OTHER TOXICOSES

3.1 Fluorosis

Fluoride has a high affinity for bone and other calcified tissues such as teeth. Chronic intake of excess amounts of fluoride results in various pathological changes in the skeleton, referred to as osteofluorosis or skeletal fluorosis.

Fig. 19.1. Cranial view of the right and left forelimb (radius and ulna) of a 6-yr-old female red-necked wallaby (Notamacropus rufogriseus) with a bone fluoride concentration of 5850 pgF/g (dry bone). Note the localised, marked, circumferential expansion of the distal half of the right radius with incorporation of the ulna. Note the spiralling grooves in the surface of the proliferative lesion, which correspond to the course of flexor tendons. The contralateral limb for comparison is normal. Photo: Claire Death

such as koalas and possums are quadrupedal and as such they distribute biomechanical forces more evenly between their forelimbs and hindlimbs, leading to differences in bony proliferations (Carlson et al.

3.2 Heavy metal toxicoses

Lead poisoning has been seen in flying-foxes (Zook et al 1970; Sutton and Wilson 1983; Sutton and Hariono 1987; Hariono and Sutton 1993; Skerratt et al 1998). Clinical signs include inability to fly, inappetence, weakness, emaciation, uncoordinated movements, muscle tremors and anaemia. Inhalation and ingestion of lead particles from industrial and vehicle emissions or lead arsenate in insecticides applied to fruit were implicated. Treatment included calcium EDTA 200 g/L diluted to 10 mg/mL, 100-200 mg/kg SC sid for 7 d (Booth 1994). Concurrent supportive therapy included par­enteral fluids, nutrition and benzodiazepines to control convulsions. The animal described by Skerratt et al. (1998) later tested positive to ABLV, which was then believed to be the primary cause of death. In view of this diagnosis, it is possible that some of the signs attributed to lead toxicity in earlier reports may have been due to Australian bat lyssavi­rus (ABLV) infection. Lead poisoning was also suspected in a young red kangaroo in managed care (Hough 1994). Clini­cal signs were ataxia, poor proprioception, knuckling and obvious hindlimb weakness. The animal recovered after treatment that included calcium EDTA.

Given the immunosuppressive effects of some heavy metals, their impact on the hookworm Unicinaria san­guinis and the health of Australian sea-lion pups in SA was recently investigated. Blood levels of lead and cad­mium showed negative associations with red blood cell parameters which suggest they may be exacerbating hookworm induced anaemia in pups (Taylor et al.

Significantly higher blood lead concentrations have been seen in managed Tasmanian devils (Sarcophilus har- risii) in comparison to free-ranging conspecifics (Hivert et al. 2018; Hutchinson et al. 2023), with older animals having higher levels than young animals due to lead’s bio­accumulative effect. While no specific clinical signs were noted, the authors recommend i) removing heads and wounds containing lead from the diet to reduce ingested lead and ii) blood lead concentrations should be below the acceptable threshold of 0.2 mmol/L (Hivert et al. 2018).

Zinc toxicity was suspected in a zoo-housed colony of feather-tailed gliders (Acrobates pygmaeus) (Johnson and Hemsley 2008) that had been introduced into a holding facility fitted with new wire. A week after introduction, five animals were found dead or moribund. Thoracic haemorrhage and red urine were common findings at necropsy and pancreatic and hepatic necrosis suggestive of zinc toxicosis was seen histologically. Toxicological screening for zinc in combined samples revealed levels of 60 mg/kg.

Chronic copper poisoning was diagnosed as the cause of acute intravascular haemolysis and death of a zoo­housed adult southern hairy-nosed wombat, maintained on a diet that included a pig supplement containing copper sulfate (Bryant and Reiss 2008). At necropsy, hae- moglobinuria was observed and generalised jaundice was apparent. The liver copper levels were over 80-fold those in livers of unaffected free-ranging wombats.

Zinc and lead GI foreign bodies have caused toxicity in cetaceans in managed care. Signs include lethargy, vomit­ing, diarrhoea and haemolytic anaemia. The foreign bodies are usually readily identified radiographically.

Research on wild cetaceans and dugongs has detected heavy metal contamination in some species. Adult common bottle-nosed dolphins (Tursiops truncatus) inhabiting the inshore gulfs of SA had higher levels of cadmium compared with other regions (Kemper et al. 1994). Adult Indo-Pacific bottle-nosed dolphins (T. adun- cus) had significant concentrations of cadmium and mercury that were far greater than those reported in Tursiops spp. from the east coast of Australia, and com­parable to levels recorded in common bottle-nosed dol­phins from the UK (Lavery et al. 2008). Metallothionein (MT) concentration, renal damage and bone malforma­tions were investigated in 38 adult Indo-Pacific bottle­nosed dolphin carcases to determine any associations with cadmium, copper, zinc, mercury, lead and selenium. Significantly higher concentrations of cadmium, copper and zinc in the liver were observed in dolphins showing evidence of more advanced renal damage. Two dolphins had high metal burdens, high MT concentrations, renal damage and evidence of bone malformations, indicating possible severe and prolonged metal toxicity (Lavery et al. 2009). Liver concentrations of arsenic, chromium, iron, lead, manganese, mercury and nickel in several dugongs (Dugong dugon) were elevated in comparison with concentrations previously reported (Haynes et al. 2005). Concentrations were similar in male and females and generally higher in mature animals. However, the authors suggest that this level of bioaccumulation does not represent a significant risk to Great Barrier Reef dugong populations, particularly in the context of other pressures associated with anthropogenic activities (Haynes et al. 2005).

