Registration Dossier

Administrative data

Description of key information

- Acute oral toxicity:.The LD50 value of 500 mg/kg was determined for Sodium Isobutyl Xanthate. This show that Sodium Isobutyl Xanthate is of a moderately order of acute oral toxicity .
-Acute Dermal Toxicity: An LD50 value of < 1000 mg/kg was obtained. Application of 1 gm/kg of sodium ethyl xanthate in the form of a paste resulted in the death of ten out of twelve animals within 24 hrs. The surviving animals developed irritant effects including oedema and pigmentation of the skin. The sulphide odour noted during the study suggests that decomposition of sodium ethyl xanthate occurred. The dermal LD50 was < 1000 mg/kg . This show that Sodium Isobutyl Xanthate (the result was read across from sodium ethyl xanthate) is of a moderately order of acute Dermal toxicity .
- Acute inhalation toxicity :Based on the results of thе study (Arkema Inc. 2010), the LC50 for Acute inhalation toxicity of carbon disulfide obtained 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. Sodium isobutyl 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 sodium isobutyl xanthate.
It is concluded that the substance Sodium isobutyl xanthate meet the criteria to be classified for human health hazards for acute oral and dermal effects.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions. Well documented and conducted study.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Method: other
GLP compliance:
no
Test type:
other: LD50
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Weight at study initiation: 200-265g

- Fasting period before study: Over night

- Housing: Group housing (5 of each sex per cage), in metal cages provided with white pine and cheddar shavings.

- Diet: Purina Laboratory Chow, ad libitum.

- Water: ad libitum
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Exploratory doses were administered to 8 rats to estimate the order of toxicity of the test compound. Based on the preliminary estimation, groups of 10 rats (5M, 5F) were administered the test compound at graded dosage levels designed to blanket the toxicity range.
Doses:
500,2000 mg
No. of animals per sex per dose:
5 female, 5 male
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Regular intervals on the day of dosing and daily thereafter for 14 days.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Gross necropsies were performed on all survivors and any animals which died during the observation period. Body weights of survivors were recorded prior to sacrifice.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: The findings of this study indicate that Sodium Isobutyl Xanthate produces adverse effects on the central nervous system, liver and kidneys.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: The findings of this study indicate that Sodium Isobutyl Xanthate produces adverse effects on the central nervous system, liver and kidneys.
Mortality:
All death occurring 1 to 2 hours after administration.
Clinical signs:
Oral administration of Sodium Isobutyl Xanthate to rats produced increased motor activity, cyanosis, irritability, increased respiration and convulsions with death occurring 1 to 2 hours after administration.
Body weight:
Weight gain amongst survivors was within normal limits.
Gross pathology:
Autopsy showed perivascular and pericellular oedema, multiple haemorrhages in the lungs, perivascular subarachnoid haemorrhages and acute
swelling of the cells of the cortex, subcortical ganglia and the brain stem. Fatty dystrophy of the liver and protein dystrophy of the twisted canaliculi of the
kidneys were observed.
Other findings:
The findings of this study indicate that Sodium Isobutyl Xanthate produces adverse effects on the central nervous system, liver and kidneys.

Table 3:

Oral toxicity of xanthates (from: Kirk-Othmer, 1984)16

Xanthate

Species

LD0

 (mg/kg)

LD50

(mg/kg)

References

Sodium ethyl

rat

500

17

Potassium ethyl

Rat

 mouse

500

1700

583

17, 18

Sodium isopropyl

rat

250

17

Potassium isopropyl

rat

mouse

— —

1700

 583

18 —

Potassium n-butyl

mouse

411

 465

19,20

Sodium isobutyl

rat

 

500

17

Potassium isobutyl

rat

mouse

— —

1290

 480

18 18

Sodium sec-butyl

rat

>2000

17

Potassium amyl (mixed)

rat

1000

1000–2000

17, 21

Potassium iso amyl

rat

mouse

— —

765

470

18 18

C5-C6 mixture

rat

1500

22

 

 

The LD50 value of 500 mg/kg was determined for Sodium Isobutyl Xanthate. This show that Sodium Isobutyl Xanthate is of a moderately order of acute oral toxicity .

 

The LD50 of the various xanthates are similar, ranging from 411 to 583mg/kg in mice and from 1000 to >2000 mg/kg in rats.

The acute oral toxic effects of one xanthate, potassium butyl xanthate, are providedin two summaries in Chemical Abstracts.

 Similar symptoms and pathologyfindings were seen in these studies carried out by Babayan.

 

References :

16.Kirk-Othmer Encyclopaedia of Chemical Technology,Vol 24, 2nd ed, pp 645-661,John Wiley & Sons, 1984.

