Haemoglobin binding in control of exposure to and risk assessment of aromatic amines

Haemoglobin is proposed as a dose monitor for aromatic amines. Metabolically formed nitrosoarenes react with sulphydryl groups of haemoglobin and, after intramolecular rearrangement, yield sulphinic acid amides. This type of adduct is stable in vivo but can readily be hydrolysed after haemoglobin is isolated from blood samples, usually yielding the parent amine, which is quantified by gas chromatography or high-performance liquid chromatography. The haemoglobin binding index was determined in rats for a series of monocyclic aromatic amines, benzidine and some benzidine congeners. The following relationships are discussed: between binding of metabolites to DNA and to proteins; between haemoglobin binding and biological endpoints such as carcinogenesis and methaemoglobin formation; and between haemoglobin binding and molecular endpoints such as DNA binding and protein binding in liver and kidney. Haemoglobin binding correlates with a biologically active dose of aromatic amines and is thus well suited for monitoring exposure. The relationship between haemoglobin binding and the dose at critical targets is more complex, and, at present, carcinogenic risk cannot be assessed from biological monitoring data.