4-Nitrobenzoesäure [MAK Value Documentation in German language, 2017]

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated 4‐nitrobenzoic acid [62‐23‐7]. Available study reports and publications are described in detail. 4‐Nitro)benzoic acid caused a statistically significantly increased incidence of adenomas and of the sum of adenomas and carcinomas of the clitoris gland in female F344 rats in an oral, 2‐year carcinogenicity study at doses of 60 mg/kg body weight and day and above. The incidence of adenomas and the sum of adenomas and carcinomas was above the range limit of the historical controls of the contract laboratory. As 4‐nitrobenzoic acid is a metabolite of 4‐nitrotoluene, which also induced tumors of the clitoral gland as well as tumors in other organs, 4‐nitrobenzoic acid is classified in analogy to 4‐nitrotoluene in Carcinogen Category 3B. 4‐Nitrobenzoic acid has a weak mutagenic potency in vitro. It did not induce micronuclei in vivo or in vitro. There are no suitable data in humans to derive a MAK value. In rats, a 15‐month study and a 2‐year study resulted in a NOAEL of 60 mg/kg and day for delayed body weight gain in the females. Toxicokinetic scaling results in a concentration of 147 mg/m3 in workplace air. The LOAEC for local effects on the olfactory epithelium of rats in a 14‐day study is 150 mg/m3, the NOAEC 20 mg/m3. Since 2014, the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. Based on this approach, a MAK value of 1 mg/m3 for the inhalable fraction was derived. The dose of 60 mg/kg body weight and day which resulted in increased incidences of clitoral gland tumors corresponds to a concentration which is about 150 times higher than the MAK value. In view of the evaluation of carcinogenicity, this margin is considered to be sufficiently large. As local effects are critical, the substance is assigned to Peak Limitation Category I. The difference between NOAEC and LOAEC is large, thus an excursion factor of 2 has been established. 4‐Nitrobenzoic acid is assigned to Pregnancy Risk Group D as the available data for prenatal toxicity are insufficient. Skin absorption does not contribute significantly to systemic toxicity and 4‐nitrobenzoic acid is not expected to lead to contact sensitization.