2-furaldehyde

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result:
A toxicokinetic assessment is available which describes the % absorption after oral, inhalation and dermal exposure to furfural for risk assessment purposes. The toxicokinetics of furfural have been reviewed in detail under the EU Existing Substances Regulation (EU RAR, 2008) and by EFSA (2004).

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

For 2-furaldehyde, information on absorption, distribution, metabolism and excretion is available from experimental animals and humans. The toxicokinetics of 2-furaldehyde have been reviewed in detail under the EU Existing Substances Regulation (EU RAR, 2008) and by EFSA (2004). An overview of the information is given below. 

After single oral gavage doses of [¹⁴C]-2-furaldehyde to rats (at 1, 10 or 60 mg/kg bw) or mice (at 1, 20 or 200 mg/kg bw), rapid absorption from the gastro-intestinal tract was observed (Parkash and Caldwell, 1994). After 72 hours, 76-100% of administered radioactivity was excreted in the urine of both species (with over 60% during the first 24h), 3-7% of the administered radioactivity was excreted in the faeces, 5% of the administered radioactivity was exhaled and less than 1% of the administered radioactivity remained in the carcass. 

Rats exposed to single doses of [¹⁴C]-2-furaldehyde (0.127, 1.15 or 12.5 mg/kg bw), gave similar results with about 86 to 89% of the dose excreted in urine, 2-4% excreted in faeces and about 7% recovered as CO₂from the expired air (Nomeir et al., 1992). No unchanged 2-furaldehyde was found in urine. The highest residues of radioactivity were found in liver and kidneys with the lowest level in the brain. 

The metabolites characterised in urine were: 

-furoylglycine; about 80% of the radioactivity in all dose groups in both mice and rats,

-furanacryloylglycine; 10-35% of the radioactivity in all dose groups in both mice and rats,

-furoic acid; about 2% of the radioactivity in high dose male mice and rats, up to 10% in mid and high dose female mice,

-furanacrylic acid; about 2% of the radioactivity in high dose female rats,

-an unidentified very polar metabolite; about 2% of the radioactivity in male rats at all dose groups; 1% in high dose male mice. 

The observed increased excretion of the free acids at higher dose levels (60 mg/kg bw/day in rats, ≥20 mg/kg bw/day in female mice, 200 mg/kg bw/day in male mice) is indicative of a capacity limitation of glycine conjugation (Parkash and Caldwell, 1994). As in laboratory animals, the predominant pathway for detoxification of 2-furaldehyde in humans is oxidation of the aldehyde, resulting in furoic acid, followed by conjugation with amino acids or condensation with acetyl CoA to produce furanacrylic acid (Flek and Sedivec, 1978).

 Respiratory and dermal uptake of 2-furaldehyde were studied in volunteers by exposure to vapour by whole body exposure, respiratory exposure (whole body without dermal exposure), dermal exposure; dermal exposure to liquid 2-furaldehyde was also studied (Flek and Sedivec, 1978).

After combined inhalation and dermal exposure for 8 hours to 30 mg/m³ 2-furaldehyde vapour, 2-furaldehyde was rapidly absorbed through the lungs and skin in human with a mean pulmonary retention of 78% (75-82%). Elimination of 2-furaldehyde in expired air was an insignificant route involving <1% of the amount retained. Furoylglycine was the major metabolite in the 24h urine (8h exposure to 30 mg/m³ furfural vapour followed by 16h non-exposure). Exposure to 2-furaldehyde vapour exclusively by inhalation resulted in a biological half-life of 2 to 2.5 hours (Flek and Sedivec, 1978).  

Whole body exposure to 2-furaldehyde vapour (30 mg/m³) resulted in significant absorption through the skin; this corresponded to 20-30% of the amount absorbed by the lungs and was dependant on the temperature and humidity of the air (Flek and Sedivec, 1978). This was confirmed by observations when dermal exposure to 2-furaldehyde vapour was studied using a gas mask to eliminate inhalation exposure. 

Dermal exposure to liquid 2-furaldehyde, studied in 3 volunteers who exposed their hands up to the wrist for 15 minutes while inhalation was prevented resulted in a mean uptake of 26.6 mg 2-furaldehyde; this was calculated to be about 3μg/cm² per minute. 

Based on the observations on excretion of radioactive metabolites in rats, it can be concluded that 2-furaldehyde is almost completely absorbed from the gastro-intestinal tract after oral absorption. For risk assessment purposes the oral absorption of 2-furaldehyde is set at 90% absorption, with comparable oral absorption in rat and human, in agreement with the EU RAR on 2-furaldehyde (EU RAR 2008). Experiments on the distribution and elimination in the rat have shown no accumulation of 2-furaldehyde in the body (Parkash and Caldwell, 1994; Nomeir et al., 1992). 

For risk assessment purposes the inhalation absorption is set at 100%, based on information on excretion of radioactive metabolites and the lung retention of 2-furaldehyde after inhalation exposure in human; this is in agreement with the EU RAR on 2-furaldehyde (EU RAR 2008). 

For the dermal route, exposure of human volunteers to 2-furaldehyde as either vapour or liquid resulted in significant dermal uptake as determined by excretion of radioactive metabolites in urine. Based on the observed absorption after dermal exposure to either liquid or vapour, the dermal absorption for risk assessment purposes is set at 100%; this is in agreement with the EU RAR on 2-furaldehyde (EU RAR 2008).