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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
Study period:
28 July 1982 - 4 September 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study is a read across from BCIXN-Na (CAS 102506-09-2).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Guinea Pig Maximisation test method.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
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 Ltd., Burton-on Trent, Stratfodshire, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 370-450g
- Housing: The animals were housed in groups of up to three in solid-floor polypropylene cages furnished with softwood shavings.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 46-72
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Intradermal induction: 1% (w/v) in distilled water
Topical induction: undiluted as supplied
Topical challenge: undiluted as supplied and 75% (v/v) in distilled water
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Intradermal induction: 1% (w/v) in distilled water
Topical induction: undiluted as supplied
Topical challenge: undiluted as supplied and 75% (v/v) in distilled water
No. of animals per dose:
20 test and 10 control animals were used for the main study
Details on study design:
RANGE FINDING TESTS:

Selection of concentrations for intradermal induction:
Two animals were intradermally injected with preparations of test material (1% or 5% w/v in distilled water). The highest concentration that did not cause local necrosis, ulceration or systemic toxixicty, was selected for the intradermal induction stage of the main study.

Selection of concentration for topical induction:
Two guinea pigs (intradermally injected with Freund's complete adjuvant twenty one days earlier) were treated with the undiluted test material and three preparations of the test material (75%, 50% and 25% v/v in distilled water). The highest concentration producing only mild to moderate dermal irritation after the 48 hour occlusive exposure, was selected for the topical induction stage of the maiin study.

Selection of concentration for topical challenge:
The undiluted test material and three preparations of the test material (75%, 50% and 25% v/v in distilled water) were applied occlusively to the flanks of two guinea pigs for a period of 24 hours. These guinea pigs did not form part of the main study but had been treated identically to the control animals of the main study, up to day 14. The highest non-irritant concentration of the test material and one lower concentration were selected for the topical challenge stage of the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
On day 0 a row of three injections (0.1ml) was made on each side of the midline. The injections were: (1) Freund's complete adjuvant plus distilled water in the ratio 1:1, (2) a 1% (w/v) dilution of test material in distilled water, (3) a 1% (w/v) dilution of test material in a 1:1 preparation of Freund's complete adjuvant plus distilled water. One week later (Day 7), the same area on the shoulder region used previously for intradermal injections was clipped again and treated with a topical application of the undiluted test material, which was applied on filter paper which was held in place occlusively for 48 hours. Erythemaeous reactions were quantified one and twenty-four hours following removal of the patches. In the case of the induction of the control animals, intradermal injections were administered using an identical procedure to that used for the test animals, except that test material was omitted and substituted with distilled water. The topical applications followed the same procedure as for the test animals except that nothign was applied to the filter paper.


B. CHALLENGE EXPOSURE
On Day 21, a quantity of the unduluted test material was applied to the shorn right flank of each animal on a square of filter paper which was held in place. To ensure that the maximum non-irritant concentration was used at challenge, the test material at a concentration of 75% (v/v) in distilled water was also similarly applied to a separate skin site on the right shorn flank. The vehicle alone was similarly applied to the left shorn flank. The patches were occluded, and torso wrapped. After 24 hours the dressing was removed, and their position identified with marker-pen. Approximately 24 and 48 hours after challenge dressing removal, erythematous reactions were quantified using the four point scale shown overleaf.
Positive control substance(s):
yes
Remarks:
DNCB (89% sensitisation rate)

Results and discussion

Positive control results:
DNCB produced an incidence on 16/18 sensitising reactions.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
Undiluted and 75% v/v in distilled water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
Undiluted and 75% v/v in distilled water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
adjuvant and distilled water in the ratio of 1:1
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
adjuvant and distilled water in the ratio of 1:1
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The result is read across from BCIXN-Na (CAS 102506-09-2). The test material was found not sensitising to guinea pig skin as reported in a reliable study conducted in compliance with GLP.