Trimethyl orthoacetate

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

Test guideline 2

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

Test material

Test material information

Constituent 1

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: with exclusion of moisture in a closed vessel in a laboratory hood

Test animals

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)

Administration / exposure

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).

Results and discussion

Effect levels

Effect levels 1

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.

Effect levels 2

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.

Applicant's summary and conclusion

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.