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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:
12 February 1986 to 21 March 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
patch test
Justification for non-LLNA method:
The guinea pig miximisation test is the recommended adjuvant test for predictive sensitisation according to the above guidelines.
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
Ten male Hartley-Albino Guinea Pigs
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
500 mg in 0.5 mL water
Route:
other: Not applicable
Vehicle:
water
Concentration / amount:
500 mg in 0.5 mL water
No. of animals per dose:
10
Details on study design:
The sensitizing potential of test substance was assessed in a multiple insult patch sensitization test in Hartley-Albino Guinea Pigs. Each group of ten male Guinea Pigs were treated with 500 mg test substance, which was moistened with water, or with 0.5 ml of a 0.05% ethanolic solution of 2,4-dinitrochlorobenzene (DNCB), which served as a positive control. The test compounds were applied to the left, shaved flank of the animals, covered by a gauze pad (ca. 16x28mm) , which was held in place by an adhesive dressing, and the animals were placed in restrainers for approximately six hours. After this period the dressings were removed. Test material was applied on days 1, 3, 6, 8, 10, 13, 15, 17, 20 and 22. The skin reactions were scored according to the Draize scheme approximately 24 hours after every application and also 48 hours after the applications on days 1 and 22.
On day 36 the animals were challenged as described above on the left flank and on a previously untreated site on the right rump. Skin reactions were scored 24 and 48 hours after the challenge.
Challenge controls:
Not applicable
Positive control substance(s):
yes
Remarks:
.05% ethanolic solution of 2,4-dinitrochlorobenzene (DNCB)
Positive control results:
See Table.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
500 mg in 0.5 ml water
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
dermal fissuring and eschar formation also observed at test sites
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 500 mg in 0.5 ml water. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: dermal fissuring and eschar formation also observed at test sites.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
500 mg in 0.5 ml water
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
eschar formation observed
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 500 mg in 0.5 ml water. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: eschar formation observed.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.5 ml DNCB
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
eschar formation observed
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.5 ml DNCB. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: eschar formation observed.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.5 ml DNCB
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
eschar formation observed
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.5 ml DNCB. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: eschar formation observed.
Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
All treated guinea pigs showed positive skin reactions to the test substance after challenge on day 36. No skin reactions were recorded 24 hours after the initial application of the test substance. It was concluded that the test substance was a potential skin sensitiser.
The reactions seen were similar to those in the positive control group, exposed to DNCB.
Executive summary:

The sensitising potential of the test substance was assessed in a multiple insult patch sensitization test in Hartley-Albino Guinea Pigs. Groups of of ten male guinea pigs were treated with 500 mg test substance, which was moistened with water, or with 0.5 mL of a 0.05% ethanolic solution of 2,4-dinitrochlorobenzene (DNCB), which served as a positive control. The test compounds were applied to the left, shaved flank of the animalson days 1, 3, 6, 8, 10, 13, 15, 17, 20 and 22. On day 36 the animals were challenged as described above on the left flank and on the previously untreated right rump. Skin reactions were scored 24 and 48 hours after the challenge.


All treated guinea pigs showed positive skin reactions to the test substance on the left flank and right rump after challenge on day 36. No skin reactions were recorded 24 hours after the initial application of benoxacor. It was concluded that the test substance was a potential skin sensitiser. The reactions seen were similar to those in the positive control group, exposed to DNCB.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Benoxacor has been tested in a study according to guideline EPA OPP 81-6 in guinea pigs (Lain, 1986). Ten male guinea pigs were treated with 500 mg benoxacor, which was moistened with 0.5 mL water. Ten further guinea pigs were treated with 2,4-dinitrochlorobenzene (DNCB), which served as a positive control. The test compounds were applied to the left flank for approximately six hours on test days 1, 3, 6, 8, 10, 13, 15, 17, 20, and 22. On test day 36 the animals were challenged by applying the test compounds to the left flank and the untreated right flank. Reactions on the right flank were assessed 24 and 48 hours after challenge. All 10 guinea pigs in the benoxacor group showed a positive reaction 24 and 48 hours after challenge. The 10 positive control animals also showed a positive response 24 and 48 hours after challenge with DNCB. Benoxacor was found to be a potential skin sensitiser.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The results from the guinea pig study indicate that the test substance is a potential skin sensitiser. The substance fulfils the criteria for classification as R43, May cause sensitisation by skin contact according to Directive 67/548/EEC Annex VI (as amended).

The results from the guinea pig study indicate that the test substance is a potential skin sensitiser. The substance fulfils the criteria for classification as Category 1 H317: May cause an allergic skin reaction according to Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.4.2.2, as amended by Regulation (EC) No. 286/2011.