Effects of variation in detoxification rate on dose monitoring through adducts.
1. Föst et al. (Human & Experimental Toxicology 1991; 10: 25) have shown that ethylene oxide (EO) added to human blood gave rise to a higher level of adducts to haemoglobin (Hb) when the donors were deficient in an erythrocytic glutathione S-transferase (GST, later found to be GST-theta) than in blood from persons possessing this enzyme, and drew the conclusion that this polymorphism in detoxification rendered Hb adducts less suitable for biological monitoring. 2. By fitting a kinetic model to the data, the present study shows that the Hb adduct level gives a correct measure of the dose (concentration integrated over time) relevant to risk estimation. 3. It does illustrate, however, the importance of knowing an individual's detoxification efficiency, when Hb adduct measurements are used to assess environmental exposure, for example in occupational surveillance.
Föst
U
U
Institut für Arbeitsphysiologie, Universität Dortmund, Sweden.
Törnqvist
M
M
Leutbecher
M
M
Granath
F
F
Hallier
E
E
Ehrenberg
L
L
D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D004781:Environmental Exposure; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005027:Ethylene Oxide / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D005978:Glutathione / Q000737:chemistry; D005982:Glutathione Transferase / Q000097:blood; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008658:Inactivation, Metabolic; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D018570:Risk Assessment
D006454:Hemoglobins; D005982:Glutathione Transferase; D005978:Glutathione; D005027:Ethylene Oxide