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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 403-610-9 | CAS number: 122795-41-9
- 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
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Between 17 May 1988 and 23 June 1988
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 988
- Report date:
- 1988
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Version / remarks:
- guideline not stated
- GLP compliance:
- yes
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- An LLNA is not performed because other reliable information is available.
Test material
- Reference substance name:
- -
- EC Number:
- 403-610-9
- EC Name:
- -
- Cas Number:
- 122795-41-9
- IUPAC Name:
- 1-ethyl-3-methoxytricyclo[2.2.1.0²,⁶]heptane; 2-ethyl-5-methoxybicyclo[2.2.1]heptane; 2-ethyl-6-methoxybicyclo[2.2.1]heptane
- Test material form:
- liquid
Constituent 1
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- Hartley
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: A reputable supplier. For full details please see full study report
- Weight at study initiation: 300 - 700 g
- Housing: Guinea pigs were housed individually in 1/2" stainless steel wire mesh cages. Size in accordance with "Guide for the Care and Use of Laboratory Animals" of the Institute of Laboratory Resources, National Research Council
- Diet: Wayne Guinea pig DietR, ad libitum
- Water: ad libitum
- Acclimation period: Minimum five (5) days.
ENVIRONMENTAL CONDITIONS
- Temperature: maintained at a temperature of 22°C ± 3°C:
- Humidity: 30 to 70%.
- Photoperiod: 12 hours light, 12 hours dark
Study design: in vivo (non-LLNA)
Induction
- Route:
- epicutaneous, semiocclusive
- Vehicle:
- other: Ethanol (80%)
- Concentration / amount:
- 2%
- Day(s)/duration:
- 3 times 6 hours
- Adequacy of induction:
- highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
- Route:
- epicutaneous, semiocclusive
- Vehicle:
- other: Ethanol (80%)
- Concentration / amount:
- 2%
- Adequacy of challenge:
- highest non-irritant concentration
- No. of animals per dose:
- Dose-range - four (4)
Test article - twenty (20)
Positive control - five (5)
Negative control - ten (10)
Naive challenge - four (4)
Naive rechallenge - four (4)*
*Four animals from the negative control group were utilized as naive control animals for rechallenge. - Details on study design:
- RANGE FINDING TESTS:
Prior to initiation of the study, the irritation potential was determined. Six (6) unexposed animals (3 males and 3 females) were each exposed to different concentrations of the test material by the technique described in site preparation and treatment. In this test, both sides of the animal were shaved and exposed to one concentration of the material. The procedure described in Table 1 for primary challenge was used in grading of the response except that only 24 hour grades were obtained. The dose chosen for induction, challenge and rechallenge was 2. 0%.
MAIN STUDY
- Site preparation and treatment:
The left shoulder of each animal was clipped free of hair with an Oster Model A2 clipper twenty-four hours prior to the 1st, 2nd and 3rd applications of the test material. The shaved area was approximately 5 x 10 cm, i.e. 10% of the body surface. The test material was applied to 20 guinea pigs (10 male and 10 female). The material was applied beneath a 37 x4 0 mm Parke-Davis Readi-Bandage , Parke-Davis and Company, Greenwood, South Carolina) and covered with a dental dam. The patch and dam were held in place with clips attached to the sides of the guinea pig restrainer. The patches were allowed to remain in place for six hours, after which the rubber dams and patches were removed. The treated sites were examined after each dosing day and scored at 24 and 48 hours according to Table 1. This procedure was performed once a week for three weeks, a total of three six-hour inductions. The initial body weight of the animals was recorded. An additional group of ten guinea pigs (5 males and 5 females) was treated with vehicle (Ethanol 80%). Fourteen days after the last induction sensitizing exposure, the animals were challenged in the same manner on a naive site on the left side. Four naive pigs (2 males and 2 females) were induced with the test material, 88-206-01, at a 2.0% concentration, on challenge day in the same manner. Seven days after the primary challenge, the experimental group and a group of four naive pigs were rechallenged on the right side with the test article at a 2.0% concentration.
Four animals from the negative control group (2 males and 2 females) were utilized as naive controls for rechallenge. Local and systemic effects were observed. Twenty-four hours after the challenge and rechallenge, all animals were depilated with Neet Cream Hair Remover (Whitehall Laboratories, Inc. New York 10017). The depilatory was placed on the test sites and surrounding areas and left for no more than 30 minutes. After this time, the animals were thoroughly rinsed with water, gently patted dry and returned to their cages. A minimum of two hours after depilation test sites were graded. The grading was repeated 24 hours later (48 hour grade).
- Frequency of applications:
Three (3) inductions: 88-206-01 (2.0%) (experimental animals)
Three (3) inductions: DNCB (0.3%) (positive control animals)
Three (3) inductions: Ethanol (80%) (negative control animals)
One (1) challenge: 88-206-01 (2.0%) (experimental animals)
One (1) challenge: DNCB (0.3%) (positive control animals)
One (1) challenge: Ethanol (80%) (negative control animals)
One ( 1) challenge: 88-206-01 (2.0%) (naive animals)
One (1) rechallenge: 88-206-01 ( 2.0%) (experimental animals)
One (1) rechallenge: 88- 206-01 ( 2.0%) (naive animals) - Challenge controls:
- A concurrent positive control group consisting of five guinea pigs (3 males and 2 females) was treated with (0.3%) 1-chloro- 2 , 4-dinitrobenzene in 80% ethanol (80:20 ethanol/distilled water).
