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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 249-277-1 | CAS number: 28874-51-3
- 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
Oral: LD50 > 2000 mg/kg bw, OECD 423, EU Method B. 1 tris, Kiss 2012a.
Dermal: LD50 > 2000 mg/kg, OECD 402, EU Method B. 3, EPA OPPTS 870. 1200, Kiss 2012b.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 07 March 2012 to 22 March 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- acute toxic class method
- Limit test:
- yes
- Species:
- rat
- Strain:
- other: CRL: (WI)
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 10 to 11 weeks old.
- Weight at study initiation: 220 to 235 g
- Fasting period before study: Animals were fasted the night before treatment, and then returned three hours after treatment.
- Housing: In groups of three, in polypropylene/polycarbonate cages.
- Diet: Complete diet for rats and mice, ad libitum.
- Water: tap water from the municipal supply ad libitum.
- Acclimation period: At least 20 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): 15 - 20 per hour.
- Photoperiod (hrs dark / hrs light): 12 hours per day, between 06:00 and 18:00 hours.
IN-LIFE DATES: From: 07 March 2012 To: 21/22 March 2012 - Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- Distilled
- Details on oral exposure:
- MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
DOSAGE PREPARATION: The test amterial was freshly formulated at a concentration of 200 mg/mL in the vehicle, on the day of administration. The formulation container was stirred continuously up to finishing the treatment.
CLASS METHOD
- Rationale for the selection of the starting dose: The initial dose level was selected by the study director to be that which is most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.
DOSING
- Method: A group of three females were tested at the dose level initially, based on the findings a second group was dosed to confirm the results. - Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- Three females per group.
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:
> Weighing: Body weights were recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
> Clinical: Observations were recorded at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsy of survivors performed: Yes, and macroscopic examination was performed on all animals. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded. - Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No mortalities were observed in either group dosed at 2000 mg/kg bw.
- Clinical signs:
- other: No treatment related observations were made during the 14 day observation period.
- Gross pathology:
- No treatment related effects were observed.
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of the study, no mortalities or signs of toxicity were observed in animals treated at 2000 mg/kg bw. The LD50 was therefore considered to be greater than 2000 mg/kg bw.
- Executive summary:
The acute oral toxicity of the test material was determined in a study conducted under GLP conditions and in line with OECD 423 and EU Method B. 1 tris, according to the acute toxic class method. Two groups of three females were dosed with the test material, formulated in distilled water, at 2000 mg/kg bw via oral gavage. Animals were observed for 14 days post treatment for mortality, clinical signs of toxicity, changes in body weight and macroscopic changes at necropsy.
Under the conditions of the study, no mortalities or signs of toxicity were observed in treated animals. The LD50 was therefore considered to be greater than 2000 mg/kg bw.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Quality of whole database:
- The quality of the dataset is considered to be high.
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 04 April 2012 to 18 April 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.3 (Acute Toxicity (Dermal))
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.1200 (Acute Dermal Toxicity)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- other: CRL: (WI)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: Young rats
- Weight at study initiation: 214 - 266g
- Housing: Individually in polypropylene/polycarbonate cages.
- Diet: Complete diet for rats and mice, ad libitum.
- Water: Municipal tap water, ad libitum.
- Acclimation period: 6 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): 15 - 20 per hour.
- Photoperiod (hrs dark / hrs light): 12 hours from 06:00 to 18:00 hours daily.
IN-LIFE DATES: From: 04 April 2012 To: 18 April 2012. - Type of coverage:
- occlusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- TEST SITE
- Area of exposure: On the back of each animal.
- % coverage: Approximately 10 % of the whole body surface area.
- Type of wrap if used: The test material was placed onto a gauze pad. The gauze pad was fixed with a hypoallergenic plaster and the entire trunk of the animal was then wrapped with semi occlusive plastic wrap.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): With body temperature water.
- Time after start of exposure: 24 hours.
TEST MATERIAL
Sufficient water to damp the material was used to ensure good contact with the skin. - Duration of exposure:
- 24 hours
- Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- 5 per sex per dose
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> Clinical: Observations were performed on the day of treatment at 1 and 5 hours after application of the test material and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
> Bodyweight: Recorded on Day 0 (before exposure) and on Days 7 and 14.
- Necropsy of survivors performed: Yes, after examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed. All macroscopic changes were recorded. - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No mortalities were observed in either males or females dosed at 2000 mg/kg bw.
- Clinical signs:
- other: No treatment related systemic or local signs of toxicity observed during the 14 day observation period.
- Gross pathology:
- No treatment related effects were observed. Bilateral uterine dilatation with clear fluid seen in 2/5 females was regarded as common background.
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of the study, no mortalities, systemic or local signs of toxicity were observed in animals treated at 2000 mg/kg bw. The LD50 was therefore considered to be greater than 2000 mg/kg bw.
- Executive summary:
The acute dermal toxicity of the test material was determined in a study conducted under GLP conditions and in line with OECD 402, EU Method B. 3 and EPA OPPTS 870.1200, according to the standard acute method. Five male and five female rats were exposed to the test material in a limit test at 2000 mg/kg bw for 24 hours under an occlusive dressing.
