Toxicity and cell proliferation in the liver, kidneys and nasal passages of female F-344 rats, induced by chloroform administered by gavage.
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 chloroform/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.
Larson
J L
JL
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.
Wolf
D C
DC
Méry
S
S
Morgan
K T
KT
Butterworth
B E
BE
D000818:Animals; D001835:Body Weight; D002455:Cell Division / Q000187:drug effects; D002725:Chloroform / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007441:Intubation, Gastrointestinal; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D009336:Necrosis / Q000139:chemically induced; D009831:Olfactory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D009929:Organ Size; D051381:Rats; D011916:Rats, Inbred F344
D002725:Chloroform