Sodium ethylenesulphonate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-02-23 to 1988-03-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

adopted 12 May 1981

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

25. April 1984

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The guinea pig test method described in OECD TG 406 provides suitable information for hazard identification.

Test material

Test material information

Constituent 1

Reference substance name:

Sodium ethylenesulphonate

EC Number:

221-242-5

EC Name:

Sodium ethylenesulphonate

Cas Number:

3039-83-6

Molecular formula:

C2H4O3S.Na

IUPAC Name:

sodium ethylenesulphonate

Constituent 2

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

oxidane

impurity 1

Reference substance name:

Sodium 2-hydroxyethanesulphonate

EC Number:

216-343-6

EC Name:

Sodium 2-hydroxyethanesulphonate

Cas Number:

1562-00-1

Molecular formula:

C2H6O4S.Na

IUPAC Name:

sodium 2-hydroxyethanesulfonate

impurity 2

Reference substance name:

Disodium 1,2-ethanedisulphonate

EC Number:

226-198-0

EC Name:

Disodium 1,2-ethanedisulphonate

Cas Number:

5325-43-9

Molecular formula:

C2H6O6S2.2Na

IUPAC Name:

disodium ethane-1,2-disulfonate

impurity 3

Reference substance name:

2,2'-Oxybis-ethanesulfonic acid disodium salt

Cas Number:

63440-92-6

Molecular formula:

C4H8O7S2.2Na

IUPAC Name:

2,2'-Oxybis-ethanesulfonic acid disodium salt

impurity 4

Reference substance name:

sodium 2-sulfonatoethyl sulfate

Molecular formula:

C2H4Na2O7S2

IUPAC Name:

sodium 2-sulfonatoethyl sulfate

impurity 5

Reference substance name:

Sodium sulphate

EC Number:

231-820-9

EC Name:

Sodium sulphate

Cas Number:

7757-82-6

Molecular formula:

H2O4S.2Na

IUPAC Name:

disodium sulfate

impurity 6

Reference substance name:

Sodium hydroxide

EC Number:

215-185-5

EC Name:

Sodium hydroxide

Cas Number:

1310-73-2

Molecular formula:

HNaO

IUPAC Name:

sodium hydroxide

Test material form:

liquid

In vivo test system

Test animals

Species:

guinea pig

Strain:

Pirbright-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: HOECHST AG, Kastengrund, SPF-breed, Germany
- Weight at study initiation: 204 g - 286 g
- Housing: groups of five animals each
- Diet: ad libitum, ERKA feed Number 8300 for guinea pigs and rabbits
- Water: tap water, ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C
- Humidity: 50 +/- 20%
- Photoperiod: 12 hrs dark / 12 hrs light

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

physiological saline

Concentration / amount:

5%

Day(s)/duration:

Day 1 / 8 days

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Induction 2

Route:

epicutaneous, occlusive

Vehicle:

physiological saline

Concentration / amount:

10%

Day(s)/duration:

Day 9 / 2 days

Adequacy of induction:

other: selected concentration induced no mild-to-moderate irritation

Challenge

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

physiological saline

Concentration / amount:

10%

Day(s)/duration:

Day 22 / 1 day

No. of animals per dose:

Pretest:
6 animals for the determination of the non-irritating concentration
3 animals for the determination of the intradermal tolerance
Main test:
5 animals satellite group
5 animals control group
10 animals treated goup

Details on study design:

RANGE FINDING TESTS:

A. Determination of the non-irritating concentration
0.5 mL on the right and left flank, occlusive, exposure time: 24 h

- undiluted solution (30 % sodium ethylene sulphonate)
- 10% test solution in 0.9 % NaCl (3 % sodium ethylene sulphonate)
- 1% test item in 0.9 % NaCl (0.3 % sodium ethylene sulphonate)

At the end of the exposure period the skin of the animals was observed for erythema and oedema formation. Signs of skin irritation were scored according to the Draize scoring system.

B. Determination of the intradermal tolerance
Intradermal injection on the back of the animals (3 areas per animal, 2 injections per area)

1. area: 2x0.1 mL 5% test solution in 0.9 % NaCl (1.5 % sodium ethylene sulphonate)
2. area: 2x0.1 mL 1% test solution in 0.9 % NaCl (0.3 % sodium ethylene sulphonate)
3. area: 2x0.1 mL 0.2% test solution in 0.9 % NaCl (0.06 % sodium ethylene sulphonate)

MAIN STUDY

A. Intradermal induction (day 1)
Intradermal injection on the back of the animals (3 areas, 2 injections per area)

1. area: 2x0.1 mL 50% Freund´s Adjuvant
2. aerea: 2x0.1 mL 5% test solution in 0.9 % NaCl (1.5 % sodium ethylene sulphonate)
3. aerea: 2x0.1 mL 5% test item in Freund´s Adjuvant (1.5 % sodium ethylene sulphonate)

B. Epicutaneous induction (day 9)
0.5 mL on the intradermal injection area (back), occlusive, exposure time: 48 h

Treated group: 10% test solution in 0. 9% NaCl (3 % sodium ethylene sulphonate)
Control/satellite group: 0.9 % NaCl

