Reaction mass of methyl acetate and methanol

Endpoint summary

Description of key information

The reaction mass of methyl acetate and methanol is assessed on the basis of the individual constituents methyl acetate and methanol using a read-across approach from the supporting substances (structural analogue or surrogate).

 

Skin irritation

Methyl acetate

In an in vivo skin irritation study according to OECD guideline 404, no skin irritating properties were observed for methyl acetate in rabbits.

Methanol

In an in vivo skin irritation study according to internal company standards (Klimisch score 2), methanol was found to be not irritating to skin.

 

Eye irritation

Methyl acetate

In an in vivo eye irritation study according to OECD guideline 405, eye irritation was observed for methyl acetate in rabbits. Methyl acetate was thus classified as eye irritant, category 2.

Methanol

In an in vivo eye irritation study according to internal company standards (Klimisch score 2), methanol induced mild to moderate eye irritation in rabbits which was fully reversible within 8 days. In another study in rabbits, application of 0.1 mL undiluted methanol resulted in mild to moderate conjunctivitis and edemas as well as mild iritis which was mainly reversible after 72 hours.

 

Conclusion

Based on the results of skin and eye irritation studies with the two source substances methyl acetate and methanol, skin or eye irritating properties of of the reaction mass of methyl acetate and methanol is assessed. Following a worst scenario, methyl acetate, the more critical of both substances, is used for assessment. Therefore, the reaction mass of methyl acetate and methanol is not considered a skin but an eye irritant (category 2).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

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 posture diet- rabbit, ad libitum plus hay (ca. 15 g per day)
- Water: Deionised and dechlorinised water ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- 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: 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

Max. score:

4

Reversibility:

other: no indication of irritation

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no indication of irritation

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no indication of irritation

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no indication of irritation

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.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Principles of method if other than guideline:

Study performed according to internal company standards (BASF-test) before actual guideline was adopted.

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount applied: Unspecified amount
- Concentration: 100 % (undiluted)

Duration of treatment / exposure:

1, 5, 15 min and 20 hours (ear: only 20 hours)

Observation period:

24, 48, 72 hours, 6 days and 8 days after beginning of application (exception: application time 20 hours: no observations after 24 hours)

Number of animals:

2 (1, 5 and 15 min); 2 (20 hours)

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm area of skin on the back and the ear
- % coverage: Not specified (application site 2.5 x 2.5 cm)
- Type of wrap: Cotton pad soaked with the undiluted test substance, covered by an impervious bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water, sometimes containing a mild detergent
- Time after start of exposure: 1, 5, 15 min, 20 hours (after the application)

SCORING SYSTEM: BASF scoring system, convertible to Draize

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

No individual animal scores given in the report.

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

No individual animal scores given in the report.

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

No individual animal scores given in the report.

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

After 1, 5, 15 min of exposure, no signs of irritation (erythema, edema) were apparent as well as after 24, 48 and 72 hours and after 6 and 8 days.

Other effects:

No mortality occurred. There were no clinical signs of systemic toxicity from the dermal exposure.

No individual animal scores given in the report.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eyes of the same animals served as controls

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL
- Concentration: Undiluted

Duration of treatment / exposure:

unspecified (not rinsed, guideline study)

Observation period (in vivo):

1, 4, 24, 48, 72 hours, 8 and 14 days

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Not rinsed (guideline study)

SCORING SYSTEM: OECD Draize

TOOL USED TO ASSESS SCORE: No data

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

No individual animal scores available.

Time point:

24/48/72 h

Score:

2.06

Max. score:

3

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

No individual animal scores available.

Time point:

24/48/72 h

Score:

2.06

Max. score:

3

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

No individual animal scores available.

Time point:

24/48/72 h

Score:

0.72

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

No individual animal scores available.

Time point:

24/48/72 h

Score:

0.72

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

No individual animal scores available.

Time point:

24/48/72 h

Score:

0.61

Max. score:

2

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

No individual animal scores available.

Time point:

24/48/72 h

Score:

0.61

Max. score:

2

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

No individual animal scores available.

Time point:

24/48/72 h

Score:

0.56

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

No individual animal scores available.

Time point:

24/48/72 h

Score:

0.56

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

conjunctivae score

Basis:

animal: 1 - 6

Time point:

24/48/72 h

Score:

2.06

Max. score:

3

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal: 1 - 6

Time point:

24/48/72 h

Score:

0.72

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

iris score

Basis:

animal: 1 - 6

Time point:

24/48/72 h

Score:

0.61

Max. score:

2

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

cornea opacity score

Basis:

animal: 1 - 6

Time point:

24/48/72 h

Score:

0.56

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Other effects:

not reported

Irritation scores as reported:

 

	Mean Scores
	Time after application [h]
	1	4	24	48	72
Conjunctivitis	0.89	2.00	1.67	2.28	2.22
Chemosis	2.00	2.00	0.67	1.00	0.50
Iritis	0.33	1.00	1.00	1.00	0.33
Corneal opacity	0.00	0.00	0.50	0.50	0.67

 

Interpretation of results:

not irritating

Conclusions:

The mean scores of the single symptoms did not exceed the respective limits for classification: therefore, this result can be interpreted in terms of a mild irritation potential not requiring classification as eye irritating.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

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
- 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: 0.1 mL applied into the left eye
- Concentration: 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: 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: according to guideline


TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days after application

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 7 days after application

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days after application

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days after application

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days after application

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days after application

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.66

Max. score:

3

Reversibility:

fully reversible within: 7 days after application

Remarks on result:

positive indication of irritation

Remarks:

After 24 and 48 hours, the conjunctivae of the animals showed white discoloration, bleedings and partly ablations.

