Sodium O-isobutyl dithiocarbonate

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic 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: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1976

Reference 2

Reference Type:

review article or handbook

Title:

Thirty-day inhalation toxicity study with potassium amyl xanthate

Author:

. Canadian Centre for Occupational Health and Safety,

Year:

1994

Bibliographic source:

Cheminfo 202, 1994.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A 30-day repeated inhalation study for potassium amyl xanthate was conducted in 1976. Animals were exposed to potassium amyl xanthate as an aqueous aerosol. Attempts at dust exposure were unsuccessful as potassium amyl xanthate is hygroscopic.
Animals were exposed to concentrations of 0, 100 and 800 mg/m3 of potassium amyl xanthate. These concentrations were equivalent to actual doses of 0, 23 and 252 mg/m3. Analysis of the particle size indicated that all the particles at the lower dose of 100 mg/m3 were less than 10μm in diameter while approximately 80% of the particles had a diameter of 10μm or less at a dose of 800 mg/m3. It is not possible to state from the description of the exposure method whether air flow was dynamic or static.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Potassium O-pentyl dithiocarbonate

EC Number:

220-329-5

EC Name:

Potassium O-pentyl dithiocarbonate

Cas Number:

2720-73-2

IUPAC Name:

potassium O-pentyl dithiocarbonate

Constituent 2

Reference substance name:

potassium amyl xanthate

IUPAC Name:

potassium amyl xanthate

Test material form:

aerosol dispenser: not specified

Remarks:

migrated information: aerosol

Details on test material:

- Name of test material (as cited in study report): potassium amyl xanthate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

10 male Sprague-Dawley rats were exposed to concentrations of 0, 200 or 800 mg/m3 of potassium amyl xanthate, 6 hrs daily for 10 exposures in 2 weeks.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Remarks on MMAD:

MMAD / GSD: Analysis of the particle size indicated that all the particles at the lower dose of 100 mg/m3 were less than 10μm in diameter while approximately 80% of the particles had a diameter of 10μm or less at a dose of 800 mg/m3. It is not possible to state from the description of the exposure method whether air flow was dynamic or static.

Details on inhalation exposure:

Animals were exposed to potassium amyl xanthate as an aqueous aerosol. Attempts at dust exposure were unsuccessful as potassium amyl xanthate is hygroscopic.
Animals were exposed to concentrations of 0, 100 and 800 mg/m3 of potassium amyl xanthate. These concentrations were equivalent to actual doses of 0, 23 and 252 mg/m3. Analysis of the particle size indicated that all the particles at the lower dose of 100 mg/m3 were less than 10μm in diameter while approximately 80% of the particles had a diameter of 10μm or less at a dose of 800 mg/m3. It is not possible to state from the description of the exposure method whether air flow was dynamic or static.
Exposure levels for the study were established by a preliminary experiment. In the preliminary experiment, three groups of 10 male Sprague-Dawley rats were exposed to concentrations of 0, 200 or 800 mg/m3 of potassium amyl xanthate, 6 hrs daily for 10 exposures in 2 weeks. No signs of toxicity were observed in animals exposed to a concentration of 200 mg/m3. Rats exposed to a concentration of 800 mg/m3 showed a statistically significant decrease in body weight after the fifth exposure. Recovery of the body weight occurred within 4 days and may not have been exposure related.
The only substance related adverse effect observed was a yellow-brown staining of the hair coat of the rats.
Overexposure of the animals exposed to a concentration of 800 mg/m3 occurred because of a technical problem in the aerosol generating apparatus.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

30-day

Frequency of treatment:

6 hrs daily, 5 days a week for a total of 20 exposures in 1 month.

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 100 and 800 mg/m3
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0, 23 and 252 mg/m3.
Basis:
other: actual doses

No. of animals per sex per dose:

10 male Sprague-Dawley rats were exposed to filtered room air or to concentrations of 100 or 800 mg/m3 of potassium amyl xanthate.
Whole body exposure was for 6 hrs daily, 5 days a week for a total of 20 exposures in 1 month.

Control animals:

yes

Details on study design:

Exposure levels for the study were established by a preliminary experiment. In the preliminary experiment, three groups of 10 male Sprague-Dawley rats were exposed to concentrations of 0, 200 or 800 mg/m3 of potassium amyl xanthate, 6 hrs daily for 10 exposures in 2 weeks. No signs of toxicity were observed in animals exposed to a concentration of 200 mg/m3. Rats exposed to a concentration of 800 mg/m3 showed a statistically significant decrease in body weight after the fifth exposure. Recovery of the body weight occurred within 4 days and may not have been exposure related.
The only substance related adverse effect observed was a yellow-brown staining of the hair coat of the rats.
Overexposure of the animals exposed to a concentration of 800 mg/m3 occurred because of a technical problem in the aerosol generating apparatus.

