The protective effect of zinc sulphate in experimental sporidesmin poisoning of sheep

Aqueous solutions of zinc sulphate were administered orally to sheep over 5 days (0.125, 0.5 and 2.0 g Zn⁺⁺/sheep/day) to bracket a 3-day period during which sporidesmin also was dosed. The zinc sulphate treatment gave protection from the effects of sporidesmin when compared with control groups dosed sporidesmin alone. Body weight changes were improved and liverdamage scores, numbers of animals showing photosensitisation, serum levels of glutamic oxaloacetic acid transaminase and total bilirubin were lower. The protective effects of zinc sulphate were obtained at levels well abovethose required for growth and maintenance. Protection increased but at a diminishing rate with increasing dose rate of zinc. Because of the small safety margin which exists between the dose rate of zinc sulphate which will provide adequate protection and that which will cause toxicity the use of zinc for the control of facial eczema is not recommended.     

Urinary excretion of immunoreactive sporidesmin metabolites in sheep in relation to factors influencing susceptibility to sporidesmin intoxication

AIM: To study the urinary disposition of orally administered sporidesmins A and D in sheep and identify factors influencing their kinetics, particularly the influence of breeding for resistance and susceptibility to sporidesmin, the mycotoxin responsible for the hepatogenous photosensitisation, facial eczema. METHODS: A competitive ELISA was used to monitor urinary output of immunoreactive metabolites after the intraruminal administration, to female Romney sheep, of either sporidesmin A or sporidesmin D, the nontoxic analogue. Preliminary characterisation of metabolites was carried out using HPLC with fractions monitored by ELISA. RESULTS: Maximum urinary excretion rates of immunoreactive metabolites occurred 2-8 h after dosing with sporidesmin D and 15-30 h after dosing with sporidesmin A. Sporidesmin D caused no liver injury, as detected by changes in serum enzyme activity, while the liver injury caused by sporidesmin A was greatest for the sheep with the highest cumulative output of metabolite. When sporidesmin D was administered in two separate doses to sheep bred for either resistance or susceptibility to facial eczema, the variability of metabolic output between sheep within groups was much less after the second dose. The mean urinary metabolite excretion was greater for the susceptible than the resistant sheep but the difference was not significant. Potentiation (caused by pre-administration of small doses of sporidesmin A) resulted in a more severe reaction to the dosed sporidesmin A. Urinary output of metabolite was less in the potentiated than in the unpotentiated sheep. When resistant and susceptible sheep were dosed with sporidesmin A after potentiation there was no difference between them in their cumulative totals or excretion rates of immunoreactive metabolites. However, the volume of urine produced by the susceptible sheep was lower and less variable than the resistant sheep and consequently the concentration of their urinary metabolites was higher. Preliminary ELISA examination of HPLC-fractionated urine from a sheep dosed with sporidesmin A indicated the presence of several metabolites of sporidesmin. CONCLUSION: Sporidesmin A and metabolites are rapidly excreted in urine but not as rapidly as sporidesmin D and its metabolites. Only minor differences between sheep bred for resistance and susceptibility were seen. Potentiation caused a more severe reaction to sporidesmin A and less urinary excretion of the sporidesmin and its metabolites. CLINICAL RELEVANCE: This work is part of a programme with the aim of identifying FE-resistant animals without the need for sporidesmin dosing.     

Effects of low dose rates of sporidesmin given orally to sheep

Aim: To examine clinical and subclinical effects of sporidesmin administered orally to sheep at very low daily dose rates for periods of 3 to 48 days.

Methods: Two experiments were conducted. In Experiment A, sporidesmin-A was administered orally to groups of 16 sheep at daily dose rates of approximately 0.0042, 0.0083 and 0.0167 mg/kg bodyweight for 48 days. In Experiment B, the highest of these doses was administered orally for 3, 6, 12, 24 or 48 consecutive days. Parameters of production, clinical findings, organ weights and pathological findings were recorded.

Results: In Experiment A, severe liver lesions and photosensitisation were evident as early as 18 days after commencement of daily low-dose administration of sporidesmin, and were associated with significant bodyweight loss. Significant bodyweight loss also occurred in non-photosensitised sporidesmin-treated sheep. Bodyweight reductions were associated with reduced carcass weights and skin weights in treated animals. Sporidesmin administration was also associated with reduced bodyweight gains and pathological changes of the liver, kidney, hepatic lymph nodes, thymus, adrenal gland, heart and spleen. In Experiment B, only moderate changes occurred in a few sheep in the groups dosed with sporidesmin at 0.0167 mg/kg for 3 or 6 days, but major changes were frequently recorded in animals dosed at this rate for 12 days or longer. These comprised changes in the liver and other organs, and photosensitisation typical of the disease, facial eczema. Results are discussed in relation to animal welfare and economic issues associated with this disease.

