Professional Documents
Culture Documents
TER:o
SUMMARY
OCCURRENCE
Address all correspondence to: Frederick W. Oehme, Comparative Toxicology Laboratories, College of
Veterinary medicine, Kansas State University, Manhattan, Kansas 66506 (USA).
104
epidermis was recently reported by Dugard and Mawdsley (8). The measurements were made to assess the hazard
resulting from clothing wetted by liquor
during NaCN manufacture. Absorption
rates showed a strong pH dependence
(pH 9.0-12.0), and the permeability constant for HCN (pka = 9.2) was calculated
13.2 C (5). Soluble salts such as sodium cyanide and potassium cyanide
form solutions by hydrolysis which are
alkaline. When hydrogen cyanide is dissolved in water, hydrocyanic acid is formed. This acid has a pka of 9.2 and is so
producing toxic effects. Their calculations showed, for example, that a large
area contact with 10% NaCN at pH 11.4
leads to clinical signs of toxicity within 25
minutes and death in about 1 hour. Observations in the small number of industrial accidents available for comparison
were in agreement with the calculations.
Therefore, cyanide absorbed by the skin
from clothing wetted with NaCN solution may lead to toxic effects in certain
cases.
105
CLINICAL SIGNS
chrome oxidase. The other signs are variable in their severity and time of appea-
blocked and the chain of cellular respiration is halted. Thus, cyanide cuases cytotoxic anoxia. As a result, oxyhemoglobin
system, the inhibition of oxidative meTIIE VETERINARY QUARTERLY. VOL, 2. No. 2. APRIL 1980
OXYHEMOGLOBIN (Fe2+)
NaNO2
METHEMOGLOBIN (F 3
11
CN
( CYANIDE INGESTED
191'
4YDROXOCOBALAMINI
CYANOCOBALAMIN
(
VITAMIN B12
p.CN
..
COMPLEX
7.1..17.1J
I 4.r)
J= z
U..1
ct
CI
V/ 0
0 cc
HCN
IN EXPIRED AIR
HCNO
c.<
SCN(THIOCYANATE)
TISSUE TOXICITY
V.
2-IMINOTHIAZOLIDINE-
CO2
4-CARBOXYL IC ACID
EXCRETED
Fig. I.
The basic processes involved in the metabolism of cyanide and treatment of cyanide poisoning.
DIAGNOSIS
108
death.
Proper preservation of samples foranalysis is imperative in order to avoid large
variation in cyanide concentration or loss
of gaseous HCN.
tion of the isolated cyanide. One disadvantage of the Aldridge method is that
benzidine, a reagent used in the colorimetric procedure, is carcinogenic. The
pyridine-pyrazalone reagent used in the
Epstein method is unstable, and pyridine
human organs.
In rats acutely poisoned with oral doses
of potassium cyanide (KCN) the minimum lethal blood cyanide concentration
was found to be in the range 2.60-2.92
pg/ ml (38). Mean blood cyanide concen-
Methods currently available for the isolation of cyanide from biological materials
are the microdiffusion methods (34, 40)
and distillation methods (41, 43). These
methods use modification of the colorimetric procedures developed by Aldridge
(44) and Epstein (45) for the determinaTHE VETERINARY QUARTERLY, VOL. 2, No. 2, APRIL 1980
atomic absorption methods are not widely used, probably because of the general
convenience and adequacy of the competing methods.
TREATMENT
any means that prevents access of cyanide (CN- ) to issues, allowing for rhodanase action and a means to supply sulfur
known to be effective antidotes for cyanide but were themselves toxic (57, 58,
Hb-Fe
2+
3+
Hb-Fe 3+
3+
NO2
Hb-Fe
CN-
Hb-Fe 2--+ CN
Cyt-Fe 2+CN
(1)
(2)
2+
Hb- Fe --CN
Cyt-Fe3+
( 3)
has been reported (66, 67). In man, hydroxocobalamin has been shown to prevent cyanide transfer from red cells and
plasma to tissue after sodium nitroprusside (Na2FE(CN)5NO 2 H20) metabolism. It thereby prevents cyanide toxicity
from large intravenous doses of the drug
(68).
known to grow.
