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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 225-791-1 | CAS number: 5080-22-8
- 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
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 16 January - 26 January 1990
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 990
- Report date:
- 1990
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- N-isopropylhydroxylamine
- EC Number:
- 225-791-1
- EC Name:
- N-isopropylhydroxylamine
- Cas Number:
- 5080-22-8
- Molecular formula:
- C3H9NO
- IUPAC Name:
- N-(propan-2-yl)hydroxylamine
- Details on test material:
- The test article, Nipha Crystals, was supplied in the form of white crystals. No purity information reported.
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- ICR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Adult male and female mice, strain ICR, were purchased from Harlan Sprague-Dawley, Inc., Frederick, MD. This healthy, random bred strain was selected to maximize genetic heterogeneity and at the same time assure access to a common source.
Animals were group-housed by sex up to five per cage. The temperature and humidity were maintained at 72±6°F and 50±20%, respectively. A 12-hour light/12-hour dark cycle was maintained. A commercial diet (Purina Certified Laboratory Chow· #5002) and water were available ad libitum for the duration of the study. The feed is analyzed by the manufacturer for concentrations of specified heavy metals, aflatoxin, chlorinated hydrocarbons, organophosphates, and specified nutrients. The water is analyzed on a retrospective basis for specified microorganisms, pesticides, heavy metals, alkalinity, and halogens. Sanitary polycarbonate cages and hardwood bedding were used. Personnel handling animals or working within the animal facilities were required to wear suitable protective garments and equipment.
Animals were quarantined for seven days before being placed on study. Animals were randomly assigned to study groups and were individually weighed prior to the initiation of the study. All animals were dosed based upon the individual body weights. Animals were uniquely identified by ear tag. Dose or treatment groups were identified by cage card.
At the termination of the study all surviving animals were euthanatized by CO2 inhalation. Any extra animals not used for the study were euthanatized at the end of the study.
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- The test article, Nipha Crystals, was supplied in the form of white crystals. The solubility of the test article was evaluated in a previously conducted dose range finding assay (HLA Study No.: 11200-0-459). Based upon the solubility data from the dose range finding assay, the vehicle used to solubilize the test article for the bone marrow micronucleus assay was 0.9% sodium chloride (Abbott, Loti 15-117-DM-03). The stability of the test article under the preparation and dosing conditions of the assay is the responsibility of the sponsor.
- Details on exposure:
- Trial 1
The animals used in the trial 1 micronucleus assay were dosed on Tuesday, January 16, 1990. The weight range of the animals used in the trial 1 micronucleus assay was 30.0 - 39.9 grams and 21.5 - 27.5 grams for the males and females. respectively. The dosing solutions for the assay were prepared by making a 140 mg/ml stock for the high dose (1400 mg/kg). Dilutions of this stock were prepared for the 467 and 140 mg/kg dose levels.
Trial 2
The animals used in the trial 2 micronucleus assay were dosed on Tuesday, January 30, 1990. The weight range of the animals used in the trial 2 micronucleus assay was 30.3 - 40.5 grams and 20.0 - 25.0 grams for the males and females, respectively. The dosing solution for the assay was prepared by making a 120 mg/ml stock for the 1200 mg/kg dose level.
In both trials, cyclophosphamide (CP, Sigma, Lot #67F-0155). the positive control, was solubilized in sterile deionized water and was administered by oral gavage at 80 mg/kg. The vehicle controls consisted of 0.9% sodium chloride and were administered concurrently with the test article at a volume of 10 ml/kg. A second group of animals (designated Secondary Dose Group) was also assigned to each study and was dosed with the high dose of the test article. These animals were only used in the assays as replacements for any which died in the primary dose groups.
The test article dosed animals were euthanatized 24, 48 and 72 hours after administration of the test article. The positive and vehicle control animals were euthanatized 24 hours after the administration of the control articles. - Duration of treatment / exposure:
- Mice received a single ip dose.
- Frequency of treatment:
- Mice received a single ip dose.
- Post exposure period:
- The test article dosed animals were euthanatized 24, 48 and 72 hours after administration of the test article. The positive and vehicle control animals were euthanatized 24 hours after the administration of the control articles.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
140, 467, 1200 and 1400 mg/kg
Basis:
nominal conc.
