Potassium O-ethyl dithiocarbonate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. Potassium ethyl xanthate readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of Potassium ethyl xanthate. In addition, xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc. Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product.

Data source

Reference

Reference 1

Reference Type:

other company data

Title:

Unnamed

Year:

2010

Reference 2

Reference Type:

review article or handbook

Title:

Acute Exposure Guideline Levels for Selected Airborne Chemicals, and includes AEGLs for acetone cyanohydrin, carbon disulfide, monochloroacetic acid, and phenol.

Author:

Committee on Acute Exposure Guideline Levels, Committee on Toxicology, National Research Council

Year:

2009

Bibliographic source:

http://www.nap.edu/catalog/12503.html

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Carbon disulphide

EC Number:

200-843-6

EC Name:

Carbon disulphide

Cas Number:

75-15-0

Molecular formula:

CS2

IUPAC Name:

dithioxomethane

Test material form:

aerosol dispenser: not specified

Remarks:

migrated information: aerosol

Details on test material:

- Name of test material (as cited in study report):carbon disulphide
Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. Potassium ethyl xanthate readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of Potassium ethyl xanthate.
In addition, xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc. Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst, Netherlands
- Age at study initiation: 9 weeks
- Weight at study initiation: males: 254.6 to 274.2 g, females: 169.9 to 183.7 g
- Fasting period before study: none
- Housing: Animals were housed in groups of 5 of the same sex in Makrolon® type-IV cages with wire mesh tops and standard softwood bedding ("Lignocel" J. Rettenmaier & Söhne GmbH & Co KG, 73494 Rosenberg / Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) including paper enrichment (Enviro-dri from Lillico, Biotechnology, Surrey, UK)
- Diet (e.g. ad libitum): Animals were housed in groups of 5 of the same sex in Makrolon® type-IV cages with wire mesh tops and standard softwood bedding ("Lignocel" J. Rettenmaier & Söhne GmbH & Co KG, 73494 Rosenberg / Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) including paper enrichment (Enviro-dri from Lillico, Biotechnology, Surrey, UK)
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum in water bottles, except during the period when they were restrained in exposure tubes
ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%): 30-70 %
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

This study was performed in an AAALAC-accredited laboratory in accordance with the Swiss Animal Protection Law under license no. 49.

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The test atmosphere was generated using a Hudson nebulizer connected to a step dose pump. The entire polyethylene injector inside the nebulizer was replaced by a stainless steel injector. The concentration of the test item in the inhalation chamber was controlled by regulating the flow of the test item to the inhalation tower and by the addition of dilution air
- Exposure chamber volume: not applicable
- Method of holding animals in test chamber: The animals were confined separately in restraint tubes which were positioned radially around the exposure chamber
- Source and rate of air: compressed air was supplied by means of an oil free compressor and passed respiratory quality filters before it was introduced to the exposure system
- Method of conditioning air: respiratory quality filters
- System of generating particulates/aerosols: The test atmosphere was generated using a Hudson nebulizer connected to a step dose pump. The entire polyethylene injector inside the nebulizer was replaced by a stainless steel injector. The concentration of the test item in the inhalation chamber was controlled by regulating the flow of the test item to the inhalation tower and by the addition of dilution air
- Method of particle size determination: not applicable as test item was generated as gas
- Treatment of exhaust air: filtered
- Temperature, humidity, pressure in air chamber: 23.5 °C, 2.4 % relative humididty, 20.0 % oxygen
TEST ATMOSPHERE
- Brief description of analytical method used: The concentration was measured at least 4 times per hour of exposure per on-line gas chromatography. The analyses were performed according to the conditions listed below.

Column: DB-624 (30m x 0.320mm x 1.80µm)
Injector: 225°C
Oven: 100 °C for 0.1min; then 50°C/min to 250°C for 0 min.
Detector: µECD, 260°C

Calibration:
A calibration curve ranging between concentrations of approximately 2.5 mg/L to approximately 14 mg/L was constructed from the test item in gas bags as part of the technical trials. The calibration gas bags were prepared at each concentration.

Acceptance Criteria:
The coefficient of variation was < 10% for all calibration gas bag samples at each concentration. The correlation coefficient of the used regression was 0.995 and therefore within the acceptance criteria.

Standards constructed from the test item in gas bags were sampled prior to initiation of each exposure at the chamber-line and used to check the integrity of the sampling line and check the GC calibration. Plots of the peak area used for the calibration were used to assess trends regarding system stability. The acceptance criterion for standard samples was an accuracy of 90 - 110% of the theoretical value.
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): none
- Concentration of test material in vehicle (if applicable):
- Justification of choice of vehicle:
- Lot/batch no. (if required):
- Purity:

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: none
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Nominal: 2.23 mg/L air
chemical: 10.35 mg/L air

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for viability were recorded once before exposure on the day of exposure (test day 1), three times during exposure, immediately and 1 h after exposure on test day 1 and twice daily during the observation period. Each animal was examined three times during exposure, immediately and 1 h after exposure on test day 1 and once daily during the observation period. Observations were detailed and carefully recorded using explicitly defined scales as appropriate. Only grossly abnormal signs were detectable during exposure as the animals were restrained in the exposure tubes. The body weight of each animal was recorded on test days 1 (before exposure), 2, 4, 8 and 15 (before necropsy).

- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,

Statistics:

no

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

10.35 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Sex:

male/female

Dose descriptor:

LC50

Effect level:

32.19 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: Conversion factors :1 mg/l(ppm)=3.11 mg/m3

Mortality:

three males and two females

Clinical signs:

other: Tachypnea was recorded in all animals during and immediately after exposure. Tachypnea persisted in all surviving animals until test day 2. Hunched or prostrate posture and/or decreased activity were observed in most of the animals one hour after end of e

Body weight:

From test day 1 to test day 2, slight to moderate body weight loss was noted in all surviving animals. Thereafter normal body weight development was recorded in these animals.

Gross pathology:

There were no macroscopic findings that were considered to be related to treatment with the test item. Red discoloration of the lung was recorded in animals that died spontaneously. This finding was considered to be due to delayed necropsy.

Other findings:

none

Any other information on results incl. tables

Test Atmosphere Conditions

Temperature, relative humidity and oxygen concentration during exposure were considered to be satisfactory for this type of study. Relative humidity values were quite low as dry air was used for atmosphere generation.

 

Data on temperature, relative humidity and oxygen concentration are presented in the following table.

 

Recording Time [hours:min]	O2Concentration [Vol %]	Temperature [°C]	Relative Humidity [% RH]
08:00	20.2	23.9	3.6
08:30	20.1	23.4	2.5
09:00	20.1	23.6	2.4
09:30	20.0	23.9	2.3
10:00	19.9	23.4	2.3
10:30	19.9	23.4	2.3
11:00	19.8	23.3	2.2
11:30	19.8	23.3	2.2
12:00	19.8	23.4	2.2
Mean	20.0	23.5	2.4
St. Dev.	0.2	0.2	0.5
N	9	9	9

 

  Determination of Nominal Atmosphere Concentration

The nominal atmosphere concentration was 12.23 mg/L air.

 

  Chemical Determination of Atmosphere Concentrations

The mean chemical atmosphere concentration determined was 10.35 mg/L air as targeted. Details on chemically determined atmosphere concentrations are presented in the following tables:

 

Measurement	Chemical Atmosphere Concentration mg/L air
1	14.01
2	12.03
3	14.13
4	13.88
5	11.52
6	12.42
7	11.54
8	6.36
9	10.51
10	9.65
11	10.67
12	10.57
13	9.39
14	12.08
15	11.41
16	12.30
17	6.86
18	11.24
19	9.98
20	10.74
21	11.16
22	9.17
23	10.26
24	12.22
25	6.98
26	11.22
27	6.10
28	12.67
29	11.22
30	5.34
31	11.29
32	10.97
33	6.62
34	10.47
35	5.13
36	10.96
37	8.40
38	8.50
39	12.75
40	13.41
41	8.79
42	9.42
43	12.02
44	11.14
45	8.10
46	9.38
47	13.00
48	7.92
Mean	10.35
SD	2.3
n	48

 

Applicant's summary and conclusion

Interpretation of results:

moderately toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results of this study, the LC50 of carbon disulfide obtained in this study was 32.19 mg/m³ air or 10.35 mg/L air (chemically determined mean atmosphere concentration). There was no indication of relevant sex-related differences in toxicity of the test item.
Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. Potassium ethyl xanthate readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of Potassium ethyl xanthate.

Executive summary:

Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. Potassium ethyl xanthate readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of Potassium ethyl xanthate.

In addition, xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc. Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product.

A group of five male and five female albino rats was exposed by nose-only, flow-past inhalation for four hours to the test item at a chemically determined mean concentration of 10.35 mg/L air. All animals were observed for clinical signs and mortality during the inhalation exposure and the subsequent 14-day observation period. Body weights were recorded prior to exposure on test day 1, and during the observation period on test days 2, 4, 8 and 15 before necropsy. On test day 15 all animals were sacrificed and necropsied. The ranges of aerosol concentration, temperature, relative humidity, oxygen content and airflow rate measured during the exposure were considered to be satisfactory for a study of this type. In addition, the test item was considered to be respirable to rats. Five animals died during the first 24 hours after exposure. All other animals survived the scheduled observation period. Tachypnea was recorded in all animals during exposure and persisted until test day 2 in the surviving ones. Hunched or prostrate posture and / or decreased activity were recorded in most of the animals after exposure up to day 2. A transient effect on body weight was observed. There were no macroscopic findings that were considered to be related to treatment with the test item.

 

Based on the results of this study, the LC50 of Carbon Disulfide obtained in this study was 32.19 mg/m³ air or10.35 mg/L air (chemically determined mean atmosphere concentration).There was no indication of relevant sex-related differences in toxicity of the test item.