Methyl acetate

Endpoint summary

Description of key information

Methyl acetate has proven to cause only weak skin irritation in humans and in rabbits (no oedema, erythema with maximum grade 1 reversible within 48 hours). Skin corrosion was not reported.
These results were obtained from in-vivo studies. An acute toxicity study by the dermal route did not indicate skin corrosion up to the limit dose level of 2000 mg/kg bw. Methyl acteate is classified as irritating to eyes. Hence, in-vitro testing on skin irritation and skin corrosion is not required according to Annex VII 8.1 column 2, bullet points 1 and 4.
Methyl acetate is irritating to eyes and consequently has been classified as R 36 ("irritating to eyes") or Eye Irrit. 2 "H319: Causes serious eye irritation", resp.
These results were obtained from in-vivo studies. Methyl acteate is classified as irritating to eyes. Hence, in-vitro testing on eye irritation is not required according to Annex VII 8.2 column 2, bullet point 1.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02.02.1988 - 05.02.1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Remarks:

QAU statement available

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HOECHST AG, Kastengrund, conventional breeding
- Age at study initiation: ca. 3 - 5 months
- Weight at study initiation: 1.9 - 2.4 kg
- Housing: in fully conditioned rooms in single cages (batteries)
- Diet: Altromin 2123 Haltungsdiät - Kaninchen, ad libitum plus hay (ca. 15 g per day)
- Water: deionised and dechlorinised water ad libitum


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

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 ml

Duration of treatment / exposure:

Exposure period: 4 hours

Observation period:

30 and 60 minutes, 24, 48 and 72 hours after tape removal

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 25 cm² of the shaved dorsal skin
- Type of wrap if used: exposed area was covered with a semiokklusive bandage

REMOVAL OF TEST SUBSTANCE
- Washing: treated skin was washed with water
- Time after start of exposure: 4 hours

SCORING SYSTEM:according to the guideline

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.2

Reversibility:

fully reversible within: 48h

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Reversibility:

fully reversible within: 48h

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Other effects:

24, 48, and 72 hours after patch removal, dry skin was observed

Table 1: Irritant response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Erythema	Edema
	Max. score: 1	Max. score: 0
30-60 min	1/1/1	0/0/0
24 h	0/1/1	0/0/0
48 h	0/0/0	0/0/0
72 h	0/0/0	0/0/0
Average 24h, 48h, 72h	0.0/0.3/0.2	0/0/0
Reversibility*)	c	c
Average time (unit) for reversion	48 hours	48 hours

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results, methyl acetate is not irritating to the skin and does not require labelling according to the dangerous substance directive.

Executive summary:

Methyl acetate was applied to the rabbit's skin. 0.5 ml of the test item was applied undiluted on the skin and covered with a patch for 4 hours. Effects were examined after 30 and 60 minutes, as well as after 24, 48 and 72 hours after patch removal. Only slight erytheme were observed after 30 -60 minutes as well as 24 hours after patch removal. Based on the results, methyl acetate can be considered as not irritant to skin and does not require labelling.

In-vitro testing for skin corrosion and skin irritation is not required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09.02.1988 - 16.02.1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Remarks:

QAU statement available

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: HOECHST AG, Kastengrund, conventional breeding
- Age at study initiation: ca. 3 - 5 months
- Weight at study initiation: 2.1 - 2.6 kg
- Housing: in fully conditioned rooms in single cages (batteries)
- Diet: Altromin 2123 Haltungsdiät - Kaninchen, ad libitum plus hay
- Water: deionised and dechloronosed water ad libitum

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

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated right eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount applied (volume or weight with unit): 0.1 ml applied into the left eye
- Concentration (if solution): pure test substance

Duration of treatment / exposure:

evaluation after 1, 24, 48 and 72 hours after application

Observation period (in vivo):

3 days plus an additional examination after 7 days

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): treated eyes were washed with a sodium chloride solution on each examination date
- Time after start of exposure: 24 hours after application and on each examination date if the treates eyes still showed secretion


SCORING SYSTEM: accordin to guideline


TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: mean values of the examinations after 24, 48 and 72 hours

Score:

1.3

Max. score:

1.7

Reversibility:

fully reversible within: 7 days after application

Remarks on result:

other: see table 1 for scores per each animal

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 7 days after appliocation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24 h

Score:

1

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 48 and 72h

Score:

2

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48 h

Score:

1

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

72 h

Score:

2

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

iris score

Basis:

mean

Time point:

other: mean values of the examinations after 24, 48 and 72 hours

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days after application

Remarks on result:

other: see table 1 for scores per each animal

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: mean values of the examinations after 24, 48 and 72 hours

Score:

2.7

Max. score:

3

Reversibility:

fully reversible within: 7 days after application

Remarks on result:

other: At 24 and 72 hours after application, conjunctivae of the animals showed white discoloration, bleedings and partly ablations. See table 1 for scores per each animal

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48 h

Score:

3

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

72 h

Score:

2

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24 h

Score:

3

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 48/72h

Score:

2

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: mean values of the examinations after 24, 48 and 72 hours

Score:

1.8

Max. score:

