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Diss Factsheets
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EC number: 233-032-0 | CAS number: 10024-97-2
- 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
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Non-GLP, limited no. of strains used
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- limited no. of strains used
- GLP compliance:
- no
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- other: S. typhimurium TA 1535, TA 100
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254
- Test concentrations with justification for top dose:
- 0, 1, 3, 9, 27, 81%
- Untreated negative controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- other: vinylidene chloride, 2-anthramine
- Species / strain:
- other: S. typhimurium TA 1535, TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
No increase in the number of revertant colonies were observed in strain TA100 or TA1535. At the maximum dose tested, 81%, no evidence of cytotoxicity was observed.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Gene mutation (bacterial)
In the published literature N2O has been investigated using the Ames methodology (Baden et al., 1979; Baden & Monk, 1981) employing limitedSalmonella typhimurium (TA1535, TA98 and TA100) tester strains. These studies did not show evidence of increases in revertants. In the Badenet al(1979) study, no evidence of toxicity was observed when tested up to 1 atmosphere. In the Baden and Monk study however, toxicity was evident at 4 atmospheres and above.
Mammalian chromosome aberration (in vitro)
Data from a sister chromatid exchange (SCE) (Whiteet al., 1979) in Chinese hamster ovary cells did not show evidence of SCE following a 24h exposure to N2O
Mammalian gene mutation (in vitro)
In a mammalian gene mutation study, using Chinese hamster lung fibroblast involving mutation at thehprtlocus, using 8-azaguanine as the selective agent, N2O failed to induce an increase in mutant colonies following a 24 h exposure period.
In vivobone marrow micronucleus
No data
QSAR data
QSAR data generated from Toxtree (v. 2.5.1) to partially address concerns over the genotoxicity of N2O returned negative results. Using the Benigni-Bossa rulebase1for mutagenicity and carcinogenicity negative results were obtained for genotoxicity and non-genotoxic carcinogenicity predictions. Also, use of the ToxMIC-ISS plug-in2to allow identification of structural alerts for thein vivomicronucleus assay were analysed. Toxtree returned negative results for this endpoint as well.
Human data
Cohen et al (1980) related the incidence of cancer specifically to occupational exposure to N2O. The study population consisted of 30650 male dentists and 30547 chair side assistants (female) and was readily divided between those who did or did not give inhaled anaesthetics to their patients. Those that only used N2O accounted for 81.3% of the study population. No effect of anaesthetic exposure was seen in the dentists. The cancer rate among female assistants exposed to waste anaesthetics for more than 8 h/wk was 1.06±0.18% vs. 0.72±0.10% in those that were not exposed. The difference was not considered to be statistically significant. Among the various cancers types, only cancer of the cervix occurred more frequently in exposed assistants (0.29±0.10%) than in unexposed (0.12%±0.04%) assistants, however this increase was not statistically significant.
Genetic Toxicology Summary
The available experimental data on N2O do not satisfy the criteria required under the requirements of REACh to conclude that N2O lacks any genotoxic potential. When these results are considered in isolation and compared against the guideline requirements each test falls short of the minimum requirements. However, with this limited data along with negative QSAR data generated in-house, a negative carcinogenicity study (in mice) along with negative epidemiological data of cancer rates or deaths among dental / operating room personnel and the widespread use of N2O as both an analgesic and anaesthetic in humans there is little reason to believe that N2O is genotoxic in the absence of convincing evidence.
References:
Benigni, R., Bossa, C., Jeliazkova, N., Netzeva, T. and Worth. A. (2008). The Benigni / Bossa rulebase for mutagenicity and carcinogenicity - a module of Toxtree, by European Commission report EUR 23241 EN
Benigni, R., Bossa, C., Tcheremenskaia, O. and Worth, A. (2009). Development of structural alerts for the in vivo micronucleus assay in rodents", European Commission report EUR 23844
Cohen E.N., Brown B.W., Wu M.L., Whitcher C.E., Brodsky J.B., Gift H.C., Greenfield W., Jones T.W. & Driscoll E.J. (1980). Occupational disease in dentistry and chronic exposure to trace anaesthetic gases. J. Amer. Dent Ass. 101; pp 21-31
NOTES
1. Benigni-Bossa rulebase: The structural alerts (SAs) for carcinogenicity are molecular functional groups or substructures known to be linked to the carcinogenic activity of chemicals. As one or more SAs embedded in a molecular structure are recognised, the system flags the potential carcinogenicity of the chemical. The list of SAs in the Benigni-Bossa rulebase refers mainly to the knowledge on the action mechanisms of genotoxic carcinogenicity (thus they apply also to the mutagenic activity in bacteria), but includes also a number of SAs flagging potential non-genotoxic carcinogens.
Because of their nature, the SAs have the role of pointing to chemicals potentially toxic, whereas no conclusions or indications about nontoxic chemicals are possible (except by exclusion). Thus the SAs are not a discriminant model on the same ground
of the Quantitative Structure-Activity Relationships (QSAR) models that produce estimates for both positive and negative chemicals.
In addition to the SAs, this software includes QSAR models for: 1) the mutagenic activity of aromatic amines in the Salmonella typhimurium TA100 strain (Ames test); 2) the carcinogenic activity of the aromatic amines in rodents (summary activity from
rats and mice); 3) the mutagenic activity of unsaturated aldehydes in theSalmonella typhimuriumTA100 strain (Ames test).
2.ToxMIC-ISS: following identification of a structural alerts for thein vivomicronucleus assay, these structural alerts provide a coarse-grain filter for the preliminary screening of potentialin vivomutagens (Benigniet al., 2009)
Justification for selection of genetic toxicity endpoint
In order to address this endpoint a single study does not provide sufficient evidence to conclude this endpoint. Therefore, a weight of evidence approach has been used to address this endpoint principally from published data, QSAR data generated in house and history of use.
Justification for classification or non-classification
Dinitrogen oxide is considered to be devoid of genotoxic potential, classification therefore is not required.
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.
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