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

6. Summary

Description

Pure furfural is a colourless, oily liquid with a pungent, aromatic odour resembling that of bitter almonds. Furfural is soluble in water (83 g/l). It has a relatively low volatility.

Environment

Furfural is a volatile component of a wide range of fruits and vegetables. It has been identified as one of the main components of smoke condensates of pine and cottonwood. No data on environmental fate has been found.

Toxicokinetics

Furfural is extensively absorbed and rapidly eliminated in humans after inhalation and in rats after oral administration. In humans, about 78% was retained by the lungs during 8 hours inhalation of the vapour. The pattern of metabolites appears to be qualitatively similar in humans and in rats, involving oxidation of furfural to furanoic acid with subsequent conjugation, primarily with glycine. The conjugate is excreted in the urine. The biological half-life in humans has been estimated to about 2 hours.

Human toxicity

The very sparse human toxicological data indicate that the main effect of furfural is eye and mucous membrane irritation observed after exposure to furfural vapour in concentrations of 20-64 mg/m³. However, no data concerning systemic effects have been found.

Animal toxicity

In animals, furfural has a relatively high degree of toxicity. An LC₅₀-value of 175 ppm (700 mg/m³) for 6 hours exposure has been reported in rat. Oral LD₅₀-values reported are in the range from 65 to 149 mg/kg in the rat.

Repeated exposure of hamsters to furfural vapour by inhalation caused irritation of the eyes and nose, and hyperplastic atrophy of the nasal olfactory epithelium. A NOAEL of 77 mg/m³ (6 hours/day, 5 days/week for 13 weeks) was considered. In oral subchronic and chronic studies, furfural were primarily associated with hepatic effects. For rats, the most sensitive animal, a LOAEL of 11 mg/kg/day (5 days/week) was considered.

Reproductive and developmental effects

No data on reproductive and developmental effects of furfural have been found.

Mutagenic and genotoxic effects

Furfural exhibits an inconsistent pattern of genotoxic activity, being generally negative in bacterial assays but positive in some eukaryotic systems. Neither chromosomal aberrations nor sister chromatid exchanges were observed in bone-marrow cells of mice treated with furfural in vivo. Gene mutation (in a single study), sister chromatid exchanges and chromosomal aberrations were induced in mammalian cells in vitro. Sex-linked recessive lethal mutations were induced in fruit fly.

Carcinogenicity

Furfural has been tested for carcinogenicity by oral administration in rats and mice. In mice, increased incidences (statistically significant in the high dose group of 175 mg/kg/day) of hepatocellular adenomas and carcinomas (males only) were observed. An increased incidence (not statistically significant) of forestomach papillomas were observed in female mice. Male rats had a low incidence of cholangiocarcinomas, which occur rarely.

There was no evidence of furfural possessing carcinogenic or co-carcinogenic activity in hamsters exposed to furfural vapour for 52 weeks.