1,2-Cyclohexanedicarboxylic Acid, 1-(phenylmethyl) ester, ester with 2,2,4-trimethyl, 1,3-petanediol mono(2-methyl propanoate)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09/06/2015-16/09/2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Sodium fluorescein dye was used at 48 and 72hr after there was no stain retention at 24hr. No impact expected since the additional observations confirm no corneal opacity.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

yes

Remarks:

Sodium fluorescein dye was used at 48 and 72hr after there was no stain retention at 24hr. No impact expected since the additional observations confirm no corneal opacity.

Principles of method if other than guideline:

Test article characterisation (Certificate of Analysis) not done to GLP by sponsor. No impact expected.

Sodium fluorescein dye procedures were performed at the 48 and 72 hour observation intervals after there was no stain retention at the 24 hour observation interval. No impact is expected since the additional information confirms there was no corneal opacity

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,2-Cyclohexanedicarboxylic Acid, 1-(phenylmethyl) ester, ester with 2,2,4-trimethyl, 1,3-petanediol mono(2-methyl propanoate)

EC Number:

950-347-5

Cas Number:

1661012-65-2

Molecular formula:

C27H40O6

IUPAC Name:

1,2-Cyclohexanedicarboxylic Acid, 1-(phenylmethyl) ester, ester with 2,2,4-trimethyl, 1,3-petanediol mono(2-methyl propanoate)

Test material form:

liquid

Specific details on test material used for the study:

Label Identity: Santicizer P-1700
Batch No: VSC1002-2
Supplied by: Valerus Specialty Chemicals
Data received: 12/05/15
Storage: Room temperature and humidity
Description: Clear light-yellow liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Remarks:

1 female & 2 male

Details on test animals or tissues and environmental conditions:

Test Animals
New Zealand White rabbits were received from Covance Research Products, Inc., Denver, PA on 06 May 2015 and 20 May 2015 and acclimated for at least five days. Only animals in apparent good health were made available for study assignment. Prior to being selected for this study, both eyes of each animal were examined according to the Draize technique for any evidence of irritation or abnormalities of the cornea, iris and/or conjunctiva. A Mini-Maglite® flashlight equipped with a high intensity bulb was used
to aid in the examination. Three rabbits (one female - two males), free from evidence of ocular irritation or abnormalities, were assigned to this study without conscious bias. The animals were born on 04 Oct 2014 or 29 Nov 2014 and/or 03 Jan 2015. The pretest body weight range was 3.2 - 3.4 kg. The animals were identified by cage notation and a uniquely numbered metal eartag. The animals were housed one per cage in suspended cages. Absorbent paper bedding was placed beneath the cages and changed at least three times per week. Fresh PMI Rabbit Chow (Diet #5321) was provided daily. Water was available ad fib/turn. The animal room, reserved exclusively for
rabbits on acute tests, was temperature controlled, had a 12-hour light/dark cycle and was kept clean and vermin free.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

The test article (0.1 mL) was placed by syringe into the conjunctival sac that was formed by gently pulling the lower eyelid away from the eye. After instillation, the lids were held together for approximately one second to insure adequate distribution of the test article. One eye of each rabbit was dosed. The contralateral eye served as a control.

Duration of treatment / exposure:

Single 0.1 mL dose into eye, observed post-dosing for 72 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

1 female, 2 males

Details on study design:

Analgesic:
An analgesic. Buprenorphine was administered subcutaneously between the shoulder blades approximately 1.5 hours prior to instillation of the test article.

Dosing
The test article (0.1 n,I) was placed by syringe into the conjunctival sac that was formed by gently pulling the lower eyelid away from the eye. After instillation, the lids were held together for approximately one second to insure adequate distribution of the test article. One eye of each rabbit was dosed. The contralateral eye served as a control.

Type and Frequency of Observations
Using a Mini-Maglite® flashlight equipped with a high intensity bulb, the treated eye of each rabbit was examined for irritation of the cornea, iris and conjunctiva at 1 24, 48 and 72 hours postdose. The control eyes were observed at the same time periods. Sodium fluorescein dye procedures were used at the 24,48 and 72 hour observation intervals. The eye was examined with the aid of an tiltraviolet light source. Ocular reactions were graded according to the numerical Draize technique. Body weights were recorded pretest and at termination. Animals were evaluated for physical signs twice daily for the first three days of the study All animals were humanely sacrificed with a 1 ml intravenous injection (via the marginal ear vein) of Fatal-Plus following study termination.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

Female

Time point:

24/48/72 h

Score:

0

Max. score:

80

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

Male

Time point:

24/48/72 h

Score:

0

Max. score:

80

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

Male

Time point:

24/48/72 h

Score:

0

Max. score:

80

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

10

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

10

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

10

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

There was no corneal opacity or iritis noted at any time point. Conjunctival redness (grade 1) was noted in one out of three eyes at 24 hours, which cleared by 48 hours [and was considered not due to test material]. The control eyes were normal at all time points.

Other effects:

There were no abnormal physical signs noted during the observation period. One animal gained weight and two animals' weights remained the same.

Any other information on results incl. tables

Table 1. Mean scores (EU and GHS)
Time Points	24 hours	48 hours	72 hours	Mean
Animal Number / Sex	H7700 / Female
Corneal Opacity	0	0	0	0.0
Iritis	0	0	0	0.0
Conjunctival Redness	0	0	0	0.0
Conjunctival Edema (chemosis)	0	0	0	0.0
Animal Number / Sex	H7706 / Male
Corneal Opacity	0	0	0	0.0
Iritis	0	0	0	0.0
Conjunctival Redness	1	0	0	0.33
Conjunctival Edema (chemosis)	0	0	0	0.0
Animal Number / Sex	H7707 / Male
Corneal Opacity	0	0	0	0.0
Iritis	0	0	0	0.0
Conjunctival Redness	0	0	0	0.0
Conjunctival Edema (chemosis)	0	0	0	0.0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the effects observed, Santicizer P1400 does not meet the criteria for classification as an ocular irritant under GHS or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. Santicizer P1700 meets the criteria for classification as Category IV (Minimal effects clearing in less than 24 hours) under the US Environmental Protection Agency system of classification for eye irritation.

Executive summary:

In a key OECD Guideline 405 study, the potential of the test material (Santicizer P1700) to cause ocular irritation or corrosion was evaluated after instillation into the rabbit eye. 1.5 hours prior to exposure, an analgesic, Buprenorphine was administered subcutaneously between the shoulder blade of three healthy New Zealand White rabbits (1 female and 2 males). 0.1 mL of the test material was placed into the conjunctival sac of one eye of each of the three rabbits, with the contralateral eye serving as control. Treated and control eyes were examined pretest and scored by the Draize technique at 1, 24, 48, and 72 hours post-exposure. Sodium fluorescein dye procedures were used at the 24, 48, and 72 hour observation intervals and animals were evaluated for physical signs twice daily for the first three days of the study. Body weights were recorded immediately pretest and at termination.

 

No abnormal physical signs were observed during the study period and one animal gained weight while the weight of the remaining two animals remained the same. No corneal opacity or iritis was observed at any observation point and conjunctival redness was observed in one animal at the 24 hour observation point. However, this has cleared by the 48 hour observation point. No other treatment-related ocular effects were observed and all control eyes appeared normal through the study period.

 

Based on the effects observed, Santicizer P1400 does not meet the criteria for classification as an ocular irritant under GHS or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. Santicizer P1700 meets the criteria for classification as Category IV (Minimal effects clearing in less than 24 hours) under the US Environmental Protection Agency system of classification for eye irritation.