2,2-dimethyl-1,3-dioxolan-4-ylmethanol

Skin sensitisation

Administrative data

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.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

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.

Test material

Test material information

Constituent 1

Reference substance name:

2,2-dimethyl-1,3-dioxolan-4-ylmethanol

EC Number:

202-888-7

EC Name:

2,2-dimethyl-1,3-dioxolan-4-ylmethanol

Cas Number:

100-79-8

Molecular formula:

C6H12O3

IUPAC Name:

(2,2-dimethyl-1,3-dioxolan-4-yl)methanol

Test material form:

other: liquid

Details on test material:

- 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%
- 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

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

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

unchanged (no vehicle)

Induction 2

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

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Challenge 2

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

Results and discussion

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).

In vivo (non-LLNA)

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

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

Results 6

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

Any other information on results incl. tables

- 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.

 

Applicant's summary and conclusion

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.