Bottom residues resulting from the synthesis of dimethyldioxane and the synthesis of isoprene from dimethyldioxane and trimethylcarbinol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May to August 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Test performed according to OECD/EU testing guideline and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Absorbent A2

IUPAC Name:

Absorbent A2

Details on test material:

- Name of test material (as cited in study report): Absorbent A2
- Substance type: UVCB
- Physical state: Brown liquid
- Stability under test conditions: months
- Storage condition of test material: room temperature, in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: from the copany Charles River Deutschland GmbH, D-97633, Sulzfeld
- Age at study initiation: data not available
- Weight at study initiation: between 156g and 177g
- Fasting period before study: yes
- Housing: the rats were kept in transparent macrolone cages (type 3-180, floor area 810 cm2) with 3 in each cage. the cages were cleaned and the bedding changed at least twice a week.
- Diet: free access to a pelleted diet "Altromin 1324"
- Water: free access to bottles of drink water of domestic quality, which was acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3°C
- Humidity: at least 30% and preferably not exceed 70%
- Air changes: 10 times/hour
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From 24-MAY-2011 to 31-MAY-2011

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: data not available
- Amount of vehicle (if gavage): 10 ml/kg bw
- Justification for choice of vehicle: data not available

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: data not available

Doses:

300 mg/kg bw and 2000 mg/kg bw

No. of animals per sex per dose:

4 x 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> each rat was observed 30 minutes, 2 hrs, 4hrs and 6hrs after the administration and therafter daily for a period of 14 consecutive days
> the body weight was determined on days 0, 7 and 14
- Necropsy of survivors performed: yes

Statistics:

not applicable

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Effect level:

300 mg/kg bw

Based on:

test mat.

Remarks on result:

other: All 6 animals survived not showing severe signs of toxicosis

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: All 6 animals survived showing slight signs of toxicosis

Mortality:

All six animas survived the treatment with the test item at a dosis of 300 mg/kg bw.
All six animas survived the treatment with the test item at a dosis of 2000 mg/kg bw.

Clinical signs:

On the day of application after 30 minutes and 2 hrs piloerection was observed in animal No. 1, No. 2 and No. 3 (group 1) receiving a dose of 300 mg/kg b.w. After 4 hrs and 6 hrs as well as from day 1 to the end of the observation period on day 14 all animals were free of any abnormalities.

On the day of application after 30 minutes piloerection was observed in animal No. 4, No. 5 and No. 6 (group 2) receiving a dose of 300 mg/kg b.w. These rats showed a hunched posture and piloerection after 2 hrs. After 4 hrs and 6 hrs as well as from day 1 to the end of the observation period on day 14 all animals were free of any abnormalities.

On the day of application after 30 minutes and 2 hrs a hunched posture and piloerection was observed in animal No. 7, No. 8 and No. 9 (group 3) receiving a dose of 2000 mg/kg b.w. These three rats showed piloerection after 4 hrs and 6 hrs. From day 1 to the end of the observation period on day 14 all animals were free of any abnormalities.

On the day of application after 30 minutes, 2 hrs, 4 hrs and 6 hrs a hunched posture and piloerection were observed in animal No. 10, No. 11 and No. 12 (group 4) receiving a dose of 2000 mg/kg b.w. From day 1 to the end of the observation period on day 14 all animals were free of any abnormalities.

Body weight:

The development of the body weight was normal in all animals.

Gross pathology:

There were no pathological signs detected in the necropsy.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information

Conclusions:

oral LD50 (rat, females) > 2000 mg/kg bw

Executive summary:

The oral LD50 of the test item in rats was found to be above 2000 mg/kg bw under the experimental conditions described in the final report. In accordance with the GHS, the test item should be categorized into category 5 or should not be classified.