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Diss Factsheets

Administrative data

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:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1992)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test

Test material

Constituent 1
Chemical structure
Reference substance name:
Methylidynetri-p-phenylene triisocyanate
EC Number:
219-351-8
EC Name:
Methylidynetri-p-phenylene triisocyanate
Cas Number:
2422-91-5
Molecular formula:
C22H13N3O3
IUPAC Name:
1-[bis(4-isocyanatophenyl)methyl]-4-isocyanatobenzene

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Crl:HA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratory, Kißlegg, Germany
- Age at study initiation: approx. 3-4 weeeks
- Weight at study initiation: 268-344 g
- Diet and water: ad libitum
- Acclimation period: at least 7 days

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: methyl ethyl ketone (MEK); dried with a molecular sieve
Concentration / amount:
1st to 3rd induction: 100% test substance (undiluted
Challenge: 50% test substance (in MEK)
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: methyl ethyl ketone (MEK); dried with a molecular sieve
Concentration / amount:
1st to 3rd induction: 100% test substance (undiluted
Challenge: 50% test substance (in MEK)
No. of animals per dose:
experimental group: 20
control group: 10
Details on study design:
RANGE FINDING TESTS:
Range finding tests for induction were performed using 5 females.
- for induction: 0.5 ml of 0%, 25%, 50% and 100% of the test item in MEK were applied occlusively to the skin for 6 hours. 30 hours and 54 hours after the start of the application 3/5 and 2/5 animals showed skin reactions (grade 1).
Range finding tests for challenge were performed using 2 animals which were treated in the same manner als the control animals during induction.
- for challenge: 0.5 ml of 0%, 12%, 25% and 50% the test item in MEK were applied occlusively to the skin for 6 hours. No signs of irritation occured.

MAIN STUDY
A. INDUCTION EXPOSURE
- the animals were treated with the test item three times at intervals of seven days. The suitable areas of the body were shaved one day (24 hours) before each treatment. The volume applied per animal was 0.5 m on a hypoallergic patch and held in place on the skin with 'ORABAND' adhesive plaster. Six hours after treatment the patches were removed and any remaining test item was washed off the skin with physiological saline solution. Treatment areas were vusally assessed 30 hours after initiation of exposure.


B. CHALLENGE EXPOSURE
- Challenge: the animals were treated with the test item four weeks after the first (two weeks after the last) dermal induction. Backs and right flanks were shaved one day (24 hours) before challenge. The test item (50% in MEK) applied per animal was 0.5 m on a hypoallergic patch and held in place on the right flank with 'ORABAND' adhesive plaster. Six hours after treatment the patches were removed and any remaining test item was washed off the skin with physiological saline solution. 24 hours later the treatment areas were shorn.
Skin reactions were assessed 30 hours after initiation of the induction exposures, and 30 and 54 hours after the beginning of the challenge.

OTHER:
In addition to the skin reactions the following data were recorded: Mortality/ Clinical signs once daily; Body weights prior to start , on day 30 and at termination of the study.
Challenge controls:
As a control a patch loaded only with the vehicle was applied and fixed also to the right flank, cranial to the test item patch.
Positive control substance(s):
yes

Results and discussion

Positive control results:
Reliability check of Buehler test with alpha-hexylcinnamicaldehyde revealed a sensitization rate of 100% (test substance concentration 30% for induction and 20% for challenge in polyethylene glycol 400). In the control group 0% of the animals reacted.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: first challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
4
Total no. in group:
20
Remarks on result:
other: Reading: other: first challenge. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 4.0. Total no. in groups: 20.0.
Reading:
other: first challenge
Hours after challenge:
24
Group:
negative control
Dose level:
none
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: first challenge. . Hours after challenge: 24.0. Group: negative control. Dose level: none. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: first challenge
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
12
Total no. in group:
20
Remarks on result:
other: Reading: other: first challenge. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 12.0. Total no. in groups: 20.0.
Reading:
other: first challenge
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: first challenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Appearance and behaviour of the test item group were not different from the control group. One animal of the control group (animal no. 1) showed following clinical signs: from day 11 - 24 : difficulty in breathing from day 13 to 15: piloerection, pale One animal of the test item group (animal no. 30) showed following clinical signs: from day 12 - 26: difficulty in breathing from day 13 to 24: piloerection, pale By the end of the study the mean body weight of the treatment group animals was in the same range than that of the control group

Applicant's summary and conclusion

Executive summary:

A skin sensitization test according to OECD guideline 406 (Buehler Patch Test) was conducted on female guinea pigs with

Triphenylmethane-4,4',4''-triisocyanate (tested as a 27% solution in ethyl acetate)

The challenge with 50% test item formulation led to skin effects (grade 1 -2) in 12 of 20 animals (60%) in the test item group and to no skin effects in the control group. Under the conditions tested the test item exhibits a skin sensitization potential.