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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: Study conducted under GLP conditions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
other: EC Council Directive 6/548/EEC, last ammended by Commission Directive 96/54EC 1996)
Deviations:
no
Qualifier:
according to
Guideline:
other: "Allergic Contact Dermatitis in the Guinea-Pig: Identification of Contact Allergens" Magnusson B, Kligman, A.M. (1970).
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An adequate Guinea Pig Maximization Test (GPMT) was conducted on the test substance prior to the requirement for LLNA or in vitro methods.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report:T-7600
- Composition of test material, percentage of components:> 97% 2-Propenoic acid, 2-[Methyl[(nonafluorobutyl)sulfonyl]amino]ethyl ester, <2% Water, < 0.01% Phenothiazine
- Lot/batch no.: Lot 1
- Expiration date of the lot/batch: 06 August 2002
- Stability under test conditions:Not indicated
- Storage condition of test material: At room temperature in the dark.

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Dunkin-Hartley, albino
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: approx. 6 weeks old.
- Weight at study initiation: 375-451 grams
- Housing: group housing of 5 animals per metal gave with wire-mesh floors.
- Diet (e.g. ad libitum): ad libitum (diet included 1000 mg/kg ascorbic acid)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 3 degrees C
- Humidity (%): 30-70 degrees C
- Air changes (per hr): 15

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
other: intradermal and epidermal (semiocclusively wrapped)
Vehicle:
corn oil
Concentration / amount:
50% test article and the vehicle (0.1 ml each)
Challengeopen allclose all
Route:
other: epidermal
Vehicle:
corn oil
Concentration / amount:
50% test article and the vehicle (0.1 ml each)
No. of animals per dose:
48 hour exposure epidermal exposure period during induction phase, 24 hours during challenge phase on Day 22.
Details on study design:
RANGE FINDING TESTS: 100%, 50%, 20%. 10%, 5%, 2% and 1% test article concentrations were used in the preliminary irritation study to determine what concentration should be used in the main study. This test was conducted identically to the main study, but some animals were from the Himalayan strain (4 to 9 weeks of age). Intradermal injections and epidermal applications were also used.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 6 (3 pairs of intradermal injections)
- Exposure period: 48 hours (epidermal exposure)
- Test groups: 1 test group (n=10 animals)
- Control group: treated as descrbed for the experimental animals except that the vehicle alone was administered. (n=5 animals)
- Site: scapular region (injections on each side of the midline and from cranial to caudal).
- Frequency of applications: single injections, single epidermal application.
- Duration:
- Concentrations: Intradermal injections concentrations consisted of 1 ml/site injections of A) 1:1 w/w mixture of Freunds' Complete Adjuvant with water B) 2% concentration of the test substance C) A 1:1 w/w mixture of the test substance, at twice the concentration used in B) and Freunds' Complete Adjuvant. 0.5 ml of a 50% test article concentration was used for the epidermal exposure.
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: The start of the challenge was on Day 22
- Exposure period: 24 hours
- Test groups: 1 test group (n=10)
- Control group: 1 control group (n=5)
- Site: scapular
- Concentrations:50% test substance (0.1 ml).
- Evaluation (hr after challenge):24 and 48 hours after removal of dressing.
OTHER: On day 8 of the induction exposure, the area of the injection sites were treated with 10% sodium-dodecyl-sulfate in vaseline.
Challenge controls:
no data
Positive control substance(s):
yes
Remarks:
Alpha-hexylcinnamic aldehyde

Results and discussion

Positive control results:
The test system is an appropriate model for sensistization.

In vivo (non-LLNA)

Results
Reading:
1st reading
Hours after challenge:
24
Group:
test group
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
See section "Any other information on results"
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: See section "Any other information on results".

Any other information on results incl. tables

"Clinical section" from section "Results and discussion".

Challenge readings were made 24 and 48 hours after the exposure period. No mortality occured during the study and body weights and body weight gain remained in the same range as controls over the study period. No edema or necrosis was observed in any of the animals.The positive reactions observed were erythema, which was observed in all test substance treated animals in the induction and challenge phases. Observations in the challenge readings indicate scaliness in 6 test animals and sensitisation in all ten test animals. The reactions observed after the epidermal induction exposure was enhanced by SDS treatment. Skin reactions varying between grades 1 and 3 were observed in all experiemental animals in response to 50% test substance concentrations in the challenge phase.

Table 1: Erythema Scores from Induction Reading(necrosis and edema scores all 0)

Treated Animal #

Intradermal Injection (1:1 FCA and water)

Intradermal Injection (2% test article)

Intradermal Injection (1:1 mixture of FCA and a 4%)

 Intradermal Injection (50% test article)

456

3

2

3

3

457

3

2

3

3

458

2

1

2

3

459

3

2

2

3

460

3

1

2

3

461

3

2

2

3

462

3

2

3

3

463

3

1

2

3

464

3

2

3

3

465

3

2

3

3

 

Table 2: Challenge Readings(all vehicle scores are 0)

Treated Animal #

Day 24: 50% test article conc.

Day 25: 50% test article conc.

456

3

2

457

3

2 (scaliness)

458

3

2 (scaliness)

459

1

1

460

2

1

461

1

1 (scaliness)

462

2

2 (scaliness)

463

2

0 (scaliness)

464

3

2

465

1

1

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The skin reactions observed in response to a 50% test substance concentration in all of the ten experimental animals in the challenge phase were considered indicative of sensitization (sensitization rate of 100%), based on the absence of any response in control animals. According to the EC criteria for classification and labelling requirements 2nd ATP of the CLP regulation, the test substance should be classified as Skin Sens. Cat 1B.
Executive summary:

The contact hypersensitivity potential of T-7600, C4 -Acrylate, in the Albino Guinea Pig (Maximisation Test) was assessed in Dunkin Hartley Guinea Pigs. This study was based on the guidelines described in OECD No. 406., EC Commission Directive 96/54/EC, EPA OPPTS 870.2600. The test substance concentrations used in the main study were based on the results of a preliminary study. In the main study, ten experimental animals were intradermally injected with a 2% concentration and epidermally exposed to a 50% concentrations of the test article. Five control animals were similarly treated, but with the vehicle alone (corn oil). Approximately 24 hours before the epidermal induction exposure all animals were treated with 10% SDS. Two weeks after the epidermal application all animals were challenged with a 50% test substance concentration and the vehicle. In the challenge phase, skin reactions varied between grades 1 and 3 were observed in all experimental animals in response to the 50% test substance concentration. No skin reactions were evident in the control animals. Scaliness was seen in some treated skin sites among the experimental animals. The skin reactions observed in response to a 50% test substance concentration in all ten experimental animals in the challenge phase were considered indicative of sensitization (sensitization rate of 100 %).

According to the EC criteria for classification and labelling requirements 2nd ATP of the CLP regulation, the test substance should be classified as Skin Sens. Cat 1B.