4,4'-thiodiethylene hydrogen -2-octadecenylsuccinate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23rd March 1981 - 22nd May 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

With 6 animals

GLP compliance:

not specified

Remarks:

Unlikely based on the time of the study

Test material

Test material information

1

Reference substance name:

4,4'-thiodiethylene hydrogen -2-octadecenylsuccinate

EC Number:

299-434-3

EC Name:

4,4'-thiodiethylene hydrogen -2-octadecenylsuccinate

Cas Number:

93882-40-7

Molecular formula:

C48H86O8S

IUPAC Name:

2-octadecenylsuccinic anhydride, thiodiethanol esterification products

Test material form:

solid

Remarks:

Waxy Solid

Specific details on test material used for the study:

Description: Off white, very thick liquid
Date of Receipt: February 26, 1981
Storaqe: Room temperature

Test material was heated to 60°C to facilitate handlinq but cooled
prior to dosing. No mixture was required.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Test Animals: Albino Rabbits
Strain: New Zealand White
Reason for Selection: Standard laboratory animal for ocular evaluations
Number: Six
Age: Young adults
Weiqht: 2.6 to 3.5 kilograms (Pretest)

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 m

Duration of treatment / exposure:

The upper and lower lids were gently held together for one second prior to releasing to Prevent loss of material.

Observation period (in vivo):

Approximately 1, 4, 24, 48, 72 hours, and 4, 7 and 14 days

Number of animals or in vitro replicates:

6 animals

Details on study design:

Preparation‘of Animals: Approximately twenty-four hours before test substance application both eyes of each animal were examined using fluorescein dye to check for presence of corneal ulceration. Just prior to test substance application, the eyes were examined again, but without fluorescein. Animals showing pre—existing corneal or conjunctival injury or irritation were not placed on study.

Administration of Test Substance: One-tenth milliliter (0.1 ml) of the test material was introduced into the lower conjunctival sac of the right eye of each animal. The upper and lower lids were gently held together for one second prior to releasing to Prevent loss of material. The contralateral eye served as the control.

Experimental Evaluation:
Viability Check: Twice Daily
Evaluation of Eye Irritation:
Intervals: Approximately 1, 4, 24, 48 and 72 hours and 4 and 7 days after treatment. If there were no signs of irritation on Day 7, no additional observations were made. If there were signs of irritation on Day 7, observations were made 14 days after treatment.

Methods: At each interval the treated and control eyes were examined and scored for ocular reactions according to the Draize scale. Fluorescein dye was used to confirm presence or absence of corneal ulceration in treated eyes starting with the 24 hour observation and at each subsequent observation until there was no stain retention for two observations. Unusual effects, such as pannus, blistering of the conjunctiva, ulceration and other effects indicative of corrosive action were also noted when present.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Remarks:

<1

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

other: Expected to be reversible in 21 Days

Remarks on result:

positive indication of irritation

Remarks:

>=1

Results 3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Remarks:

<2

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Remarks:

<2

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

>=1

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

>=1

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

>=2

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Remarks:

<2

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Remarks:

<1

Results 10

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

>=1

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Remarks:

<2

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Remarks:

<2

Results 13

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Remarks:

<1

Results 14

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

>=1

Results 15

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

>=2

Results 16

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Remarks:

<2

Results 17

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Remarks:

<1

Results 18

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

>=1

Results 19

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

>=2

Results 20

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Remarks:

<2

Results 21

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

>=1

Results 22

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

>=1

Results 23

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Remarks:

<2

Results 24

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

<2

Irritant / corrosive response data:

Ulceration of the cornea and necrosis or ulteration of the conjuctivae were observed from the 1 hour observation in all 6 animals. Five out of six animals demonstrated fully recovery by Day 14. Although animals were only observed up to Day14 , based on the recovery of all the other animals it is also expected that the sixth animal is likely to have recovered by Day 21.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The Substance is considered to be an eye irritant.

Executive summary:

This study was conducted to evaluate the ocular irritation produced by the Substance. Test material was heated to 60°C to facilitate handlinq but cooled prior to dosing. No mixture was required. Six New Zealand White Rabbits were used. One-tenth milliliter (0.1 ml) of the test material was introduced into the lower conjunctival sac of the right eye of each animal. The upper and lower lids were gently held together for one second prior to releasing to Prevent loss of material. The contralateral eye served as the control.Approximately 1, 4, 24, 48, 72 hours and at 4 , 7 and 14 days after treatment.At each interval the treated and control eyes were examined and scored for ocular reactions according to the Draize scale. Fluorescein dye was used to confirm presence or absence of corneal ulceration in treated eyes starting with the 24 hour observation and at each subsequent observation until there was no stain retention for two observations. Unusual effects, such as pannus, blistering of the conjunctiva, ulceration and other effects indicative of corrosive action were also noted when present.

All animals exhibited positive signs for ocular irritation. Five of the six animals were free of all signs of ocular irritation within 14 days after instillation. Although animals were only observed up to Day14 , based on the recovery of all the other animals it is also expected that the sixth animal is likely to have recovered by Day 21. The Substance is considered to be an eye irritant.