Methyl benzoylformate

Endpoint summary

Description of key information

Guideline studies conducted prior to GLP requirements.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

according to guideline

Guideline:

other: Federal Register 38, No. 187, §1500.41, S. 27029

Version / remarks:

1973

Deviations:

yes

Remarks:

Exposure period extended to 24 hours, no scoring at 48 hour observation, and observation period shortened to 8 days.

Principles of method if other than guideline:

2 animals were tested applying the test substance for 5 min and 2 hours under occlusive conditions, respectively. The test substance was rinsed with Lutrol and observed after 24, 48 hours and 8 days.

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: mean: female: 3.44 kg

Type of coverage:

occlusive

Preparation of test site:

other: abraded and intact

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): undiluted

Duration of treatment / exposure:

5min, 2h or 24 hours

Observation period:

24, 72 hours and 8 days

Number of animals:

3 (24h exposures)
2 (5min and 2h exposure)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
SCORING SYSTEM: Draize

Irritation parameter:

erythema score

Basis:

mean

Remarks:

Animal 1

Time point:

other: 24, 72 hours

Score:

2.5

Max. score:

3

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: intact skin (24h exposure), 48h reading was not taken due to study design and age of the study.

Irritation parameter:

edema score

Basis:

mean

Remarks:

Animal 1

Time point:

other: 24, 72 hours

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: intact skin (24h exposure), 48h reading was not taken due to study design and age of the study.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

Animal 2

Time point:

other: 24, 72 hours

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: intact skin (24h exposure), 48h reading was not taken due to study design and age of the study.

Irritation parameter:

edema score

Basis:

mean

Remarks:

Animal 2

Time point:

other: 24, 72 hours

Score:

0.5

Max. score:

1

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: intact skin (24h exposure), 48h reading was not taken due to study design and age of the study.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

Animal 3

Time point:

other: 24h, 72 hours

Score:

2.5

Max. score:

3

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: intact skin (24h exposure), 48h reading was not taken due to study design and age of the study.

Irritation parameter:

edema score

Basis:

mean

Remarks:

Animal 3

Time point:

other: 24, 72 hours

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: intact skin (2h exposure), 48h reading was not taken due to study design and age of the study.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

Animal 4

Time point:

24/48 h

Score:

0.5

Max. score:

1

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: 2 hour exposure, 72h reading was not taken due to study design and age of the study.

Irritation parameter:

edema score

Basis:

mean

Remarks:

Animal 4

Time point:

24/48 h

Score:

0

Max. score:

0

Remarks on result:

other: 2 hour exposure, 72h reading was not taken due to study design and age of the study.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

Animal 5

Time point:

24/48 h

Score:

0.5

Max. score:

1

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: 2 hour exposure, 72h reading was not taken due to study design and age of the study.

Irritation parameter:

edema score

Basis:

mean

Remarks:

Animal 5

Time point:

24/48 h

Score:

0

Max. score:

0

Remarks on result:

other: 2 hour exposure, 72h reading was not taken due to study design and age of the study.

Other effects:

Scaling was found in all animals on day 8 of observation.

Results for 24h exposure:

	reading time	animal 1	animal 2	animal 3
erythema
intact skin	24h	2	2	2
	72h	3	2	3
	8d	2 S	0 S	2 S o
	mean 24,72h	2.5	2	2.5
abraded skin	24 h	3	3	2
	72h	3	3	3 o
	8d	2 S	1 S	2 sS o
	mean 24,72h	3	3	2.5
edema
intact skin	24 h	2	0	2
	72h	2	1	2
	8d	0	0	0
	mean 24,72h	2	0.5	2
abraded skin	24 h	2	2	2
	72h	3	3	3 o
	8d	0	0	0
	mean 24,72h	2.5	2.5	2.5

S: scaling; sS: strong scaling; overall

Results for internal method: After 2 hour exposure with the test substance to the skin of two rabbits erythema of score 1 was observed 24 hours later. This effect was fully reversible within 48 hours (score 0). 8 days after application scaling was still observed. No edema was observed at any reading time point.

Exposure Time	Animal No.	1. Redness - Corossion			2. Oedema
		24 hrs	48 hrs	8 Days	24 hrs	48 hrs	8 Days
2 hrs	1	1	0	0 S	0	0	0
	2	1	0	0 S	0	0	0

S = scaling

Interpretation of results:

GHS criteria not met

Conclusions:

The test material achieved mean erythema scores in 2 of 3 test animals of 2.5 each after a 24 hour occlusive exposure. After a 2 hour expsoure the test material achieved a mean erythema score of 0.5 in both animals tested, fully reversible within 8 days. Due to the non-standard exposure period, the test material is considered not to fulfill the criteria for skin irritation under EU regulation 12772/2008.

