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1000
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Abstract/Summary
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The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated carcinogenicity of nitrobenzene [98‐95‐3], considering all endpoints. Available publications and unpublished study reports are described in detail. The genotoxic potential of nitrobenzene is low and might be a result of reactive oxygen species. Long‐term studies with exposure by inhalation resulted in a significant increase in liver and kidney adenomas in rats, and lung and mammary adenomas in mice. In severely toxic concentrations a nonsignificant increase in carcinomas was observed, probably resulting from a chronic toxic mechanism, supported by secondary genotoxic or DNA‐damaging effects at high doses. In view of other aromatic amines and the known mechanisms of action via phenylhydroxylamine, nitrobenzene is considered to be carcinogenic. Because of the non‐linear dose‐response relationship of the tumour incidences and as genotoxic effects play a minor part, nitrobenzene is classified in Carcinogen Category 4. Eye and skin irritation from nitrobenzene is low. The critical effect is the bronchialisation in the lungs of mice in a long‐term inhalation study. However, the incidence of bronchialisation at the lowest tested concentration of 5 ml/m3 is too high to calculate a NAEC. One long‐term inhalation study in Sprague‐Dawley rats resulted in a NOAEC of 1 ml/m3, another one in F344 rats showed minimal extramedullary haematopoesis in the spleen of males at the lowest tested concentration of 1 ml/m3. Using this concentration as point of departure, a MAK value of 0.1 ml/m3 is calculated, which is far below the LOAEC of the critical effect in the mouse lung. As the MAK value is derived from a systemic effect, nitrobenzene is assigned to Peak Limitation Category II. Because of the initial half‐life of 5 hours, the excursion factor of 4 is set. Skin contact may contribute significantly to systemic toxicity; therefore, the “H” notation is retained. Damage to the embryo or foetus is unlikely when the MAK value is observed and thus, the substance is classified in Pregnancy Risk Group C. Sensitization is not expected from the limited data.
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