MOLECULAR DOSIMETRY OF 2,4-DIFLUOROANILINE IN HUMANS AND RATS BY DETERMINATION OF HEMOGLOBIN ADDUCTS

Exposure to 2,4-difluoroaniline (DFA) was monitored by GC-MS of DFA ad ducts bound to hemoglobin (Hb). in two studies, involving 20 and 16 wo rkers potentially exposed to low concentrations of DFA, median concent rations of 10 (range 1-83) and 20 (range 4-322) pmole/g Hb were found, respectively. For better interpretation of these results, the in vivo binding of DFA to Hb was investigated. DFA was administered orally at doses of 0, 0.078, 0.775, 7.75, and 77.5 mu mole/kg/day, to 10 male a nd 10 female Fischer 344 rats for 10 consecutive days (2 rats/sex/dose group). A linear relation between dose and adduct concentration was o bserved. At the two lowest doses (0.078 and 0.775 mu mole/kg/day) no m ethemoglobinemia was observed, but adducts could easily be measured. A t these doses, the mean adduct levels were in the same range as found in the human studies. As yet, no occupational exposure limit for DFA h as been established. The German biological tolerance value (BAT-value) for aniline was set at 7.2 nmole/g Hb. This BAT-value is based on the relation between methemoglobinemia and adduct formation. The amount o f Hb binding by aniline and DFA was found to be similar in the rat. As suming that this is also the case in humans, the BAT-value for aniline may tentatively be used for DFA as well. in both studies of occupatio nally exposed workers, the adduct levels were well below this BAT-valu e.