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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):1,3-Dioxolane
- Physical state: liquid
- Analytical purity: 99.99%
- Expiration date of the lot/batch: 18 April 2010
- Storage condition of test material: In refrigerator in the dark
- Stability under storage conditions: stable

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation:approx. 9 weeks old
- Weight at study initiation: BW variation was within +/-% of the sex mean
- Housing: individual housing in labeled Macrolon cages containing sterilized sawdust as bedding material and paper was supplied as cage-enrichment before dosing and after scoring of the ears.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.7-23.9
- Humidity (%):39-65
- Air changes (per hr):15
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: From: To: 080Feb 2010 to 22 Feb 2010

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
0, 25, 50, 100 % test substance (w/w)
No. of animals per dose:
5 animals per dose
Details on study design:
PRELIMINARY IRRITATION STUDY:
-conc. tested: 50 and 100 %
Two young adult animals were treated with one concentration on three consecutive days. Approximately 3-4 hours after the last exposure, the irritation of the ears was assessed.

MAIN STUDY
- Criteria used to consider a positive response: If the results indicate a SI ≥3, the test substance may be regarded as a skin sensitizer, based on the guideline and recommendations done by ICCVAM. The results were evaluated according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007) and the Regulation (EC) No 1272/2008 of the European arliament and of the Council of 16 December 2008 on classification, labeling and packaging of substances and mixtures.
Consideration was given to the EC3 value (the estimated test substance concentration that will give a SI =3).

TREATMENT PREPARATION AND ADMINISTRATION:
The dorsal surface of both ears was epidermally treated (25 μL/ear) with the test substance concentration on days 1, 2 and 3. The control animals were treated the sam e as the experimental animals, except that the vehicle alone was administered.
Irritation was scored on day 3 (3-4 hours after treatment).
On day 6, each anmal was injected via the tail with 20 μCi of 3H-methyl thymidine. After approximately 5 hours, all animals were killed , and the draining (auricular) lymph node of each ear was excised. The relative size of the nodes (as compared to normal) was estimated by visual examination. A single suspension of pooled lymph nodes for each animal was prepared in PBS. On day 7, radioactivity was measured by means of a Packard scintillation counter.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:
The SI values calculated for the substance concentrations 5, 10 and 25 % were 1.4, 1.2 and 5.1 respectively. An EC3 value of 16.9 % was calculated using linear interpolation (in the acceptable range of 2 and 20 %).

In vivo (LLNA)

Resultsopen allclose all
Key result
Parameter:
SI
Value:
1.4
Test group / Remarks:
5 %
Remarks on result:
other: Test substance SI ± SEM 0% (vehicle) 1.0 ± 0.2 25% 0.7 ± 0.1 50% 0.8 ± 0.2 100 % 1.6 ± 0.4
Key result
Parameter:
SI
Value:
1.2
Test group / Remarks:
10 %
Key result
Parameter:
SI
Value:
5.1
Test group / Remarks:
25 %
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: Test substance DPM ± SEM 0% (vehicle) 450 ± 79 25% 311 ± 38 50% 372 ± 30 100 %; 739 ± 106

Any other information on results incl. tables

The slight irritation of the ears as shown by the animals treated a 50% and 100% concentration was considered not to have a toxicologically significant effect on teh activity of the noes. No oedema was observed in any of the animals examined.

The auricular lymph nodes were considered normal in size, except for the nodes in one animal of the 100% group which was found to be smaller . No macroscopic abnormalities of the surrounding area were noted.

Body weights and body weight gain of experimental animals remained in the same range as controls ove rthe study period.

No mortality occurred and no symptoms of systemic toxicity were observed.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Conclusions:
Since there was no indication that the test substance elicit an SI ≥ 3 when tested up to 100%, 1,3-Dioxolane is considered to be a non skin sensitizer.
Executive summary:

The SI values calculated for the substance concentrations 25, 50 and 100% were 0.7, 0.8 and 1.6, respectively. Since the test substance did not elicit an SI ≥3 when tested up to 100%, 1,3 -Dioxolane is considered to be a non skin sensitizer, according to the recommendations made in the test guidelines and does not have to be classified and has no obligatory labeling requirement for sensitization by skin contact according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007) and the Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures.