2,2'-[1,2-ethanediylbis(oxy)]bis(ethanethiol)

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study performed before the implementation of the REACH regulation

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-[1,2-ethanediylbis(oxy)]bis(ethanethiol)

EC Number:

239-044-2

EC Name:

2,2'-[1,2-ethanediylbis(oxy)]bis(ethanethiol)

Cas Number:

14970-87-7

Molecular formula:

C6H14O2S2

IUPAC Name:

2,2'-[1,2-ethanediylbis(oxy)]bis(ethanethiol)

Test material form:

liquid

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River France, 76410 Saint-Aubin-lès-Elbeuf, France
- Females nulliparous and non-pregnant: yes
- Microbiological status of animals, when known:
- Age at study initiation: approximately three months old
- Weight at study initiation: 354 ± 11 g for the males and 335 ± 15 g for the females
- Housing: individually in polycarbonate cages
- Diet: "106 pelleted diet" (U.A.R., 91360 Villemoisson-sur-Orge, France), ad libitum
- Water: water filtered by a F.G. Millipore membrane (0.22 micron), ad libitum
- Acclimation period: at least 5 days
- Indication of any skin lesions: none

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±2
- Humidity (%): 30 to 70
- Air changes (per hr): 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

paraffin oil

Concentration / amount:

5 %

Day(s)/duration:

Day 1

Adequacy of induction:

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

Induction 2

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100 %

Day(s)/duration:

Day 8

Adequacy of induction:

non-irritant substance, but skin pre-treated with 10% SDS

Challenge

Route:

epicutaneous, occlusive

Vehicle:

paraffin oil

Concentration / amount:

10 %

Day(s)/duration:

Day 22

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

10

Details on study design:

On day 1, intradermal injections of Freund's complete adjuvant mixed with the test substance (treated group) or the vehicle (control group) were performed in the interscapular region.
On day 8, this same test site received a cutaneous application of the test substance (treated group) or the vehicle (control group) and was then covered by an occlusive dressing for 48 hours.
On day 22, after a rest period of 12 days, ail animais of the treated and control groups were challenged by a cutaneous application of the test substance to the right flank. The left flank served as control and received the vehicle only. Test substance and vehicle were maintained under an occlusive dressing for 24 hours.
Skin reactions were evaluated approximately 24 and 48 hours after removal of the dressing.
Test substance concentrations were as follows:
Induction (treated group)
intradermal injections: 1,8-DIMERCAPT0-3,6-DIOXAOCTANE at the concentration of 5% (w/w) in paraffin oil
. topical application: l,8-DIMERCAPT0-3,6-DIOXAOCTANE undiluted.
Challenge (all groups)
topical application: 1,8-DIMERCAPT0-3,6-DIOXAOCT ANE at the concentration of 10% (w/w) in paraffin oil
At the end of the study, animais were killed without examination of internai organs.
No skin samples were taken from the challenge application sites.

Challenge controls:

left flank: vehicle
right flank: test substance at the concentration of 10 % (w/w)

Positive control substance(s):

yes

Remarks:

DNCB and MERCAPTOBENZOTHIAZOLE

Results and discussion

Positive control results:

The species and strain which were used showed a satisfactory sensitization response in 90% animais treated with DNCB and in 30% animais treated with MERCAPTOBENZOTHIAZOLE.

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

10%

No. with + reactions:

0

Total no. in group:

10

Results 2

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

10%

No. with + reactions:

0

Total no. in group:

10

Results 3

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

Results 4

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

1,8-DIMERCAPT0-3,6-DIOXAOCTANE does not induce delayed contact hypersensitivity in guinea-pigs.

Executive summary:

The potential of 1,8-DIMERCAPT0-3,6-DIOXAOCTANE to induce delayed contact hypersensitivity was evaluated in guinea-pigs according to the maximization method of Magnusson and Kligman and to O.E.C.D. (No. 406, l 7th July 1992) and E.C. (92/69/E.E.C., B6, 31st July 1992) guidelines. The study was conducted in compliance with the Principles of Good Laboratory Practice Regulations. Thirty guinea-pigs were allocated to two groups: a control group 1 (five males and five females) and a treated group 2 (ten males and ten females). On day 1, intradermal injections of Freund's complete adjuvant mixed with the test substance (treated group) or the vehicle (control group) were performed in the interscapular region. On day 8, this same test site received a cutaneous application of the test substance (treated group) or the vehicle (control group) and was then covered by an occlusive dressing for 48 hours. On day 22, after a rest period of 12 days, all animals of the treated and control groups were challenged by a cutaneous application of the test substance to the right flank. The left flank served as control and received the vehicle only. Test substance and vehicle were maintained under an occlusive dressing for 24 hours. Skin reactions were evaluated approximately 24 and 48 hours after removal of the dressing.

Test substance concentrations were as follows:

Induction (treated group):

. intradermal injections: 1,8-DIMERCAPT0-3,6-DIOXAOCTANE at the concentration of 5% (w/w) in paraffin oil

. topical application: l,8-DIMERCAPT0-3,6-DIOXAOCTANE undiluted.

Challenge (all groups):

. topical application: 1,8-DIMERCAPT0-3,6-DIOXAOCTANE at the concentration of 10% (w/w) in paraffin oil.

At the end of the study, animals were killed without examination of internal organs. No skin samples were taken from the challenge application sites. The sensitivity of the guinea-pigs was checked with positive sensitizers DNCB and MERCAPTOBENZOTHIAZOLE.

No clinical signs and no deaths were noted during the study. No cutaneous reactions were observed after the challenge application. The species and strain which were used showed a satisfactory sensitization response in 90% animals treated with DNCB and in 30% animals treated with MERCAPTOBENZOTHIAZOLE. 1,8-DIMERCAPT0-3,6-DIOXAOCTANE does not induce delayed contact hypersensitivity in guinea-pigs.