Methyl benzoate

Endpoint summary

Description of key information

Methyl Benzoate is not irritating to the skin and eyes.

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:

1985-04-11 to 1985-04-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Leicestershire
- Age at study initiation: 12 to 16 weeks
- Weight at study initiation: 2.24 to 2.66 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): rabbit diet, AW Tindall Limited, Holbeach, Lincolnshire ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least five days prior to the start of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 51 to 55
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

IN-LIFE DATES: From: 11 April 1985 To: 14 April 1985

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL of the neat test material was applied onto the skin

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

three

Details on study design:

TEST SITE
- Area of exposure: test substance was applied onto a test site on the back of each rabbit
- % coverage: substance was evenly distributed onto a patch (surgical gauze) with a surface area of 6.25 cm2
- Type of wrap if used: sleek adhesive strapping

REMOVAL OF TEST SUBSTANCE
- Washing (if done): any residual test material was removed by gentle swabbing with cotton wool soaked in ether
- Time after start of exposure: 4 hours after exposure

SCORING SYSTEM: Scoring was done according to the scale developed by Draize JH 1959, Association of Food and Drug Officials of the United States, Austin, Texas: The appraisal of the safety of chemicals in foods, drugs and cosmetics.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

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: not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The test material produced no evidence of primary cutaneous irritation in any rabbit throughout the observation period of 72 hours. Desquamation extending beyond the site of application was observed in all three rabbits at the 72 hours reading only.

Other effects:

No other effects were reported.

Table 1: Individual erythema and oedema scores

		Individual scores (according to Draize)
Skin reaction	Reading (hours)	Rabbit 1 (417)	Rabbit 2 (427)	Rabbit 3 (459)	Total
Erythema and Eschar formation	1	0	0	0	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
Oedema formation	1	0	0	0	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

The test material was found to be non-irritant to rabbit skin.

Executive summary:

The skin irritation potential of the test substance methyl benzoate was studied under GLP condition in an in-vivo rabbit study according to OECD guideline No 404. The backs and the flanks of three healthy albino rabbits of the New Zealand White strain (aged 12 to 16 weeks and weighing between 2.2 and 2.6 kg) were clipped off the fur the day prior to the start of the test. On the day of the test, an aliquot of 0.5 mL of the neat test substance was applied onto the undamaged skin of the animals. To this end, the test material was distributed evenly onto a semi-occlusive patch with a surface area of 6.25 cm2, which was then fixed on the skin with adhesive strapping. The patch was removed after four hours of exposure and remaining test substance was removed by gentle swabbing with cotton wool soaked in ether. The skin reaction was graded in accordance with the scoring system developed by Draize (1959). The test material produced no evidence of primary cutaneous skin irritation in any rabbit throughout the observation period of 72 hours and the individual scores for erythema and oedema were "zero" at observation time points 24, 48 and 72 hours after treatment. Desquamation extending beyond the exposure site was observed in all three animals at the 72 hours reading only. On the basis of the test results it was concluded that methyl benzoate is non-irritant to the rabbit skin.

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:

1985-04-15 to 1985-04-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Leicestershire, UK
- Age at study initiation: 12 to 16 weeks
- Weight at study initiation: 2.63 to 3.16 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): standard rabbit diet (A.W. Tindall Limited, Holbeach, Lincolnshire, UK) ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: minimum five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2 °C
- Humidity (%): 50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 mL of neat substance

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

up to 21 days, if eye irritation persisted at the 72 hours observation

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Test substance was not removed

SCORING SYSTEM:
Assessment of damage/irritation was made according to the numerical evaluation system according to Draize JH, 1959, Association of Food and Drug Officials of USA, Austin, Texas "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics".

TOOL USED TO ASSESS SCORE: examination of the eye was facilitated by use of a standard ophtalmoscope (Keeler)

EVALUATION OF DATA: The numerical data obtained from the observations was evaluated according to a modified version of the system described by Kay JH and Calandra JC, J Soc Cosmet Chem 1962, 13, 281-289.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

All animals showed some response at the first reading that was performed 1 hour after treatment. Irritation effects were transient and all three tested animals showed only slight irritation effects 24 hours after the treatment that consisted mainly of redness of the conjunctivae (all three animals) and weak chemosis (two out of three animals). All effects had disappeared after 72 hours.

Other effects:

No other effects were noted.

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is non-irritating to the rabbit eye.

Executive summary:

The eye irritation potential of the substance methyl benzoate was studied under GLP conditions in rabbits according to OECD guideline No 405. Three healthy New Zealand White rabbits aged 12 to 16 weeks and weighing 2.6 to 3.2 kg and showing no evidence of ocular lesions were used in the test. An aliquot of 0.1 mL of the neat test material was instilled into the right eye of each rabbit by gently pulling the lower lid away from the eyeball. The eyelids were then held together for about one second. The left eyes remained untreated and served as a control. Damage and irritation of the eyes were assessed after 1, 24, 48 and 72 hours after treatment according to the numerical evaluation scheme developed by Draize. The observation made at 24 hours after treatment revealed no effects in the cornea or iris of all three animals. Redness of the conjunctivae was observed in all three animals and chemosis was seen in 2 out of three animals. All effects were transient and had disappeared at the observation made 72 hours after treatment. The scores for conjunctival redness and chemosis (mean of gradings at 24, 48 and 72 hours) were not exceeding 0.66. The substance hence is considered as non-irritating to the rabbit eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion

Key study

Methyl benzoate is considered to be not irritating to the skin. The result from a fully reliable study conducted according to OECD TG 404 showed no evidence of primary cutaneous irritation throughout the observation period of 72 hours.

Eye irritation/corrosion

Key study

The result from a fully reliable study conducted according to OECD TG 405 showed only slight irritation effects 24 hours after the treatment that consisted mainly of redness of the conjunctivae (all three animals) and weak chemosis (two out of three animals). All effects disappeared after 72 hours. Therefore methyl benzoate is considered to be not irritating to the eye.

Justification for selection of skin irritation/corrosion endpoint:
The full reliable study performed according to principles equivalent to those of OECD TG was chosen as the key study.

Justification for selection of eye irritation endpoint:
Only one valid and reliable study is available.

Justification for classification or non-classification

Skin irritation/corrosion:

Based on the above-stated assessment of the irritating properties of methyl benzoate, the results from reliable studies show that the substance is not irritating to the skin. Accordingly, methyl benzoate does not need to be classified according to CLP (Regulation (EC) No 1272/2008).

 

Eye irritation/corrosion:

Based on the above-stated assessment of the irritating properties of methyl benzoate, the results from a reliable study show that the substance is not corrosive or irritating to the eye. Accordingly, the substance does not need to be classified according to CLP (Regulation (EC) No 1272/2008).