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Diss Factsheets

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:
15 Nov - 23 Dec 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted Jul 1992
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
The Department of Health of the Government if the United Kingdom
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data was included to avoid unnecessary testing.

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2-bis[[(1-oxodocosyl)oxy]methyl]propane-1,3-diyl didocosanoate
EC Number:
262-895-6
EC Name:
2,2-bis[[(1-oxodocosyl)oxy]methyl]propane-1,3-diyl didocosanoate
Cas Number:
61682-73-3
Molecular formula:
C93H180O8
IUPAC Name:
3-(docosanoyloxy)-2,2-bis[(docosanoyloxy)methyl]propyl docosanoate (non-preferred name)

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, Staffordshire, UK
- Age at study initiation: 8 -12 weeks
- Weight at study initiation: 332 - 383 g (range)
- Housing: The animals were housed singly or in pairs in solid-floor polyporpylene cages furnished with woodflakes.
- Diet: Guinea Pig FD1 Diet (Special Diets Services Limited, Essex, UK), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): Approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

- IN-LIFE DATES: From: 15 Nov 1999 To: 23 Dec 1999

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
arachis oil
Concentration / amount:
1% (w/w)
Day(s)/duration:
Single injection on Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
25% (w/w)
Day(s)/duration:
Applied on Day 7, 48 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, open
Vehicle:
arachis oil
Concentration / amount:
10 and 25% (w/w)
Day(s)/duration:
Applied on Day 21, 24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 (test groups), 5 (controls)
Details on study design:
RANGE FINDING TESTS: To determine a suitable concentration for the intradermal induction in the main study, 2 concentrations of the test substance (1 and 5% w/w) in arachis oil BP were selected. A total of 2 female guinea pigs each received 4 injections of 0.1 mL of one concentration only. The degree of erythema at the injection sites was recorded approximately 24, 48 and 72 h, and 7 days after injection. Clinical signs of systemic toxicity were also recorded. A concentration of 5% w/w in arachis oil BP induced erythema (grade 1) after seven days, therefore a concentration of 1% w/w was selected for the intradermal induction stage of the main study. To determine a suitable concentration for the epicutaneous induction in the main study, 2 females were intradermal injected with Freund's Complete Adjuvant on Day 0, and then each treated by epicutaneous application with 5, 10, 25 and 50% w/w of the test substance in arachis oil BP. The test substance was applied to the clipped flanks of the animals under occlusive dressings for 48 hours, and the degree of erythema and oedema was assessed approximately 1, 24 and 48 h after patch removal. A concentration of 50% w/w in arachis oil BP induced erythema (grade 2) and edema (grade 1) after 48 h, therefore a concentration of 25% w/w was selected for the epicutaneous induction stage of the main study.
To determine a suitable concentration for the epicutaneous challenge in the main study, 2 females were treated by epicutaneous application with 5, 10, 25 and 50% w/w of the test substance in arachis oil BP. The test substance was applied to the clipped flanks of the animals under occlusive dressings for 48 hours, and the degree of erythema and oedema was assessed approximately 1, 24 and 48 h after patch removal. The concentrations of the test material selected for the main study topical challenge were 25 and 10% w/w in arachis oil BP.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture v/v FCA/water
Injection 2: a 1% w/w formulation of the test substance in arachis oil BP
Injection 3: a 1% w/w formulation of the test material in a 1:1 mixture v/v FCA/water
Epicutaneous: 25% w/w of the test substance in arachis oil BP
- Control group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture v/v FCA/water
Injection 2: arachis oil BP
Injection 3: a 50% w/w formulation of arachis oil BP in a 1:1 mixture v/v FCA/water
Epicutaneous: blank patch
- Site: shoulder region (intradermal and epicutaneous)
- Frequency of applications: Day 0 (intradermal) and Day 7 (epicutaneous)
- Duration: Days 0 - 7
- Concentrations: intradermal 1% w/w, epicutaneous 25% w/w

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (challenge)
- Day(s) of challenge: 21
- Exposure period: 24 h
- Test groups: test substance in arachis oil BP
- Site: right flank (25% w/w), left flank (10% w/w)
- Concentrations: 10 and 25% w/w
- Evaluation (hr after challenge): 25 and 48 h after patch removal

OTHER: Approximately 24 and 48 h after intradermal injection the degree of erythema at the injection sites was evaluated. The degree of erythema and oedema was assessed approximately 1 and 24 h after patch removal following the topical induction. Any evidence of systemic toxicity was recorded. The bodyweight of each animal was recorded at the start and end of the study.
Positive control substance(s):
yes

Results and discussion

Positive control results:
Reliability checks were performed at least every 6 months at the testing laboratory to assess the sensitivity and reliability of the test method. A summary of the studies performed from Dec 1996 to Jul 1999 under same experimental conditions was included in the study report. The animals were administered 2-mercaptobenzothiazole. A response of 70-100% of the animals was observed in all the reliability checks. Therefore the positive control is considered to be valid.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Induction: 1% (intradermal), 25% (epicutaneous); challenge: 10 and 25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No local skin irritation reactions and no signs of systemic toxicity were observed
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Induction: 1% (intradermal), 25% (epicutaneous); challenge: 10 and 25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No local skin irritation reactions and no signs of systemic toxicity were observed
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: arachis oil (intradermal), arachis oil (epicutaneous); challenge: 10 and 25%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No local skin irritation reactions and no signs of systemic toxicity were observed
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: arachis oil (intradermal), arachis oil (epicutaneous); challenge: 10 and 25%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No local skin irritation reactions and no signs of systemic toxicity were observed
Key result
Group:
positive control
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

Following the intradermal induction, discrete or patchy erythema (grade 1) or moderate to confluent erythema (grade 2) were observed at the injection sites of 10/10 treatment animals (1% test material in arachis oil) and discrete or patchy erythema (grade 1) were noted in 4/5 control animals (arachis oil), both at the 24-hour reading time point. At the 48-hour reading time point, in 10/10 treatment animals discrete or patchy erythema (grade 1), moderate to confluent erythema (grade 2) or intense erythema and swelling (grade 3) and in 4/5 control animal discrete or patchy erythema (grade 1) were observed, respectively. Following the topical induction (25% in arachis oil BP), discrete or patchy erythema (grade 1) or moderate to confluent erythema (grade 2) were observed at the application site in 10/10 treatment animals at the one-hour reading time point and at the 24-hour reading time point. Bleeding from the intradermal induction site was noted in 9/10 treatment animals at the one-hour reading time point following the topical induction, while hardened dark brown/black coloured scabs were noted at the topical induction sites in 1/10 treatment animals at the 24-hour observation time point. 3/5 control animals at the one-hour reading time point and 2/5 animals at the 24-hour reading time point showed discrete or patchy erythema (grade 1) or moderate to confluent erythema (grade 2) following the topical induction, moreover, bleeding from the intradermal induction site was noted in 2/5 control animals at the one-hour reading time point, while hardened dark brown/black coloured scabs were noted at the topical induction sites in 1/5 control animals at the 24-hour observation time point.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
CLP: not classified