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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 223-055-4 | CAS number: 3710-84-7
- 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 cell study: DNA damage and/or repair
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 15 March 2022 to 20 Dec 2022
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- DECISION ON SUBSTANCE EVALUATION: SEV-D-2114534345-52-01/F
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 022
- Report date:
- 2022
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 489 (In vivo Mammalian Alkaline Comet Assay)
- Deviations:
- yes
- Remarks:
- All deviations are not considered to affect the accuracy, integrity, or validity of the study.
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian comet assay
Test material
- Reference substance name:
- N,N-diethylhydroxylamine
- EC Number:
- 223-055-4
- EC Name:
- N,N-diethylhydroxylamine
- Cas Number:
- 3710-84-7
- Molecular formula:
- C4H11NO
- IUPAC Name:
- N,N-diethylhydroxylamine
- Test material form:
- liquid
- Details on test material:
- Purity (%): 99.32 (DEHA content)
Expiry Date: 03 February 2023
Specific Gravity: 0.869
Dissociation constant (pKa): 12.88
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Male and female range finding experiment. Only male used for main experiment.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Solutions of N,N-diethylhydroxylamine were prepared in purified water.
- Ethyl Methanesulfonate, was used as the positive control compound. A solution was prepared using purified water at a concentration of 20 mg/mL just prior to administration.
- Dose volume of DEHA solutions and vehicle control: 15 mL/kg. Dose volume of the positive control group: 10 mL/kg. - Details on exposure:
- All animals in the vehicle control and N,N-diethylhydroxylamine-treated groups were dosed orally using a dose volume of 15 mL/kg
All main comet experiment formulations were prepared on the first day of dosing, stored at 2-8℃ and used within 24 hours. - Duration of treatment / exposure:
- N,N-diethylhydroxylamine was administered on two occasions approximately 21 hours apart.
- Frequency of treatment:
- Two occasions approximately 21 hours apart.
- Post exposure period:
- Tissue sampling occurred approximately 3 hours after the second dose.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day
- Remarks:
- Vehicle
- Dose / conc.:
- 437.5 mg/kg bw/day
- Dose / conc.:
- 875 mg/kg bw/day
- Dose / conc.:
- 1 750 mg/kg bw/day
- No. of animals per sex per dose:
- 6 male per dose
- Control animals:
- yes
- Positive control(s):
- EMS - Ethyl methanesulfonate
- A solution was prepared using purified water at a concentration of 20 mg/mL just prior to administration.
- Route of administration: oral
- Doses / concentrations: 200 mg/kg/day
Examinations
- Tissues and cell types examined:
- Sections of the liver, duodenum, stomach and testes
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: Male animals only were selected to test up to the higher possible dosage
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Single cell suspensions were prepared using a tissue specific method
DETAILS OF SLIDE PREPARATION:
For each tissue type an appropriate dilution was prepared.
These were stored at 2 - 8ºC overnight prior to electrophoresis
METHOD OF ANALYSIS: Electrophoresis; Microscopic Examination. - Evaluation criteria:
- The following criteria were applied for assessment of assay acceptability:
- The concurrent vehicle control is considered comparable to the laboratory historical vehicle control data for each tissue.
- The positive control should induce responses that are compatible with those generated in the historical positive control database and produce a statistically significant increase compared with the concurrent vehicle control.
- Adequate numbers of cells and doses have been analysed.
- The high dose is considered to be the MTD, the maximum recommended dose or the maximum practicable dose.
For valid data, the test article will be considered to induce DNA damage if:
1. At least one of the test doses exhibits a statistically significant increase in tail intensity, in any tissue, compared with the concurrent vehicle control
2. The increase is dose related in any tissue
3. The increase exceeds the laboratory’s historical control data for that tissue.
The test article will be considered positive in this assay if all of the above criteria are met.
The test article will be considered negative in this assay if none of the above criteria is met and target tissue exposure has been confirmed.
Results which only partially satisfy the criteria will be dealt with on a case-by-case basis. Biological relevance will be taken into account, for example comparison of the response against the historical control data, consistency of response within and between dose levels and any confirmatory experiments. Analysis of additional cells from vehicle and / or treated animals or further experimental work may be deemed necessary to aid evaluation of the data.
A positive response will be based on scientific judgement and will include analysis of related, concurrent cytotoxicity information (such as hedgehog assessment, histopathological changes and any clinical pathology results) and the historical control data. Positive results at clearlycytotoxic dose levels will be interpreted with caution and - Statistics:
- Significant differences between the groups compared were expressed at the 5% (p<0.05) or 1% (p<0.01) level.
Results and discussion
Test results
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- No mortalities were observed throughout the duration of the main comet experiment.
There was no effect on the stomach or duodenum of animals administered
N,N-diethylhydroxylamine at 437.5 mg/kg/day, or in the liver and testes at any concentration tested.
Applicant's summary and conclusion
- Conclusions:
- Liver
It is concluded that N,N-diethylhydroxylamine has not shown any evidence of causing an increase in DNA strand breaks in the liver of male Crl:CD(SD) rats when administered orally by gavage in this in vivo test procedure.
Duodenum
It is concluded that N,N-diethylhydroxylamine has shown evidence of causing an increase in DNA strand breaks in the duodenum of male Crl:CD(SD) rats at 875 and 1750 mg/kg/day only, when administered orally by gavage in this in vivo test procedure. However, due to the confounding presence of hedgehog cells and substantial evidence of cytotoxicity this is not considered to be genotoxic in nature.
Stomach
It is concluded that N,N-diethylhydroxylamine has shown evidence of causing an increase in DNA strand breaks in the stomach of male Crl:CD(SD) rats at 875 and 1750 mg/kg/day only, when administered orally by gavage in this in vivo test procedure. The damage observed is considered to be cytotoxic in nature, however, due to insufficient evidence of cytotoxicity at the 875 mg/kg/day dosage to provide a definitive conclusion, N,N-diethylhydroxylamine is considered unlikely to be genotoxic in nature.
Testes
It is concluded that N,N-diethylhydroxylamine has not shown any evidence of causing an increase in DNA strand breaks in the testes of male Crl:CD(SD) rats when administered orally by gavage in this in vivo test procedure. - Executive summary:
N,N-diethylhydroxylamine is considered unlikely to be genotoxic in nature.
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.