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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995-04-19 to 1995-04-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it is well-documented, follows OECD Guideline 406, and was conducted in accordance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
This study was conducted before the in-vitro testing became a requirement in 2016. This in-vivo skin sensitization study meet the requirements set out in Article 13(3) first subparagrahp, and Article 13(4) and shal be considered appropriate to address this standard information.

Test material

Constituent 1
Reference substance name:
Octane-1-thiol (CAS # 111-88-6)
IUPAC Name:
Octane-1-thiol (CAS # 111-88-6)
Details on test material:
- Test article name: n-octyl mercaptan (Octane-1-thiol)
-Purity 99.44%
- Substance type: Heavy Mercaptan
- Physical state: Liquid
- Lot/batch No.: 94-000605
- Storage condition of test material: At room temperature protected from light

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: Centre d'Elevage Lebeau
- Weight at study initiation: 331 +/- 25 g (males) and 345 +/- 25 g (females)
- Housing: housed individually in polycarbonate cages (48 x 27 x 20 cm) equipped with a polypropylene bottle.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 5 days before the beginning of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 30 to 70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 1994-12-08 To: 1995-01-09

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: paraffin oil
Concentration / amount:
In the presence of Freund's complete adjuvant, 0.1 ml of the test substance at a concentration 1% (w/w) in the vehicle was administered intradermally. 0.5 ml of the test substance in its original form was applied via the cutaneous route during 48 hours by means of an occlusive dressing. After a period of 12 days without treatment, a challenge cutaneous application of 0.5 ml of the vehicle (left flank) and 0.5 ml of the test substance at a concentration of 75% (w/w) in the vehicle (right flank) were administered to all animals.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: paraffin oil
Concentration / amount:
In the presence of Freund's complete adjuvant, 0.1 ml of the test substance at a concentration 1% (w/w) in the vehicle was administered intradermally. 0.5 ml of the test substance in its original form was applied via the cutaneous route during 48 hours by means of an occlusive dressing. After a period of 12 days without treatment, a challenge cutaneous application of 0.5 ml of the vehicle (left flank) and 0.5 ml of the test substance at a concentration of 75% (w/w) in the vehicle (right flank) were administered to all animals.
No. of animals per dose:
20
Details on study design:
RANGE FINDING TESTS:
-intradermal administration of the test substance (volume 0.1 ml) at increasing concentrations was performed in order to determine the minimum concentration causing irritation.
-0.5 ml of each concentration was applied to a dry gauze pad of approximately 4 cm2 and then held in place by an occlusive dressing for 24 hours.

MAIN STUDY
A. INDUCTION EXPOSURE
-Intradermal Route
On day 1, 6 intradermal injections were made into a clipped area (4 cm x 2 cm) in the scapular region, using a needle mounted on a 1 ml glass syringe
Three injections of 0.1 ml were injected into each side of the animal, as follows:

Control group
-Freund's complete adjuvant diluted to 50% (v/v) with a sterile isotonic saline solution (0.9% NaCl),
-vehicle,
-a mixture of 50/50 (w/v) Freund's complete adjuvant diluted to 50% (v/v) with a sterile isotonic aqueous NaCl solution and the vehicle.

Treated group
-Freund's complete adjuvant diluted to 50% (v/v) with a sterile isotonic saline solution (0.9% NaCl),
-test substance at a concentration of 1% (w/w) in the vehicle,
-a mixture 50/50 (w/v) of Freund's complete adjuvant diluted to 50% (v/v) with a sterile isotonic saline solution (0.9% NaCI), and, the test substance at a concentration of 1% (w/w) in the vehicle.

Cutaneous Route
On day 7, the scapular area was clipped. As the test substance is shown to be non-irritating after occlusive cutaneous treatment during preliminary test, the animals were treated with 0.5 ml of sodium laurylsulphate (10%) in vaseline to provoke local irritation. On day 8, a cutaneous application on the 6 injection areas (4 cm x 2 cm) of the scapular region was performed.

Control group
-application of 0.5 ml of the vehicle.

Treated group
-application of 0.5 ml of a slight irritant concentration of the test substance i.e. in its original form.

The test substance and the vehicle were prepared on a dry gauze pad, which was then applied to the scapular region and held in place for 48 hours by means of an adhesive hypoallergenic dressing.

