INDUCTION OF P-450 IN WORKERS EXPOSED TO DIOXIN

Objectives-To examine the effects of occupational exposure to substanc es contaminated with 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) on cy tochrome P-4501A2 activity in a cross sectional medical survey. Method s-The exposed workers had been employed at two chemical plants >15 yea rs earlier in the manufacture of 2,4, 5-trichlorophenol and its deriva tives. The control group consisted of people with no occupational expo sure to phenoxy herbicides and who lived within the communities of the exposed workers. A total of 58 workers and 125 unexposed controls par ticipated in the analysis. Cytochrome P-450 activity was assessed with a test that measures caffeine metabolites in the urine. A ratio of me tabolites of caffeine (CMR) constituted a measure of P-4501A2 activity . Results-Compared with the control group in multivariate logistic reg ression, raised non-significant associations were found for three of f our categories of TCDD in exposed workers (TCDD <20 pg/g, odds ratio ( OR) 1.7, 95% confidence interval (95% CI) 0.6 to 5.0, TCDD 20-66, OR 0 .3, 95% CI 0.0 to 1.7; TCDD 67-147, OR 2.3, 95% CI 0.6 to 8.8; TCDD gr eater than or equal to 148, OR 3.1, 95% CI O.8 to 12.5). We found a st rongly significant association of CMR and urinary cotinine, a measure of smoking, and urinary free ethanol. We found weak non-significant as sociations between P-4501A2 activity and increased serum TCDD among wo rkers. Conclusions-The absence of an association between serum TCDD an d cytochrome F4501A2 may be due to the size of the study, insensitivit y of the CMR to assess cytochrome P-4501A2 activity, or inadequate lev els of exposure, although these were among the highest in human groups tested.