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EC number: 286-304-6 | CAS number: 85204-10-0
- 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
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
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Well documented and reported study fully adequate for assessment. The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a recognized contract research organization.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- of 2010
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- of 2008
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- CBA
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Mouse (healthy females only), strain: CBA/J Rj with appropriate range of bodyweight at study start.
- Source: ELEVAGE JANVIER, Route des Chènes Secs B.P. 4105, 53940 Le Genest-St-Isle, France
- Hygienic level at arrival: SPF
- Age at treatment start (1st induction): 8 to 9 weeks.
- Weight at treatment start (1st induction): Minimum 20.0 g, maximum 21.7 g.
- Housing: Group caging (4 animals/cage) in Type II polypropylene/polycarbonate cages
- Bedding material: Woodbased, Lignocel Hygienic Animal Bedding,
J. Rettenmaier & Söhne GmbH + Co. KG, Rosenberg, Germany
- Cage enrichment: Glass tunnel tubes
- Diet (ad libitum): Ssniff SM R/M-Z+H, autoclavable complete breeding and maintenance diet for rats and mice,
Ssniff Spezialdiäten GmbH, Soest, Germany.
- Water (ad libitum): Tap water from municipal supply
- Acclimation period: 6 days before treatment start under laboratory conditions.
Water was regularly analysed for contaminants, detailed information on diet and bedding material were provided by the suppliers. Water, diet and bedding material used in the present study were not considered to adversely affect the purpose or integrity of the study.
ENVIRONMENTAL CONDITIONS
Controlled environment, environmental conditions were set at:
- Ventilation, air changes per hour: 15-20
- Temperature (°C): 22 ± 3°C
- Relative Humidity (%): 30 to 70%
- Photoperiod (artificial lighting): 12 hrs day / 12 hrs night
There was no mentioning of any deviations from these ranges, which compromised the integrity or validity of the study. - Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- Induction administrations on Days 1, 2 and 3 at the following concentrations of WS400402 in vehicle (% w/v):
- Pre-screen Test: 25, 50
- Main Study: 0 (vehicle control), 10, 25, 50
Induction administration at the following concentration of Hexyl cinnamic aldehyde (positive control) in vehicle (% w/v):
- Main Study : 25 - No. of animals per dose:
- Pre-screen Test: 2 female animals per dose level
Main Study, Vehicle Control: 8 female animals (1 group)
Main Study, Test Groups: 4 female animals per dose level
Positive Control: 4 female animals (1 dose group) - Details on study design:
- TEST SUBSTANCE SOLUBILITY
WS400402 is a viscous liquid at room temperature, which is not applicable to the animals undiluted. A vehicle trial has demonstrated that WS400402 is soluble in 4:1 v/v acetone:olive oil at 50% w/v suitable for dose administration.
TREATMENT PREPARATION AND ADMINISTRATION
- Pre-screen Test
Administration of WS400402 at 25 or 50% w/v in the selected vehicle did not produce deaths, signs of ill health or systemic toxicity, relevant increases in ear thickness or excessive local irritation over the treated area. The only findings were erythema grade 1 (very slight in degree) confined to Day 4 in all animals. Based on this information 50% w/v of WS400402 was selected as high dose level for the main study.
- Main Study
On three consecutive days, groups of 4 female mice were treated by topical application to the dorsal surface of both ears with 25 μL/ear/day at the test or positive control substance concentrations listed above in the field "LLNA – Concentration". A group of 8 control females received only the vehicle, acetone:olive oil (v/v 4:1). All formulations were freshly prepared on each day of administration.
OBSERVATIONS, MEASUREMENTS AND ENDPOINTS (POOLED TREATMENT GROUP APPROACH) DURING THE MAIN STUDY
Each animal was checked twice a day (before and after treatment) on Days 1 to 3 and once daily on Days 4 to 6 for signs of ill health or toxicity. At the same intervals, the ears were examined for signs of irritation. In addition, individual bodyweights were recorded on Days 1 (prior to treatment) and 6 (three days after the third induction administration). On Day 6, all animals were injected into the tail vein Tritiated (^3H)-methyl Thymidine (^3HTdR) diluted in sterile phosphate buffered saline at a nominal dose of 20 µCi per mouse, in order to measure lymphocyte proliferation by radioactive labelling. Five hours (± 30 minutes) afterwards the draining (auricular) lymph nodes were excised and pooled for each experimental group. After sample processing and precipitating macromolecules (DNA) of the lymph node cells in 5% trichloracetic acid (TCA), radioactivity measurements were performed on Day 7. Radioactivity was expressed as the number of radioactive disintegrations per minute (DPM). The ratio of the proliferation (reflected by the magnitude of measured DPM/node) in treated groups to that in the vehicle control group, termed the stimulation index (SI) or test/control ratio, was subsequently calculated for each group. Background ^3HTdR levels were also measured in two 1 mL aliquots of 5% TCA and accounted for in the study results.
Criteria Used to Consider a Positive Response:
The test material is regarded as a sensitizer if at least one concentration of the test substance produces a stimulation index (SI) ≥ 3. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- Data were not statistically analysed.
- Positive control results:
- A stimulation index (SI) of 10.6 was attained in a concomittant positive control assay with the same strain of mice (CBA/J Rj) in response to 25% w/v hexyl cinnamic aldehyde in acetone:olive oil (4:1 v/v), thus demonstrating the reliability and sensitivity of this test system and assay to detect skin sensitization potential in this laboratory. In addition, the disintegrations per lymph node value attained was within the historical reference range. Mortality, cutaneous reactions or signs of toxicity were not evident in the postive control group.
- Key result
- Parameter:
- SI
- Value:
- 41.1
- Test group / Remarks:
- 50% test substance concentration
- Key result
- Parameter:
- SI
- Value:
- 45.8
- Test group / Remarks:
- 25% test substance concentration
- Key result
- Parameter:
- SI
- Value:
- 9.7
- Test group / Remarks:
- 10% test substance concentration
- Interpretation of results:
- other: sensitising according to Regulation 1272/2008
Reference
The lymph nodes were visibly larger in animals of the test material treated groups and the positive control group than in vehicle control animals. This is consistent with the sensitization response attained in the treated groups and positive control group.
Premature deaths, signs of ill health or systemic toxicity, or excessive local irritation over the treated area were not evident in the pre-screen or main tests. The only irritation findings recorded were erythema grade 1 (very slight in degree) confined to Day 4 in all animals treated with 25 or 50% w/v test material dilutions in the pre-screen test, and seen on Days 4, 5 and 6 in all animals treated with 50% w/v test material dilution in the main test. Ear punch weight and ear thickness were also unaffected by treatment during the pre-screen test.
Marginal bodyweight loss was seen in a few pre-screen and main test animals in this study, but this was not attributable to treatment with the test material.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
In a local lymph node assay with mice, the stimulation index (SI) threshold of ≥ 3.0, indicating a positive sensitisation response, was attained in all treated groups. Therefore, according to EU classification rules the test substance was classified as “Category 1” (Warning: May cause an allergic skin reaction) [REGULATION (EC) 1272/2008].
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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