Assay of free and acid labile carbon disulphide (free and total CS2 respectively) in human blood was performed by gas chromatography/ spectrometry. The method used a large dynamic head space volume and a "cryogenic trap". Blood CS2 concentration was measured in 42 subjects not occupationally exposed to CS2 (group A) and in 11 alcoholic subjects (group B) treated with disulfiram. Free CS2 concentration showed a mean value of 261 ng/l in the 42 subjects in group A and 9482 ng/l in eight subjects ofgroup B. Total CS2 concentration was 897 ng/l and 40 084 ng/l in groups A and B respectively. Differences between the groups were highly significant for concentrations of both free and total CS2. Total CS2 concentration was about four times as high as free CS2 concentration in both groups. A significant correlation was found between free and total CS2 concentration both in group A and in group B. In the alcoholic subjects (group B), blood concentrations ofboth free and total CS2 were related to time of sampling after treatment with disulfiram.

Both disulfiram (tetraethylthiuram disulfide), an alcohol aversive drug, and thiram (tetramethyl-thiuram disulfide), a widely used pesticide, significantly increased the dopamine pool in the adrenal glands of dosed rats. The dopamine increase was detectable within 4 h of oral dosing with 100 mg/kg of either dithiocarbamate and peaked 24 h later at 10 times control values. In control rats the dopamine turnover was 0.51 h-1 as calculated by the assumed first order decline of dopamine after a single injection of alpha-methyl-p-tyrosine (alpha-MT, 400 mg/kg i.p.) resulting in a dopamine-beta-hydroxylase (DBH) activity of 0.73 nmol/h per pair of adrenals. In the adrenals of rats pretreated with thiram and then injected with alpha-MT, the adrenal dopamine content did not significantly decline, indicating that thiram reduced the conversion of dopamine to noradrenaline, eventually leading to the observed dopamine increase. Plasma DBH activity was significantly reduced 4 h and 24 h after dosing with thiram, but was unchanged after treatment with disulfiram. The determination of plasma DBH activity could be a marker to monitor the effect of thiram on catecholamine metabolism in occupationally exposed workers but not that of disulfiram in abstinent alcoholics.

1 In humans CaNa 2EDTA increases urinary excretion of lead as well as that of essential metals such as zinc, ferrum and manganese but not that of copper. 2 We studied the effect of CaNa2EDTA injection on serum dopamine-β-hydroxylase, a copper-dependent enzyme, in three male lead welders hospitalized for suspected lead poisoning. 3 injection of CaNa 2EDTA (1000 mg i.v.) resulted in rapid reduction of serum dopamine-β-hydroxylase activity which returned to normal level within 24 hours. 4 Copper sulphate (8 μM) but not ethylmaleimide (10 mM) restored in vitro serum dopamine-β-hydroxylase activity to pre-dosing values which indicates that CaNa2EDTA inhibits dopamine-β-hydroxylase by removing copper from the enzyme. 5 An inverse dose effect relationship between injected CaNa2EDTA and residual serum dopamine-β-hydroxylase activity was observed. 6 In spite of the reported lack of changes in copper serum concentration, CaNa2EDTA significantly affects the activity of a copper-dependent enzyme in the serum. 7 As CaNa 2EDTA is currently the drug of choice for the treatment of asymptomatic lead poisoning in children, the effect of CaNa2EDTA on copper-enzymes requires further investigation.

The aim of this study was to investigate the effects of single and repeated disulfiram doses on serum dopamine-beta-hydroxylase activity and blood carbon disulphide concentrations in a group of abstinent alcoholics. The increase in the blood concentration of carbon disulphide was dose dependent after the oral administration of 100-400 mg of disulfiram. Free carbon disulphide peaked at 12 h while the protein-bound fraction increased at least up to 24 h. Both single (100-400 mg p.o.) and repeated (200 mg daily p.o. for ca. 1 month) administrations failed to inhibit the activity of serum dopamine-beta-hydroxylase. The repeated daily administration of 200 mg of disulfiram also had no influence on copper-activated serum dopamine-beta-hydroxylase, which was the same before and after 1-month treatment period. Contrary to the disulfiram group, the activity of the copper-activated enzyme in the serum of abstinent alcoholics declined significantly during the same 30 days.