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EC number: 939-657-1 | CAS number: -
- 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
Additional information
The substance was not mutagenic in a Bacterial Reverse Mutation (Ames) Test according to OECD TG 471 with Salmonella typhimurium TA 1535, TA 100, TA 1537, TA 98, and TA 102 tested without and with metabolic activation. As vehicle ethylene glycol dimethyl ether was used.
For assessing further genotoxicity endpoints a read across from a substance with a very similar chemical composition (comparable allophanate-type HDI oligomerisation product, EC 900 -066 -9, CAS 197393 -84 -3) is applied. The read across is based on physicochemical and toxicological similarity of the two substances. Especially a recently conducted comparative pulmonary irritant potency study based on the recommendations of TRGS 430 (Technical Rule for Hazardous Substances 430, published by the German Federal Ministry of Labour and Social Affairs, last update in 2009), confirmed for both allophanate-type HDI oligomerisation products the same toxicological mode of action and a nearly identical potency (both NOAEL at 3.4 mg/m³). For further justification of the grouping and read-across according to regulation (EC) No 1907/2006, Annex XI, 1.5 see document attached to chapter "Assessment Reports".
The read-across substance revealed no mutagenic potential in a mammalian cell gene mutation assay according to OECD 476 (HPRT) using V79 cells. This assay was conducted in two independent experiments: The first experiment was performed with and without liver microsomal activation and a treatment period of 4 hours, the second experiment was performed with a treatment time of 4 hours with and 24 hours without metabolic activation. As vehicle ethylene glycol dimethyl ether was used.
Two in vitro micronucleus assays were performed with the
read-across substance. In one a positive and in the other a negative
test result was obtained. In principle, both assays solely vary by the
use of the solvent applied, which is ethylene glycol dimethylether
(EGDE) versus dimethyl suloxide (DMSO). Indeed, the suitability of
solvents used in genotoxicity tests with diisocyanates has already been
a subject of scientific examination, especially in the case of aromatic
diisocyanates (Gahlmann et. al., Zbl Arbeitsmed 43, 1993, 34-38; Herbold
et al., Mutation Research 412, 1998, 167-175; Seel et. al., Mutation
Research 438, 1999, 109-123). For aromatic diisocyanates like MDI (CAS
number 26447-40-5), the products of aqueous hydrolysis, i.e. the
aromatic amines, were suspected of causing positive results in Ames
tests. It could be shown that if DMSO is used as solvent for MDI a rapid
degradation of the isocyanate function occurs. One of the degradation
products was found to be the corresponding aromatic amine
4,4’-methylenedianiline (MDA), which is a known genetic toxin. If EGDE
was used as a representative of a less polar solvent, analytical data
revealed that MDI was quite stable and no formation of MDA could be
detected.
EU risk assessment of MDI (final report, 2005) states that “It is
evident from the results of studies .... that the solvent used for
solubilisation of MDI in genotoxicity assays is crucial with respect to
a valid and representative evaluation of MDI in such assays. There is
adequate evidence to demonstrate that use of EDGE as solvent is
appropriate whereas DMSO can give rise to false positives due to
solvent-catalysed conversion to MDA.”
In fact, DMSO is not chemically inert. In synthetic organic chemistry it is known to react with certain polar groups to "activated dimethyl sulfoxide", which can further be used as reagent in organic synthesis (Tidwell, Synthesis, 1990, 857-870; Mancuso & Swern, Synthesis, 1981, 165-185). Moreover reactions of isocyanates and DMSO or at least reactions with catalytical activity of DMSO in chemical conversions of isocyanates are reported (Arbuzov et. al., Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (Engl. Translation) 24, 1975, 1113-1114; Sorenson, J. Org. Chem. 24, 1959, 978-980). Therefore, it is assumed, that single positive results of isocyanates in genotoxicity assays conducted with DMSO as solvent does not reflect a genotoxic property of the isocyanate, but reflects positive genotoxicity of a reaction product that is formed in this mixture of isocyanate, DMSO and possibly substances from liver homogenate also.
The in vitro micronucleus assay performed with EGDE (Bayer, 2012) can therefore be considered to be more reliable to assess the in vitro cytogenicity of the allophanate-type HDI oligomerisation product in mammalian cells compared to the assay performed with DMSO (BASF, 2006), which is therefore marked as "disregarded study".
The micronucleus assay with EGDE was conducted in accordance to OECD 487 using Chinese Hamster V79 cells. Two independent assays were performed in this study, the first conducted with a treatment time of 4 hours, with and without a metabolizing system (S9 mix), the second assay with a treatment time of 24 hours (continuous treatment) without S9 mix and with a treatment time of 4 hours with S9 mix.
No biologically relevant increase in the frequencies of micronucleus containing V79 cells were found either in the absence (4 hours or 24 hours treatment) or in the presence (4 hours treatment) of S9 mix when tested up to cytotoxic or precipitating concentrations, thus no genotoxicity potential is concluded based on this in vitro MNT.
The overall negative genotoxicity is supported by an in vivo Mammalian Erythrocyte Micronucleus Test (OECD 474) in NMRI mice. In this test the substance, dissolved in corn oil, was administered twice orally, with a 24 -hour interval between administrations, to groups of 5 male animals at dose levels of 500 mg/kg, 1000 mg/kg and 2000 mg/kg body weight. Bone marrow was prepared 24 hours after the second administration.
The two oral substance administrations did not lead to any increase in the number of polychromatic erythrocytes containing either small or large micronuclei. The rate of micronuclei was always close to the same range as that of the concurrent negative control in all dose groups and within the range of the historical control data. A slight inhibition of erythropoiesis, determined from the ratio of polychromatic to normochromatic erythrocytes, was reported. Therefore, no indications for genotoxicity in vivo can be concluded from this study.
Justification for selection of genetic toxicity endpoint
No study was selected, since all available genotoxicity studies were assessed.
Endpoint Conclusion: No adverse effect observed (negative)
Justification for classification or non-classification
No classification required for genotoxicity according to Regulation (EC) No. 1272/2008, Annex I.
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