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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
Description of key information
Key value for chemical safety assessment
Acute toxicity: via oral route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day)
- Deviations:
- yes
- Remarks:
- yes limited pathology and blood work undertaken
- GLP compliance:
- no
- Test type:
- other: 90-d
- Limit test:
- no
- Species:
- mouse
- Strain:
- Swiss Webster
- Sex:
- male/female
- Route of administration:
- inhalation: gas
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Duration of exposure:
- ca. 4 h
- Concentrations:
- 0, 5000, 50000 or 500000 ppm
- No. of animals per sex per dose:
- 15/sex/gp
- Control animals:
- yes
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- > 500 000 ppm
- Exp. duration:
- 4 h
- Conclusions:
- Swiss Webster mice (15/sex/gp) were exposed to N2Oviawhole body inhalation at concentrations of 0, 5000, 50000 or 500000 ppm [0, 0.5, 5, 50%] for 4/h/d, 5d/wk over 14 wks. At necropsy limited histopathology and haematology / biochemistry parameters were measured.
All animals survived to the scheduled necropsy. The study failed to demonstrate exposure related haematopoietic changes. There was no change in the white blood cell count nor was granulocytopenia or thrombocytopenia observed. The lack of effect suggests that either the strain of mouse was insensitive to N2O, or more likely that continuous exposure is necessary to induce leucocytopenia, as previous demonstrated following continuous exposure to N2O at high concentrations (20-80%). Furthermore, no treatment related changes in organ weights, biochemical or histopathological parameters were observed.
Treatment related decreases in body weight were observed in high dose group animals, with a depression of 77 and 63% in body weight gain in males and females respectively. This depression in weight gain was statistically significant (p<0.025 and p<0.01, respectively).
The objective of the study was to demonstrate the maximum tolerated concentration of N2O, which was deemed to be 50% (500000 ppm). In terms of establishing a NOAEL, based on the results of this study and the data presented, 50000 ppm (5%) was deemed to be the NOAEL, based on statistically significant reductions in body weight gains observed at the LOAEL (500000 ppm [50%]). - Executive summary:
Swiss Webster mice (15/sex/gp) were exposed to N2Oviawhole body inhalation at concentrations of 0, 5000, 50000 or 500000 ppm [0, 0.5, 5, 50%] for 4/h/d, 5d/wk over 14 wks. At necropsy limited histopathology and haematology / biochemistry parameters were measured.
All animals survived to the scheduled necropsy. The study failed to demonstrate exposure related haematopoietic changes. There was no change in the white blood cell count nor was granulocytopenia or thrombocytopenia observed. The lack of effect suggests that either the strain of mouse was insensitive to N2O, or more likely that continuous exposure is necessary to induce leucocytopenia, as previous demonstrated following continuous exposure to N2O at high concentrations (20-80%). Furthermore, no treatment related changes in organ weights, biochemical or histopathological parameters were observed.
Treatment related decreases in body weight were observed in high dose group animals, with a depression of 77 and 63% in body weight gain in males and females respectively. This depression in weight gain was statistically significant (p<0.025 and p<0.01, respectively).
The objective of the study was to demonstrate the maximum tolerated concentration of N2O, which was deemed to be 50% (500000 ppm). In terms of establishing a NOAEL, based on the results of this study and the data presented, 50000 ppm (5%) was deemed to be the NOAEL, based on statistically significant reductions in body weight gains observed at the LOAEL (500000 ppm [50%]).
Reference
OBSERVATIONS:
Clinical signs of toxicity:
All animals survived to the scheduled necropsy.
Bodyweight and bodyweight gain:
Treatment related decreases in body weight were observed in high dose group animals, with a depression of 77 and 63% in body weight gain in males and females respectively. This depression in weight gain was statistically significant (p<0.025 and p<0.01, respectively).
Haematology & clinical chemistry:
No treatment related changes were observed in any of the parameter measured.
