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Description of key information

Acute Toxicity oral: standard acute method (rigid stomach tube), rat (Wistar) m/f (OECD TG 401, GLP): LD50 > 2000 mg/kg b.w. (nominal) m/f

Acute Toxicity dermal: standard acute method (semiocclusive coverage), rat (Wistar) m/f (OECD 402, GLP): LD50 > 2000 mg/kg b.w. (nominal) m/f

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
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
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- Fasting period before study: about 16 hours before administration of the test substance food was withdrawn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)
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.
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:
other: 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 f
Gross pathology:
Dissection at the end of the test revealed no evidence of gross changes in organs.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The available data meets fully the tonnage-driven data requirements of REACH. The study and its results are sufficiently reliable due to the applied method, documentation and plausibility. Hence, the database is of good quality.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995-06-19 - 1995-07-06 (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
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
Hsd/Cpb: WU (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Animals were bred by Harlan Winkelmann GmbH, Gartenstrape 27, 33176 Borchen, Germany
- Age at study initiation: not specified
- Weight at study initiation: 200-300 g, the weight of the animal not differing by more than ± 20% from the average for all those of the same sex
- Fasting period before study: not specified
- Housing: conventionally, singly in type III Makrolon cages; Bedding: soft wood fibres of type HW 300/500 W supplied by JELU-Werk, Ludwigsmuhle, 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, Germany. The feed is provided ad libitum. The manufacturer carries out regular analyses of the feed.
- Water (e.g. ad libitum): Drinking water ad libitum, supplied by Gelsenwasser, Wasserwerk, 45721 Haltem, 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% (brief deviations due to cleaning of the animal room)
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12-hour light/dark rhythm (artificial light)
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: an area of the back
- % coverage: 10% of the body surface area
- Type of wrap if used: The treated skin was covered with gauze and the patch was fixed with an elastic dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressing was removed 24 hours after administration, and the substance remaining on the skin was wiped off using MEH 56 corn oil.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.08 cm3/kg of bodyweight or 2000 mg/kg of bodyweight
Duration of exposure:
24h
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
5/sex/dose
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were examined for clinical signs 1/2 and 1 hour, 2, 3, 4, 5 and 6 hours after administration, and once a day for the next two weeks. The skin in the area of application was examined for reactions caused by the test substance. The time of occurrence and the nature of the signs were recorded separately for each animal. The bodyweights of the animals were determined on the day of application (day 0), day 7 and at the end of the test (day 14).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: clinical signs, body weight and gross changes in organs (see above).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: All animals survived the 14 day observation period.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: All animals survived the 14 day observation period.
Mortality:
No mortality occurred during the observation period.
Clinical signs:
other: After a single administration of the test item in a dose of 2000 mg/kg of bodyweight, neither the male nor the female animals showed signs of toxicity or cutaneous reactions in the area of application during the observation period.
Gross pathology:
Dissection at the end of the test revealed no evidence of gross changes in organs related to the test substance. In particular, there were no changes in the skin and the subcutaneous tissue in the area of application.
Interpretation of results:
other: EU GHS criteria not met
Conclusions:
The study was conducted under GLP according to OECD guideline 402 on the registered substance itself. 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 animals did not show any general clinical signs. No pathological changes on the treated skin of males and females were found. All animals survived the experiment. The bodyweight change was normal for all the test animals. Gross examination did not reveal any pathological changes in the examined animals. So it may be stated that the median lethal dose (LD50) of TMOA is greater than 2000 mg/kg b.w. Since no animal showed at no observation time any pathological changes on the treated skin or other signs of irritation, it may be concluded that, under the conditions of this test, TMOA does not need to be considered as irritating to rat skin.
According to the Regulation (EC) No. 1272/2008, it may be concluded that TMOA is beyond categorization.
Executive summary:

The test for acute dermal toxicity of Trimethyl orthoacetate (TMOA) for rats (according to OECD 402 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 dermally (with semiocclusive dressing) in a volume of 2.08 cm3/kg of bodyweight with an exposure time of 24 hours.

None of the male or female animals showed cutaneous reactions in the form of erythema or oedema in the area of application during the observation period.

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, nor any alterations in subcutaneous tissue or in the area of application.

The limit test for dermal 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. Since no animal showed at no observation time any pathological changes on the treated skin or other signs of irritation, it may be concluded that, under the conditions of this test, TMOA does not need to be considered as irritating to rat skin. According to Regulation (EC) No 1272/2008, it may be concluded that TMOA is beyond categorization.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The available data meets fully the tonnage-driven data requirements of REACH. The study and its results are sufficiently reliable due to the applied method, documentation and plausibility. Hence, the database is of good quality.

Additional information

Justification for classification or non-classification

Within the studies according to OECD 401 and OECD 402 on Trimethyl orthoacetate, the LD50 was determined to be > 2000 mg/kg bw/day, which is above the limit value for classification.