Toxicity and cell proliferation in the liver, kidneys and nasal passages of female F-344 rats, induced by chloroform administered by gavage

• Published in: Food and chemical toxicology Vol. 33; no. 6; pp. 443 - 456
• Main Authors: Larson, J.L., Wolf, D.C., Méry, S., Morgan, K.T., Butterworth, B.E.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 1995; New York, NY Elsevier Science
• Subjects: Animals; Biological and medical sciences; Body Weight; Cell Division - drug effects; cell growth; chloroform; Chloroform - administration & dosage; Chloroform - toxicity; Dose-Response Relationship, Drug; Female; Food toxicology; Intubation, Gastrointestinal; Kidney - cytology; Kidney - drug effects; Kidney - pathology; kidneys; liver; Liver - cytology; Liver - drug effects; Liver - pathology; Medical sciences; mice; Necrosis - chemically induced; nose; Olfactory Mucosa - cytology; Olfactory Mucosa - drug effects; Olfactory Mucosa - pathology; Organ Size; Rats; Rats, Inbred F344; toxicity; Toxicology; PBS; NBF; ULLI; IM; OSOM; ISOM; NOEL; LI; BrdU; Volatile compound; Cell proliferation; Drinking water; Chloroform; Rat; Toxicity; Liver; Rodentia; Oral administration; No observed effect level; Contamination; Kidney; Dose activity relation; Carcinogen; Vertebrata; Mammalia; Organochlorine compounds; Animal; Nose
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/0278-6915(95)00013-R

Dose-response relationships were determined for the induction of cytolethality and regenerative cell proliferation in the established target organs (liver, kidneys, and nasal passages) of female F-344 rats given chloroform daily by gavage. Rats were administered chloroform dissolved in corn oil at doses of 0, 34, 100, 200 or 400 mg/kg/day for 4 consecutive days or for 5 days/wk for 3 wk. Bromodeoxyuridine (BrdU) was administered through an implanted osmotic pump 3.5 days prior to autopsy to label cells in S-phase. Cells in S-phase were visualized immunohistochemically in tissue sections and the labelling index (LI) calculated as the percentage of cells in S-phase. Mild degenerative centrilobular changes and dose-dependent increases in the hepatocyte LI were observed after administration of 100 mg or more chloroform/kg/day. Rats given 200 or 400 mg/kg/day for 4 days or 3 wk had degeneration and necrosis of the proximal tubules of the renal cortex. Regenerating epithelium lining proximal tubules was seen histologically and as an increase in LI. Dose-dependent increases in LI were observed in the kidneys at doses of 100 mg or more cholorform/kg/day at both 4 days and 3 wk. Two distinct treatment-induced responses were observed in specific regions of the olfactory mucosa lining the ethmoid region of the nose. A peripheral lesion was seen at all doses used and included new bone formation, periosteal hypercellularity and increased cell replication. A central lesion was seen at doses of 100 mg or more chloroform/kg/day and was characterized by degeneration of the olfactory epithelium and superficial Bowman's glands. These observations define the dose-response relationships for the liver, kidneys and nasal passages as target organs for chloroform administered by gavage in the female F-344 rat.