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Necropsies on Toggenburg goats culled from a small farm in the Manawatū district of New Zealand, performed at Massey University (Palmerston North, NZ) over a period of 29 years (1991–2019), revealed soft tissue mineralisation, particularly of cardiovascular tissues. The farm spans 10 acres and runs between 15 and 30 Toggenburg goats. The goats are predominantly on pasture comprising a variety of types. Necropsies were performed on all adult goats (n = 45) that died or were euthanised. Histopathology was performed on 42 goats (93%), of which 33 (73%) included sufficient tissues diagnostically relevant to soft tissue mineralisation. The most significant gross findings were in various arteries, with the aorta most commonly affected, followed by the heart and lungs. The aortic intima showed prominent, multifocal to coalescing, raised, wrinkled, white plaques. Microscopically there were multiphasic lesions of mineralisation, chondroid, and osseous metaplasia in the elastic arteries, aorta, heart and lungs. A lumbar vertebra from one goat had prominent, basophilic, fibrillar, tangled matrix lining Haversian canals and lamellae. Blood samples were collected from 15 adult goats in the affected herd and from 10 adult Toggenburg goats from an unaffected herd. Samples were collected by jugular venipuncture at 2-month intervals for 12 months (April 2018–March 2019). Concentrations of calcium, phosphorus, 25-hydroxyvitamin D2 and D3 (25OHD2, 25OHD3) in serum were analysed. The concentration of total 25OHD in serum was 34.2 (95% CI = 18.9–49.4) nmol/L (p < 0.001) higher in goats from the affected herd than in goats from the unaffected herd. Serum 25OHD2 concentration was 46.2 (95% CI = 39.2–53.2) nmol/L higher (p < 0.001) in goats from the affected herd compared to the unaffected herd. Serum Ca concentrations in affected goats were 0.101 (95% CI = 0.005–0.196) mmol/L higher (p = 0.039) than unaffected goats, but remained within the reference range. There was no evidence of a difference in serum 25OHD3 and P concentration between the herds. All paddocks on the property were surveyed every 2 months along evenly spaced line transects, and then further traversed perpendicularly to form a grid. No known calcinogenic species were identified. Known plant sources of vitamin D identified on the farm included mushrooms (species not defined), Dactylis glomerata, lichen, pine pollen, and algae. Soft tissue mineralisation and enzootic calcinosis. Veterinarians are alerted to the possibility of either enzootic calcinosis in goats and the potential occurrence of calcinogenic plants in New Zealand; or chronic vitamin D toxicosis of non-plant origin. [ABSTRACT FROM AUTHOR]

Three outbreaks of photosensitisation in 4-5-month-old lambs were investigated near Palmerston North, New Zealand. The first grazed paddock comprised chicory ( I Cichorium intybus i ), the second lucerne (alfalfa, I Medicago sativa i ), and the third perennial ryegrass ( I Lolium perenne i ) and white clover ( I Trifolium repens i ); these paddocks appeared virtually weed-free. In those days the term "trefoil" implied medicks and clovers, whereas nowadays this name is reserved for I Lotus i spp. Since, to date, the weight of evidence is limited to field evidence of primary phototoxicity only, both I Lotus i spp., as well as the clovers and lucerne fall into the recently proposed B1 confidence ranking classification (Collett [5]). [Extracted from the article]

Cattle occasionally develop brassica-associated liver disease (BALD) and photosensitisation when grazing turnip or swede ( Brassica spp.) forage crops. The liver toxin in these brassica varieties has yet to be discovered. Progoitrin is the dominant glucosinolate in incriminated crops. Apart from goitrin, progoitrin hydrolysis yields the nitrile, 1-cyano-2-hydroxy-3-butene (CHB), and the epithionitrile, 1-cyano-2-hydroxy-3,4-epithiobutane (CHEB). The two compounds were custom-synthesised. In a small pilot trial, New Zealand White rabbits were given either CHB or CHEB by gavage. Single doses of 0.75 mmol/kg of CHB or 0.25 mmol/kg of CHEB were subtoxic and elicited subclinical effects. Higher doses were severely hepatotoxic, causing periportal to massive hepatic necrosis associated with markedly elevated serum liver biomarkers often resulting in severe illness or death within 24 h. The possibility that one or both of these hepatotoxic nitriles causes BALD in cattle requires further investigation.

