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EC number: 219-280-2 | CAS number: 2402-58-6
- 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
The available acute oral toxicity study within this category (according to OECD TG 423) resulted in an acute oral LD50 value > 5000 mg/kg bw.
The available acute dermal toxicity study within the category (according to OECD TG 402) resulted in an acute dermal LD50 value > 5000 mg/kg bw.
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
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP - Guideline Study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Version / remarks:
- (adopted 17 Dec 2001)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
- Version / remarks:
- (adopted 30 May 2008)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.1100 (Acute Oral Toxicity)
- Version / remarks:
- adopted Dec 2002
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Japan MAFF Testing Guideline of 12 Nosan No. 8147
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Landesanstalt für Umwelt, Messungen und Naturschutz Baden-Württemberg
- Test type:
- acute toxic class method
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: 10 weeks (nulliparous, non-pregnant females)
- Weight at study initiation: 164 - 178 g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: single housing in Makrolon cage, type III
- Diet: VRF1 (P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: tap water ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: March 04, 2013 To: March 27, 2013 - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Due to the chemical structure of the test substance acute toxicity was not expected. Thus a dose level of 2000 mg/kg bw was selected as starting dose. - Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- Group 1: 3 females
Group 2: 3 females - Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
- Necropsy of survivors performed: Necropsy with gross-pathology examination on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with increasing concentrations over time. - Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No mortality occurred in both 2000 mg/kg bw test groups throughout the study.
- Clinical signs:
- other: In all animals of the first 2000 mg/kg bw test group impaired general state and piloerection were observed at hour 1 and persisted in two animals until hour 4 or 5 after administration. Diarrhea was noted in one animal at hour 0 while cowering position wa
- Gross pathology:
- There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of this study the median lethal dose of Didodecyl fumarate after oral administration was found to be greater than 2000 mg/kg bw in female rats.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
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
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP - Guideline Study
- 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))
- Version / remarks:
- (adopted 30 May 2008)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.1200 (Acute Dermal Toxicity)
- Version / remarks:
- (adopted Aug 1998)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: - Japan MAFF Testing Guideline of 12 Nosan No. 8147 402.
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Landesanstalt für Umwelt, Messungen und Naturschutz Baden-Württemberg
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks (nulliparous and non-pregnant)
- Weight at study initiation: males: 219-241 g, females: 198-218 g
- Fasting period before study: no
- Housing: single housing in Makrolon cage, type III
- Diet: VRF1 (P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: tap water ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: To: 04 to 19 Mar 2013 - Type of coverage:
- semiocclusive
- Vehicle:
- corn oil
- Details on dermal exposure:
- TEST SITE
- Area of exposure: about 40 cm² clipped skin of the dorsal and dorsolateral parts of the trunk
- % coverage: at least 10% of the body surface
- Type of wrap if used: The test item was covered with an air-permeable dressing (4 layers of absorbent gauze and stretch bandage.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water
- Time after start of exposure: 24 hours
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 12.50 mL/ kg
- Concentration (if solution): 400 mg/mL
- Constant volume or concentration used: yes
- For solids, paste formed: yes, preparation was prepared and applied lukewarm - Duration of exposure:
- 24 hours
- Doses:
- 5000 mg/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- not required
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weight shortly before administration (day 0), weekly thereafter and on the last day of observation. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
- Necropsy of survivors performed: yes
- Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), several times and on the last day of observation. Scoring was performed according to Draize. - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 5 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No mortality occurred within the study period.
- Clinical signs:
- other: No systemic clinical signs were observed during clinical examination within the study period.
- Gross pathology:
- No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.
- Other findings:
- Skin effects at the application site comprised very slight erythema (grade 1) in one out of five male animals and in one out of five female animals and was observed on study day 1.
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of this study the median lethal dose (LD50) of Didodecyl fumarate after dermal application was found to be greater than 5000 mg/kg bw in male and female rats.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Additional information
Justification for grouping of substances and read-across
The PFAE fumarates (Polyfunctional Aliphatic Ester) category consists of six members, which are either well-defined mono-constituent substances or related UVCB substances, with varying fatty alcohol chain lengths. The distinguishing feature of this category of chemicals is that its members are diester derivatives of fumaric acid (CAS 110-17-8). The alcohol moiety of the dicarboxylic esters generally falls in the C8-C22 carbon number range, including linear, even numbered alcohols.
In order to avoid the need to test every substance for every endpoint, the category concept is applied for the assessment of environmental fate, environmental toxicity and human health hazards. Thus where applicable, environmental and human health effects are predicted from adequate and reliable data for source substance(s) within the group by inter- or extrapolation to the target substances in the group (read-across approach) applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. Structural similarities and similarities in properties and/or activities of the source and target substances in the category are the basis of read-across.
