Furfuryl alcohol

Endpoint summary

Description of key information

No guideline skin and eye irritation studies are available for furfuryl alcohol.   However, overall the data available for skin irritation are insufficient to classify the material as a skin irritant.  It is concluded furfuryl alcohol has eye irritating properties. Signs of respiratory tract (specifically nasal) irritation were seen in rats after repeated exposure and based on these observations furfuryl alcohol is classified for respiratory irritation.   

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin irritation

Animal data

No guideline study is available for furfuryl alcohol. Some limited data are available as reviewed by US NIOSH (1979). The study reported by Chernousov (1974) used acetone as a solvent. Acetone itself was classified under DSD as causing skin dryness and cracking after repeated exposure (R66) and therefore no conclusion regarding skin irritation potential of furfuryl alcohol can be made. As discussed in the sensitisation endpoint summary (see CSR section 5.5.3), there was evidence of skin irritation in the LLNA studies reported by Frank et al., 2012 and Burleson, 2004. Overall, the existing information is insufficient to conclude that no classification is appropriate and, based on the evidence that there is some skin irritation, it is proposed that furfuryl alcohol should be viewed as a skin irritant under CLP. Note that this is a proposed change to the entry in Annex I of the 31st ATP of the DSD which did not include classification as a skin irritant.

Human data

In relation to skin irritation, there is no reported evidence of skin irritation reported in the workplace e.g. Apol (1973).

Eye irritation

Animal data

For furfuryl alcohol eye irritating effects are reported (as reviewed by NIOSH, 1979). Although information is limited (all Klimisch 4), based on the reported observations, the weight of evidence indicates that furfuryl alcohol should be concluded to have eye irritating properties.

Human data

No substantive information available

Respiratory irritation

Animal data

In the acute inhalation toxicity study effects included respiratory tract irritation (Muijser, 2005). In repeated dose inhalation toxicity studies with furfuryl alcohol, irritating effects were reported (see IUCLID 7.5.2 and 7.7 and CSR Chapter 5.6 and 5.8).

In the 16-day carcinogenicity dose range-finding mouse and rat studies with furfuryl alcohol (NTP, 1999), at the lower doses of 16, 31, 63 and 125 ppm, all exposed rats exhibited acute and/or suppurative inflammation, necrosis, regeneration and squamous cell metaplasia of the respiratory epithelium and necrosis and degeneration of the olfactory epithelium. The respiratory changes can be considered an adaptive response to irritation, with increasing severity with increasing dose. In contrast to rats, at the same dosages, not all exposed mice were affected and there was lower incidence and severity of respiratory and olfactory changes. At the lowest dose of 16 ppm in the mouse, the changes were only minimal.  

After chronic exposure, extensive non-neoplastic alterations in the respiratory and olfactory epithelia and hyperplastic Bowman’s glands were observed in both species. A small increase in the incidence of nasal epithelial tumours was reported in male rats at the top dose of 32 ppm, but not in female rats or in mice (NTP, 1999).  Sustained extensive chronic damage was necessary for tumour development (see IUCLID Section 7.7 and CSR Chapter 5.8) and the NTP (1999) study report notes that the hyperplasia and squamous cell metaplasia in the rat represent conversion of highly specialised nasal tissue into more resistant types of epithelium, representing an adaptive response to chronic irritation. Based on these observations, furfuryl alcohol is considered to have respiratory irritating properties.

Human data

In relation to respiratory irritation, in one study (Ahman et al., 1991) the results indicated an acute restrictiveness induced by exposure to furan resin sand and was most likely induced by furfuryl alcohol in combination with dust and formaldehyde or other chemicals, but the underlying mechanism was unclear. Chronic impairment of lung function was not reported.  In another study (Low & Mitchell, 1985) onset of symptoms in relation to exposure to various fumes and vapours suggested that both irritant and hypersensitivity mechanisms were present.

In conclusion, from these studies it appears that furfuryl alcohol in combination with dust and formaldehyde or other chemicals, or exposure to various fumes and vapour might cause slight irritation and or acute restrictiveness of the lungs. However, a direct correlation with furfuryl alcohol exposure levels could not be clearly established since, in these studies, humans were exposed to mixtures and/or reactions products and not to furfuryl alcohol alone.

In most European countries, a national OEL of 5 or 2 ppm has been established for exposure to furfuryl alcohol in the workplace. In the present dossier on furfuryl alcohol, the limit value of 2 ppm is considered for risk assessment purposes (see CSR Section 5.11).  In repeated dose inhalation toxicity studies in rats, local effects on the nasal epithelium have been reported that warrant classification of furfuryl alcohol under DSD as "irritating for the respiratory system" (Xi, R37).  However, no significant nasal irritation has been reported by workers exposed to furfural alcohol despite its extensive use over the last 60 years or more. To confirm this, a statement ("no nasal irritation has been reported in workers exposed to furfuryl alcohol in a plant which could be attributed to furfuryl acohol") from a production plant is available from Illovo.  Based on the absence of adverse effects reported in workers at the OEL of 2 ppm, equivalent to 8 mg/m3, this limit value is considered as a realistic limit value for assessment of safe use. 

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Effects on respiratory irritation: irritating

Justification for classification or non-classification

Although not classified under Annex VI of CLP, the applicant proposes that furfuryl alcohol is classified as irritating to the skin based on limited evidence, including from the dermal sensitisation studies. The proposed classification is R38 and H315 according to DSD (Dir 67/548/EEC) and CLP (Regulation (EC) No 1272/2008) , respectively.

Furfuryl alcohol is irritating to eyes, leading to classification with R36 and H319 according to DSD (Dir 67/548/EEC) and CLP (Regulation (EC) No 1272/2008), respectively. Irritating effects were shown in the respiratory system (nasal tissue) of rats after repeated exposure. Based on these observations furfuryl alcohol is classified with R37 and H335 according to DSD and CLP, respectively.