A NONLINEAR DOSIMETRIC MODEL FOR HEMOGLOBIN ADDUCT FORMATION BY THE NEUROTOXIC AGENT ACRYLAMIDE AND ITS GENOTOXIC METABOLITE GLYCIDAMIDE

被引：22

作者：

CALLEMAN, CJ ^{[1
]}

BERGMARK, E ^{[1
]}

STERN, LG ^{[1
]}

COSTA, LG ^{[1
]}

机构：

[1] UNIV WASHINGTON HOSP,DEPT APPL MATH,SEATTLE,WA 98195

来源：

ENVIRONMENTAL HEALTH PERSPECTIVES | 1993年 / 99卷

关键词：

D O I：

10.2307/3431486

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

Hemoglobin (Hb) adducts, formed by the neurotoxic agent acrylamide (AA) and its genotoxic metabolite glycidamide (GA), were measured in the rat by means of a method for simultaneous determination of the adducts formed to cysteine. A novel, nonlinear dosimetric model was developed to describe Hb adduct formation. This model incorporates the saturable kinetics of the metabolic conversion in vivo of AA to GA. The pharmacokinetic parameters V(max) and K(m) and the first-order rates of elimination, k1 and k2, for AA and GA from all processes except conversion of AA to GA, were estimated directly from Hb adduct data to 19 M hr-1, 66 mM, 0.21 hr-1, and 0.48 hr-1, respectively. At low concentrations, approximately 60% of AA was metabolized to GA. The nonlinear dosimetric model for adduct formation has potential general applicability in high-to-low-dose extrapolation of genotoxic effects.

引用

页码：221 / 223

页数：3

共 10 条

[1] MONITORING EXPOSURE TO ACRYLAMIDE BY THE DETERMINATION OF S-(2-CARBOXYETHYL)CYSTEINE IN HYDROLYZED HEMOGLOBIN BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY [J].