kenzodtoxoles are metabolfsed predcminantly by dmethylenation. The resulting catechols may be readily oxldised in the cell to semiguinones and &nones leading to redox cycling with oxidation of glutathione. To ascertain whether this pathway is involved in the toxicity, tbe effects of a group of beusodioxoles and related structures on glutathione concent and viability of ieolated rat bepatoqtes have bean investigated. Safrole, isosafrale. dihydrasafrole, d~et~~~~p~lb~ene and eugenol all caused a rapid decrease in glutatbione content followed by a decrease in cell viability, although dimetboxypropsnylbenxene had a smaller effect on glutathione and eugenol had a smaller effect on cell viability than the other canpounds. Wexenyl- and octenyl-benzodioxole were the most toxic campounds examined, bowever in each case the decrease in viability preceded the decrease in glutathione content indicating that damage to the plasma membrane may be a prfmary site of action subsequently leading to glutathione leakage. Ally1 benzene had little effect on either glutathione or cell viability whereas catechol caused a marked and prolonged depletion of glutathiene while maintaining higher viability over the 3 hour incubation period then untreated hepatocytes. These results demmetrate that, a) prolonged glutathfone depletion does not necessarily result in cell death, b) there may be a correlation between the ability to form catechol metabolites, glutathione depletion and toxicity among the benzodioxoles and cl an alkenyl side chain can also contribute significantly to the toxicity.

Ergotiem in Livestock Resultinlg frua Ingestion of Slightly Ccmtminated Feeds: Toxicol- ogy Cbsmical Anslysie

KRIEGER, R.I., FLOKES, I.A., MENUEZ-CUERRU, A., HENNINCSEN, C&l., NASER, L.J., PARNELL, M.J., PORTER, J.K., StlUlH, P.38.. and STEELE, E.E. Ml1 Reg. Prog. in Vet. Med. Educ., Dept. of Animal and Vet. Sci., Wash. State Univ. and Univ. of Idaho, Pullman, WA and Maecow, ID.

Severe ergotim in livestock resulted from consumption of feeds which apparently contained such less than g.li; (weight) ergot bodies, Clevice s 1 p purpuresf. Uarl;;: Kentucky blue grass, and possibly other grasses and cecea s were mvo vsd. principal ergot alkaloids were ergotmine, ergoeristine, ergocornine, and ergakryptine in berley, wheat, and blue grass. Lasenesa, gangrene, end poor performance were abserved following week to months of feeding erg&y rations to cattle and swine. Neonatal deaths occurred in swine as a reault of egelactia and the clumsiness of lane sows. Reduced milk productim and abortim in dairy coue wee temporally related to the ergot contmin&ed feeds. Milk productim in goats and egg production in chickena was aherply reduced with mly a b- to i-dny cmtainated feed exposure. These cases have been backed by feeding studies in chicks which have demunetrated dose-dependent toxicity using diets cmtainirq up to ~.LTK ergot bodies. The most significant effect was reduced feed coneunptim end low weight gain. only upon gravi@etric meaaurenents,

Grain grading standards which rely e.g., berley grades ergoty at 0.174, are not

adequate to protect livestock health due to the lack of knowledge concerning the quantitative relationship between ergot body weight, ergot alkaloid content and toxicity.