C. CHALLENGE EXPOSURE (day 22, epicutaneous)
0.5 mL on the left flank, occlusive, exposure time: 24 h

Treated group and control group: 10% test solution in 0.9 % NaCl (3 % sodium ethylene sulphonate)

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10% test solution in 0.9% NaCl (3% sodium ethylene sulphonate)

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no clinical signs were observed

Results 2

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10% test item in 0.9% NaCl (3 % sodium ethylene sulphonate)

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no clinical signs were observed

Results 3

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10% test item in 0.9% NaCl (3 % sodium ethylene sulphonate)

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

no clinical signs were observed

Results 4

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10% test item in 0.9% NaCl (3 % sodium ethylene sulphonate)

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

no clincal signs were observed

Results 5

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

no clincal signs were observed

Results 6

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

no clincal signs were observed

Results 7

Group:

positive control

Remarks on result:

not measured/tested

Any other information on results incl. tables

Evaluation:

A response to challenge of at least 30% of the animals is considered as positive.

 

RANGE FINDING TESTS:

A. Determination of the non-irritating concentration

undiluted test solution (30% sodium ethylene sulphonate): Erythema and pustule formation, slight edema

10% test solution in 0.9% NaCl (3% sodium ethylene sulphonate): no skin irritation

1% test solution in 0.9% NaCl (0.3% sodium ethylene sulphonate): no skin irritation

 

B. Determination of the intradermal tolerance

5% test solution (1.5% sodium ethylene sulphonate): slight redness and edema on the injection site.

1% test solution (0.3% sodium ethylene sulphonate): no skin irritation

0.2% test solution (0.06% sodium ethylene sulphonate): no skin irritation

MAIN STUDY

A. Intradermal induction

50% Freund´s Adjuvant: Redness and edema on the injection site which turned into indurations

5% test solution in Freund´s Adjuvant (1.5% sodium ethylene sulphonate): Redness and edema on the injection site which turned into indurations

B. Epicutaneous induction

The control and satellite group showed injection sites with open wound, scabbing and necrosis when the occlusive gauze was removed (day 11).

C. CHALLENGE EXPOSURE

24 h and 48 h after the occlusive gauze was removed the animals of the treated and the control group revealed no signs of skin irritation.

Body weight and clinical signs:

No clinical signs were observed during the study period. The body weight gains of the treated animals were mostly normal. Two animals if the control group showed only a slight increase in body weight development.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the condition of this study a test solution containing 30% sodium ethylene sulphonate did not induce skin sensitisation. Even if the concentrations at epicutaneous induction were too low according to the guideline requirements (i.e. the selected concentration induced no mild-to-moderate irritation), in combination with intradermal application irritation was observed and therefore, the study is acceptable and revealed that the substance has no sensitisation potential.

Executive summary:

In a guinea pig maximisation test according to OECD 406 and GLP guideline (Hoechst AG (a), 1988) a test solution containing 30% sodium ethylene sulphonate was used. For the determination of the non-irritating concentration and of the intradermal tolerance a range finding test was conducted. Thereby, 0.5 mL undiluted test solution (30% sodium ethylene sulphonate) induced erythema, slight oedema and pustles whereas 10% test solution (3% sodium ethylene sulphonate) induced no skin irritations after epicutaneous occlusive exposure (24 hours) on the right and left flank of 6 animals. In the main study ten female Pribright-Hartley guinea pigs were treated on day 1 by two intradermal injections on the back in three areas with 50% Freund´s Adjuvant (1. area, 2 x 0.1 mL), 5% test solution in 0.9% NaCl (2. area 2 x 0.1 mL, 1.5 % sodium ethylene sulphonate) and 5% test solution in Freund´s Adjuvant (3. area, 2 x 0.1 mL, 1.5% sodium ethylene sulphonate). On day 9, ten animals received 0.5 mL of the test solution by dermal application on the intradermal injection area (back), occlusive, for an exposure time of 48 hours. Thereby, animals were treated with 10% test solution in 0.9% NaCl (3% sodium ethylene sulphonate). Five control animals and five animals of a satellite group were treated with a 0.9% NaCl solution. On challenge exposure (day 22) animals (ten for the treated group and five for the control group) were treated with 0.5 mL of the test solution on the left flank by an occlusive dressing for an exposure time of 24 hours. All animals received 10% test solution in 0.9% NaCl (3% sodium ethylene sulphonate). 24 h and 48 h after the occlusive gauze was removed the animals of the treated and the control group revealed no signs of skin irritation.No clinical signs were observed during the study period. The body weight gains of the treated animals were mostly normal. Two animals of the control group showed only a slight increase in body weight development. After intradermal induction in animals treated with 50% Freund´s Adjuvant and with 5% test solution in Freund´s Adjuvant redness and oedema on the injection site were observed which turned into indurations. After the dermal induction, the control and satellite group showed injection sites with open wound, scabbing and necrosis when the occlusive gauze was removed (day 11). In conclusion, even if the concentrations at epicutaneous induction were too low according to the guideline requirements (i.e. the selected concentration induced no mild-to-moderate irritation), in combination with intradermal application skin irritation was observed and therefore, the study is acceptable and revealed that the substance has no sensitisation potential. Furthermore, the numberof 10 animals chosen is considered sufficient since a clear negative result has been observed.