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EC number: 692-762-1 | CAS number: 166524-65-8
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation, other
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Study period:
- 16 April 1997 to 18 July 1997
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 997
- Report date:
- 1997
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 81-6 (Skin Sensitisation)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Japanese MAFF Testing Guideline 59 NohSan No. 4200
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- Buehler test
- Justification for non-LLNA method:
- Available method
Test material
- Reference substance name:
- Automatically generated during migration to IUCLID 6, no data available
- IUPAC Name:
- Automatically generated during migration to IUCLID 6, no data available
- Test material form:
- liquid: viscous
- Details on test material:
- - Name of test material (as cited in study report): 2-ethoxy-4,6-difluoropyrimidine (DFEP) tar bottoms
- Appearance: dark brown, viscous liquid
- Storage condition of test material: room temperature
Constituent 1
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- Hartley
- Sex:
- male
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Strain: Crl:(HA)BR
- Age at study initiation: 4 - 9 weeks
- Weight at study initiation: 380 - 619 g
- Housing: individually housed in suspended, screen-bottom stainless steel cages
- Diet: Certified Guinea Pig Diet ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 26 °C
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light
IN-LIFE DATES: From 23 April 1997 to 18 July 1997
Results and discussion
- Positive control results:
- Not available.
In vitro / in chemico
Results
- Parameter:
- other: Not setermined
In vivo (non-LLNA)
Results
- Reading:
- other: Not determined
In vivo (LLNA)
Results
- Parameter:
- other: Not determined
Any other information on results incl. tables
Table 1: Individual Dermal Reactions - Definitive Study
Animal no. |
Induction Phase |
Challenge application |
||||||||||
Dose 1 (20 % w/v)* |
Dose 2 (20 % w/v)* |
Dose 3 (20 % w/v)* |
Initial (5 % w/v)* |
Second (5 % w/v)* |
Second (vehicle) |
|||||||
24 h |
48 h |
24 h |
48 h |
24 h |
48 h |
24 h |
48 h |
24 h |
48 h |
24 h |
48 h |
|
Test Group |
||||||||||||
1 |
0.5 |
0.0 |
0.5 |
1.0 |
2.0 |
2.0 |
0.0 |
0.5 |
0.5 |
0.5 |
0.0 |
0.0 |
2 |
0.5 |
0.5 |
1.0 |
2.0 b |
2.0 b |
2.0 b |
0.5 |
0.5 |
1.0 |
0.5 |
0.0 |
0.0 |
3 |
0.5 |
0.5 |
2.0 |
2.0 b |
2.0 a |
3.0 a |
0.5 |
0.5 |
2.0 |
1.0 |
0.0 |
0.0 |
4 |
0.5 |
0.5 |
2.0 b |
2.0 b |
2.0 |
2.0 b |
0.5 |
0.5 |
2.0 |
1.0 |
0.0 |
0.0 |
5 |
0.5 |
0.0 |
2.0 b |
2.0 b,f |
3.0 a |
3.0 a |
0.0 |
0.5 |
0.5 |
0.5 |
0.0 |
0.0 |
6 |
0.5 |
0.5 |
2.0 b |
2.0 b |
2.0 b |
2.0 b |
0.0 |
1.0 |
1.0 |
0.5 |
0.0 |
0.0 |
7 |
0.5 |
0.5 |
2.0 b |
2.0 b |
2.0 b |
2.0 b |
0.0 |
0.5 |
0.5 |
0.5 |
0.0 |
0.0 |
8 |
0.5 |
0.0 |
1.0 |
1.0 |
1.0 |
1.0 |
0.0 |
0.0 |
0.5 |
0.0 |
0.0 |
0.0 |
9 |
0.5 |
0.0 |
2.0 a,b |
2.0 b,f |
2.0 b |
2.0 b |
0.0 |
0.0 |
0.5 |
0.5 |
0.0 |
0.0 |
10 |
0.0 |
0.0 |
1.0 |
1.0 |
2.0 b |
2.0 b |
0.5 |
0.5 |
0.5 |
0.5 |
0.0 |
0.0 |
11 |
0.0 |
0.0 |
2.0 |
2.0 |
2.0 |
2.0 b |
0.0 |
0.0 |
0.5 |
0.0 |
0.0 |
0.0 |
12 |
0.5 |
0.5 |
1.0 |
2.0 b |
2.0 b |
2.0 b |
0.0 |
0.0 |
2.0 |
1.0 |
0.0 |
0.0 |
13 |
0.5 |
0.5 |
2.0 b |
2.0 a,b |
2.0 b |
2.0 b |
0.5 |
0.5 |
3.0 |
2.0 |
0.0 |
0.0 |
14 |
0.0 |
0.0 |
2.0 b |
2.0 |
2.0 a,b |
3.0 a,b |
0.5 |
1.0 |
1.0 |
1.0 |
0.0 |
0.0 |
15 |
0.5 |
0.5 |
2.0 b |
2.0 b |
2.0 a,b |
2.0 a,b |
0.0 |
0.0 |
1.0 |
0.5 |
0.0 |
0.0 |
16 |
0.5 |
0.5 |
1.0 |
1.0 |
3.0 |
3.0 |
0.5 |
0.0 |
1.0 |
0.5 |
0.0 |
0.0 |
17 |
0.5 |
0.0 |
0.5 |
1.0 |
2.0 |
2.0 |
0.0 |
0.0 |
0.5 |
0.5 |
0.0 |
0.0 |
18 |
0.5 |
0.5 |
2.0 b |
2.0 b |
3.0 a,b |
3.0 a,b |
0.0 |
0.0 |
1.0 |
1.0 |
0.0 |
0.0 |
19 |
0.5 |
0.5 |
2.0 b |
2.0 b |
2.0 a,b |
2.0 a,b |
0.5 |
0.5 |
2.0 |
2.0 |
0.0 |
0.0 |
20 |
0.5 |
0.0 |
2.0 b |
2.0 b |
2.0 b |
2.0 b |
0.5 |
0.5 |
1.0 |
0.5 |
0.0 |
0.0 |
Naïve Control Group |
||||||||||||
1C |
0.5 |
0.0 |
||||||||||
2C |
0.0 |
0.0 |
||||||||||
3C |
0.0 |
0.0 |
||||||||||
4C |
0.0 |
0.0 |
||||||||||
5C |
0.0 |
0.0 |
||||||||||
6C |
0.5 |
0.0 |
||||||||||
7C |
0.0 |
0.0 |
||||||||||
8C |
0.0 |
0.0 |
||||||||||
9C |
0.0 |
0.0 |
||||||||||
10C |
0.0 |
0.0 |
||||||||||
Additional Naïve Control Group |
||||||||||||
11C |
0.0 |
0.0 |
0.0 |
0.0 |
||||||||
12C |
0.0 |
0.0 |
0.0 |
0.0 |
||||||||
13C |
0.0 |
0.0 |
0.0 |
0.0 |
||||||||
14C |
0.5 |
0.0 |
0.0 |
0.0 |
||||||||
15C |
0.5 |
0.0 |
0.0 |
0.0 |
||||||||
* concentration of test material in bis-2-methoxyethyl ether (vehicle)
a = subcutaneous haemorrhaging
b = blanching
f = fissuring
Definitive Study Results
- Clinical Observations and Body Weights
