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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 500-240-0 | CAS number: 68958-77-0
- 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
Based on the results of an in vivo LLNA study, the test substance is considered to be sensitizing to skin
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 06 June 2012 to 25 June 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2600 (Skin Sensitisation)
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- other: CBA/J
- Sex:
- female
- Details on test animals and environmental conditions:
- - Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: Young adult animals (approx. 9 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean (19 - 24 grams)
- Housing: Animals were group housed in labeld makrolon cages.
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days
ENVIRONMENTAL CONDITIONS
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.
IN-LIFE DATES: From: 06 June to 25 June 2012 - Concentration:
- 0, 10, 30 and 60%
- No. of animals per dose:
- 5
- Details on study design:
- The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.
RANGE FINDING TESTS:
In the interest of animal welfare and to minimize any testing likely to produce severe responses in animals, a weight of evidence analysis was performed prior to start of this study. All available information was evaluated (e.g. existing human and animal data, literature, substance data supplied by the sponsor, analysis of structure activity relationships (SAR), physicochemical properties and reactivity (pH, buffering capacity).
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node Assay
- Criteria used to consider a positive response:DPM values are presented for each animal and for each dose group. A Stimulation Index (SI) is calculated for each group. The SI is the ratio of the DPM/group compared to DPM/vehicle control group. If the results indicate a SI ≥ 3, the test substance may be regarded as a skin sensitizer. The results were evaluated according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (20011) and the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on Classification, Labelling and Packaging of substances and mixtures.
ANIMAL ASSIGNMENT
Three groups of five animals were treated with one test substance concentration per group. One group of five animals was treated with vehicle.
TREATMENT PREPARATION AND ADMINISTRATION:
Test substance preparation: The test substance formulations (w/w) were prepared within 4 hours prior to each treatment. Homogeneity was obtained to visually acceptable levels.
Rationale for vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.
Induction - Days 1, 2 and 3; Excision of nodes - Day 6; Tissue processing for radioacitivity - Day 6; Radioactivity measurements - Day 7; Performed according to test guidelines.
Observations:
Mortality/Viability: Twice daily.
Body weights: On Day 1 (pre-dose) and Day 6 (prior to necropsy).
Clinical signs: Once daily on Days 1-6 (on Days 1-3 between 3 and 4 hours after dosing).
Irritation: Once daily on Days 1-6 (on Days 1 - 3 immediately after dosing) according to the following numerical scoring system. Furthermore, a description of all other (local) effects was recorded according to guidelines.
Necropsy: All animals surviving to the end of the study were sacrificed by intra-peritoneal injection with Euthasol® 20% (0.2 mL/animal). - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- Not performed.
- Positive control results:
- The six-month reliability check with Alpha-hexylcinnamicaldehyde indicates that the Local Lymph Node Assay as performed at NOTOX is an appropriate model for testing for contact hypersensitivity. See attached document 'Reliability check'.
- Key result
- Parameter:
- SI
- Value:
- 1
- Test group / Remarks:
- at 10% test concentration
- Key result
- Parameter:
- SI
- Value:
- 1.5
- Test group / Remarks:
- at 30% test concentration
- Key result
- Parameter:
- SI
- Value:
- 5.1
- Test group / Remarks:
- at 60% test concentration
- Key result
- Parameter:
- EC3
- Value:
- 42.5
- Test group / Remarks:
- test concentration estimated to produce SI =3
- Interpretation of results:
- other: sensitising
- Conclusions:
- Under the conditions of the study, the test substance was therefore considered to be sensitizing to skin
- Executive summary:
A study was conducted to determine the skin sensitization potential of the test substance '4,4'-Isopropylidenediphenol, polymer with 1-chloro-2,3-epoxypropane, propane-1,2-diol acrylate and succinic anhydride'in mouse using the local lymph node assay according to OECD Guideline 429 and EU Method B.42, in compliance with GLP. The test substance concentrations selected for the main study were based on the results of a pre-screen test. In the main study, three experimental groups of five female CBA/J mice were treated with test substance concentrations of 10, 30 or 60% w/w on three consecutive days, by open application on the ears. Five vehicle control animals were similarly treated, but with vehicle alone (Methyl ethyl ketone). Three days after the last exposure, all animals were injected with 3H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised and pooled for each animal. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed. The activity was expressed as the number of Disintegrations Per Minute (DPM) and a stimulation index (SI) was subsequently calculated for each group.The very slight irritation, or up to well-defined irritation in case of the 60% treated animals, of the ears as shown by all animals was considered not to have a toxicologically significant effect on the activity of the nodes. All animals at 60% showed bald areas around the ears on Day 5 and 6. Based on the pre-screen data and the maximal erythema grade 2, this bald skin is considered not to have a toxicologically significant effect on the activity of the nodes.No mortality occurred and no clinical signs of systemic toxicity were observed. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period. The body weight loss noted for some animals across the dose groups was considered not toxicologically significant since the changes were slight in nature and no concentration-related incidence was apparent.All auricular lymph nodes of the animals treated at 60% were considered larger in size, as compared to the other treated groups. No macroscopic abnormalities of the surrounding area were noted in any of the animals. The SI values calculated for the substance concentrations 10, 30 and 60% were 1.0, 1.5 and 5.1 respectively. These results indicate that the test substance could elicit an SI ≥ 3. An EC3 value (the estimated test substance concentration that will give a SI =3) of 42.5% was calculated. Under the conditions of the study, the test substance was therefore considered to be sensitizing to skin (WIL Research Europe, 2012).
