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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995-05-02 - 1995-05-18 (experimental phase)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well-documented GLP OECD guideline study without relevant deviations on the registered substance itself

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
OECD Guidelines for Testing of Chemicals, Section 4, No. 401, "Acute Oral Toxicity" OECD 1992
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
EC Directive B.1. acute toxicity (oral); appendix to Directive 92/69/EEC of the Commission dated 31 July 1992 to the seventeenth amendment of Directive 67/548/EEC of the council for adaptation of the legal and administrative regulations for classification, packaging and labelling of hazardous substances to technical progress
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Trimethyl orthoacetate
EC Number:
215-892-9
EC Name:
Trimethyl orthoacetate
Cas Number:
1445-45-0
Molecular formula:
C5H12O3
IUPAC Name:
1,1,1-trimethoxyethane
Test material form:
liquid
Details on test material:
- Substance type: pure substance
- Storage condition of test material: in a closed vessel under protective gas in a hood

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Cpb/Win:WU (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Bred by: Harlan Winkelmann GmbH, Gartenstraße 27, 33176 Borchen, Germany
- Females (if applicable) nulliparous and non-pregnant: [yes/no] : not specified
- Age at study initiation: healthy young adults
- Weight at study initiation: male animals: 125 - 157 g, female animals: 121 - 143 g
- Fasting period before study: about 16 hours before administration of the test substance food was withdrawn
- Housing: conventionally, each sex separate, maximum 5 animals/type III Makrolon cage
- Bedding: soft wood fibres of type HW 300/500 W supplied by JELU-Werk, Ludwigsmühle, 73494 Rosenberg, Germany; the manufacturer provides regular reports on tests for contaminants
- Diet (e.g. ad libitum): Ssniff R 10 complete feed for rats supplied by Ssniff, Spezialfutter GmbH, 59494 Soest; the manufacturer carries out regular analyses of the feed. Feed is available at libitum apart from a period of about 16 hours before administration of the test substance and 3 hours after administration.
- Water (e.g. ad libitum): Drinking water ad libitum, supplied by Gelsenwasser, Wasserwerk, 45721 Haltern, Germany; samples of the tap water are tested in-house each quarter.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±3 C
- Humidity (%): 30 - 70%
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12-hour light/dark rhythm (artificial light)

Administration / exposure

Route of administration:
other: rigid stomach tube
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
2000 mg/kg of bodyweight in a volume of 2.08 cm3/kg of bodyweight
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 male and 5 female animals
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were inspected for clinical signs 1/2 and 1 hour, 2, 3, 4, 5 and 6 hours after administration and once a day for the following 2 weeks. The time of occurrence of the symptoms and their nature were recorded separately for each animal. The bodyweights of the animals were determined on the day of administration (day 0), on day 7 and at the end of the test (day 14).
- Necropsy of survivors performed: yes. After the 14-day observation period, all the animals were sacrificed by inhalation of carbon dioxide, dissected and examined for gross changes to organs. The results of the dissection were recorded separately for each animal.
Statistics:
The toxicity was estimated without use of a statistical model.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured in any of the five male and five female animals.
Clinical signs:
After administration all the male animals showed signs of toxicity, starting after 1/2 hour, in the form of a crouched posture, staggering gait and ruffled fur. All the males showed a crouched posture and ruffled fur after 1 to 2 hours. Three males were free of signs of toxicity after 3 hours. Two males still showed a crouched posture and ruffled fur. After 4 hours, all the male animals were free of signs of toxicity. No females showed signs of toxicity throughout the observation period.
Body weight:
All the animals showed a normal weight gain.
Gross pathology:
Dissection at the end of the test revealed no evidence of gross changes in organs.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
LD50 > 2000 mg/kg b.w.
Conclusions:
The study was conducted under GLP according to OECD guideline 401 on the registered substance itself without deviations and therefore considered to be of the highest quality (reliability Klimisch 1). The method is to be considered scientifically reasonable with no deficiencies in documentation. Hence, the results can be considered as reliable to assess the acute oral toxicity in rats.
Following single application of Trimethyl orthoacetate (TMOA) at a dose of 2000 mg/kg bw the test material did not induce mortality. The bodyweight change was normal for all the test animals. Gross examination did not reveal any pathological changes in the examined animals. Hence, the test material was considered to be non-toxic under the conditions of the test and not requiring classification according to Regulation (EC) No 1272/2008.
Executive summary:

The test for acute oral toxicity of Trimethyl orthoacetate (TMOA) for rats (according to OECD 401 under GLP) showed, that the liquid test substance led to no mortality in five male and five female animals in a 14 -day limit test with a dose of 2000 mg/kg of bodyweight. No signs of systemic toxicity were observed during the observation period. The test substance was applied orally (with a rigid stomach tube) in a volume of 2.08 cm3/kg of bodyweight with an exposure time of 24 hours.

The changes in bodyweight were normal for all the animals.

Dissection at the end of the test revealed no evidence of gross changes in organs related to the test substance.

The limit test for oral toxicity of TMOA in rats following single application of the test item revealed the following median lethal dose (LD50):

male animals > 2000 mg/kg

female animals > 2000 mg/kg

Accordingly, TMOA is of low toxicity based on the LD50 determined. Hence, the test material was considered to be non-toxic under the conditions of the test and not requiring classification according to Regulation (EC) No 1272/2008.

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