A large outbreak of liver toxicity in dairy cows that were consuming swede (rutabaga, Brassica napus ssp. napobrassica ) crops in Southland and Otago, New Zealand in 2014 prompted the search for the toxin(s) responsible for brassica-associated liver disease (BALD). Analysis of swede plant material showed that the ultra-dominant glucosinolate was progoitrin. The two nitrile derivatives of progoitrin, 1-cyano-2-hydroxy-3-butene (CHB, also known as crambene) and 1-cyano-2-hydroxy-3,4-epithiobutane (CHEB), were custom-synthesised. In this pilot trial, individual progoitrin nitriles were administered by gavage to rats in order to establish a "subtoxic" dose, i.e. the dose where apparently clinically normal rats show liver injury based on altered serum biochemical indicators and histological lesions. We found that consecutive daily doses of 1 mmol/kg CHB produced severe pancreatic and mild liver histological lesions in the absence of notable biochemical changes in clinically normal rats. No evidence of a cumulative effect was seen. Single doses of 1 mmol/kg of CHEB caused elevated concentrations of serum creatinine and distinctive renal and stomach histological lesions in apparently clinically normal rats. Consecutive daily 1 mmol/kg doses of CHEB had a considerable cumulative effect and proved severely hepato- and nephrotoxic with creatinine concentrations peaking after three daily doses. Three other commercially available nitriles (3-butenenitrile, 4-pentenenitrile and 5-hexenenitrile) derived from minor glucosinolates in the swedes were also investigated in this pilot trial. Single combined 1 mmol/kg doses of both progoitrin nitriles as well as these two nitriles plus small doses of the other three failed to demonstrate any synergism, however, the characteristic and apparently dominant effects of CHEB were consistently demonstrated. The results of this pilot study confirmed the previously reported pancreatotoxicity of CHB and nephrotoxicity of CHEB. CHEB also caused intraepithelial pustules, submucosal oedema, erosions and ulcers in the squamous portion of the stomach. These stomach lesions, as well as the renal lesions, appear identical to those caused by another epithionitrile, 1-cyano-3,4-epithiobutane, derived from gluconapin, which was a minor glucosinolate in the swedes. Because of the fact that cyanide can be released with the metabolism of some nitriles, we analysed cyanide in the livers of treated rats. The liver of a rat dosed with 1 mmol/kg of 3-butenenitrile contained 0.5 μg/g of cyanide. The hypothesis that BALD is due to nitrile toxicity requires further testing., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

Introduction: Photosensitization is a common clinical sign in cows suffering from liver damage caused by the mycotoxin sporidesmin. This disease, called facial eczema (FE), is of major importance in New Zealand. Current techniques for diagnosing animals with subclinical sporidesmin-induced liver damage (i.e. without photosensitization) are nonspecific. In addition, little is known of the mechanisms involved in sporidesmin resistance, nor the early effects seen following low-dose sporidesmin intoxication., Objective: The objective of this study was to identify individual metabolites or metabolic profiles that could be used as serum markers for early stage FE in lactating cows., Methods: Results are presented from a 59-day sporidesmin challenge in Friesian-cross dairy cows. Serum metabolite profiles were obtained using reversed phase ultra-performance liquid chromatography (UPLC) electrospray ionization mass spectrometry (MS) and UPLC tandem MS. Multivariate and time series analyses were used to assess the data., Results: Statistical analysis, both with and without the temporal component, could distinguish the profiles of animals with clinical signs from the others, but not those affected subclinically. An increase in the concentrations of a combination of taurine- and glycine-conjugated secondary bile acids (BAs) was the most likely cause of the separation. This is the first time that MS methods have been applied to FE and that bile acids changes have been detected in cattle exposed to sporidesmin., Conclusions: It is well known that BA concentrations increase during cholestasis due to damage to bile ducts and leakage of the bile. This is the first study to investigate metabolomic changes in serum following a sporidesmin challenge. Further work to establish the significance of the elevation of individual BAs concentrations in the serum of early-stage sporidesmin-poisoned cows is necessary., Competing Interests: Compliance with ethical standardsThe authors declare no conflicts of interest.All experimental procedures were approved by the Massey University Animal Ethics Committee (MUAEC; Protocol No. 11/23), and animals were cared for in accordance with the New Zealand Animal Welfare Act (1999).