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Description of key information

In a Guinea Pig Maximization Test, 2,2-Dimethyl-1,3-dioxolane-4-methanol did not induce skin sensitization.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 15 May 2009 to 06 November 2009
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP study conducted in compliance with OECD Guideline 406 with some restrictions: In challenge period, the control group was exposed to the vehicle and not to the test substance; three intradermal injections were applied in the tested animals in the period of the first induction instead of three pairs of injections, as described in the study plan.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
(Control group exposed to the vehicle and not to the test substance for challenge. No impact on the study, since no skin reactions were observed; 3 intradermal injections in tested animals for 1st induction instead of 3 pairs of injections.)
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
24 February 2009
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study performed in Brazil prior to the intention of the company to register it for Reach.
Specific details on test material used for the study:
Name of test material (as cited in study report): PEX-01; 2,2-Dimetil-4-Hidroximetil-1,3-Dioxolano
- Physical state: Clear liquid
- Analytical purity: 99.5%
- pH of test substance = 6
- Composition of test material, percentage of components: 99.9% 2,2-Dimethyl-1,3-dioxolane-4-methanol; water: 0.02%; Acidity (Acetic acid): 0.0021%
- Lot/batch No.: 081001
- Expiration date of the lot/batch: 01 October 2009
- Stability under test conditions: Stable at room temperature and under normal conditions of use
- Storage condition of test material: at room temperature
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Anilab, Paulinea-SP
- Age at study initiation: 2 months
- Weight at study initiation: at least 300 g
- Housing: Individually in polypropylene cage
- Diet: Pelleted commercial diet (Biotecnicas, Biobase biotec), ad libitum
- Water: filtered water, ad libitum
- Acclimation period: At least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature: from 17ºC to 22ºC
- Humidity: 64%
- Air changes: No data
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From: 20 July 2009 To: 14 August 2009
Route:
intradermal and epicutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Range finding test:
- Intradermal induction exposure: undiluted
- Topical induction exposure: undiluted

Main test:
- Intradermal induction exposure: undiluted
- Topical induction exposure: undiluted
- Topical challenge exposure: undiluted
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Range finding test:
- Intradermal induction exposure: undiluted
- Topical induction exposure: undiluted

Main test:
- Intradermal induction exposure: undiluted
- Topical induction exposure: undiluted
- Topical challenge exposure: undiluted
No. of animals per dose:
- Range finding test: 2 females
- Main test: 5 animals (3 males and 2 females) for control and 10 animals (5 males and 5 females) for treatment group
Details on study design:
RANGE FINDING TEST:
- Intradermal induction exposure: Undiluted test substance (0.1mL) was applied by intradermal injection in the left shoulder area of one animal.
- Topical induction exposure: In another guinea pig, 0.5 mL of undiluted test substance was applied topically in an occlusive patch and held in contact with the skin for 6 hours.

MAIN STUDY
A. INDUCTION EXPOSURE: INTRADERMAL
- No. of exposures: One
- Day of induction: Day 0
- Test group: Intradermally injected with 3 injections (0.1 mL each) of a mixture of 1:1 (v/v) of Freund adjuvant (FCA) and sterile deionized water, undiluted test substance, mixture of 1:1 (v/v) of undiluted test substance + mixture of 1:1 (v/v) of Freund adjuvant (FCA) and sterile deionized water (v/v), on Day 0.
- Control group: Intradermally injected with 3 injections (0.1 mL each) of a mixture of 1:1 (v/v) of Freund adjuvant (FCA) and sterile deionized water, sterile water, mixture of 1:1 (v/v) of sterile water + mixture of 1:1 (v/v) of Freund adjuvant (FCA) and sterile deionized water (v/v), on Day 0.
- Site: left shoulder

B. INDUCTION EXPOSURE: TOPICAL
- No. of exposures: One
- Day of induction: Day 8
- Exposure period: 48 h
- Test group: After a 24h-topical exposure to 0.5 mL of Sodium Lauryl sulfate (10% in Vaseline), an occlusive patch fully loaded with undiluted test substance was applied topically.
- Control group: After a 24h-topical exposure to 0.5 mL of Sodium Lauryl sulfate (10% in Vaseline), an occlusive patch fully loaded with deionized water was applied topically.
- Site: Same intradermally injected area (left shoulder)
- Frequency of applications: Single application

C. CHALLENGE EXPOSURE: TOPICAL
- No. of exposures: One
- Day of challenge: Day 22
- Exposure period: 24 h
- Test and control groups: The untreated right flank of treated and control animals were cleared of hair and an occlusive patch loaded with undiluted test substance or deionized water, respectively, was applied topically.
- Site: Right shoulder (untreated flank)
- Evaluation (h after removal of challenge patch): 48 and 72 h

OTHER:
- Body weight: Animals were weighed before the first induction exposure and at the end of the test.
- A 24h-topical exposure to 0.5 mL of Sodium Lauryl sulfate (10% in Vaseline) was performed before topical induction phase in order to induce skin irritation.

