Toxicological evaluation and limit values for Methyl-tertiary-butyl ether (MTBE), Formaldehyde, Glutaraldehyde, Furfural

2. Toxicokinetics

Furfural is extensively absorbed in humans after inhalation and in rats after oral administration (IARC 1995).

In a series of experiments, humans (healthy male volunteers aged 30-55 years) were exposed to 7 to 30 mg/m³ furfural vapour for a period of 8 hours. Inspired and expired air was analysed and pulmonary retention was calculated to be 78% (75-82%) and was not related to the level or duration of exposure. (Flek & Sedivec 1978).

Furfural vapour was also absorbed percutaneously. The amount absorbed by the skin corresponded to about 20-30% of the dose retained in the lungs. However, it was rather variable and increased with rising temperature and relative humidity. (Flek & Sedivec 1978).

After administration by gavage of [carbonyl-¹⁴C]furfural to rats at single doses of 0.127, 1.15 or 12.5 mg/kg in corn oil, 86-89% the dose was absorbed. After 72 h, high concentrations of radiolabel were found in liver and kidney, brain had the lowest concentration. The concentrations in liver and kidney were approximately proportional to the dose. (Nomeir et al 1992 - quoted from IARC 1995).

The major route of metabolism of furfural is oxidation to furoic acid, followed by conjugation with glycine to furoylglycine. A minor pathway involves condensation of furoic acid with acetate to form furanacrylic acid, followed by conjugation with glycine to furanacryluric acid. The metabolites are excreted primarily via the kidneys into the urine.

In humans, the main metabolite in the urine was furoylglycine with slight amounts of furanacryluric acid. No free furoic acid was found in urine from exposed persons. The biological half-life was estimated to be 2-2.5 hours. (Flek & Sedivec 1978).

After administration by gavage of [carbonyl-¹⁴C]furfural to rats at single doses of 0.127, 1.15 or 12.5 mg/kg in corn oil, more than 60% of the dose was excreted after 12 h, reaching a plateau after 24 h. The major route of excretion was urine, which contained 83-88% of the dose. About 7% of a dose of 12.5 mg/kg was exhaled as ¹⁴C-carbon dioxide, and 2-4% of the dose was detected in the faeces. Furoylglycine was the major urinary metabolite (73-80% of dose), and furanacrylic acid (3-8%) and furoic acid (1-6%) were minor metabolites. The extent and rate of excretion of furfural metabolites were unaffected by dose. (Nomeir et al 1992 - quoted from IARC 1995).

2.3 Toxicological mechanisms

No data have been found.