Human health risk assessment and biological reactive intermediates: hemoglobin binding

There is ample evidence to show that the demonstration of adducts to hemoglobin and other proteins of electrophilically reactive compounds or biological reactive intermediates (BRI) is a relevant indication of the formation of the corresponding DNA adducts, and also that the rates of formation of protein- and DNA adducts are proportional. Measurement of hemoglobin and DNA adducts are therefore complementary. The former has so far been used mainly in the monitoring of low-mol.wt alkylators and BRI whereas DNA adduct monitoring has been applicable mostly to bulky compounds. Since dose-response curves are presumably linear, demonstration of adducts should be taken as identification of genotoxic risk factors. The fast development of analytical methods renders quantification of associated risks increasingly important: For instance, using adduct analysis in the search for a priori unknown carcinogens/mutagens, analytical procedures should be developed towards a power permitting detection of unacceptable risks, at the same time as unnecessary banning of factors originating from beneficial procedures should be avoided.