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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1997-10-20 to 1997-11-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as "reliable without restriction" because the study follows internationally accepted testing guidelines in which all parameters described are closely related/comparable to a guideline method.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): C20-C24 Alkenes, Branched and Linear
- Substance type: Alkenes, C20-24
- Physical state: Straw coloured liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, UK
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 300 to 326 grams
- Housing: Housed singly or in pairs in solid floor polypropylene cages
- Diet (e.g. ad libitum): Guinea Pig FD1 Diet; ad libitum
- Water (e.g. ad libitum): Mains tap water; ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 22
- Humidity (%): 40 to 66
- Air changes (per hr): 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours dark

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
100 % test material for topical induction; 75%, and 50% for challenge phase and 25% for intradermal induction
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
100 % test material for topical induction; 75%, and 50% for challenge phase and 25% for intradermal induction
No. of animals per dose:
20 test animals; 10 control
Details on study design:
RANGE FINDING TESTS:
Yes, performed using 4 animals

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1
- Exposure period: 48 hours
- Test groups: 20
- Control group: 10
- Site: Shoulder region
- Frequency of applications: Single application
- Concentrations: 100% test material


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1
- Exposure period: 24 hours
- Test groups: 20
- Control group: 10
- Site: Left and right flank
- Concentrations: 75 and 50% of test material in arachis oil
- Evaluation (hr after challenge): 24 and 48 hours after removal of occlusive wrap


Challenge controls:
10 animals
Positive control substance(s):
not specified

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st 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: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
50 or 75%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50 or 75%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Based on the results of the initial “sighting tests” the following concentrations of the test material were selected for the main study:

 

Intradermal induction: 25% w/v in arachis oil

Topical induction: Undiluted as supplied

Topical Challenge: 75 and 50% v/v in arachis oil

 

In the main study, very slight to moderate to severe erythema was noted at the intradermal induction sites of all test group animals at the 24 hour observation period. These effects had lessened to very slight to well-defined erythema at the 48 hour observation. Very slight erythema was noted at the intradermal induction sites of all control animals at the 24 and 48 hour observation period.

There were no changes in animal body weights during course of the study.

 

In the topical induction test, very slight erythema was noted at the induction sites of 14 test animals at the 1 hour observation period. Bleeding from injection sites of six test group animals was noted at the 1 hour observation period. No skin reactions were noted at the induction site of any of the test animals at the 24 hour observation period. Bleeding from the injection sites was noted in two control group animals at the 1-hour observation. No signs of erythema or oedema were noted at the treatment sites of control group animals at the 1 and 24-hour observations.

  

Following topical challenge, no skin reactions were noted at the challenge sites of the test or control animals at the 24 and 48 hour observation period.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
The study authors concluded that test material produced a 0% (0/20) sensitization rate in the female albino guinea pigs.
Executive summary:

In a guinea pig maximization skin test, concentrations for the main study were determined by “sighting tests” in which groups of guinea pigs were treated with various concentrations of test material.

 

Based on the outcome of the “sighting tests”, a group of 30 female guinea pigs were used in the main study with 20 serving as test animals and 10 as controls. In the induction phase, immediately before treatment, on day 0, the animals were clipped free of hair on the shoulder region and a row of three injections comprised of 0.1 mLFreund's Complete Adjuvant plus distilled water in the ratio 1:1, a 25% w/v formulation of test material in arachis oil, and a 25% w/v formulation of test material in a 1:1 preparation of Freund's Complete Adjuvant plus distilled water were made on each side of the mid-line. The degree of erythema was evaluated at 2 and 48 hours using the Draize scale (Draize,J.H.; 1977). A week later (day 7), the same area on the shoulder was clipped free of hair again and treated with a topical application of the undiluted test material that was secured with occlusive wrap. This occlusive dressing was kept in place for 48 hours. The degree of erythema and oedema was determined 24 hours later after the patches were removed using the Draize scale (1977). Any other toxicologically relevant reactions were also recorded. Control animals were induced in a manner similar to the test animals.

 

The challenge phase was initiated on day 21 following the induction phase. Shortly before treatment an approximate area of 50 X 70 mm on both flanks of the each animal was clipped free of hair and the test material was applied to saturation to the shorn right flank of each animal on a filter paper which was held in place with an occlusive wrap. To ensure that maximum non-irritant concentration was used in the challenge phase, the test material at a concentration of 50% v/v in arachis oil was also similarly applied to a separate skin site on the left shorn flank of the animals. These patches were also occluded to keep the test material in contact with the skin. After a 24 hour contact period, the dressing was carefully removed and the challenge sites were cleaned with cotton wool soaked in diethyl ether to remove any residual test material. Approximately 24, and 48 hours after removal of the challenge dressing, the degree of erythema and oedema was quantified using the Draize scale (1977). Any other toxicologically relevant reactions were also noted.

 

In the main study, very slight to moderate to severe erythema was noted at the intradermal induction sites of all test group animals at the 24 hour observation period. These effects had lessened to very slight to well-defined erythema at the 48 hour observation. Very slight erythema was noted at the intradermal induction sites of all control animals at the 24 and 48 hour observation period.

 

In the topical induction test, very slight erythema was noted at the induction sites of 14 test animals at the 1 hour observation period. Bleeding from injection sites of six test group animals was noted at the 1 hour observation period. No skin reactions were noted at the induction site of any of the test animals at the 24 hour observation period. Bleeding from the injection sites was noted in two control group animals at the 1-hour observation. No signs of erythema or oedema were noted at the treatment sites of control group animals at the 1 and 24-hour observations.

 

 

Following topical challenge, no skin reactions were noted at the challenge sites of the test or control animals at the 24 and 48 hour observation period. There were no changes in animal body weights during course of the study. Based on these results, the study authors concluded that test material produced a 0% (0/20) sensitization rate in the female albino guinea pigs.

 

This study received a Klimisch score of 2 and was classified as "reliable without restriction" because the study follows internationally accepted testing guidelines in which all parameters described are closely related/comparable to a guideline method.