title: Molecular dosimetry of 2,4-difluoroaniline in humans and rats by determination of hemoglobin adducts.
abstract: Exposure to 2,4-difluoroaniline (DFA) was monitored by GC-MS of DFA adducts bound to hemoglobin (Hb). In two studies, involving 20 and 16 workers potentially exposed to low concentrations of DFA, median concentrations 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 mumole/kg/day, to 10 male and 10 female Fischer 344 rats for 10 consecutive days (2 rats/sex/dose group). A linear relation between dose and adduct concentration was observed. At the two lowest doses (0.078 and 0.775 mumole/kg/day) no methemoglobinemia was observed, but adducts could easily be measured. At 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 has 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 of Hb binding by aniline and DFA was found to be similar in the rat. Assuming 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 occupationally exposed workers, the adduct levels were well below this BAT-value.
authors.affiliation: Shell Internationale Petroleum Maatschappij, B.V., Health, Safety, and Environment Division, The Hague, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Boogaard
authors.forename: G N
authors.initials: GN
authors.lastname: Fokkema
authors.forename: G D
authors.initials: GD
authors.lastname: Beulink
authors.forename: J
authors.initials: J
authors.lastname: Bouskill
authors.forename: N J
authors.initials: NJ
authors.lastname: van Sittert
mesh_terms: D000814:Aniline Compounds / Q000032:analysis*; D000818:Animals; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D008297:Male; D016273:Occupational Exposure; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000814:Aniline Compounds; D006454:Hemoglobins; C043454:2,4-difluoroaniline