Cyanide animal exposure

These experts collectively have knowledge of cyanide s physical and chemical properties, toxicokinetics, key health end points, mechanisms of action, human and animal exposure, and quantification of risk to humans. All reviewers were selected in conformity with the conditions for peer review specified in Section 104(i)(13) of the Comprehensive Environmental Response, Compensation, and Liability Act, as amended. 

A skin redness reported in experimental animals (rats, rabbits, cats and monkeys) after inhalation exposure to acrylonitrile may be due to a vasodilatory effect, rather than a direct irritant action (Ahmed and Patel 1981). Guinea pigs, which do not exhibit the cyanide-type effects of acrylonitrile poisoning (see Section 2.2.1.4), were observed to have nose and eye irritation from the acrylonitrile vapors (Dudley and Neal 1942). 

In animals, deaths from acrylonitrile have been reported in several species following inhalation, oral or dermal exposure. In most species, death appears to be related to cyanide poisoning. That the cyanide moiety is involved in human toxicity of acrylonitrile has been reported in a case study in which a human male was sprayed with acrylonitrile when a valve burst (Vogel and Kirkendall 1984). This individual suffered symptoms characteristic of cyanide poisoning, and treatments designed to reduce cyanide levels in the blood were required in order to save his life. 

Acute-Duration Exposure. Information is available regarding the effects of acute-duration inhalation exposure of humans to acrylonitrile and the effects are characteristic of cyanide-type toxicity. Quantitative data are limited but are sufficient to derive an acute inhalation MRL. Further studies of humans exposed to low levels of acrylonitrile in the workplace would increase the confidence of the acute MRL. Studies in animals support and confirm these findings. No studies are available on the effects of acute-duration oral exposure in humans however, exposure to acrylonitrile reveals neurological disturbances characteristic of cyanide-type toxicity and lethal effects in rats and mice. Rats also develop birth defects. Animal data are sufficient to derive an acute oral MRL. Additional studies employing other species and various dose levels would be useful in confirming target tissues and determining thresholds for these effects. In humans, acrylonitrile causes irritation of the skin and eyes. No data are available on acute dermal exposures in animals. 

Neurotoxicity. Clinical signs indicative of disturbances of the nervous system in exposed humans have been well documented in short-term studies at high doses and appear to be reversible. These effects are characteristic of cyanide toxicity. Animal studies confirm findings in humans. In longer-term studies, effects on the nervous system have also been reported, but it is not certain if these effects are permanent or reversible following termination of acrylonitrile exposure. 

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). 

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. 

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). 

The systemic effects observed in humans and animals after inhalation exposure to cyanide are discussed below. The highest NOAEL values and all reliable LOAEL values for each systemic effect in each species and duration category are recorded in Table 2-1 and plotted in Figure 2-1. 

No studies were located regarding endocrine effects in animals after inhalation exposure to cyanide. 

Information regarding ocular effects in animals after inhalation exposure to cyanide is limited to a report of eye irritation in rats acutely exposed (7.5-120 minutes) to 250 ppm cyanogen (500 ppm cyanide) (McNemey and Schrenk 1960). 

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