Inorganic arsenic toxicosis in a beef herd

Abstract

Over a 44-day period, 4 of 5 affected calves in a 170-head herd of beef cattle died after exhibiting clinical signs of lethargy, ataxia, anorexia, and diarrhea. Histopathological examination of tissues and toxicological analysis of a suspicious powder discovered in the pasture confirmed arsenic trioxide toxicosis.

A northern Ontario cow-calf producer managed a 170-head mixed beef herd as 2 uniform herds named East and West. All calves were treated prophylactically at birth with vitamin E-selenium and were vaccinated against respiratory pathogens and multiple clostridial toxins at 2.5 to 6 wk of age, approximately 1 to 2 wk before they were allowed access to pasture. The owner had recently rented 400 acres to which only the West herd had access. Problems arose in May, shortly after the calves in the West herd were turned out to pasture.

On day 1, the producer observed that a 2-month-old calf (calf 1) was lethargic, depressed, and anorexic. When examined, the calf had a normal rectal temperature; however, the heart rate was low (54 bpm) and the respiratory rate (60 bpm) was elevated. The calf was also ataxic and had several parallel lacerations through the dermis in the perineal region, with associated emphysema. The differential diagnosis at the time included bacterial meningitis, blackleg (caused by Clostridium chauvei), bovine viral diarrhea (BVD), or predator attack.

The calf was treated with electrolytes (Calf Lyte II He; Vétoquinol, Lavaltrie, Quebec), 2 L, PO; a combination of vitamin E and selenium (Dystosel; Pfizer Canada Animal Health Group, London, Ontario), 6.04 IU/kg bodyweight (BW) and 0.13 mg/kg BW, respectively, IM; vitamin B complex (Biocid; Ayerst, Guelph, Ontario), 5 mL, IM; penicillin (Longisil; Vétoquinol), 8900 IU/kg BW, IM; and flumethasone (Flucort; Ayerst), 0.018 mg/kg BW, IM.

Calf 1 was found dead on the morning of day 2. A postmortem examination revealed a well-muscled calf with mortem 2 small focal areas of dark musculature located superficially on the left and right semimembranosus muscles, brush stroke hemorrhages on the cortices of both kidneys, partially digested hair filling the abomasum, and diffuse congestion of both lungs. A sample of skin taken from the perineal region was submitted to the Animal Health Laboratory (AHL) (University of Guelph, Guelph, Ontario) for a bovine viral diarrhea (BVD) virus antigen detection enzyme linked immunosorbent assay (ELISA) test (Syracuse Bioanalytical, East Syracuse, New York, USA). Also submitted to the AHL were samples of brain, trachea, esophagus, heart, lung, thymus, diaphragm, duodenum, colon, liver, spleen, kidney, mesenteric lymph node, semimembranosus muscle, and skin from the perineal region for histopathological examination; in addition, a swab taken from the duodenal contents was submitted for bacterial culture. No organisms were isolated from the intestinal swab. The perineal skin sample was negative for BVD virus antigen. Histopathological examination of the diaphragm showed acute myofiber degeneration, suggestive of either vitamin E-selenium deficiency or ionophore toxicity. There was also myofiber necrosis of skeletal muscle, and severe pulmonary congestion and edema were evident. The lesions located in the perineal area were attributed to predator attack. On being questioned, the producer indicated that the calves might have received feed containing an unidentified ionophore 2 wk prior to the observation of clinical signs in calf 1.

Calf 2 presented with lethargy, anorexia, depression, and diarrhea on day 16. This calf was treated with vitamin E-selenium and ampicillin (Synergistin; Pfizer Canada), 6.6 mg/kg BW, IM. Four hours later, the calf was found dead. A necropsy revealed paintbrush hemorrhage on the cortical surface of both kidneys. Sections of lung, heart, trachea, esophagus, diaphragm, liver, kidney, spleen, and duodenum were collected at necropsy within 1 h of death and submitted in 10% buffered formalin for histopathological examination. On microscopic examination marked congestion of the cortico-medullary junction and the red pulp of the spleen was observed. However, a diagnosis could not be determined.

