1-Naphthol--single and repeated dose (30-day) oral toxicity studies in the mouse.
The oral toxicity of 1-naphthol in Charles River CD1 mice was investigated in single (2, 1 and 0.5 g/kg body weight) and 30-day repeat dosing (200, 100 and 50 mg/kg body weight) studies. In the single-dose study, animals dosed by oral gavage at 2 g/kg body weight either died or were killed in extremis between 15 and 90 min after dosing, and although the animals treated at 1 g/kg body weight survived to the end of the study (14 days post-dosing), one male in the 0.5 g/kg body weight dose group was killed in extremis approximately 2 hr after treatment. Acute dosing was associated with histopathological lesions seen in the kidneys and stomachs of mice from all treatment groups. The kidney lesions consisted of degeneration of the distal tubule epithelium, papillary necrosis and tubular dilatation. Gastric changes characterized by splitting of the epithelium of the forestomach and sloughing of the superficial epithelium of the glandular mucosa were generally accompanied by vascular congestion and acute inflammatory cell infiltration. In the 30-day study, mice dosed by oral gavage at 50 and 100 mg/kg body weight tolerated the treatment well, as did the female mice treated at 200 mg/kg body weight. Three male mice in the 200 mg/kg body weight group did, however, show gastric histopathological effects. Two of the mice (one killed in extremis on the fourth day of the study with the other surviving treatment) showed focal mucosal erosion, and a third (killed in extremis on the twentieth day of the study) exhibited peeling of the mucosa of the forestomach. Both of these gastric lesions were considered to be related to treatment at 200 mg/kg body weight. None of the mice in the 30-day study showed any kidney lesions or changes in haematology or clinical chemistry parameters.
Poole
A
A
Department of Toxicology, Smith Kline and French Research Limited, Herts, UK.
Buckley
P
P
D000284:Administration, Oral; D000818:Animals; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D006400:Hematocrit; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D009284:Naphthols / Q000008:administration & dosage / Q000633:toxicity*; D012737:Sex Factors; D013194:Staining and Labeling
D009284:Naphthols; C029350:1-naphthol