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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: The sensitization potential was evaluated according to the procedure provided by Imperial Chemical Industries Ltd, after the ear/flank method of Stevens (1967)
Version / remarks:
(Stevens MA, 1967. Use of the albino Guinea pig to detect the skin sensitizing ability of chemicals. Brit. J. Ind. Med. 24:189-202)
Deviations:
not specified
Principles of method if other than guideline:
Induction: Approximately 0.1 ml per ear per day of test substance in a suitable solvent was applied daily to the outer surface of the ears with a glass Pasteur pipette, of six of the group of 10 Guinea pigs on Days 0, 1 and 2. The other 4 animals acted as controls and remained untreated.

Challenge: Immediately before the challenge applications on Day 7, an area approximately of 110 x 50 mm on each flank of all test animals was clipped free of hair. The challenge application was then carried out over a range of 3 concentrations of test substance in a logarithmic series. The dilutions followed sequentially down the series, including the induction concentration which was the highest level, i.e. 10, 1 and 0.1% in dimethylformamide (DMF). Approximately 0.2 ml of each solution was applied, again with a glass Pasteur pipette, to separate 10 mm diameter circular areas. Each concentration was applied to both flanks of all 10 Guinea pigs with the highest concentration posterior to the next lower concentration. On Day 8, any erythema present at the challenge sites was rated on a 5 point scale. Only erythematous responses displayed by the pre-treated (test) animals in excess of that displayed by the controls was considered to denote sensitization. That present in the controls was deemed simple primary irritation.
GLP compliance:
no
Type of study:
other: Guinea pig ear/flank method of Stevens (1967)
Justification for non-LLNA method:
The study was conducted before the requirements for LLNA were published.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: granular

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Tuck, Rayleigh, Essex, UK
- Females (if applicable) nulliparous and non-pregnant: [not specified]
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 250-350 g
- Housing: Plastic-coated metal cages, 60 x 90 x 25 cm
- Diet (e.g. ad libitum): Labsure RGP pellet
- Water (e.g. ad libitum): yes
- Acclimation period: at least 6 days
- Indication of any skin lesions: none

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 2°C
- Humidity (%): 50 +/- 10 R.H.
- Photoperiod (hrs dark / hrs light): 12:12

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, open
Vehicle:
not specified
Concentration / amount:
0.1 ml
Day(s)/duration:
3
Adequacy of induction:
not specified
Challenge
No.:
#6
Route:
epicutaneous, open
Vehicle:
N,N-dimethylformamide
Concentration / amount:
10, 1 and 0.1%
Day(s)/duration:
1
Adequacy of challenge:
not specified
No. of animals per dose:
4 controls
6 test animals
Details on study design:
INDUCTION
Approximately 0.1 ml per ear per day of test substance in a suitable solvent was applied daily to the outer surface of the ears with a glass Pasteur pipette, of six of the group of 10 Guinea pigs on Days 0, 1 and 2. The other 4 animals acted as controls and remained untreated.

CHALLENGE
Immediately before the challenge applications on Day 7, an area approximately of 110 x 50 mm on each flank of all test animals was clipped free of hair. The challenge application was then carried out over a range of 3 concentrations of test substance in a logarithmic series. The dilutions followed sequentially down the series, including the induction concentration which was the highest level, i.e. 10, 1 and 0.1% in dimethylformamide (DMF). Approximately 0.2 ml of each solution was applied, again with a glass Pasteur pipette, to separate 10 mm diameter circular areas. Each concentration was applied to both flanks of all 10 Guinea pigs with the highest concentration posterior to the next lower concentration. On Day 8, any erythema present at the challenge sites was rated on a 5 point scale. Only erythematous responses displayed by the pre-treated (test) animals in excess of that displayed by the controls was considered to denote sensitization. That present in the controls was deemed simple primary irritation. Bodyweight and clinical signs were recorded regularly.
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Results
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10, 1 and 0.1%
No. with + reactions:
0
Total no. in group:
6
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the test substance was considered not to be sensitizing to Guinea pig.
Executive summary:

A study was conducted to determine the skin sensitisation potential of the test substance (in the form of blue grains, purity not given) according to the procedure provided by Imperial Chemical Industries Ltd, after the ear/flank method of Stevens (1967) (Brit. J. Ind. Med. 24:189-202). In the induction phase, approximately 0.1 ml per ear per day of test substance in a suitable solvent was applied daily with a glass Pasteur pipette to the outer ear surface of six female Dunkin Hartley Guinea pigs on Days 0, 1 and 2. A further 4 animals acted as controls and remained untreated. Immediately before the challenge applications on Day 7, an area approximately of 110 x 50 mm on each flank of all test animals was clipped free of hair. The challenge application was then carried out over a range of 3 concentrations of test substance in a logarithmic series. The dilutions followed sequentially down the series, including the induction concentration which was the highest level, i.e. 10, 1 and 0.1% in dimethylformamide (DMF). Approximately 0.2 ml of each solution was applied, again with a glass Pasteur pipette, to separate 10 mm diameter circular areas. Each concentration was applied to both flanks of all 10 Guinea pigs with the highest concentration posterior to the next lower concentration. On Day 8, any erythema present at the challenge sites was rated on a 5 point scale. Only erythematous responses displayed by the pre-treated (test) animals in excess of that displayed by the controls was considered to denote sensitization. That present in the controls was deemed simple primary irritation. Bodyweight and clinical signs were recorded regularly. No responses were provoked in any of the animals at any of the test concentrations. Animals showed normal bodyweight changes throughout the study and remained in good health. Under the study conditions, the test substance was considered not to be sensitizing to Guinea pig (Lightowler, 1978).