Effects of variation in detoxification rate on dose monitoring through adducts

• Published in: Human & experimental toxicology Vol. 14; no. 2; pp. 201 - 203
• Main Authors: Föst, U., Törnqvist, M., Leutbecher, M., Granath, F., Hallier, E., Ehrenberg, L.
• Format: Journal Article
• Language: English
• Published: Thousand Oaks, CA SAGE Publications 01.02.1995; Arnold
• Subjects: Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; Dose-Response Relationship, Drug; Drug Monitoring - methods; Environmental Exposure; Erythrocytes - drug effects; Erythrocytes - enzymology; Ethylene Oxide - adverse effects; Ethylene Oxide - metabolism; Ethylene Oxide - pharmacokinetics; Gas, fumes; Glutathione - chemistry; Glutathione Transferase - blood; Hemoglobins - chemistry; Hemoglobins - metabolism; Humans; Inactivation, Metabolic; Medical sciences; Occupational Exposure; Polymorphism, Genetic; Regression Analysis; Risk Assessment; Toxicology; hemoglobin adducts; GST-poly morphism; dose; GST-theta; ethylene oxide; Human; Enzyme; Glutathione transferase; Transferases; Interindividual comparison; Hemoglobin; Biological marker; Ethylene oxide; Occupational exposure; Molecular adduct; Biological monitoring; Polymorphism
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/096032719501400208

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 pos sessing 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) rele vant 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 environmen tal exposure, for example in occupational surveillance.