Hydrogen cyanide animal exposure

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. 

For chronic exposure in animals, only one oral study in rats (hydrogen cyanide) was located (Howard and Hanzal 1955). However, the reliability of this study is low because of the unstable cyanide levels in their feed throughout the experiment due to evaporation of cyanide. Furthermore, no effects were found in the study besides nondose-related changes in weight gain in female rats, but not in male rats. No chronic studies in animals were located for the inhalation and dermal routes. Therefore, data are not sufficient to derive MRL values for chronic exposure. Additional chronic-duration studies in animals would be helpful to determine thresholds for target organs. 

No studies were found that examined distribution in humans after dermal exposure to hydrogen cyanide there are limited data on the distribution in experimental animals after dermal exposure. Rabbits exposed by the dermal route to 33.75 mg CNYkg as hydrogen cyanide had cyanide concentrations of 310 fig/dL in the blood, 144 fig/dL in the serum, 26 fig/100 g in the liver, 66 fig/100 g in the kidney, 97 /rg/100 g in the brain, 10 fig/100 g in the heart, 120 jug/100 g in the lungs, and 21 fig/100 g in the spleen (Ballantyne 1983a). 

There are numerous experimental animal studies examining hydrogen cyanide toxicity after acute exposure. The studies are summarized below, experimental... 

TABLE 6-3 Experimental Animal Toxicity Data, Exposure to Hydrogen Cyanide... 

On the basis of its review of human and experimental animal health-effects and related data, the subcommittee concludes that the Navy s proposed SEAL 2 of 4.5 ppm for hydrogen cyanide is too conservative. The subcommittee recommends a SEAL 2 of 15 ppm. The recommended SEAL 2 is also based on the El Ghawabi et al. (1975) study, which is discussed under the derivation of SEAL 1. It is supported by studies in monkeys that show some central nervous system effects (e.g., changes in brain wave activity and reduced auditory cortical evoked potential) occur after a 30-min exposure at a concentration of 60 ppm (Purser et al. 1984). The subcommittee concludes that exposures of submariners to hydrogen cyanide at a concentration of 15 ppm for only 1 d is not likely to produce any irreversible health effects. 

Hydrogen cyanide and cancer Information on the carcinogenicity of hydrogen cyanide in hnmans or animals for oral exposure is unavailable. Similarly, there are no reports that cyanide can cause cancer in animals and hnmans. The U.S. EPA has classified cyanide as a group D, meaning that it is not classifiable as to human carcinogenicity. ... 

Blank et al. (1983) carried ont inhalation toxicity stndies of hydrogen cyanide on Spragne-Dawley rats. Exposnre at 68 ppm HCN in air 6 honrs per day for three consecutive days showed symptoms of hypoactiv-ity, breathing difficnlties, signs of hypoxia, convnlsions, and chromorhinorrhea. Death resulted in three of the five male rats after 1 day of exposure, caused by cyanosis of the extremities, moderate to severe hemorrhage of the lung, and pulmonary edema. All female rats survived. In a 4-week study, no mortality was observed at concentrations up to 58 ppm HCN. A brief exposure to 125 ppm HCN for 15 minutes, however, was fatal to 20% of the test animals. Increased urine thiocyanate levels were observed in test animals However, no adverse effects were observed in rats exposed at 29 ppm HCN 6 hour s weekday in 4-week studies. 

Cyanide is readily diffusible through epithelium. This property contributes to its lethal toxicity after inhalation of hydrogen cyanide (HCN) gas (the usual route of military exposure), ingestion of cyanide salts or cyanogens, or percutaneous absorption of cyanide from high-concentration solutions. Because cyanides are present at low concentrations in several naturally occurring environmental sources, it is not surprising that most animals have intrinsic biochemical pathways for detoxification of the cyanide ion. 

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