Registration Dossier

Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guideline
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.

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2-dichloro-1-[(3R)-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethan-1-one; 2,2-dichloro-1-[(3S)-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethan-1-one
EC Number:
619-372-6
Cas Number:
98730-04-2
Molecular formula:
C11H11Cl2NO2
IUPAC Name:
2,2-dichloro-1-[(3R)-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethan-1-one; 2,2-dichloro-1-[(3S)-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethan-1-one

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
Ten male Hartley-Albino Guinea Pigs

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
500 mg in 0.5 mL water
Challengeopen allclose all
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)

Results and discussion

Positive control results:
See Table.

In vivo (non-LLNA)

Resultsopen allclose all
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.

Applicant's summary and conclusion

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.