Registration Dossier

Administrative data

Description of key information

One key study was identified to evaluate the skin and eye irritation potential of di-tert-nonyl polysulfide. Based on the lack of adverse effects observed in rabbits, di-tert-nonyl polysulfide is not considered to be a skin or ocular irritant.

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:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
other: JO RF 21/4/71, 5/6/73
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.5 - 3.5 kg
- Housing: kept in individual cages measuring 540 x 360 x 315 mm, cages are ventilated
- Water (e.g. ad libitum): ad libitum
Type of coverage:
occlusive
Preparation of test site:
other: right flank scarified, left flank in tact
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL of liquid TPS 37 were applied per zone (2 zones were tested).
Duration of treatment / exposure:
23 hours
Observation period:
2 days, readings taken at 24 and 72 hours of beginning of the test.
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 14 x 14 cm
- Type of wrap if used: four layers of gauze pads (2cm square) under a patch with a surrounding adhesive, hypoallergenic, perforated plaster 10 mm wide. Adhesive tape is wound around the animal to complete fixing the patches.
- Other: The right flank is scarified with a sterile scalpel blade, making three parallel superficial incisions 2 cm long and 0.5 cm apart. The incisions are epidermal and do not damage the dermis. The test substance is applied to both the intact left flank and scarified right flank.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None

SCORING SYSTEM:
Erythema
No erythema =0
Very slight erythema =1
Well defined erythema =2
Moderate to severe erythema =3
Severe erythema, crimson red, with slight eschar formation =4

Oedema
No oedema =0
Very slight oedema = 1
Slight oedema=2
Moderate oedema=3
Severe oedema = 4
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
1.88
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
probability of mild irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
probability of mild irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
probability of mild irritation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
probability of mild irritation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
probability of mild irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation

Evaluation of irritation

 

Rabbits N

 

Zones

24 hours

72 hours

Total

Erythema

Oedema

Total

Erythema

Oedema

Total

(24 h + 72 h)

175 bis

Normal

2

1

3

2

1

3

6

Scarified

2

1

3

2

1

3

6

176

Normal

0

0

0

0

0

0

0

Scarified

1

0

1

0

0

0

1

177

Normal

2

0

2

2

0

2

4

Scarified

2

0

2

2

0

2

4

178

Normal

2

0

2

2

0

2

4

Scarified

2

0

2

2

0

2

4

179

Normal

2

0

2

2

0

2

4

Scarified

2

0

2

2

0

2

4

180

Normal

2

0

2

2

0

2

4

Scarified

2

0

2

2

0

2

4

Interpretation of results:
Category 3 (mild irritant) based on GHS criteria
Remarks:
Not classified according to Regulation (EC) No. 1272/2008
Conclusions:
TSP 37 is classified as slightly irritating based on the dermal irritation index and scoring after application of 0.5 mL of test material to the rabbits.
Executive summary:

In a primary dermal irritation study, male New Zealand white rabbits were dermal exposed (using a patch) to 0.5 mL of liquid TPS 37 for 23 hours and observed for 72 hours. Pads containing TPS 37 were placed on the skin covering the right flank, which had been scarified, and to the left flank, which was still intact. Irritation was scored using the index of primary irritation.

 

After 23 hours, the skin patches were removed and erythematous lesions were noted. Either no erythema, very slight, or well defined erythma were observed among test animals. Oedmatous lesions were also noted. Test animals were only observed to have no oedema, very slight, or slight oedma. In this study, TPS 37 is classified as slightly irritating based on the dermal irritation index and scoring after application of 0.5 mL of test material to the rabbits for 24 hours. It does not meet the criteria for classification as a skin irritant according to Regulation (EC) No 1272/2008.

 

This study received a Klimisch score of 2 and is classified as reliable with restrictions because it is similar or equivalent to JO RF 21/4/71, 5/6/73.

