Inhibitory effects of ethionine, an analogue of methionine, on wool growth

Varying amounts of DL-, L- or D-ethionine were administered intravenously to sheep, either as a continuous infusion, usually over 2 days, or as a single injection. Groups of sucking mice and rats, in their first cycle of hair growth, were given subcutaneous injections of DL-ethionine at several dose rates. Ethionine was a potent inhibitor of wool growth in sheep; the L- and D-isomers appeared equally effective. An infusion of 20 mg/kg DL-ethionine (c. 50 mg/kg0.75) given at a daily rate of 10 mg/kg for 2 days, or an injection of 40 mg/kg DL-ethionine (c. 100 mg/kg0.75), were sufficient to cause the growth of very weak wool and allow the fleece to be readily removed by hand within 3 weeks after dosing. The inhibition of wool growth was usually associated with a concentration of ethionine in blood plasma, during intravenous infusion, of 10 mumol/l or higher. An infusion of DL-ethionine at a daily rate of 1 mg/kg for 12 days caused the growth of weak fibres and substantially reduced both length growth rate and diameter of fibres. The toxicity of ethionine to sheep was dependent on the total dose and the duration of administration. An infusion of 40 mg/kg (20 mg/kg daily for 2 days) produced severe effects, but the sheep recovered; a dose of 14 mg/kg (2 mg/kg daily for 7 days) was lethal. The effects of ethionine on wool growth were reduced or prevented by the concurrent infusion of methionine (10-15 mol/mol ethionine). Doses of DL-ethionine as high as 460 mg/kg0.75 failed to cause hair loss in sucking mice. While body growth was severely retarded at this dose, no deaths occurred. Likewise, DL-ethionine failed to cause hair loss in sucking rats, but was lethal to some rats at a dose of 360 mg/kg0.75.