Executive summary:

In this guideline study (Federal Register 38, No. 187, §1500.41, S. 27029; 1973) the test material was tested twice with exposure times of 24 hours and 2 hours. After the 24 hour exposure period, the test material achieved mean erythema scores in 2 of 3 animals of 2.5 each. After the 2 hour exposure, the test material achieved a mean erythema scores in both test animals of 0.5, reversible in 8 days. As the standard exposure period is 4 hours, the test material is considered not to meet the criteria cor skin irritation classificaiton according to EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

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:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: Federal Register 38, No. 187, §1500.41, S. 27019 vom 27.09.73

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

72h observation period only (acceptable, as very mild findings only)

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: mean: 3.0 kg

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 µl
- Concentration (if solution): undiluted

Duration of treatment / exposure:

24 hours not washed out

Observation period (in vivo):

24, 48, 72 hours

Number of animals or in vitro replicates:

3 female

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: according to Draize

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

Animal 1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

Animal 2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

Animal 3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

Animal 1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

Animal 2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

Animal 3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

Animal 1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

Animal 2

Time point:

24/48/72 h

Score:

0.66

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

Animal 3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

Animal 1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

Animal 2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

Animal 3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results:

				Conjunctivae
animal	time after application	cornea	iris	Redness	Chemosis
1	24 hours	0	0	1	0
	48 hours	0	0	1	0
	72 hours	0	0	1	0
2	24 hours	0	0	1	0
	48 hours	0	0	1	0
	72 hours	0	0	0	0
3	24 hours	0	0	1	0
	48 hours	0	0	1	0
	72 hours	0	0	1	0
1	mean 24-72 h	0.0	0.0	1.0	0.0
2		0.0	0.0	0.7	0.0
3		0.0	0.0	1.0	0.0
mean 24-72h		0.0	0.0	0.9	0.0

Interpretation of results:

GHS criteria not met

Conclusions:

The test material did not provoke an irritating response in the test model. The test material does not fulfill the criteria for classification and labelling according to EU regulation 1272/2008.

Executive summary:

In this guideline (Federal Register 38, No. 187, §1500.41, S. 27019) study conducted prior to GLP adoption, the test material (EC 239-263-3), was found to be non-irritating to the rabbit eye. The test was conducted in three female rabbits. The test material did not fulfill the criteria for classification as an eye irritant according to the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Assessment of skin irritating properties is derived from effects observed at 2h or 24 h exposure. Whereas the EU classification system is based on effects observed after 4h semi-occlusive exposure, data is only available for 2h or 24h exposure for occlusive conditions.

Effects observed at 2h a clearly below the threshold for classification, whereas the erythema finding for the 24h exposure are above the classification threshold in the 24 -72h mean. It is considered that the values obtained for 4h semi-occlusive exposure would be in the non-irritating range. This is supported by secondary information on data from Bayer AG is summarized in the ECB IUCLID document (23-OCT-95)

Eye irritation:

Installation of the test item into eyes caused mild conjunctival irritation which did not resolved within 72h. All effects observed are below the threshold of regulation and the substance is therefore not considered to be irritating to eyes. This is supported by secondary information on data from Bayer AG is summarized in the ECB IUCLID document (23-OCT-95)

Justification for classification or non-classification

Skin irritation:

Given the non-standard exposure durations used in the key study (2 hours and 24 hours), a review of both test results was undertaken to assess the substance for skin irritation under the criteria of the EU Classificaiton, Labelling, and Packaging (CLP) regulation (1272/2008).

Average Erythema and Oedema scores over 72 hour exposure period for each test animal:

Test animal	2 hour exposure test		24 hour exposure test
	Erythema	Oedema	Erythema	Oedema
1	0.5	0	2.5	2
2	0.5	0	2	0.5
3	-	-	2.5	2

Although the results from the 24 hour classification meet the criteria for classification as a skin irritant, because the exposure period is 6 times longer than that indicated in the CLP regulation use of the result for classificaiton and labelling was considered to be overly conservative. As the 2 hour exposure test is only half the recommended exposure time, it is the registrants decision to use a range between the two tests. A average score range of 1 -2 across all three animals was considered by the registrant to be suitable for classificaiton and labelling. Based upon this range the substance does not meet the criteria of the EU CLP regulation for classification as a skin irritant.

Eye irritation:

Based upon the result of the key study, the substance does not meet the criteria of the EU CLP regulation for classification as an eye irritant.