Oral toxicity in weanling and adult rats and in vitro genotoxicity of the veterinary anthelmintic rafoxanide.
The oral toxicity of the veterinary anthelmintic Rafoxanide was evaluated in newborn rats exposed in utero and during lactation. In another group, 3 months of oral treatment started after weaning. Rafoxanide administration to dams (10 mg kg-1) decreased the number of pups per litter, induced high mortality (42%) and delayed the growth of offsprings before weaning. Histopathological examination of the central nervous system revealed vacuolation of the white matter. Vacuolation was particularly severe in the cerebellum of the 14-21-day-old rats. Rafoxanide induced, in some pups (35%), the formation of cataracts. These toxic effects seemed to be reversible and were no longer detectable after a further 3-month administration of Rafoxanide (10 mg kg-1) to rats born of treated dams. In adult rats treated orally for 3 months with 1, 5 or 25 mg kg-1 Rafoxanide, biochemical and haematological tests did not reveal dose-related effects. Rafoxanide had no mutagenic activity in the Ames and CHO/HGPRT tests.
Poul
J M
JM
Centre National d'Etudes Vétérinaires et Alimentaires Laboratoire des Médicaments Vétérinaires, Javené, Fougères, France.
Verlinde
V
V
Abjean
J P
JP
Laurentie
M
M
D000375:Aging / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D004435:Eating / Q000187:drug effects; D005260:Female; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D066298:In Vitro Techniques; D007774:Lactation / Q000187:drug effects; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011888:Rafoxanide / Q000097:blood / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000235:genetics
D009153:Mutagens; D011888:Rafoxanide; D007041:Hypoxanthine Phosphoribosyltransferase