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Diss Factsheets

Administrative data

Description of key information

A reliable guinea pig maximisation test is available conducted in accordance with OECD 406 and GLP. No data is available to assess respiratory sensitisation.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The test was conducted in 1995 which is prior to the OECD 429 study being available as an acceptable test guideline.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D Hall Ltd, Burton on Trent, UK.
- Age at study initiation: Four to six weeks old
- Weight at study initiation: 400 to 500 g
- Housing: Up to 5 guinea pigs were accommodated in suspended polypropylene cages with open tops and stainless steel mesh fron panels.
- Diet (e.g. ad libitum): SQC FD1 (pelleted) diet was freely available to animals at all times.
- Water (e.g. ad libitum): Mains water was provided ad libitum.
- Acclimation period: At least 5 days
- Indication of any skin lesions: A veterinary inspection was performed prior to study commencement to ensure all animals were suitable for study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70% relative humidity
- Air changes (per hr): At least 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle
Route:
intradermal
Vehicle:
corn oil
Concentration / amount:
0.1 mL/site
0.5% m/v test substance (site: middle)
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
intradermal
Vehicle:
other: Freunds Complete Adjuvant
Concentration / amount:
0.1 mL/site
0.5% m/v test substance (site: posterior)
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
0.5 mL of 50% m/m test substance
Day(s)/duration:
Days 8, 9 and 10
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
40% m/m test substance
Day(s)/duration:
Day 23
Adequacy of challenge:
highest non-irritant concentration
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
20% m/m test substance
Day(s)/duration:
Day 23
Adequacy of challenge:
not specified
No. of animals per dose:
Test group: 20 male guinea pigs
Control group: 10 male guinea pigs
Details on study design:
RANGE FINDING TESTS:
Screening test for intradermal injection phase: The vehicle and 6 formulations were selected based on solubility trials. On Day 1, 0.1 mL/site of the test substance at concentrations ranging from 0.1 to 5% m/v in corn oil (the maximum practical dose) were applied. Dermal reactions were assessed 24 and 72 hours later.

Screening test for topical application phase: Four formulations incorporating from 5 to 50% m/m in petrolatum (the maximum practical concentration) were selected. Two guinea pigs were prepared by receiving two 0.1 mL intradermal injections of FCA emulsion fifteen days prior to the application of the test substance. The animals on Day 1 were subject to occluded topical exposure of the test substance of 0.2 mL of the test formulations. These patches were left on for 48 hours and then dermal reactions were assessed 24 and 96 hours after removal of the patches.

Screening test for the topical application at challenge: Four formulations were chosen to identify the maximum non-irritant concentration of test substance after topical occlusion. Three guinea pigs were prepared by receiving two 0.1 mL intradermal injections of FCA emulsion eleven days prior to application of the test formulations. Approximately 0.1 mL of the selected formulations was then applied and removed after 24 hours. Dermal reactions were assessed 24 and 48 hours after removal of the chambers.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 intradermal exposure and 1 topical application
- Exposure period:
Intradermal exposure: Occured on Day 1
Topical exposure: Occured on Day 8. The animals were occluded for 48 hours.
- Test groups:
Intradermal exposure (each animal at different positions): FCA emulsion alone, test substance 0.5% m/v in corn oil and test substance 0.5% m/v in FCA emulsion.
Topical exposure: 50% m/m test substance in petrolatum
- Control group:
Intradermal exposure (each animal at different positions): FCA emulsion alone, corn oil alone, 50% corn oil in FCA emulsion.
Topical exposure: Petrolatum alone
- Site: Anterior, middle and posterior for the intradermal injections. The dorsum was used for the topical applications.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 23
- Exposure period: 24 hours
- Test groups: 20 and 40% m/m test substance in petrolatum
- Control group: Petrolatum alone
- Site: Applied to the right flank
- Evaluation (hr after challenge): 24 and 48 hours after challenge

Challenge controls:
Petrolatum applied to left flank of each animal
Positive control substance(s):
yes
Remarks:
2-mercaptobenzothiazole (MBT)
Positive control results:
In the latest positive control study, 8/8 animals provided a positive reponse indicating the test system was working as expected.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
20% m/m in petrolatum
No. with + reactions:
7
Total no. in group:
20
Clinical observations:
None noted
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
20% m/m in petrolatum
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
None noted
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
40% m/m in petrolatum
No. with + reactions:
7
Total no. in group:
20
Clinical observations:
None noted
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
40% m/m in petrolatum
No. with + reactions:
7
Total no. in group:
20
Clinical observations:
None noted
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Control site (petrolatum)
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
None noted
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
Control site (petrolatum)
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
None noted
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
other: Positive control group not included on study but conducted seperately.

Clinical observations: 1 animal had very red ears on Day 25 but this had resolved by the following day. No other signs were noted.

Bodyweights: Bodyweight increases were recorded for all animals over the study duration.

Challenge response: A patchy erythematous response was apparent 24 and/or 48 hours after bandage removal at the control site of one control and 6 test animals. there were no dermal reactions seen in control animals at sites receiving the test item formulations. The changes at the sites of test substance application in seven of the test animals were more marked than those seen in the controls; patchy to moderate erythema was commonly accompanied by scabs , with desquamation also apparent in one animal . A further two animals showed inconclusive reactions to challenge.

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
The results from the challenge procedure indicated that 35% of the test animals gave a positive response to challenge with the substance indicative of delayed contact hypersensitivity.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The intradermal induction dose used on study was 0.5% m/v in corn oil. Classification as a skin sensitiser category 1B is warranted when > 30 to < 60% respond at > 0.1% to < 1% of the intradermal induction dose. In this case 35% of animals provided a positive response for sensitisation which means that classification as a skin sensitiser (1B) is warranted in accordance with the CLP Regulation (EC No. 1272/2008, as amended).