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 7 days after application

Remarks on result:

positive indication of irritation

Remarks:

After 24 and 48 hours, the conjunctivae of the animals showed white discoloration, bleedings and partly ablations.

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 7 days after application

Remarks on result:

positive indication of irritation

Remarks:

After 24 and 48 hours, the conjunctivae of the animals showed white discoloration, bleedings and partly ablations.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 7 days after application

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 7 days after application

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days after application

Remarks on result:

positive indication of irritation

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:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Based on the results, methyl acetate is classified as irritant 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.

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

limited documentation

Principles of method if other than guideline:

Study performed according to internal company standards (BASF-test) before actual guideline was adopted.

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

other: saline-treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.05 mL
- Concentration: 100 %

Duration of treatment / exposure:

unspecified (not rinsed)

Observation period (in vivo):

1 hour, 24 hours, 8 days (no further time points reported)

Number of animals or in vitro replicates:

2

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Not rinsed

SCORING SYSTEM: BASF-code, convertible to DRAIZE

TOOL USED TO ASSESS SCORE: No data

Irritation parameter:

iris score

Remarks:

No iris score given.

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no iris score measured

Remarks on result:

no indication of irritation

Remarks:

no iris score measured

Irritation parameter:

iris score

Remarks:

No iris score given.

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: no iris score measured

Remarks on result:

no indication of irritation

Remarks:

no iris score measured

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

No individual animal scores available.

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

probability of mild irritation

Remarks:

only 24 h time point measured

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

No individual animal scores available.

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

probability of mild irritation

Remarks:

only 24 h time point measured

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

No individual animal scores available.

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 8 days

Remarks on result:

probability of mild irritation

Remarks:

only 24 h time point measured

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

No individual animal scores available.

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 8 days

Remarks on result:

probability of mild irritation

Remarks:

only 24 h time point measured

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

No individual animal scores available.

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

probability of mild irritation

Remarks:

only 24 h time point measured

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

No individual animal scores available.

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

probability of mild irritation

Remarks:

only 24 h time point measured

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

probability of mild irritation

Remarks:

only 24 h time point measured

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 8 days

Remarks on result:

probability of mild irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

probability of mild irritation

Irritant / corrosive response data:

After 1 h, mild erythema and cornea opacity as well as moderate edema associated with secretion were observed. After 24 h, the effects were assessed as mild. After 8 days the animals were without symptoms.

This screening test gave evidence of mild to moderate irritation of the mucous membrane on contact with pure methanol, which was fully reversible within 8 days. Therefore, there was no need for classification as eye irritating.

Exposure to an atmosphere saturated by methanol vapours at 20°C produced severe irritation of mucous membranes and milky corneal opacity in rats (time not specified) and eventually led to mortality of all animals within 8 h.

Interpretation of results:

not irritating

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Irritation/corrosion, methyl acetate

Skin irritation (rabbit), RL1

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 erythema 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).

 

Skin irritation (human), RL4

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).

 

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) and not requiring classification.

 

Eye Irritation (rabbit), RL1

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

In ECHA disseminated dossiers, a RD50 of 829 ppm for mice was reported for respiratory irritation by Muller and Greff (1984), citied in EU RAR for methyl acetate.

 

Conclusion: 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 eyes") or Eye Irrit. 2 "H319: Causes serious eye irritation", resp. 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.

 

Irritation/corrosion, methanol

Skin irritation (rabbit), RL2

The irritation potential of an unspecified dose of undiluted methanol in rabbits was examined under occlusive conditions after exposure intervals of 1, 5, and 15 minutes and 20 hours. According to Draize scoring, no signs of skin irritation were observed 24 hours and 8 days after treatment for any of the exposure time periods (BASF, 1975).

 

Eye irritation (rabbit), RL2

One hour after instillation of 0.05 mL undiluted methanol into the eyes of two rabbits, slight erythemas and corneal opacity as well as moderate edemas associated with secretion were observed. After 24 hours, the effects were assessed as mild, and after 8 days the animals had no symptoms (BASF, 1975).

 

Eye irritation (rabbit), RL2

In another study, mild to moderate conjunctivitis and edemas as well as mild iritis were produced in six rabbits after instillation of 0.1 mL undiluted methanol into the eyes. Average scores after 24, 48, and 72 hours were approximately 2 for conjunctivae and < 1 for other effects. Primary irritation subsided after 72 hours, although redness of the conjunctivae persisted at that time. Information on effects after 8 and 14 days was not available (Jacobs, 1990).

 

Conclusion

Based on the results of skin and eye irritation studies with the two source substances methyl acetate and methanol, the skin or eye irritation potential of the reaction mass of methyl acetate and methanol is assessed. Following a worst scenario, methyl acetate, the more critical of both substances, is used for assessment. Therefore, the reaction mass of methyl acetate and methanol is considered as an eye irritant.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The reaction mass of methyl acetate and methanol is assessed on the basis of the individual constituents methyl acetate and methanol using a read-across approach. The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Following a worst scenario, methyl acetate, the more critical of both substances, is used for the classification. The test item is not considered to be classified for skin irritation/corrosion but for eye irritation (category 2) according to EU Regulation (EC) No 1272/2008 (CLP), as amended for fifteenth time in Regulation (EU) No 2020/217.