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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009-11-27 to 2010-02-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-[[2,2,4-trifluoro-5-(trifluoromethoxy)-1,3-dioxolan-4yl]oxy-ethanol
EC Number:
700-535-6
Cas Number:
1190931-34-0
Molecular formula:
C6F6H6O5
IUPAC Name:
2-[[2,2,4-trifluoro-5-(trifluoromethoxy)-1,3-dioxolan-4yl]oxy-ethanol
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): DIOX Alkohol
- Physical state: organic mono-constituent substance
- Analytical purity: 95.5%
- Impurities (identity and concentrations): dimer impurity 3.5%, DIOX FH impurity 1%
- Purity test date: no data
- Lot/batch No.: 107-31
- Expiration date of the lot/batch: 31 December 2020
- Stability under test conditions: no data
- Storage condition of test material: Ambient temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Italy S.r.l., 33049 San Pietro al Natisone (UD), Italy
- Age at study initiation: 6 to 7 weeks old
- Weight at study initiation: 164 to 174 grams
- Fasting period before study: Overnight prior to dosing (Day –1) up to 4 hours after dosing.
- Housing: Polycarbonate cages measuring 59x38.5x20 cm, with stainless steel mesh lid and floor.
- Diet (e.g. ad libitum): 4 RF 18, ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 2°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): Approximately 15 to 25 air changes per hour
- Photoperiod (hrs dark / hrs light): Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours


IN-LIFE DATES: From: 22 October 2009 To: 2009-12-29

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 and 30 mg/ml
- Amount of vehicle (if gavage): Dose volume of 10 ml/kg of body weight for each animal.
- Justification for choice of vehicle: no justification given
- Lot/batch no. (if required):
- Purity: no data


MAXIMUM DOSE VOLUME APPLIED: Dose volume of 10 ml/kg of body weight for each animal.


DOSAGE PREPARATION (if unusual):


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A first sub-group of 3 female animals was dosed at a level of 2000 mg/kg (Step 1). 2000 mg/kg bw was chosen as this is the upper threshold value for the classification of oral toxic properties of a test substance.
Doses:
2000 and 300 mg/kg bw
No. of animals per sex per dose:
3 animals for the high dose group (Step 1); 2 groups each consisting of 3 animals for testing 300 mg/kg bw (Step 2 and step 3, respectively).
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and morbidity : Twice daily. Clinical signs 0.5, 2 and 4 hours after dosing, daily thereafter (14 days)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
No statistics applied.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Mortality occurred in all animals dosed at 2000 mg/kg body weight (Step 1); two animals were found dead approximately 5 hours after dosing and the remaining animal was found dead on Day 4.
No mortality was observed in the animals dosed at 300 mg/kg body weight (Steps 2 and 3).
Clinical signs:
2000 mg/kg bw: Piloerection, prone posture, unconscious and lachrymation were observed in all animals on the day of dosing. Prior to death the surviving animal appeared moribund on Days 2 and 3.
Clinical signs observed on the day of dosing in the first sub-group of animals treated at 300 mg/kg (Step 2) were piloerection and hunched posture. Piloerection was still observed on Day 2. Recovery occurred in the animals by Day 3. Hairloss on the sacral region was seen in a single animal (no. 49) by Day 13 up to the end of the observation period (Day 15).
Clinical signs observed in the second sub-group of animals dosed at 300 mg/kg were limited to piloerection observed on Days 1 and 2. Recovery occurred by Day 3 in all animals.
Body weight:
Changes in body weight observed during the study were within the expected range for this strain and age of animals.
Gross pathology:
No abnormalities were observed at necropsy examination performed in early decedent animals dosed at 2000 mg/kg (Step 1) and in those treated at 300 mg/kg (Steps 2 and 3) at the end of the observation period.
Other findings:
none reported

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The mortality pattern of DIOX alcohol demonstrates the LD50 to be greater than 300 mg/kg but less than 2000 mg/kg body weight. European Directives concerning the classification, packaging and labelling of dangerous substances and mixtures would indicate the classification "Acute oral toxicity - Category 4".
Executive summary:

The acute toxicity of DIOX alcohol was investigated following a single oral administration to the Sprague Dawley rat followed by a 14-day observation period. The study followed the protocol according to OECD Guideline 423.

A first sub-group of 3 female animals was initially dosed at 2000 mg/kg body weight (Step 1). Mortality occurred in all animals between Day 1 and 4 after dosing. Piloerection, prone posture, lachrymation, unconscious and moribund appearance were observed prior to death with a various incidence.

A second and third subgroup, each composed of 3 females, were then dosed at 300 mg/kg body weight (Steps 2 and 3). No mortality was recorded in any animal. Clinical signs related to treatment were limited to hunched posture and/or piloerection. Body weight changes recorded during the study were within the expected range for this strain and age of animals. No abnormalities were observed at necropsy examination performed on the animals treated at 2000 or 300 mg/kg.

The results indicate that the test item, DIOX alcohol, has a mortality pattern of a LD50 to be greater than 300 mg/kg but less than 2000 mg/kg body weight. European Directives concerning the classification, packaging and labelling of dangerous substances and mixtures would indicate the following:

Classification : Acute oral toxicity - Category 4

Signal word : Warning

Hazard statement (Oral) : H302 Harmful if swallowed

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