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Cyanide compounds are acutelyThe presence in human populations of data on cyanide and thiocyanate levels is critical in establishing safe levels of cyanide, especially for long-term exposures.  Cliff et al (1986) found that levels of 250 μmol SCN-/l serum (14.5 μg SCN-/ml) did not lead to an increased incidence of goitre in a cassava eating population that was not iodine deficient; iodine deficiency exacerbated thyroid toxicity.  The cassava-eating population by Cliff et al., (1986) included 276 individuals (subset of 27 for some measurements) between 5 and 60 years old that had lived on this staple diet all their life (control group aged 19 – 85).  Similar findings were reported by Banerjee (1997) for electroplating workers in which serum concentrations of 316 μmol/l (18 μg SCN-/ml) did not lead to goitre.  Both of the latter populations had slight changes in thyroid hormone levels that can be considered as an adaptive response.  From human studies by Knudsen and Barrere, (2000), a nutritional iodine deficiency increases the sensitivity of the thyroid gland to the goitrogenic effects of cyanide.   Due to background variations in co-exposure to cyanogenic sources (e.g., environmental (combustion), dietary (cyanogenic foods) and habitual (i.e. smoking)) and levels of dietary iodine, it is not possible to distinguish precisely the effects of exogenous CN- on thyroid hormone levels. 
A level of 15 μg SCN-/ml can be used as a starting point to derive a safe concentration of cyanide for humans. Sensitive sub-populations would include individuals with insufficient dietary iodine, insufficient thiosulphate supply (e.g., in the case of malnutrition) or impaired renal function. Whereas the human studies relied upon for development of the critical value typically included several hundred to several thousand individuals from as young as 5 to 80 years old, this value is protective for sensitive individuals in the general population. See discussion on DNEL derivation.

Additional information

Cyanide compounds are acutely toxic by the oral, dermal and inhalation routes. This is recognized in the cyanides industry, based on accidental occupational exposures and intentional suicide

attempts. Acute toxicity is due to binding of cyanide with the iron in cytochrome oxidase, resulting in inhibition of cellular respiration. Toxicity from repeated dose exposure is seen as either acute toxicity or thyroid toxicity. The primaryin vivo metabolic pathway for cyanide is conversion into thiocyanate, catalysed by the mitochondrial enzyme rhodanese, and excretion into urine. Thiocyanate is a competitive inhibitor of iodine uptake by the thyroid gland; iodine deficiency leads to goitere of the thyroid gland. 

 The available literature, although limited, indicates that chronic occupational exposure to cyanides in certain industries (silver reclamation and electroplating) is linked to thyroid enlargement (goitre) and a wide range of subjective symptoms. The study of El Ghawabi et al (1975) suggests initally that these clinical effects are consistent with relatively low occupational exposures; however, these findings are more likely due to higher chronic levels prior to generation of quantitative air monitoring data, and this study cannot be used as the basis for establishing an occupational NOAEL.

Foods derived from cassava roots and leaves have been consumed on a regular basis by over 300 million people throughout the tropics of Africa, Central and South America, Southern Asia, Micronesia and Melanesia. Variation in food preparation techniques has contributed to variable levels of residual dietary cyanide and resultant chronic cyanide intoxication in these regions. The published literature includes numerous epidemiological and cross-sectional studies on the health effects of dietary cyanide. In the study of Jackson (1988), it was shown that dietary intake of up to 2 mg CN‾/kg bw/d in humans did not result in any effect on the thyroid, and are in accord with the serum levels of thiocyanate (250 µmol/l) and lack of overt hypothyroidism reported by Cliff et al (1986) for a rural population in Mozambique with adequate iodide intake. Thiocyanate levels from these populations and from patients administered potassium thiocyanate (Barker et al, 1950, Barker 1951) provide a basis for establishing no-effect levels in humans without the need to extrapolate from animals studies.

Adequacy of dietary iodide is a key parameter to be assessed in the design, conduct and interpretation of studies with cyanides. From the ECETOC review it is apparent that the NOAEL for goitrogenic effects in humans receiving adequate iodide is probably in excess of 2 mg CN‾/kgbw/d.

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