Title
Subacute (28-day) toxicity of furfural in Fischer 344 rats: A comparison of the oral and inhalation route
Author
Arts, J.H.E.
Muijser, H.
Appel, M.J.
Kuper, C.F.
Bessems, J.G.M.
Woutersen, R.A.
TNO Voeding
Publication year
2004
Abstract
The subacute oral and inhalation toxicity of furfural vapour was studied in Fischer 344 rats to investigate whether route-to-route extrapolation could be employed to derive the limit value for inhalation exposure from oral toxicity data. Groups of 5 rats per sex were treated by gavage daily for 28 days at dose levels of 6-192 mg/kg bw/day, or exposed by inhalation to concentrations of 20-1280 mg/m3 (6 h/day, 5 days/week) or 160-1280 mg/m3 (3 h/day, 5 days/week) for 28 days. Controls received vehicle (corn oil) or were exposed to clean air. Daily oral treatment with the highest dose of furfural (initially 192 mg/kg bw/day, later reduced to 144 mg/kg bw/day and finally to 120 mg/kg bw/day) resulted in mortality, and in increases in absolute and relative kidney and liver weight in surviving females of this group. Exposure of rats by inhalation for 6 h/day, 5 days/week for 28 days induced mortality at concentrations of 640 mg/m3 and above within 1-8 days. At 640 mg/m3 (3 h/day) and at 320 mg/m3 (3 and 6 h/day) and below, however, exposure was tolerated without serious clinical effects. In contrast, histopathological nasal changes were seen even at the lowest concentration of 20 mg/m3. With increasing exposure concentration, the nasal effects increased in incidence and severity and also expanded from the anterior part to the posterior part, including the olfactory epithelium. It was concluded that the no-observed-adverse-effect level (NOAEL) for oral toxicity was 96 mg/kg bw/day. The NOAEL for systemic inhalation toxicity was comparable, i.e. 92 mg/kg bw/day (corresponding to 320 mg/m3 (6 h/day) or 640 mg/m3 (3 h/day)) assuming 100% absorption. The presence of the histopathological nasal changes at the lowest tested concentration of 20 mg/m3 (corresponding to 6 mg/kg bw/day) proves that for locally acting substances like furfural extrapolation from the oral to the inhalation route is not valid. © 2004 Elsevier Ltd. All rights reserved.
Subject
Biology Health
Toxicology and Applied Pharmacology
Fischer rat
Furfural
Inhalation
Oral
Route-to-route extrapolation
Subacute toxicity
corn oil
furfural
air
animal experiment
animal model
animal tissue
article
comparative study
concentration response
controlled study
exposure
female
histopathology
kidney mass
liver weight
male
mortality
nonhuman
olfactory epithelium
rat
survival
toxicity testing
Administration, Inhalation
Administration, Oral
Animals
Dose-Response Relationship, Drug
Female
Furaldehyde
Kidney
Liver
Longevity
Male
No-Observed-Adverse-Effect Level
Olfactory Mucosa
Organ Size
Rats
Rats, Inbred F344
Zea mays
To reference this document use:
http://resolver.tudelft.nl/uuid:b8e0e4e7-eba6-4f4d-adbd-338545c50fb0
DOI
https://doi.org/10.1016/j.fct.2004.03.014
TNO identifier
237988
ISSN
0278-6915
Source
Food and Chemical Toxicology, 42 (9), 1389-1399
Document type
article