Brent Hoff, Herman J. Boermans, John D. Baird
- During the 5-year period from January 1, 1990, to December 31, 1995, 887 diagnoses of metal toxicosis in domestic animals and wild birds were documented at the Veterinary Laboratory Services Branch of the Ontario Ministry of Agriculture, Food and Rural Affairs. Most of these cases involved cattle, sheep, and birds. Lead toxicosis was diagnosed in 399 cases, copper toxicosis in 387, zinc toxicosis in 49, mercury toxicosis in 44, iron toxicosis in 4, and selenium in 4 cases. Trends in species affected and sources of metals are discussed.
Can Vet J 1998; 39: 39-43
There are approximately 15 essential trace elements, namely, arsenic, chromium, cobalt, copper, fluoride, iodine, iron, manganese, molybdenum, nickel, selenium, silicone, tin, vanadium, and zinc (1). Ten of these have been associated with clinical problems in animals, when in excess or deficiency. These are arsenic, cobalt, copper, fluoride, iron, manganese, molybdenum, nickel, selenium, and zinc. Supplementation of animal diets has resulted in numerous incidents of poisoning (2). Organic arsenicals are often used as feed additives for disease control and to improve weight gain and feed efficiency in swine and poultry (2). Poisoning with these arsenicals has often been due to misformulations or insufficient water intake. Because .of major differences among species with regard to copper requirements and the influence of low molybdenum intake, copper toxicosis has been common in sheep and calves (3-5). The high species sensitivity of young pigs to iron supplementation has been a common cause of iron toxicosis in swine (6). Supplementation of selenium in selenium-deficient areas has resulted in selenium toxicosis through miscalculation in feed mixing and in the use of injectables (7-9). Although zinc has been added to animal feeds, its low toxicity has resulted in only occasional incidents of toxicosis (10,11); however, heavy use of this element in galvanized coatings has resulted in toxicosis in pets (12).
Cadmium, lead, mercury, and nickel are metals that have become common environmental contaminants (1). As a result of mining, industrial activities, and commercial applications, these metals may be released into the environment. Cadmium, lead, and nickel are often components of sewage sludge used as a soil amendment for agriculture or home gardening applications (12).
Cadmium and nickel tend to be taken up into the leafy portions of plants and may reach high concentrations in grains (13). Domestic animals that graze are exposed to heavy metals in soil and plants in ways that humans and other animals are not. Several of these heavy metals accumulate in animal tissues and often lead to chronic toxicosis or residues, particularly in organ meats (14). All forms of mercury entering the environment are converted to methyl mercury and to a lesser extent ethyl mercury by anaerobic bacteria. Methyl mercury is the principle residue accumulating in aquatic organisms and birds from polluted watersheds (15). Mercurial diuretics and dermatological ointments are no longer commonly used (16). Although the use of lead in gasoline and paint has been reduced, lead is still commonly used in plumbing, batteries, fishing sinkers, and shotgun pellets. These products provide a significant source of environmental contamination. Heavy metals, such as, cadmium, lead, and mercury are able to exert toxic effects at low doses in all species (15-17).
In the past, mixtures of inorganic arsenic, cadmium, copper, chromium, mercury, and zinc were used as fungicides, herbicides, and insecticides in agriculture. These metals accumulated in the soil and their use resulted in frequent animal poisonings (16-18). These pesticides are now primarily of historical importance and no longer a practical threat, since they have been replaced with the new organic pesticides (19). Today, wood and insulation products are frequently treated with arsenic, copper, or chromium as preservatives (20). After burning these products, the ash may present a danger to domestic animals. Prohibiting the use of thallium as a rodenticide and insecticide has dramatically reduced the occurrence of thallium toxicosis in North America (20). Copper sulfate, however, commonly used as an algicide in water and fungicide in foot baths, is a source of acute animal poisoning.
In Ontario, the significance of lead toxicosis has been reported previously (21-23); however, very litttle has been documented on the excess of other metals in domestic animals. The objectives of this study were to document the frequency of requests of suspected heavy metal toxicosis in Ontario between 1990 and 1995, to report the positive diagnosis of heavy metal toxicosis during this period, and to determine if any other metal analysis should be made available to Ontario veterinarians.