17.Dow Chemical Company, 1964, unpublished toxicological data to C.B. Shaffer,American Cyanamid; data from P. Avotin, American Cyanamid, privatecommunication, 1982 as cited in Kirk-Othmer Encyclopaedia of Chemical

18.Babayan, E.A., 1963, “Toxicology of Potassium Butyl Xanthate” Material 2-oi[Vtoroi] Itog. Nauchn. Konf. Inst. Gigieny Truda I Prof. Zabolevan Posvyashch.Vopr. Gigieny Truda I Prof. Patol. Erevan, pp 75-77 (Pub 1964)(Russ)Chem Abstract,64, 8836e (1966).

19.Babayan, E.A., “Toxicological Characteristics of the Flotation Agent PotassiumButyl Xanthate”, Mater. Itogovoi Nauch. Konf. Vop. Gig Tr Profpatol. Khim.Gornorud. Prom., 3rd 1966 (Pub 1968) 97-102 (Russ) inChemical Abstracts,Vol 73,1970.

20.Fronk, N.G., The Dow Chemical Company, private communication, 1982, as cited inKirk-Othmer Encyclopaedia of Chemical Technology,Vol 24, 2nd Ed, pp 645-661,John Wiley & Sons, 1984.

21.Buzina, A.Z., Burkhanov, A.I. and Abeuev, Kh.B., 1977 Zdravookhr. Kaz., 88 ascited inKirk-Othmer Encyclopaedia of Chemical Technology,Vol 24, 2nd Ed, pp645-661, John Wiley & Sons, 1984.

22.Chemical Abstracts,Vol 64, 1966.

 

Interpretation of results:
moderately toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 value of 500 mg/kg was determined in a reliable study. This show that Sodium Isobutyl Xanthate is of a moderately order of acute oral toxicity .
Based on the data provided in this review, Sodium Isobutyl Xanthate shall be classified for acute oral toxicity.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
500 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting 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. Sodium isobutyl 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 sodium isobutyl 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.
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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.
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
Sex:
male/female
Dose descriptor:
LC50
Effect level:
10.35 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
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

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

 

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.
Executive summary:

Carbon disulphideis both a reagent in the manufacture, as well as a decomposition product of xanthates.Sodium isobutyl 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 sodium isobutyl 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.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
32.19 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Qualifier:
no guideline followed
Principles of method if other than guideline:
This study was conducted in 1951 and was repeated later in the same year. Exposure in both studies was for 18 hrs and was not according to the OECD Guidelines for acute dermal irritation (4 hrs) or for dermal toxicity (24 hrs). The initial study was performed to assess dermal irritation but deaths during the study led to further studies. Sodium ethyl xanthate was administered by occlusive application to the shaved abdomen of the rabbits either as 1.0 ml/kg of a 10% aqueous solution or as 1 gm/kg of the 100% dry material in a paste formed with water. The animals were observed for 12 days.
GLP compliance:
no
Test type:
other: LD50
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
male
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
Sodium ethyl xanthate was administered by occlusive application to the shaved abdomen of the rabbits either as 1.0 ml/kg of a 10% aqueous solution or as 1 gm/kg of the 100% dry material in a paste formed with water. The animals were observed for 12 days.
Duration of exposure:
The animals were observed for 12 days.
Doses:
1.0 ml/kg of a 10% aqueous solution or as 1 gm/kg
No. of animals per sex per dose:
12
Control animals:
yes
Details on study design:
This study was conducted in 1951 and was repeated later in the same year. Exposure in both studies was for 18 hrs and was not according to the OECD Guidelines for acute dermal irritation (4 hrs)or for dermal toxicity (24 hrs).The initial study was performed to assess dermal irritation but deaths during the study led to further studies. Sodium ethyl xanthate was administered by occlusive application to the shaved abdomen of the rabbits either as 1.0 ml/kg of a 10% aqueous solution or as 1 gm/kg of the 100% dry material in a paste formed with water. The animals were observed for 12 days.
Sex:
male
Dose descriptor:
LD50
Effect level:
< 1 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: The dermal irritation/toxicity study in rabbits indicates that sodium ethyl xanthate powder has an LD50 of <1000 mg/kg and is a moderate irritant while the 10% solution is non irritating to the skin.
Mortality:
Application of 1 gm/kg of sodium ethyl xanthate in the form of a paste resulted in the death of ten out of twelve animals within 24 hrs. The surviving animals developed irritant effects including oedema and pigmentation of the skin.
Clinical signs:

Clinical Observations :surviving animal had moderate irritation with oedema and pigmentation of the skin.
Gross pathology:
Moderate amount of peritoneal fluid, visceral organs were normal.
Haemorrhagic lungs and peritoneal and pleural fluid. Other changes were markedly cyanotic ears (2/5), haemorrhagic conditions (2/5) and evidence of diarrhoea (3/5).
The liver appeared darkand mottled and the kidneys showed spotty haemorrhages

The dermal irritation/toxicity study in rabbits indicates that sodium ethyl xanthate powder has an LD50 of <1000 mg/kg and is a moderate irritant while the10% solution is non irritating to the skin.

