1,1-dimethylheptanethiol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994-12-08 to 1995-01-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable without restriction because it adheres to OECD Guideline 406 recommendations.

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

Test material

Test material information

Constituent 1

Reference substance name:

1,1-dimethylheptanethiol (CAS # 25360-10-5)

IUPAC Name:

1,1-dimethylheptanethiol (CAS # 25360-10-5)

Details on test material:

- Name of test material (as cited in study report): t-nonyl mercaptan
- Substance type: Heavy Mercaptan
- Physical state: Liquid
- Analytical purity: 99%
- Lot/batch No.: 94-000606
- Storage condition of test material: At room temperature protected from light
- Other: colourless 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: Centre d'Elevage Lebeau, Gambais, France
- Age at study initiation: not reported
- Weight at study initiation: Male - 329 ± 25 grams; Females - 342 ± 14 grams
- Housing: Individually in polycarbonate cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

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

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

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

paraffin oil

Induction 2

Concentration / amount:

Preliminary study: Intradermal route - 0.1, 1, and 5% (w/w); Cutaneous route - 75% and 100% (w/w)
Main study: Induction phase - 1% (w/w); Challenge phase - 75% (w/w)

Challenge

Challenge 1

Route:

other: cutaneous and occlusive

Vehicle:

paraffin oil

Challenge 2

Concentration / amount:

Preliminary study: Intradermal route - 0.1, 1, and 5% (w/w); Cutaneous route - 75% and 100% (w/w)
Main study: Induction phase - 1% (w/w); Challenge phase - 75% (w/w)

No. of animals per dose:

Control group - 5 animals/sex/dose
Treatment group - 10 animals/sex/dose

Details on study design:

RANGE FINDING TESTS:
Intradermal route - 24 hours before treatment, the dorsal region of the animals was clipped and the test substance was prepared in an appropriate vehicle. Intradermal administration of the test substance (volume 0.1 ml) at increasing concentrations (0.1%, 1% and 5% (w/w/)) was then performed in order to determine the minimum concentration which causes an irritation. Evaluation of the potential cutaneous reactions was conducted 24 and 48 hours after injection.

Cutaneous route - 24 hours before treatment, the dorsal region of the animals was clipped and the test substance was prepared in an appropriate vehicle (if necessary). 0.5 ml of each concentration (75% and 100% (w/w)) was applied to a dry gauze pad of approximately 4 cm2 and then held in place by an occlusive dressing for 24 hours. Potential cutaneous reactions were subsequently evaluated 24 and 48 hours after removal of the gauze pads.

MAIN STUDY
A. INDUCTION EXPOSURE - Intradermal Route
- No. of exposures: 1
- Exposure period: 7 days
- Test groups: FCA diluted with 0.9% NaCl (50% v/v); TS (1% w/w) in paraffin oil; Mixture of FCA diluted with 0.9% NaCl (50% v/v) and TS (1% w/w) in paraffin oil
- Control group: FCA diluted with 0.9% NaCl (50% v/v); Vehicle (Paraffin oil); Mixture of FCA diluted with 0.9% NaCl (50% v/v) and paraffin oil
- Site: Scapular area - both flanks (4 cm x 2 cm)
- Frequency of applications: 1
- Duration: 0-6 d
- Concentrations: same throughout

B . INDUCTION EXPOSURE - Cutaneous Route
- No. of exposures: 6
- Exposure period: 48 hours
- Test groups: 0.5 mL of TS in original form
- Control group: 0.5 mL of paraffin oil
- Site: Scapular area - both flanks (4 cm x 2 cm)
- Frequency of applications: 1
- Duration: 7-8 d
- Concentrations: same throughout

C. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
- Exposure period: 22-23 d
- Test groups: TS (75% w/w) in paraffin oil
- Control group: 0.5 mL Paraffin oil
- Site: TS - RF; Control - LF
- Concentrations: same throughout
- Evaluation (hr after challenge): 24 hrs

Positive control substance(s):

yes

Remarks:

2,4-dinitrochlorobenzene

Results and discussion

Positive control results:

At a concentration of 1% (w/w) 2,4 DNCB induced positive skin sensitization reactions in 95% of the guinea-pigs.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0.5 mL

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No erythema or oedema observed

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.5 mL. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No erythema or oedema observed.

