Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From 26 February 2013 to 24 June 2013
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was performed on the analogue substance 2,2-Dimethyl-1,3-dioxolane-4-methanol (for justification of read-across between the registered substance and its analogue, please refer to corresponding assessment report in Section 13). The study was GLP compliant and performed according to OECD guideline 402 without any deviations.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Commission Regulation (EC) No. 440/2008, Part B.3, 30 May 2008
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
Certificate n° : 2012/96 ; 10 January 2013
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): 2,2-Dimethyl-1,3-dioxolane-4-methanol
- Physical state: colorless (clear) liquid
- Analytical purity: 99.9%
- 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.: BR12K853
- Expiration date of the lot/batch: 05 November 2013
- Storage condition of test material: at room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: Approximately 8 weeks old
- Weight at study initiation: Males: 352 g (333 g to 381 g); females: 208 g (203 g to 216 g)
- Housing: Housed by five from the same sex and group in polycarbonate cages.
- Diet: SSNIFF R/M-H pelleted maintenance diet (SSNIFF Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: Drinking water filtered with a 0.22 µm filter, ad libitum
- Acclimation period: At least 6 or 8 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 50 ± 20 %
- Air changes: Approximately 12 cycles/h of filtered, non-recycled air
- Photoperiod: 12 h dark / 12 h light

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal area, approximately 5 cm x 7 cm for males and 5 cm x 6 cm for females
- % coverage: Approximately 10 % of the total body surface area
- Undiluted test item was applied as a film (as thin and uniform as possible) to the clipped area of skin. The application site was then covered with a hydrophilic gauze pad. The test item and the gauze pad were held in contact with the skin for 24 h by means of an adhesive hypoallergenic aerated semi-occlusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test item was removed using a dry cotton pad.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: Yes
Duration of exposure:
24h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
other: historical control data
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: Each animal was checked for mortality and morbidity, frequently during the hours following treatment, then once a day until the end of the observation period, including weekends. Animals were observed at least once during the first 30 minutes, periodically during the first 4 hours, then once a day, at approximately same time, for the recording of clinical signs. Any clinical signs observed were recorded individually for each animal, along with the times of onset and recovery. From Day 2, any local reaction at the treatment site was recorded.
Bodyweight of each animal was recorded on the day of group allocation then on the day of treatment and on days 8 and 15.
- Necropsy of survivors performed: Yes; all animals were deeply anesthetized by an intraperitoneal injection of pentobarbital sodium and euthanized by exsanguination.
Statistics:
None

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No clinical signs indicative of systemic toxicity were observed in any animals.
Body weight:
- When compared to historical control animals, the mean body weight gain was unaffected by the test item treatment in females.
- When compared to historical control animals, a lower mean body weight gain was noted in males (+24 g vs. 32 ± 9.1 g in control data base) between day 1 and day 8 due to one animal which had lost weight during this period. The mean body weight gain returned to normal thereafter. This change in males was considered incidental.
Gross pathology:
No macroscopic abnormalities were observed at necropsy.
Other findings:
Skin reactions:
On the application site, two females presented scabs from day 11 or 12 and up to day 13 or 14, and a very slight erythema was noted in one of these two females on days 3 and 4.
No cutaneous reactions were observed in any males.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the dermal LD50 of the test item, AUGEO SL191, was higher than 2000 mg/kg in rats and no mortality occurred at this concentration. Therefore AUGEO SL191 should not be classified for acute dermal toxicity according to the Regulation (EC) N° 1272-2008 (CLP) and the Directive 67/548/EEC.
Executive summary:

2,2-Dimethyl-1,3-dioxolane-4-methanol was tested for acute dermal toxicity in Sprague-Dawley rats in a GLP-compliant limit dose assay according to OECD guideline 402. Groups of rats (5/sex) were administered a single dermal dose of undiluted test material at 2000 mg/kg bw on clipped skin (approximately 10 % of the total body surface area) using a semi-occlusive patch held in place for 24 h. Residual test item was removed using a dry cotton pad at the end of the 24 h exposure period. Examinations for mortality, clinical signs, body weight gain and dermal reactions were performed during a 14-day observation period. All surviving animals were necropsied at the end of the observation period.

No deaths occurred during the observation period. When compared to historical control animals, the mean body weight gain was unaffected by the test item treatment in females. A lower mean body weight gain was noted in males between day 1 and day 8 due to one animal which had lost weight during this period. The mean body weight gain returned to normal thereafter. This change in males was considered incidental. At necropsy, macroscopic examination of main organs showed no abnormalities. The acute dermal combined LD50 was greater than 2000 mg/kg bw.

Some dermal changes were observed in some animals. On the application site, two females presented scabs from day 11 or 12 and up to day 13 or 14, and a very slight erythema was noted in one of these two females on days 3 and 4. No cutaneous reactions were observed in any males.

Under the test conditions, the dermal LD50 of the test item, 2,2-Dimethyl-1,3-dioxolane-4-methanol, was higher than 2000 mg/kg in rats and no mortality occurred at this concentration. Therefore AUGEO SL191 should not be classified for acute dermal toxicity according to the Regulation (EC) N° 1272-2008 (CLP) and the Directive 67/548/EEC.