Induction of P-450 in workers exposed to dioxin.
OBJECTIVE
To examine the effects of occupational exposure to substances contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on cytochrome P-4501A2 activity in a cross sectional medical survey.


METHODS
The exposed workers had been employed at two chemical plants > 15 years earlier in the manufacture of 2,4, 5-trichlorophenol and its derivatives. The control group consisted of people with no occupational exposure to phenoxy herbicides and who lived within the communities of the exposed workers. A total of 58 workers and 125 unexposed controls participated in the analysis. Cytochrome P-450 activity was assessed with test that measures caffeine metabolites in the urine. A ratio of metabolites of caffeine (CMR) constituted a measure of P-4501A2 activity.


RESULTS
Compared with the control group in multivariate logistic regression, raised non-significant associations were found for three of four 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 > or = 148, OR 3.1, 95% CI 0.8 to 12.5). We found a strongly significant association of CMR and urinary cotinine, a measure of smoking, and urinary free ethanol. We found weak non-significant associations between P-4501A2 activity and increased serum TCDD among workers.


CONCLUSIONS
The absence of an association between serum TCDD and cytochrome P-4501A2 may be due to the size of the study, insensitivity of the CMR to assess cytochrome P-4501A2 activity, or inadequate levels of exposure, although these were among the highest in human groups tested.
Halperin
W
W
National Institute for Occupational Safety and Health, Cincinnati, Ohio, USA.
Kalow
W
W
Sweeney
M H
MH
Tang
B K
BK
Fingerhut
M
M
Timpkins
B
B
Wille
K
K
D000328:Adult; D000368:Aged; D002110:Caffeine / Q000378:metabolism; D002617:Chemical Industry; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D016273:Occupational Exposure; D010088:Oxidoreductases / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D012907:Smoking / Q000378:metabolism
D000072317:Polychlorinated Dibenzodioxins; D002110:Caffeine; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019388:Cytochrome P-450 CYP1A2