3.3 Persistent organic pollutants

Persistent organic pollutants (POPs) are organic com­pounds that are resistant to environmental degradation. Some are described as endocrine disruptors, causing long-term effects on the endocrine systems of animals and some cause immunosuppression, neurotoxicity, development defects, decreased body weight and liver pathology.

• polychlorinated biphenyls (PCBs)

• dioxins and furans (both industrial byproducts)

• organochlorine pesticides (OCP) (DDT, its metabo­lites, DDE and DDD and lindane, dieldrin, aldrin)

• organophosphate pesticides (OPP) (38 are used in Aus­tralia including coumaphos, parathion, malathion, phosmet, trichlorfon, fenitrothion)

• Per- and polyfluroalkyl substances (PFAS).

POPs analysed in Tasmanian platypus (Ornithorhyn- chus anatinus) tail fat samples varied in different geo­graphical regions. Levels of OCP were related to intensity of agricultural activity, while levels of PCBs were higher near industrial and/or hydroelectric developments (Munday et al. 1998).

Significant differences in POPs concentrations were seen in alopecic Australian fur seals (Arctocephalus pusil- lus doriferus) from Lady Julia Island in Vic. in compari­son to unaffected animals. Causal inference has not yet been established (Taylor et al. 2018). Another recent study investigating POPs and trace elements in livers of long­nosed fur seals (Arctocephalus forsteri) in NSW showed that OCPs, PCBs and PFAS were variably present but OPPs were found not to be chemicals of concern. Lead was detected in the livers of 48% of the wild seals, while the liver selenium to total hepatic mercury molar ratio (Se:THg molar ratio) was >1 which is thought to indicate that selenium is counteracting the pathophysiological effects of mercury on various systems (Hall et al. 2023).

As many species of dasyurid are insectivorous, expo­sure to OPP is a concern, particularly in agricultural areas. Fat-tailed dunnarts and the stripe-faced dunnart (S. macroura) were found to be 10-14 times more sensi­tive to fenitrothion (used to control locusts) compared to eutherian mammals (Story et al. 2011). By contrast in another study, the stripe-faced dunnart was less sensitive to fipronil (used as a crop protectant) than other euthe­rian mammals (Story et al.

Information on OCP levels in marine mammal species in Australian waters is sparse but suggests that levels are low compared with other regions of the world. Significant levels of DDT and PCBs were recorded in common bottle­nosed dolphins (Tursiops truncatus), short-beaked common dolphins (Delphinus delphis) and cape fur seals (Arctocephalus pusillus) (Kemper et al. 1994). Recent data shows that levels of several POPs in dolphins have increased in SA between 1989 to 2014, resulting in more animals that surpass available toxicity thresholds (Weijs et al. 2020).

Concentrations of DDT and PCBs present in sperm whales (Physeter macrocephalus) involved in mass strand­ing events in Tas. were higher than those documented in this species in the Southern Hemisphere previously, but lower than those documented in the Northern Hemi­sphere (Evans et al. 2004).

Dieldrin, DDT (and metabolites) were detected in over half of stranded dugong blubber samples (Haynes et al. 2005). The authors suggest that the bioaccumulation of OCP (other than dioxins) does not represent a significant risk to Qld dugong populations (Haynes et al. 2005).

Bats can be exposed to POPs via consumption of con­taminated water, inhalation or ingestion of contaminated prey (Allinson et al. 2006). POPs have been detected in bats in the NT (Best 1973) and a range of OCP detected in the carcases of southern bent-winged bats (Miniopterus orianae bassanii) were considered a possible cause of population decline (Allinson et al. 2006). Concentrations of other compounds found in synthetic high-density pol­ymers and agrochemicals were also found in these bats (Allinson et al. 2006).

Per- and polyfluoroalkyl substances (PFAS) known for their immunosuppressive and immunotoxicity effects have been recently identified in the livers of Australian pinnipeds from several colonies with higher concentra­tions noted in Australian fur seals (from Vic.) in compari­son to Australian sea-lions (from SA). Maternal transfer of PFAS was also demonstrated (Taylor et al. 2021).

