2,2-bis[(allyloxy)methyl]butyl (3-{[({2,2-bis[(allyloxy)methyl]butoxy}carbonyl)amino]methyl}-3,5,5-trimethylcyclohexyl)carbamate

Endpoint summary

Description of key information

Skin Irritation (in vivo)

Under the conditions of this study, the test material was considered to be non-irritating to the skin.

Eye Irritation (in vivo)

Under the conditions of this study the test material was considered to be non-irritating to 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:

07 August 2009 to 20 October 2009

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: The Guidelines for the Testing of Chemicals Section 4: Health Effects (ministry of environmental protection of People's Republic of China).

Deviations:

no

GLP compliance:

not specified

Remarks:

Not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: adults
- Acclimation period: 5 days prior to the test

ENVIRONMENTAL CONDITIONS
- Temperature: 20 to 24°C
- Humidity: 50 to 70%

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

4 animals

Details on study design:

TEST SITE
- Area of exposure: 2 x 3 cm^2 area on the scapular to lumbar region of the back.
- Type of wrap if used: The application sites were covered with two layers of polyethylene sheet, secured with adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing: After 4 hours, coverings were removed and the application sites were rinsed completely with warm water.

OBSERVATION TIME POINTS
Animals were observed continually for 14 days, Skin irritation was evaluated at approximately 1, 24, 48 and 72 hoursr after patches were removed from the sites. Animals were observed daily for mortality and signs of morbidity.

SCORING SYSTEM:
The degree of irritation was scored according to the procedure of the Guidelines for the Testing of Chemicals.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Remarks:

Max score not specified

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Remarks:

Max score not specified

Other effects:

Individual skin irritation scores are presented in Table 1. No abnormal clinical signs were observed during the whole study period. The mean skin irritation score was 0.

Table 1: Skin irritation scores

Animal No.	Position	Skin Irritation scores
		1 h		24 h		48 h		72 h
		R	L	R	L	R	L	R	L
1	Erythema	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0
2	Erythema	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0
3	Erythema	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0
4	Erythema	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0
Total		0	0	0	0	0	0	0	0
Mean		0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0

Interpretation of results:

other: Not classified in accordance with EU criteria

Conclusions:

Under the conditions of this study, the test material was determined to be non-irritating to the skin.

Executive summary:

The skin irritation potential of the test material was investigated in accordance with the Guidelines for the Testing of Chemicals Section 4; Health Effects (ministry of environmental protection of People's Republic of China). The test material was administered to a 2 x 3 cm² area on the scapular to lumbar region of the back that had been shaved on the previous day. The application sites were covered with two layers of polyethylene sheet, secured with adhesive tape. After 4 hours, coverings were removed and the application sites were rinsed completely with warm water. Animals were observed continually for 14 days. Skin irritation was evaluated at approximately 1, 24, 48 and 72 hours after patches were removed from the sites. Animals were observed daily for mortality and signs of morbidity. No abnormal clinical signs were observed during the whole study period. The mean skin irritation score was 0. Under the conditions of this study, the test material was considered to be non-irritating to the 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:

07 August 2009 to 20 October 2009

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: Guidelines for the Testing of Chemicals Section 4; Health Effects (ministry of environmental protection of People's Republic of China).

Deviations:

no

GLP compliance:

not specified

Remarks:

Not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: adults
- Acclimation period: 5 days prior to the test

ENVIRONMENTAL CONDITIONS
- Temperature: 20 to 24ºC
- Humidity: 50 to 70%

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 g

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

4 animals

Details on study design:

TREATMENT METHOD
- 0.1 g of the test material was applied to the conjunctival sac of right eye of each rabbit. The lids were then gently held together for about one second to prevent loss of the test material. No washing to eyes was taken for 24 hours after application.

OBSERVATIONS
- Eye irritation was evaluated at 1, 24, 48 and 72 hours after test material application. The degree of irritation was scored according to the procedure of the Guidelines for the Testing of Chemicals. Animals were observed daily for mortality and signs of morbidity. Survival animals were euthanatised after observation period.

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Max score not specified

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Remarks:

Max score not specified

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Remarks:

Max score not specified

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Remarks:

Max score not specified

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Remarks:

Max score not specified

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Remarks:

Max score not specified

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Max score not specified

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Remarks:

Max score not specified

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Remarks:

Max score not specified

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Max score not specified

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Remarks:

Max score not specified

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Remarks:

Max score not specified

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Chemosis scores were not measured

Other effects:

Individual eye irritation scores are presented in Table 1. No abnormal clinical signs were observed during the whole study period. No delayed damnification was observed for all animals. The highest mean eye irritation score in the first 4 days (mean of sum of the scores from cornea, iris and conjunctivae) was 2.5 and the score was 0 at 48 hours. All controls scored 0. Based on these results and the irritation grading criteria in the Guidelines for the Testing of Chemicals, the test article is light irritating to eye (the grade is 3).

