Binding characteristics of ortho-toluidine to rat hemoglobin and albumin.
The binding characteristics of [14C]ortho-toluidine (OT), a suspect human carcinogen, were investigated in male Sprague-Dawley rats. Rats were administered [14C]OT i.p. at 10, 20, 40, 50, or 100 mg/kg body weight, then sacrificed at 2, 4, 8, 18, 24, 48, or 72 h, or 7, 14, or 28 days. Hemoglobin (Hb) and albumin (Alb) were isolated from blood, and OT binding was determined by liquid scintillation counting. For Alb, peak binding occurred at 50 mg/kg at the 4-h time point (15.6 ng OT/mg Alb), while for Hb peak binding was observed at 24 h at the 100 mg/kg dose (23.0 +/- 5.1 ng OT/mg Hb). OT-Alb binding was not linear; however, OT-Hb binding appeared to increase linearly in a dose-dependent manner. Biological half-lives of OT bound to Alb or Hb were observed to be 2.6 and 12.3 days, respectively, after rats were administered a single dose of [14C]OT and sacrificed after 4 h to 28 days. The effect of route of administration on OT-Hb adduct formation was investigated, and approximately a two-fold increase in radioactivity bound to Hb was observed after i.p. administration of 100 mg/kg [14C]OT versus oral intubation. Additional studies were carried out to investigate the effect of microsomal enzyme induction. An increase in OT-Hb binding was seen in rats pretreated with phenobarbital compared to rats pretreated with beta-naphthoflavone or without pretreatment; however, this increase was not statistically significant. These results suggest that OT-Hb and OT-Alb adduct formation may be a valuable biomarker for assessing workplace exposure.
DeBord
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Department of Health and Human Services, National Institute for Occupational Safety and Health, Cincinnati, Ohio 45226.
Swearengin
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Cheever
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Booth-Jones
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Wissinger
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LA
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005069:Evaluation Studies as Topic; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008297:Male; D016273:Occupational Exposure; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014052:Toluidines / Q000378:metabolism*
D000418:Albumins; D015415:Biomarkers; D001798:Blood Proteins; D006454:Hemoglobins; D014052:Toluidines; C023622:2-toluidine