3-[(3-sulfanylbutanoyl)oxy]-2,2-bis{[(3-sulfanylbutanoyl)oxy]methyl}propyl 3-sulfanylbutanoate

Endpoint summary

Description of key information

Skin irritation (OECD 404): not irritating
Eye irritation (OECD 405): not irritating

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

Study period:

21 - 30 Jan 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

No analytical purity is given.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

THE DEPARTEMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM:

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK
- Age at study initiation: 12 - 20 weeks old
- Weight at study initiation: 2.0 - 3.5 kg
- Housing: The animals were individually housed in suspended cages.
- Diet: 2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK; ad libitum
- Water: drinking water; ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: Not required, untreated sites of the same animal served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

3 min, 1 and 4 h

Observation period:

72 h
Reading time points: 1, 24, 48 and 72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 3 suitable sites were selected on the back of the rabbit. The test substance was introduced under a 2.5cm x 2.5cm cotton gauze patch.
- Type of wrap if used: Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 3 min, 1 h and 4 h

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

Following 3 min, 1 h and 4 h exposure, there were no signs of skin irritation at the treated skin sites. All scores at any observation time point were 0.

Other effects:

All animals showed expected gain in body weight during the study.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Under the conditions of the Acute Dermal Irritation/Corrosion Test in rabbits the test substance does not possess any skin irritating potential.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 - 12 Feb 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

No analytical purity is given.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK
- Age at study initiation: 12 - 20 weeks old
- Weight at study initiation: 2.53 - 2.95 kg
- Housing: individually housing in suspended cages
- Diet: 2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK: ad libitum
- Water: drinking water; ad libitum
- Acclimation period: att least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated left eye served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

Reading time points: 1, 24, 48 and 72 h

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: Examination of the eyes was facilitated by the use of the light source from a standard ophthalmoscope.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

Ocular Reactions
At 1 h post application, conjunctival redness (score 2) and chemosis (score 1) were noted in all animals. However, the effects were fully reversible within 24 h for chemosis and within 48 h for redness (see table 2). No effects on iris or cornea were observed during the study period.

Other effects:

Body weight
All animals showed expected gain in body weight during the study (table 3).

Table 2. Results of the eye irritation study.

Rabbit #	Time [h]	conjunctivae		iris	cornea		conjunctivae		iris	cornea
		redness	swelling				redness	swelling
1	1	2	1	0	0
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.3	0.0	0.0	0.0	Time to reversion	48.0	24.0	0.0	0.0
2	1	2	1	0	0
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.3	0.0	0.0	0.0	Time to reversion	48.0	24.0	0.0	0.0
3	1	2	1	0	0
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.3	0.0	0.0	0.0	Time to reversion	48.0	24.0	0.0	0.0

 

Table 3: Individual body weights and body weight changes

Rabbit Number	Individual body weight [kg]		Body weight change [kg]
	Day 0	Day 3
#1	2.95	3.05	0.10
#2	2.82	2.90	0.08
#3	2.53	2.61	0.08

All animals showed expected gain in body weight during the study.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Under the conditions of this eye irritation study in rabbits the test substance was not irritating to the eye according to Regulation (EC) No 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The skin irritation/corrosion study was performed in accordance with OECD 404 (Pooles, 2009). The undiluted test substance was applied to the intact skin of rabbits and covered with a gauze patch. Under semi-occlusive conditions, the gauze patch was held in place with an adhesive tape for exposure periods of 3 min, 1 h or 4 h. After the respective exposure, the gauze patch was removed and the treated skin site was cleaned with distilled water. Evaluation of the treated skin sites was done 1, 24, 48 and 72 h after patch removal. There were no signs of skin irritation at the treated skin sites. All scores at any observation time points were 0. Under the test conditions, the test substance was not irritating to the skin.

Eye irritation

According to OECD 405, the undiluted test substance was placed into the conjunctival sac of the right eye of each rabbit (Pooles, 2009). The left eye remained untreated and was used as control. 1, 24, 48 and 72 h after test substance instillation, the grades of ocular reaction (conjunctivae redness, conjunctivae chemosis, cornea, iris) were assessed. 1 h post application, conjunctival redness and chemosis (score 1-2) were noted in all animals. However, the effects were fully reversible within 24 h for chemosis and within 48 h for redness. No effects on iris or cornea were observed during the study period. Under the test conditions, the test substance was not irritating to the eyes.

Justification for classification or non-classification

The available data on skin and eye irritation of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.