US EPA

1008333 

Book/Book Chapter 

Haemoglobin adduct formation by acrylonitrile in rats and mice 

Fennell, TR; Macneela, JP; Turner, MJ; Swenberg, JA 

1991 

IRL Press at Oxford University Press 

Oxford, England 

Human carcinogen exposure: Biomonitoring and risk assessment 

Biomonitoring and Risk Assessment 

241-246 

is also published as 1008439 Hemoglobin adduct formation by acrylonitrile in rats and mice
is a chapter of 1061267 Human carcinogen exposure: Biomonitoring and risk assessment

A study was conducted on adducts formed between hemoglobin and acrylonitrile (107131) (AN). Male Fischer-344-rats and male B6C3F1-mice were gavaged with up to 28mg/kg or 10mg/kg radiolabeled AN, respectively, and blood was collected either 24 or 72 hours later. The formation of hemoglobin/acrylonitrile adducts was assessed by chromatography. The reaction of erythrocytes from rats or mice and labeled acrylonitrile was also studied in-vitro, and the extent of globin binding was measured by scintillation counting following globin isolation. Rat hemoglobin bound a greater amount of acrylonitrile compared with mice; however, the shape of the dose response curves was similar in both species. A nonlinear binding curve was seen with higher levels of binding at higher doses. The major peaks detected from hydrolyzed rat and mice globin samples and in-vitro treated samples had the same retention times as S-(2-carboxyethyl)-cysteine. The formation of this species was postulated to result from the direct reaction of AN with cysteine in hemoglobin yielding S-(2-cyanoethyl)cysteine, which was detected as S-(2-carboxyethyl)cysteine following acid hydrolysis. 

DCN-230017; Nitriles; Chemical reactions; Chemical kinetics; Metabolism; Comparative toxicology; Hemoproteins; Dose response; Biological monitoring; Chromatographic analysis 

Garner, RC; Farmer, PB; Steel, GT; Wright, AS 

9780199631858