Hemoglobin Adducts and Urinary Metabolites of Arylamines and Nitroarenes

• Published in: Chemical research in toxicology Vol. 30; no. 10; pp. 1733 - 1766
• Main Author: Sabbioni, Gabriele
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 16.10.2017
• Subjects: Amines - chemistry; Amines - metabolism; Amines - urine; Animals; Hemoglobins - analysis; Hemoglobins - chemistry; Hemoglobins - metabolism; Humans; Molecular Structure; Nitro Compounds - chemistry; Nitro Compounds - metabolism; Nitro Compounds - urine
• ISSN: 0893-228X; 1520-5010; 1520-5010
• DOI: 10.1021/acs.chemrestox.7b00111

Arylamines and nitroarenes are intermediates in the production of pharmaceuticals, dyes, pesticides, and plastics and are important environmental and occupational pollutants. N-Hydroxyarylamines are the toxic common intermediates of arylamines and nitroarenes. N-Hydroxyarylamines and their derivatives can form adducts with hemoglobin (Hb-adducts), albumin, DNA, and tissue proteins in a dose-dependent manner. Most of the arylamine Hb-adducts are labile and undergo hydrolysis in vitro, by mild acid or base, to form the arylamines. According to current knowledge of arylamine adduct-formation, the hydrolyzable fraction is derived from the reaction products of the arylnitroso derivatives that yield arylsulfinamide adducts with cysteine. Hb-adducts are markers for the bioavailability of N-hydroxyarylamines. Hb-adducts of arylamines and nitroarenes have been used for many biomonitoring studies for over 30 years. Hb-adducts reflect the exposure history of the last four months. Biomonitoring of urinary metabolites is a less invasive process than biomonitoring blood protein adducts, and urinary metabolites have served as short-lived biomarkers of exposure to these hazardous chemicals. However, in case of intermittent exposure, urinary metabolites may not be detected, and subjects may be misclassified as nonexposed. Arylamines and nitroarenes and/or their metabolites have been measured in urine, especially to monitor the exposure of workers. This review summarizes the results of human biomonitoring studies involving urinary metabolites and Hb-adducts of arylamines and nitroarenes. In addition, studies about the relationship between Hb-adducts and diseases are summarized.