Blood cyanide

Nitroprusside 0.25-3 mcg/kg per minute BP, HR, liver and kidney function, blood cyanide and/or thiocyanate concentrations if toxicity suspected (nausea, vomiting, altered mental function)... 

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). 

Figure 8. Relationship of blood carboxyhemoglobin levels and blood cyanide levels in fire death victims.

Establishing what the lethal level of blood cyanide is for humans is a difficult task. Based on extensive inhalation studies of HCN in mice a level of 1 mg/L of blood was suggested (12). In rats, a level of 2 mg/L of blood was found to be lethal (15). In limited experiments with cynomolgus monkeys, an exposure concentration of 150 ppm for 30 min would result in 3 mg/L of blood cyanide and would be lethal for these primates. Thus we have a range of 1 to 3 mg/L in experimental animals. The lethal level, however, has been found to be somewhat dependent upon exposure concentration and duration of exposure (12). 

No evidence of injuries or disease. Yellow fluorescent particles found in mouth appeared like those placed in NaCN ejector mechanisms used in predator control. However, blood cyanide concentration was similarto that found in nonexposed vultures, including two captive California condors... 

Yamamoto, K., Y. Yamamoto, and C. Kuwahara. 1979. A blood cyanide distribution study in the rabbits intoxicated by oral route and by inhalation. Zeit. Rechtsmedizin 83 313-317. 

Time to incapacitation for the 100, 102, 123, 147, and 156 ppm concentrations were 19, 16, 15, 8, and 8 min, respectively the relationship between exposure and time to incapacitation was linear. During exposures, effects consisted of hyperventilation (within 30 s), loss of consciousness, and bradycardia with arrhythmias and T-wave abnormalities recoveries were rapid after exposure. The animal inhaling 147 ppm stopped breathing after 27 min and required resuscitation. Two additional exposures were terminated prior to the end of the 30 min due to severe signs. Animals rapidly recovered and were active during the first 10 min after exposure even though blood cyanide remained at levels that initially caused incapacitation. Purser (1984) states that the hyperventilatory response followed by incapacitation occurs at >80 ppm, but neither paper (Purser 1984 Purser et al. 1984) provides the experimental data for the 80 ppm concentration. At 180 ppm, hyperventilation occured almost immediately, and at 90 ppm the response was delayed for 20 min. 

HCN in the blood is almost completely contained in the red blood cells where it is bound to methemoglobin. Immediately after infusion of sodium nitroprusside into patients, 98.4% of the blood cyanide was found in the red blood cells (Vesey et al. 1976). At normal physiological levels of body methemoglobin (0.25% to 1% of the hemoglobin), a human adult can bind about 10 mg of HCN (Schulz 1984). 

Venous blood levels of cyanide reached a steady state (mean value, 200 g/100 mL) within 10 min of exposure of cynomolgus monkeys at 100-156 ppm (Purser et al. 1984). The blood level stayed constant during the remainder of the 30-min exposure, during which time the animals lost consciousness the blood level remained the same for 1 h after exposure, even though the monkeys recovered consciousness within 10 min. The mean concentration of whole blood cyanide in rabbits that died following inhalation exposure was 170 pg/100 mL the mean plasma concentration was 48 figHOO mL (Ballantyne 1983). 

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) ... 

Individuals with high blood pressure might be considered a susceptible population. Schulz et al. (1982) reported on the infusion of 70 patients, ages 17 to 78, with nitroprusside solutions to lower blood pressure. Administration of nitroprusside with or without thiosulfate continued for several hours to several days, apparently without adverse symptoms. Schulz (1984) states that at 150 to 250 /.imol/L of erythrocyte concentrate headaches, palpitations, and hyperventilation occur. Unfortunately, blood cyanide levels were ex... 

The 8-h no-effect mean geometric concentration of 1 ppm (with excursions up to 6 ppm) from the Leeser et al. (1990) study was used as the basis for time scaling the AEGL-1 values. This study was chosen because it was well conducted all workers had full medical examinations and routine blood tests, including measurements of blood cyanide and carboxyhemoglobin. Atmospheric HCN concentrations were monitored in the plant several times during the year. Because of the extrapolation from a long-term exposure, the... 

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... 

A number of compounds act in synergy with cyanide to produce toxic effects. In smoke, hydrogen cyanide may interact with other toxicants (Birky and Clarke 1981). High blood cyanide levels were found in fire victims however, the carboxyhemoglobin levels were also high. Thus, it is difficult to assess the... 

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... 

Laforge M, Buneaux F, Houeto P, et al. 1994. A rapid spectrophotometric blood cyanide determination applicable to emergency toxicology. J Anal Toxicol 18 173-175. 

Maseda C, Matsubara K, Shiono H. 1989. Improved gas chromatography with electron-capture detection using a reaction pre-column for the determination of blood cyanide a higher content in the left ventricle of fire victims. J Chromatogr 82 319-327. 

Seto Y, Tsunoda N, Ohta H, et al. 1993. Determination of blood cyanide by headspace gas chromatography with nitrogen phosphorus detection and using a megabore capillary column. Analytica ChimicaActa 276 247-259. 

Two human subjects inhaled 160 ppm for 4 hours one of them experienced a slight flushing of the face 2 hours later and a slight feeling of bronchial tightness 5 hours later. A week before this, the same two subjects had inhaled 80 ppm with no effects. Blood cyanide and urine thiocyanate levels did not correlate with exposure and, therefore, are not reliable indicators of brief exposure to low concentrations. 

The US Army Medical Research Institute of Chemical Defence employs an automated microdistillation assay for cyanide in blood, using fluorometric detection (67). For assaying free CN , plasma is mixed with and dialyzed against pH 7.4 phosphate buffer. For an assay of total blood cyanide, blood is mixed with saline containing Triton X (which hemolyzes the red cells), treated with 0.5 % sulfuric acid and dialyzed against 0.25 % sulfuric acid. Cyanide is... 

Y. Seto, Determination of physiological levels of blood cyanide without interference by thiocyanate, Jap. J. Toxicol. Environ. Health, 42, 319-325 (1996). 

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