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Hemoglobin dosimetry and comparative toxicity of acrylamide and its metabolic glycidamide
Stockholms universitet, Naturvetenskapliga fakulteten.
1992 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Hemoglobin is a useful in vivo dosimeter for electrophilic compounds that react with nucleophilic sites in macromolecules and form covalently bound adducts. With the purpose of increasing the sensitivity of analysis of haemoglobin adducts, a method was developed for enriching adducted globin chains based on ion-exchange chromatography. The method has general applicability to adducts that cause a charge difference between adducted chains and normal globin chains. A 10 to 30-fold enrichment was achieved.

Hemoglobin dosimetry was used to study the industrial chemical acrylamide. Acrylamide induces a variety of adverse health effects, including neurotoxicity, reproductive and genetic toxicity and carcinogenicity. In rats, acrylamide was found to be metabolized to the genotoxic epoxide glycidamide. At low doses of acrylamide over 50 % was metabolized to glycidamide, whereas at high doses the formation of glycidamide was saturated. The role of glycidamide in the toxicity induced by acrylamide was studied in rats. Effects on motor performance and the male reproductive system were assessed. Peripheral neuropathy was ascribed to the parent compound while reproductive toxicity seemed to be primarily induced by the metabolite glycidamide.

Gas chromatography-mass spectrometry methods were developed for the quantitation of hemoglobin adducts formed by acrylamide and glycidamide in rats and humans. Two approaches were used. The first was based on analysis of adducts to cysteine and N-terminal valine in globin hydrolysates, and the second was an application of the modified Edman degradation method for adducts to Nterminal valine.

A group of highly exposed workers in the People's Republic of China wasstudied. They were involved in the production of acrylamide (from acrylonitrile) and polyacrylamides. Several workers showed symptoms of peripheral neuropathy. Hemoglobin adducts of acrylamide and acrylonitrile were detected in all exposed workers. Glycidamide adducts were also detected in exposed workers. The levels were linearly correlated to acrylamide adduct levels, indicating that acrylamide is metabolized to glycidamide in humans. Glycidamide is hypothesized as being responsible for the cancer-initiating properties of acrylamide. A tentative cancer risk estimation for acrylamide in the studied workers is presented.

sted, utgiver, år, opplag, sider
Stockholm: Stockholm University, 1992. , s. 47
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URN: urn:nbn:se:su:diva-152986ISBN: 91-7153-055-X (tryckt)OAI: oai:DiVA.org:su-152986DiVA, id: diva2:1182695
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Tilgjengelig fra: 2018-02-14 Laget: 2018-02-14 Sist oppdatert: 2018-02-14bibliografisk kontrollert

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