Subchronic oral toxicity study of furan in Fischer-344 rats.
Rodent studies have shown that furan is a hepatocarcinogen. Previous studies conducted with high doses showed tumors at nearly 100% incidence at all doses. In this paper, a ninety-day gavage experiment conducted with lower doses (0.0, 0.03, 0.12, 0.5, 2.0, and 8.0 mg/kg bw) to identify a no-observed adverse effect level for hepatotoxicity and to characterize non-neoplastic effects including gross changes and histopathology, clinical biochemistry, hematology, and immunotoxicology is reported. As indicated by changes in serum biomarkers, increased liver weights and gross and histological lesions, the liver is the major target organ affected by furan. There were no changes in body weights, food consumption, or histology in other organs. Some of the serum electrolyte markers, including phosphorus, were altered. There was a significant increase in serum thyroxine and triidothyronine in males. This increase was not accompanied by histological thyroid changes. Immunophenotypic analysis showed that thymic lymphocyte maturation was altered in male rats. Although altered clinical biochemistry and hematological parameters were observed at a dose of > 0.5 mg/kg bw, mild histological lesions in the liver were observed at > 0.12 mg/kg bw. Based on this finding, a furan dose of 0.03 mg/kg bw was proposed as the no-observed adverse effect level for hepatic toxicity.
Toxicology Research Division, Health Products and Food Branch, Bureau of Chemical Safety, Health Canada, Ottawa, Canada. Santokh_gill@hc-sc.gc.ca
S
S
Gill
G
G
Bondy
D E
DE
Lefebvre
A
A
Becalski
M
M
Kavanagh
Y
Y
Hou
A M
AM
Turcotte
M
M
Barker
M
M
Weld
E
E
Vavasour
G M
GM
Cooke
D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004032:Diet; D005260:Female; D005663:Furans / Q000008:administration & dosage / Q000633:toxicity*; D006651:Histocytochemistry; D015994:Incidence; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000378:metabolism
D015415:Biomarkers; D005663:Furans; C039281:furan