Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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.
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: 928-729-8 | CAS number: 188416-20-8
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 21 July to 21 August 1998
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study run to a method comparable with current guidelines.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 998
- Report date:
- 1998
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- no
- GLP compliance:
- not specified
- Type of study:
- guinea pig maximisation test
Test material
- Reference substance name:
- 3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride
- EC Number:
- 928-729-8
- Cas Number:
- 188416-20-8
- Molecular formula:
- C16H13ClF3N5O.HCl
- IUPAC Name:
- 3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride
- Details on test material:
- Batch No.: 5ABJ002
Purity: 90%
Constituent 1
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- male
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Obtained from D. Hall, Newchurch, Staffs, UK.
- Age at study initiation: approximately four to seven weeks of age
- Weight at study initiation: 353 - 445g
- Housing: The guinea-pigs were housed in groups of five in suspended metal cages with wire mesh floors.
- Diet (e.g. ad libitum): A vitamin C enriched guinea-pig diet (Harlan Teklad 9600 FD2 SQC)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: five days days prior to the start of the main study
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16.5 to 29
- Humidity (%): 43 - 70
- Air changes (per hr): Air exchange was maintained at approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): Lighting was contorlled by means of a time switch to give 12 hours of artificial light (0700 - 1900 hours) in each 24 hours period.
IN-LIFE DATES: From: To:
Study design: in vivo (non-LLNA)
Inductionopen allclose all
- Route:
- intradermal and epicutaneous
- Vehicle:
- other: Alembicol D (A product of coconut oil)
- Concentration / amount:
- Induction interadermal injection- 2.5% w/v in Alembicol D
Induction topical application- 7.5% w/v in Alembicol D
Topical challenge- 7.5 and 3.75% w/v in Alembicol D
Challengeopen allclose all
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: Alembicol D (A product of coconut oil)
- Concentration / amount:
- Induction interadermal injection- 2.5% w/v in Alembicol D
Induction topical application- 7.5% w/v in Alembicol D
Topical challenge- 7.5 and 3.75% w/v in Alembicol D
- No. of animals per dose:
- 10 test animals
5 control animals - Details on study design:
- RANGE FINDING TESTS:
The intradermal and topical irritancy of a range of dilutions of the test substance was investigated to identify where possible (a) concentrations of the test substance that would produce irritation suitable for the induction phase of the main study and (b) a maximum non-irritant concentration by the topical route of adminstration for the challenge phase.
The animals for the topical irritancy investigations were pre-treated with an intradermal injection of Freund's complete adjuvant, 50:50 with water for irrigation (Ph.Eur.), approximately one week prior to the start of the preliminary investigations.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Once (injection) and once (topical)
- Exposure period: Single injection and topical 48 hours
- Test groups: 10 males for intradermal injections and topical application
- Control group: 5 males for intradermal injections and topical application
- Site: Scapular region
- Frequency of applications: Topical followed one week after injection
- Duration: 21 days
- Concentrations:
1. Intradermal injections
Control animals: 1) 0.1ml of Freund's complete adjuvant 50:50 with sterile water for irritation (Ph. Eur.). 2) 0.1ml of Alembicol D. 3) 0.1ml of Freund's complete adjuvant 50:50 with Alembicol D.
Test animals: 1) 0.1ml of Freund's complete adjuvant 50:50 with sterile water for injection (Ph.Eur.). 2) 0.1ml of the test substance, 2.5% v/v in Alembicol D. 3) 0.1ml of the test substance, 2.5% v/v in a 50:50 mixture of Alembicol D and Freund's complete adjuvant.
A volume of 0.1ml was injected into both the left and right injection sites.
2. Topical application
Control animals : Alembicol D
Test animals: The test substance, 7.5% w/v in Alembicol D
B. CHALLENGE EXPOSURE
- No. of exposures: Once
- Day(s) of challenge: Two weeks after the topical induction.
- Exposure period: 24 hours
- Test groups: 10 males
- Control group: 5 males
- Site: left flank
- Concentrations: The test substance, 7.5 and 3.75% w/v in Alembicol D.
- Evaluation (hr after challenge): The challenges sites were evalutaed 24 and 48 hours after removal of the patches.
OTHER: - Challenge controls:
- The control animals was challenged topically two weeks after the topical induction application using the same procedure for test animals but with vehicle control.