The data were compiled from the Ontario Ministry of Agriculture, Food and Rural Affairs' (OMAFRA) toxicology laboratory records from January 1, 1990, to December 31, 1995. Submissions, each representing a single animal, were from veterinarians or wildlife officers (all wildlife districts) in Ontario. Submissions represented suspected metal toxicosis or imbalance in nutritional status on the grounds of a history of exposure, or the clinical signs or lesions. The animal groupings used were bovine, equine, canine, feline, avian, and "other" species. The "other" species were predominantly sheep, goats, and pigs. The metals requested during the study included lead, copper, selenium, zinc, mercury, iron, and arsenic. In many cases, requests for analysis included a combination of metals. Samples submitted for metal analysis were whole blood, serum, liver, or kidney.
Samples were analyzed quantitatively for copper, zinc, iron, and arsenic using atomic absorption (AA) flame spectrometry techniques. Lead was analyzed by graphite furnace, Mercury by AA vapor. Samples were classified as positive, if results were in the "toxic" range according to the reference values for this laboratory.
There were 4601 submissions for suspected metal poisoning or nutritional imbalance (Table 1). Lead toxicosis was diagnosed in 399 cases, copper toxicosis in 387, zinc toxicosis in 49, mercury toxicosis in 44, iron toxicosis in 4, and selenium in 4 cases. Cattle were most frequently affected by lead (291 animals) but also copper (67 animals), zinc (16 animals), and iron (1 animal). Horses were poisoned by copper (21 animals), lead (8 animals), and zinc (3 animals). Birds were poisoned by lead (89), mercury (83), zinc (20), and copper (4). Sheep were poisoned by copper (280 animals) and selenium (2 animals). One pig was confirmed with iron poisoning. Pets, including dogs and cats, represented only 134 cases submitted for suspect metal toxicosis. Dogs were poisoned by copper (15 animals), lead (4 animals), and zinc (3 animals), while 2 cats were positive for lead toxicosis. Selected toxicoses with tissue levels are also reported in Table 2.
Lead poisoning has been reported in most domestic animals and humans (20). This survey supports previous findings that cattle are the species most commonly affected by lead poisoning (22-29). Lead poisoning has been shown to be 10 times more common in cattle than in any other domesticated species (22). However, this laboratory also received substantial submissions for lead analyses from birds and horses. As the OMAFRA laboratory predominantly serves the agricultural community, there is a differential fee stucture for farm animals that may have been the reason for the low numbers of canine and feline samples. The large number of lead toxicoses in wild birds was expected; however, the number of positive equine samples was an unexpected finding, although this species appears to be quite susceptible to lead poisoning after chronic ingestion of lead (28). The clinical signs of chronic lead toxicity previously reported in horses located next to a smelter included laryngeal paralysis, colic, unthriftines, and respiratory distress (28). Six of the 8 horses in this present study consistently had clinical signs of anorexia, unthriftiness, weight loss, muscular weakness, laryngeal paralysis, and respiratory distress. The levels of lead in the liver ranged from 4 ppm to 10 ppm (tissue wet weight), which are compatible with the findings of others (25,26,28).
The most common sources of lead were old batteries, paint chips, and old asphalt shingles, which accounted for 42% of the bovine cases. However, the source of the lead could not be determined in 48% of the bovine cases. In earlier reports (24,25,27), a common source of lead for domestic species was identified as crankcase oil, with the lead derived from leaded gasolines. In the equine cases, no source could be identified. In birds, particularly ducks and loons, a common source of lead was fishing sinkers and lead shot.
