Registration Dossier

Toxicological information

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non guideline human volunteer study, published in peer reviewed literature, minor restrictions in reporting, fully adequate for assessment.

Data source

Reference
Reference Type:
publication
Title:
The absorption, metabolism and excretion of furfural in man.
Author:
Flek, J. and Sedivec, V.
Year:
1978
Bibliographic source:
Int. Arch. Occup. Environ. Hlth., 41, 159-168

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
basic toxicokinetics
Principles of method if other than guideline:
The absorption, metabolism and excretion of furfural following inhalation or dermal exposure were determined in human volunteers.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Method

Type of population:
general
Subjects:
Six healthy male volunteers (30-55 years old)
Ethical approval:
not specified
Reason of exposure:
intentional
Exposure assessment:
measured
Details on exposure:
Whole body xposure experiments were carried out in a 5.4 x 3.4 x 3.5 m laboratory. The calculated quantity of liquid furfural was evaporated on a hot plate and the vapours were dispersed by ventilators into the laboratory; the atmosphere was analysed at five minutes intervals using GC. Exposure was for 7.5 h (actual) to 7 to 30 mg/m3. Volunteers were dressed in a shirt, trousers and overall. Additionally subjects were exposed by inhalation via a mask and dermally (15min contamination of one hand).
Examinations:
Urine was collected the day prior to exposure and during and after exposure in 2h and 8h intervals. In urine samples, total furoic acid, free furoic acid, furoylglycine and total 2-furanacrylic acid were measured by using GC. Expired air was analysed for furfural using GC.

Results and discussion

Outcome of incidence:
Pulmonary retention was independent of inhaled concentration; the mean value was 77.9%. After termination of exposure, less than 1% of the retained furfural was eliminated in expired air. No unchanged furfural was excreted in urine. The main urinary metabolite of furfural was furoylglycine; 2-furanacryluric acid was determined as minor metabolite. A biological half-life of 2-2.5h was determined. Whole body exposure to furfural vapour not only resulted in inhalation absorption, but also dermal absorption was significant. The amount absorbed by the skin corresponded to 20% to 30% of the dose retained in the lungs. Skin absorption appeared to be dependent on environmental temperature and relative humidity. Dermal exposure (one hand up to wrist) to liquid furfural (inhalation prevented) of 3 volunteers during 15 minutes resulted in uptake of about 26.6 mg furfural, indicating absorption of about 3 microgram furfural/cm2 per minute.

Applicant's summary and conclusion