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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:
21 May - 27 July 2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
only 5 instead of 10 animals in the test group

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
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 were included to avoid unnecessary testing.

Test material

Constituent 1
Chemical structure
Reference substance name:
Isooctadecanoic acid, ester with oxybis[propanediol]
EC Number:
277-361-8
EC Name:
Isooctadecanoic acid, ester with oxybis[propanediol]
Cas Number:
73296-86-3
Molecular formula:
C24H50O7
IUPAC Name:
16-methylheptadecanoic acid; 3-(2,3-dihydroxypropoxy)propane-1,2-diol
Test material form:
liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Remarks:
Aai: (HA) Outbred
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: not specified
- Microbiological status of animals, when known: viral antibody free
- Age at study initiation: 4 - 6 weeks
- Weight at study initiation: 360 - 450 g
- Housing: stainless steel cages, not further specified
- Diet: Lab Diet Certified Guinea Pig Diet #5026, ad libitum
- Water: tap water, ad libitum
- Acclimation period: min. 7 days
- Indication of any skin lesions: animals were carefully checked prior to test initiation for respiratory or intestinal disease, skin eruptions, mucosal membrane irritation, postural difficulties and general condition

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15.6 - 29.4
- Humidity (%): 30 - 70
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 / 12

- IN-LIFE DATES: 22 May - 22 June 2002

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: TiterMax/distilled water (1:1)
Concentration / amount:
100% and 5%
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
Challenge
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
screening study with test group: 3 male, 2 females
test group: 3 males, 2 females
negative control group for test item: 2 males, 3 females
screening study with positive control group: 2 males, 3 females
positive control group: 3 males, 2 females
negative control group for positive control item: 2 males, 3 females
Details on study design:
RANGE FINDING TESTS:
A. INTRADERMAL SCREEN:
It was determined if the test item, injected intradermally, causes local necrosis or ulceration or any systemic toxicity. Skin corrosion potential was screened using 1 guinea pig. 3 injections of 0.1 mL volume were made.

injection 1: 5% in a 50/50 emulsion of TiterMax and distilled water
injection 2: 100%
injection 3: 50% in distilled water

No necrosis or ulceration was noted at 24 and/or 48 h after the injections.

B. TOPICAL SCREEN:
The highest non-irritating concentration (HNIC) for a topical application of the test item was also determined. The test item was diluted in distilled water. 4 animals (2 males and 2 femals) were prepared by close-clipping the dorsal area of their trunks. During all shaving procedures, care was taken to avoid abrading the shaved skin. On the same day, 4 sites on each animal were treated with the test item at decreasing concentrations: 100%, 50%, 25% and 10%. 0.4 mL of the test item were applied to each site. The animals were wrapped after dosing with a piece of 3 inch elastic tape. The wraps remained in place for 24 h before they were removed. Any excess test item was wiped away with ethanol 45 h after application. The test sites were scored 3 h after the ethanol wipe and again 24 h later. The test article elicited no irritation at 100% and therefore that concentration was chosen for the challenge phase.

MAIN STUDY
A. INTRADERMAL INDUCTION EXPOSURE
A 4x6 cm section of the shoulder area of each animal in the test groups was shaved, as detailed previously. 3 pairs of subcutaneous injections (0.1 mL volume) were made in 2 rows; 1 row on each side of the midline. The injection sites were just within the boundaries of the 2x4 cm patch, which was applied 1 week later in the course of the topical induction procedure.

- No. of exposures: 1 (intradermal injection)
- Exposure period: single injection (intradermal)
- Test groups:
Intradermal (3 pairs of injections)
1st pair: TiterMax/water emulsion (1:1), without the test item
2nd pair: 100% test item
3rd pair: 5% test item in TiterMax/distilled water (1:1)
- Control group: not treated
- Site: shoulder region
- Frequency of applications: on first day of induction

B. TOPICAL INDUCTION EXPOSURE
6 days after the injections were made the sites were again shaved. Sodium lauryl sulfate (SLS) at 10% in petrolatum, was then applied to the induction site of each animal to enhance a possible sensitization reaction by provoking a mild inflammatory reaction. 7 days after the injections were made, the test item at 100% was applied to the injection sites. 0.5 mL of the test item was spread onto a 2x4 cm patch of filter paper. The filter paper was placed on the test site and covered with a piece of tape. Further tapes were then wound around the test site of the animal. The wraps and patches were removed after 48 h.

- No. of exposures: 1 (epicutaneous)
- Exposure period: 48 h
- Test groups: 100% test item after treatment with sodium lauryl sulfate (SLS) (10% in petrolatum) to provoke skin irritation
- Control group: not treated
- Site: shoulder region
- Frequency of applications: 7 days after intradermal injection
- Concentrations: 100%

B. CHALLENGE EXPOSURE
2 weeks after the topical induction applications, the challenge application was made. Prior to dosing, a 5x5 cm area of the flank of each guinea pig, in the test group as well as the negative control group was shaved. 0.4 mL of the undiluted (100%) test item was applied to each site. The animals were wrapped after dosing with a piece of 3 inch elastic tape. The wraps remained in place for 24 h. 21 h after unwrapping, any remaining test item was removed with an ethanol wipe and the test site was shaved if necessary. 3 h later, the test site was scored according to the Draize Scale. 24 and 48 h later, the sites were again scored.

- No. of exposures: 1 (epicutaneous)
- Day(s) of challenge: 2 weeks after topical induction exposure
- Exposure period: 24 h
- Test groups: test item only
- Control group: test item only
- Site: flanks
- Concentrations: 100%
- Evaluation (hr after challenge): 24, 48 and 72
Challenge controls:
The control group is actually a challenge control
Positive control substance(s):
yes
Remarks:
1-Chloro-2,4-dinitrobenzene

Results and discussion

Positive control results:
The positive control substance (1-chloro-2,4-dinitrobenzene, induction: 5% in corn oil, challenge: 0.05% in petroleum jelly) induced positive reactions in 4/5 animals (80%) in both the 1st and the 2nd readings after challenge, thus demonstrating the validity of the test.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0%; challenge:100%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Induction and challenge: 100%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Induction: 5% in corn oil; challenge: 0.05% in petroleum jelly
No. with + reactions:
4
Total no. in group:
5
Clinical observations:
erythema formation
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: 0%; challenge:100%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Induction and challenge: 100%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Induction: 5% in corn oil; challenge: 0.05% in petroleum jelly
No. with + reactions:
4
Total no. in group:
5
Clinical observations:
erythema formation
Remarks on result:
positive indication of skin sensitisation

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.