Dimethyl disulphide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From June 2nd 2004 to July 16th 2004

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:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes

Remarks:

U.S. EPA Good Laboratory Practice Standards (40 CFR Part 160) and OECD Principles of Good Laboratory Practice

Test type:

standard acute method

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

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS:
- Source: Charles River Laboratories, Raleigh, North Carolina, USA
- Age: 8 to 12 weeks
- Weight at study initiation: 254 g to 307 g for males and from 226 g to  260 g for females
- Acclimatation: for a minimum of 7 days.

HOUSING
Individual suspended wire-mesh cages

FOOD and WATER
- Food: PMI Nutrition International, LLC, Certified Rodent LabDiet 5002, ad libitum
- Water: ad libitum municipal water, delivered by an automatic watering  system

ENVIRONMENTAL CONDITIONS
- Temperature : 21.5°C to 21.9°C
- Relative humidity : 33.0% to 48.3%
- Light/dark cycle : 12h/12h
- Ventilation : filtered, not recycled air

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The acute inhalation toxicity of dimethyl disulfide (DMDS) was evaluated  in a 4-hour, single-exposure study in rats. DMDS was initially  administered to a single group of five male and five female  Sprague-Dawley albino rats via whole-body vapor exposure at  concentrations of 847, 1188, 1308 and 1650 ppm. Exposures were conducted in an approximately 165-L plexiglas whole-body  exposure chamber, which allowed all animals to be easily seen and  observed during exposure. Animals were housed individually during  exposure. Food and water were withheld during the exposures. Exposure  atmosphere conditions (temperature, relative humidity and oxygen content)  were recorded approximately hourly during each exposure. 

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Analyzed  exposure concentrations were obtained using a GC. Samples of the exposure  atmospheres were collected at least once every 30 minutes.

Duration of exposure:

4 h

Concentrations:

847, 1188, 1308 and 1650 ppm (3.26, 4.57, 5.04 and 6.35 mg/L)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Mortality, clinical observations for pharmacotoxic signs and body weight  changes were evaluated over a 14-day observation period. Detailed  clinical observations (to determined peak effect of test article  exposure) were conducted immediately following each exposure and at 1, 2,  4, 6 and 8 hours post-exposure. All animals were subjected to a gross  necropsy.

Statistics:

LC50 values (in ppm) and slopes (with 95% confidence limits) were calculated by the method of Litchfield and Wilcoxon.57,

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1 310 ppm

95% CL:

1 167 - 1 471

Exp. duration:

4 h

Remarks on result:

other: (5.05 (4.49-5.66) mg/l) Clinical signs consisted of rales, decreased defecation and dried material on various body surfaces, including the mouth and nose.

Mortality:

847 ppm  : 0/10
1188 ppm : 4/10
1308 ppm : 4/10
1650 ppm : 9/10 

All deaths were noted during exposure or immediately following exposure

Clinical signs:

other: see below

Body weight:

Slight body weight losses (2 to 7 grams) were noted for one or more  females each in the 847, 1188, 1308 ppm groups during the study. There  were no other remarkable body weight changes. All surviving animals met  or surpassed their initial (study day 0) body weight by study day 14.

Gross pathology:

Dark red discoloration of the lungs was noted for animals found dead  during or immediately following exposure in the 1308 and 1650 ppm groups.  One male in the 1308 ppm group also was noted with lungs that did not  fully collapse at necropsy. There were no gross findings for any of the  found dead animals in the 1188 ppm group or for the surviving animals at  the scheduled necropsy.

Other findings:

details on clinical signs : Toxicologically relevant pharmacotoxic signs consisted of rales in the 1188 and 1650 ppm groups, decreased defecation in the 1188 ppm group and dried material on various body surfaces, including the mouth and nose for the surviving 1650 ppm female. Detailed clinical observations immediately following exposure consisted of salivation in the 1188, 1308 and 1650 ppm group males and/or females, tremors in the 847 and 1308 ppm group females, low arousal in the 847, 1188 and 1308 ppm group females, ataxia and impaired mobility in the 1188 ppm group females, hunched gait in the 1308 and 1650 ppm group females, and increased difficulty in removing from cage/handling in females in all groups. Over the course of the 8-hour observation interval, females in all groups had tremors, low arousal levels and were harder to remove from their cages and handle. Hunched gait was noted in the 1188 and/or 1308 ppm groups throughout the 8-hour period.

