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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
Study period:
April, 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted in compliance with recognised guidelines.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
On one occasion, the animal room temperature range [67-75°F (19-24°C)] exceeded the preferred range [63-73°F (17-23°C)] during this study. This occurrence was considered to have had no adverse effect on the outcome of this study.
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
yes
Remarks:
On one occasion, the animal room temperature range [67-75°F (19-24°C)] exceeded the preferred range [63-73°F (17-23°C)] during this study. This occurrence was considered to have had no adverse effect on the outcome of this study.
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
See discussion of supporting LLNA results (Sanders, 2012)

Test material

Constituent 1
Chemical structure
Reference substance name:
Thiophene, tetrahydro-, 1,1-dioxide, 3-(C9-11-isoalkyloxy) derivs., C10-rich
EC Number:
800-172-4
Cas Number:
398141-87-2
Molecular formula:
Complex UVCB substance
IUPAC Name:
Thiophene, tetrahydro-, 1,1-dioxide, 3-(C9-11-isoalkyloxy) derivs., C10-rich
Test material form:
other: Clear pale yellow liquid
Details on test material:
- Physical state: Clear pale yellow liquid
- Lot No.: 252724-3
- Batch No.: 3
- Date of receipt: 01/16/2004
- Expiration date of the lot/batch: 01/09/2009
- Storage condition of test material: stored at room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Hartley-derived albino guinea pigs
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hartley-derived albino guinea pigs were received from Hilltop Lab Animals, Inc., Scottdale, Pennsylvania.
- Age at study initiation: male: ca 7 weeks; female: ca 8 weeks
- Weight at study initiation: male: 332-445 g; female: 310-385 g
- Housing: The animals were housed individually in suspended stainless steel cages
- Diet: PMI Certified Guinea Pig Chow #5026 (PMI Nutrition International) was provided ad libitum
- Water: Municipal tap water treated by reverse osmosis was available ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-24 °C
- Humidity: 35-64%
- Air changes: 10-15 air changes/hour
- Photoperiod: 12 h light / 12 h dark

IN-LIFE DATES: From: January 28, 2004; to: February 27, 2004

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
other: topical, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Range-finding test: 100 %

Main test:
Induction phase: 100 %
Challenge phase: 100 %
Challengeopen allclose all
Route:
other: topical, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Range-finding test: 100 %

Main test:
Induction phase: 100 %
Challenge phase: 100 %
No. of animals per dose:
- Range-finding test: 2 males and 2 females
- Main test: 10 males and 10 females for test group; 5 males and 5 females for challenge control
Details on study design:
RANGE FINDING TESTS:
- On Day 0, up to 4 closed chambers at 4 different concentrations of the test substance were prepared and a 0.3 mL dose of each concentration was applied to the clipped area of each topical range-finding animal. The chambers were applied to the clipped surface as quickly as possible. The trunk of the animal was wrapped with elastic wrap which was secured with adhesive tape to prevent removal of the chambers and the animal was returned to its cage.
- Approximately 6 hours after chamber application, the binding materials were removed. The test sites were then wiped 2 times with gauze moistened in deionized water, followed by dry gauze to remove test substance residue, and the animals were returned to their cages.


MAIN STUDY
A. INDUCTION EXPOSURE:
- No. of exposures: Three (Day 0, 7 and 14)
- Exposure period: 6 hours
- Test groups: 0.3 ml of the test substance was placed on a 25 mm Hilltop chamber backed by adhesive tape (occlusive patch).
- Control group: None
- Site: Left side of test animals
- Frequency of applications: Once
- Duration: on Day 0, 7 and 14
- Concentrations: 100 %
- Evaluation (hr after induction): 24 and 48 hours

B. CHALLENGE EXPOSURE:
- No. of exposures: One
- Day(s) of challenge: Day 28
- Exposure period: 6 hours
- Test groups: 0.3 mL dose of the appropriate test substance was placed on a 25 mm Hilltop chamber backed by adhesive tape (occlusive patch).
- Control group: 0.3 mL dose of the appropriate test substance was placed on a 25 mm Hilltop chamber backed by adhesive tape (occlusive patch).
- Site: Right side of test animals
- Concentrations: 100 %
- Evaluation (hr after challenge): 24 and 48 hours


