Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guideline
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

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): PEX-2 (previous public name of the registered substance)
- Storage condition of test material: at room temperature

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels
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).

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.