Copper compounds are widely used in agriculture and veterinary practice as fungicides, bactericides, molluscicides, anthelmintics, and feed additives (31). The 280 sheep with liver and or kidney copper in the toxic range was expected. The clinical and pathological findings in these cases were similar to those previously reported (3,31). Both acute and chronic manifestations were noted; however, these terms are misleading, because "chronic" refers to a long cumulative poisoning that may suddenly develop into an acute hemolytic crisis (27). The ingestion and absorption of copper that is stored in the liver is termed "chronic copper poisoning" (3,5,6). In this study, the source of the copper was determined in 52% of the cases. Some of the more common sources were mineral mixes formulated for cattle, drinking water that had been treated with copper to control algae, and copper sulfate foot baths in 2 cases involving sheep. In a recent case involving 150 yearling ewes, 5 died after being lethargic and anorectic for 12 h prior to death. The copper and molybdenum concentrations in the liver were 1006 ,ug/g and
Of the 35 submissions for copper analysis from dogs, 15 had copper levels in the toxic range. Of these 15, 4 were Bedlington terriers, 2 were West Highland white terriers, and 3 were Doberman pinchers, all with copperassociated hepatitis. The Bedlington terrier and West Highland white terrier exhibit a genetically-linked liver storage disease that leads to copper poisoning (33). Doberman pinscher hepatic disease has been called "chronic active hepatitis" and "copper storage disease," although its pathogenesis is not yet clear (33). The other dogs came from a variety of breeds, including cocker spaniel, Labrador retriever, and 1 golden retriever. Of the 67 cases of high copper levels detected in cattle, 55 were calves and 12 were adult cattle. Calves have been shown to be more susceptible than adult cattle to high copper intake (31). There are areas in eastern Ontario known for peat soil that is high in molybdenum, which has resulted in copper deficiency problems and farmers routinely supplementing with copper. Three cases of copper toxicity in adult cattle were as a consequence of copper supplementation. Adult cattle, goats, deer, and pigs are considered tolerant, but they can also be affected (6,32).
The absence of domestic animal poisoning by mercury varies from previous reports of mercury toxicosis in domestic animals due to consumption of mercurial medicaments or seed grain treated with organic mercury (34,35,37) and may be due to to the recognition of the danger of these mercurial compounds, which lead to the discontinuance of their use in Ontario. All the cases of mercury poisoning were in raptors. These fish-eating birds were found weak or dead and no obvious cause of illness or death could be found at necropsy. Although paper mills and mines are reported to be the major sources of elemental mercury in Ontario, natural mercury contamination of lakes in Ontario does occur (37).
Elemental mercury is converted to methyl mercury in aquatic environments. Methyl mercury then accumulates to high concentrations in aquatic animals, particularily fish (15,18). The consumption of contaminated fish by raptors appears to be a primary source of the mercury toxicosis in the 83 birds examined in this study. Of interest was the 23 birds with tissue levels of both lead and mercury in the toxic range. Most of the birds were loons, and the tissue levels were in the lower part of the toxic range; the possibility of an additive effect of these toxic metals is possible with lower tissue levels having toxic effects. This could involve a greater number of water birds having heavy metal toxicosis than considered in previous estimates.
Industrial pollution with zinc is common (23,27). Toxicity has been documented in farm animals after treatment for lupinosis with zinc compounds or after feed supplementation (27). Zinc sulphate has also been used in the treatment of footrot (27). In the present study, 10 of the 77 birds with zinc levels in the toxic range were parrots and cockatoos that lived in metal cages, most of which had been recently galvanized. One case involved a young emu that was in contact with a galvanized fence. Several of the other birds with zinc levels in the toxic range were cormorants and great blue herons. No source of zinc could be identified in these cases. Of the 3 dogs with zinc toxicosis, 2 were young puppies that had swallowed metal objects with a high content of zinc. One was a zinc-coated nut and the other was an American penny, which after 1978 is known to contain abundant zinc (17). No source for the zinc was noted in the 16 cattle and 1 sheep with serum levels in the toxic range. Two typical selenium poisoning syndromes occur as a result of ingestion of selenium. A subacute form called "blind staggers" and a chronic form called "alkali disease" (27). In many areas of the world, soil is rich in selenium and certain plants are able to absorb selenium in quantities that are toxic to grazing animals (7-9). Therefore, it is easy to appreciate the significance of these diseases in selenium-rich regions. The OMAFRA toxicology laboratory is located in an area of selenium deficiency where supplementation is common. Only 4 cases of selenium excess was recorded in this period, 2 were in calves and 2 were in lambs. All had been injected with excess selenium. There were no reported cases of porcine focal symmetrical poliomylomalacia, a neurological disease in young feeder pigs receiving high dietary levels of selenium (7). From these findings, selenium toxicity due to supplementation does not appear to account for many losses in Ontario. Most of the 723 submissions from cattle for selenium analysis were because of concern about selenium deficiency.
