Sodium O-isobutyl dithiocarbonate

Endpoint summary

Description of key information

Sodium isobutyl xanthate has not bioaccumulation potential. Xanthates are metabolised in humans and animals to Carbon disulphide. Animal data for Sodium isobutyl xanthate (the result was read across from sodium ethyl xanthatе and potassium ethyl xanthate) indicate that up to 7% of dose may be eliminated as CS2 in breath.
The kinetics of absorption, distribution and elimination of CS2 is by the excretion of the "biomonitoring metabolite TTCA" in the urine. Uptake in the blood is rapid and a blood equilibrium was reached in about 90 min, although a slight increase continued thereafter. Elimination was also rapid and biphasic (rapid and more slow phase). Terminal elimination times varied from 41 to 77 min.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - dermal (%):

1

Additional information

Sodium isobutyl xanthate has not bioaccumulation potential.Xanthates are metabolised in humans and animals to Carbon disulphide. Animal data for Sodium isobutyl xanthate (the result was read across from sodium ethyl xanthatе andpotassium ethyl xanthate)indicate that up to 7% of dose may be eliminated as CS2 in breath.

It is known that Sodium isobutyl xanthate (the result was read across from sodium ethyl xanthatеandpotassium ethyl xanthate)is metabolised to CS2 due to the presenceof the CS2/cysteine (glutathione) conjugation product, 2-thiothiazolidine-4-carboxylic acid (TTCA)

 

The kinetics of absorption, distribution and elimination of CS2 is by the excretion of the "biomonitoring metabolite TTCA" in the urine. Uptake in the blood is rapid and a blood equilibrium was reached in about 90 min, although a slight increase continued thereafter. Elimination was also rapid and biphasic (rapid and more slow phase). Terminal elimination times varied from 41 to 77 min.

 

Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. Sodium isobutyl xanthate readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of sodium isobutyl xanthate.

Toxicokinetics, metabolism and distribution

It is generally considered that adverse effects from exposure to xanthates (inhumans and animals) are associated with CS2 toxicity. It is not known whatcontribution to human toxicity is likely from inhalation/dermal absorption of CS2per se, as a xanthate decomposition product, and CS2 as a xanthate metabolite.

If metabolism to CS2 is associated with critical effects, then the limited dataavailable on xanthate metabolism indicates that similar toxicological profilesmight be expected for animals and humans.

Animal and human studies indicate that the nervous system is the critical targetorgan for CS2 from inhalation exposure.

Xanthates are metabolised in humans and animals to CS2. Animal data forSodium isobutyl xanthate(the result was read across from sodium ethyl xanthatе andpotassium ethyl xanthate)indicate that up to 7% of dose may be eliminated as CS2in breath. The eliminationvs time curves for sodium ethyl xanthate in humansand guinea pigs indicate that biotransformation to CS2 is not saturated at dosesstudied (250 mg or 3.5 mg/kg in humans).

It is known that Sodium isobutyl xanthate (the result was read across from sodium ethyl xanthatеandpotassium ethyl xanthate) is metabolised to CS2 due to the presenceof the CS2/cysteine (glutathione) conjugation product, 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine of exposed workers.

A single metabolism study (in French) published by Merlevede and Peters (1965)was identified in the above literature search. In this study, humans and guineapigs were dosed with various xanthate compounds and the amount of expired CS2 monitored.

 

Following sub-cutaneous injection (70-200 mg/kg) of potassium ethyl xanthate inguinea pigs, up to 7% of the dose was expired as CS2 after 8 h, with maximumelimination between 1 - 2 h in most animals. The rate of elimination was doserelated,however the total percentage recovered was independent of dose. A morerapid rate of elimination was seen following sub-cutaneous injection (50 and 100mg/kg) of sodium ethyl xanthate, with CS2 expiration complete after 6 h, withmaximum elimination at 1 h (total recovery of CS2 was not reported).

 

Following oral intake in human volunteers, of 150 and 250 mg sodium ethylxanthate, a maximum rate (13 – 57 μg/m3/h) of CS2 elimination in breath wasseen between 1-2 h, with complete elimination by 6 h (total recovery of CS2 wasnot reported).

 

The effect of alcohol on xanthate metabolism was also studied. In guinea pigs,concomitant sub-cutaneous injection of sodium diethyl xanthate and alcoholresulted in an increased rate of elimination, together with a greater total recoveryof CS2. These increases were directly related to the dose of alcohol.

 

An increased rate of elimination was also apparent in humans administered 250mg sodium ethyl xanthate, following intake of 200 ml of alcohol (approximately18% by volume), however, the lack of a suitable control group preventedquantitative assessment.

 

The critical health effects from exposure to sodium ethyl xanthate in humans andanimals are eye and skin irritation and possible neurological effects.

 

Acute effects, mainly gastrointestinal and CNS, were reported in one xanthateworker which were associated with possible inhalation and dermal exposure.

Retrospective monitoring indicated that exposure to CS2 levels may have been in excess of 60 ppm (187 mg/m3).

 

 

In 30 day inhalation (aerosol) studies with potassium amyl xanthate hepatotoxic effects were seen in dogs and mice at 23 mg/m3 (7.5ppm), and nephrotoxic effects in rats at 252 mg/m3 (81.5 ppm).

It is generally considered that adverse effects from exposure to xanthates (inhumans and animals) are associated with CS2 toxicity. It is not known what contribution to human toxicity is likely from inhalation/dermal absorption of CS2per se, as a xanthate decomposition product, and CS2 as a xanthate metabolite.

If metabolism to CS2 is associated with critical effects, then the limited data available on xanthate metabolism indicates that similar toxicological profiles might be expected for animals and humans.

Animal and human studies indicate that the nervous system is the critical targetorgan for CS2 from inhalation exposure. Apparently only one chronic inhalation study has been carried out in animals for CS2 and there are no chronic animal orhuman data pertaining to neurological effects following dermal exposure(ATSDR 1996).

Notwithstanding the available epidemiological data, it has generally beenconsidered that chronic adverse effects in humans from inhalation exposure toCS2 are associated with levels in excess of 10 ppm2.