3-Nitrobenzanthrone (3-NBA) has been isolated from
diesel exhaust and airborne particles and identified as a potent direct-acting
mutagen in vitro and genotoxic agent in vivo. In order to evaluate the in vivo toxicity and carcinogenicity of 3-NBA in a situation corresponding to inhalation, a combined short-term and lifetime study with intratracheal (i.t.) instillation in female F344 rats was performed.
DNA adduct formation, as a marker for the primary effect and analyzed by 32P-HPLC after single instillation, showed a few major
DNA adducts and a rapid increase with a peak after 2 days, followed by a decline. No
DNA adducts above the background level were observed after 16 days. The highest
DNA adduct formation was observed in lung [approximately 250
DNA adducts/10(8) normal
nucleotides (NN)] closely followed by kidney (approximately 200
DNA adducts/10(8) NN), whereas liver contained only 12% (approximately 30
DNA adducts/10(8) NN) of the levels of
DNA adducts found in lung. In the
tumor study,
squamous cell carcinomas were found after 7-9 months in the high-dose group (total dose of 2.5 mg 3-NBA) and after 10-12 months in the low-dose group (total dose of 1.5 mg 3-NBA). The fraction of
squamous cell carcinoma out of the total amount of
tumors observed at the end of experiment at 18 months, corresponded to 3/16 and 11/16 in the low- and high-dose group, respectively. A single case of
adenocarcinoma was also observed in each group. In the control group, no
tumors were observed during the entire study of 18 months. In addition, a few cases of squamous
metaplasia were also observed in the lung in both dose groups but not in the controls. In conclusion, 3-NBA forms
DNA adducts in the lung immediately after i.t. administration but almost all
DNA adducts were eliminated after 16 days.
Tumor formation in two dose groups was observed in a dose-dependent manner with
squamous cell carcinomas as the predominant
tumor type at high exposure.