2022/03/31 by Hartwig, Andrea, MAK Commission
#1-Amino-4-nitrobenzol #4-Nitroanilin #4-Nitrobenzolamin #4-nitroaniline #Entwicklungstoxizität #Fertilität #Gefahrstoff #Gentoxizität #Hautresorption #Hämangiosarkom #Kanzerogenität #Keimzellmutagenität #Methämoglobin #Sensibilisierung #Toxizität #carcinogenicity #developmental toxicity #fertility #genotoxicity #germ cell mutagenicity #haemangiosarcoma #hazardous substance #methaemoglobin #p-Nitrophenylamin #sensitization #skin absorption #toxicity
paper · doi:10.34865/mb10001e7_1ad
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re-evaluated 4-nitroaniline [100-01-6] considering all toxicological end points. Available publications are described in detail. The critical effect of 4-nitroaniline is methaemoglobin formation in humans and animals. 4-Nitroaniline induces mutations in bacteria and is clastogenic to mammalian cells, although not in vivo. Long-term animal studies did not demonstrate that the germ cells are reached. Compared with other aromatic amino and nitro compounds, 4-nitroaniline has a much lower genotoxic potential in vitro and in vivo. Therefore, an assignment to a Germ Cell Mutagenicity Category is not necessary. The substance is not carcinogenic in Sprague Dawley rats up to doses of 9.9 mg/kg body weight and day, which are toxic to the spleen. In male B6C3F1 mice, however, incidences of haemangiosarcomas in the liver and of haemangiomas or haemangiosarcomas (combined) at all sites were increased. Thus, a carcinogenic potential of 4-nitroaniline is likely. This is also supported by its structural similarity with other carcinogenic aromatic amino and nitro compounds as well as its genotoxicity in vitro. 4-Nitroaniline is therefore assigned to Carcinogen Category 3 B. As the substance is genotoxic in vitro, a maximum concentration at the work place (MAK value) cannot be derived. Prenatal toxicity studies found lower foetal body weights in rats at 85 mg/kg body weight and day, but no developmental toxicity in rabbits up to the highest dose tested of 125 mg/kg body weight and day. Clinical data in humans did not describe a discrete contact sensitizing effect for 4-nitroaniline. Also, animal studies performed with low concentrations did not provide explicit evidence of a contact sensitizing potential. In spite of the suspected contact sensitizing effect, the substance is not designated with an “Sh” notation. For lack of data, the “Sa” designation is not applied. Dermal absorption is higher than the systemically tolerable amount calculated after oral administration in rats. Hence, the “H” designation is retained.