- Positive control substance(s):
- yes
- Remarks:
- 1-chloro-2,4 dinitrobenzene (DNCB)
Results and discussion
- Positive control results:
- A positive response was elicited in the animals receiving the positive control article, 1-chloro-2,4 dinitrobenzene (DNCB)
In vivo (non-LLNA)
Resultsopen allclose all
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 2.0%
- No. with + reactions:
- 2
- Total no. in group:
- 20
- Clinical observations:
- 2 animals with score [1] 1 = slight or confluent or moderate patchy erythema
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 2.0%
- No. with + reactions:
- 3
- Total no. in group:
- 20
- Clinical observations:
- 3 animals with score [1] 1 = slight or confluent or moderate patchy erythema
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- other: naive animals
- Dose level:
- 2.0%
- No. with + reactions:
- 0
- Total no. in group:
- 4
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- other: naive animals
- Dose level:
- 2.0%
- No. with + reactions:
- 0
- Total no. in group:
- 4
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- positive control
- Dose level:
- DNCB (0.3%)
- No. with + reactions:
- 5
- Total no. in group:
- 5
- Clinical observations:
- All animals had score of [3] 3 = severe erythema with/without edema
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- DNCB (0.3%)
- No. with + reactions:
- 5
- Total no. in group:
- 5
- Clinical observations:
- All animals had score of [3] 3 = severe erythema with/without edema
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- Ethanol (80%)
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Ethanol (80%). No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- Ethanol (80%)
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Reading:
- rechallenge
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 88-206-01 (2.0%)
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Reading:
- rechallenge
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 88-206-01 (2.0%)
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Reading:
- rechallenge
- Hours after challenge:
- 24
- Group:
- other: naive animals
- Dose level:
- 88-206-01 (2.0%)
- No. with + reactions:
- 0
- Total no. in group:
- 4
- Reading:
- rechallenge
- Hours after challenge:
- 48
- Group:
- other: naive animals
- Dose level:
- 88-206-01 (2.0%)
- No. with + reactions:
- 0
- Total no. in group:
- 4
Any other information on results incl. tables
Animal no |
Sex |
24 hour scores |
|||
Site 1 |
Site 2 |
Site 3 |
Site 4 |
||
1 |
♂ |
0 |
3 |
3 |
0 |
2 |
♂ |
0 |
3 |
3 |
0 |
3 |
♀ |
0 |
3 |
3 |
0 |
4 |
♀ |
0 |
3 |
3 |
0 |
Site 2 = 10%
Site 3 = 25%
Site 4 = 100%
Animal no |
Sex |
24 hour scores |
|||
Site 1 |
Site 2 |
Site 3 |
Site 4 |
||
1 |
♂ |
0 |
0 |
0 |
0 |
2 |
♀ |
0 |
0 |
0 |
3 |
Site 2 = 2.5%
Site 3 = 5.0%
Site 4 = 7.5%
Challenge A positive response was elicited in the animals receiving the positive control article, 1-chloro-2,4 dinitrobenzene (DNCB). No responses were observed in the animals treated with 80% ETOH. No responses were observed in the naive group at 24 or 48 hours after challenge. Two positive responses were observed at 24 hours and three positive responses were observed at 48 hours after challenge in the experimental animals receiving the test article at a 2.0% concentration. Rechallenge Responses were observed in the naive animals at 24 and 48 hours after rechallenge. No positive responses were observed in the experimental animals at 24 or 48 hours after rechallenge.
Applicant's summary and conclusion
- Interpretation of results:
- other: Not sensitising according to EU CLP (EC 1272/2008 and its amendments).
- Conclusions:
- Based upon the observations made in the Delayed Contact Hypersensitivity Study, test article, induced, challenged and rechallenged at a 2.0% concentration did not cause delayed contact hypersensitivity in guinea pigs.
- Executive summary:
The sensitising potential of the test substance was tested according to OECD TG 406, GPMT test. In preliminary dose-range-finding studies to determine the highest non irritating dose, six animals (three males and three females) were each exposed to four concentrations of BB-206-01 (Neoproxen). Based upon the results of the dose-range-finding studies the dose chosen for induction, challenge and rechallenge was 2.0%.
In order to determine if the test article is capable of causing delayed contact hypersensitivity, BB-206-01 was dermally applied to twenty guinea pigs (ten males and ten females) for a total of three six-hour insult periods at a 2.0% concentration.
A positive control was also included: A group of five guinea pigs (three males and two females) was treated with 1-chloro-2, 4 dinitrobenzene (DNCB) at a 0.3% concentration for a total of three six-hour insult periods. An additional group of ten guinea pigs (five males and five females) was treated with vehicle (ethanol-80% [ETOH]) for a total of three six-hour insult periods.
Fourteen days after the last induction period, all animals were challenged at a naive site. A positive response was elicited in the animals receiving the positive control article, l-chloro-2, 4 dinitrobenzene (DNCB). No responses were observed in the animals treated with 80% ETOH. No responses were observed in the naive group at 24 or 48 hours after challenge. Two positive responses were observed at 24 hours and three positive responses were observed at 48 hours after challenge in the experimental animals receiving the test article at a 2.0% concentration.
The experimental animals were rechallenged seven days after challenge, with the test article at a 2.0% concentration. Four animals from the negative control group (2 males and 2 females) served as naive control animals for the rechallenge. Responses were observed in the naive control animals at 24 and 48 hours after rechallenge, being indicative for irritation. No positive responses were observed in the experimental animals at 24 or 48 hours after rechallenge.
Based upon the observations made in the Delayed Contact Hypersensitivity Study, test article, BB-206-01 (Neoproxen) induced, challenged and rechallenged at a 2.0% concentration did not cause delayed contact hypersensitivity in guinea pigs.
It can be argued that the concentration (2%) used for induction and challenge is quite low, though some slight irritation was observed during rechallange in the naive control group animals. Neoproxen as such does not contain skin sensitizing structural alerts as can be seen when running the OECD Toolbox and/or Derek Nexus. This further supports the non-skin sensitizing potential.
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.