Trichlorobenzene (all isomers)

The German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) has re-evaluated the occupational exposure limit value (maximum concentration at the workplace, MAK value) of trichlorobenzene isomers (1,2,3-trichlorobenzene [87-61-6], 1,2,4-trichlorobenzene [120-82-1] and 1,3,5-trichlorobenzene [108-70-3]) considering all toxicological end points. Relevant studies were identified from a literature search and also unpublished study reports were used. The critical effects of the trichlorobenzenes are adverse effects on the livers of mice and rats and on the kidneys of rats. These effects were more pronounced after exposure to 1,2,4-trichlorobenzene with the rat being the most sensitive species. However, as the isomers all have a similar primary toxicological mode of action and follow similar metabolic pathways, they have been evaluated together. After exposure to 1,2,4-trichlorobenzene, liver toxicity was manifest in rats and mice as increased liver weights and histological changes in the liver were preceded by an induction of metabolic enzymes. The most sensitive end point, a disruption of porphyrin biosynthesis, was observed in a 90-day inhalation study in rats with a NOAEC of 3 ml/m. On this basis, the maximum concentration at the workplace (MAK value) has been set at 0.5 ml/m. As the critical effect of the trichlorobenzenes is systemic, Peak Limitation Category II has been assigned with an excursion factor of 2. The trichlorobenzenes are not genotoxic. The neoplasms detected in rats and mice in carcinogenicity studies with 1,2,4-trichlorobenzene are considered to be of no human relevance. In rats, the NOAEC for developmental toxicity was 840 mg/m for 1,2,3-trichlorobenzene and 1,3,5-trichlorobenzene and 420 mg/m for 1,2,4-trichlorobenzene. The NOAEC for perinatal toxicity was 54 mg/m for 1,2,4-trichlorobenzene. As no teratogenicity was observed and the margins between the NOAECs and the MAK value are sufficiently large, the trichlorobenzenes have been assigned to Pregnancy Risk Group C. Data for skin sensitizing effects are limited to experiments performed with 1,2,3-trichlorobenzene that confirmed the induction of sensitizing effects. Therefore, only 1,2,3-trichlorobenzene has been designated with "Sh". There are no data for sensitization of the respiratory tract. According to skin absorption models, 1,2,4-trichlorobenzene is expected to be taken up via the skin in toxicologically relevant amounts. Therefore, all trichlorobenzenes remain designated with "H".