OTHER:
- Mortality/moribundity checks: Any unusual observations were recorded. The animals were observed for general health/mortality twice daily, once in the morning and once in the afternoon
- Dermal Observations: The test sites were graded for irritation at approximately 24 and 48 hours following chamber application (induction) or chamber removal (challenge) using the Dermal Grading System
- Body Weights: Individual body weights were obtained for all sensitization study animals on the day prior to the first induction (day -1) and for the appropriate test and challenge control animals on the day prior to challenge dosing
- Scheduled Euthanasia: Each sensitization study animal was euthanized by carbon dioxide inhalation following its final scoring interval. Gross necropsy examinations were not required for these animals
Challenge controls:
10 previously untreated (naive) challenge control guinea pigs were topically treated with 100 % test material
Positive control substance(s):
yes
Remarks:
HCA (Study no. 999.201)

Results and discussion

Positive control results:
Study No. 999.201, an HCA positive control study, demonstrated that a valid test was performed and indicated that the test design would detect potential contact sensitizers.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100 % induction and 100 % challenge application
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: 100 % induction and 100 % challenge application . No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100 % induction and 100 % challenge application
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: 100 % induction and 100 % challenge application . No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

Table 7.4.1/1: Individual challenge data

 

    Dermal Score  
  ANIMAL NO./ SEX 24h 48h
Test Group G7378/M 0 0
   G7379/M 0 0
  G7380/M 0 0
  G7381 /M ± 0
  G7382/M ± 0
  G7383/M ± ±
  G7384/M 0 0
  G7385/M 0 0
  G7386/M ± 0
  G7387/M ± 0
       
  G7505/F 0 0
  G7506/F 0 0
  G7507/F 0 0
  G7508/F ± 0
  G7509/F 0 0
  G7510/F ± 0
  G7511 IF 0 0
  G751 2/F ± 0
  G7513/F ± 0
  G7514/F ± 0
       
       
Challenge Control G7388/M  0 0
  G7389/M 0 0
  G7390/M  0 0
  G7391 /M  0 0
  G7392/M  0 0
       
  G7515/F  ± 0
  G7516/F  0 0
  G7517/F  0 0
  G7518/F  0 0
  G7519/F 0 0

For purposes of calculation, ± = 0.5;

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is not sensitizing under these test conditions.
Executive summary:

Test Guidance

In a Guinea Pigs-Modified Buehler test performed according to OECD Guideline 406 and in compliance with GLP.

The dermal sensitization potential of the test material was evaluated in Hartley-derived albino guinea pigs. Ten male and ten female guinea pigs were topically treated with 100% test material, once per week, for three consecutive weeks. Following a two-week rest period, a challenge was performed whereby the 20 test and 10 previously untreated (naive) challenge control guinea pigs were topically treated with 100% test material. Challenge responses in the test animals were compared with those of the challenge control animals.

Test Group

Following challenge with 100% test material, dermal reactions in the test and challenge control animals were limited to scores of 0 to ±. Group mean dermal scores were noted to be similar in the test animals as compared to the challenge control animals.

HCA

Using a-Hexylcinnamaldehyde (HCA) as a positive control, Charles River Laboratories, Inc., Spencerville, Ohio, has completed a study during the past six months which provided historical control data for contact sensitization to this agent utilizing the test system described herein (Modified Buehler Design). Following induction at 5% w/v HCA in ethanol, challenge at levels of 2.5% and 1% w/v HCA in acetone and rechallenge at a level of 2.5% w/v HCA in acetone, a contact sensitization response was observed, thereby demonstrating the susceptibility of the test system to this sensitizing agent.

Conclusion

Number of Test Animals with Score > 1/Number Dosed

 

24h

48h

Test Group

0/20

0/20

 

Note: All challenge control animals had scores of ± and 0.

The test substance is not sensitizing under these test conditions.