Thiocyanate, urinary

Urinary excretion patterns of thiocyanate suggest that there are quantitative species differences in acrylonitrile metabolism (Ahmed and Patel 1981). Thiocyanate was identified as a metabolite in rats, mice, rabbits and Chinese hamsters. About 20 to 23% of the administered dose was excreted as thiocyanate in rats, rabbits and Chinese hamsters, while 35% was excreted as thiocyanate in mice (Gut et al. 1975). It has also been observed that mice metabolize acrylonitrile more rapidly than rats (Ahmed and Patel 1981 Gut et al. 1975). Maximum blood cyanide concentrations were observed 1 hour after dosing in mice, but 3 hours after dosing in rats (Ahmed and Patel 1981). In mice, thiocyanate was present in the urine within 4 hours of dosing, while in rats, thiocyanate was present in urine only at time intervals longer than 4 hours (Gut et al. 1975). 

Tardif R, Talbot D, Gerin M, et al. 1987. Urinary excretion of mercapturic acids and thiocyanate in rats exposed to acrylonitrile Influence of dose and route of administration. Toxicol Lett 39 255-261. 

Following chronic occupational exposure to 0.19-0.75 ppm hydrogen cyanide, 24-hour urinary levels of thiocyanate were 6.23 (smokers) and 5.4 pg/mL (nonsmokers) in exposed workers as compared with 3.2 (smokers) and 2.15 pg/mL (nonsmokers) in the controls (Chandra et al. 1980). This study demonstrates that tobacco smoking contributes to higher thiocyanate levels excreted in the urine. No studies were located regarding excretion of cyanide in animals after inhalation exposure to cyanide. 

Levels of cyanide and its metabolite thiocyanate in blood serum and plasma, urine, and saliva have been used as indicators of cyanide exposure in humans, particularly in workers at risk of occupational exposures, in smokers or nonsmokers exposed to sidestream or environmental tobacco smoke, in populations exposed to high dietary levels of cyanide, and in other populations with potentially high exposures (see Section 5.6). The correlation between increased cyanide exposure and urinary thiocyanate levels was demonstrated in workers exposed to 6.4-10.3 ppm cyanide in air (El Ghawabi et al. 1975). In another study, blood cyanide concentrations were found to vary from 0.54 to 28.4 pg/100 mL in workers exposed to approximately 0.2-0.8 ppm cyanide in air, and from 0.0 to 14.0 pg/100 mL in control workers... 

Chandra et al. 1988). Similar elevations in urinary thiocyanate levels were observed, with concentrations for exposed workers and controls ranging from 0.05 to 2.80 and 0.02 to 0.88 mg/mL, respectively. 

Enander, Sundwall, and Sorbo - -- 7 found that either oral or Intramuscular administration of 11 to rats at 500 or 100 mg/kg, respectively, increased by many times the urinary excretion of thiocyanate. From the amount of thlocynanate excreted above the base line, the quantity of hydrogen cyanide produced in metabolism of the oxime was calculated to be 0.1 mg/kg—a little more than one-third the LD50 for rats by lntraperitoneal injection. Urine from rats given 120 ymol of II intramuscularly or 400 pmol by mouth contained 3.9-7.8% N-methylpyridinlum-2-nltrlle methanesulfonate. When this compound was injected Intramuscularly into rats at 90 mg/kg, thiocyanate was excreted in the urine in Increased amounts. Also present in the urine was a metabolic product that yielded cyanide on acidification of the urine, similar to a cyanide-yielding metabolite of II found earlier. 

Urinary metabolites of acrylonitrile include 5 -(2-cyanoethyl)mercapturic acid, N-acet T-3-carboxy-5-cyanotctrahydro-I,4-3//-thiazine and thiocyanate (Kopecky et al., 1979 Langvardt et al., 1980 Gut c/ al., 1981 Sapota, 1982). The proportion excreted as thiocyanate by rats is far higher (23% of dose) after oral dosing than after intraperitoneal, intravenous or subcutaneous administration (1-4% of dose Gut et al., 1981). Other metabolites derived from the mercapturic acid pathway include. S -carboxymethylcys-teine,. S -hydroxyethylmercapturic acid [jV-acetyl-5 -(2-hydroxyethyl)cysteine] and thiodi-glycolic acid (Muller et al., 1987). 

Connolly, D. Barron, L., and Pauli, B. Determination of urinary thiocyanate and nitrate using fast ion-interaction chromatography. /. Chromatogr. B. 2002, 767, 175-180. 

A 67-year-old woman with lymphoma presented with a neuromyopathy following treatment with laetrile. She had high blood and urinary thiocyanate and cyanide concentrations (7). Sural nerve biopsy specimen showed a mixed pattern of demyelination and axonal degeneration, the latter being prominent. Gastrocnemius muscle biopsy specimen showed a mixed pattern of denervation and myopathy with type II atrophy. 

Methods to detect cyanide exposure in human urine, saliva, and either serum or plasma have concentrated on thiocyanate. These methods include derivatization with HPLC/UV detection, derivatization with spectrophotometric detection or GC with BCD detection. Some urine methods have measured the urinary metabolite, 2-aminothiozoline-4-carboxylic acid. 

When l-[14C]methyl-pyridinium aldoxime iodide or radioactive pralidoxime [14C]-labelled in the oxime group was parenterally administrated to rats, 90% of the radioactivity was recovered in urine and 6% in the faeces, irrespective of the position of the label. About 90% of the urinary radioactivity was associated with intact pralidoxime. In addition, some 5% of the dose was excreted as l-methyl-2-pyridone, indicating some cyanogenesis (Enandcret al., 1962). In humans, the l-methyl-2-cyanopyridinium ion was detected in urine of male volunteers without significantly increased urinary thiocyanate. Since 90% of pralidoxime chloride, 5 mg kg 1 IV, was recovered from urine, cyanide formation is probably of no toxicological concern (Garrigue etal., 1990). 

Figure 28.5 shows the iodine concentrations in urine and milk from nonsmoking and smoking mothers, and in urine from their neonates. Whereas urinary iodine concentrations were not different between groups of mothers, the iodine content of breast milk and of neonatal urine was reduced to around 50% if the mother was a smoker. This effect of smoking varied with the cotinine concentrations in mothers, and with the levels of thiocyanate in serum from the mothers and in cord serum (Laurberg et al., 2004). 

Urinary iodine concentrations in Tibet are very similar to those observed in Sudan (Moreno-Reyes et ai, 1993), but the frequency of goiter or hypothyroidism is lower. The lack of goitrogens in Tibet probably explains the lower frequency of hypothyroidism and goiter despite similar urinary iodine concentrations to those in Central Africa. Experimentally, the involvement of thiocyanate in the pathogenesis of myxedematous cretinism has recently been corroborated (Contempre et al, 2004). 

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