In southern Australia, selenium (Se) intoxication is a risk when livestock are overdosed either by miscalculating the dilution of Se concentrates, miscalculating the dose by bodyweight of injectable trace minerals or through the simultaneous administration of selenium-containing drenches, vaccines, and injectable formulations.
Gabbedy (1970) reported on eight cases of Se poisoning in sheep. Lambs were commonly affected because they risked receiving an adult dose, their weight was overestimated and/or oral Se might be more available in lambs during their pre-ruminant phase. As little as 5 mg of Se by intramuscular injection (1.0 mg/kg) and 10 mg Se orally (2.2 mg/kg) was sufficient to kill lambs. Diarrhoea occurred in the survivors. In another case, 50 mg Se killed 15/39 heavily pregnant Merino ewes while 180/190 two-to-six week-old lambs died following a dose of 64 mg Se. Most deaths occurred within the first three days but continued for 10 days.
The signs of acute Se toxicity are elevated pulse rate and temperature, diarrhoea, tissue haemorrhage, respiratory distress, oedema and pulmonary congestion. Death is due to circulatory failure and cardiomyopathy (Suttle 2022; Grace et al. 2010). Acute toxicity is reported in the literature when sodium selenite or selenate solutions are injected at doses between 1-3 mg Se/kg bodyweight (BW) (Grace et al. 2010). Suttle (2022 ) mentions that toxicity occurred at injected doses of 0.4-0.6 mg Se/kg BW in sheep with no history of Se deficiency.
In this case the affected lambs weighed between 5-10 kg and received 3 mg Se as sodium selenite and selenate (1 mg Se orally, 1mg Se by injection from the vaccination and 1 mg Se by injection from an injectable trace mineral supplement)
Lambs from two mobs of Merino ewes were marked in October 2021. The first mob of 209 lambs, the progeny of 165 Merino ewes joined to White Suffolk rams, were marked on 8 October 2021. At marking, rubber rings were applied on the tails and scrotums with tails docked below the rings. The lambs were drenched with 2 ml of a triple combination product for sheep, (Triguard, Boehringer Ingelheim, 1.0 g/L abamectin, 22.7 g/L oxfendazole, 33.9 g/L levamisole), 0.5 g/L Se (as sodium selenate) and 2.2 g/L cobalt and vaccinated against clostridial diseases and caseous lymphadenitis plus Se (Glanvac 6S, Zoetis containing 1 mg/ml of selenium as sodium selenate and 2 mg/ml of hydroxocobalamin). The lambs were also treated with dicyclanil (CLiK, Elanco) on the breech, ear marked, and ear tagged. Ewe lambs were vaccinated against ovine Johne's disease (Gudair, Zoetis) below the ear.
The second mob of 227 lambs, the progeny of 175 Merino ewes joined to Border Leicester rams, were marked on 17 October 2021. Lambs received the same treatments as the first mob, and were also treated with 0.2 ml Multimin Copper-free injection for Sheep and Cattle, (Virbac, zinc as disodium zinc EDTA 40 mg/mL, manganese as disodium manganese EDTA 10mg/mL, and Se as sodium selenite 5 mg/mL) mostly in the right axilla.
There were no deaths seen in the lambs from the first mob while at least 24 lambs died post-marking in the second mob.
Two lambs died as the ewes and lambs were returned to the paddock (less than 1 km away). Before death, the lambs were observed drooling profuse, clear liquid and showed signs of respiratory distress. The next day, 19 lambs were found dead in the paddock and three lambs were found dead the following morning.
The mob of ewes with affected lambs were examined in the paddock. Most of the lambs were lethargic and some were lame on the right front leg, although some were lame on the left front leg.
Three lambs were necropsied on 19 October 2021.
Lamb 1. Male lamb weighing approximately 8 kg. Lungs heavy, pink and wet especially the anterior ventral lobes but the transition was gradual. There was white foam in the trachea.
Lamb 2. Male lamb weighing approximately 10 kg. The lungs were heavy wet, dark pink with multiple red blotches up to 1 cm diameter across surface of all lung lobes. Abundant white froth in trachea.
