Hemoglobin adducts of the human bladder carcinogen o-toluidine after treatment with the local anesthetic prilocaine

Prilocaine, a widely used local anesthetic, is metabolized to o-toluidine which is classified as human carcinogen. We aimed to assess the impact of prilocaine-treatment on hemoglobin adducts from o-toluidine. Blood samples were obtained before and 24 h after receiving prilocaine local anesthesia (Xylonest®, 100 mg) from 20 head and neck surgery patients and 6 healthy volunteers. Hemoglobin adducts of o-toluidine and 4-aminobiphenyl were determined by gas chromatography/mass spectrometry. Hemoglobin adducts of o-toluidine were significantly increased 24 h after 100 mg prilocaine-treatment by 21.6 ± 12.8 ng/g hemoglobin (mean ± S.D., N = 26; P < 0.0001). This corresponds to a 6–360-fold increase of o-toluidine adduct levels in 25 patients from 0.54 ± 0.95 ng/g before treatment to 22.0 ± 13.2 ng/g 24 h after surgery (mean ± S.D.). Because of an extremely high background level the increase was only 1.6-fold in one patient (40.9 ng/g before and 64.4 ng/g 24 h after prilocaine injection). Current smoking had no influence on background values and on the increase of o-toluidine adducts. No treatment-related differences were seen in mean hemoglobin adduct levels of 4-aminobiphenyl which were significantly higher in smokers, 0.149 ± 0.096 ng/g (mean ± S.D., N = 8) as compared to nonsmokers 0.036 ± 0.035 ng/g (mean ± S.D., N = 16; P < 0.01). In conclusion, prilocaine anesthesia leads to a massive increase of hemoglobin adducts of the carcinogenic arylamine o-toluidine. This implies a carcinogenic risk which should be taken into account in preventive hazard minimization.