Dimethyl disulphide

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Study period:

22 March 2005 to 13 April 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

no guideline available

GLP compliance:

yes

Limit test:

no

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

Details on test material:

Test article : Dimethyl disulphide
Batch number: 06025PB (TM 16-1-2)
Purity (%): 99.8

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 (UK) Ltd, Margate
- Age at study initiation: approximately 7 to 9 weeks old on Day 1
- Weight at study initiation: 217 to 254 g (males) and 185 to 227 g (females) on Day -1
- Fasting period before study: no data
- Housing: up to five during acclimatisation and in pairs during the study
- Diet (ad libitum): SQC Rat and Mouse Maintenance Diet No 1, Expanded
- Water (ad libitum): Mains water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 40 to 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

intravenous

Vehicle:

other: Intralipid 20, Fresenius, Basingstoke, UK.

Details on exposure:

Each rat was dosed once on Day 1, by single intravenous bolus injection into a tail vein. The rat was held in a restraint device throughout the dosing procedure. Plastic syringes and disposable hypodermic needles were used.
Individual dose volumes (mL) were calculated using the body weights of the rats on the morning of dosing (Day 1) and the selected dose volume (2 mL/kg).

Doses:

1, 5 and 50 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

EXPERIMENTAL OBSERVATIONS
- Clinical signs
Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs were recorded immediately post-dose (50 mg/kg dose group only), at approximately 15 and 30 minutes post-dose, hourly between 1 and 4 hours post-dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. Individual records of clinical signs and times of death were maintained for each treated rat.
- Body weights
Rats were weighed on Day –1, on Day 1, Day 4 and Day 8. The weight of the carcass of each animal found dead or killed before Day 8 was also recorded.

TERMINAL PROCEDURES
- Necropsy
Animals dying during the observation period were subject to necropsy with the least possible delay. Carcasses may be stored in a refrigerator until necropsy commences. The necropsy procedure included inspection of external surfaces and orifices, all viscera and tissue within the abdominal, thoracic and cranial cavities, free-hand sectioning of the liver and kidneys and examination of representative sections of mucosal surfaces of the stomach, small and large intestines.
Rats surviving treatment were killed by intraperitoneal injection of sodium pentobarbitone on Day 8. No necropsies were performed on these animals.

Results and discussion

Mortality:

One male dosed at 50 mg/kg died approximately 5 minutes after dosing. The second male dosed at 50 mg/kg died approximately 10 minutes after dosing. No other mortalities were noted.

Clinical signs:

Clinical signs of reaction to treatment noted in animals dosed at 50 mg/kg were prone posture, limpness, cyanosis, dyspnoea, lethargy and hunched posture. Recovery of the females, as judged by external appearance and behaviour, was complete by one hour after dosing.
No clinical signs were noted in animals dosed at 1 mg/kg or 5 mg/kg except for an isolated incident of bloated abdomen noted in on Day 3 in one male dosed at 1 mg/kg.

Body weight:

All surviving rats achieved body weight gains during the study period.

Gross pathology:

Macroscopic changes noted at necropsy of animals that died during the study were mottled and dark liver and enlarged atria of the heart.

Applicant's summary and conclusion

Conclusions:

Dimethyl disulphide, was found to be well-tolerated in female rats at the dose levels administered, but was not tolerated in male rats at 50 mg/kg.

Executive summary:

Three groups of two male and two female rats were given the test article as a single dose on Day 1 by intravenous injection at dose levels of 1, 5 and 50 mg/kg. Dimethyl disulphide was dispersed in vehicle ( Intralipid 20) and administered at a dose volume of 2 mL/kg. Animals surviving treatment were killed on Day 8. Necropsies were only performed on animals that died during the observation period.

Both males dosed at 50 mg/kg died within 10 minutes of dosing. No other mortalities were noted. Clinical signs of reaction to treatment noted in animals dosed at 50 mg/kg were prone posture, limpness, cyanosis, dyspnoea, lethargy and hunched posture. Recovery of the females, as judged by external appearance and behaviour, was complete by one hour after dosing. No clinical signs were noted in animals dosed at 1 mg/kg or 5 mg/kg except for an isolated incident of bloated abdomen noted in on Day 3 in one male dosed at 1 mg/kg. All surviving rats achieved body weight gains during the study period. Macroscopic changes noted at necropsy of animals that died during the study were mottled and dark liver and enlarged atria of the heart. Dimethyl disulphide, was found to be well-tolerated in female rats at the dose levels administered, but was not tolerated in male rats at 50 mg/kg.