Table 1: Eye irritation scores

Animal No.	Position	Eye Irritation scores
		1 h		24 h		48 h		72 h
		R	L	R	L	R	L	R	L
1	Conjunctivae	2	0	2	0	0	0	0	0
	Cornea	0	0	0	0	0	0	0	0
	Iris	0	0	0	0	0	0	0	0
2	Conjunctivae	2	0	0	0	0	0	0	0
	Cornea	0	0	0	0	0	0	0	0
	Iris	0	0	0	0	0	0	0	0
3	Conjunctivae	4	0	2	0	0	0	0	0
	Cornea	0	0	0	0	0	0	0	0
	Iris	0	0	0	0	0	0	0	0
4	Conjunctivae	2	0	4	0	0	0	0	0
	Cornea	0	0	0	0	0	0	0	0
	Iris	0	0	0	0	0	0	0	0
Total		10	0	8	0	0	0	0	0
Mean		2.5	0.0	2.0	0.0	0.0	0.0	0.0	0.0
Mean score (4 days)		2.5, 0 (48 h)
Irritation		Light irritation
Grade		3

 

R = right eye, L = left eye

Interpretation of results:

study cannot be used for classification

Conclusions:

Under the conditions of this study, based on the Guidelines for the Testing of Chemicals the test material is light irritating to eye (the grade is 3).

Executive summary:

The eye irritation potential of the test material was investigated in accordance with the Guidelines for the Testing of Chemicals Section 4; Health Effects (ministry of environmental protection of People's Republic of China). 0.1 g of test material was administered into the conjunctival sac of right eye of four healthy rabbits with eye lids gently held together for about one second to prevent loss of the test material. The left eye was used as control for evaluation of eye irritation. No washing to eyes was taken for 24 hours after application. Eye irritation was evaluated at 1, 24, 48 and 72 hours after test material application. The degree of irritation was scored according to the procedure of the Guidelines for the Testing of Chemicals. Animals were observed daily for mortality and signs of morbidity; surviving animals were euthanatised after the observation period. Under the conditions of this study the highest mean eye irritation score in the first 4 days was 2.5 and the score was 0 at 48h. Based on the Guidelines for the Testing of Chemicals, the test material is 'lightly' irritating to the eye (the grade is 3).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation (in vivo)

The skin irritation potential of the test material was investigated in accordance with the Guidelines for the Testing of Chemicals Section 4; Health Effects (ministry of environmental protection of People's Republic of China). The test material was administered to a 2 x 3 cm² area on the scapular to lumbar region of the back that had been shaved on the previous day. The application sites were covered with two layers of polyethylene sheet, secured with adhesive tape. After 4 hours, coverings were removed and the application sites were rinsed completely with warm water. Animals were observed continually for 14 days. Skin irritation was evaluated at approximately 1, 24, 48 and 72 hours after patches were removed from the sites. Animals were observed daily for mortality and signs of morbidity. No abnormal clinical signs were observed during the whole study period. The mean skin irritation score was 0. Under the conditions of this study, the test material was considered to be non-irritating to the skin.

Eye Irritation (in vivo)

The eye irritation potential of the test material was investigated in accordance with the Guidelines for the Testing of Chemicals Section 4; Health Effects (ministry of environmental protection of People's Republic of China). 0.1 g of test material was administered into the conjunctival sac of right eye of four healthy rabbits with eye lids gently held together for about one second to prevent loss of the test material. The left eye was used as control for evaluation of eye irritation. No washing to eyes was taken for 24 hours after application. Eye irritation was evaluated at 1, 24, 48 and 72 hours after test material application. The degree of irritation was scored according to the procedure of the Guidelines for the Testing of Chemicals. Animals were observed daily for mortality and signs of morbidity; surviving animals were euthanised after the observation period. Under the conditions of this study the highest mean eye irritation score in the first 4 days was 2.5 and the score was 0 at 48 hours. Based on the Guidelines for the Testing of Chemicals, the test material is 'lightly' irritating to the eye (the grade is 3).

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance does not require classification with respect to irritation to skin or eyes.