3,3'-thiodi(propionic acid)

Endpoint summary

Description of key information

skin irritation: not irritating (OECD TG 404)

eye irritation: irreversible damage (REET)

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

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

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: twelve to twenty weeks
- Weight at study initiation: 2.0 - 2.5 kg
- Housing: The animals were individually housed in supended cages.
- Diet (e.g. ad libitum) + Water (e.g. ad libitum): Free access to mains drinking water and food
- Acclimation period: 5 days




ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23°C
- Humidity (%): 30 - 70%
- Air changes (per hr): fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light and twelve hours darkness

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Amount / concentration applied:

TEST MATERIAL
- Concentration: 0.5 g of test material moistened with 0.5 ml of distilled water.

Duration of treatment / exposure:

one patch was removed at each time of three time points: 3 minutes, 1 hour and 4 hours after application.

Observation period:

One hour following the removal of the patches, and 24, 48 and 72 hours later, the test sides were examined for evidance of primary irritation.

Number of animals:

3 animals

Details on study design:

TEST SITE
- Area of exposure: shorn skin
- % coverage: 2.5*2.5 cm
- Type of wrap if used: a strip of surgical adhesive tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.



SCORING SYSTEM: Draize classification scheme

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Individual Skin reaktions (3 minutes and 1 hour):

Skin Reaction	Observation Time	Individual scores- Rabbit Number and Sex
		65966 Male
		3-minutes exposure		1 hour exposure
Erythema/Eschar Formation	1 hour 24 hours 48 hours 72 hours	0 0 0 0	0 0 0 0		0 0 0 0
Odema formation	1 hour 24 hours 48 hours 72 hours	0 0 0 0	0 0 0 0		0 0 0 0

Individual skin reaktion (4 -hour exposure):

Skin Reaction	Observation Time	Individual scores- Rabbit Number and Sex
		65966 male	65983 male	65985 male
Erythema/Eschar Formation	1 hour 24 hours 48 hours 72 hours	1 0 0 0	1 0 0 0	1 0 0 0
Odema formation	1 hour 24 hours 48 hours 72 hours	1 0 0 0	0 0 0 0	0 0 0 0
Sum of 24 and 72 hour readings: 0
Primary Irritation Index 8S/6): 0/6 = 0.0
Classification: NON IRRITANT

The test material produced a primary irritation index of 0.0 and was classified as NON-IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

Interpretation of results:

GHS criteria not met

Conclusions:

not irritating to skin (OECD TG 404)

Executive summary:

In a primary dermal irritation study according to OECD Guideline 404 (July 17, 1992), 3 young adult New Zealand white rabbits were dermally exposed to 0.5 g of 3,3´-Thiobispropanoic acid moistened with 0.5 ml of distilled water to 2.5 x 2.5 cm² skin surface for 3 minutes, 1 hour and 4 hours under semiocclusive conditions. Animals then were observed for 72 h. Irritation was scored by the method of Draize. 

After 3 min and 1 hour exposure erythema and edema scores were 0 at all observations. After 4 h exposure very slight erythema (grade 1) was present in all tree animals, and very slight edema (grade 1) in 1/3 animals. These effects were reversible within 24 h. No other signs of irritation were observed during the study.

In this study 3,3´-Thiobispropanoic acid is classified as not irritating to rabbit skin according the criteria of CLP, EU GHS (Regulation (EC) No 1272/2008). 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

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)

Species:

other: rabbit eyes

Strain:

not specified

Details on test animals or tissues and environmental conditions:

Enucleated eyes were used for the test.

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

Irritation parameter:

percent corneal swelling

Run / experiment:

1 h observation

Value:

15.1

Negative controls validity:

valid

Irritation parameter:

percent corneal swelling

Run / experiment:

2 h observation

Value:

18.1

Negative controls validity:

valid

Irritation parameter:

percent corneal swelling

Run / experiment:

4 h observation

Value:

21.8

Negative controls validity:

valid

Irritation parameter:

cornea opacity score

Remarks:

Corneal Opacity x Area

Run / experiment:

1 h observation

Value:

0

Negative controls validity:

valid

Irritation parameter:

cornea opacity score

Remarks:

Corneal Opacity x Area

Run / experiment:

2, 3, 4 h observation

Value:

2

Negative controls validity:

valid

Irritation parameter:

morphological effects

Run / experiment:

3, 4 h observation

Negative controls validity:

valid

Remarks on result:

other: Sloughing

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 %

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation

In a primary dermal irritation study according to OECD Guideline 404 (July 17, 1992), 3 young adult New Zealand white rabbits were dermally exposed to 0.5 g of 3,3´-Thiobispropanoic acid moistened with 0.5 ml of distilled water to 2.5 x 2.5 cm² skin surface for 3 minutes, 1 hour and 4 hours under semiocclusive conditions. Animals then were observed for 72 h. Irritation was scored by the method of Draize. 

After 3 min and 1 hour exposure erythema and edema scores were 0 at all observations. After 4 h exposure very slight erythema (grade 1) was present in all tree animals, and very slight edema (grade 1) in 1/3 animals. These effects were reversible within 24 h. No other signs of irritation were observed during the study.

In this study 3,3´-Thiobispropanoic acid is classified as not irritating to rabbit skin according the criteria of CLP, EU GHS (Regulation (EC) No 1272/2008). 

 

Eye irritation

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 (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.

Respiratory irritation

No data on the respiratory irritation of 3,3´-Thiobispropanoic acid are available.

 

There are no data gaps for the endpoint irritation/corrosion. No human information is available for this endpoint. However, there is no reason to believe that these results would not be applicable to humans.

Justification for classification or non-classification

Skin irritation

Based on reliable, adequate and relevant data, 3,3´-Thiobispropanoic acid does not need to be classifiedfor skin irritation according to regulation (EC) 1272/2008.

 

Eye irritation

Based on reliable, adequate and relevant data, 3,3´-Thiobispropanoic acid has to be classified as Category 1, irreversible effects on the eye according to CLP, EU GHS (Regulation (EC) No 1272/2008) and is assigned the hazard statement H318 and the signal word “Danger”.