Thiocyanate was found in the urine of non-exposed people at average concentrations of 2.16 mg/litre urine for non-smokers and 3.2 mg/litre urine for smokers (Chandra et al., 1980). Urinary excretion of thiocyanate was monitored in a man after ingestion of about 3–5 g potassium cyanide (15–25 mg cyanide/kg body weight) (Liebowitz & Schwartz, 1948; ATSDR, 1997). The results indicated that the patient excreted 237 mg of thiocyanate over a 72-h period. This quantity was substantially more than the normal average amount of thiocyanate in urine, which varies from 0.85 to 14 mg/24 h (ATSDR, 1997).
After administration of an intravenous dose of 3–4 mg potassium cyanide to beagle dogs, blood levels decreased in a manner consistent with first-order elimination kinetics for the first 80 min (Bright & Marrs, 1988). The half-time for this phase was about 24 min, corresponding to an elimination rate constant of 0.03/min. After 80 min, the blood cyanide concentrations fell at a slower rate, with a half-time of 5.5 h. In rats, after a single oral dose, the blood elimination half-time of cyanide was 14.1 min, corresponding to a rate constant of 0.05/min (Leuschner et al., 1991).
Some chemical properties of other cyanides are given in Table 2. Copper cyanide is a white to cream-coloured solid. Its common name is cuprous cyanide, and its synonym is cupricin. Potassium silver cyanide occurs as white crystals; its common synonym is potassium dicyanoargentate. It is sensitive to light. Sodium ferrocyanide decomposes at 435 °C, forming sodium cyanide.
Cyanides in environmental media are usually collected in sodium or potassium hydroxide solution and measured by spectrophotometry (Agrawal et al., 1991), colorimetry, or ion-specific electrode or by headspace gas chromatography with a nitrogen-specific detector or electron capture detector (Maseda et al., 1989; Seto et al, 1993). Cyanide in aqueous matrices is usually measured by colorimetric, titrimetric (US EPA, 1983), or electrochemical methods after pretreatment to produce hydrogen cyanide and absorption in sodium hydroxide solution. Total cyanide (irrespective of origin) includes all of the available cyanide in a sample; in drinking-water, it is measured by semi-automated colorimetry (EPA Method 335.4) as well as by selective electrode, ultraviolet/distillation/spectrophotometry, and ion chromatography (EPA Method 300.0) (US EPA, 1993a). Free cyanide can also be determined by one method (SM-4500-CN-F) approved for drinking-water compliance monitoring analysis that does not require distillation, the specific ion electrode method (US EPA, 2003a). Weak acid dissociable cyanide analysis (used principally by the precious metals mining industry) includes those cyanide species liberated at moderate pH 4.5, such as aqueous hydrogen cyanide and cyanide anion, the majority of copper, cadmium, nickel, zinc, silver, and tin complexes, and others with similar low dissociation constants. Weak acid dissociable cyanide can be determined in wastewaters by a ligand exchange/flow injection/amperometric technique (EPA Method 1677) (Milosavlievic et al., 1995; US EPA, 1997).
Hydrogen cyanide is principally produced by two synthetic catalytic processes involving the reaction of ammonia and natural gas (or methane) with or without air. It is also obtained as a by-product in the production of acrylonitrile by the ammoxidation of propylene, which accounts for approximately 30% of the worldwide production of hydrogen cyanide.
No effects were noted in Sprague-Dawley rats fed potassium cyanide at concentrations up to 187.5 mg/100 g diet (750 mg cyanide/kg diet) for 56 days. On protein-deficient diets, the lowest body weight gain was obtained at the highest dietary cyanide concentration (Tewe & Maner, 1985).
In a 3-month study, weanling male Wistar rats were given potassium cyanide at 0, 0.15, 0.3, or 0.6 mg/kg body weight per day daily (0, 0.06, 0.12, and 0.24 mg cyanide/kg body weight per day) by gavage (Soto-Blanco et al., 2002b). In plasma samples collected on the last day of the administration, no changes were observed in the concentrations of T3, T4, or glucose, while a decrease was observed in the concentration of cholesterol, significant at the highest dose (45%,
All rats survived, but there was a dose-dependent loss of body weight, an increase in thyroid weight, and a decrease of blood haemoglobin and serum T4 levels in rats after 14 weeks on a diet containing 5 or 10 g potassium cyanide/100 g diet (corresponding to approximately 800 and 1600 mg cyanide/kg body weight per day) (Olusi et al., 1979).
In a 40-week study in rabbits, the animals were fed potassium cyanide at a level of 1.76 g/kg diet (corresponding to 24–17 mg cyanide/kg body weight per day) (Okolie & Osagie, 1999). The weight gain of the treated animals was decreased by 33%; at the end of the experimental period, serum urea and creatinine levels were elevated, as were the activities of serum lactate dehydrogenase, sorbitol dehydrogenase, ALAT, and alkaline phosphatase.
In a 13-week study, male Sprague-Dawley rats were administered potassium cyanide in drinking-water at a dose level of 40, 80, or 160/140 mg/kg body weight per day. These doses correspond to 16, 32, and 64/56 mg cyanide/kg body weight per day (Leuschner et al., 1989). Histopathological investigation of the brain, heart, liver, testes, thyroid, and kidneys did not reveal adverse effects. Urinary protein excretion was increased in dosed animals, and dose-dependent increases were observed in organ weights; these were interpreted to have arisen from decreased food and water consumption caused by decreased palatability.
Forty-six male adult inbred Wistar rats were used in four experimental groups and one control group and treated with 0, 0.3, 0.9, 3.0, or 9.0 mg potassium cyanide/kg body weight per day in the drinking-water for 15 days. This was equivalent to 0, 0.12, 0.36, 1.2, and 3.6 mg cyanide/kg body weight per day. The high-dose group exhibited a 70% lower body weight gain than the control animals. In qualitative histological analysis, without statistical treatment or morphometric analysis, changes were observed in the kidney, liver, and thyroid. Cytoplasmic vacuolation, considered to reflect hydropic degeneration of proximal tubular epithelial cells, was noted in animals treated at doses of 3.0–9.0 mg potassium cyanide/kg body weight per day and in hepatocytes of those animals treated at a dose of 9.0 mg potassium cyanide/kg body weight per day. A dose-dependent increase in the number of reabsorption vacuoles on follicular colloid in the thyroid gland was noted in all animals of the experimental groups. No changes were observed in serum triiiodothyronine (T3), thyroxine (T4), creatinine, or urea levels; a decrease was observed in serum alanine aminotransferase (ALAT) activity at the two lowest exposure levels. Serum aspartate aminotransferase (ASAT) was elevated by 30% at the two lowest dose levels and by 21% at the 3.0 mg potassium cyanide/kg body weight per day dose; it was decreased by 29% at the highest dose level (Sousa et al., 2002).
In a neuropathological study (Soto-Blanco et al., 2002a), goats, 30–45 days old at the beginning of the study, were given potassium cyanide in milk (until weaning) and in drinking-water thereafter at a dose level of 0.3, 0.6, 1.2, or 3.0 mg (0.12, 0.24, 0.48, or 1.2 mg cyanide)/kg body weight per day for 5 months. In a qualitative morphological and immunohistochemical study, presence of gliosis and spongiosis in the medulla oblongata and spinal cord and gliosis in the pons and damage to Purkinje cells in the cerebellum were observed at the highest dose, but no increase in apoptotic cells was reported. Congestion and haemorrhage in the cerebellum were observed at the 0.48 mg cyanide/kg body weight per day group. No quantification or statistical analysis of the findings was presented.