Dimethyl disulphide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: National Standard of the People’s Republic of China Toxicological Test Methods of Pesticides for Registration (GB 15670-1995)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

study with 4 rabbits

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl disulphide

EC Number:

210-871-0

EC Name:

Dimethyl disulphide

Cas Number:

624-92-0

Molecular formula:

C2H6S2

IUPAC Name:

(methyldisulfanyl)methane

Test material form:

liquid: volatile

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Covance Research Products Inc., Denver, PA, USA
- Age at study initiation: The male animals were born on 01 Nov 2014 and/or 22 Nov 2014 and the female animals were born on 01 Nov 2014 and/or 08 Nov 2014
- Weight at study initiation: 2.8 - 3.2 kg
- Housing: individually housed in suspended cages
- Diet: Fresh PMI Rabbit Chow (Diet #5321) was provided daily
- Water: ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
No data

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

0 and 60 minutes and at 24, 48 and 72 hours and on Days 4 through 6 in all four animals and on Days 7 through 14 for one animal

Number of animals:

4

Details on study design:

TEST SITE
- Area of exposure: 2.3 cm
- % coverage:
- Type of wrap if used: Porous, non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gently washing with distilled water
- Time after start of exposure:4h

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 6 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 6 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks:

score 1

Results 4

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 6 days

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 6 days

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 6 days

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 6 days

Results 8

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 5 days

Other effects:

Systemic Observations: There were no abnormal physical signs observed.
Body Weight: Two animals gained body weight by study termination and two animals’ weight remained the same.

Applicant's summary and conclusion

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Conclusions:

Dimethyl disulfide is considered to be a mild irritant.

Executive summary:

The potential of Dimethyl Disulfide to cause skin irritation was evaluated when administered dermally to rabbits (Yasso, 2015). This study was designed to comply with the standards set forth in the National Standard of the People’s Republic of China Toxicological Test Methods of Pesticides for Registration (GB 15670-1995), which is comparable to the OECD TG 404. This study was conducted in accordance with the Good Laboratory Practices of the US EPA. Four healthy New Zealand White rabbits (two male - two female) were dosed dermally with Dimethyl disulfide. The test article (0.5 ml) was applied dermally to one intact site per rabbit and wrapped with a semi-occlusive dressing. The test article was kept in contact with the skin for 4 hours at which time the wrappings were removed. Erythema and edema were scored at 0 and 60 minutes and at 24, 48 and 72 hours and on Days 4 through 6 in all four animals and on Days 7 through 14 for one animal. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction at these time periods. Animals were observed for mortality, toxicological and pharmacological effects at each dermal observation period. Body weights were recorded pretest and at termination. Erythema scores over 24, 48 and 72h were 3.0, 1.66, 2 and 1.33 for animals 1 to 4, respectively. Edema scores over 24, 48 and 72h were 2.0, 1.66, 1.66 and 1.66 for animals 1 to 4, respectively. All lesions were fully reversible within 6 days excepted an erythema score of 1 on one animal (#3) still present at the end (D14) of the observation period. There were no abnormal physical signs observed. Two animals gained body weight by study termination and two animals’ weight remained the same. Dimethyl disulfide is considered to be a mild irritant.