Smokers cyanide

Retrospective identification of cyanide poisoning in a CW context would be complicated by exposure from other sources, which include cigarette smoke, smoke from fires and some foods, e.g. cyanogenic glycosides in bitter almonds, fruit seeds and a number of plants. Quoted blood concentrations in non-smokers vary from a few ng/ml to >100 ng/ml. In nine fire victims, the concentrations determined were 687 597 ng/ml (Ishii et al., 1998). In smokers, cyanide levels in blood may rise to 500 ng/ml. 2-Aminothiazoline-4-carboxylic acid was detected in the urine of moderate cigarette smokers at concentrations between < 44-162 ng/ml (Lundquist et al., 1995). 

The monomeric non-polar molecular structure enables it to pass through cell walls relatively easily (myocrisin passes easily into the red blood cells of smokers, possibly owing to ingested cyanide in the smoke reacting to form monomeric Au(SR)CN ). 

Thiocyanate in blood 40 (rg/l 00 mL in control nonsmokers 100 (rg/l00 mL in control smokers 420 (ig/100 mL in cyanide-exposed nonsmokers 480 pg/100 mL in cyanide-exposed smokers Maehly and Swensson (1970) Found no relationship between exposure and blood cyanide levels Blood CN—of control nonsmokers ranged from 3.5-10.1 pg/100 mL Blood CN—of control smokers ranged from 2.0-13.0 pg/100 mL Blood CN—of control and cyanide-exposed workers combined ranged from 2.0-15 pg/100 mL (Separate data were not provided for cyanide workers) Aitken et al. (1977) Male and female patients, ages 13-66, presurgery mean 2.7 pg/100 mL Following infusion of sodium nitroprusside 13-205 pg/100 mL Metabolic acidosis at >90 pg/100 mL Nitroprusside doses 12-783 pg/kg (0.8-9.8 pg/kg/min over durations of 15 to 86 min) ... 

Several studies provided data on blood and urine concentrations of cyanide and thiocyanate following occupational exposures at low concentrations. These values are generally similar to those of smokers who have not been occupationally exposed to HCN. Whole-blood cyanide concentrations during... 

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... 

Table 5-3. Cyanide and Thiocyanate Concentrations ( jg/mL)a in Smokers and Nonsmokers... 

Exposure Levels in Humans. The levels of cyanide and thiocyanate in various human tissues and body fluids of both control and occupationally exposed groups and of smokers and nonsmokers are available (see Sections 2.3.4, 2.6.1, and 5.5). The levels of these chemicals in humans consuming foods containing cyanogenic materials also are available. 

Tobacco smoke contains more than 3800 different compounds. About 10% of these constimte the particulate phase, which contains nicotine and tar. The remaining 90% contains volatile substances such as carbon monoxide, carbon dioxide, cyanides, various hydrocarbons, aldehydes, and organic acids. Although all of these substances affect the smoker to some degree, nicotine is generally considered to be the primary substance responsible for the pharmacological responses to smoking (Nielsen et al. 2001). 

PCC, a common by-product of PCP s illicit manufacture (sometimes accounting for 10-25% of the mixture), causes abdominal cramps, diarrhea, and in sufficient doses, coma. PCC is an unstable compound, degrading to piperidine. Contaminated batches of PCP can sometimes be recognized by a strong fishy odor. When heated, as when it is smoked and inhaled, PCC liberates hydrogen cyanide, so cyanide poisoning in PCP smokers is also a strong possibility. 

Numerous methods have been reported for the analysis of cyanide and thiocyanate in biomedical samples, mostly for the determination of cyanide levels in smokers and fire victims rather than cases of deliberate poisoning. These methods include visible, ultraviolet (UV) and fluorescence based spectrometric methods, electrochemical methods using ion selective electrodes, and GC with nitrogen-phosphorus detection (NPD), electron capture detection (ECD), or MS. It is not intended to cover all of these but focus mainly on chromatographic methods. 

