Potassium O-isobutyl dithiocarbonate

Respiratory sensitisation

Administrative data

Endpoint:

respiratory sensitisation: in vivo

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:

not specified

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

Test system

Route of induction exposure:

inhalation

Route of challenge exposure:

inhalation

Vehicle:

other: aqueous aerosol

Concentration:

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. of animals per dose:

10

Details on study design:

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.

Positive control substance(s):

not specified

Negative control substance(s):

not specified

Results and discussion

Results:

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. No signs of irritation of respiratory tract and Nasal effects were observed.

Any other information on results incl. tables

Table 5 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 and irritation of respiratory tract	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 and irritation of respiratory tract	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

Interpretation of results:

not sensitising

Conclusions:

The results of the study (Dow Chemical Company 1976) indicate that Potassium isobutyl xanthate (the result was read across from 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. No signs of irritation of respiratory tract and Nasal effects were observed.

Executive summary:

In the 30-day study, three groups of animals, each consisting of 10 male Swiss-Webster mice, 10 male Sprague-Dawley rats, 4 male New Zealand White rabbits and 2 male beagle dogs were exposed to either filtered room air or to concentrationsof 100 or 800 mg/m3 of potassium amyl xanthate. Whole body exposure was for 6 hrsdaily, 5 days a week for a total of 20 exposures in 1 month.

Ten mice of the 800 mg/m3group died along with 5/6 replacement mice.

The animals were observed during the exposures and body weights were recordedthree times a week throughout the experiment. Body weight data, organ to bodyweight ratios and clinical laboratory parameters were analysed statistically usinganalysis of variance and Dunnett’s test.

 

Most of the mice died when exposed to 800 mg/m3. Five of the 16 mice that diedshowed convulsions and hyperactivity prior to death. The adverse effects produced by the two doses of potassium amyl xanthate are shown in Table1.

 

The results of this study indicate that potassium amyl xanthate has an adverseeffect at concentration of 252mg/m3on the central nervous system and liver in mice, the liver and kidneys in ratsand the liver in dogs. There were no treatment-related changes in thehaematological or urinalysis values in any of the animals.No signs of irritation of respiratory tract and Nasal effectswere observed.