Animal studies cyanide toxicity

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. 

Reproductive Toxicity. No data were located regarding reproductive effects of cyanide in humans. One animal study reported increased resorptions in rats following oral exposure to a cassava diet (Singh 1981). Because some human populations use cassava roots as the main source of their diet, further... 

In animal studies acetone has been found to potentiate the toxicity of other solvents by altering their metabolism through induction of microsomal enzymes, particularly cytochrome P-450. Reported effects include enhancement of the ethanol-induced loss of righting reflex in mice by reduction of the elimination rate of ethanol increased hepatotoxicity of compounds such as carbon tetrachloride and trichloroethylene in the rat potentiation of acrylonitrile toxicity by altering the rate at which it is metabolized to cyanide and potentiation of the neurotoxicity of -hexane by altering the toxicokinetics of its 2,4-hexane-dione metabolite.Because occupationally exposed workers are most often exposed to a mixmre of solvents, use of the rule of additivity may underestimate the effect of combined exposures. ... 

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

The systemic toxicity of CK results from its transformation to free cyanide thus, CK is expected to elicit the same toxic effects as cyanide. Therefore, in the absence of chemical-specific subchronic or chronic human or animal studies for CK, an oral RfDe can be derived based on results of experimental studies with HCN or other cyanides. The nervous system, reproductive system, and thyroid are considered target organs for chronic toxicity of cyanides. 

Cyanogen Chloride (CK). RfDe = 3 x 10 mg kg d . Data were not available to derive an RfDe directly from studies conducted on CK. Because the systemic toxicity of CK results from its transformation to free cyanide, CK is expected to elicit the same toxic effects as cyanide. Therefore, an oral RfDe for CK was derived from studies conducted on cyanide. Two studies were considered cocritical in the derivation of the RfDe one animal study and one human epidemiological study. In the animal study, a NOAEL was identified and a total uncertainty factor of 300 was applied to account for protection of sensitive subpopulations (10), animal-to-human extrapolation (10), and extrapolation from a subchronic to chronic exposure (3). A full factor of 10 was not used for the latter UF because chronic oral data were also available which showed that the subchronic NOAEL was adequately protective. In the human epidemiological study, a LOAEL was identified and a total uncertainty factor of 30 was applied to account for extrapolation from a subchronic to chronic exposure (3) and extrapolating from a LOAEL to a NOAEL (10). A uncertainty factor for sensitive human subpopulations was not used because the subject population... 

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. 

The 12.5 mg/kg/day dose was identified as the LOAEL, based on all the reproductive effects observed in male rats, and the 4.5 mg/kg/day dose was identified as the NOAEL. This NOAEL was used with an uncertainty factor of 100 (10 for extrapolation of animals to humans and 10 for human variability) to derive an MRL. It is important to note that this MRL was based on a study using sodium cyanide, which is a soluble form of cyanide. In addition, a LOAEL of 1.04 mg/kg/day based on systemic and reproductive effects in dogs was identified (Kamalu 1993). However, this study was not used to derive the intermediate oral MRL because dogs are not a good model for human toxicity because dogs have very low levels of rhodenase, an enzyme which is used to detoxify cyanide. 

Developmental Effects. No studies were located regarding developmental effects in humans after any route of exposure and in animals after inhalation and dermal exposure. However, studies in rats (Singh 1981) and hamsters (Frakes et al. 1986a) fed a cassava diet suggested that cyanide may have teratogenic and fetotoxic effects at maternally toxic doses, but Singh (1981) indicated that the results... 

Urea-formaldehyde apparently, at least in some formulations, can produce highly toxic combustion products compared to other cellular materials. The University of Utah foimd it only slightly less toxic than phenolic foam, although with nonflaming combustion (830°C) it was found to be the fastest material to incapacitate test animals. Cyanide was found to be the causative agent of death. CO, CO2, and aimnonia are also produced in combustion, all of which are toxic. University of Pittsburgh studies showed UF foam to be only slightly less toxic than PTFE (solid, not foam) (6). 

---