Table 4:

Effects of sodium ethyl xanthate following dermal application

Animals

Dose

Clinical Observations

Gross pathology

3 rabbits

1 ml/kg, as 10%

solution

 

No skin irritation.

No substance related

changes.

 

3 rabbits

1 gm/kg, as a paste

2/3 died; surviving animalhad moderate irritationwith oedema andpigmentation of the skin.

 

Moderate amount of

peritoneal fluid, visceral

organs were normal.

 

5 male

rabbits

 

1 gm/kg, as a paste

5/5 died following

overnight exposure; oedemaof the skin with

pigmentation.

 

Haemorrhagic lungs andperitoneal and pleural fluid.

Other changes were

markedly cyanotic ears

(2/5), haemorrhagic

conditions (2/5) and

evidence of diarrhoea (3/5).

 

1 male

rabbit

 

1 gm/kg, as a more

liquid paste than

above

 

Moderate oedema and

pigmentation of the skin.

 

No substance related

changes.

 

3 rabbits

1 gm/kg as a paste

All 3 animals died within24 hrs; retropulsion,salivation, loss of rightingreflex and haemorrhagicand oedematous areas of the

skin were noted.

 

The liver appeared dark

and mottled and the kidneysshowed spotty

haemorrhages.

 

Interpretation of results:
moderately toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, application of 10% solution of sodium ethyl xanthate (pH 10.5 to 11) for 18 hrs did not cause skin irritation in rabbits. Similar application of 1 gm/kg of sodium ethyl xanthate in the form of a paste resulted in the death of ten out of twelve animals within 24 hrs. The surviving animals developed irritant effects including oedema and pigmentation of the skin. The sulphide odour noted during the study suggests that decomposition of sodium ethyl xanthate occurred. The dermal LD50 was < 1000 mg/kg.

Executive summary:

Under the conditions of the study of Hazleton Laboratories, application of 10% solution of sodium ethyl xanthate (pH 10.5 to 11) for 18 hrs did not cause skin irritation in rabbits.

Similar application of 1 gm/kg of sodium ethyl xanthate in the form of a paste resulted in the death of ten out of twelve animals within 24 hrs. The surviving animals developed irritant effects including oedema and pigmentation of the skin. The sulphide odour noted during the study suggests that decomposition of sodium ethyl xanthate occurred. The dermal LD50 was < 1000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 000 mg/kg bw

Additional information

    

Oral toxicity

Table 3:

Oral toxicity of xanthates (from: Kirk-Othmer, 1984)16

Xanthate

Species

LD0

 (mg/kg)

LD50

(mg/kg)

References

Sodium ethyl

rat

500

17

Potassium ethyl

Rat

 mouse

500

1700

583

17, 18

Sodium isopropyl

rat

250

17

Potassium isopropyl

rat

mouse

1700

 583

18

Potassium n-butyl

mouse

411

 465

19,20

Sodium isobutyl

rat

 500

17

Potassium isobutyl

rat

mouse

1290

 480

18 18

Sodium sec-butyl

rat

>2000

17

Potassium amyl (mixed)

rat

1000

1000–2000

17, 21

Potassium iso amyl

rat

mouse

765

470

18 18

C5-C6 mixture

rat

1500

22

 The LD50 of the various xanthates are similar, ranging from 411 to 583 mg/kg in mice and from 1000 to >2000 mg/kg in rats.

The acute oral toxic effects of one xanthate, potassium butyl xanthate, are provided in two summaries in Chemical Abstracts.

Similar symptoms and pathology findings were seen in these studies carried out by Babayan.

 

References :

16.Kirk-Othmer Encyclopaedia of Chemical Technology,Vol 24, 2nd ed, pp 645-661,John Wiley & Sons, 1984.

17.Dow Chemical Company, 1964, unpublished toxicological data to C.B. Shaffer,American Cyanamid; data from P. Avotin, American Cyanamid, privatecommunication, 1982 as cited in Kirk-Othmer Encyclopaedia of Chemical

18.Babayan, E.A., 1963, “Toxicology of Potassium Butyl Xanthate” Material 2-oi[Vtoroi] Itog. Nauchn. Konf. Inst. Gigieny Truda I Prof. Zabolevan Posvyashch.Vopr. Gigieny Truda I Prof. Patol. Erevan, pp 75-77 (Pub 1964)(Russ)Chem Abstract,64, 8836e (1966).

