Trimethyl orthoacetate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-04-24 - 1995-05-08 (experimental phase)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well-documented study conducted under GLP according to OECD guideline 404 on the registered substance itself without deviations.

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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

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: in a closed vessel under protective gas in a hood

Test animals

Species:

rabbit

Strain:

other: small white Russian, Chbb:HM, SPF

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bred by: Dr. Karl Thomae GmbH, Chemisch-Pharmazeutische Fabrik, 88400 Biberach an der Riss 1, Germany
- Weight at study initiation: Animal 1: 2.6 kg, Animal 2: 2.4 kg, Animal 3: 2.6 kg
- Housing: conventional, singly in stainless steel cages
- Diet (e.g. ad libitum): Ssniff K 4 complete feed for rabbits ad libitum, supplied by Ssniff, Spezialfutter GmbH, 59494 Soest, Germany. The manufacturer carries out regular tests on the feed.
- 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 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±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)

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: The animals were shorn dorsally using a shearing apparatus for small animals (Aesculap Favorita II, shearing head GT 730, cutting height 1/2 mm).

Remarks:

Only healthy animals whose skin was intact after shearing were used for the test.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 cm3 test material / 6 cm2 of skin

Duration of treatment / exposure:

4 h

Observation period:

13 d

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6cm² dorsal skin
- Type of wrap if used: The area of application was covered with a gauze. This area was then covered with a non-irritant plaster and held in place for 4 hours using a semiocclusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
(indicate if minutes, hours or days)
The irritant effect was assessed 30-60 minutes, 24, 48 and 72 hours after removal of the patch, and after 7, 9 and 13 days.

SCORING SYSTEM:
- Method of calculation: Draize-grading

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.89

Max. score:

2

Reversibility:

fully reversible within: 13 d

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

2.33

Reversibility:

fully reversible within: 13 d

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

7 d

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 13 d

Results 4

Irritation parameter:

edema score

Basis:

mean

Time point:

7 d

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 13 d

Results 5

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 13 d

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 13 d

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

After exposure to the test item for 4 hours, and 30 to 60 minutes after removal of the patch there was found to be erythema of the skin which was very slight in two animals and well-defined in one animal. Two animals showed slight oedema, and one animal showed very slight oedema.
After 24 hours, erythema was well-defined in two animals and still very slight in one animal. Oedema was very slight to moderate. After 48 and 72 hours, all the animals had well-defined erythema and slight oedema.
After 7 days, all the animals showed very slight erythema and oedema. After 9 days, the skin of one animal still showed very slight erythema and oedema.
After 13 days, all the animals were free of signs of skin irritation in the area of application. Accordingly, test item is not a skin irritant.

Other effects:

- Other adverse local effects: After 7 and 9 days, all the animals were scaling and the skin surface showed detachment.

Applicant's summary and conclusion

Interpretation of results:

other: EU GHS criteria not met

Conclusions:

The study was performed according to the OECD TG404 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1). The validity criteria of the test system are fulfilled. The test material produced an average irritation index of 1.89 for erythema and eschar formation and an average irritation index of 2.0. for oedema formation 24, 48 and 72 hours after the end of exposure. After 13 days, all the animals were free of signs of irritation. Therefore, the test material was classified as non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

Executive summary:

A study was performed to assess the irritancy potential of the test material Trimethyl orthoacetate (TMOA) to the skin of small white russian rabbits. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 17 July 1992) and Method B4 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). The test was carried out by exposing three animals to the substance for 4 hours. The test showed that dermal application of the liquid test substance with a semiocclusive dressing resulted in well-defined erythema in two animals, and very slight erythema in one animal, after 24 hours. At this time, the animals showed very slight to moderate oedema. After 48 and 72 hours, all the animals were found to have well-defined erythema and slight oedema. After 7 days, all the animals showed very slight erythema and very slight oedema, together with scaling. After 9 days, one animal still showed very slight erythema and very slight oedema. All the animals still showed scaling. After 13 days, all the animals were free of signs of irritation.

The following averages were calculated from the numerically scored individual findings based on inspection 24, 48 and 72 hours after the end of exposure:

 

Exposure time 4 hours	Animal 1	Animal 2	Animal 3	Average
Erythema and eschar formation	2.00	2.00	1.67	1.89
Oedema	2.00	2.33	1.67	2.00

 

Since the test material produced a primary irritation index of 0.0 for erythema and oedema formation after 13 days, it was classified as non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. Thus, the test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations. No symbol and risk phrase are required.