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1% w/w

No. with + reactions:

7

Total no. in group:

19

Clinical observations:

No to well defined erythema observed in 7 of 19 animals (one animal was found dead but this was not considered treatment-related)

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1% w/w. No with. + reactions: 7.0. Total no. in groups: 19.0. Clinical observations: No to well defined erythema observed in 7 of 19 animals (one animal was found dead but this was not considered treatment-related).

Results 3

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1% w/w

No. with + reactions:

4

Total no. in group:

19

Clinical observations:

Very slight erythema observed in 4 of 19 of animals

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1% w/w. No with. + reactions: 4.0. Total no. in groups: 19.0. Clinical observations: Very slight erythema observed in 4 of 19 of animals.

Results 4

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

1% w/w

No. with + reactions:

20

Total no. in group:

20

Clinical observations:

Very slight to severe erythema and no to slight oedema observed

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 1% w/w. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: Very slight to severe erythema and no to slight oedema observed.

Results 5

Reading:

1st reading

Hours after challenge:

48

Group:

positive control

Dose level:

1% w/w

No. with + reactions:

20

Total no. in group:

20

Clinical observations:

Very slight to severe erythema and no to slight oedema observed

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 1% w/w. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: Very slight to severe erythema and no to slight oedema observed.

Any other information on results incl. tables

Challenge Application:

Groups	Sex	Erythema Score	Scoring of the cutaneous parameters
			24 hours		48 hours
			LF	RF	LF	RF
Control 1	Male	0	5/5	5/5	4/4	4/4
Treated 2	Male	0	9/9	4/9	9/9	6/9
		1	-	4/9	-	2/9
		2	-	1/9	-	1/9
Control 1	Female	0	5/5	5/5	5/5	5/5
Treated 2	Female	0	10/10	8/10	10/10	9/10
		1	-	1/10	-	1/10
		2	-	1/10	-	-

Applicant's summary and conclusion

Interpretation of results:

other: weak sensitiser (Not classified)

Conclusions:

According to the maximisation method established by Magnusson and Kligman, cutaneous reactions attributable to the sensitisation potential of the test substance, 1,1-dimethylheptanethiol, at the concentration of 75% (w/w) were observed in 10% of the guinea-pigs. 1,1-dimethylheptanethiol was considered to be a weak sensitiser.

Executive summary:

In a dermal sensitisation study, the skin sensitising potential of 1,1-dimethylheptanethiol was evaluated using Dunkin-Hartley guinea-pigs (5/sex – control; 10/sex - treatment) using the method of Magnusson and Kligman. The sensitisation potential of the test substance was evaluated after a 10-day induction period during which time the animals were treated with paraffin oil (control group) or the test substance (treated group). On day 1, in presence of Freund's complete adjuvant, 0.1 ml of the test substance at a concentration of 1% (w/w) in the vehicle was administered by intradermal route. On day 8, 0.5 ml of the test substance in its original form was applied by 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% (wlw) in the vehicle (right flank) were administered to all animals. The test substance and the vehicle were prepared on a dry gauze pad then applied to the skin and held in place for 24 hours by means of an occlusive dressing. Cutaneous reactions on the challenge application sites were then evaluated 24 and 48 hours after removal of the dressing. After the final scoring period, the animals were killed and cutaneous samples were taken from the challenge application sites from the animals. The sensitivity of the guinea-pigs in C.I.T. experimental conditions were checked in a recent study with a positive sensitiser: 2,4-dinitrochlorobenzene. During induction period the test substance was applied at 0.1% (day 1) and 5% (day 8) concentrations. At cutaneous challenge application, 1% (w/w) was tested on the right flank.

 

No treatment-related clinical signs or deaths were noted during the study. Well-defined erythema was observed in 2/19 animals 24 and 48 hours after removal of the dressing. No effects of the treatment were noted in the control group. The guinea-pigs which were used in a recent study showed a satisfactory sensitisation response in 95% animals using a positive sensitizer (2,4-DNCB).

1,1-dimethylheptanethiol was considered to be weakly sensitising to the skin of guinea pigs.

 

This study received a Klimisch score of 1 and is classified as reliable without restriction because it adheres to OECD Guideline 406 recommendations.