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:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
other: JO RF 21/04/71 & 05/06/73
Deviations:
not specified
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: approximately 2.5 kg
- Housing: 540x360x315 mm cages individually housed or in restraining devices.
- Diet (e.g. ad libitum): 200 g granules per animal per day
- Water (e.g. ad libitum): ad libitum and automatically softened and filtrated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C minimum
- Air changes (per hr): 12 times per hour; pre-filtered
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: Left eye served as control
Amount / concentration applied:
undiluted
Amount applied: 0.1 mL
Duration of treatment / exposure:
24 hour(s)
Observation period (in vivo):
Observations recorded at 1 hour, 24 hours, 2 days, 3 days, 4 days, and 7 days after administration. 
When the irritation is persistent, readings are made each week over a maximum period of 5 weeks.
Number of animals or in vitro replicates:
6
Details on study design:
Comment: not rinsed
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 48 h
Remarks on result:
positive indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 48 h
Remarks on result:
positive indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 48 h
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 48 h
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
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
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 48 h
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 48 h
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 48 h
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.6
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 48 h
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 48 h
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 48 h
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 48 h
Remarks on result:
no indication of irritation
Remarks:
Scores at 72 hours were not given in the study report, but interpreted to be the same as the scores at 48 hours.
Irritant / corrosive response data:
Four of the 6 rabbits showed opacity of the cornea after the first hour of administration. Symptoms were fully reversible within 24 hours of test substance administration. Effects to the conjunctiva and iris were all scored at 1 or below and effects were fully reversible after 7 and 4 days, respectively. Chemosis was noted and scored as high as a 2 in some animals but was fully reversible by 7 days.

Conjuncitva:

No. of rabbits

1 Hour

24 Hours

48 Hours

193

194

195

196

197

198

193

194

195

196

197

198

193

194

195

196

197

198

Chemosis

1

1

1

1

1

1

1

2

2

2

2

1

1

0

1

1

1

1

Discharge

2

1

1

1

1

1

0

0

0

1

0

0

0

0

0

0

0

0

Enanithema

1

1

1

1

1

1

1

1

1

1

1

1

1

0

0

0

1

1

(A+B+C) x 2 (max. = 20)

8

6

6

6

6

6

4

6

6

8

6

4

4

0

2

2

4

4

Iris:

No. of rabbits

1 Hour

24 Hours

48 Hours

193

194

195

196

197

198

193

194

195

196

197

198

193

194

195

196

197

198

Congestion

1

1

1

1

1

1

1

1

1

1

1

0

1

1

0

0

1

0

X 5 (max. = 10)

5

5

5

5

5

5

5

5

5

5

5

0

5

5

0

0

5

0

Cornea:

No. of rabbits

1 Hour

24 Hours

48 Hours

193

194

195

196

197

198

193

194

195

196

197

198

193

194

195

196

197

198

Opacity (0-4)

1

0

1

1

1

0

0

0

0

0

0

0

0

0

0

0

0

0

Area Affected (1-4)

1

0

1

1

1

0

0

0

0

0

0

0

0

0

0

0

0

0

A x B x 5 (max. = 80)

5

0

5

5

5

0

0

0

0

0

0

0

0

0

0

0

0

0

Ulceration

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Area Affected (a-d)

/

/

/

/

/

/

/

/

/

/

/

/

/

/

/

/

/

/

Granulation

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Area Affected (a-d)

/

/

/

/

/

/

/

/

/

/

/

/

/

/

/

/

/

/

Individual ocular irritation score (max: 110)

18

11

16

16

16

11

9

11

11

13

11

4

9

5

2

2

9

4

Interpretation of results:
GHS criteria not met
Conclusions:
In an eye irritation test, the study authors found TPS 37 to be an eye irritant when based on the index of ocular irritation at 1 and 48 hours respectively. However, according to EU guidelines, TPS 37 is not an eye irritant based on the gained mean scores for conjunctiva, iris and cornea.
Executive summary:

In an eye irritation test, six male albino New Zealand rabbits were exposed to 0.1mL of TPS 37 in the right eye. The left eye served as a control. Animals were observed at 1, 24, 48, 72, 86, and 168 hours after test substance administration. Scores for anomalies in the conjunctiva, alternations in pupil or iris, degree and extent of opacity of the cornea, and any ulceration or granulation of the cornea were scored and recorded for each animal during each observation point. The mean index of ocular irritation and index of acute ocular irritation (greatest mean index of ocular irritation) were calculated based on the methods of Kay and Calandra (1962) and used to classify the test substance. Mean conjunctiva, iris and cornea scores were calculated by averaging all of the animal scores from the 24-, 48-, and 72-hour observations points. 

