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EC number: 233-271-0 | CAS number: 10102-43-9
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- The report’s conclusion is confirmed: no chromosome dammage or bone marrow cell toxicity in vivo on male rats.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 001
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- 1997
- Deviations:
- not specified
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian erythrocyte micronucleus test
Test material
- Reference substance name:
- Nitrogen monoxide
- EC Number:
- 233-271-0
- EC Name:
- Nitrogen monoxide
- Cas Number:
- 10102-43-9
- Molecular formula:
- NO
- IUPAC Name:
- oxidoamine
Constituent 1
- Specific details on test material used for the study:
- The tested batch contained 900 ppm NO in nitrogen; tested concentrations are expressed as pure NO
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- The preliminary study with males and females evidenced an absence of difference in sensitivity between sexes
Animals were weighing between 140 and 150 grams.
Animals were acclimatised for a minimum of 5 days, examined daily and weighed prior to dosing.
ENVIRONMENTAL CONDITIONS :
Temperature : 21 +/- 2 °C
Relative humidity : 55 +/- 15%
Light : artificial light for 12 hours per day
Food and water ad libitum
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Vehicle:
- Air
- Details on exposure:
- Snout only inhalation exposure
- Duration of treatment / exposure:
- 6 hours of exposure
- Frequency of treatment:
- 1
- Post exposure period:
- 24 or 48 hours
Doses / concentrationsopen allclose all
- Dose / conc.:
- 30 ppm
- Dose / conc.:
- 75 ppm
- Dose / conc.:
- 150 ppm
- Remarks:
- Corresponds approximately to the MTD
- No. of animals per sex per dose:
- 30 ppm : 7 rats
75 ppm : 7 rats
150 ppm : 14 rats
Negative control : 14 rats
Positive control : 5 rats - Control animals:
- yes
- yes, concurrent no treatment
- Positive control(s):
- Cyclophosphamide (batch number : 108H0568). It was prepared as a solution in purified water at a concentration of 2 mg/ml just prior to administration. It was administrated orally by gastric intubation at a volume dosage of 10ml/kg bw.
Examinations
- Tissues and cell types examined:
- Femurs are dissected out from each animals. The femurs were cleared of tissue and the proximal apiphys removed from each bone.
- Details of tissue and slide preparation:
- Due to the presence of mast cell granules in rat bone smears, which appear identical to micronuclei when stained using the Romanowsky methods, a modified Feulgen staining method is employed for the rat micronucleus test in this laboratory. This method specifically stains DNA-containing bodies deep purple while leaving mast cell granules unstained. The method also allows reasonable differentiotion of mature and immature erythrocytes and produces permanent preparations.
The slides were fixed and stained as described in the following schedule :
1/ Fixed for 10 minutes in methanol
2/ Hydrolysed in Bouin's fluid at room temperatur for 30 hours
3/ Washed three times in purified water (5 minutes per wash)
4/ Stained in Schiff's reagent for one hour at room temperature
5/ Washed three times in purified water
6/ Counter-stained for ten minutes in very dilute aqueous Eosin yellowish
7/ Washed for five minutes in purified water
8/ Stained for 30 minutes in Mayer's Haemalum diluted 9 volumes : 1 volume with aqueous acridine orange solution in purified water (1 mg/ml)
9/ Rinsed in purified water
10/ Rinsed in running tap water
11/ Washed for 5 minutes in purified water
12/ Air dried
13/ Slides were mounted with coverslips using DPX mountant
14/ The mountant was allowed to harden
The stained smears were examined by light microscopy to determine the incidence of micronucleated cells per 2000 polychromatic erythrocytes per animal. Usually only one smear per animals was examined. The remaining smears were held temporarily in reserve in case of technical problems with the first smeat. - Evaluation criteria:
- Micronuclei are identified by the following criteria:
- Large enough to discern morphological characteristics
- Should possess a generally rounded shape with a clearly defined outline
- Should be deeply stained and similar in colour to the nuclei of other cells - not black
- Should lie in the same focal plane as the cell
- Lack internal structure, ie they are pyknotic
- There should be no micronucleus-like debris in the area surrounding the cell
The proportion of immature erythrocytes for each animal was assessed by examination of at least 1000 erythrocytes. A record of the number of micronucleated mature erythrocytes observed during assessment of this proportion was also kept.
Results for each treatment group were compared with the results for the concurrent control group using non-parametrics statistics.
A positive response is normally indicated by a statistically significant dose-related increase in the incidence of micronucleated immature erythrocytes for the treatment group compared with the concurrent control group (P <0.01); individual and/ or group mean values should exceed the laboratory historical control range (Morrison and Ashby 1995). A negative result is indicated where individual and group mean incidences of micronucleated immature erythrocytes for the group treated with the test substance are not significantly greater than incidences for the concurrent control group (P >0.01) and where these values fall within the historical control range. An equivocal response is obtained when the results do not meet the criteria specified for a positive or negative response.
Bone marrow cell toxicity (or depression) is normally indicated by a substantial and statistically significant dose-related decrease in the proportion of immature erythrocytes (P<0.01). - Statistics:
- Non-parametric statistical methods were chosen for analysis of results because:
• They are suited to analysis of data consisting of discrete/ integer values with ties such as the incidence of micronucleated immature erythrocytes
• The methods make few assumptions about the underlying distribution of data and therefore the values do not require transformation to fit a theoretical distribution (where data can be approximately fitted to a normal distribution, the results of non-parametric analysis and classical analysis of variance are very similar)
• “Outliers” are frequently found in the proportion of immature erythrocytes for both control and treated animals; non-parametric analysis based on rank does not give these values an undue weighting.
For incidences of micronucleated immature erythrocytes, exact one-sided p-values are calculated by permutation (StatXact, CYTEL Software Corporation, Cambridge, Massachussetts). Comparison of several dose levels is made with the concurrent control using the Linear by Linear Association test for trend, in a step-down fashion if significance is detected (Agrestu et al. 1990); for individual intergroup comparisons (ie the positive control group) this procedure simplifies to a straightforward permutation test (Gibbons 1985). For assessment of effects on the proportion of immature erythrocytes, equivalent permutation tests based on rank scores are used, ie exact versions of Wilcoxon's sum of ranks test and Jonckheere's test for trend.
Results and discussion
Test results
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- at 150 ppm 2 males were found dead after 6 hours of exposure. At post mortem examination, one animal showed no abnormalities and the other moderate congestion in all lungs lobes
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- For more details, please refer to the illustration summing results below
Applicant's summary and conclusion
- Conclusions:
- In a OECD 474 study, NO did not induce micronuclei in erythrocytes, and was therefore non genotoxic, in rats exposed for 48h by inhalation up to 150 ppm (exceeding the maximum tolerated dose).
- Executive summary:
No statistically significant increase in the frequency of micronucleated immature erythrocytes and no substantial decrease in the proportion of immature erythrocytes were observed in rats treated with nitric oxide and killed 24 or 48 hours later, compared to vehicle control values (P>0.01 in each case).
It is concluded that nitric oxide did not show any evidence of causing chromosome damage or bone marrow cell toxicity when administred by snout only inhalation exposure in this in vivo test procedure.
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