Conclusions: Sporidesmin caused significant clinical and sub-clinical disease and reduced animal production at relatively low daily dose rates. The effects of repeated daily low-dose administration of sporidesmin appear to be cumulative. There was considerable variation in susceptibility between individual animals.These results emphasise the considerable production losses and animal welfare effects associated with sporidesmin toxicity in sheep.     

Effects of low dose rates of sporidesmin given orally to sheep

AIM: To examine clinical and subclinical effects of sporidesmin administered orally to sheep at very low daily dose rates for periods of 3 to 48 days. METHODS: Two experiments were conducted. In Experiment A, sporidesmin-A was administered orally to groups of 16 sheep at daily dose rates of approximately 0.0042, 0.0083 and 0.0167 mg/kg bodyweight for 48 days. In Experiment B, the highest of these doses was administered orally for 3, 6, 12, 24 or 48 consecutive days. Parameters of production, clinical findings, organ weights and pathological findings were recorded. RESULTS: In Experiment A, severe liver lesions and photosensitisation were evident as early as 18 days after commencement of daily low-dose administration of sporidesmin, and were associated with significant bodyweight loss. Significant bodyweight loss also occurred in non-photosensitised sporidesmin-treated sheep. Bodyweight reductions were associated with reduced carcass weights and skin weights in treated animals. Sporidesmin administration was also associated with reduced bodyweight gains and pathological changes of the liver, kidney, hepatic lymph nodes, thymus, adrenal gland, heart and spleen. In Experiment B, only moderate changes occurred in a few sheep in the groups dosed with sporidesmin at 0.0167 mg/kg for 3 or 6 days, but major changes were frequently recorded in animals dosed at this rate for 12 days or longer. These comprised changes in the liver and other organs, and photosensitisation typical of the disease, facial eczema. Results are discussed in relation to animal welfare and economic issues associated with this disease. CONCLUSIONS: Sporidesmin caused significant clinical and sub-clinical disease and reduced animal production at relatively low daily dose rates. The effects of repeated daily low-dose administration of sporidesmin appear to be cumulative. There was considerable variation in susceptibility between individual animals. These results emphasise the considerable production losses and animal welfare effects associated with sporidesmin toxicity in sheep.     

Facial eczema in goats: the toxicity of sporidesmin in goats and its pathology

Groups of six goats were orally dosed with sporidesmin at rates of 0.3, 0.6, 1.2 and 2.4 mg of sporidesmin per kg body weight and their responses up to 6 weeks later compared with those of sheep dosed at the same time. Clinical facial eczema and pathological lesions similar to those found in sheep were found in all the goat breeds, but at higher dose rates of sporidesmin than those which caused equivalent lesions in sheep. Saanens were the most susceptible goat breed, requiring 2-4 times as much sporidesmin as sheep to achieve similar effects. G4 and feral goats required 4-8 times the sheep dose of sporidesmin to obtain similar responses. Gamma-glutamyltransferase reached its highest serum levels after 20 days while glutamate dehydrogenase and aspartate aminotransferase reached their highest levels between 10 and 20 days. Alkaline phosphatase did not rise consistently to high levels in affected goats. The elevation in aspartate aminotransferase levels tended to be early and transient; glutamate dehydrogenase early and prolonged; gamma-glutamyltransferase late and prolonged, and'alkaline phosphatase late and minor. There was considerable individual variation in the time at which elevations occurred and the levels which enzymes reached. Cholesterol and bilirubin levels were high if liver injury was severe.     