Calf 3 was noticed by the producer on day 17 to be dyspneic and salivating, and to have fluid diarrhea. This calf was euthanized and necropsied immediately. The lungs were edematous, with froth present in the trachea; the mesenteric lymph nodes were enlarged; and there were areas of hemorrhage in the kidney cortices. No organisms were isolated on culture from a swab taken from the duodenal contents. Specimens submitted to the AHL for histopathological examination included heart, lung, spleen, liver, duodenum, lymph node, and kidney. On microscopic examination, marked pulmonary congestion and congestion of the red pulp of the spleen, marked lympholysis of lymph node follicles, and chronic focal tubulo-interstitial nephritis were observed. A diagnosis of chronic focal tubulo-interstitial nephritis of unknown etiology was made.

Calf 4 was examined on day 43 because of anorexia, ataxia, lethargy, and diarrhea. The pulse and respiratory rates were in the normal range; however, the rectal temperature was 41°C. A blood sample was drawn for a complete blood cell (CBC) count and a serum biochemical profile. The calf was treated with vitamin E-selenium, ampicillin, penicillin, electrolytes, as previously described, and also administered trimethoprim sulpha (Trimadox; Vétoquinol), 48 mg/kg BW, IM; ceftiofur (Excenel RTU sterile suspension; Pharmacia and Upjohn, Orangeville, Ontario), 1.1 mg/kg BW, IM; and a sulphonamide combination (Cocci Bol-O-Tab Jr.; Intervet, Whitby, Ontario), 47 mg/kg BW, PO. The calf died on the following day. On postmortem examination, the liver was diffusely friable and orange, the meninges and epicardium contained areas of hemorrhage, and there were erosive lesions in the abomasum, duodenum, colon, and rectum. The differential diagnoses included toxicosis due to an organophosphate, plant, or heavy metal. Formalin-fixed tissues, (abomasum, small intestine, colon, liver, kidney, heart, and spleen) were submitted to the AHL for histopathological examination, and frozen tissues (liver, kidney, logical brain, and rumen content) were submitted for toxicological evaluation. Results of the CBC count and biochemical profile (Table 1) indicated a pathological chemical process affecting the kidneys, liver, and, possibly, bone marrow. There was marked necrosis of the proximal tubules of the kidney; marked congestion of the red pulp of the spleen; focal areas of subepicardial hemorrhages and edema in the heart; and focal areas of necrosis in periportal areas of the liver, with marked swelling and vacuolation of hepatocytes. There was submucosal edema of the abomasum and colon, and segmental congestion, hemorrhage, and necrosis of the intestinal mucosa. A diagnosis of hepatitis, nephrosis, and necrotizing hemorrhagic enteritis was determined on histopathologic rhagic examination, suggestive of a heavy metal toxicosis.

Table 1.

Hematologic and serum biochemical test results for a beef calf (calf 4) exposed to arsenic trioxide

Parameter	Result	Reference range
White blood cells (× 109 cells/L)	4.6	5.05–13.3
Red blood cells (× 1012 cells /L)	14.4	4.9–7.5
Hemoglobin (g/L)	162	84–120
Hematocrit (L/L)	0.44	0.21–0.30
Mean corpuscular volume (fL)	31	36–50
Mean corpuscular hemoglobin (pg)	11	14–19
Mean corpuscular hemoglobin concentration (g/L)	370	380–431
Red blood cell distribution width (%)	25.4	16–20
Monocytes (× 109 cells /L)	0	0.1–0.7
Segmented neutrophils (× 109 cells /L)	0.83	1.7–6.0
Phosphorus (mmol/L)	3.28 1	46–2.83
Total protein (g/L)	61	70–94
Globulin (g/L)	26	31–56
Albumin: globulin ratio	1.35	0.6–1.2
Urea (mmol/L)	24.4	3.0–8.3
Creatinine (μmol/L)	333	40–80
Glucose (mmol/L) 1.5	1.5	2.1–3.8
Cholesterol (mmol/L)	2.33	2.90–8.00
Total bilirubin (μmol/L)	9	0–5
Conjugated bilirubin (μmol/L)	4	0–2
Free bilirubin (μmol/L)	5	0–4
Alkaline phosphatase (U/L)	412	33–114
Gamma glutamyl transferase (U/L)	73	13–52
Aspartate aminotransferase (U/L)	1263	56–176
Glutamate dehydrogenase (U/L)	436	7–57
Creatine kinase (U/L)	3986	65–234
Beta-hydroxybutyrate (μmol/L)	164	291–1235

Calf 5 was found on day 44 separated from the herd, anorexic, depressed, diarrheic, and with an elevated respiratory rate of 42 bpm. Treatment for this calf was identical to that for calf 4. Over the next 72 h, the calf started to nurse and the diarrhea decreased significantly.