Toxicity from large doses of iron administration is an uncommon finding in this laboratory. During the period from 1990 to 1995, 1 1 cases of iron toxicosis were diagnosed histologically. Only 3 of these cases were confirmed with serum or liver iron analysis. The 2 piglets and 1 calf with iron levels in the toxic range were due to overdosage of iron dextran.
No requests for arsenic analysis were received during the 5-year period of this study, although a diagnosis of organic arsenic toxicity was made 4 times using history and histopathologic lesions. During an 8-year period in the 1960s, 21 animals with arsenic toxicity were reported from this laboratory (2). The decreased occurrence in recent years may be due to the marked reduction in the use of arsenical pesticides (2). Nevertheless arsenic is still a constant source of poisoning in both man and animals (2). Chronic arsenic poisoning in animals is rare, because arsenic is rapidly excreted from the body (2).
No requests were made for cadmium, nickel, or chromium analysis. Cadmium and nickel are environmental contaminants, which could result in chronic low level ingestion (20). They have been shown to be carcinogenic (10,11). The chronic nature and lack of overt toxicity with these elements would make diagnosis difficult for veterinarians. Therefore, the lack of requests for analysis of cadmium and nickel does not preclude the possibility of subclinical effects or accumulation in liver or kidney of domestic animals.
Chromium is now being considered in Ontario as a feed additive for ruminants (18). The use of chromium in feed may result in formulation errors not uncommon with any feed additive. With newer technologies, such as Inductively Coupled Plasma Atomic Emission Spectrometry, samples can be screened for numerous metals simultaneously similar to serum biochemistry profiles. Such technology would provide a means to monitor for metal induced disease or residues. Public environmental concerns, as well as feed mixing errors, would make this a valuable addition to toxicological investigations in the future.
1. Sharma RP, Street JC. Public health aspects of toxic heavy metals in animal feeds. J Am Vet Med Assoc 1980; 177: 149-153.
2. Hatch RC, Funnell HS. Inorganic arsenic levels in tissues and ingesta of poisoned cattle: An eight-year survey. Can Vet J 1969; 10: 117-120.
3. Bostwick JL. Copper toxicosis in sheep. J Am Vet Assoc 1982; 180: 386-387.
4. Suttle NF, Field AC. Effect of intake of copper, molybdenum and sulphate on copper metabolism in sheep. J Comp Pathol 1969; 79: 453-464.
5. Gopinath C, Howell JM. Experimental chronic copper toxicity in sheep. Changes that follow the cessation of dosing at the onset of haemolysis. Res Vet Sci 1975; 19: 35-43.
6. Puls R. Mineral levels in animal health. Clearbrook, British Colombia: Sherpa International, 1994.
7. Harr JR, Muth OH. Selenium poisoning in domestic animals and its relationship to man. Clin Toxicol 1972; 5: 175-186.
8. Shortridge EH, O'Hara PJ, Marshall PM. Acute selenium poisoning in cattle. NZ Vet J 1971; 19: 47-50.
9. Koller LD, Exon JH. The two faces of selenium-deficiency and toxicity are similar in animals and man. Can J Vet Res 1986; 50: 297-306.
10. Graham TW, Goodger WC, Christiansen V, Thurmond MC. Economic losses from an episode of zinc toxicosis on a California veal calf operation using a zinc sulfate-supplemented milk replacer. J Am Vet Med Assoc 1987; 6: 668-671.
11. Graham TW, Thurmond MC, Clegg MS, Keen CL. An epidemiologic study of mortality in veal calves subsequent to an episode of zinc toxicosis on a California veal calf operation using zincsulfate- supplemented milk replaser. J Am Vet Med Assoc 1987; 10: 1296-1301.