Spectrofluorometric analysis of phylloerythrin (phytoporphyrin) in plasma and tissues from sheep suffering from facial eczema

AIMS: To study the increase in phylloerythrin concentration in plasma and the disposition of phylloerythrin in skin and other tissues of sheep in which the hepatogenous photosensitisation,facial eczema, had been experimentally induced by dosing with the mycotoxin, sporidesmin. Spectroscopic differences between plasma and skin measurements of animals kept inside and outside after dosing were also studied in order to establish whether phylloerythrin undergoes photodegradation when exposed to sunlight. METHODS: Twenty-six Romney x Polled Dorset (25-30 kg)weaned female lambs were purchased from a commercial flock in the Waikato region, New Zealand. Twenty-two of these lambs were dosed with 0.25 mg sporidesmin/kg liveweight on each of two consecutive days (Days -1 and 0); the remaining four lambs served as controls. Both sporidesmin-dosed lambs and controls were randomly divided into two penned groups, one group housed inside in a darkened room and the others outside, exposed to natural sunlight. The lambs were fed green lucerne pellets and lucerne chaff ad libitum for 10 days prior to dosing and until Day 12 after the first dose; thereafter, all the lambs were fed fresh, cut grass (mainly ryegrass) ad libitum, until the end of the experimental period on Day 26. Plasma samples collected on Days -2, 7, 10, 12, 14, 17, 20 and 25were analysed for gamma glutamyltransferase (GGT) activity, bilirubin concentration, and the fluorescence spectrum of phylloerythrin. Spectrofluorometric analysis of phylloerythrin in skin was performed in vivo on the same days, using an external fiber-optic probe. RESULTS: Eight of 11 lambs (73%) kept outside after sporidesmin dosing became photosensitised during the experimental period. None of the sporidesmin-dosed animals kept inside showed clinical signs of photosensitisation. The GGT activity in plasma increased exponentially during the experimental period in all sporidesmin-dosed animals until it reached a plateau. All plasma obtained from sporidesmin-dosed sheep had spectral characteristics similar to those of phylloerythrin, namely a peak in the excitation spectrum at 422 nm and strong emission band at 650 (SE 1) and 709 (SE 1) nm. The fluorescence under excitation at 422 nm of phylloerythrin added to plasma from control lambs had identical peaks. Emission spectra obtained from plasma from healthy sheep without addition of phylloerythrin showed either no fluorescence or minor fluorescence at around 671 nm. Fluorescence in skin of sporidesmin-dosed animals had similar spectra to that in plasma. The appearance of the phylloerythrin-like spectra occurred 2-3 days later in the skin than in plasma, and phylloerythrin in sunlight-exposed skin did not suffer photodegradation during the course of the study. CONCLUSION: Plasma concentrations of phylloerythrin in healthy sheep were <0.1 micromol/l, and clinical signs of photosensitisation were not evident until concentrations exceeded 0.3 micromol/l. Plasma concentrations of phylloerythrin rose as high as 4.9 micromol/l in some animals. The concentration of phylloerythrin in skin began increasing 2-3 days later than that in blood. Hepatogenous photosensitisation can be diagnosed by analysis of plasma phylloerythrin concentrations using a spectroscopic method.     

First case of pithomycotoxicosis (facial eczema) in the Netherlands

Between mid September and the beginning of November 2005, the Animal Health Service (AHS) received thirteen reports offarms on which several animals showed severe symptoms of solar eczema. Blood chemistry showed very high levels of GOT/AST and GGT indicative of severe liver damage. Farm visits to eight farms showed that the animals--previous to the start of the symptoms--had been grazing 24 hours/day and received no additional feed. Ingestion of poisonous plants or medications was considered unlikely to have caused the liver damage, and liver fluke infections were present on only two farms. Microscopic examination of specimens of grass revealed the presence of spores of Pithomyces chartarum in samples taken from six of nine farms. This fungus produces the mycotoxin sporidesmin, which causes severe liver damage and pithomycotoxicosis (facial eczema). This article is the first to describe Pithomyces chartarum in cattle in mainland Europe. Further research on the distribution and re-occurrence of Pithomyces chartarum infection and sporidesmin survival in grass silage is recommended.     

Protection by iron salts against sporidesmin intoxication in sheep

A number of iron compounds have been shown to protect sheep against the harmful effects of the facial eczema toxin, sporidesmin. Various salts were found to be effective; the oxidation state of the metal was not important although water-solubility did appear to be a prerequisite for prophylactic activity. The effect of iron salts was additive with that of zinc, and it is suggested that the protective action of these compounds results from their ability to inhibit the absorption of copper, consistent with the previously-proposed freeradical mechanism for sporidesmin toxicity.     

Protection by iron salts against sporidesmin intoxication in sheep

A number of iron compounds have been shown to protect sheep against the harmful effects of the facial eczema toxin, sporidesmin. Various salts were found to be effective; the oxidation state of the metal was not important although water-solubility did appear to be a prerequisite for prophylactic activity. The effect of iron salts was additive with that of zinc, and it is suggested that the protective action of these compounds results from their ability to inhibit the absorption of copper, consistent with the previously-proposed free-radical mechanism for sporidesmin toxicity.     

