The comparative toxicology of narasin in laboratory animals.
The toxicology of narasin has been extensively investigated in several species of laboratory animals. Acute median lethal po doses varied considerably between species (> 10 to 40.8 mg/kg). Animals of various species given acutely toxic doses of narasin manifested similar clinical signs of toxicity, including anorexia, hypoactivity, leg weakness, ataxia, depression and diarrhea. Clinical effects were usually delayed 1 to several days, depending on the dose, and some were reversible even with continued narasin administration. In repeated dose toxicity studies, narasin dosages have been demonstrated at which animals could be exposed daily for long periods of time without producing harmful effects. The no-observed effect levels (NOELs) by the dietary route were 60 ppm in mice and 15 ppm in rats after 3 mo of dosing and 15 ppm in rats after 1 y. In dogs, NOELs were 1 mg/kg body weight after 3 mo and 0.5 mg/kg body weight after 1 y of dosing. In breeding animals, narasin did not affect reproductive performance through 4 generations and was not teratogenic. Two-y chronic bioassays in 2 rodent species showed that narasin did not produce cumulative toxicity or carcinogenicity. In genetic toxicity tests narasin was not mutagenic to bacterial or mammalian cells and did not induce DNA repair or sister chromatid exchange. Narasin neither caused dermal toxicity nor skin sensitization, but was a severe eye irritant in rabbits. In dogs, local irritation and systemic toxicity occurred following repeated inhalation exposure to narasin aerosol concentrations greater than 0.114 mg/M3 of air.(ABSTRACT TRUNCATED AT 250 WORDS)
Novilla
M N
MN
Lilly Research Laboratories, Division of Eli Lilly and Company, Greenfield, IN 46140.
Owen
N V
NV
Todd
G C
GC
D000280:Administration, Inhalation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D011247:Pregnancy; D011714:Pyrans / Q000008:administration & dosage / Q000633:toxicity*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects
D000900:Anti-Bacterial Agents; D011714:Pyrans; C013612:narasin