Disodium 3,3'-dithiobis[propanesulphonate]

Eye irritation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

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)

Test material

Test material information

Constituent 1

Reference substance name:

Disodium 3,3'-dithiobis[propanesulphonate]

EC Number:

248-324-3

EC Name:

Disodium 3,3'-dithiobis[propanesulphonate]

Cas Number:

27206-35-5

Molecular formula:

C6H14O6S4.2Na

IUPAC Name:

disodium 3,3'-disulfanediyldipropane-1-sulfonate

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report) : SPS
- Physical state : white powder
- Analytical purity : no data
- Batch number : 1060020/051
- Storage conditions of test material : ambient temperature (<25°C) , under artificial light

Test animals / tissue source

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

Test system

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

Results and discussion

In vivo

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 72 h

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 72 h

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 72 h

Results 7

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

Results 8

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

Results 9

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

Results 10

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

Results 11

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

Results 12

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

Results 13

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

Results 14

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

Results 15

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 .

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.