Toxicological studies on tylosin: its safety as a food additive.

Abstract Tylosin has been shown to be relatively non-toxic following oral administration of large single doses to mice, rats and dogs. Intravenous injection of solutions of various salts showed the acute lethal dose in mice and rats to be 580–695 mg/kg. The toxicity in guinea-pigs was of the same order as erythromycin and penicillin. Diets containing tylosin base up to 1% were well tolerated by rats for 2 yr. Growth was normal and no visceral or haematopoietic damage was produced. Reproduction and lactation studies through three generations showed no alterations in growth or viability at a concentration of 1% in the diet. In an attempt to produce toxic effects, diets containing levels of 2 and 5% tylosin were well tolerated for 2 yr. Lack of palatability of higher concentrations caused retardation of growth and death from malnutrition. Studies designed to demonstrate the possible toxicity of transformation products of tylosin formed during food processing revealed no effect on growth nor any visceral damage. 2-Yr studies in dogs showed that doses up to 100 mg/kg/day, equivalent to 4000 ppm of the diet, produced no visceral or haematopoietic damage. Two dogs had slight sulphobromophthalein retention that returned to normal within 2 wk after withdrawal of treatment. No alteration in the faecal flora was found. Higher daily doses of 200 mg/kg were well tolerated for 2 yr with one of four dogs showing mild pyelonephritis. Of the four dogs that received 400 mg/kg/day for over 2 yr, one revealed bilateral nephrosis, mild chronic pyelonephritis and mild chronic cystitis. Serum levels of tylosin in dogs were detectable at a dietary level of 10 mg/kg/day and were quite high after larger doses. There was no evidence of accumulation in the serum after 2 yr. The no-effect level in rats was 10,000 ppm or higher and in dogs, 4000 ppm. These studies have demonstrated the safety of tylosin and should justify a tolerance for the use of tylosin as a direct food additive.