Furan

Basic toxicokinetics

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

Test material information

Constituent 1

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.