ENVIRONMENTAL ASSESSMENT
cal manufacturing and agricultural industries. Continuous monitoring of cyanide levels in effluents from industrial
and municipal plants, and adequate record of these levels are necessary. Farmers should be aware of factors which
influence the cyanogenetic potential of
forage crops and should conduct regular
inspection of grazing fields for cyanogenetic plants. Hays and silage should be
REFERENCES
I. Davies, D. W., Kadar, D., Steward, D. J., and Munro,
I.: A sudden death associated with the use
of sodium nitroprusside for induction of hypotension during anesthesie. Ca. Anaest h. Soc. J., 22,547,
(1975).
2. Merrifield, A. Y. and Blumdell, M. D.: Toxicity of sodium
nitroprusside. Br. J. Anaesth., 46, 324,
(1974).
3.
Jack, R. D.: Toxicity of sodium nitroprusside. Br. J. Anaesth., 46, 952, (1974).
4. Buck, W. B. and Osweiler, G. D.: Cyanide, Clinical and diagnostic veterinary toxicology. Ed. G. A.
VanGelder, Kendal/ Hunt, Dubuque, Iowa, pp. 105-108, 1976.
5. The Merck Index, 9th edition, Merck and Co., Inc. Ed. Martha Windholz, New Yersey, p. 632, 1976.
6. Potter, A. L.: The successful treatment of two
recent cases of cyanide poisoning. Br. J. Ind. Med.,
7, 125, (1950).
7. Goodman, L. S. and Gilman, A.: Hydrocyanic Acid, The pharmacological basis of therapeutics.
Macmillan, New York, p. 904, 1975.
8. Dugard, P. H. and Mawdsley, S. J.: Percutaneous absorption of cyanide from aqueous sodium
cyanide. Abstracts, Seventh annual meeting, Society of Toxicology, San Francisco, California, March
12-16, p. 264, 1978.
9. Clarke, E. G. C. and Clarke, M. L.: Cyanides; Garner's veterinary
toxicology, 3rd edition, Williams
and Wilkins Co., Baltimore, pp. 75-80, 1967.
10. Winek, C. L., Fusia, E., Collom, W. D., and Shanor, S. P.: Cyanide poisoning as a mode of
18.
Hurst, E. W.: Experimental demyelination of the central nervous systerfi. 3. Poisoning with
potassium cyanide, sodium azide, Hydroxylamine, Narcotis, carbon monoxide, etc. with some consideration of bilateral necrosis occuring in the basal muscles. J. Exp. Biol. Med. Sci., 20, 297, (1942).
19. Hicks, S. P.: Brain metabolism in vivo. Arch. Pathol., 49, 111, (1950).
20. Brierly, J. B., Brown, A. W., and Jane Calverley: Cyanide intoxication in the rat: physiological and
neuropathplogical aspects. J. Neurology, Neurosurgery, and Psychiatry, 39, 141, (1976).
21. Osuntokun, B. 0.: Ataxic Neuropathy associated with high cassava diets in West Africa, in Chronic
Cassava toxicity: Proceedings of an interdisciplinary workshop, London, England, 29-30 Jan., 1973,
p. 127. Int. Develop res. Centre Mongr. IDRC-101e. Int'l Devel. Research Centre, Box 8500,
Ottawa, Box 8500, Ottawa Canada K IG 3119.
112
22. Ekpechi, 0. L.: Endemic goitre in high cassava diets in Eastern Nigeria, In chronic cassava toxicity.
Proceedings of an inter-disciplinary workshop, London, England, 29-30 Jan. 1973, p. 139. Int.
Develop. Res. Centre Monogr. IDRC-010e. Intl Devel. Research Centre, Box 8500, Ottawa Canada,
KIG 3H9.
23. Casarett, L. J. and Doull, J.: Toxicology: The basic science of poisons. Macmillan, New York, p.238,
1975.
