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

Eye irritation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

946-937-7

Molecular formula:

C36H62N2O8

IUPAC Name:

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

Test material form:

liquid

Details on test material:

- Storage: cool and dark

Test animals / tissue source

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%

Test system

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.

Results and discussion

In vivo

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

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

Results 6

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

Results 7

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

Results 8

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

Results 9

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

Results 10

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

Results 11

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

Results 12

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

Results 13

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).

Any other information on results incl. tables

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

Applicant's summary and conclusion

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).