Methyl acetate

Endpoint summary

Description of key information

Oral route: LD 50 = 6482 mg/kg (rats)
Dermal route: LD50 > 2000 mg/kg bw (rats)
Inhalative route: LC50 >49.2 mg/L

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Study similar to OECD 401. Deviation: only male rats used. Full data is not available for method and individual animal weight clinical effects because it is a publication. Non -GLP

GLP compliance:

no

Test type:

acute toxic class method

Species:

rat

Strain:

other: Carworth-Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

4 - 5 weeks old, 90-120 grams in weight. Reared in private colony fed Rockland rat diet.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

Dosages were arranged in a logarithmic series differing by a factor of two

No. of animals per sex per dose:

5

Control animals:

no

Statistics:

Estimated by the method of Thomson using the Tables of Weil.

Sex:

male

Dose descriptor:

LD50

Effect level:

6 482 mg/kg bw

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 = 6482 mg/kg bw (rat).

Executive summary:

LD50 = 6482 mg/kg bw (rat).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

6 482 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Source EU risk assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Concentrated vapor inhalation consists of exposing 6 male or female albino rats to a following stream of vapor-ladened air. The vapor-air mixture is generated by passing 2.5L /minute of dried air at room temperature through a fritted glass disc immersed to a depth of at least one inch in approximately 50 ml of the test chemical contained in a gas-washing bottle. Inhalations are continued for time periods in a logarithmic series with a ratio of two extending from one-fourth to eight hours, until the inhalation period killing about half the number of rats within 14 days is defined. Inhalation of metered vapor concentrations by rats is conducted with flowing streams of vapor prepared by various styles of proportioning pumps. Inhalation periods are usually four hours' duration unless slight toxicity enforces an eight hour period. Concentration recorded are nominal and not analytically verified. They are in an essentially logarithmic series with a factor of two, and the Table records the concentration yielding fractional mortaility among 6 rats within 14 days. Where no fractional mortality was observed, usually both the concentration yielding no mortality and that yielding complete mortality are indicated.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

other: albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

Not available

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Concentrations:

16,000 ppm
32,000 ppm

No. of animals per sex per dose:

6

Control animals:

no

Key result

Dose descriptor:

LC0

Effect level:

49.2 mg/L air

Exp. duration:

4 h

Dose descriptor:

LC100

Effect level:

98.4 mg/L air

Exp. duration:

4 h

49.2 mg/l < LC50< 98.4 mg/l

Interpretation of results:

GHS criteria not met

Executive summary:

Smyth et al screened industrial chemicals for acute toxicity values. For methylacetate the following values were determined.

LC0 = 49.2 mg/l/4h

LC50 > 49.2 mg/l/4h

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

49 200 mg/m³ air

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:

02.02.1988 - 16.02.1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Remarks:

QAU statement is included

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Kastengrund, SPF-Zucht. Internal strain Hoe: WIDSKf (SPF71)
- Age at study initiation: male ca. 8 weeks, female ca. 9 weeks
- Weight at study initiation: male 201 g, female 196 g (mean values)
- Housing: Animals were held in fully conditioned rooms in single cages (Makrolon cages type 3) on soft wood granules
- Diet: Rattendiät Altromin ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 50 +/- 20%
- Photoperiod: 12 hours dark / 12 hours light

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: ca. 30 cm² of the shaved dorsal skin
- Type of wrap if used: skin was covered with aluminium foil and in addition with an adhesive bandage


REMOVAL OF TEST SUBSTANCE
- Washing (if done): treated skin ws washed with water
- Time after start of exposure: 24 hours after exposure


TEST MATERIAL
- Amount applied: 2000 mg/kg bw. Weight was calculated assuming a density of the test tem of 0.932 kg/l
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 male plus 5 female animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed once per day, weighing was performed once per week
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Not applicable (limit test)

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

none

Clinical signs:

other: no clinical signs of toxicity were observed

Gross pathology:

no effects observed

Interpretation of results:

GHS criteria not met

Conclusions:

After an application period of 14 days followed by an observation period of 14 days, no mortality and other adverse effects were observed.

Executive summary:

The dermal toxicity of methyl acetate was assessed in a limit test. 2000 mg/kg bw of the test item was applied on the skin of Wistar-rats. The exposure period was 24 hours followed by an observation period of 14 days. No mortalities or other adverse effects were observed. It can therefore be concluded that the dermal LD50 is above the tested concentration of 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Oral route:

A study by Smyth et al. (1962) was conducted according to a standardized method [similar to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)] by using rats.

Single oral dose by gastric intubation to 5 non-fasted Carworth Wistar male rats, 4-5 weeks of age, 90 to 120 grams in weight reared in own colony on Rockland rat diet. Dosages were arranged in a logarithmic series differing by a factor of two. Based on the mortality during a 14 day observation period, the most probable LD50 value and its fiducial range were estimated using the method of Thomson using the Tables of Weil. LD50 was determined to be 6482 mg/kg bw (rat).

When methyl acetate was administered to rats in drinking water at a single dose level of 50mg/kg bw no mortality was reported (EPA, 1994).

 

Dermal route:

The most reliable data are by Hofmann and Jung (1988). The dermal toxicity of methyl acetate was assessed in a limit test. 2000 mg/kg bw of the test item was applied on the skin of Wistar-rats. The exposure period was 24 hours followed by an observation period of 14 days. No mortalities or other adverse effects were observed. It can therefore be concluded that the dermal LD50 is above the tested concentration of 2000 mg/kg bw.

The result is supported by a study with guinea pigs (EPA, 1994): Guinea pigs had 5-20 ml/kg of the sample applied to a gauze pad and the pad held in contact with the depilated skin under a rubber cuff for 24 hours. This allowed the resulting irritation to be classified and at the same time, it could be determined whether toxic effects by skin absorption resulted from the 24 hour contact. LD50 > 18684 mg/kg bw.

An other supporting study is by Moreno (1976). 10 rabbits were used. Animals were observed for mortality and systemic effects over 14 day period. No further details were provided.

Inhalative route:

The most reliable study is by Smyth et al. (1962). Smyth et al. used the following procedure for the screening of chemicals regarding their inhalation toxicity. Concentrated vapor inhalation consists of exposing 6 male or female albino rats to a following stream of vapor-loaded air. The vapor-air mixture is generated by passing 2.5L /minute of dried air at room temperature through a fritted glass disc immersed to a depth of at least one inch in approximately 50 ml of the test chemical contained in a gas-washing bottle. Inhalations are continued for time periods in a logarithmic series with a ratio of two extending from one-fourth to eight hours, until the inhalation period scarifying about half the number of rats within 14 days is defined. Inhalation of metered vapor concentrations by rats is conducted with flowing streams of vapor prepared by various styles of proportioning pumps. Inhalation periods are usually four hours' duration unless slight toxicity enforces an eight hour period. Concentration recorded are nominal and not analytically verified. They are in an essentially logarithmic series with a factor of two, and the Table records the concentration yielding fractional mortality among 6 rats within 14 days. Where no fractional mortality was observed, usually both the concentration yielding no mortality and that yielding complete mortality are indicated.

Test concentrations of methyl acetate were 16,000 ppm and 32,000 ppm.

The following results were obtained:

LC0 = 49.2 mg/l/4h = 49200 mg/m³/4h

LC50 > 49.2 mg/l/4h or > 49200 mg/m³/4h

 

 

Justification for classification or non-classification

The acute toxicity effect levels do not justify a classification for acute toxicity. Methyl acetate was evaluated in an EU Risk assessment and has a harmonized classifcation for STOT SE 3 (H336).