3,3'-thiodi(propionic acid)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study with acceptable restrictions Rabbit eyes tested

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: ICCVAM-Recommended Test Method Protocol Isolated Rabbit Eye Test Method

Deviations:

yes

Remarks:

no positive control, no fluorescein retention tested

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

3,3'-thiodi(propionic acid)

EC Number:

203-841-3

EC Name:

3,3'-thiodi(propionic acid)

Cas Number:

111-17-1

Molecular formula:

C6H10O4S

IUPAC Name:

3-[(2-carboxyethyl)sulfanyl]propanoic acid

Details on test material:

- Name of test material (as cited in study report): 3,3´-Thiobispropanoic acid
- Analytical purity: 99.5 %
- Lot/batch No.: NT-463

Test animals / tissue source

Species:

other: rabbit eyes

Strain:

not specified

Details on test animals or tissues and environmental conditions:

Enucleated eyes were used for the test.

Test system

Vehicle:

physiological saline

Controls:

other: control eyes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of the test material (ca. 79 g)

Duration of treatment / exposure:

10 seconds

Observation period (in vivo):

60, 120, 180 and 240 minutes following treatment

Number of animals or in vitro replicates:

Three eyes were treated with test material, two additional eyes remained untreated for control purposes

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after 10 seconds the test material was washed off the cornea using a minimum of 20 mL of saline solution.
The untreated eyes were similarly washed and used for control

SCORING SYSTEM: REET parameters


TOOL USED TO ASSESS SCORE: slit lamp-biomicroscope

Results and discussion

In vitro

Results

Results 1

Irritation parameter:

percent corneal swelling

Run / experiment:

1 h observation

Value:

15.1

Negative controls validity:

valid

Results 2

Irritation parameter:

percent corneal swelling

Run / experiment:

2 h observation

Value:

18.1

Negative controls validity:

valid

Results 3

Irritation parameter:

percent corneal swelling

Run / experiment:

4 h observation

Value:

21.8

Negative controls validity:

valid

Results 4

Irritation parameter:

cornea opacity score

Remarks:

Corneal Opacity x Area

Run / experiment:

1 h observation

Value:

0

Negative controls validity:

valid

Results 5

Irritation parameter:

cornea opacity score

Remarks:

Corneal Opacity x Area

Run / experiment:

2, 3, 4 h observation

Value:

2

Negative controls validity:

valid

Results 6

Irritation parameter:

morphological effects

Run / experiment:

3, 4 h observation

Negative controls validity:

valid

Remarks on result:

other: Sloughing

Any other information on results incl. tables

Rabbit enucleated eye test- Individual scores for Corneal Opacity:

	Test eye												Control Eye
Chamber number	1				2				3				1				2
Time after treatmen (Minutes)	60	120	180	240	60	120	180	240	60	120	180	240	60	120	180	240	60	120	180	240
Degree of Corneal Opacity	0	1	1	1	0	1	1	1	0	1	1	1	0	0	0	0	0	0	0	0
Area of Corneal Opacity	0	2	2	2	0	2	2	2	0	2	2	2	0	0	0	0	0	0	0	0

Some loss of transparency was noted in the test eyes during the study. No corneal effect were noted in the control eyes during the study.

Rabbit enucleated eye test- Individual measurements for Corneal thickness (µm):

Test eye
Time after treatment (minutes)		60						120						180						240
Corneal position		oc	1	2	3	4	mean	oc	1	2	3	4	mean	oc	1	2	3	4	mean	oc	1	2	3	4	mean
Chamber number	1	401	398	395	406	400	400	421	416	416	420	422	419	425	433	434	444	442	435.6	444	443	424	430	440	436.2
	2	437	445	436	439	425	436.4	461	447	446	444	443	448.2	484	475	476	479	480	478.8	463	461	458	438	462	456.4
	3	413	403	410	410	430	413.2	422	402	410	411	432	415.4	445	418	415	414	439	426.2	438	420	418	422	448	429.2

Control Eyes
Time after treatment (minutes)		60						120						180						240
Corneal position		oc	1	2	3	4	mean	oc	1	2	3	4	mean	oc	1	2	3	4	mean	oc	1	2	3	4	mean
Chamber number	1	395	373	375	381	386	382	385	371	364	372	374	373.2	383	365	364	370	368	370	388	362	362	371	377	372
	2	427	399	396	413	410	409	385	395	387	400	401	393.6	403	388	389	392	396	393.6	398	383	392	402	394	393.8

Corneal swelling of the test eyes was greater than observed in the control eyes over the same period.

Sloughing was noted in all test eyes . Control eyes were normal.

Rabbit enucleated eye test-Corneal Epithelium condition:

Test Eyes
Time after treatment (minutes)		60	120		180	240
Chamber number	1	normal	normal	Sloughing		Sloughing
	2	normal	normal	Sloughing		Sloughing
	3	normal	normal	normal		Sloughing

Control Eyes
Time after treatment (minutes)		60	120		180	240
Chamber number	1	normal	normal	normal		normal
	2	normal	normal	normal		normal

Rabbit enucleated eye test- Determination of corneal swelling:

Test Eye:

Mean corneal swelling 1 hour following treatment: 15.1 %

Mean corneal swelling 2 hours following treatment: 18.1 %

Mean corneal swelling 4 hours following treatment: 21.8 %

Control Eye:

Mean corneal swelling 1 hour following treatment: 9.9 %

Mean corneal swelling 2 hours following treatment: 6.5 %

Mean corneal swelling 4 hours following treatment: 6.4 %

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Executive summary:

For the assessment of the eye irritation potential of 3,3´-Thiobispropanoic acid data from an Isolated Rabbit Eye Test (REET) are available.

Three enucleated rabbit eyes were exposed to a single application of 0.1 mL test sample for 10 seconds followed by a 20 mL saline rinse. Two untreated eyes were similarly washed and used as control. Observations were made 60, 120, 180 and 240 minutes following treatment.

Some loss of transparency was noted in the test eyes during the study (opacity score 1, area score 2). No corneal effects were noted in the control eyes during the study. Corneal swelling of the test eyes was greater than observed in the control eyes over the same period. Sloughing was noted in all test eyes. Control eyes were normal. Based on the morphological effects (sloughing) the test material was considered to have the potential to cause severe ocular damage.