B. CHALLENGE EXPOSURE
At the end of the rest period on day 22, the test substance was applied at the Maximum NonIrritant Concentration (M.N.I.C.) i.e. at a concentration of
75% (w/w) in the vehicle.
Positive control substance(s):
yes
Remarks:
2,4-dinitrochlorobenzene

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Paraffin Oil Only
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Paraffin Oil Only. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
Paraffin Oil only
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Paraffin Oil only. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
75% v/v in Paraffin Oil
No. with + reactions:
17
Total no. in group:
20
Clinical observations:
very slight to well-defined erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75% v/v in Paraffin Oil. No with. + reactions: 17.0. Total no. in groups: 20.0. Clinical observations: very slight to well-defined erythema.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
75% v/v in Paraffin Oil
No. with + reactions:
17
Total no. in group:
20
Clinical observations:
very slight to well-defined erythema and dryness of skin in some animals
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 75% v/v in Paraffin Oil. No with. + reactions: 17.0. Total no. in groups: 20.0. Clinical observations: very slight to well-defined erythema and dryness of skin in some animals.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
1%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
Very slight to severe erythema and slight oedema is some animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 1%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: Very slight to severe erythema and slight oedema is some animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
1%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
Very slight to severe erythema and slight oedema is some animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 1%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: Very slight to severe erythema and slight oedema is some animals.

Any other information on results incl. tables

No clinical signs or mortalities were observed during the study.

 

The body weight gain of the treated animals was normal when compared to that of the control animals.

 

End of the induction period

On day 10, after removal of the dressing, signs of irritation were observed at the intradermal

injection sites in control and treated groups.

 

Challenge application

After the challenge application, a very slight (score of 1), well-defined (score of 2) or moderate to severe (score of 3) erythema was observed at the following frequency:

Group

Sex

Erythema Score

Scoring of the cutaneous parameters

24 hours

48 hours

 

 

 

LF

RF

LF

RF

Control 1

Male

0

5/5

5/5

5/5

5/5

Treated 2

Male

0

10/10

-

10/10

-

 

 

1

-

5/10

-

6/10

 

 

2

-

5/10

-

4/10

Control 1

Female

0

5/5

5/5

5/5

5/5

Treated 2

Female

0

10/10

3/10

10/10

3/10

 

 

1

-

3/10

-

4/10

 

 

2

-

3/10

-

3/10

 

 

3

-

1/10

-

-

LF: left flank (control)

RF: right flank (treated)

 

In the treated group, 24 hours after removal of the dressing, very slight, well-defined and

moderate to severe erythema (grades 1, 2 and 3) was observed in 8/20,8/20 and 1/20 animals, respectively. Forty-eight hours after removal of the dressing, very slight and well-defined erythema was observed in 10/20 and 7/20 animals, respectively. Dryness of the skin was noted in 11 animals.

 

No effects of the treatment were seen in the control group. Crusts were noted on the treated flank of 1 animal at both readings; they were attributed to an effect of the dressing.

Reactions attributable to a sensitising effect (well-defined or more marked erythema) were seen in 45% of the animals.

 

No oedema were observed 24 and 48 hours after removal of the dressing of the challenge coetaneous application of the test substance.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
According to the maximisation method established by Magnusson and Kligman, cutaneous reactions attributable to the sensitisation potential of octane-1-thiol, at the concentration of 75% (w/w) were observed in 45% of the guinea-pigs.
Executive summary:

In a dermal sensitisation study using octane-1-thiol in paraffin oil, Dunkin-Hartley guinea pigs (10/sex) were tested using the method of Maximization by Magnusson, B. and Kligman, A.M.

 

No clinical signs or mortalities were observed during the study. The body weight gain of the treated animals was normal when compared to that of the control animals. In the treated group, 24 hours after removal of the dressing, very slight, well-defined and moderate to severe erythema (grades 1, 2 and 3) was observed in 8/20,8/20 and 1/20 animals, respectively. Forty-eight hours after removal of the dressing, very slight and well-defined erythema was observed in 10/20 and 7/20 animals, respectively. Dryness of the skin was noted in 11 animals. Reactions attributable to a sensitising effect (well-defined or more marked erythema) were seen in 45% of the animals. In this study, octane-1-thiol is a slight dermal sensitiser.

 

This study received a Klimisch score of 1 and is classified as reliable without restrictions because it is well-documented and follows OECD Guideline 406 and was conducted in accordance with GLP.