The study authors calculated the index of acute ocular irritation to be 14.67 after one hour of test substance administration. The index of ocular irritation after 48 hours was 5.17. Based on these values the study authors classified TPS 37 as irritating. 

The mean conjunctiva, iris and cornea scores were 0.5, 0.61, and 0 respectively. All effects were fully reversible in 4 days for the iris and 7 days for the conjunctivae. Based on these results, TPS 37 is not classified according to EU guidelines. 

This study received a Klimisch score of 2 because it generally follows OECD guideline 405.  

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation

 

One key study in rabbits was identified to evaluate the dermal irritation potential of di-tert-nonyl polysulfide. 

 

In a key primary dermal irritation study (Gonnet and Guillot, 1979; Klimisch score = 2), six male white rabbits were dermally exposed to 0.5 mL di-tert-nonyl polysulfide (TPS 37) for 23 hours and observed for a period of 72 hours post-exposure. Pads containing TPS 37 were placed on the skin covering the right flank, which had been scarified, and to the left flank, which was still intact. After 23 hours, the skin patches were removed and erythematous lesions were noted. At 24 hours, very slight to well-defined erythema that persisted through 72 hours was observed in 5 of 6 rabbits (mean erythema score = 1.67). Very slight oedema was observed in one animal at 24 hours and this persisted through 72 hours (mean oedema score = 0.167). All other animals appeared normal through the study period. Skin reactions were observed at identical grades in at both intact and scarified sites. The study authors concluded that di-tert-nonyl polysulfide was slightly irritating to the skin based on a primary irritation index of 1.88.

Two skin irritation studies are available for the analogue substance di-tert-butyl polysulfides (CAS: 6893-96-2) and one for di-tert-dodecyl polysulfides (CAS: 68425-15-0):

In two separate skin irritation studies, both conducted according to OECD TG 404 and in compliance with GLP, the test substance di-tert-butyl polysulfide was considered as an irritant when administered by cutaneous route in rabbits (Clouzeau, 1992 & Ollivier, 2006).

 

In a skin irritation study, conducted according to OECD TG 404 and in compliance with GLP, di-tert-dodecyl polysulfides (CAS: 68425-15-0) was considered as slightly irritant for the skin of rabbits (Guillot (Hazleton-IFT), 1986).

Eye Irritation

One key study in rabbits was identified to evaluate the ocular irritation potential of di-tert-nonyl polysulfide

In a key eye irritation study (Gonnet and Guillot, 1979; Klimisch score = 2), six male albino rabbits were exposed to 0.1mL of di-tert-nonyl polysulfide in the right eye. The left eye served as a control and observations were conducted at 1 hour, 24 hours, 48 hours, 72 hours,and on days 4 and 7 post-exposure. Scores for anomalies in the conjunctiva, alternations in pupil or iris, degree and extent of opacity of the cornea, and any ulceration or granulation of the cornea were scored and recorded for each animal at each observation point. 

 

The study authors calculated the index of acute ocular irritation to be 14.67 after one hour of test substance administration. The index of ocular irritation after 48 hours was 5.17. The mean conjunctiva, iris and cornea scores were determined to be 0.5, 0.61, and 0, respectively. All effects were fully reversible in 4 days for the iris and in 7 days for the conjunctiva. Based on these results, di-tert-nonyl polysulfide is not considered to be an ocular irritant.

Eye irritation studies are also available for the analogue substances di-tert-butyl polysulfides (CAS: 6893-96-2) and di-tert-dodecyl polysulfides (CAS: 68425-15-0). Neither of the substances was considered to be irritating to eyes (Clouzeau, 1992; Guillot, 1986).

Respiratory Irritation

No data available.

Justification for classification or non-classification

Di-tert-nonyl polysulfide does not meet the criteria for classification and labelling as a skin irritant under CLP Regulation (EC) No 1272/2008.

Di-tert-nonyl polysulfide does not meet the criteria for classification and labelling as an eye irritant as defined by CLP Regulation (EC) No 1272/2008.