Reference
Results Pre-screen test:
Well-defined erythema was noted in both animals at 60% on Days 2-5 (very slight on Day 6) and very slight erythema was noted in both animals at 30% on Days 2-6. Variations in ear thickness during the observation period were less than 30% from Day 1 pre-dose values. All animals showed bald areas on the head from Day 3 onwards.
Based on these results, the highest test substance concentration selected for the main study was a 60% concentration.
Other results - main study:
Skin reactions / Irritation:
The very slight irritation, or up to well-defined irritation in case of the 60% treated animals, of the ears as shown by all animals was considered not to have a toxicologically significant effect on the activity of the nodes.All animals at 60% showed bald areas around the ears on Day 5 and 6. Based on the pre-screen data and the maximal erythema grade 2, this bald skin is considerednot to have a toxicologically significant effect on the activity of the nodes.
Systemic toxicity/Body weights:
No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period. The body weight loss noted for some animals across the dose groups was considered not toxicologically significant since the changes were slight in nature and no concentration-related incidence was apparent.
Macroscopy of the auricular lymph nodes and surrounding area:
All auricular lymph nodes of the animals treated at 60% were considered larger in size, as compared to the other treated groups. No macroscopic abnormalities of the surrounding area were noted in any of the animals.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
A study was conducted to determine the skin sensitization potential of the test substance '4,4'-Isopropylidenediphenol, polymer with 1-chloro-2,3-epoxypropane, propane-1,2-diol acrylate and succinic anhydride' in mouse using the local lymph node assay according to OECD Guideline 429 and EU Method B.42, in compliance with GLP. The test substance concentrations selected for the main study were based on the results of a pre-screen test. In the main study, three experimental groups of five female CBA/J mice were treated with test substance concentrations of 10, 30 or 60% w/w on three consecutive days, by open application on the ears. Five vehicle control animals were similarly treated, but with vehicle alone (Methyl ethyl ketone). Three days after the last exposure, all animals were injected with 3H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised and pooled for each animal. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed. The activity was expressed as the number of Disintegrations Per Minute (DPM) and a stimulation index (SI) was subsequently calculated for each group.The very slight irritation, or up to well-defined irritation in case of the 60% treated animals, of the ears as shown by all animals was considered not to have a toxicologically significant effect on the activity of the nodes. All animals at 60% showed bald areas around the ears on Day 5 and 6. Based on the pre-screen data and the maximal erythema grade 2, this bald skin is considered not to have a toxicologically significant effect on the activity of the nodes.No mortality occurred and no clinical signs of systemic toxicity were observed. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period. The body weight loss noted for some animals across the dose groups was considered not toxicologically significant since the changes were slight in nature and no concentration-related incidence was apparent.All auricular lymph nodes of the animals treated at 60% were considered larger in size, as compared to the other treated groups. No macroscopic abnormalities of the surrounding area were noted in any of the animals. The SI values calculated for the substance concentrations 10, 30 and 60% were 1.0, 1.5 and 5.1 respectively. These results indicate that the test substance could elicit an SI ≥ 3. An EC3 value (the estimated test substance concentration that will give a SI =3) of 42.5% was calculated. Under the conditions of the study, the test substance was therefore considered to be sensitizing to skin (WIL Research Europe, 2012).
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Based on the results of an in vivo LLNA study as well as its calculated EC3 value, the test substance qualifies for classification as Skin sens. Cat 1B (H317 – May cause an allergic skin reaction) according to CLP (EC 1272/2008) criteria.
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.