Registration Dossier

Administrative data

Description of key information

Skin sensitisation: Based on the results of this study, the test material was considered to be a contact sensitizer in guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
Guinea Pig Maximisation Test (GPMT)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 October 1996 to 2 November 1996
Reliability:
1 (reliable without restriction)
Justification for type of information:
Data pre-dates requirements for in-vitro methods.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
Study data conducted prior to LLNA requirements.
Specific details on test material used for the study:
Sponsor's ID: CUVAN®826, Lot No.: 107-1
Physical Description: Clear gold liquid
Receipt Dates: January 10, 1996 and April18, 1996
Expiration Date: None provided
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Externally
- Age at study initiation: Young
- Weight at study initiation: Males: ranged from 393 to 777g and Females: ranged from 322 to 428g
- Housing: housed individually in suspended stainless steel cages
- Diet: PMI Certified Guinea Pig Chow #5026 (Purina Mills, Inc.) was provided ad libitum
- Water: ad libitum
- Acclimation period: A minimum of five days
- Indication of any skin lesions: The animals chosen for study use were arbitrarily selected from healthy stock animals to avoid potential bias. All animals received a detailed pretest observation prior to dosing.

ENVIRONMENTAL CONDITIONS
- Temperature and humidity: The animal room temperature and relative humidity ranges (62-72 °F and 43-72%, respectively) exceeded the preferred ranges (63-7 °F and 40-70%, respectively) but
did not affect the study outcome.
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12-hour light / 12-hour dark cycle
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
0.3 ml of 15% (w/v) test material
Day(s)/duration:
Treated once per week, for three consecutive weeks
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
5% (w/v)
Day(s)/duration:
Treated once / Following a 2-week rest period
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
2.5% and 1% (w/v)
Day(s)/duration:
Treated once / Following a 7-day rest period
Details on study design:
Following treatment application, the trunk of the animal was wrapped with elastic wrap to prevent removal of the treatment application. Approximately six hours after the treatment application, the elastic wrap and the treatment applications were removed. The test sites were wiped with gauze moistened in distilled water, followed by dry gauze, to remove test substance residue.
Challenge controls:
Following a two-week rest period, a challenge was performed whereby the 10 test animals and 10 naive challenge control guinea pigs (5/sex) were topically treated with 5% (w/v) test material in mineral oil. Following a seven-day rest period, a rechallenge was performed whereby the 10 test animals and 10 naive rechallenge control guinea pigs (5/sex) were topically treated with 2.5% and 1% (w/v) test material in mineral oil
Key result
Reading:
1st reading
Group:
test group
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
rechallenge
Group:
test group
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
other: historical data
Group:
positive control
Remarks on result:
positive indication of skin sensitisation

Following challenge with 5% test material , dermal scores of 1 to 2 (most with slight oedema) were noted in 9/10 test animals at the 24 hour scoring interval and in 6/10 test animals at the 48 hour scoring interval. Dermal reactions in the remaining test and all challenge control animals were limited to scores of 0. Group mean dermal scores were noted to be higher in the test animals as compared with the challenge control animals.

Following rechallenge with 2.5% (w/v) test material, dermal scores of 1 to 2 (one with slight oedema) were noted in 4/10 test animals at the 24 hour scoring interval and in 2/10 test animals at the 48 hour scoring interval. Dermal reactions in the remaining test and all rechallenge control animals were limited to scores of 0. Group mean dermal scores were noted to be higher in the test animals as compared with the rechallenge control animals.

Following rechallenge with 1% (w/v) test material, dermal scores of 1 were noted in 5/10 test animals at the 24 hour scoring interval and in 1/10 test animals at the 48 hour scoring interval. Dermal reactions in the remaining test and all rechallenge control animals were limited to scores of 0. Group mean dermal scores were noted to be higher in the test animals as compared with the rechallenge control animals.

The results of the 1-chloro-2,4-dinitrobenzene (DNCB) historical positive control study completed during the past six months in the laboratory demonstrated that the test design utilized would detect potential contact sensitizers.

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
Based on the results of this study, the test material was considered to be a contact sensitizer in guinea pigs.
Executive summary:

A study to determine the potential of the test material to be a skin sensitiser was performed in accordance to OECD guidelines, conducted with a modified Buehler design and according to GLP. The study has been given a Klimisch score of 1 and is considered to be a key study.

Guinea pigs (5/sex) were topically treated with 0.3 ml of 15% (w/v) test material in mineral oil, once per week, for three consecutive weeks. Following a two-week rest period, a challenge was performed whereby the 10 test animals and 10 naive challenge control guinea pigs (5/sex) were topically treated with 5% (w/v) test material in mineral oil. Following a seven-day rest period, a rechallenge was performed whereby the 10 test animals and 10 naive rechallenge control guinea pigs (5/sex) were topically treated with 2.5% and 1% (w/v) test material in mineral oil. Following treatment application, the trunk of the animal was wrapped with elastic wrap to prevent removal of the treatment application. Approximately six hours after the treatment application, the elastic wrap and the treatment applications were removed. The test sites were wiped with gauze moistened in distilled water, followed by dry gauze, to remove test substance residue. The test sites were graded for irritation at approximately 24 and 48 hours following induction, challenge, or rechallenge application using the Dermal Grading System. Challenge and rechallenge responses in the test animals were compared with those of the challenge and rechallenge control animals, respectively. The animals were observed for general health/mortality twice daily. All animals were euthanized following each animal's final scoring interval. No gross necropsy examinations were performed.

Evaluations: Following challenge with 5% test material, dermal scores of 1 to 2 (most with slight oedema) were noted in 9/10 test animals at the 24 hour scoring interval and in 6/10 test animals at the 48 hour scoring interval. Dermal reactions in the remaining test and all challenge control animals were limited to scores of 0. Group mean dermal scores were noted to be higher in the test animals as compared with the challenge control animals.

Following rechallenge with 2.5% (w/v) test material, dermal scores of 1 to 2 (one with slight oedema) were noted in 4/10 test animals at the 24 hour scoring interval and in 2/10 test animals at the 48 hour scoring interval. Dermal reactions in the remaining test and all rechallenge control animals were limited to scores of 0. Group mean dermal scores were noted to be higher in the test animals as compared with the rechallenge control animals.

Following rechallenge with 1% (w/v) test material, dermal scores of 1 were noted in 5/10 test animals at the 24 hour scoring interval and in 1/10 test animals at the 48 hour scoring interval. Dermal reactions in the remaining test and all rechallenge control animals were limited to scores of 0. Group mean dermal scores were noted to be higher in the test animals as compared with the rechallenge control animals.

The results of the 1-chloro-2,4-dinitrobenzene (DNCB) historical positive control study completed during the past six months in the laboratory demonstrated that the test design utilized would detect potential contact sensitizers.

Under the conditions of this study, the test material was considered to be a contact sensitizer in guinea pigs.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the results of this study, the test material was considered to be a contact sensitizer in guinea pigs.