Challenge controls:
In challenge period, the control group was exposed to the vehicle and not to the test substance.
Positive control substance(s):
yes
Remarks:
α-hexylcinnamaldehyde
Positive control results:
Results of the last reliability check using undiluted α-hexylcinnamaldehyde (positive historical control) was found to induce an appropriate response in guinea-pig (40% of animals at 48 h and 80 % of animals at 72 h).
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Undiluted
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
Undiluted
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
undiluted
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
none
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
positive control
Dose level:
undiluted
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
none
Remarks on result:
positive indication of skin sensitisation

- Bodyweight gains of guinea pigs in the test group were comparable to those observed in the control group animals.


- During the experimental period, all the animals (control and treated groups) presented mild to moderate edema. One animal from the treated group presented mild erythema and to animals presented mild skin erosion.


- No erythema or edema was observed after 48 and 72 h patch removal.


 

Interpretation of results:
GHS criteria not met
Conclusions:
Under these test conditions, PEX-01 is not classified as skin sensitiser according to the Regulation (EC) N° 1272-2008 (CLP) and UN GHS criteria.
Executive summary:

In a GLP Guinea Pig maximisation study (GPMT) performed according to OECD Guideline 406, 5 male and 5 female Hartley guinea pigs were induced with three intradermal injections (0.1 mL each) of a mixture of 1:1 (v/v) of Freund adjuvant (FCA) and sterile deionized water, undiluted test substance ( 2,2-Dimethyl-1,3-dioxolane-4-methanol), mixture of 1:1 (v/v) of undiluted test substance + mixture of 1:1 (v/v) of Freund adjuvant (FCA) and sterile deionized water (v/v), on Day 0 on three different sites on the left shoulder. Control group of 3 males and 2 females was intradermally induced with 0.1 mLof FCA plus water, water and mixture of water plus FCA/water mixture. On Day 7, a topic application of 10% sodium lauryl sulfate solution in Vaseline was performed on the same area of injections. On Day 8, a topic application was performed using an occlusive patch fully loaded with undiluted test substance (experimental group) or deionized water (control group) held in contact to the tested area for 48 hours. After a rest period, on Day 22, challenge exposure began: an occlusive patch fully loaded with test substance (experimental group) or deionized water (control group) was applied on the right flank of the animals. The test concentration for the main study was determined from a range-finding study using two animals (one for intradermal induction and another for topical application). To note in challenge period, the control group was exposed to the vehicle and not to the test substance, as described in the study plan. No impact was observed in the study, since no skin reactions were observed in the animals during the challenge period.


 


No skin reactions were noted at the challenge sites of the test or control group animals at the 48 or 72 h observations. 2,2-Dimethyl-1,3-dioxolane-4-methanol produced a 0 % (0/10) sensitization rate and was considered to be a non-sensitizer to guinea pig skin. Positive control (Undiluted α-hexylcinnamaldehyde) exhibited evidence of sensitization.


 


Under these test conditions, 2,2-Dimethyl-1,3-dioxolane-4-methanol is not classified as skin sensitizer according to the Annex VI to the Regulation (EC) N° 1272-2008 (CLP) and according to the UN GHS criteria.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In a GLP Guinea Pig maximisation study (GPMT) performed according to OECD Guideline 406, 5 male and 5 female Hartley guinea pigs were induced with three intradermal injections (0.1 mL each) of a mixture of 1:1 (v/v) of Freund adjuvant (FCA) and sterile deionized water, undiluted test substance ( 2,2-Dimethyl-1,3-dioxolane-4-methanol), mixture of 1:1 (v/v) of undiluted test substance + mixture of 1:1 (v/v) of Freund adjuvant (FCA) and sterile deionized water (v/v), on Day 0 on three different sites on the left shoulder. Control group of 3 males and 2 females was intradermally induced with 0.1 mLof FCA plus water, water and mixture of water plus FCA/water mixture. On Day 7, a topic application of 10% sodium lauryl sulfate solution in Vaseline was performed on the same area of injections. On Day 8, a topic application was performed using an occlusive patch fully loaded with undiluted test substance (experimental group) or deionized water (control group) held in contact to the tested area for 48 hours. After a rest period, on Day 22, challenge exposure began: an occlusive patch fully loaded with test substance (experimental group) or deionized water (control group) was applied on the right flank of the animals. The test concentration for the main study was determined from a range-finding study using two animals (one for intradermal induction and another for topical application).


 


No skin reactions were noted at the challenge sites of the test or control group animals at the 48 or 72 h observations. 2,2-Dimethyl-1,3-dioxolane-4-methanol produced a 0 % (0/10) sensitization rate and was considered to be a non-sensitizer to guinea pig skin. Positive control (Undiluted α-hexylcinnamaldehyde) exhibited evidence of sensitization.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

As the submission substance is not expected to be a skin sensitizer in a Guinea-Pig Maximisation Test, 2,2-Dimethyl-1,3-dioxolane-4-methanol is not classified as skin sensitizer according to the Regulation (EC) N° 1272 -2008 (CLP) and GHS UN.