All animals appeared normal and exhibited body weight gain throughout the study with the exception of 4 test animals which exhibited nonformed faeces at various times during the study and one of these four test animals which exhibited few faeces on Days 21 and 22. Two of the additional naïve control animals exhibited insignificant weight losses of 4 and 5 g between days 42 and 44. These findings were not considered to be treatment-related.
- Dermal Reactions to the Test Material
Faint to strong erythema reactions were elicited from all 20 test animals to the test material as a 20 % w/v mixture in bis-2-methoxyethyl ether during the induction phase of the study. Subcutaneous haemorrhaging, blanching and fissuring were also observed within the test sites of 16 test animals during the induction phase.
Very faint to faint erythema reactions (scores of 0.5 to 1.0) were elicited from 13 of the 20 animals in the test group following the initial challenge application of the test material as a 5 % w/v mixture in bis-2-methoxyethyl ether. Very faint erythema reactions (scores of 0.5) were seen in two of the 10 animals in the initial naïve control group following the initial challenge application of the test material as a 5 % w/v mixture in bis-2-methoxyethyl ether. Two of the reactions in the test group exceeded the highest naïve reaction.
Very faint to strong erythema reactions (scores of 0.5 to 3.0) were elicited from all 20 test animals while very slight erythema reactions (scores of 0.5) were seen in two of the five additional naïve control animals when the test material was applied as a 5 % w/v mixture in bis-2-methoxyethyl ether at the second challenge application. No dermal reactions were observed in the test sites receiving the vehicle alone at the second challenge application. Twelve of the reactions in the test group exceeded the highest naïve control reaction during the second challenge phase of the study.
Applicant's summary and conclusion
- Interpretation of results:
- sensitising
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of the study the test material was considered to be a dermal sensitiser.
- Executive summary:
The test material was evaluated for delayed contact hypersensitivity potential using the Buehler methodology in albino guinea pigs in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 406, EU Method B.6, EPA OPP 81-6 and the Japanese MAFF Testing Guideline 59 NohSan No. 4200.
During the study, 20 male Hartley albino guinea pigs received one application of 0.4 mL test material as a 20 % w/v mixture in bis-2-methoxyethyl ether per week, for three weeks, during the induction period. The condition of the test sites was assessed approximately 24 and 48 hours after the application. Two weeks following the administration of the third induction dose, a challenge dose of 0.4 mL test material as a 5 % w/v mixture in bis-2-methoxyethyl ether was administered to the test group animals. At this time, 10 naïve control animals were also treated in the same manner with a challenge application of test material. To further examine the sensitisation potential of the test material, a second challenge dose was conducted two weeks after the initial challenge application. A new naïve site was selected on each animal in the test group. In addition, five new naïve control animals were selected.
Faint to strong erythema reactions were elicited from all 20 test animals to the test material as a 20 % w/v mixture in bis-2-methoxyethyl ether during the induction phase of the study. Subcutaneous haemorrhaging, blanching and fissuring were also observed within the test sites of 16 test animals during the induction phase. Very faint to faint erythema reactions were elicited from 13 of the 20 animals in the test group following the initial challenge application of the test material. Very faint erythema reactions were seen in two of the 10 animals in the initial naïve control group following the initial challenge application. Two of the reactions in the test group exceeded the highest naïve reaction.
Very faint to strong erythema reactions were elicited from all 20 test animals while very slight erythema reactions were seen in two of the five additional naïve control animals when the test material was applied at the second challenge. No dermal reactions were observed in the test sites receiving the vehicle alone at the second challenge application. Twelve of the reactions in the test group exceeded the highest naïve control reaction during the second challenge phase of the study.
Therefore, under the conditions of the study, the test material did cause delayed contact hypersensitivity in guinea pigs and can be considered a dermal sensitiser.
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