- No. of animals per sex per dose:
- See Table below
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide (CP, Sigma, Lot #67F-0155) was used as positive control.
Examinations
- Tissues and cell types examined:
- The frequency of PCEs versus NCEs was determined by scoring the number of NCEs observed in the optic fields while scoring the 1000 PCEs for micronuclei.
- Details of tissue and slide preparation:
- The coded slides were then scored for micronuclei and the polychromatic (PCE) to normochromatic (NCE) cell ratio. Standard forms were used to record these data. One thousand PCEs per animal were scored. The frequency of micronucleated cells was expressed as percent micronucleated cells based on the total PCEs present in the scored optic field. The normal frequency of micronuclei in this mouse strain is about 0.0-0.4%.
- Evaluation criteria:
- General
The criteria for the identification of micronuclei were those of Schmid (1976). Micronuclei were darkly stained and generally round, although almond and ring-shaped micronuclei occasionally occur. Micronuclei had sharp borders and were generally between 1/20 and 1/5 the size of the PCE. The unit of scoring was the micronucleated cell, not the micronucleus; thus the occasional cell with more than one micronucleus was counted as one micronucleated PCE, not two (or more) micronuclei. The staining procedure permitted the differentiation by color of PCEs and NCEs (bluish-grey and red, respectively).
Reference
Schmid (1976). - Statistics:
- Data were summarized to include tables indicating the individual animal results and in tables with animal results summarized by sex and dose groups at the different time points. The analysis of the data was performed using an Analysis of Variance (p
The criteria for determining a positive response involved a statistically significant dose-related increase in micronucleated PCEs, or the detection of a reproducible and statistically significant positive response for at least one dose level. A test article that induced neither a statistically significant dose response nor a statistically significant and reproducible increase at one dose level was considered negative. In either case, the final decision was based on scientific judgment.
References
Sokal, R.R. and Rohlf, J.J.: Biometry, Freeman, 1981.
Results and discussion
Test results
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Negative controls validity:
- not specified
- Positive controls validity:
- valid
- Additional information on results:
- All animals were observed immediately after dosing and periodically throughout the duration of the assay for toxic symptoms and/or mortalities. In both trials, all animals in the vehicle and positive control groups appeared normal after dosing and remained healthy until the appropriate harvest times.
Trial 1
Within one hour of dosing 35 animals in the 1400 mg/kg dose groups had expired. Due to this toxicity, the 1400 mg/kg dose level was eliminated from the study. All animals surviving at this dose level were euthanized the following morning. Within 15 minutes of dosing the animals in the 467 mg/kg dose group became languid. The animals dosed at 140 mg/kg were slightly ataxic. The following morning, approximately 16 hours after dosing, all animals in the 140 and 467 mg/kg dose levels appeared normal and they remained healthy until the appropriate harvest times. The test article, Nipha Crystals, induced no significant increases in micronucleated polychromatic erythrocytes over the levels observed in the vehicle controls in either sex or at any of the harvest times. The positive control, CP, induced significant increases in micronucleated PCEs in both sexes, with means and standard errors of 1.72% ± 0.41% and 1.90% ± 0.23% for the males and females, respectively.
Trial 2
Within 30 minutes of dosing, the animals dosed with the test article (1200 mg/kg) had become prostrate with dyspnea. A few animals exhibited convulsions. Approximately 30 minutes after dosing two females (#'s 5660 and 5682) expired. Two additional females (#'s 5662 and 5663) died within 3 hours of dosing. All other animals dosed with the test article were languid and several had squinted eyes. The following morning, approximately 22 hours after dosing, all animals appeared normal and they remained healthy until the appropriate harvest times. The test article, Nipha Crystals, induced no significant increases in micronucleated polychromatic erythrocytes over the levels observed in the vehicle controls in either sex or at any of the harvest times. The positive control, CP, induced significant increases in micronucleated PCEs in both sexes, with means and standard errors of 2.42% ± 0.61% and 1.42% ± 0.39% for the males and females, respectively.
Any other information on results incl. tables
TABLE 1. MICRONUCLEUS DATA SUMMARY TABLE
% Micronucleated PCEs Mean of 1000 per animal + SE |
Ratio PCE:NCE Mean + SE |
||||||
Treatment | Dose | Harvest Time (hr) | Males | Females | Total | Males | Females |
Vehicle Control (0.9% sodium chloride) |
10 ml/kg | 24 | 0.02 + 0.02 | 0.04 + 0.04 | 0.03 + 0.02 | 0.80 + 0.18 | 0.87 + 0.27 |
Positive Control CP |
80 mg/kg | 24 | 1.72 + 0.41* | 1.90 + 0.23* | 1.81 + 0.23* | 0.46 + 0.13 | 0.56 + 0.09 |
NIPHA | 140 mg/kg | 24 | 0.12 + 0.06 | 0.04 + 0.02 | 0.08 + 0.03 | 0.50 + 0.12 | 0.71 + 0.11 |
48 | 0.14 + 0.07 | 0.02 + 0.02 | 0.08 + 0.04 | 0.46 + 0.07 | 0.74 + 0.10 | ||
72 | 0.12 + 0.06 | 0.08 + 0.02 | 0.10 + 0.03 | 0.60 + 0.13 | 0.75 + 0.10 | ||
467 mg/kg | 24 | 0.08 + 0.04 | 0.12 + 0.04 | 0.10 + 0.03 | 0.66 + 0.24 | 0.82 + 0.15 | |
48 | 0.08 + 0.04 | 0.10 + 0.03 | 0.09 + 0.02 | 0.61 + 0.07 | 0.65 + 0.07 |
||
72 | 0.04 + 0.02 | 0.04 + 0.02 | 0.04 + 0.02 | 0.59 + 0.08 | 0.53 + 0.05 |
* Significantly greater than the corresponding vehicle control, p<0.05.
TABLE 2 MICRONUCLEUS DATA SUMMARY TABLE
% Micronucleated PCEs Mean of 1000 per animal + SE |
Ratio PCE:NCE Mean + SE |
||||||
Treatment | Dose | Harvest Time (hr) | Males | Females | Total | Males | Females |
Vehicle Control 0.9% Sodium Chloride |
10 ml/kg | 24 | 0.10 + 0.03 | 0.04 + 0.02 | 0.07 + 0.02 | 0.62 + 0.09 | 0.93 + 0.25 |
Positive Control CP |
80 mg/kg | 24 | 2.42 + 0.61* | 1.42 + 0.39* |
1.92 + 0.38* | 0.85 + 0.16 | 1.30 + 0.35 |
Test Article | 1200 mg/kg | 24 | 0.08 + 0.04 | 0.08 + 0.04 | 0.08 + 0.02 | 0.47 + 0.03 | 1.10 + 0.17 |
48 | 0.12 + 0.08 | 0.16 + 0.07 | 0.14 + 0.05 | 0.69 + 0.07 | 0.69 + 0.16 | ||
72 | 0.14 + 0.05 | 0.08 + 0.02 | 0.11 + 0.03 | 0.50 + 0.03 | 0.73 + 0.15 |
* Significantly greater than the corresponding vehicle control, p<0.05.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
The test material, Nipha Crystals, did not induce a significant increase in micronuclei in bone marrow polychromatic erythrocytes under the conditions of this assay and is considered negative in the mouse bone marrow micronucleus test. - Executive summary:
The objective of this in vivo assay was to evaluate the ability of the test article, Nipha Crystals, to induce micronuclei in bone marrow polychromatic erythrocytes of ICR mice. The test article was solubilized in 0.9% sodium chloride and dosed by intraperitoneal injection at 140, 467, and 1400 mg/kg based upon the results of a previously conducted dose range finding assay (HLA Study No.: 11200-0-459). The 1400 mg/kg dose group was eliminated from the initial study due to excessive toxicity. A subsequent study was performed at 1200 mg/kg (one dose level only) to replace the high dose eliminated from the initial study. Ten animals (five males and five females) were randomly assigned to each dose/harvest time group. Vehicle and positive control groups euthanatized 24 hours after dosing were included in both studies. The animals were dosed with the test article and were euthanatized 24, 48 and 72 hours after dosing for extraction of the bone marrow. The test material, Nipha Crystals, did not induce a significant increase in micronuclei in bone marrow polychromatic erythrocytes under the conditions of this assay and is considered negative in the mouse bone marrow micronucleus test.
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.