Commonwealth of Australia 2010
Summary of kinetics and metabolism in animals
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- 32.Environmental Hazard Assessment
- Mode of action of cyanide toxicity
- Effects on avian species
31.5Summary of kinetics and metabolism in animalsRapid onset of symptoms after exposure to cyanide through the gastrointestinal tract, lungs and skin indicates that cyanide is readily absorbed via these routes. Sodium cyanide has high acute oral toxicity (LD50 = 2.7 – 8 mg/kg bw) in rats and high acute dermal toxicity (LD50 = 14.6 mg/kg bw) in rabbits. Distribution of cyanide in various body tissues is fairly uniform with highest levels found in the liver, lungs, blood and brain in rats and rabbits. The majority of cyanide metabolism occurs within tissues in animals. The major metabolic pathway is the conversion of cyanide to thiocyanate by either rhodanese or 3-mercaptopyruvaten sulphur transferase. The distribution of rhodanese in tissues is highly variable in different animal species. Monkeys, rabbits and rats had the highest rhodanese activity in the liver and kidneys, with relatively low levels of activity in adrenals. In dogs, the highest activity of rhodanese was in the adrenal gland. The total rhodanese activity in dogs was lower compared to monkeys, rabbits and rats. The rate of metabolism of cyanide to thiocyanate depends on the species. The biological half-life of thiocyanate in plasma was highest in the goat (~14 h). Absorbed cyanide is mainly excreted as thiocyanate in the urine. Traces of cyanide may also be excreted unchanged or as a variety of metabolites in expired air, saliva and sweat. 32.Environmental Hazard AssessmentThis chapter discusses available ecotoxicity data for cyanide to terrestrial and aquatic species. These data indicate the nature and extent of the hazard presented by cyanide to various organisms and enable suitable toxicity endpoints to be determined for subsequent risk assessment. Data on sodium cyanide have been supplemented with data from other cyanogenic compounds, as cyanide (as hydrogen cyanide) originates in aqueous environments, such as in vivo, following dissociation of cyanogenic compounds (e.g. sodium and potassium cyanide) or arising from catabolism of cyanogenic glycosides. The use of such data is considered well founded for systemic effects, but may not be suitable for any effect that may occur on local contact. Therefore endpoints that involve local reactions at the initial site of contact (e.g. irritation, and sensitisation in this instance) have been evaluated with data on sodium cyanide. For an environmental risk assessment, it is a standard practice to use data from tests carried out according to standard guidelines with standard test species as surrogates for wild local species. However, for cyanide, much of the available data for terrestrial and avian species are with tests that do not meet current guidelines, and several of the avian studies are with non-standard species, including wild species from North America. No data are available specifically for Australian mammals or birds, but there are some data for Australian aquatic species. References in the report that have not been sighted are marked with an asterisk (*).
The main toxic effects of cyanide are attributed to the disruption of energy metabolism. Cyanide inhibits mitochondrial cytochrome c oxidase by binding with the ferric ion of cytochrome a3, the terminal oxidase of the respiratory chain, leading to cytotoxic hypoxia and respiratory system failure (Ballantyne, 1987). A two-step process for inhibition of cytochrome c oxidase has been proposed: initial penetration of cyanide into a protein crevice of cytochrome c oxidase (*Stannard and Horecker, 1948) followed by binding to the trivalent iron ion of the enzyme (*Van Buuren et al., 1972). This blockage to the electron transfer chain and cessation of aerobic metabolism causes a shift to anaerobic metabolism and depletion of energy rich compounds such as adenosine triphosphate (ATP) and results in the accumulation of pyruvic and lactic acid, that leads to respiratory arrest and death (*Rieders, 1971; *Way, 1984). In addition to binding to cytochrome c oxidase, cyanide also binds to catalase, peroxidase, methemoglobin, hydroxycobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, and succinic dehydrogenase. These reactions may also contribute to cyanide toxicity (*Ardelt et al., 1989; *DiPalma, 1971; *Rieders, 1971). Cyanide affects a range of organs including the CNS, cardiovascular and/or respiratory system, thyroid, reproductive organs, gastro-intestinal tract, skin, liver and kidneys (Isom, 2002; *Okalie and Osagie, 1999; Faust, 1994; Kamalu, 1993; Ballantyne, 1987; *Palmer and Olson, 1979; Philbrick et al, 1979). Due to its high dependency on oxidative metabolism and limited anaerobic capacity, the CNS is particularly vulnerable to cyanide intoxication (*Way, 1984). Blindness is common in cyanide-treated animals and is considered to be a result of persistent anoxia in the brain (NTP, 1993). Exposure to a high sublethal dose of cyanide may have long-term consequences. In humans, these have included cerebellar and sub-cortical disturbances with concomitant impairment of co-ordination and movement and Parkinsonian-like symptoms (Fischbein et al., 2000; *Rosenow et al., 1995; *Valenzula et al., 1992; *Grandas et al., 1989). Parkinsonian-like effects have also been recorded in animals (*Rosenberg et al., 1989). Cyanide is a neurotoxin that produces selective brain degeneration (lesions). In intraperitoneal studies in mice, cyanide resulted in two distinct brain (doperminergic neuron) lesions: non-gliotic lesions in the motor cortex, and gliotic lesions in the substantia nigra (Mills et al., 1999). These are thought to be due to two distinct modes of cell death: necrosis (substantia nigra region) and apoptosis (cortical region). Oxidative stress is considered a common activator of the lesions.
This sub-section describes the toxicity to birds, and most of the studies have been sourced from the Eisler (1991) review. No toxicity data were available for reptiles (e.g. snakes, lizards, tortoise). Data from mammals and birds are considered indicative in the absence of reptilian data, as it has been suggested that there is little difference in the interspecies sensitivity to acute doses of cyanide between modern eutherian carnivores and endemic species (Marks et al., 2002). However, the limited details reported reduce the reliability that can be attached to this qualitative statement. Nevertheless, a wide-range of wildlife species are susceptible to the effects of cyanide (Adams et al., 2008a,b; Donato et al., 2007; Smith et al., 2007; Donato, 2002; Eisler et al., 1999; Donato, 1999; ATSDR, 2004; Sinclair et al., 1997; Wiemeyer et al., 1986) and toxicity data show little variation in the acute toxicity of cyanide to various animals. Data available for birds include acute inhalation, oral and repeat oral studies. These studies are presented below. Directory: data -> assets -> word doc -> 0017 0017 -> National Industrial Chemicals Notification and Assessment Scheme word doc -> Priority Existing Chemical word doc -> Rail safety news issue 6 – October 2011 word doc -> Review of Multiple Chemical Sensitivity: Identifying 0017 -> Rail Safety News Edition 8, December 2012 0017 -> Real-Time License Plate Localisation on fpga 0017 -> Careers network bulletin issue 6 July 16 2012 0017 -> Wiser science: Finding References inspec for Physics and Engineering 0017 -> Part A: Depth Study: The globalising world Popular culture and public policy Download 2.29 Mb. Share with your friends:
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