Potassium isopentyl dithiocarbonate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was regarded not reliable since there is not enough data for assessment. Read-across justification: Target substance belongs into the group of substances called xanthates. The xanthates are generally prepared from the reaction of the alkoxide, which reacts with carbon disulphide to give the xanthate. These substances contain common functional group which is dithiocarbonate (-OCSS-). Though they are structural analogues with the target substance. All these analogue substances are also used in similar use application as water solutions. All xanthates decompose in the presence of water. In neutral to alkaline media, they will release carbon disulphide, particular alcohol(s) and carbonates and dithiocarbonates. Carbon disulphide is the major and the most volatile and the most hazardous decomposition product of xanthates. It is also more toxic to human health than the target substance. As the xanthates can be considered as a group of substances which have structural similarity and similar behaviour in contact with water and in the physiological processes, their irritation as well as acute and systemic adverse effects to human health are similar. Therefore, and in order to avoid the unnecessary animal testing, the read-across data from the analogue xanthates is used to evaluate the irritation, and short term and/or long-term toxicological effects of the target substance. As the target substance is an unstable compound, the apparent toxicity reflects to the toxicity of the degradation products. The selection of the most critical degradation products for the hazard assessment are based on the known decomposition reaction of the target substance and based on the physicochemical properties and toxicological properties of the degradation products. The adverse effects through inhalation route are not relevant for the substance itself, which is a solid non-volatile pellet form substance. However, the most serious human health hazards are related to CS2 released from the target substance. Therefore, the formation of carbon disulphide by decomposition is the driving force for human health hazard assessment via inhalation and taken into account in DNEL derivation and in the exposure assessment of the target substance.

Data source

Reference

Reference Type:

publication

Title:

The Toxicological Characteristics of the Flotation Reagent Potassium Butyl Xanthate

Author:

Babayan, E.A.

Year:

1968

Bibliographic source:

Materials from the 3rd General Scientific Conference on Occupational Hygiene and Occupational Pathology in the Chemical and Mining Industries

Materials and methods

Principles of method if other than guideline:

Potassium butyl xanthate was administered orally (10mg/kg) to rats for 4 months.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Potassium O-butyl dithiocarbonate

IUPAC Name:

Potassium O-butyl dithiocarbonate

Constituent 2

Reference substance name:

Potassium O-butyl dithiocarbonate

EC Number:

212-808-2

EC Name:

Potassium O-butyl dithiocarbonate

Cas Number:

871-58-9

IUPAC Name:

potassium O-butyl dithiocarbonate

Test animals

Species:

rat

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Duration of treatment / exposure:

4 months

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
10 mg/kg
Basis:
actual ingested

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

not specified

Behaviour (functional findings):

effects observed, treatment-related

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Details on results:

CLINICAL SIGNS AND MORTALITY
From the 6-7th week, the animals of the first two groups developed signs of intoxication. Apathy, drowsiness, limited movement, rapid breathing, cyanotic eye mucous membranes, fur loss, seizures, and paresis and paralysis of the limbs were all noted, and many rats lacked reaction to pain stimulus. Some of the animals died during and after the experiments. Some animals died during the administration.

BODY WEIGHT AND WEIGHT GAIN
A statistically significant (P≤0.05) weight loss (of 23%),

CLINICAL CHEMISTRY
an increase in blood sugar (of 72-85%) and cholesterol (of 49%) in the blood and in sulfhydryl groups of serum proteins (from 70% to more than double), a reduction in the albumin/globulin ratio, a change in the fractional composition of serum proteins (hyperglobulinemia with dominant β fraction). Also, the animals from these groups showed significant changes in the metabolism of a series of mineral substances, namely zinc, copper, manganese, magnesium, molybdenum, titanium, silicon, phosphorus, iron, aluminium, and calcium. In some organs the content of some of these elements increased, while in other organs it decreased. The most typical changes were in the metabolism of the microelements Zn and Cu: they decreased in all organs, and there was a parallel increase in their excretion from the body.

NEUROBEHAVIOUR
A change in the ability of the central nervous system to register subthreshold impulses.

GROSS PATHOLOGY
The main changes in the nervous system are severe vascular damage in various parts of the brain, dystrophic changes in the nerve cells of the cortex, basal ganglia, thalamohypothalamic area and brain stem in the form of swelling with severe vacuolization of protoplasm in individual nerve cells and karyolysis and cytolysis with the formation of ghost cells. Dystrophic changes in the form of swelling and vacuolization of the protoplasm of nerve cells and the death of individual neurons were found in nerve cells of the anterior horn of the spinal cord. Local myelin disintegration on Nissl bodies and bead-like deformation of axons were observed in peripheral nerves. The latter coincides with clinical manifestations of paralysis.
Dystrophic changes in the liver and kidneys are pronounced.

Effect levels

Dose descriptor:

NOAEL

Effect level:

< 10 mg/kg bw/day (actual dose received)

Based on:

test mat.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Potassium butyl xanthate was administered orally at dose level of 10 mg/kg/day in rats. Mortality and severe adverse effects were observed during administration. Thus, the NOAEL is determined to be < 10mg/kg/day.

Executive summary:

The subacute toxicity study was conducted for potassium butyl xanthate, the analogue substance of potassium isoamyl xanthate. This study showed pathological and morphological changes in several tissues. Severe vascular changes were observed in the brain and spinal cord, dystrophic changes were identified in the nerve cells of various parts of the brain and in the anterior horn of the spinal cord, and gross morphological changes were found in the peripheral nerves. Animals also developed dystrophic changes in the liver (steatosis) and in the kidneys (proteinosis of convoluted tubule epithelium).

 

Animal developed a series of changes in physiological and biochemical indicators, which are largely similar to those from carbon disulfide intoxication. The following effects were obseved: weight loss, an increase in oxygen consumption, a change in the ability of the central nervous system to register subthreshold impulses, an increase in blood sugar and cholesterol in the blood, as well as the content of sulfhydryl groups of serum proteins (hyperglobulinemia with dominant β fraction and a reduction in the albumin/globulin ratio), and changes in the metabolism of elements Zn, Cu, Mn, Mo, Mg, Ti, P, Si, Fe, Al and Ca.

The result of this study is used as a weight of evidence in hazard assessment.