Determination of Hemoglobin Adducts in Humans Occupationally Exposed to Acrylamide

Abstract

Hemoglobin (Hb) adduct determinations were used to monitor occupational exposure to acrylamide (AA) and acrylonitrile (AN). Forty-one workers in a factory in the People's Republic of China who were involved in the synthesis of AA by catalytic hydration of AN and the manufacturing of polyacrylamides were studied. Ten nonexposed workers in the same city served as controls. AA and AN exposures were monitored using the modified Edman degradation procedure for the determination of their respective Hb adducts to N-terminal valine. The adduct levels in the exposed workers were 0.3-34 nmol/g Hb for AA and 0.02-66 nmol/g Hb for AN, as determined by gas chromatography-mass spectrometry (GC-MS). The formation of glycidamide (GA), the epoxide metabolite of AA, in humans was demonstrated by GC-MS analysis of its Hb adduct to N-terminal valine following acid hydrolysis, ion-exchange chromatography, and derivatization. The GA adduct was detected in samples from the exposed persons with levels of 1.6-32 nmol/g Hb. There was a linear relationship between the AA and GA adduct levels (r = 0.96) and the ratio of the in vivo doses of GA and AA was 3:10. These results suggest that AA is metabolized to GA in humans, as had previously been shown in the rat. The high AA adduct levels in the exposed workers, as compared to those expected from air concentrations, indicate that dermal exposure may contribute significantly to the total uptake of AA. The average daily in vivo doses of AA and GA in the highest exposed workers were comparable to the in vivo doses in rats injected with 3 mg/kg AA. Since a regimen of 2 mg/kg/day is known to cause a significant increase of tumors in rats, preventive measures may be necessary for humans exposed to high levels of AA in industrial settings.