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Description of key information

Information of the analogue substance, potassium ethyl xanthate:
Animal data shows that 7% of dose is eliminated as CS2 in breath. The elimination versus time curves for sodium ethyl xanthate in human sand guinea pigs indicate that biotransformation to CS2 is not saturated at doses studied (250 mg or 3.5 mg/kg in humans).
Information from the most hazardous decomposition product, carbon disulphide, since the target substance is decomposed to CS2:
Readily absorbed via inhalation and dermal routes. CS2 is mainly metabolized (70-90%), 1% excreted unchanged and remainder exhaled. Final, metabolic products of CS2 are various sulphur compounds and CO2, which are excreted in urine and exhaled, respectively.
Information from another decomposition products, 3-methyl-1-butanol and 1-pentanol:
Rapidly oxidised by way of corresponding aldehydes and fatty acid dehydrogenases.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

No studies were available on potassium isoamyl xanthate toxicokinetics. The assessment of the toxicokinetic behaviour of the substance is based on the physical and chemical properties of the substance and the available toxicokinetic information from the analogue substances, sodium and potassium ethyl xanthate. Toxicokinetic data of carbon disulphide (CS2) is also considered in this assessment as it is the most hazardous decomposition product of potassium isoamyl xanthate. CS2 is formed when the substance is in contact with moisture or water. It is relevant to be considered in the chemical safety assessment as the substance is only used as water solutions. In addition, CS2 is considered relevant as it is also a product of the xanthate metabolism in animals and humans.

Potassium isoamyl xanthate in the presence of moisture decomposes to carbon disulphide (CAS no 75-15-0), 3-methyl-1-butanol (CAS no 123-51-3), 1 -pentanol (CAS no 71 -41 -0). The minor degradation products of xanthate are also potassium carbonate (CAS no 584-08-7) and potassium trithiocarbonate (CAS no 26750-66-3). Toxicokinetics of CS2 is discussed below since it is classified for toxic to reproduction (Repro Cat 2 with SCL of 1 %, H361fd). Also toxicokinetics of other hazardous degradation products are discussed briefly.

It is known that sodium ethyl xanthate is metabolised to CS2 of exposed workers. In a single metabolism study by Merlevede and Peters (1965), humans and guinea pigs were dosed sodium and potassium ethyl xanthate, and the amount of expired CS2 monitored. Following sub-cutaneous injection (70-200 mg/kg) of potassium ethyl xanthate in guinea pigs, up to 7% of the dose was expired as CS2 after 8 h, with maximum elimination between 1 - 2 h in most animals. The rate of elimination was dose-related, however the total percentage recovered was independent of dose. A more rapid rate of elimination was seen following sub-cutaneous injection (50 and 100 mg/kg) of sodium ethyl xanthate, with CS2 expiration complete after 6 h, with maximum elimination at 1 h (total recovery of CS2 was not reported). Following oral intake in human volunteers, of 150 and 250 mg sodium ethyl xanthate, a maximum rate (13 – 57 µg/m3/h) of CS2 elimination in breath was seen between 1-2 h, with complete elimination by 6 h (total recovery of CS2 was not reported).

Animal studies indicate that carbon disulphide is readily absorbed by inhalation. Absorption of carbon disulphide was studied by evaluating pulmonary and urinary excretion of carbon disulphide during and after exposure. Studies in rabbits indicate that an equilibrium concentration of carbon disulphide is reached after inhalation exposure to 20-150 ppm for 1.5-2.0 hours. About 70-80 % of inhaled carbon disulphide was absorbed. After termination of exposure, 15-30% of the absorbed carbon disulphide was excreted through the lungs and less than 0.1 % by the kidneys (Toyama and Kusano, 1953 cited in DHHS/ATSDR, 1996).

Studies also indicate that carbon disulphide as a liquid, such as a solvent or aqueous solution, is absorbed through the skin. Dutkiewicz and Baranowska, 1967 (cited in WHO, 2002), reported that rates of absorption of carbon disulphide, determined from analysis of aqueous solutions into which subjects had immersed their hands for 1 h, ranged from 0.323 to 0.798 mg/m3 per hour.

Studies in humans have shown that approximately 70–90% of carbon disulphide absorbed into the body is metabolised, with 1% excreted unchanged and the remainder exhaled (WHO, 1979). Due to its affinity for lipid-rich tissues and organs, carbon disulphide rapidly disappears from the bloodstream. In humans, carbon disulphide is metabolised to give 2-mercapto-2-thiazolinone-5, thiocarbamide and TCCA (thio-thiazolidine-4-carboxylic acid) (WHO, 2002), which are excreted in urine. TTCA represents 2-6% of the total carbon disulphide absorbed in humans and has been used for biomonitoring. Alternatively, carbon disulphide can be metabolized in the liver by cytochrome P-450 system to various sulphur compounds to be excreted in urine and to carbon dioxide to be exhaled (WHO, 2002).

When in contact with water or moisture, the substance releases alcohol mainly 3 -methyl-1-butanol. Also trace amounts of 1-pentanol is released from potassium amyl xanthate which is an impurity (~ 11%) of the substance. Since these alcohols are structural isomers, their toxicokinetic and toxicological properties are expected to be identical. Thus only the toxicokinetics of 3-methyl-1-butanol is discussed below.

3-methyl-1-butanol is very rapidly metabolised following serial (four 15-minute intervals) intraperitoneal (ip) injections (Snyder, 1992). Only 1-1.5% of the administered doses of 3-methyl-1-butanol were excreted in the expired air plus urine as the pentanol. The blood concentration of 3-methyl-1-butanol decreased from 37 mg/100 ml at 1 hr (ie, 15 min after the last pentanol injection) to <1 mg/100 ml at 5 hr. In the rabbit, limited amount of 3-methyl-1-butanol is conjugated to yield the glucuronide, and 7-10% of the administered dose is excreted as the urinary glucuronide.