Urinalysis:
None undertaken
Sacrifice and Gross Pathology:
No treatment related changes were observed in any of the parameter measured.
Organ weights:
No discussion of organ weight data.
Endpoint conclusion
- Dose descriptor:
- LC50
- Value:
- 900 061 mg/m³ air
Acute toxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
N2O is an approved medical product in accordance with applicable medical regulations. It has been used in clinical anaesthetic practice for more than 150 yr, and its longevity should be considered within the context of all the major advances in anaesthetic practice over that time. No acute toxicity effects to humans have been reported throughout its use.*
As N2O is a gas the oral and dermal route of exposure are not considered relevant.
From the available acute inhalatory toxicity data conducted with N2O one study is available to address the concern of acute toxicity. The Hoechst (1993) study would appear to address the points required by REACh for the acute inhalation toxicity endpoint, with this data referenced by all agencies that have summarised the available data on N2O. In this study the 4 h LC50of >250 ppm in rats (equivalent to >450 mg/m3) was reported. On closer examination, the source of N2O used in this study was contaminated with methyl nitrate. The result therefore from this study is considered unreliable and cannot be used to address this toxicity endpoint.
Looking at the repeat dose toxicity studies conducted on N2O, continuous exposure to rats in the initial days of treatment (Rice et al1983) at doses up to 500000 ppm for 4 h/day did not result in deaths, initially or 14 days post treatment the first exposure, with all animals surviving to the scheduled necropsy. These data can be used to address the acute toxicity endpoint. Whilst an actual LC50value is lacking the data repeat dose data demonstrate a lack of mortality or morbidity at high concentrations, which would lead to an LC50value of >500000 ppm.
The mechanism of toxicological action of N2O isviadepression of the respiratory system. Lung effects during high concentrations of N2O result in oxygen in the lungs being rapidly used up, with the resultant anoxia increased respiratory effort causes rapid depletion of CO2in tissues. Absence of CO2and depression of the medullary centres by N2O quickly leads to respiratory failure, with cerebral function failing to recover from cerebral damage caused by prolonged anoxia. Therefore, the limited dose of 250 ppm in the 4 h acute inhalation, whilst meeting the requirements of REACh is inconsistent with the both the knowledge of how N2O exerts its toxicological action and also from the available sub-acute, sub-chronic and chronic toxicity testing where doses are in excess of 3-orders of magnitude greater than the LC50value reported in the Hoechst (1993) study.
The data from the Rice et alstudy (1983), whilst not meeting the testing requirements of REACh for acute inhalation toxicity are deemed sufficient to conclude that acute exposure to N2O is insufficient for classification.
[1]Conversion of ppm to mg/m3= ppm * MWT / 24.45. [MWT of N2O = 44.013]
[Conversion of ppm to mg/m3= ppm * MWT1/ 24.45]
1. MWT of N2O = 44.013
References
* Sanders, RD et al (2008) Biologic effects of Nitrous Oxide. Anesthesiology 109: 707 -722
Justification for selection of acute toxicity – oral endpoint
In accordance with ANNEX VII column 2 of the REACH regulation: this study does not need to be conducted as the substance is a gas.
Justification for selection of acute toxicity – inhalation endpoint
The Rice study, whilst deemed to be a sub-chronic study, a 4h exposure/day was used. No morbidity or mortality was observed initally, with the all animals suriving 14d post the initial exposure. This is therefore deemed an appropriate study to address this endpoint in the absence of specific data.
Justification for selection of acute toxicity – dermal endpoint
In accordance with ANNEX VII column 2 of the REACH regulation: this study does not need to be conducted as the substance is a gas.
Justification for classification or non-classification
Acute oral toxicity:waiver requested as N2O is a gas the oral route of exposure is not relevant.
Acute toxicity inhalation:insufficient for classification.
Acute toxicity dermal:waiver as N2O is a gas the dermal route of exposure is not relevant.
STOT SE H336: May cause drowsiness or dizziness based on the anaesthetic properties.
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