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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 14 Nov 2006 to 08 Mar 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to an international test guideline and to GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
up-and-down procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: 11 weeks
- Weight at study initiation: 179.7 to 196.3 g
- Fasting period before study: No
- Housing: Individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz) during treatment and observation.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 48/06 (Provimi Kliba AG, CH-4303 Kaiseraughst/Switzerland) ad libitum. Results of analyses for contaminants are archived at RCC Ltd.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr):10-15
- Photoperiod (hrs dark / hrs light):12/12 (music during the daytime light period)

IN-LIFE DATES: From: 22 Nov 2006 to 19 Dec 2006

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.90 mL/kg

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after adminitration on test day 1 (with the clinical signs) and twice daily during days 2-15.
- Frequency of weighing: On test day-1 (prior to removal of food), on test days 1 (prior to administration), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs: daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after adminitration on test day 1. Once daily during days 2-15. All abnormalities were recorded.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
All animals showed slightly ruffled fur from the 30-minute, 1-hour or 2-hour reading until the 5-hour observation timepoint. This sign persisted in four animals until test day 2, 3 or 4. Hunched posture was also observed in 4 animals from the 30- minute or 2-hour reading until the 3-hour, 5-hour reading or test day 3. Slight sedation was also noted in 2 animals from the 3- to the 5-hour reading.
Body weight:

All the animals gained body weight during the study period. The body weight of the animals was within the range commonly observed for this strain and age.
Gross pathology:
Effects on organs:
No macroscopic findings were recorded at the scheduled necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material is not harmul by the oral route.
Executive summary:

In an acute oral toxicity study (RCC 2007 study n° B05657), 5 Wistar female rats were given a single oral dose of undiluted Dimethyl 2-methyl glutarate at the dose of 2000 mg/kg bw and observed for 14 days.

 

Oral LD50Females > 2000  mg/kg bw.

 

Dimethyl 2-methyl glutarate is not classified based on the LD50 in females.             

 

No mortality was observed. The clinical signs consisted of slightly ruffled fur, hunched posture and slight sedation in most animals. There was no effect on body weight gain.

 

This acute oral study is classified as acceptable.  It does satisfy the guideline requirement for an acute oral study (OECD425) in the rat.