The HBM4EU scoping document on anilines provides background information on anilines, identifies relevant policy questions on the group of substances and outlines research activities under HBM4EU.
The scoping document was produced by Tiina Santonen of the Finnish Institute of Occupational Health in November 2017.
These webpages were last updated on 5 December 2018.
Introduction to the aniline group
Aniline is the simplest member of the primary aromatic amines, in which one or more hydrogen atoms of the benzene ring are replaced by amino (-NH2) group, as shown in the figure below.
Derivatives of aniline include a wide variety of different substances. Some of these (like benzidine and MOCA) are composed of two combined aromatic rings.
Many aromatic amines may cause methemoglobinemia in humans. Aniline and many of its derivatives are known or suspected human carcinogens. Several aniline derivatives can also cause skin sensitization. Classical members of this family are bladder carcinogens 2-naphtylamine and benzidine, both of which have been restricted in the European Union (EU) implying that there is no exposure to these compounds.
A large number of substances in the aniline group are on the market in the EU. Several aniline derivatives can be found also from the list of substances restricted under REACH. Aniline compounds are also formed as degradation products from azo-colourants, pharmaceuticals and from aromatic isocyanates used for polyurethane polymers, lacquers, foams and adhesives.
When looking at those aniline substances that are produced or imported in the EU at amounts above 1,000 tonnes per year (tpa) according to the European Chemical Agency’s (ECHA) registration database and that have significant health hazards (other than only irritation/corrosion) the following substances can be retrieved (links take the reader to the substance infocard produced by ECHA):
- aniline, CAS: 62-53-3
- o-toluidine, CAS: 95-53-4
- 4,4′-methylenedianiline (MDA), CAS: 101-77-9
- 4,4′-methylenebis[2-chloroaniline] (MOCA), CAS: 101-14-4
- p-toluidine, CAS: 106-49-0
- 1,3-diphenylguanidine, CAS: 102-06-7
- p-phenylenediamine, CAS: 106-50-3
Many anilines have been registered under the REACH Regulation for intermediate use only. These include for example 4-aminoazobenzene, 4-methyl-m-phenylenediamine, 6-methoxy-m-toluidine, 5-nitro-o-toluidine, and 4,4’-methylenedi-o-toluidine. Although also these compounds have serious health hazards, they are not considered further because of the limited exposure due to intermediate use.
In contrast, MOCA and MDA are currently authorized under REACH. Both of these chemicals are genotoxic carcinogens to which a threshold for carcinogenic effects cannot be assigned. Both MOCA and MDA are easily absorbed via the skin. Therefore, biomonitoring is the best method for assessing occupational exposure to these substances. MDA is also a degradation product and a metabolite of MDI, one of the Diisocyanates.
Below, some anilines are discussed in some detail.
MOCA is mainly used as a curing agent of the polyurethane products. It has a low vapour pressure and it is well absorbed through the skin. Therefore biomonitoring is the best method to assess occupational exposure to MOCA. Exposure to MOCA can be biomonitored by measuring MOCA excreted into the urine (free and conjugated MOCA). These methods are well established and used in occupational surveillance of workers.
ECHA has recently made a dose-response analysis for the carcinogenicity of MOCA and calculated cancer risk levels for different urinary MOCA levels measured as total urinary MOCA in the end of the work-shift in the end of the work week (ECHA, 2015a). In addition, the EU Scientific Committee on occupational exposure limits (SCOEL) has recommended a biological guidance value (BGV) for MOCA (SCOEL, 2013).
MOCA is listed as a substance of very high concern under the REACH Regulation, and its uses are subject to authorisation. An application for authorisation for the use of MOCA was submitted to ECHA in 2016 (ECHA, 2016a). The request for authorisation covers up to 89 sites in EU using MOCA as a curing agent in polyurethane production. The estimated number of workers exposure to MOCA in the EU is only about 200. Authorization has been applied for 12 years. There is, however, no European Commission (EC) decision nor ECHA’s Risk Assessment Committee (RAC) and Socio-Economic Analysis Committee (SEAC) recommendation on the authorization available yet.
The applicant has used biomonitoring data to assess the workers’ exposure to MOCA. In addition, there are established methods available and published studies, especially from UK, on the biomonitoring of MOCA. Since there are substitutes for MOCA available for the use in polyurethane production, the use of MOCA may cease within becoming years when companies are able to move to the substitutes.
Therefore, MOCA might not be a very relevant candidate for further studies under HBM4EU although biomonitoring of MOCA would still be needed in EU as long as there are authorized uses in the EU. Furthermore, biomonitoring in workers should reveal a decrease over time (monitoring policy effectiveness). The general population is not exposed to MOCA, and the levels of MOCA and its metabolites in the urine of the general population are below the detection limits.
Policy-related questions on anilines
- What is the current occupational exposure to aniline and different aniline derivatives (including diamine forming diisocyanates) in the EU?
- What is the exposure to paracetamol (aniline metabolite) among the general population?
- What are the risks related to these exposures?
- What is the possible impact of risk management measures taken under the REACH Regulation on the exposure and risks?