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Description of key information

Skin Sensitisation

In a GLP compliant study in accordance with the standardised guideline EPA OPP 81-6, the test material was found not to be sensitising.

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
Study period:
03 September 1987 to 05 October 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study conducted prior to adoption of LLNA guideline by the OECD.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: yes
- Weight at study initiation: 337-436 g
- Housing: five animals per aluminium cage
- Diet: ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-21 °C
- Humidity: mean 56 %
- Photoperiod: 12 hours light/12 hours dark
Route:
other: intradermal and topical
Vehicle:
paraffin oil
Concentration / amount:
Intradermal: 0.10 mL at 2 % (w/v)
Day(s)/duration:
The topical application was applied 7 days after the intradermal injection for 48 hours.
Adequacy of induction:
highest technically applicable concentration used
No.:
#1
Route:
other: topical
Vehicle:
paraffin oil
Concentration / amount:
25 % (w/v)
Day(s)/duration:
Two weeks after the topical induction. The challenge was applied for 24 hours.
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Twenty
Details on study design:
RANGE FINDING TESTS:
A. INDUCTION EXPOSURE
- Injections were made in the shaved scapular region and topical application on the shaved flanks. Two animals were subjected to intradermal injections (10, 5, 2 and 1 % w/v) and a further two to topical application (25, 10, 5 and 2 % w/v). The injection sites were assessed for irritancy at 24, 48 and 72 hours after injection. The topical application was assessed for irritancy 24, 48 and 72 hours after patch removal.

B. CHALLENGE EXPOSURE
- Test material was applied to the shaved flanks of two animals for 24 hours at concentrations of 25 and 10 % w/v.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: two (injection; topical)
- Test groups: 20 animals
- Control group: 20 animals (treated with vehicle instead of test material)
- Site: 4 x 6 cm shaved area in scapular region
- Frequency of applications: six intradermal injections, three in a line each side of and parallel to mid-line in shaved region of (i) 0.1 mL Freund's Complete Adjuvant, (ii) 0.1 mL test material and (iii) 0.05 mL test material emulsified with 0.05 mL Freund's complete adjuvant.
- Exposure Period/Duration: six days after the injection phase, the injection site was shaved and wetted with 10 % SLS to provoke a mild inflammatory response. After 24 hours, filter paper with 10 % w/v test material was added to the pre-treated area of the animals and the patch given an occlusive covering and the dressing left in place for 48 hours.
- Concentrations: 2 % w/v (injection) - actual value 10 % w/v due to calculation error; 10 % w/v (topical)

B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: two weeks after topical induction
- Exposure period: 24 hours
- Test groups: 20 animals
- Control group: 20 animals (treated with vehicle instead of test substance)
- Site: 2 cm x 25 cm area on the left flank
- Concentrations: 25% w/v
- Evaluation (hr after challenge): 24 and 48 hours after removal of patch
Challenge controls:
Test material at 25 % w/v in paraffin oil administered to control group animals.
Positive control substance(s):
yes
Remarks:
2,4-dinitro-chlorobenzene (DNCB)
Positive control results:
- The sensitivity of the strain of guinea-pig was checked at 6 monthly intervals to a known sensitiser (2,4-dinitro-chlorobenzene (DNCB)).
- In the most recent positive control test 11/20 of the test group reacted positively to challenge with DNCB at a concentration of 0.1 % (w/v) in propylene glycol.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
DNCB 0.1% w/v
No. with + reactions:
11
Total no. in group:
20
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
20

None of the 20 test animals showed positive reactions of the challenge application. None of the 20 control animals showed a positive reaction to the vehicle application.

Body weight gains were within an acceptable range.

No clinical signs, other than skin reactions induced by treatment were noted.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the test, the test material was determined to be a non-sensitiser.
Executive summary:

In a GLP compliant study the sensitising potential of the test material was assessed in accordance with the standardised guideline EPA OPP 81-6 in guinea-pigs (guinea pig maximisation test).

Under the conditions of the test, the test material was found not to be sensitising.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The key study (Cuthbert and Carr, 1988) was performed in line with GLP and a standardised guideline with a sufficient level of detail to assess the quality of the study. The study was performed to a good standard and was assigned a reliability score of 1 using the principle for assessing data quality as set out in Klimisch (1997).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance is considered to be unclassified for skin sensitisation.