Competition of a sporidesmin-producing Pithomyces strain with a non-toxigenic Pithomyces strain

Sporidesmin, a mycotoxin produced by some strains of Pithomyces chartarum, is responsible for the hepatogenous photosensitisation disease facial eczema, which causes severe losses in agricultural revenue in New Zealand. A sporidesmin-producing strain of P. chartarum, isolated in New Zealand, was grown in co-culture with a South African strain that does not produce the mycotoxin. Competition occurred between the two strains when grown both on agar plates and on dried ryegrass, with a significant decrease in the total amount of sporidesmin produced. Biological control of toxigenic P. chartarum can thus occur under laboratory conditions, raising the possibility of similar control in the field situation.     

Epidemiological and microbiological study of an outbreak of infectious keratoconjunctivitis in sheep

After several thousand sheep had been imported from Australia and New Zealand to Croatia during 1995, many native sheep that had been in contact with the imported animals acquired a severe ocular disease closely resembling infectious keratoconjunctivitis. In affected flocks glucose-fermenting mycoplasma were isolated from 48 per cent of conjunctival swabs and Branhamella ovis from 58 per cent. Twelve of 42 culturally and biochemically identical isolates were identified as Mycoplasma conjunctivae by polymerase chain reaction. From the conjunctivae of two animals M conjunctivae and M arginini were isolated in mixed culture. For many reasons most farmers removed the imported animals from their flocks and only sporadic cases of the disease were recognised in 1996. At the end of 1997, six flocks which were clinically free of the disease but had been affected during 1995, and five flocks with no history of the severe ocular disease were examined clinically and microbiologically, and were found to be free of M conjunctivae infection. At the time, B ovis was cultured almost exclusively from sheep originating from flocks which had been affected during 1995 and/or 1996. It was usually isolated in pure culture or as the predominant bacterial species, and was often accompanied by mild conjunctivitis. There were no microbiologically confirmed new cases of infectious keratoconjunctivitis during 1998 and 1999.     

Parasitic otitis in sheep associated with psoroptes infestation: a clinical and epidemiological study.

Parasitic otitis associated with psoroptes infestation was diagnosed in a small pedigree flock of sheep with aural haematomas, abscessation and cauliflower ears. Thirteen of the 15 lambs were affected but the clinical signs were mild; small, discrete, crusty lesions on the inner aspect of the ear at the junction of its anterior and posterior borders were typical. Nine of the 20 adults were affected but the lesions were more severe. Eighteen of the 64 members of the breed society who responded to a telephone survey reported sheep with similar clinical signs in their flocks. The proportion of animals affected ranged from 1 to 60 per cent with a median value of 16 per cent.     

Effect of dietary composition on abomasal and duodenal myoelectrical activity

The changes in the frequency of abomasal slow waves and their propagation, the abomasal spike burst rate and the duodenal spike burst rate were assessed in sheep fed three diets containing either 100 per cent concentrate, 50 per cent concentrate and 50 per cent forage, or 100 per cent forage. The frequency of abomasal slow waves and spike burst frequency were both significantly reduced in sheep fed the diets high in concentrate when compared with animals fed the 100 per cent roughage diet. The velocity of propagation of the slow waves and the duodenal spike burst frequency were not significantly affected by the dietary composition. The sheep consumed significantly less of the 100 per cent concentrate diet in the 45 minutes before recording than of the other two diets, but the amount of feed consumed was not correlated significantly with the changes observed in the myoelectrical activity. These findings are consistent with an inhibitory effect of concentrate on abomasal motility.     

Pharmacokinetics of ampicillin and pentobarbital in the course of subclinical fascioliasis in sheep

Pharmacokinetics of two common veterinary drugs, ampicillin and pentobarbital, were determined in sheep before and four, eight, 12, 17 and 21 weeks after infestation of animals by an oral administration of 150 metacercariae of Fasciola hepatica. The parasite infestation was ascertained by clinical observation of the animals. The pharmacokinetics of ampicillin were not significantly affected by the liver parasitism but the disposition of pentobarbital changed. A significant increase in elimination half-life (around 180 per cent), volume of distribution (130 per cent) and mean residence time (154 to 170 per cent) was observed in sheep infected by the parasite for four to 12 weeks. In these animals, duration of narcosis caused by pentobarbital was prolonged 1.8-fold. The results suggested that both reduced elimination of pentobarbital and impaired distribution of the drug would be responsible for the prolonged duration of narcosis in infected animals.     

