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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 224-166-0 | CAS number: 4221-80-1
- 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
Key value for chemical safety assessment
Effects on fertility
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- the study does not need to be conducted because a pre-natal developmental toxicity study is available
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- no study available
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
No data available; waiving arguments were applied.
Effects on developmental toxicity
Description of key information
No teratogenic effects occurred during reproduction studies from day 6 until day 15 of gestation with rats and mice.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- compared to current guidelines, less parameters were investigated.
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Obtained from a closed SPF breeding colony.
- Weight at study initiation: 210 g
- Housing: successfully mated females were kept in groups of 5 in Macrolon cages in an air-conditioned room
- Diet: Nafag No. 890
- Water: Tap water
ENVIRONMENTAL CONDITIONS
- Temperature: 20 °C +/- 0.5 °C
- Humidity: 60 +/- 5 %
- Photoperiod: The room was illuminated for 12 hours - Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 2 % aqueous solution
- Details on exposure:
- VEHICLE
- Concentration in vehicle: 2 mL/100g of body weight - Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- - Impregnation procedure: Mated overnight with males of proven fertility
- M/F ratio: 1 M / 3 F
- Any other information: The day on which spermatozoa were found in the vaginal smear was designated as Day = 0 of pregnancy - Duration of treatment / exposure:
- From day 6 until day 15 of gestation, inclusive.
- Frequency of treatment:
- daily
- Duration of test:
- 21 days
- Dose / conc.:
- 300 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 3 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 25 females per dose
25 females for the vehicle controle - Control animals:
- yes, concurrent vehicle
- Maternal examinations:
- BODY WEIGHT: Yes
- Time schedule for examinations: checked daily from day 0 to day 21
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice: On day 21 shortly before delivery
- Organs examined: ovaries and uterus, foetuses - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of corpora lutea: No
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - Examination of the viscera: Yes: According to the slicing technique of Wilson: 1/3 of the foetuses were fixed in a mixture of ethyl aclohol and formol to which acetic acid was added
- Skeletal examinations: Yes: In 2/3 of the foetuses following clearing in potassium hydroxide and staining with Alizarine Red S. - Details on results:
- No clearcut reaction to treatment with the test item were noted. The average body-weight gain and the feed consumption were roughly comparable for all groups.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 3 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Remarks on result:
- other: No adverse effects observed at tested doses
- Key result
- Abnormalities:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- The gross inspection of the foetuses revealed facial aplasia associated with microencephaly and bilateral anophthalmia in one out of 269 specimens of the 3000 mg/kg bw/d dose group. This one instance of malformation is considered to be of a spontaneous origin and not related to treatment with the test item. Malformations concerning the facial differentiation of the skull are found spontaneously at a relatively high incidence in the breed of rats used in the present study.
By applying the slicing technique two foetuses of the high-dose group showed anasarca, i.e. slight oedema-like changes of siabcutaneous tissue, an anomaly occasionally observed in controls, too. The one of those two foetuses affected is identical to the aforementioned malformed one.
Skeletal assessment revealed no clearcut deviations between experimental groups and controls with the exception of a slightly increased number of not yet ossified phalangeal nuclei of hind-limb in both the intermediate and high dose group as well as not yet ossified calcanei in the high-dose group. Findings of this kind are considered to be entirely non-specific and may reflect mild toxicity of the compound in the dams. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 3 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: teratogenicity
- Key result
- Abnormalities:
- not specified
- Key result
- Developmental effects observed:
- not specified
Reference
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 3 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Comparable to guideline requirements
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
In the key study, the test item was administered orally to pregnant rats from day 6 until day 15 of gestation, inclusive. The doses were 300, 1000 and 3000 mg/kg of body weight. Concerning the progeny, the foetuses of the low-dose group were found to be entirely unaffected by the administration of the compound to the dams. At the intermediate and high-dose level a slight delay of the physiological growth of the foetuses was indicated by an increase in the number of not yet ossified phalangeal nuclei of the hind-limb as well as calcanei (high-dose group only). Findings of this kind are considered to be entirely non-specific and may reflect mild toxicity of the compound in the dams. No teratogenic effects were observed. The NOAEL was 3000 mg/kg bw/d.
In a supporting study, the test item was administered orally to pregnant mice from day 6 until day 15 of gestation, inclusive. The doses were 300, 1000 and 3000 mg/kg of body weight. Except for a slightly reduced feed consumption during the late period of treatment and the post-treatment period of the experiment, the dams of the three dose groups did not show any signs of intolerability of the compound. The progeny was not adversely affected by the test item. The reproduction data were comparable for all experimental groups and vehicle control. No teratogenic effects were observed. The NOAEL was 3000 mg/kg bw/d.
Justification for classification or non-classification
Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are also reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified under Regulation (EC) No 1272/2008, as amended for the eighth time in Regulation (EU) No 2016/218 for toxicity to reproduction.
Additional information
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.