Also on day 44, a search of a small section of pasture accessible to the West herd uncovered a dumpsite containing an open metal tin partially filled with white powder. On investigation, it was determined that the owner of the rental acreage had cleaned out and deposited the contents of a shed at that site in 1997. Tentatively, the powder was identified as a potato dust. Toxicological analysis showed that it contained arsenic trioxide at a concentration of 700 000 ppm. Further analysis of the tissues of calf 4 demonstrated arsenic trioxide at a concentration of 350 ppm in the liver and 1200 ppm in the ruminal contents. Because clinical signs, histopathological findings, and accessibility to the powder were similar for all 5 affected calves, all were considered to have suffered from inorganic arsenic toxicosis. It is not known how many animals had ingested the arsenic.

Arsenic poisoning is rare. As a result of awareness of the toxic properties of arsenic and availability of safer alternatives, there has been a significant decline in the use of arsenic-containing compounds. As in this case, most occurrences of livestock intoxication are attributed to accidental access to arsenical compounds (1).

Arsenic, a heavy metal, is an essential trace element. Animals are able to tolerate low levels of arsenic; the normal level in cattle tissues is <0.5 ppm (1,2). Arsenic levels > 10 to 15 ppm in the liver, accompanied by clinical signs, are considered diagnostic of acute arsenic toxicosis (3). Arsenic poisoning may be peracute, with clinical signs including depression, prostration, and sudden death. The clinical signs displayed by the affected calves in this case were typical of acute arsenic intoxication, which develops 20 to 50 h after toxicant ingestion (4). Animals that survive the acute phase may live for 2 to 7 d and exhibit clinical signs of ataxia and convulsions. Chronic arsenic poisoning is rarely seen in domestic animals because arsenic is rapidly excreted in the urine (2,4). Arsenic may be absorbed percutaneously, causing blistering, edema, and necrosis of the skin due to capillary dilatation and degeneration (2,4).

The trivalent form of inorganic arsenic is up to 10 times more toxic than the pentavalent form and causes most of the toxic effects (5). Pentavalent and organic forms of arsenic are reduced and metabolized in the rumen and converted to the trivalent form, producing toxicosis. Trivalent inorganic arsenic binds to and inactivates intracellular sulfhydryl-containing compounds, especially lipoic acid and α-keto oxidases, thereby disrupting cellular metabolism and inhibiting enzyme systems essential for oxidative phosphorylation. The tissues of most organs affected by arsenic have high oxidative energy requirements, principally the alimentary tract, kidney, liver, lung, brain, and epidermis (1,2,4). This disruption in energy metabolism may have caused the ataxia and lethargy displayed by the calves in this investigation.

Arsenic also affects capillary integrity through an unknown mechanism (5). Increased permeability of capillaries systemically allows for transudation of plasma fluid into the gastrointestinal tract, which causes submucosal congestion, edema, diarrhea, dehydration, acidosis, and shock (1,5). The absence of gastrointestinal lesions, as in the case of calf 1, is unusual in acute arsenic poisoning. It is possible that the arsenic ingested by calf 1 produced a very mild gastrointestinal lesion. As a result, little fluid entered the intestinal lumen and the animal died of other effects. Capillary dilatation also contributes to reduced blood volume, hypotension, and cardiovascular collapse. Decreased nephric perfusion, as well as direct arsenic-induced necrosis of the proximal tubular cells, causes renal damage (5), which was evident macroscopically and microscopically in all 4 calves examined.

A diagnosis of arsenic intoxication must be supported by clinical signs, identification of a source of the suspected toxicant, elevated levels of the toxicant in the tissues, and pathological lesions (2,4). The treatment regime for livestock includes supportive and decontamination procedures, administration of sodium thiosulfate, IV and PO, and antidotal therapy. Chelating sulfate, antidotes contain sulfhydryl groups that compete with sulfhydryl-containing enzymes for available arsenic (4). The classic chelating antidote for arsenic toxicosis is dimercaprol (BAL). Thioctic acid, mesodimercaptosuccinic acid, and dimercaptosuccinic acid are alternative cinic chelating agents (5).

The prognosis following acute arsenic toxicosis is grave if the diagnosis and, therefore, treatment are delayed. The survival of calf 5 despite acute arsenic poisoning suggests that a smaller amount of toxicant was ingested. When gests livestock ingest large amounts of arsenic for a short period of time, meat and other products from affected animals are not suitable for human consumption (5).