Genomgång av CLH-rapporten "Proposal for harmonised classification and labelling - substance name - Anthraquinone"
Publish date: 2015-06-26
Report number: FOI-R--4081--SE
Pages: 17
Written in: Swedish
Keywords:
- Anthraquinone
- anthracene
- 9-nitroantracene
- mutagenicity
- cancerogenicity
Abstract
A proposal for EU harmonization of rules concerning chemicals including anthraquinone (AQ) has been presented which require substantial changes in the industry. The scientific evidence of the proposal has been reviewed by FOI on behalf of Wibax AB. In conclusion, this report reveals flaws in the material for the assessment of AQ. The EU harmonization of these rules which are proposed in the CLH-report (Proposal for harmonised classification and labelling - Substance name: Anthraquinone) seems in turn to rely on a comprehensive report [NTP 2005] from the US National Toxicology Program (NTP). NTP is basing its statement on the assumption that AQ is biotransformed to 1- hydroxyAQ and 2-hydroxyAQ in animals. The suspected carcinogenic metabolite 2- hydroxy-AQ may not have been present as a separate chemical substance in rat urine. Experiments with rats have shown that AQ is excreted as sulphate conjugate, 2- hydroxy-AQ sulphate and not as 2-hydroxy-AQ. The conjugate was split during the analysis process to 2-hydroxy-AQ and sulphate, probably due to contact with oxygen in the air, and can thus giving misleading results regarding excretion of AQmetabolites. It has not yet been confirmed that the biotransformation described above actually takes place in humans. It has not been shown which impurities/by-products is formed in each production method of AQ. The question can be raised if by-products can be avoided with certain production techniques. The source of AQ and the impurities within, due to the production method used, is not presented properly in the NTP-report. Hence, it has not been fully investigated what role in the observed effects the impurities may have. Both natural and anthropogenic sources of AQ exist. How can we differentiate between these sources in exposure situations? This applies both to occupational and civil life? The literature review on AQ mutagenic properties gave no clear indication whether the chemical might be a mutagen or not. However, it is clear that AQ manufactured according to the process developed by Kawasaki Kasei Chemicals was not mutagen in any of the test systems used. The results of the tests on AQ purchased from Zeneca Fine Chemicals vary from none to a dose-dependent mutagenicity. Thus, this clearly indicates that the AQ samples used by the NTP study may be affected by an unknown pattern of toxic impurities. The literature presents only a few reports bridging in vitro results to in vivo results concerning 9-NA. Delgado-Rodriguez et al. [1995] reported a mutagenic potential of 9-NA in a bacteria assay, a mammalian cell line, and a Drosophila wing spot mutagenicity assay. Remaining gaps of knowledge and scientific questions to resolve are: Is there an AQ production method which generates no impurities? Is pure AQ a mutagen and a carcinogen to experimental animals? Is pure AQ a mutagen and a carcinogen to humans? Does 2-hydroxy-anthraquinone appear in humans? To what degree is 2-hydroxy-anthraquinone mutagenic and carcinogenic in humans? To what degree is 9-nitroanthracene mutagenic and carcinogenic in humans?