OBJECTIVES: To examine internal exposure and targeted health outcomes of employees exposed to 3-(3,5-dichlorophenyl)-5-methyl-5-vinyl-1,3-oxazolidine-2,4-dione; chemical abstracts service (CAS) number: 50471-44-8 (vinclozolin). METHODS: A cross sectional study of 67 men exposed to vinclozolin for one to 13 years during synthesis and formulation operations and 52 controls. Biomonitoring was based on determination of urinary metabolites that contained a 3,5-dichloroaniline (3,5-DCA) moiety. Targeted health endpoints were the same as in previous subchronic and chronic animal studies--namely, reversible changes in the concentrations of hormones of the adrenocorticotrophic and gonadotrophic feedback systems, signs of liver injury, haemolytic anaemia, cataract formation (uniquely in rats), and hormonally induced hyperplasia and tumours at high doses. The clinical investigation consisted of a medical and occupational history questionnaire, physical examination, laboratory determinations (including testosterone, LH, and FSH measurements), ultrasonography of the liver and prostate, a detailed eye examination, and routine spirometry. RESULTS: The mean 3,5-DCA concentration for two thirds of the study group exceeded an equivalent of the vinclozolin acceptable daily intake (ADI) used for consumer regulatory purposes. Even the highest concentrations were, however, at least 10 times below the no observable adverse effect level (NOAEL) based on animal studies. Analysis of physical examination and laboratory data provided no evidence of hormonal responses induced by vinclozolin. Furthermore, no evidence of liver injury, prostate changes, cataract formation, or haemolytic anaemia was found. CONCLUSION: There was no evidence of any health effects induced by vinclozolin among employees with potential long term exposure. In particular, no antiandrogenic effects were found.
OBJECTIVES: To examine internal exposure and targeted health outcomes of employees exposed to 3-(3,5-dichlorophenyl)-5-methyl-5-vinyl-1,3-oxazolidine-2,4-dione; chemical abstracts service (CAS) number: 50471-44-8 (vinclozolin). METHODS: A cross sectional study of 67 men exposed to vinclozolin for one to 13 years during synthesis and formulation operations and 52 controls. Biomonitoring was based on determination of urinary metabolites that contained a 3,5-dichloroaniline (3,5-DCA) moiety. Targeted health endpoints were the same as in previous subchronic and chronic animal studies--namely, reversible changes in the concentrations of hormones of the adrenocorticotrophic and gonadotrophic feedback systems, signs of liver injury, haemolytic anaemia, cataract formation (uniquely in rats), and hormonally induced hyperplasia and tumours at high doses. The clinical investigation consisted of a medical and occupational history questionnaire, physical examination, laboratory determinations (including testosterone, LH, and FSH measurements), ultrasonography of the liver and prostate, a detailed eye examination, and routine spirometry. RESULTS: The mean 3,5-DCA concentration for two thirds of the study group exceeded an equivalent of the vinclozolin acceptable daily intake (ADI) used for consumer regulatory purposes. Even the highest concentrations were, however, at least 10 times below the no observable adverse effect level (NOAEL) based on animal studies. Analysis of physical examination and laboratory data provided no evidence of hormonal responses induced by vinclozolin. Furthermore, no evidence of liver injury, prostate changes, cataract formation, or haemolytic anaemia was found. CONCLUSION: There was no evidence of any health effects induced by vinclozolin among employees with potential long term exposure. In particular, no antiandrogenic effects were found.