Abattoir survey of acquired reproductive abnormalities in ewes.

Abnormalities of the reproductive tract of female sheep were studied by examining 9970 reproductive tracts from cull ewes and 23,536 tracts from nulliparous sheep (prime lambs) over a period of 12 months in abattoirs in south-west England. Overall, 3.37 per cent of the tracts were pregnant (8.11 per cent of cull ewes, and 1.36 per cent of nulliparous sheep), with a peak incidence between September and December. A total of 655 ewes (6.57 per cent) and 459 nulliparous sheep (1.95 per cent) had acquired abnormalities of the reproductive tract. Within these totals, abnormalities of the ovaries accounted for 3.51 per cent (for the ewes) and 10.68 per cent (for the nulliparous sheep) of all the abnormalities, and abnormalities of the ovarian bursa and uterine tube accounted for 42.1 per cent (for the ewes) and 5.23 per cent (for the nulliparous sheep). In addition, uterine lesions (hydrometra and metritis) accounted for 9.92 per cent (for the ewes) and 13.51 per cent (for the nulliparous sheep); lesions of the cervix and vagina (total of 1.44 per cent) and Cysticercus tenuicollis cysts associated with the reproductive tract (total of 3.05 per cent) were less common. Among the ewes the most common ovarian lesions were ovulation tags, and follicular cysts were the most common in nulliparous animals. Lesions such as bursitis, parametritis and abscesses of the reproductive tract were much more common in cull ewes than in nulliparous sheep, probably having arisen from peripartum infections. Hydrosalpinx and hydrometra, in which the intraluminal fluid was clear, were present at relatively high incidence in nulliparous animals, but not in cull ewes. The proportion of tracts containing macerated fetal remnants (2.14 per cent of all abnormalities in cull ewes) was lower than expected. It was considered that the functional significance of many of the lesions, such as ovulation tags and C tenuicollis cysts, was likely to be low, although in some cases of the latter calcification of the cyst had occluded the uterine tubes. Other lesions, notably hydrosalpinx, bursitis and metritis were likely to have made the affected animals sterile. The acquired abnormalities were therefore more significant in terms of individual animal infertility than as a major cause of infertility in flocks.     

Detection and distribution of toxigenic Pasteurella multocida in pig herds with different degrees of atrophic rhinitis

Four herds of pigs were selected which had different degrees of clinical atrophic rhinitis and used different specific counter-measures. In two of them, the clinical signs occurred spasmodically and were slight. The sows, suckling pigs and growing pigs in all the herds were sampled for toxigenic Pasteurella multocida. In one of the slightly affected herds (herd D), the weaners were moved to a second farm for finishing. No toxigenic P multocida were found at the breeding farm, but 50 per cent of the large growing pigs were positive. It seemed that the organism had entered only at the finishing farm and that the mild clinical signs were due to the infection starting in older pigs than usual. In the second mildly affected herd, 47 per cent of the sows and 42 per cent of the growers were infected. Three toxigenic isolates from this herd produced as severe turbinate damage experimentally in specific-pathogen-free pigs as a stock pathogenic strain. Except in herd D, toxigenic P multocida were found in all the age groups of pigs sampled. However, the pattern of distribution of the organism within the herds was not obviously correlated with the severity of the disease. In a fifth herd there were obvious cases of clinical atrophic rhinitis, with marked turbinate atrophy, from which toxi-genic P multocida were recovered in abundance. Subsequently, the clinical disease disappeared and, despite extensive and repeated sampling, the organism was not found again.     

Ruminal lactic acidosis in sheep and goats.

The clinical findings in 37 sheep and goats with acute ruminal lactic acidosis included a disturbed general condition characterised by anorexia, apathy, teeth grinding and muscle twitching, ruminal stasis, and the excretion of soupy or watery faeces. The ruminal fluid of affected animals was milky, had a sour odour and a low pH. There was a predominance of Gram-positive bacteria in smears of ruminal fluid. In comparison with 10 control animals, the rumen fluid of 23 sheep with ruminal lactic acidosis had higher lactic acid and lower volatile fatty acid concentrations. In addition, the affected animals often had haemoconcentration and metabolic acidosis. Treatment included single or repeated transfer of ruminal fluid from healthy cows and, depending on the severity, the administration of antacids, yeast and chlortetracycline, and the intravenous infusion of isotonic sodium chloride and 5 per cent sodium bicarbonate solutions. Of the 37 treated sheep and goats, four died within 24 hours, and three others were euthanased after one, two and three days because their condition rapidly deteriorated. Thirty animals were discharged one to nine days after treatment. Twenty-nine of them (78.4 per cent) recovered completely but one was euthanased later.     