19.Babayan, E.A., “Toxicological Characteristics of the Flotation Agent PotassiumButyl Xanthate”, Mater. Itogovoi Nauch. Konf. Vop. Gig Tr Profpatol. Khim.Gornorud. Prom., 3rd 1966 (Pub 1968) 97-102 (Russ) inChemical Abstracts,Vol 73,1970.

20.Fronk, N.G., The Dow Chemical Company, private communication, 1982, as cited inKirk-Othmer Encyclopaedia of Chemical Technology,Vol 24, 2nd Ed, pp 645-661,John Wiley & Sons, 1984.

21.Buzina, A.Z., Burkhanov, A.I. and Abeuev, Kh.B., 1977 Zdravookhr. Kaz., 88 ascited inKirk-Othmer Encyclopaedia of Chemical Technology,Vol 24, 2nd Ed, pp645-661, John Wiley & Sons, 1984.

22.Chemical Abstracts,Vol 64, 1966.

 

 Dermal toxicity

Table 4:

Effects of sodium ethyl xanthate following dermal application

Animals

Dose

Clinical Observations

Gross pathology

3 rabbits

1 ml/kg, as 10%

solution

 

No skin irritation.

No substance related

changes.

 

3 rabbits

1 gm/kg, as a paste

2/3 died; surviving animalhad moderate irritationwith oedema andpigmentation of the skin.

 

Moderate amount of

peritoneal fluid, visceral

organs were normal.

 

5 male

rabbits

 

1 gm/kg, as a paste

5/5 died following

overnight exposure; oedemaof the skin with

pigmentation.

 

Haemorrhagic lungs andperitoneal and pleural fluid.

Other changes were

markedly cyanotic ears

(2/5), haemorrhagic

conditions (2/5) and

evidence of diarrhoea (3/5).

 

1 male

rabbit

 

1 gm/kg, as a more

liquid paste than

above

 

Moderate oedema and

pigmentation of the skin.

 

No substance related

changes.

 

3 rabbits

1 gm/kg as a paste

All 3 animals died within24 hrs; retropulsion,salivation, loss of rightingreflex and haemorrhagicand oedematous areas of the

skin were noted.

 

The liver appeared dark

and mottled and the kidneysshowed spotty

haemorrhages.

 

Based on the results of thе study (Arkema Inc. 2010), the LC50 for Acute inhalation toxicity of carbon disulfide obtained 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. Sodium isobutyl 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 sodium isobutyl xanthate.

Justification for classification or non-classification

Based on the hazard assessment of Sodium isobutyl xanthate,in section 2.1 and 2.2. in IUCLID 5.4., available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health”, according to the EU’s list of dangerous substances (OJEC No L200/130.7.99)and according to the criteria described in Directive 67/548 and in the CLP Regulation:

Directive 67/548

Very Toxic (T+)

R28: Very toxic if swallowed

R27: Very toxic in contact with skin

R26: Very toxic by inhalation

R39/26 R39/27 R39/28: Dangerous of very serious irreversible effects

Toxic (T): 

R25: Toxic if swallowed

R24: Toxic in contact with skin

R23: Toxic by inhalation

R39/23 R39/24 R39/25: Danger of very serious irreversible effects

Harmful (Xn):

R22: Harmful if swallowed

R21: Harmful in contact with skin

R20: Harmful by inhalation

R65: Harmful may cause lung damage if swallowed

R21/22 Harmful; Harmful in contact with skin and if swallowed.

R68/20 R68/21 R68/22: Possible risk of irreversible effects

Other toxicological properties

R67: Vapours may cause drowsiness and dizziness

CLP

H300 Acute Tox. 2 Fatal if swallowed

H310 Acute Tox. 1 Fatal in contact with skin

H330 Acute Tox. 2 Fatal if inhaled

H370 STOT SE 1

H301 Acute Tox. 3 Toxic if swallowed

H311 Acute Tox. 3 Toxic in contact with skin

H331 Acute Tox. 3 Toxic if inhaled

H370 STOT SE 1

H302 Acute Tox. 4 Harmful if swallowed

H312 Acute Tox. 4 Harmful in contact with skin

H332 Acute Tox. 4 Harmful if inhaled

H304 Asp. Tox. 1

H371 STOT SE 2 (May cause damage to organs (or state all organsaffected if known) (state route of exposure if it is conclusively proventhat no other routes of exposure cause the hazard)

Other toxicological properties

H336 STOT SE 3 May cause drowsiness or dizziness

 

 

 

It is concluded that the substance Sodium isobutyl xanthate, meet the criteria to be classified for human health hazards for acute oral and dermal effects:

R22: Harmful if swallowed

R21: Harmful in contact with skin

H302 Acute Tox. 4 Harmful if swallowed

H312 Acute Tox. 4 Harmful in contact with skin