Disodium 3,3'-dithiobis[propanesulphonate]

Endpoint summary

Description of key information

Skin irritation: In vivo dermal irritation study, rabbit (New Zealand White), 4h exposure, semiocclusive, SPS, OECD 404, GLP: not irritating
Skin irritation: In vivo dermal irritation study, rabbit (New Zealand White), 24h exposure, occlusive, MPS, OECD 404, GLP: not irritating
Eye irritation: In vivo eye irritation study, rabbit (New Zealand White), unchanged, no wash-out, SPS, OECD 405, GLP: mild irritant (modified Kay and Calandra classification), not irritating (EU, 92/69/EEC)
Eye irritation: In vivo eye irritation study, rabbit (New Zealand White), unchanged, MPS, OECD 405, GLP: not irritating (EU)

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:

19 June - 22 June 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

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 Department 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: David Percival Ltd. , Moston , Sandbach , Chesire , UK
- Age at study initiation: 12 - 16 weeks
- Weight at study initiation: 2.62 - 3.05 kg
- Housing: animals were individually housed in suspended metal cages
- Diet (e.g. ad libitum): STANRAB SQC Rabbit Diet (Special Diets Services Ltd. , Witham , Essex , UK)
- Water (e.g. ad libitum): mains drinking water , ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 20
- Humidity (%): 60 - 62
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Remarks:

(the substance was moistened with 0.5 ml distilled water)

Controls:

no

Amount / concentration applied:

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

VEHICLE
- Amount(s) applied (volume or weight with unit): the substance was moistened with 0.5 ml distilled water

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6.25 cm²
- Type of wrap if used: the test site was covered with a 2.05 x 2.5 cm cotton gauze patch that was held in place with a strip of surgical adhesive tape (BLENDERM : approximate size 2.5 cm x 4.0 cm) . The trunk of the rabbits was then wrapped in an elasticated corset (TUBIGRIP) .

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

SCORING SYSTEM: Draize scoring system . The test sites were examined 1 , 24 , 48 and 72 hours after the exposure ended .

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(of all 3 animals)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

(of all 3 animals)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Very slightly erythema was noted at all treated skin sites one hour after patch removal . All treated skin sites appeared normal at the 24-hour observation .

Interpretation of results:

GHS criteria not met

Conclusions:

The study was performed according to the OECD TG404 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1). The validity criteria of the test system are fulfilled. 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.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 17 July 1992) and Method B4 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight erythema. All treatment sites appeared normal at the 24-hour observation. 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.

The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations. No symbol and risk phrase are required.

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:

From 24 June to 29 June 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

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: David Percival Ltd. , Moston , Sandbach , Chesire , UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.6-3.2 kg
- Housing: animals were individually housed in suspended metal cages
- Diet (e.g. ad libitum): STANRAB SQC Rabbit Diet (Special Diets Services Ltd. , Witham , Essex , UK) , ad libitum
- Water (e.g. ad libitum): mains drinking water , ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-20
- Humidity (%): 58-69
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml , weighing approximately 81 mg

Observation period (in vivo):

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

Number of animals or in vitro replicates:

3

Details on study design:

Immediately before the start of the test , both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope . Animals showing evidence of ocular lesions were rejected and replaced .
One animal was treated . After consideration of the ocular responses in the first treated animal , two additional animals were treated . In order to minimise pain on application of the test material , one drop of local anaesthetic ("Ophthaine" , 0.5% proxymetacaine hydrochloride , E R Squibb & Sons Limited , Hounslow , Middlesex , UK) was instilled into both eyes of these animals 1 to 2 minutes before treatment .

The test substance was placed into the conjunctival sac of the right eye , formed gently pulling the lower lid away from the eyeball . The upper and lower eyelids were held together for about one second immediately after application , to prevent loss of the test material , and then released . The left eye remained untreated and was used for control purposes . Immediatelly after administration of the test material , an assessment of the initial pain reaction was made . Assessment of ocular damage/irritation was made approximately 1 hour and 24 , 48 and 72 hours after treatment .

