of HDL levels: 8.6% in the unadjusted data (p-value = 0.006), 4.8% in the adjusted data (p-value = 0.08), and 9% in the adjusted data for the susceptible subpopulation with low thyroxine (p-value = 0.02). An effect modification of the inverse triglycerides-HDL relation was observed in association with 2,4-D. Among subjects with low HDL, urinary 2,4-D was associated with increased levels of triglycerides, insulin, C-peptide, and thyroid stimulating hormone, especially in the susceptible subpopulations. In contrast, subjects with high HDL did not experience adverse 2,4-D associated effects.


CONCLUSIONS
The results indicate that exposure to 2,4-D was associated with changes in biomarkers that, based on the published literature, have been linked to risk factors for acute myocardial infarction and type-2 diabetes.
Schreinemachers
Dina M
DM
Epidemiology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, 109 TW Alexander Drive, Research Triangle Park, NC 27711, USA. schreinemachers.dina@epa.gov
D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity* / Q000652:urine; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism; D003430:Cross-Sectional Studies; D050171:Dyslipidemias / Q000139:chemically induced / Q000378:metabolism; D004781:Environmental Exposure / Q000032:analysis*; D005260:Female; D044882:Glucose Metabolism Disorders / Q000139:chemically induced / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity* / Q000652:urine; D006801:Humans; D016014:Linear Models; D008055:Lipids / Q000097:blood*; D008075:Lipoproteins, HDL / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009749:Nutrition Surveys; D013974:Thyroxine / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D015084:2,4-Dichlorophenoxyacetic Acid; D001786:Blood Glucose; D008076:Cholesterol, HDL; D006442:Glycated Hemoglobin; D006540:Herbicides; D008055:Lipids; D008075:Lipoproteins, HDL; D013974:Thyroxine; D014280:Triglycerides; C034396:HDL-triglyceride