Lamb 3. Male lamb weighing approximately 5 kg. The lungs were grossly normal with no foam in the trachea. There were gelatinous subcutaneous tissues in the right axilla.
Liver, kidney and pleural cavity blood samples were submitted to the Regional Laboratory Services in Benalla, VIC via the Elizabeth Macarthur Agricultural Institute to test Se levels.
|Sample||Liver Se||Serum Se||Kidney Se|
|Reference||1.3-19 umol/kg wet wt.||0.5-6.5 umol/L||8-38 umol/kg wet wt.|
|Sample 1||147.0 H||7.4 H||43.7 H|
|Sample 2||203 H||5.4||33.9|
|Sample 3||67.3 H||12.0 H||35.0|
H&E-stained sections of lung and liver from the three lambs, and kidney from Lambs 2 and 3 were examined microscopically.
Degeneration of periacinar hepatocytes was noted in all three lambs, with possible early transition to necrosis in Lamb 2, and slightly more prominent in subserosal parenchyma. Sinusoids were congested, most severely in Lamb 3, particularly in the subserosal parenchyma.
The lungs of the three lambs were congested with variably severe haemorrhages, variable evidence of alveolar oedema (mostly in Lamb 2), and variable minimal to mild neutrophilic inflammatory response (Lambs 1 and 2).
No significant changes were noted in the kidney.
The affected lambs from the second mob presented clinical signs and pathological changes associated with Se toxicity. The changes in lung and liver were acute, mild and non-specific. Target organs in acute Se toxicosis are the same as those affected in Se deficiency. Cardiac muscle lesions are the most significant and common histological lesions reported in ruminants in acute cases, accounting for respiratory distress and death due to cardiac failure. Skeletal muscle lesions are seen in some cases (McKenzie, 2017). Myocardial lesions have also been reported in acute plant-associated selenium intoxications (Davis, 2021) and in chronic intoxications (Gardiner, 1966), although chronic intoxications more typically affect other organ systems, particularly the integument (O'Toole, 1995). Lesions in the liver (Davis 2021) and kidney (Gardiner, 1966) have also been described in association with Se toxicoses in ruminants. With the benefit of hindsight more attention would have been paid to the presumed primary site of intoxication, the heart.
The recommended dose rate of Se as sodium selenate or selenite is 0.1 mg/kg BW as a drench or injectable solution (Grace et al. 2010). Lambs sampled from the affected mob weighed approximately 5, 8 and 10 kg and they received 3 mg Se in total or 0.6, 0.4 and 0.3 mg Se/kg BW respectively. Therefore, lambs received 3-6 times the recommended dose rate. The dose received by these lambs agrees with the reference values for toxicity reported by Suttle (2022).
Se as sodium selenate or selenite is rapidly absorbed and can reach circulation 2-8 hours after subcutaneous injection (Grace et al. 2010). In addition, oral and injectable Se formulations can have different absorption rates; very young lambs (potentially the lighter in the mob) might have been more affected not only because of the larger dose but also because oral Se can be more available in the monogastric phase, when the rumen is not fully developed and functional as in older lambs.
The average weight of the unaffected mob is unknown, but they were the same age so presumably had similar weight to the affected mob. The non-affected lambs received 2 mg of Se in total, hence lambs between 5-10 kg BW may have received between 0.2 and 0.4 mg Se/kg BW, which is still higher than the recommended dose but lower than the toxic margin. This difference may explain the absence of deaths in the unaffected mob.
Although the vaccine was used as per label recommendations, the drench (Triguard) and injectable trace mineral (Multimin Copper-Free) were both used off-label. For these products, the dose rates are 1 mL/5 kg BW and 0.2 mL/10 kg BW respectively and in this case, the lighter animals (5 kg) received double the dose of both products.
Virbac recommends Multimin in lambs at weaning to deliver a more accurate dose (0.2 mg/10 kg BW) and not to use it concurrently with drenches, boluses or other animal health products containing selenium or copper.
This case serves as a warning of the risk of treating animals with several products containing selenium simultaneously and contrary to label recommendations.