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Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
other: published data
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Potassium O-pentyl dithiocarbonate is similar to S-allyl O-pentyl dithiocarbonate . Comparable metabolism would occur.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
A 30-day Repeated Inhalation Toxicity Study of Potassium Amyl Xanthate (Z-6) in Laboratory Animals”,
Author:
Dow Chemical Company
Year:
1976
Bibliographic source:
Dow Chemical Company, Michigan, USA, 1976.
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

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
aerosol dispenser: not specified
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 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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 100 and 800 mg/m3
Basis:
nominal conc.
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 the substance 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

open allclose all
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.
Remarks on result:
other: No statistically significant effects were noted in the study at the concentration tested.
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
Remarks on result:
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 the substance 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. Potassium O-pentyl dithiocarbonate is similar to S-allyl O-pentyl dithiocarbonate . Comparable metabolism would occur.

Executive summary:

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

The results of this study indicate that the substance 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.