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N-Methylanilin [MAK Value Documentation in German language, 2017]


Hartwig, A; MAK Commission; et al; Arand, Michael (2017). N-Methylanilin [MAK Value Documentation in German language, 2017]. The MAK Collection for Occupational Health and Safety, 2(2):642-666.

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the workplace (MAK value) of N‐methylaniline [100‐61‐8] considering all toxicity endpoints. Available publications and unpublished study reports are described in detail. Critical effect is the formation of methaemoglobin (MetHb). Adequate data in humans to derive a MAK value are not available; thus, data with rats are used. In rats, N‐methylaniline forms MetHb 2.7 times more efficiently than aniline. Based on the MAK value for aniline of 2 ml/m3, the MAK value for N‐methylaniline of 0.5 ml/m3 is confirmed. As the critical effect is systemic, Peak Limitation Category II is retained; as the half‐life in blood is unknown, the default excursion factor of 2 is also retained. N‐Methylaniline remains in Pregnancy Risk Group D because developmental toxicity studies are lacking. The substance does not induce mutations in bacteria, but is clastogenic in mammalian cells. Studies on genotoxicity in vivo have not been performed. Adequate data to assess the carcinogenic potential of N‐methylaniline are not available. Data for the metabolite aniline are used to assess the carcinogenic potential of N‐methylaniline. Aniline induces spleen tumours in rats, but not in mice. The putative mode of action is an indirect tumour development by induction of MetHb and haemolytic effects which result in erythrocyte toxicity and its consequences, perturbations in iron metabolism in the spleen. The metabolites phenylhydroxylamine and nitrosobenzene are mainly responsible for the erythrocyte toxicity of aniline. As nitrosobenzene is also a metabolite of N‐methylaniline, a similar mode of action has to be assumed for N‐methylaniline. Therefore, a non‐genotoxic mode of action is of prime importance and genotoxic effects play at most a minor part provided the MAK and BAT values are observed. Thus, N‐methylaniline is classified as a suspected carcinogen in Carcinogen Category 3B. Skin contact may contribute significantly to systemic toxicity and the “H” notation is retained. There are no clinical data concerning the sensitizing activity of the substance. Results of a local lymph node assay in mice were negative.

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the workplace (MAK value) of N‐methylaniline [100‐61‐8] considering all toxicity endpoints. Available publications and unpublished study reports are described in detail. Critical effect is the formation of methaemoglobin (MetHb). Adequate data in humans to derive a MAK value are not available; thus, data with rats are used. In rats, N‐methylaniline forms MetHb 2.7 times more efficiently than aniline. Based on the MAK value for aniline of 2 ml/m3, the MAK value for N‐methylaniline of 0.5 ml/m3 is confirmed. As the critical effect is systemic, Peak Limitation Category II is retained; as the half‐life in blood is unknown, the default excursion factor of 2 is also retained. N‐Methylaniline remains in Pregnancy Risk Group D because developmental toxicity studies are lacking. The substance does not induce mutations in bacteria, but is clastogenic in mammalian cells. Studies on genotoxicity in vivo have not been performed. Adequate data to assess the carcinogenic potential of N‐methylaniline are not available. Data for the metabolite aniline are used to assess the carcinogenic potential of N‐methylaniline. Aniline induces spleen tumours in rats, but not in mice. The putative mode of action is an indirect tumour development by induction of MetHb and haemolytic effects which result in erythrocyte toxicity and its consequences, perturbations in iron metabolism in the spleen. The metabolites phenylhydroxylamine and nitrosobenzene are mainly responsible for the erythrocyte toxicity of aniline. As nitrosobenzene is also a metabolite of N‐methylaniline, a similar mode of action has to be assumed for N‐methylaniline. Therefore, a non‐genotoxic mode of action is of prime importance and genotoxic effects play at most a minor part provided the MAK and BAT values are observed. Thus, N‐methylaniline is classified as a suspected carcinogen in Carcinogen Category 3B. Skin contact may contribute significantly to systemic toxicity and the “H” notation is retained. There are no clinical data concerning the sensitizing activity of the substance. Results of a local lymph node assay in mice were negative.

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Item Type:Journal Article, not_refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:German
Date:31 May 2017
Deposited On:18 Oct 2019 08:02
Last Modified:18 Oct 2019 08:02
Publisher:Wiley-VCH Verlag
ISSN:2509-2383
ISBN:9783527600410
OA Status:Closed
Publisher DOI:https://doi.org/10.1002/3527600418.mb10061d0063

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