Under the conditions of the study, no mortalities or treatment related systemic or local signs of toxicity were observed in animals treated at 2000 mg/kg bw. The LD50 was therefore considered to be greater than 2000 mg/kg bw.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Quality of whole database:
- The quality of the dataset is considered to be high.
Additional information
Oral
Acute toxicity via the oral route is addressed with one key study and two supporting studies.
The key study (Kiss 2012a) was conducted under GLP conditions and in line with OECD 423 and EU Method B. 1 tris, according to the acute toxic class method and hence has been awarded a reliability score of 1, in accordance with the criteria for assessing data quality as set forth by Klimisch et al. (1997). Two groups of three females were dosed with the test material, formulated in distilled water, at 2000 mg/kg bw via oral gavage. Animals were observed for 14 days post treatment for mortality, clinical signs of toxicity, changes in body weight and macroscopic changes at necropsy. Under the conditions of the study, no mortalities or signs of toxicity were observed in treated animals. The LD50 was therefore considered to be greater than 2000 mg/kg bw.
The supporting study (Ichimura & Kirimura 1969) was performed using read across substance, sodium 5-oxo-DL-prolinate. Read across is considered to be suitable based on structural similarities between the read across substance and the substance. The study was performed following similar or equivalent methodology to the standardised guideline OECD 401. The study has been translated into English, however the full the study report is not available; therefore there is insufficient information to how the study was performed, hence this study has been designated a reliability score of 4, in accordance with the criteria for assessing data quality as set forth by Klimisch et al. (1997). Acute oral toxicity of sodium 5 -oxo-DL-prolinate was assessed using optional test groups of dd-line mice, which consisted of 10 mice in each group. In the case of the control group, solvent alone was administered in accordance with the case of the test groups. The dose levels administered are as follows: 7.02, 8.19, 9.36, 10.8, 12.3 and 14.0 g/kg. These concentrations were administered to each mouse in a constant volume per 10 g of mouse body weight by a stomach tube. The animals were under observation for 7 days and any mortality was recorded. Under the conditions of the study, the LD50 was found to be 10.4 g/kg (95 % confidence limit between 9.08 and 11.8 g/kg).
Another supporting study (Ishida 1997) was also performed using read across substance, 5-oxo-L-proline. Read across is considered to be suitable based on the structural similarities between read across substance, 5-oxo-L-proline and substance sodium 5-oxo-L-prolinate. The study was performed following similar or equivalent methodology to the standardised guideline OECD 401. As this study has been used for read across, and performed to standardised guidelines, it was awarded a reliability score of 2 in accordance with the criteria for assessing data quality as set forth by Klimisch et al. (1997). During the study, 5 male and 5 female (ICR) mice received a test material dose of 2000 mg/kg administered in a 0.5 w/v % carboxymethylcellulose sodium solution via gavage. The observation period was 14 days in which external appearance, nutritional value and behaviour were examined. No deaths were observed. Under the conditions of this study, the acute oral LD50 of the test material in male and female (ICR) mice was greater than 2000 mg/kg.
Inhalation
In accordance with point 8.5.2, Column 2 (Specific rules for adaptation from Column 1), Annex VIII of Regulation (EC) No. 1907/2006, an acute inhalation study does not need to be performed as use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. The acute toxicity endpoint has been addressed by assessing the toxicity via the oral and dermal routes, which are more appropriate when considering the use pattern of this substance.
Dermal
The acute dermal toxicity of the test material was determined in a study conducted under GLP conditions and in line with OECD 402, EU Method B. 3 and EPA OPPTS 870.1200, according to the standard acute method. Five male and five female rats were exposed to the test material in a limit test at 2000 mg/kg bw for 24 hours under an occlusive dressing.
Under the conditions of the study, no mortalities or treatment related systemic or local signs of toxicity were observed in animals treated at 2000 mg/kg bw. The LD50 was therefore considered to be greater than 2000 mg/kg bw.
Justification for selection of acute toxicity – oral endpoint
This study was performed under GLP conditions and in accordance with standardised guidelines. It was assigned a reliability score of 1 in accordance with the criteria outlined in Klimisch (1997). It was therefore considered suitable to be the key study for this endpoint.
Justification for selection of acute toxicity – inhalation endpoint
A data waiver has been submitted to address acute toxicity via the inhalation route.
Justification for selection of acute toxicity – dermal endpoint
This study was performed under GLP conditions and in accordance with standardised guidelines. It was assigned a reliability score of 1 in accordance with the criteria outlined in Klimisch (1997). It was therefore considered suitable to be the key study for this endpoint.
Justification for classification or non-classification
Acute Oral Toxicity:
In accordance with criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the test material does not require classification as no signs of toxicity were noted during the course of the study.
Acute Dermal Toxicity:
In accordance with criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the test material does not require classification as no signs of toxicity were noted during the course of the study.
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.