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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:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study, according to OECD guideline 406

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report date:
1996

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
test was done before this legislation entered into force

Test material

Constituent 1
Reference substance name:
Pseudoionon
IUPAC Name:
Pseudoionon
Details on test material:
- Name of test material (as cited in study report): Pseudoionon
- Physical state: clear yellow liquid
- Lot/batch No.: 05076
- Storage condition of test material: room temp/under nitrogen

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Darley Oaks, Burton-on-Trent, Staffordshire, England
- Weight at study initiation: 300-350 g
- Housing: in groups of up to 5 in stainless steel cages
- Diet (e.g. ad libitum): a pelleted diet, SQC FD1 guinea pig diet with added vitamin C (Special Diets Services, Witham, Essex, England), ad libitum
- Water (e.g. ad libitum): mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 36-68
Air changes (per hr): air conditioned
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
intradermal induction of 5 % v/v test article in water
topical induction of 12.5 % v/v test article in water
challenge with 6.25 % v/v test article in water
rechallenge with 3.125 and 1.563 % v/v test article in water
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
intradermal induction of 5 % v/v test article in water
topical induction of 12.5 % v/v test article in water
challenge with 6.25 % v/v test article in water
rechallenge with 3.125 and 1.563 % v/v test article in water
No. of animals per dose:
20 test and 10 control animals
Details on study design:
RANGE FINDING TESTS:
Intradermal Injection Concentration Ranging Study
The ranging study was performed in one animal which, 7 days previously, had been pretreated with 4 intradermal injections of a 1:1 mixture of FCA and water.
0.1 mL aliquots of 50, 25, 10, 5, 1 and 0.5 % v/v concentrations of the test article in water were injected intradermally into the flanks of the guinea pig. The animal was examined on the day of dosing and then daily thereafter for a further 5 days and the response at each injection site was noted. From the result of this range finder, it was considered that a 5 % v/v concentration of the test article in water would not provoke an unacceptable irritant response and this concentration was therefore selected for use at the intradermal injection phase of the main study.

Topical Irritancy Ranging Study
The topical concentration ranging study was assessed using 4 animals previously treated with 1:1 FCA/water as described above. The concentrations used were undiluted test article and 50, 25 and 12.5 % v/v test article in water. A test article concentration of 12.5 % in water was selected for the topical induction phase in the main study. The results of the preliminary range finder indicated that 6.25 % v/v test article in water was the highest non-irritant concentration which could be applied to the skin without obscuring the site by intense staining and was therefore selected for use at the challenge phase.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 7 = 3 pairs of intradermal injections + 1 topical application
- Exposure period: 8 days
- Test groups: one group of 20 animals. Intradermal induction: 1) 50 % v/v FCA emulsified in water, 2) 5 % v/v test article in water, 3) 5 % v/v concentration of the test article in a 1:1 emulsion of FCA and water
- Control group: one group of 10 animals. Intradermal induction: 1) 50 % v/v FCA emulsified in water, 2) water, 3) water mixed with a 1:1 emulsion of FCA and water to give a vehicle concentration of 50 % v/v.
- Site: dorsal area between the shoulders
- Frequency of applications: intradermal induction on day 0, topical induction on day 7
- Duration: topical induction: 48 hours
- Concentrations: topical induction: 12.5 % v/v test article in water

B. CHALLENGE EXPOSURE
- No. of exposures: 2 = challenge + rechallenge
- Day(s) of challenge: 40 days after the topical induction application
- Exposure period: 24 hours
- Test groups: challenge: 6.25 % v/v test article in water, rechallenge (7 days later after challenge): 3.125 and 1.563 % v/v in water
- Control group: water
- Site: on the left flank
- Evaluation (hr after challenge):24 and 48 hours after removal of the patches and dressings
Positive control substance(s):
yes
Remarks:
Mercaptobenzothiazole

Results and discussion

Positive control results:
Four of the 10 test animals exhibited positive responses to challenge with 10 % Mercaptobenzothiazole (MBT) at the 24 and the 48 hour observations, resulting in a response incidence of 40 %. None of the test animals responded to challenge with the vehicle at any of the observations. None of the control animals responded to challenge with either 10 % MBT or the vehicle at any of the observations. These results confirm that MBT is a moderate sensitizer under the conditions of this study and the test system is therefore considered to be valid.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
3.125 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 3.125 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
3.125 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 3.125 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
1.563 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 1.563 %. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
1.563 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 1.563 %. No with. + reactions: 0.0. Total no. in groups: 20.0.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
The test article, Pseudoionon Ro 02-2438, at the concentrations which allowed for testing, did not cause a sensitisation response in the animals under the conditions of this study.
Executive summary:

In order to assess the skin sensitisation potential of the test article the Maximisation Test in accordance with OECD guideline 406 and GLP was carried out in 20 test and 10 control female albino guinea pigs. The intradermal induction of sensitisation was carried out with 5 % v/v suspension of the test article in water or in emulsion with Freund's Complete Adjuvant (FCA). The epicutaneous induction of sensitisation was conducted under occlusion with 12.5 % v/v test article in water. Two weeks after epidermal induction, the challenge was completed by epicutaneous application of the test article in the highest appreciable non irritating concentration, i.e. 6.25 % v/v in water (as determined in the range finding phase of the study) under occlusive dressing. Following removal of the occlusive dressings, it was found that in the majority of test and control animals red/brown skin staining produced by the test article was so intense as to prevent the assessment of cutaneous reactions. None of the test or control animals exhibited positive responses to water alone. A rechallenge using test article concentrations of 3.12 % and 1.56 % v/v in water was therefore conducted 7 days after the initial challenge. Although slight brown staining of the treated site occured on most animals this did not prevent cutaneous reactions, i.e., erythema and eschar as well as oedema formation, from being evaluated at 24 and 48 hours after removal of the dressing. None of the test or control animals responded positively to rechallenge with either of the test article concentrations 24 or 48 hours after removal of the dressings. It is considered that the test article, Pseudoionone, at the concentrations which allowed for testing, did not cause a sensitisation response in the animals under the conditions of this study.

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