- Positive control substance(s):
- yes
- Remarks:
- Hexyl cinnamic aldehyde (HCA), Benzocaine and 2-mercaptobenzothiazole (MBT)
Results and discussion
- Positive control results:
- The MBT produced evidence of skin sensitisation (delayed contact hypersensitivity) in all of the ten animals.
In vivo (non-LLNA)
Resultsopen allclose all
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 7.5 and 3.75% w/v in Alembicol D
- No. with + reactions:
- 10
- Total no. in group:
- 10
- Clinical observations:
- Marked dermal reactions were seen in all ten test animals
- Remarks on result:
- other: see Remark
- Remarks:
- Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 7.5 and 3.75% w/v in Alembicol D. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Marked dermal reactions were seen in all ten test animals.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 7.5 and 3.75% w/v in Alembicol D
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Clinical observations:
- No reactions
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 7.5 and 3.75% w/v in Alembicol D. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No reactions.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 7.5 and 3.75% w/v in Alembicol D
- No. with + reactions:
- 10
- Total no. in group:
- 10
- Clinical observations:
- Marked dermal reactions were seen in all ten test animals
- Remarks on result:
- other: see Remark
- Remarks:
- Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 7.5 and 3.75% w/v in Alembicol D. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Marked dermal reactions were seen in all ten test animals.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 7.5 and 3.75% w/v in Alembicol D
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Clinical observations:
- No reactions
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 7.5 and 3.75% w/v in Alembicol D. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No reactions.
Any other information on results incl. tables
A few days after removal of the bandages from the induction topical application the entire site turn necrotic for most animals. This necrosis gradually resolved over the period of the study. No signs of ill health or toxicity were recorded.
Bodyweight increases were recorded for all guinea-pig over the period of the study.
Dermal reactions observed after the challenge application.
Freund's treated controls:
Guinea-pig number |
E= Erythema O= Oedema |
Score |
|||
24 Hours |
48 Hours |
||||
A |
P |
A |
P |
||
2940 |
E O |
0 0 |
0 0 |
0 0 |
0 0 |
2941 |
E O |
0 0 |
0 0 |
0 0 |
0 0 |
2942 |
E O |
0 0 |
0 0 |
0 0 |
0 0 |
2943 |
E O |
0 0 |
0 0 |
0 0 |
0 0 |
2944 |
E O |
0 0 |
0 0 |
0 0 |
0 0 |
A Anterior site, exposed to the substance, 7.5% w/v in Alembicol D
P Posterior site, exposed to the substance, 3.75% w/v in Alembicol D
Test animals:
Guinea-pig number |
E= Erythema O= Oedema |
Score |
Results Positive(+) Negtive(-) Inconclusive(±) |
|||
24 Hours |
48 Hours |
|||||
A |
P |
A |
P |
|||
2945 |
E O |
NP2 2 |
NE2 2 |
N 3 |
N 2 |
+ |
2946 |
E O |
NP2 2 |
2 2 |
N 3 |
2 1 |
+ |
2947 |
E O |
NE2 2 |
2 2 |
N 2 |
2 2 |
+ |
2948 |
E O |
2 2 |
2 2 |
2 2 |
2 1 |
+ |
2949 |
E O |
NP2 2 |
NE2 2 |
N 3 |
N 2 |
+ |
2950 |
E O |
NP2 2 |
NE2 2 |
N 2 |
NE2 2 |
+ |
2951 |
E O |
NP2 3 |
NP2 NE2 |
N 3 |
N 2 |
+ |
2952 |
E O |
NP2 2 |
2 2 |
NP2 2 |
2 1* |
+ |
2953 |
E O |
NE2 2 |
2 2 |
NE2 2 |
2 2* |
+ |
2954 |
E O |
NP2 2 |
2 2 |
N 2 |
Ø2 2 |
+ |
N Necrosis
NE Necrotic edge
NP Necrotic path
* Dryness and sloughing of the epidermis
Ø Thickening, dryness and slouging of the epidermis
A Anterior site, exposed to the substance, 7.5% w/v in Alembicol D
P Posterior site, exposed to the substance, 3.75% w/v in Alembicol D
Applicant's summary and conclusion
- Interpretation of results:
- sensitising
- Remarks:
- Migrated information
- Conclusions:
- The substance produced evidence of skin sensitization (delayed contact hypersensitivity) in all of ten test animals.
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.