12. Beasley VR. A systems affected approach to veterinary toxicology. Urbana: Univ of Illinois Pr, 1994: 326.
13. Clarke EGC, Clarke ML. Veterinary Toxicology, 3rd ed. London: Bailliere Tindall, 1967: 55-132.
14. Sexton JW, Buck UB. Metal Toxicosis. In: Current Veterinary Therapy: Food Animal Practice. Philadelphia, WB Saunders, 1986: 439-440.
15. Koestner A, Norton S. Nervous system. In: Haschek WA, Rousseaux CG, ed. Handbook of Toxicological Pathology. Toronto: Academic Press, 1991: 625-674.
16. Wren C. Mammals as biological monitors of environmental metal levels. Environ Monitor Assess 1986; 6: 127-144.
17. Frank R, Suda P, Luyken H. Cadmium levels in bovine liver and kidney from agricultural regions and off the Canadian Shield, 1985-1988. Bull Environ Contam Toxicol 1969; 43: 737-741.
18. Bray BJ, Dowdy RH, Goodrich RD, Pamp DE. Trace metal accumulations in tissues of goats fed silage produced on sewage sludge-amended soil. J Environ Qual 1985; 14: 114-118.
19. Sundlof SF. Drugs and chemical residues in livestock. Vet Clin North Am Food Animal Pract 1989; 5: 411-449.
20. Osweiler GD, Carson TL, Buck WB, Van Gelder GA. Clinical and Diagnostic Veterinary Toxicology, 3rd ed. Dubuque, Iowa: Kendall/Hunt, 1976.
21. Hatch RC, Funnell HS. Lead levels in tissues and stomach contents of poisoned cattle: A fifteen-year survey. Can Vet J 1969; 10: 258-262.
22. Priester WA, Hayes HM. Lead poisoning in cattle, horses, cats, and dogs as reported by 11 colleges of veterinary medicine in the United States and Canada from July, 1968, through June, 1972. Am J Vet Res 1974; 35: 567-569.
23. Willoughby RA, MacDonald E, McSherry BJ, Brown G. Lead and zinc poisoning and the interaction between Pb and Zn poisoning in the foal. Can J Comp Med 1972; 36: 346-360.
24. Blakley BR, Brockman RP. Lead toxicosis in cattle in Saskatchewan. Can Vet J 1976; 17: 16-18.
25. Aronson AL. Lead poisoning in cattle and horses following longterm exposure to lead. Am J Vet Res 1972; 33: 627-629.
26. Buck WB. Laboratory toxicologic tests and their interpretations. J Am Vet Med Assoc 1969; 155: 1928-1941.
27. Blood DC, Radistits OM. Veterinary Medicine, 8th ed. London: Bailliere Tindall, 1994: 1469-1507.
28. Knight HD, Burau RG. Chronic lead poisoning in horses. J Am Vet Med Assoc 1973; 162: 781-786.
29. Zook BC. Lead intoxication in urban dogs. Clin Toxicol 1973; 6: 377-388.
30. Blakeley BR, Berezowski JA, Schiefer HB, Armstrong KR. Chronic copper toxicity in a dairy cow. Can Vet J 1982; 23: 190-192.
31. WeiFs E, Baur P, Plank P. Chronic copper poisoning in calves. Vet Med Rev 1968; 1: 62-76.
32. Bradley C. Copper poisoning in a dairy herd fed a mineral supplement. Can Vet J 1993; 34: 287-292.
33. Sevelius E, Jonsson LH. Pathogenic aspects of chronic liver disease in the dog. In: Kirk's Current Veterinary Therapy XII. Philadelphia: WB Saunders. 1995: 740-742.
34. Buck WB. Toxic materials and neurologic disease in cattle. J Am Vet Med Assoc 1975; 166: 222-226.
35. Buck WB. Physical and chemical disorders. In: Howard JL, ed. Current Veterinary Therapy 2. Philadelphia: WB Saunders, 1986: 335-466.
36. Goyer RA. Toxic effects of metals. In: Klassen CD, ed. Casarett and Doull's Toxicology. The Basic Science of Poisons. McGraw- Hill Co, 1996: 691-736.
37. Domingo JL. Metal-induced developmental toxicity in mammals: A review. J Toxicol Enviro Health 1994; 42: 123-141.