Positive control:

no data

Examinations

Observations and examinations performed and frequency:

Animals were exposed to concentrations of 0, 100 and 800 mg/m3 of potassium amyl xanthate. These concentrations were equivalent to actual doses of 0, 23 and 252 mg/m3. Analysis of the particle size indicated that all the particles at the lower dose of 100 mg/m3 were less than 10μm in diameter while approximately 80% of the particles had a diameter of 10μm or less at a dose of 800 mg/m3. It is not possible to state from the description of the exposure method whether air flow was dynamic or static.
Exposure levels for the study were established by a preliminary experiment. In the preliminary experiment, three groups of 10 male Sprague-Dawley rats were exposed to concentrations of 0, 200 or 800 mg/m3 of potassium amyl xanthate, 6 hrs daily for 10 exposures in 2 weeks. No signs of toxicity were observed in animals exposed to a concentration of 200 mg/m3. Rats exposed to a concentration of 800 mg/m3 showed a statistically significant decrease in body weight after the fifth exposure. Recovery of the body weight occurred within 4 days and may not have been exposure related.
The only substance related adverse effect observed was a yellow-brown staining of the hair coat of the rats.
Overexposure of the animals exposed to a concentration of 800 mg/m3 occurred because of a technical problem in the aerosol generating apparatus.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, the presence of tumours in the lungs, liver, kidneys, pancreas, spleen and any other organs were recorded.
HISTOPATHOLOGY: Yes, the lungs, liver, kidneys, pancreas, spleen and any other organs with tumours were sampled at necropsy.

Other examinations:

See table 1.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

See table 1.

Mortality:

no mortality observed

Description (incidence):

See table 1.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

See table 1.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Description (incidence and severity):

No statistically significant treatment related effects were observed.See table 1.

Clinical biochemistry findings:

no effects observed

Description (incidence and severity):

No statistically significant treatment related effects were observed.

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

No significant differences were observed between the test and control groups. See table 1.

Gross pathological findings:

no effects observed

Description (incidence and severity):

No statistically significant treatment related effects were observed.See table 1.

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

o statistically significant treatment related effects were observed.See table 1.

Histopathological findings: neoplastic:

no effects observed

Description (incidence and severity):

No statistically significant treatment related effects were observed.See table 1.

Details on results:

NOAEC of 23 mg/m3 was established based on no effects in rats.
The results of this study indicate that potassium amyl xanthate has an adverse effect at concentration of 252mg/m3 on the central nervous system and liver in mice, the liver and kidneys in rats and the liver in dogs. There were no treatment-related changes in the haematological or urinalysis values in any of the animals.

Effect levels

1

Dose descriptor:

NOAEC

Effect level:

23 mg/m³ air

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No statistically significant effects were noted in the study at the concentration tested.

2

Dose descriptor:

dose level:

Effect level:

252 mg/m³ air

Based on:

test mat.

Sex:

male

Basis for effect level:

other: Nephrotoxic effects.High serum alanine aminotransferase activity,Microscopically visible granular degeneration, One Death, but not related to exposure

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 1 Results of repeated inhalation study with potassium amyl xanthate in laboratory animals

 

		Dogs (2 animals)	Rabbits (4 animals)	Rats (10 animals)	Mice (10,6 animals)
100 mg/m3	Eyes	No irritation	No irritation	No irritation	No irritation
	Nasal effects	No effects	No effects	No effects	No effects
	Hair coat	Yellow brown staining.	Progressive yellow brown staining	Yellow brown stainingof the hair coat of the rats.	No staining
	Other effects	Staining of the appendages and scrotum; ulceration of the skin in the scrotal region.	None	None	None
	Body weight	No change	No change	No change	No change
	Organ weight	No change	No change	No change	Higher liver to body weight ratio than controls
	Liver enzyme changes	Marked elevation of serum alanine aminotransferase and alkaline phosphatase activities	No change	No change	No change
	Histopathology changes	Hepatocellular degeneration, necrosis and inflammation	No treatment related change	No treatment related change	No treatment related change
	Deaths	None	None	None	None
800 mg/m3	Eye changes	Excessive lacrimation	Conjunctival redness	No irritation	No changes
	Nasal effects	None	None	Reddish nasal discharge	None
	Hair coat	Yellow brown staining	A more intense yellow brown	Yellow brown staining	No effects
	Skin	Ulceration of the skin	No effect	No effect	No effect
	Body weight	No effect	No effect	No effect	No effect
	Organ weight	No change	No change	Higher liver to body weight ratio than controls	Higher liver to body weight ratio than controls
	Liver enzyme changes	Marked elevations of serum alanine aminotransferase and alkaline phosphatase activities.	No changes	High serum alanine aminotransferase activity	No changes
	Histopathology changes	Hepatocellular degeneration, necrosis and inflammation	No changes	Microscopically visible granular degeneration	No changes
	Deaths	None	None	One, but not related to exposure	10 from the original group and 5/6 replacement animals died. Convulsions hyperactivity in 5/16 prior to death.

 

Applicant's summary and conclusion

Conclusions:

NOAEC of 23 mg/m3 was established based on no effects in rats.
The results of this study indicate that potassium amyl xanthate has an adverse effect at concentration of 252mg/m3 on the central nervous system and liver in mice, the liver and kidneys in rats and the liver in dogs. There were no treatment-related changes in the haematological or urinalysis values in any of the animals.

Executive summary:

NOAEC of 23 mg/m3 was established based on no effects in rats.

The results of this study indicate that potassium amyl xanthate has an adverse effect at concentration of 252 mg/m3 on the central nervous system and liver in mice, the liver and kidneys in rats and the liver in dogs. There were no treatment-related changes in the haematological or urinalysis values in any of the animals.