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the eye was not washed after treatment

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: opthalmoscope

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 72 h

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 72 h

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.25

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.25

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.5

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Remarks:

Chemosis

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Remarks:

Chemosis

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Remarks:

Chemosis

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.25

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Remarks:

Discharge

Basis:

animal #1

Time point:

other: mean over 1,24,48,72 h

Score:

0.75

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Remarks:

Discharge

Basis:

animal #2

Time point:

other: mean over 1,24,48,72 h

Score:

0.25

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Remarks:

Discharge

Basis:

animal #3

Time point:

other: mean over 1,24,48,72 h

Score:

0.25

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

Minimal to moderate conjunctival irritation was noted in all treated eyes 1 and 24 hours after treatment . Minimal conjunctival irritation was noted in two treated eyes at the 48-hour observation .

Other effects:

No other evidence of eye irritation was noted during the study .

Table 1 : Individual total scores and group scores for ocular irritation

at  at at  at    1 hour 24 hours 48 hours 72 hours  animal #1  12  8  4  0  animal #2  10  6  4  0  animal #3  6  2  0  0  group total  28  16  8  0  group mean score  9.3  5.3  2.7  0.0

Table 2 : Individual and mean scores for cornea , iris and conjunctivae required for EU labelling regulations

Time after treatment  Corneal Opacity  Iridial Inflammation  Conjunctival Redness  Conjunctival Chemosis  animal #1  24 hours 0  0 2 1  animal #1  48 hours 0  0 1 1  animal #1  72 hours 0  0 0  0  total    0  0  3  2  mean    0.0 0.0  1.0  0.7   animal #2  24 hours 0  0  2 1   animal #2  48 hours 0 0 1  1   animal #2  72 hours 0 0 0  0   total   0 0 3 2   mean    0.0 0.0  1.0  0.7   animal #3  24 hours 0  0  1  0   animal #3  48 hours 0  0  0  0  animal #3  72 hours 0  0  0  0  total   0  0  1  0  mean   0.0  0.0  0.3  0.0

Interpretation of results:

GHS criteria not met

Conclusions:

The study was performed according to the OECD TG405 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1). The validity criteria of the test system are fulfilled. The test material produced a maximum mean score of 9.3 and was classified as a MILD IRRITANT (CLASS 4 ON A 1 TO 8 SCALE) to the rabbit eye according to a modified Kay and Calandra classification system .
The test material did not produce positive criteria in any rabbit according to the EU labelling regulations . No symbol and risk phrase are therefore required .

Executive summary:

 A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" (adopted 24 February 1987) and Method B5 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). A single application of the test material to the non-irrigated eye of three rabbits produced minimal to moderate conjunctival irritation. The test material produced a maximum group mean score of 9.3 and was classified as a mild irritant (Class 4 an a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test material did not meet the criteria for classification as irritant according to EU labelling regulations. No symbol and risk phrase are required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

For both endpoints skin and eye irritation, there are each an in vivo Klimisch 1 GLP OECD guideline study on SPS and a supporting in vivo GLP OECD guideline study on MPS (1-Propanesulfonic acid, 3-mercapto-, monosodium salt), which is an acceptable read-across substance, available. All available studies gave consistent results, i.e. that SPS does not need to be classified as skin or eye irritant according to EU classification and labelling criteria. The available database is of high quality, no indication is given that the available results are not relevant for humans, hence, no data gaps were identified and no additional testing is required, It can be safely concluded that disodium 3,3'-dithiobis[propanesulphonate] (SPS) is not a skin or eye irritant in humans, no hazard was identified.

Justification for selection of skin irritation / corrosion endpoint:
Klimisch 1 key study on SPS itself.

Justification for selection of eye irritation endpoint:
Klimisch 1 key study on SPS itself.

Justification for classification or non-classification

All available data gave consistent results that the criteria for classification as skin or eye irritant according to Directive 67/548/EEC and amendatory directives are not met. These criteria are similar to the recent ones of Regulation (EC) 1272/2008, hence, SPS does not need to be classified as skin or eye irritant, neither according to Directive 67/548/EEC nor Regulation (EC) 1272/2008.