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Toxicological information

Skin sensitisation

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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:
2004

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
A reliable in vitro test with a Bühler protocol was already available, therefore no LLNA was performed.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): TP-90B Rubber Chemical
- Analytical purity: no data

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 4-5 weeks

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction: undiluted test item
Challenge: 75% of the test substance in sterile water
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction: undiluted test item
Challenge: 75% of the test substance in sterile water
No. of animals per dose:
Pretest: 5
Main study: control group - 10 females, test group 20 females
Details on study design:
Induction
On the day of dosing (days 1, 8, 15), the hair was clipped from the left flank of each animal. Animals of the test group were treated with the undiluted test item. A gauze patch measuring 20 x 20 mm was covered with 0.4 mL of the test item and was placed onto the selected skin site. This was secured in position by encircling the trunk of the animal with a length of adhesive strapping. All animals of the test group were treated with the test item in this manner and animals of the control group were similarly treated with the selected vehicle (sterile water).


Challenge
On day 29, 0.4 mL aliquot of the test item at 75% concentration in sterile water was spread evenly over an absorbent patch measuring approximately 20 x 20 mm. This was placed onto the skin of the posterior region of the prepared site on the right flank. A similar patch, this containing 0.4 mL of the vehicle selected for the challenge (sterile water) was placed onto the anterior region of the prepared site. The patches were secured in position by encircling the trunk of the animal with a length of adhesive strapping. All animals of both the test and control groups were treated with both the test item and vehicle in this manner.

After an exposure period of 6 hours (induction and challenge) the dressings were removed and the treated sites cleaned of remaining test item by washing with warm water.


Evaluation
Approximately 24 and 48 hours after removal of the patches, the treated sites were examined for signs of reaction to treatment. Each site was assessed and scored using the following scale:

0 = No reaction
± = Slight, patchy erythema (barely perceptible or questionable)
1 = Slight, but confluent or moderate but patchy erythema
2 = Moderate erythema
3 = Severe erythema with or without edema

The test is considered positive if 15% or more animals in the test group exhibited erythema or dermal swelling following challenge with a non-irritant concentration of the test item.


Protocol deviations
During the challenge phase, the clipping procedure to be undertaken approximately 3 hours prior to evaluation of skin reaction was not performed due to oversight.
Positive control substance(s):
yes
Remarks:
a-hexylcinnamaldehyde

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
75%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
75%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

Pretest 

A slight, patchy erythema was observed in 1 animal at the site treated with the undiluted test item. No reaction was apparent in the remaining animals at any of the 10 concentrations investigated, suggesting that the test item at a concentration of 100% was reasonably tolerated. This concentration was selected for use during the induction phases of the main study. A concentration of 75% in sterile water was selected for use at challenge, being judged non-irritant.

 

Induction

No response was seen to either the test item or the vehicle alone in animals of the test and control groups following 6 hours topical exposure.  

 

Challenge

No response was observed to the test item in either test or control group animals 24 and 48 hours following 6 hours topical exposure. No reaction was observed to the vehicle alone.  

Applicant's summary and conclusion