3.4 Bufotoxins

The cane toad (Rhinella marina) first introduced near Cairns in 1935 has since spread south to northern NSW, north to Cape York and west into the NT and WA. Cane toads secrete a mixture of bufotoxins and other com­pounds from the large parotid glands on their neck and almost all life stages of the cane toad are toxic (Hayes et al. 2009). Northern quolls (D. hallucatus) are particu­larly sensitive to bufotoxins and animals will die after simply mouthing a toad without actually consuming it. Death appears to be rapid and there have been no oppor­tunities to treat any animals. Distinctive signs of toxic­ity include intense reddening of lips, gingiva, hard palate, nose, ears, eyes and pouch, epistaxis, ear bleeds and bright purple teats and commonly there is evidence of sand in the mouth (Ujvari et al. 2013). Cane toads have been responsible for the loss of northern quolls across most of Kakadu and elsewhere in NT (Shine 2010; Woinarski et al. 2010; Doody et al. 2021) and maybe implicated in the decline of the northern phascogale (P. pirate), fawn antechinus (A. bellus) and Kakadu dunnart (S. bindi) (Woinarski et al. 2010). In order to mitigate the effects of cane toads, conditioned taste aversion has been successfully used in northern quolls bred in man­aged care in an effort to increase survival of animals bred in managed care when released into areas with known cane toad infestation (O’Donnell et al. 2010). The yellow-footed antechinus (A. flavipes) is thought unlikely to face declines caused by cane toad poisoning because they are more resistant to the effects of the toxin. Red-cheeked dunnarts (S. virginiae) may avoid cane toads and the common planigale (Planigale macu- lata) selectively consumes smaller cane toads (Webb et al. 2008; Webb et al. 2011; Kamper et al. 2013). Bufo- toxin toxicity has also been reported in zoo-housed Tasmanian devils in Qld (Holz 2008). Diagnosis of bufo- toxicosis is presumptive and based on association with having eaten or mouthing a cane toad. There is no spe­cific treatment for bufotoxicosis, although some animals can recover with supportive care.

3.5 Calcinosis cutis/hypervitaminosis D

Soft tissue mineralisation presumed to be caused by vita­min D toxicity has been described in managed common brush-tailed possums (Fowler and Fraser 1993) and man­aged bare-nosed wombats (Vombatus ursinus) (Booth 1999). It is thought to be a syndrome of metastatic calcifi­cation subsequent to persistent elevations in serum calcium levels, most likely from hypervitaminosis D (Bryant and Reiss 2008). In wombats, clinically swollen paws and lameness are seen and radiography of pad lesions demonstrates radiodense calcium deposits in soft tissues. Signs of renal failure are seen and uroliths may be present (Bryant and Reiss 2008). It has been suggested that because wombats are nocturnal they may have a lower requirement for vitamin D3 than eutherian mammals and that condi­tions while in managed care may result in pathologically high levels, leading to excessive uptake of dietary calcium (Bryant and Reiss 2008). Management is dietary modifica­tion and supportive care or euthanasia. Surgical excision of skin lesions was attempted but recurrence was common (Booth 1999).

3.6 Sporidesmin toxicity

An eastern grey kangaroo exhibited polydipsia, weight loss and eventually died. Necropsy revealed a severe dif­fuse chronic cholangiohepatopathy consistent with expo­sure to sporidesmin, the toxic metabolite in the fungus Pithomyces chartarum (Hum 2005).

3.7 Veterinary drug toxicities

Mebendazole at high doses was associated with the devel­opment of a condition termed haemorrhagic septicaemic syndrome in zoo-housed red-legged pademelons (T. stig- matica) (Speare et al. 2004). Animals dosed with mebenda­zole became lethargic, anorexic and developed diarrhoea 5-9 d after the first dose; 80% of animals died or were euthanased 5-11 d after the first dose. Haematology con­firmed thrombocytopenia and leucopenia. Necropsy lesions included haemorrhages in many organs, including the GIT, which was ulcerated and associated with peritoni­tis. It was concluded that illness and deaths were from a compromised inflammatory response and that macropods are more sensitive to the effects of mebendazole on bone marrow than are humans and other animals (Speare et al. 2004).

Fluphenazine decanoate, a long-acting neuroleptic drug, used at 2 mg/kg IM in southern hairy-nosed wom­bats, resulted in profound and prolonged tranquilisation and inappetence (Bryant and Reiss 2008).

Terbinafine toxicity has been reported in a red kanga­roo (T Portas pers. comm.) following oral administration for 21 d at 30 mg/kg sid to treat a fungal otitis externa. At 4 wk after cessation of treatment, the kangaroo was found recumbent with leucopenia and severe anaemia. After initial clinical improvement following blood transfusion, the animal deteriorated, necessitating euthanasia. Histo­pathology of bone marrow revealed a severe blood dys- crasia of all cell lineages.

ACKNOWLEDGEMENTS

I thank Dr Paul Eden for content from the Dasyurid chapter, Dr Lucy Woolford for help with the manuscript and my wife Katrina and son Jamie for their support.