Lack of toxicity of a non-sporidesmin-producing strain of Pithomyces chartarum in cell culture and when dosed to lambs

In New Zealand the fungus Pithomyces charturum normally produces sporidesmin, a mycotoxin, which is responsible for the hepatogenous photosensitisation disease known as facial eczema. Cultures from an isolate of P. charturum, which does not produce sporidesmin, were examined by cell culture and by dosing to lambs to determine whether other toxic metabolites were produced. Acute and long term toxicity studies were conducted with the toxic response being assessed by weight changes, postmortem and histological examination of tissues, blood biochemistry and haematology tests. An extract from a sporidesmin-producing isolate was highly toxic in cell culture, while extracts of the nonsporidesmin-producing isolate did not cause a cytotoxic response to HEp 2 cells. After dosing with a sporidesmin-producing isolate, lambs developed liver lesions and clinical signs of facial eczema. Serum biochemistry changes occurred which were consistent with sporidesmin poisoning. Lambs dosed with the nonsporidesmin-producing isolate, at the rate of thirty times the number of spores of the sporidesmin-producing isolate, showed no observable toxic effects. All organs were of normal appearance, and histological examination of tissues, blood biochemistry and haematology results showed no abnormal changes. Similarly, long term dosing of extracts of the nonsporidesmin-producing isolate, at a rate equivalent to 100,000 spores/g of grass, produced no indication of a toxic response. It was concluded that the nonsporidesmin-producing isolate of P. churtarum contained no toxic metabolites in significant concentration.     

Lack of toxicity of a nonsporidesmin-producing strain of Pithomyces chartarum in cell culture and when dosed to lambs

In New Zealand the fungus Pithomyces charturum normally produces sporidesmin, a mycotoxin, which is responsible for the hepatogenous photosensitisation disease known as facial eczema. Cultures from an isolate of P. charturum, which does not produce sporidesmin, were examined by cell culture and by dosing to lambs to determine whether other toxic metabolites were produced. Acute and long term toxicity studies were conducted with the toxic response being assessed by weight changes, postmortem and histological examination of tissues, blood biochemistry and haematology tests.

An extract from a sporidesmin-producing isolate was highly toxic in cell culture, while extracts of the nonsporidesmin-producing isolate did not cause a cytotoxic response to HEp 2 cells.

After dosing with a sporidesmin-producing isolate, lambs developed liver lesions and clinical signs of facial eczema. Serum biochemistry changes occurred which were consistent with sporidesmin poisoning.

Lambs dosed with the nonsporidesmin-producing isolate, at the rate of thirty times the number of spores of the sporidesmin-producing isolate, showed no observable toxic effects. All organs were of normal appearance, and histological examination of tissues, blood biochemistry and haematology results showed no abnormal changes. Similarly, long term dosing of extracts of the nonsporidesmin-producing isolate, at a rate equivalent to 100 000 spores/g of grass, produced no indication of a toxic response. It was concluded that the nonsporidesmin-producing isolate of P. churtarum contained no toxic metabolites in significant concentration.     

Selenium deficiency, the drug metabolising enzymes and mycotoxicoses in sheep

An examination was made of the relationship in Romney sheep between selenium deficiency and (i) the state of the liver drug metabolising enzyme system, (ii) subclinical liver damage, (iii) susceptibility to facial eczema, and (iv) susceptibility to ryegrasss staggers. The microsomal electron transport detoxifying enzymes based on cytochrome P-450 were unaffected by Se deficiency, suggesting that these enzymes are uninduced on ryegrass/clover pastures. Selenium deficiency had no effect on sporidesmin-induced liver damage, which makes it unlikely that peroxidative events countered by Se-dependent glutathione peroxidase (E.C.1.11.10) have a major role in the mechanism of sporidesmin toxicity. Selenium deficiency did appear to suppress the development of photosensitisation. There was no major effect on ryegrass staggers and no deficiency-induced subclinical liver damage.