phomopsin and Body-Weight

Pure phomopsin was administered to young Merino x Border Leicester wethers by single subcutaneous (SC) and by single and multiple intraruminal (IR) injection. The toxicity after IR injection was influenced by the size of individual doses and the time over which the total dose was given. At high levels of ingestion the toxicity of phomopsin may be limited by absorption rates; with low daily doses the capacity to repair liver damage may be sufficient to prevent cumulative effects. By SC injection a single dose of 10 micrograms/kg approximated the LD50. By IR injection the overall clinical, biochemical and histological responses closest to these of this SC dose resulted from a single dose of 1,000 micrograms/kg. The same total dose administered at daily rates of 50 or 200 micrograms/kg was more toxic and killed all sheep. A single dose of 500 micrograms/kg caused significant liver damage, but no deaths. Single doses of 125 and 250 micrograms/kg and repeated daily doses of 12.5 micrograms/kg over 16 weeks caused no detectable tissue damage. Inappetence was the most sensitive indicator of phomopsin toxicity. About 10% of the sheep differed substantially from the rest of the flock in their susceptibility to phomopsin poisoning.

Topics: Administration, Oral; Animals; Appetite; Aspartate Aminotransferases; Bile Acids and Salts; Bilirubin; Body Weight; Chemical and Drug Induced Liver Injury; Eating; gamma-Glutamyltransferase; Injections, Subcutaneous; Liver; Liver Diseases; Male; Mitosis; Mycotoxins; Sheep; Sheep Diseases; Sulfobromophthalein

The effect of phomopsin, the mycotoxin of Phomopsis leptostromiformis responsible for lupinosis, was examined in pregnant rats and their embryos. A single injection of the rate of 0.025-0.4 mg/kg was administered on days 6, 8, 10, 12 or 14 of pregnancy or repeated injections at the daily rate of 0.03 or 0.09 mg/kg were given on days 6-10 or 11-15. Effects on embryonic development were examined on day 20. A single dose of 0.4 mg/kg or repeated doses of 0.09 mg/kg caused heavy embryonic mortality. Repeated doses of 0.03 mg/kg over days 6-10 caused a lower mortality. Foetuses that survived the higher dose rates were severely retarded in their growth and skeletal ossification was irregular. The incidence of other developmental defects was too low for phomopsin to be unequivocally implicated. The dose levels used induced lesions of lupinosis of varying severity in the dams. Toxicity for dams and embryos was greater when the total dose was administered over 5 days than after a single injection.

Topics: Animals; Ascites; Autolysis; Body Weight; Bone Development; Dose-Response Relationship, Drug; Embryo, Mammalian; Female; Liver; Microphthalmos; Mycotoxins; Ossification, Heterotopic; Placenta; Pregnancy; Pregnancy, Animal; Rats; Rats, Inbred Strains