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Administrative data

Description of key information

- One Acute oral toxicity study (Gemio dos Reis, 2011; OECD 423, Rel. 1) is available and showed a LD50 > 2000 mg/kg bw in female WIstar rats. This study indicates that the acute toxicity of 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol is low for the oral route.
- One acute dermal toxicity study (R. Leclère, 2013; OECD 402, Rel. 2) is available on the analogue substance 2,2-dimethyl-1,3-dioxolane-4-methanol and showed a LD50 > 2000 mg/kg bw in rats . By analogy, 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol is expected to be of no to low acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 04 February 2011 to 06 May 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Test guideline and GLP-compliant study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: TECAM Animal Facility (Sao Roque, SP - Brazil)
- Age at study initiation: 9-12 weeks
- Weight at study initiation: 174-224 g
- Fasting period before study: approximately 12 hours prior to the test substance administration
- Housing: Group caging, 3 per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 47-50
- Air changes (per hr): 10-12
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 04 February 2011 To: 10 March 2011
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
According to the guideline, the test substance was tested using a stepwise procedure starting with the dose of 300 mg/kg bw (based on prior information about toxicity of the active ingredient). Initially, one group of three female rats received 300 mg/kg bw of the test substance dilulted in corn oil. After five days, a second group of three female rats was treated at the same dose level. Based on the outcome of these groups, one group of three female rats was tested at 2000 mg/kg bw of the undiluted test substance and, after eight days, another three females rats were treated at the same dose level. Based on initial body weights, test substance concentration and the selected dose, volumes of administration were calculated as 0.20 mL/100 g bw (300 mg/kg bw) and 0.19 mL/100 g bw (2000 mg/kg bw). animals returned to ad libitum feeding after the first four hours of observation.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
6 per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations at 30 minutes, 1, 2, 3, 4 and 24 hours after dosing then daily for 14 days.
Bodyweight immediately beodre adiministration (Day 0), Day 7, Day 14
- Necropsy of survivors performed: yes
Statistics:
No
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality
Clinical signs:
No clinical signs were reported in any animals treated at 300 mg/kg bw.
At 2000 mg/kg bw, clinical signs consisting mainly in mild to severe prostation and ataxia were seen in most animals between 30 minutes and 4 hours post dosing. Incidence and severity tended to decrease with time. Moderate salivation was also noted in 3/6 females 1 hours post dosing and mild dyspnea was reported in one female 3 and 4 hours post dosing. No clinical signs were reported after 4 hours post-dosing up to the end of the observation period (day 14).
Body weight:
All animals had normal body weight gain throughout the study.
Gross pathology:
For animals treated at 300 mg/kg, macroscopic alterations were observed in the lungs (mild congestion in three animals) and liver (mild congestion in two animals, moderate in four, mild multifocal pale areas in one animal and moderate in another one).
At 2000 mg/kg bw, congestion was also reported in the lungs (mild in one animal) and in the liver (mild in three animals and moderate in other three).

The median lethal dose of 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol after a single oral administration to female rats, observed over a period of 14 days is: LD50 (female rat): greater than 2000 mg/kg body weight.

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
2-isobutyl-2-methyl-1,3-dioxolane-4-methanol is not classified as hazardous by ingestion according to the criteria of EU DSD or EU GHS.
Executive summary:

In an acute oral toxicity study, performed in compliance with the GLP and according to the OECD 423 Guideline, 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol was administered sequentially, by oral gavage, to female Wistar rats at the doses of 300 and 2000 mg/kg bw (6 animals/dose level). At 300 mg/kg bw, the test substance was diluted in corn oil. Clinical signs, mortality and body weight gain were checked for a period of up to 14 days. All animals were sacrificed at the end of the study and necropsied for gross abnormalities. 

Oral LD50in female rats > 2000 mg/kg bw

 

No mortalities occurred in any animals at the tested doses. No clinical signs were observed at 300 mg/kg bw. Animals treated at 2000 mg/kg bw presented prostration, ataxia, salivation and/or dyspnea in the first 4 hours post dosing. These clinical signs had totally ceased afterwards. Body weight gain was not affected by the test substance treatment. Macroscopic observations consisted in congestion with or without multifocal pale areas in the liver of all animals at both doses and congestion in the lungs in few animals at both doses.

 

Based on the results of this study, 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol is not classified for acute oral toxicity according to the Regulation (EC) 1272/2008 (CLP) and the Directive 67/548/EEC.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The study is GLP and OECD guideline compliant and has Klimish score 1.

Acute toxicity: via dermal route

Link to relevant study records
Reference
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.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Reference:
Composition 0
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 information:
Composition 1
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
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
Preliminary study:
Not applicable
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.

None

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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw

Additional information

Oral:

In a GLP-compliant acute oral toxicity study performed in accordance with OECD 423, no mortality and no major clinical signs were observed in Wistar rats given a single oral administration of 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol at the doses of 300 or 2000 mg/kg bw . Therefore,

2-isobutyl-2-methyl-1,3-dioxolane-4-methanol LD50 is > 2000 mg/kg bw.

Dermal:

In a GLP-compliant acute dermal toxicity study performed in accordance with OECD guideline 402, no mortality was observed in Sprague Dawley rats given a single dose of the analogue substance 2,2-Dimethyl-1,3-dioxolane-4-methanol at the limit test dose of 2000 mg/kg bw. Thus, by analogy,

2-isobutyl-2-methyl-1,3-dioxolane-4-methanol dermal LD50 is considered to be > 2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
only one study available

Justification for selection of acute toxicity – dermal endpoint
GLP and OECD guideline compliant study conducted on the analogue substance 2,2-dimethyl-1,3-dioxolane-4-methanol (Klimish score 2).

Justification for classification or non-classification

In the absence of mortality following oral exposure of rats to the limit test dose of 2000 mg/kg bw and a 2-week observation period , no classification for acute oral toxicity is warranted according to the criteria of Annex VI Directive 67/548/EEC or EU Regulation 1272/2008 (CLP).

The dermal LD50 of the analogue substance 2,2-Dimethyl-1,3-dioxolane-4-methanol was higher than 2000 mg/kg in rats and no mortality occurred at this concentration. Therefore, by analogy, 2 -isobutyl-2 -methyl-1,3-dioxolane-4-methanol is not classified for acute dermal toxicity according to the Regulation (EC) N° 1272-2008 (CLP) and according to the Directive 67/548/EEC.