24. Lenninger, A. L.: Biochemistry. 2nd, Ed., New York, Worth Publishers, pp. 486-500, 1975.
25. Williams, R. T.: Detoxification Mechanisms. Chapman and Hall, p. 393, 1959.
26.
Ansell, M. and Lewis, F. A. S.: A review of cyanide concentrations found in human organs.
31. Wood, J. L. and Cooley, S. L.: Thiocyanate formation from cysteine derivatives. Fed. Proc., 11,
314, (1952).
32. Hyde, W., Kiesey, J., Ross, P. F., and Stahr, H. M.: Cyanide, Analytical toxicology methods
manual. Ed. H. M. Stahr, Iowa State University Press, Ames, pp. 63-64, 1977.
33. Egekeze, J. 0. and Oehme, F. W.: Direct potentiometric determination of cyanide in biological materials. J. Anal. Toxicol., 3, 119, (1979).
34. Feldstein, M. and Klendshoj, N. C.: The determination of cyanide in body fluid by microdiffusion
analysis. J. Lab. Clin. Med., 44, 166, (1954).
35. Symington, S., Anderson, R. A., Oliver, J. S., Thomson, I., Harland, W. A., and Kerr, J. W.: Cyanide
exposure in fires. The Lancet, 2, 91, (1978).
36. Gettler, A. 0. and Baine, J. C.: The toxicity of cyanide. Am. J. Med. Sci., 195, 182, (1938).
37. Sunshine, J. and Finkle, B.: The necessity for tissue studies in fatal cyanide poisoning, Int. Archiv.
Arbeitsned., 20, 558, (1964).
38. Egekeze, J. 0. and Oehme, F. W.: Blood and liver cyanide concentrations in rats poisoned with oral
doses of potassium cyanide. Toxicology Letters, 3, 243, (1979).
39. Ballantyne, B., Bright, J., swanston, D. W., and Williams, P.: Toxicity and distribution of free
and its application to the study of conversion of cyanide to thiocyanate. Clin. Chem., 19, 466, (1973).
41. Boxer, G. E. and Rickards, J. C.: Chemical determination of vitamin B12, II. The quantitative
isolation and colorimetric determination of millimicrogram quantities of cyanide. Arch. Biochem.,
30, 372, (1951).
42. Rodkey, F. C. and Collison, H. A.: Determination of cyanide and nitroprusside in blood and plasma.
Clin. Chem., 23, 1969, (1977).
43. Shanaham, R.: The determination of submicrogram quantities of cyanide in biological materials.
J. Forensic Sci., 18, 25, (1973).
44. Aldridge, W. M.: The estimation of microquantities of cyanide and thiocyanate. Analyst (London),
70, 4741, (1945).
45. Epstein, J.: Estimation of microquantities of cyanide. Anal. Chem., 19, 272, (1947).
46. Morgan, R., Isom, G. E., and Way, J. L.: A fluormetric method for the determination of cyanide in
biological fluids. Proc. West. Pharmacol. Soc., 19, 392, (1976).
47. Groff, W. A., Cucinell, S. A., V icario, P., and Kaminskis: A completely automated fluorometric blood
cyanide method: A specific assay incorporating dialysis and ditillation. Clin. Toxicol.,11, 159, (1977).
48. Valentour, J. C., Aggarwal, V., and Sunshine, I.: Sensitive gas chromatographic determination of
cyanide. Anal. Chem., 46, 924, (1974).
49. Pranitis, P. A. F. and Stolman, A.: Spectrophotometric determination of cyanide in biological
51. Danchik, R. S. and Boltz, D. F.: Indirect atomic absorption spectrophomotric methods for the
determination of cyanide. Anal. Chim. Acta, 49, 567, (1970).
52. Kiese, M. and Weger, N.: Formation of ferrihemoglobin with aminophenols in the human for the
113
56. Burrows, G. E., Williams, C. E., and Way, I. L.: Antagonism of cyanide toxicity in sheep. Abstracts.
Seventh Annual Meeting, Society of Toxicology, San Francisco, California, March 12-16, 1978,
pp. 359-360.
