Dimethyl disulphide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

4 rats/sex

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

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:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Raleigh NC
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation:
- Weight at study initiation: 307 – 340 g for males and 216 - 236 g for females.
- Fasting period before study: no
- Housing: individually housed in suspended stainless steel wire bottom cages
- Diet: ad libitum fresh PMI Rat Chow (Diet #5012)
- Water: ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- temperature controlled
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: The clipped area began at the shoulders and extended to the hipbone and half way down the flank of each side of the animal
- % coverage: 10
- Type of wrap if used: porous dressing to retain the gauze dressing (semi-occlusive) and porous non-irritating tape

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.54-0.60 ml/rat
- Constant volume or concentration used: no

Duration of exposure:

4 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

4

Control animals:

no

Details on study design:

Animals were observed at 4 hours post-dosing on Day 0 and once daily thereafter for 14 days. Observations included, but were not limited to, evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects including tremors and convulsions, changes in the level of activity, gait and posture, reactivity to handling or sensory stimuli, altered strength, and stereotypies or bizarre behavior (e.g., self-mutilation, walking backwards). All animals were observed twice daily for mortality on Days 1 through 14.
Body weights were recorded pretest, Day 7 and at termination.
All animals were humanely sacrificed using CO2 following study termination and were examined for gross pathology. Additional signs were described.

Statistics:

None

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

All four males and four females survived, following the 4-hour dermal exposure at 2000 mg/kg.

Clinical signs:

other: Abnormal physical signs including wetness of the anogenital area was observed.

Gross pathology:

The gross necropsy revealed no observable abnormalities.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD0 of Dimethyl disulfide is greater than 2000 mg/kg in rats.

Executive summary:

The dermal toxicity of Dimethyl Disulfide was evaluated in a study performed following the National Standard of the People’s Republic of China Toxicological Test Methods of Pesticides for Registration (GB 15670-1995), which is similar to the OECD TG 402. This study was conducted in accordance with current Good Laboratory Practice Regulations of the US EPA. Four healthy male and four healthy female Sprague Dawley rats were dosed dermally with Dimethyl disulfide at 2000 mg/kg of body weight. The test article was kept in contact with the skin for 4 hours at which time the wrappings were removed. Animals were observed at 4 hours post-dosing on Day 0 and once daily thereafter for 14 days. Observations included, but were not limited to, evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects including tremors and convulsions, changes in the level of activity, gait and posture, reactivity to handling or sensory stimuli, altered strength, and stereotypies or bizarre behavior (e.g., self-mutilation, walking backwards). All animals were observed twice daily for mortality on Days 1 through 14. Body weights were recorded pretest, Day 7 and at termination. All animals were examined for gross pathology.

All four males and four females survived, following the 4-hour dermal exposure at 2000 mg/kg. Abnormal physical signs including wetness of the anogenital area was observed. All eight animals gained body weight by study termination. The gross necropsy revealed no observable abnormalities.

The dermal LD0 of Dimethyl disulfide is greater than 2000 mg/kg in rats.