Kage et al. (75) applied their GC/ECD/GC/MS method to the analysis of blood levels in two casualties who died from cyanide poisoning. Blood levels of cyanide and thiocyanate in a subject who died following ingestion of sodium cyanide were 0.52 and 0.10 umol/ml respectively (= 13 and 5.6 xg/ml). Levels determined in a fatal victim of smoke inhalation were 0.28 and 0.13umol respectively (= 7.3 and 7.5 xg/ml). Fatal levels of cyanide are estimated as 0.05-0.1 umol/ml (= 1.3-2.6 xg/ml). The lower levels of thiocyanate in comparison to cyanide in the blood were attributed to the sudden death they were twice the mean levels ( 0.06 pmol/ml) found in cigarette smokers. 2-Aminothiazoline-4-carboxylic acid was detected in the urine of moderate cigarette smokers at concentrations between <0.3-1.1 xM (76). 

Standard Cyanide Solutions. Dissolve 0.025 g of potassium cyanide in sufficient water to produce 10 ml. This solution contains 1 mg of CN" in 1 ml. Serially dilute diis solution with normal blood or serum, as appropriate, taken from non-smokers, to produce solutions containing 0.5, 1.0, 2.0, and... 

Blood-cyanide concentrations of up to 0.02 iLig/ml may be found in normal individuals who do not smoke smokers may have concentrations of up to about 0.05 LLg/ml. Acute toxicity is associated widi blood concentrations of 0.5 iLig/ml or more such concentrations may be encountered during sodium nitroprusside therapy for hypertension. Concentrations above 1 iLig/ml have been reported in fatalities. Cyanide is concentrated in the erythrocytes. 

Thiocyanate is a metabolite of cyanide and in addition to its toxicological significance, measurement of blood-thiocyanate concentrations aids in the verification of an individual s compliance with an anti-smoking programme. Plasma concentrations in non-smokers range fi om 0.1 to 4 jJg/ml, whereas in smokers concentrations range from about 5 jJ g/ml up to 20 g/ml. Serum concentrations of up to about 200 g/ml have been recorded in fatalities. 

Quantitative assays have shown that the plasma of nonsmoking, healthy adults contains MeCbl (250 pg cm ), AdoCbl, and hydroxocobalamin (OH-Cbl) [AdoCbl + OH-Cbl (125 pg cm with AdoCbl > OH-Cbl)]. The blood of smokers contains CN-Cbl ( 2% of total cobalamin), which is derived from hydrogen cyanide in tobacco smoke. CN-Cbl can also develop from the consumption of foods (e.g., cassava) that release cyanide ions. In erythrocytes, the chief cobalamin is AdoCbl (> 50% of total cobalamin) followed by OH-Cbl (25%), MeCbl (10-15%), and small amounts of CN-Cbl. Cobalamin-dependent enzymatic reactions in animals and microorganisms (see below) involve AdoCbl and MeCbl and the reduced form of OH-Cbl, cob(I)alamin, whereas CN-Cbl has no established role. 

Cyanide can be regenerated from methaemo-globin by treatment with acid. There are many methods for detecting free and bound cyanide, and thiocyanate in blood these have recently been reviewed (Black and Muir, 2003 Black and Noort, 2005). They have been applied mostly to the determination of cyanide levels in smokers and fire victims rather than cases of deliberate poisoning. 2-Aminothiazoline-4-carboxylic acid has been analysed in urine using LC with fluorescence detection after conversion to N -carbamylcysteine (Lundquist et al, 1995), and by GC-MS after conversion to its tris-trimethylsilyl derivative (Logue etal., 2005). The analyte was concentrated from urine on a cation exchange resin. 

Cyanide is present in the air as hydrogen cyanide (HCN), in soil and water as cyanide salts (e.g., NaCN), and in foods as cyanoglycosides. Most of the cyanide in the air usually comes from automobile exhaust. Examples of populations with potentially high exposures include active and passive smokers, people who are exposed to house or other building fires, residents who live near cyanide- or thiocyanate-containing hazardous waste sites, and workers involved in a number of manufacturing processes (e.g., photography or pesticide application.)... 

---