The available studies providing information on the human health hazard assessment within the PFAE fumarates category were conducted with the category member Didodecyl fumarate (CAS 2402-58-6). This substance was selected for testing, because it represents the category member with the shortest fatty alcohol side chain, and consequently with the lowest molecular weight, which is regarded as worst-case approach in terms of hazard assessment of the PFAE fumarates for the local as well as for systemic effects.
Furthermore, the category is supported by another polyfunctional aliphatic ester, namely Bis(2-ethylhexyl) adipate (CAS 103-23-1). This supporting chemical is used to cover toxicological endpoints, exclusively. The read across of Bis(2-ethylhexyl) adipate (CAS 103-23-1) to the PFAE fumarate category is justified due to the similar structural and physico-chemical properties, as well as their toxicological, and ecotoxicological profiles.
A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Sections 7.1 and 13) and within Chapter 5.1 of the CSR.
Endpoint specific data matrix:
ID # |
CAS |
Acute toxicity - oral |
Acute toxicity - inhalation |
Acute toxicity - dermal |
1 |
2402-58-6 |
Experimental result: LD50 > 2000 mg/kg bw |
Waiving statement |
Experimental result: LD50 > 5000 mg/kg bw |
2 |
10341-03-4 |
RA: CAS 2402-58-6 |
Waiving statement |
RA: CAS 2402-58-6 |
3 |
68610-90-2 |
RA: CAS 2402-58-6 |
Waiving statement |
RA: CAS 2402-58-6 |
4 |
68921-51-7 |
RA: CAS 2402-58-6 |
Waiving statement |
RA: CAS 2402-58-6 |
5 |
68921-52-8 |
RA: CAS 2402-58-6 |
Waiving statement |
RA: CAS 2402-58-6 |
6 |
68921-53-9 |
RA: CAS 2402-58-6 |
Waiving statement |
RA: CAS 2402-58-6 |
Acute toxicity - oral
CAS 2402-58-6
In a GLP-compliant study according OECD guideline 423, the acute oral toxicity of Didodecyl fumarate (CAS 2402-58-6) was studied in female Wistar rats (Höger, 2013). Two groups of three female rats consecutively received the test substance in corn oil at a dose of 2000 mg/kg bw and were observed for a period of 14 days. During the whole study, no mortalities were reported.In all animals of the first 2000 mg/kg bw test group impaired general state and piloerection were observed at hour 1 and persisted in two animals until hour 4 or 5 after administration. Diarrhea was noted in one animal at hour 0 while cowering position was observed in all animals at hour 1.Clinical signs in the second 2000 mg/kg bw test group revealed impaired general state and piloerection and were observed in one animal from hour 0 until hour 2 after administration. In two animals of this test group no clinical signs were observed during clinical examination.The mean body weight of the test groups increased throughout the study period within the normal range.There were no macroscopic pathological findings in any of the animals sacrificed at the end of the observation period.
Under the conditions of this study, the oral LD50 value of Didodecyl fumarate was greater than 2000 mg/kg bw.
Acute toxicity - inhalation
PFAE fumarates are pasty solids with calculated vapour pressures below 0.0001 Pa at 20 °C. Therefore, exposure via the inhalation route can be considered negligible under the identified use conditions.
Acute toxicity – dermal
CAS 2402-58-6
The acute dermal toxicity of Didodecyl fumarate (CAS 2402-58-6) was tested in a GLP-conform study according to OECD guideline 402 (Höger, 2013). The clipped skin of dorsal and dorsolateral parts of 5 Wistar rats per sex was exposed to the test substance in corn oil at a limit dose of 5000 mg/kg bw for 24 h under semiocclusive conditions. After removal of the test substance, animals were observed for a period of 14 days. No mortality and no clinical signs of toxicity were observed up to the end of the observation period. Overall body weight gains were not affected by treatment with the test substance in male and female animals. Necropsy and histopathological examination revealed no substance-related findings. Skin effects at the application site comprised very slight erythema (grade 1) in one out of five male and female animals at day 1. Animals had fully recovered by day 2.
Based on these results, the dermal LD50 value of Didodecyl fumarate was greater than 5000 mg/kg bw.
Conclusion for acute toxicity
One study is available studying the acute oral toxicity of PFAE fumarates category members resulting in oral LD50 values greater than 5000 mg/kg bw. As PFAE fumarates are pasty solids with calculated vapour pressures below 0.0001 Pa at 20 °C exposure via the inhalation route can be considered negligible under the identified use conditions and no further test are necessary. In the available acute dermal toxicity study with the same category member an LD50 value of 5000 mg/kg bw was determined.
Thus, the available data indicate a very low level of acute toxicity for the category members and thus no hazard for acute oral, inhalation and dermal toxicity was identified.
A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR.
Justification for selection of acute toxicity – oral endpoint
GLP study
Justification for selection of acute toxicity – dermal endpoint
GLP Study
Justification for classification or non-classification
The category assessment for acute toxicity states that there is no concern. No acute toxicity classification is deemed necessary
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.
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