Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was well documented and meets generally accepted scientific principles, but was not conducted in compliance with GLP.

Data source

Reference
Reference Type:
publication
Title:
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). p. 63 404
Author:
IARC
Year:
1995
Bibliographic source:
http://monographs.iarc.fr/ENG/Monographs/vol63/mono63-16.pdf

Materials and methods

Objective of study:
absorption
distribution
excretion
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Radiolabelled ADME study
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Furan
EC Number:
203-727-3
EC Name:
Furan
Cas Number:
110-00-9
Molecular formula:
C4H4O
IUPAC Name:
furan
Details on test material:
- Name of test material (as cited in study report): Furan
- Radiochemical purity: 99%
- Specific activity: 56mCi/mmol
- Locations of the label: 2, 5
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Duration and frequency of treatment / exposure:
once daily for up to 8 days
Doses / concentrations
Remarks:
Doses / Concentrations:
8 mg/kg/day
No. of animals per sex per dose / concentration:
not stated
Control animals:
no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Furan absorbed rapidly and extensively and only approx. 14% of administered dose was expired as unchanged furan, 11% within the first hour.
Details on distribution in tissues:
Of the 19% of administered radiolabel that remained in tissues, 68% (13% of the dose) was in the liver, with lesser amounts detected in the kidney and gastrointestinal tract.
Concentration of radiolabel increased with multiple doses, by approx 6-fold in the kidney and 4-fold in the liver after 8 doses.
Only 20% of radiolabelled material in the liver could be extracted with organic solvents, remaining radiolabel assumed to be bound covalently to tissue macromaolecules; none of radiolabel was bound to liver DNA.
Blood concentration of radiolabel remained approx. 2-5 nmol equivalents per gram for 8 days after a single dose.
Details on excretion:
After a single dose, 14C-CO2 accounted for 25% of radiolabel, 20% was found in urine and 22% in faeces within 24 hours.
After repeated doses the percentage of radiolabel eliminated in urine increased to 33% after 4 days dosing.
Elimination from the liver appeared to follow first-order kinetics with a half-life of 1.8 days.

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
Analysis of 0-24 hour urine showed at least 10 peaks.
Pattern of metabolites did not change appreciably after multiple doses.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
Furan rapidly and extensively absorbed by rats after oral administration; part of absorbed dose becomes covalently bound to protein, mainly in the liver.