57. Evans, C. L.: Cobalt compounds as antidotes for hydrocyanic acid. Brit. J. Pharmacol, 23, 455,
(1964).
58. Isom, G. and Way, J. L.: Cyanide intoxication: protection with cobaltous chloride. Toxicol. and
Appl. PharmacoL, 24, 449, (1973).
59. Saikkonen, J.: Cobalt as a producer of porphynuria and polycythemia in humans. Fed. Proc., 14,
331, (1955).
60. Frankenberg, L. and Sorbo, B.: Effect of cyanide antidotes on the metabolic conversion of cyanide to
thiocyanate. Arch. Toxicol., 33, 81, (1975).
61. Hillman, B., Bardhan, K. S., and Bain, J. T. B.: The use of dicobalt edetate (Kelocyanor) in cyanide
poisoning. Postgrad. Med. J., 50, 171, (1974).
62. Conn, J. B., Norman, S. L., and Wartman, J. G.: The equilibrium between vitamin BI2 (cyanocobalamin) and cyanide ion. Science, 113, 658, (1951).
63. Mushett, C. W., Kelly, K. L., Boxer, G. E., and Rickards, J. C.: Antidotal efficacy of vitamin B12a
(hydroxocabalamin) in experimental cyanide poisoning. Proc. Soc. Exp. Biol., 81, 234. (1952).
64. Posner, M. A., Tobey, R. E., and McElroy, H.: Hydroxocabalamin therapy of cyanide intoxication
in guinea pigs. Anesthesiology, 44, 157, (1976).
65. MacRae, W. R. and Owen, M.: Severe metabolic acidosis following hypotension induced with sodium
nitroprusside. Br. J. Anaesth., 46, 795, (1975).
66. Wilson, J., Linnell, J-C., and Mathws, D. M.: Plasma-cobalamins in neuro-ophthalmological
diseases. Lancet, 1, 259, (1971).
67. Yacoub, J., Faure, J., Morena, H. et al.: Acute cyanide poisoning Current data on the metabolism
of cyanide and treatment with vitamin B12a. Eur. J. Toxicol., 71, 22, (1974).
68. Cottrell, J. E., Pierre Castheley, M. D., Jonathan, M.D. et al: Prevention of nitroprusside-induced
cyanide toxicity with hydroxocobalamin. New England J. Med., 2, 98, 809, (1978).
69. Graham, D. J., Laman, D., Theodore, J., and Robin, E. D.: Acute cyanide poisoning complicated
by lactic acidosis and pulmonary edema. Arch. Intern. Med, 137, 1051, (1977).
70. Rose, C. L., Worth, R. M., and Chen, K. K.: Hydroxocobalamin and acute cuanide poisoning in dogs.
Life Sci., 4, 1785, (1965).
71. Towill, L. E., Drury, J. S., Whitfield, B. L., Lewis, E. B., Galyan, E. L., and Hammons, A. S.:
Reviews of the environmental effects of pollutants: V. Cyanide, PB-289920, U.S. Department of
Commerce, National Technical Information Service, Springfield, VA 22161.
72. McKain: Gas dialysis speeds cyanide analysis. Environmental Science and Technology, 11,31 , (1977).
73. Dodge, B. F.: Am. Electroplaters Soc. Res., 14, 1, 46, (1949).
74. Ludzack, F. J. et al.: Sew. and Ind. Wastes, 23, 1298, (1951).
75. Rawlings, G. D. and Samfield, M.: Textile plant wastewater toxicity. Environmental Science and
Technology, 13, 160, (1979).
76. Goang-Shin Liaw and Woodbridge, D.: Effects of gamma radiation on aqueous solutions of cyanide.
Bull. Environ. Contam. Toxicol., 17, 6, 714, (1977).
77. Hulbert, L. C. and Oehme, F. W.: Plants poisonous to livestock. 3rd Ed. Kansas State University
printing Service, Manhattan, 1968.
78. Conn, E. E.: Cyanogenetic glycosides, toxicants occurring naturally in foods. National Academic of
Sciences, pp. 299-308, 1973.
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