Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 220-168-0 | CAS number: 2650-18-2
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Results of available in vitro studies:
- AMES tests: negative;
- Gene mutation study in mammalian cells: negative
- Transformation study in mammalian cells: negative
- DNA damage and/or repair study: negative
- Cytogenicity /Chromosome aberration study in mammalian cells: negative
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
Results of available in vitro studies:
- Mammalian somatic cell study: cytogenicity /erythrocyte micronucleus: negative
- Comet Assay: negative
- Mammalian cell study: DNA damage and/or repair: negative
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
In this summary a bacterial reverse mutation study on Target Substance has been reported as key study. Furthermore, a series of different genotoxicity studies on Similar Substance 1 are reported to complete the assessment for the target substance.
IN VITRO STUDIES
The substance was assayed for the mutagenicity by the Bacterial Reverse Mutation Testtill concentration 5000μg/plate. Four indicator Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and one indicator Escherichia coliWP2 uvrA strain were used. Experiments were performed both in the absence and presence of metabolic activation, using liver S9 fraction from rats. The results showed that the test item was non-mutagenic for all the used tester strains without as well as with metabolic activation.
Similar Substance 1 was tested in a valid GLP compliant Ames test following OECD guideline 471. Tester strains Salmonella typhimurium TA 98, 100, 1535, 1537 and 102 as well as E. coli WP2 uvrA were used. Water was used as a vehicle. A moderate to marked coloration was observed in the Petri plates when scoring the revertants at all dose-levels. This coloration made the plates unreadable at dose-levels > 1 mg/plate. No noteworthy toxicity was noted towards the strains used, with and without S9 mix. No precipitate was observed in the Petri plates when scoring the revertants at all dose-levels. No increase in the mutant frequency was observed. Positive and negative control incubations confirmed the quality of the study performance.
Similar Substance 1 was tested in a valid GLP compliant mammalian cell culture assay (Mouse lymphoma assay) according to OECD guideline 476 (RCC 2000). The assay was performed with two independent experiments, each with two parallel cultures. For the first experiment, an exposure period of 4h was used both with and without metabolic activation. The second experiment was performed in the absence of metabolic activation with an exposure period of 24h. Doses of up to 5 mg per plate were applied. There was no precipitation and no cytotoxicity. No mutagenicity was observed. There was no shift in the ratio of small to large colonies. Positive and negative control incubations confirmed the quality of the study performance.
In addition to the information of the above described studies, a results of in-vitro genotoxicity tests have been published in the literature since 1977. No genotoxic hazard was identified. In the Ishidate et al. study (1984), the chromosomal aberration test (Chinese hamster fibroblast cell line, CHL) was reported as positive. However, these results were accompanied by excessive variations in the osmolality of the culture medium and were therefore not considered relevant.
IN VIVO STUDIES
Similar Substance 1 was tested in a micronucleus assay in male mice published by Hayashi 1988, the substance was administered by one to four intraperitoneal injections (0, 500, 1000, 2000 mg/kg bw). It was part of a project of the Japanese Food Chemistry Division, Environmental Health Bureau, Ministry of Health and Welfare. The procedure is identical to that of the current OECD testing guideline 474 with the exception that only 1000 instead of 2000 femoral marrow cells per animal were scored. This is however acceptable, as the study consists of two separate experiments, which means that in sum, a sufficiently high number of cells were scored. In the first experiment, groups of each 6 rats were injected with a single dose of 500, 1000 or 2000 mg/kg bw and the animals were sacrificed 26h after dosing. One animal of the high dose group died. In the second study, animals were given one injection of 1010 mg/kg bw per day for four consecutive days and the animals were sacrified 24h after the last application. Physiological saline served as vehicle. MMC was used as positive control. No increase in micronuclei was observed as a result of treatment with Similar Substance 1.
Results of a comet assay in male ddY mice were published by Sasaki in 2002. Groups of four animals were treated by gavage once with the limit dose of 2000 mg/kg bw. Three and 24h after dosing, the comet assays were performed on glandular stomach, colon, liver, kidney, urinary bladder, lung, brain, and bone marrow. Treatment did not yield a statistically significant increase in DNA damage in any organs. Although in this study, several deviations from the standard protocol can be observed, the study seems to be sufficiently reliable.
Another study is reported on Similar Substance 1 for unscheduled DNA synthesis (OECD 486) showing absence of an in-vivo genotoxic potential. This study is reported in EFSA expert panel (EFSA, 2010).
As it can be evinced from the results of the reported studies, Target Substance shows a similar behaviour in the bacterial reverse mutation assay (AMES test) to Similar Substance 1. It is therefore expected a similar behaviour in other tests too. A detailed justification for Read Across is given in Section 13 of IUCLID. Further studies on Target Substance are in conclusion not considered necessary to complete the assessment of genetic toxicity.
References:
- Ishidate et al. 1984. Primary mutagenicity screening of food additives currently used in Japan.Fd Chem. Toxic22: 623-636.
- Hayashi et al. 1988.Micronucleus tests in mice on 39 food additives and eight miscellaneous chemicals.Fd. Chem. Toxicol.26, 487-500.
- Sasaki et al. 2002. The comet assay with 8 mouse organs: results with 39 currently used food additives.Mutation Research,519: 103-119
- EFSA 2010. Scientific Opinion on the re-evaluation of Brilliant Blue FCF (E 133) as a food additive1, EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS).
Justification for classification or non-classification
The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. No hazard for genotoxicity was identified. As a result, according to the CLP Regulation (EC 1272/2008), the substance is not considered to be classified for genetic toxicity.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.