2

Reversibility:

fully reversible within: 7 days after application

Remarks on result:

other: see table 1 for scores per each animal

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48 h

Score:

2

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

72 h

Score:

1

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24 h

Score:

3

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 48/72h

Score:

1

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24 h

Score:

3

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

48 h

Score:

2

Reversibility:

fully reversible within: 7 days after application

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

72 h

Score:

1

Reversibility:

fully reversible within: 7 days after application

Table 1: Irritant response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 1	Max. score: 1	Max. score: 3	Max. score: 4
60 min	1/1/1	1/1/1	2/2/1	4/4/3
24 h	1/1/1	1/1/1	3/3/3	2/3/3
48 h	1/2/1	1/1/1	3/2/3	2/1/2
72 h	1/2/2	1/1/1	2/2/3	1/1/1
Average 24h, 48h, 72h	1.3	1.0	2.7	1.8
Maximum average score	1.7	1.0	3.0	2.0
Reversibility*)	c	c	c	c
Average time (unit) for reversion	7 days	7 days	7 days	7 days

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible 

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results, methyl acetate is classified as irritant (Xi) and has to be labelled with R36 (irritant to eyes).

Executive summary:

Methyl acetate was applied to the rabbit's eye.The test concentration was 0.1 ml test substance per eye. Effects were examined after 1, 24, 48 and 72 hours after application. Due to the fact that effects were still observed 72 hours after application, an additional examination took place 7 days after application. At this time point, no effects were observed anymore. Based on the results, methyl acetate has to be classified as irritant to eyes.

In-vitro testing is not required.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin Irritation

Methyl acetate was tested according to OECD Guideline 404 for its skin irritation potential. 0.5 ml of the test item were applied undiluted on the skin of the rabbits and covered with a patch for 4 hours. Effects were examined after 30 and 60 minutes, as well as after 24, 48 and 72 hours after patch removal. Only slight erytheme were observed after 30 -60 minutes as well as 24 hours after patch removal. Based on the results, methyl acetate can be considered as not irritant to skin. (Kreilling und Jung, 1988).

Application of 2 drops of methyl acetate to human skin caused cooling and desquamation but no irritation (von Oettingen, 1960). No further more data are available. Exposure to the vapours for 5 minutes leads to irritation of the eyes, nose, throat and trachea from approximately 15 mg/l (Reus, 1933, cited by BG Chemie, 1995).

Skin Corrosion

Methyl acetate has proven to cause only weak skin irritation in humans and in rabbits (no oedema, erythema with maximum grade 1 reversible within 48 hours).

Eye Irritation

Methyl acetate was examined for its eye irritation potential according to OECD Guideline 405 by application to the rabbit's eye. The test concentration was 0.1 ml test substance per eye (Kreilling und Jung, 1988). Effects were examined after 1, 24, 48 and 72 hours after application. Due to the fact that effects were still observed 72 hours after application, an additional examination took place 7 days after application. At this time point, no effects were observed anymore. Based on the results, methyl acetate has to be classified as irritant to eyes.

The maximum average score was 1.7 for the cornea, 1.0 for the iris, 3.0 for the conjunctivae and 2.0 for chemosis. There was a complete reversibility within 7 days for all 4 responses.

Respiratory Irritation

Data for respiratory irritation are given by Muller and Greff (1984), citied in EU RAR for methyl acetate. The quotation from the RAR is: "A RD50 of 829 ppm for mice was reported (Muller and Greff, 1984)."

Summary

Methyl acetate has proven to cause only weak skin irritation in humans and in rabbits (no oedema, erythema with maximum grade 1 reversible within 48 hours). Skin corrosion was not reported. These results were obtained from in-vivo studies. An acute toxicity study by the dermal route did not indicate skin corrosion up to the limit dose level of 2000 mg/kg bw. Methyl acetate is classified as irritating to eyes. Hence, in-vitro testing on skin irritation and skin corrosion is not required according to Annex VII 8.1 column 2, bullet points 1 and 4. Methyl acetate is irritating to eyes and consequently has been classified as R 36 ("irritating to exes") or Eye Irrit. 2 "H319: Causes serious eye irritation", resp. These results were obtained from in-vivo studies. Methyl acetate is classified as irritating to eyes. Hence, in-vitro testing on eye irritation is not required according to Annex VII 8.2 column 2, bullet point 1.

Literature

von Oettingen WF (1960). The aliphatic acids and their esters: Toxicity and potential dangers. The saturated monobasic aliphatic acids and their esters. Arch. Ind. Health 21, 28-65.

Muller J, Greff G (1984). Recherche de relations entre toxicité de molécules d’intérêt industriel et proprieties physico-chimiques: Test d’irritation des voies aeriennes supérieures appliqué à quatre familles chimiques. Fd. Chem. Toxicol. 22, 661-664.

Effects on eye irritation: irritating

Justification for classification or non-classification

Methyl acetate is classified as irritating to eyes. Hence, in-vitro testing on eye irritation is not required according to Annex VII 8.2 column 2, bullet point 1. Fort he same reasonin-vitro testing on skin irritation and skin corrosion is not required according to Annex VII 8.1 column 2, bullet points 1 and 4.