Any other information on results incl. tables

Total Incidence of Clinical Observations Immediately Following Exposure

(Number of Occurrences/Number of Animals)

	DMDS (ppm)
	Males				Females
	847	1188	1308	1650	847	1188	1308	1650
Number of Rats	5	2	3	0	5	4	3	1
Salivation (slight)	-	1/2	1/3	-	-	-	1/3	-
Salivation (severe)	-	-	-	-	-	3/4	2/3	1/1
Tremors (slight - 1.5 mm)	-	-	-	-	1/5	-	1/3	-
Ease of Removal (moderately difficult)	-	-	-	-	-	-	1/3	-
Ease of Handling (moderately low)	-	-	-	-	4/5	4/4	3/3	1/1
Low Arousal	-	-	-	-	1/5	1/4	1/3	-
Hunched Gait	-	-	-	-	-	-	3/3	1/1
Ataxia	-	-	-	-	-	1/4	-	-
Impaired Mobility (moderately)	-	-	-	-	-	1/4	-	-

- = No observations at this interval.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The LC50 of dimethyl disulfide was 1310 ppm (with 95% confidence limits of 1167-1471 ppm) when male and female albino rats were exposed whole-body to a vapor of the test article for a single, 4-hour period. The time of peak effect of DMDS was considered to be immediately following to 1 hour post-exposure.

Executive summary:

The acute inhalation toxicity of dimethyl disulfide (DMDS) was evaluated in 4-hour, single-exposure study in rats performed in compliance with the EPA/OPPTS Guideline 870.1300 (1998) and the OECD Guidelines # 403 (1981). DMDS was initially administered to a single group of five male and five female Crl:CD(SD) albino rats via whole-body vapor exposure at concentrations of 847, 1188, 1308 and 1650 ppm. Mortality, clinical observations for pharmacotoxic signs and body weight changes were evaluated over a 14-day observation period. Detailed clinical observations (to determined peak effect of test article exposure) were conducted immediately following each exposure and at 1, 2, 4, 6 and 8 hours post-exposure. All animals were subjected to a gross necropsy.

 

Mortality was 0/0, 4/10, 4/10 and 9/10 animals for the 847, 1188, 1308 and 1650 ppm groups, respectively. All deaths were noted during exposure or immediately following exposure. Toxicologically relevant pharmacotoxic signs consisted of rales in the 1188 and 1650 ppm groups, decreased defecation in the 1188 ppm group and dried material on various body surfaces, including the mouth and nose for the surviving 1650 ppm female. Detailed clinical observations immediately following exposure consisted of salivation in the 1188, 1308 and 1650 ppm group males and/or females, tremors in the 847 and 1308 ppm group females, low arousal in the 847, 1188 and 1308 ppm group females, ataxia and impaired mobility in the 1188 ppm group females, hunched gait in the 1308 and 1650 ppm group females, and increased difficulty in removing from cage/handling in females in all groups. Over the course of the 8-hour observation interval, females in all groups had tremors, low arousal levels and were harder to remove from their cages and handle. Hunched gait was noted in the 1188 and/or 1308 ppm groups throughout the 8-hour period.

Slight body weight losses (2 to 7 grams) were noted for one or more females each in the 847, 1188, 1308 ppm groups during the study. There were no other remarkable body weight changes. All surviving animals met or surpassed their initial (study day 0) body weight by study day 14.

Dark red discoloration of the lungs was noted for animals found dead during or immediately following exposure in the 1308 and 1650 ppm groups. One male in the 1308 ppm group also was noted with lungs that did not fully collapse at necropsy. There were no gross findings for any of the found dead animals in the 1188 ppm group or for the surviving animals at the scheduled necropsy.

 

Based on the results of this study, the LC50 of dimethyl disulfide was 1310 ppm (with 95% confidence limits of 1167-1471 ppm) when male and female albino rats were exposed whole-body to a vapor of the test article for a single, 4-hour period. The time of peak effect of DMDS was considered to be immediately following to 1 hour post-exposure.