Carbon disulphide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 April 2010 to 22 June 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

carbon disulfide

IUPAC Name:

carbon disulfide

Details on test material:

Description: Clear liquid
Batch Number: 0600809041160
Purity: > 99%
Stability of Test Item: Stable under storage conditions
Expiry Date: 19-Sep-2011
Stability of Test Item Dilution: Unknown in corn oil; excluded from the statement of compliance.
Storage Conditions: At room temperature (range of 20 ± 5 °C, provided by Harlan Laboratories Ltd.), light protected.
Safety Precautions: Routine hygienic procedures were used to ensure the health and safety of the personnel.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Animals: Rat, RccHan: WIST(SPF)

Rationale: Recognized by international guidelines as a recommended test system

Breeder: Harlan Laboratories B.V., Kreuzelweg 53, 5961 Horst / The Netherlands

Number of Animals per Group: 3 females
Total Number of Animals: 6 females
Age (when treated): 10 weeks
Body Weight Range (when treated): 174.8 g – 189.0 g

Identification: Unique cage number and corresponding color-coded spots on the tail. The animals were marked at acclimatization start.
Randomization: Selected by hand at time of delivery. No computer generated randomization program.

Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

Environmental Conditions: Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour, and continuously monitored environment with a room temperature of 22 ± 3 °C and a relative humidity between 30-70%, automatically controlled light cycle of 12 hours light and 12 hours dark and music played during the daytime light period.

Accommodation: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding (‘Lignocel’ J. Rettenmaier&Söhne GmbH&CoKG, 73494 Rosenberg / Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland).

Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 83/09 (Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) ad libitum (except for the overnight fasting period prior to treatment and approximately 3-4 hours post dose). Results of analyses for contaminants are archived at Harlan Laboratories Ltd.

Water: Community tap water from Füllinsdorf ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at Harlan Laboratories Ltd.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE:
The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. Since the Sponsor indicated that the test item was barely soluble in water and potentially could be chemically modified by polyethylene glycol, corn oil was used as appropriate vehicle for the oral applications. A preparation of 20% (w/w) in corn oil resulted in a white to yellow emulsion, which was considered orally applicable.

Batch Number: 049103168
Source: Carl Roth GmbH & Co., 76185 Karlsruhe / Germany
Stability of the Vehicle: Stable under storage conditions
Expiry Date: 31-Jan-2014
Storage Conditions: At room temperature (range of 20 ± 5 °C), light protected.
Safety Precautions: Routine hygienic procedures were used to ensure the health and safety of the personnel.

DOSE FORMULATION:
The substance was present at levels of 200 mg/ml in the vehicle.
Test material was made into a solution with the vehicle at a dose level of 2000 mg/kg.

The dose formulations were prepared shortly before each dosing occasion using a magnetic stirrer as homogenizer. The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

TEST ITEM ADMINISTRATION:
The animals received a single dose of the test item by oral gavage administration at 2000 mg/kg body weight after being fasted for approximately 18 hours (access to water was permitted). Food was provided again approximately 3 hours after dosing. The dosing volume was 10 mL/kg body weight.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3 females per dose

Control animals:

no

Details on study design:

OBSERVATIONS:
Viability / Mortality: Daily during acclimatization. Once before treatment and within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after treatment on test day 1 (in common with the clinical signs). Twice daily during days 2 – 15.

Clinical Signs: Daily during acclimatization and treatment. Additionally, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1.

Body Weights: On test days 1 (prior to administration), 8 and 15.

Necropsy: All animals were killed at the end of the observation period by carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. An external examination and opening of the abdominal and thoracic cavities for examinations of major organs was performed. The appearance of any macroscopic abnormalities was recorded. No organs or tissues were retained.

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Individual mortality data are given in Attachment 1 - Table 1. No intercurrent deaths occurred during the course of the study.

Clinical signs:

other: Individual clinical observations are given in Attachment 2 - Table 2. Slightly ruffled fur was observed in all animals within the first day (from the first 30 minutes or 1 hour to 1, 2, 3 or 5 hours observation) and persisted up to 2 days in one animal af

Gross pathology:

Individual necropsy findings are given in Attachment 4 - Table 4. No macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dose of carbon disulfide after single oral administration to female rats, observed over a period of 14 days, is: LD50 (female rat): greater than 2000 mg/kg body weight.
Based upon the referred classification criteria (Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008), Carbon disulfide is not classified with respect to acute oral toxicity in the rat.

Executive summary:

Two groups, each consisting of three female RccHan:WIST (SPF) rats, were treated with Carbon disulfide by single oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was formulated in corn oil at a concentration of 0.2 g/mL and administered at a dosing volume of 10 mL/kg. The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs immediately before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded immediately before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. No intercurrent deaths occurred during the course of the study. Slightly ruffled fur was observed in all animals on test day 1 and in one animal also on test day 2. The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were recorded at necropsy. The median lethal dose of Carbon disulfide after single oral administration to female rats, observed over a period of 14 days, is: LD50 (female rat): greater than 2000 mg/kg body weight.

Based upon the referred classification criteria (Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008), carbon disulfide is not classified with respect to acute oral toxicity in the rat.