Furfuryl alcohol

Endpoint summary

Description of key information

Considering the available data, the acute oral LD50 in the rat lies in the range of 132-275 mg/kg.  The acute dermal LD50 lies in the range of 400 to 657 mg/kg.
The inhalation LC50, derived from GLP studies, is > 1000 mg/m3 (1350, 1170 and 820 -2070 mg/m3).   

Additional information

Several reviews of acute toxicity data for furfuryl alcohol are available, which have been summarised by, for example, US NIOSH (1979); JECFA (2001) and INRS (2010). 

Oral

For the rat, reported acute oral LD50 values range from 132 – 275 mg/kg (Woods & Seevers, 1954; Gajewski & Alsdorf, 1949). The only signs of toxicity observed in the rat were convulsions and respiratory paralysis proceeding death at lethal doses (INRS, 2010).  Available data for the mouse do not conflict with these values (NIOSH, 1979; INRS, 2010).

Since furfuryl alcohol rapidly and extensively metabolises to furfural (see CSR Section 5.1), for systemic endpoints it is also relevant to consider the toxicity of furfural. This has recently been evaluated and reported in the EC Risk Assessment Report for furfural (2-furaldehyde) (EC RAR, 2008) with the acute oral LD50 concluded to be in essentially the same range and warranting classification under CLP (Category 3).

Inhalation

There are 3 GLP and guideline studies (Muijser, 2005; Walker, 2016a, b). These studies give LC50 values of 0.820 to 2.07, 1.35 and 1.17 mg/L, respectively. In the studies of Muijser and Walker 2016a exposure was to vapour alone. This was achieved by keeping the vapouriser in a heated water bath to increase the saturated vapour concentration and hence have a vapour only atmosphere containing no liquid aerosol. The heating of the substance prior to administration is a forced condition and does not necessarily reflect real conditions. Therefore, based on the physical properties ( low vapour pressure and high boiling point) in the second study by Walker (2016b) inhalation toxicity was assessed as an aerosol. The obtained LC50 in aerosol was 1.17 mg/L which is in the same range as the obtained LC50 value of 1.35 mg/L in vapour.

In all three studies decedents showed clinical signs consistent with respiratory irritation (decreased breathing rate, rales, gasping, encrustations around the nose) and at post mortem animals had discoloured (red or dark red) lungs. Surviving animals also showed clinical signs of respiratory irritation but these were less severe and typically there were no findings at necropsy (1 animal showed distention of the GI tract).

Other supporting studies report LC50 values of 0.95 mg/L (Jacobson et al, 1958) and 0.88 mg/L (Terrill et al, 1989).

Dermal

Limited data are available. After acute dermal exposure to furfuryl alcohol, the rabbit appears to be more susceptible than the rat. The LD50 has been reported to be in the range of 400 to 657 mg/kg (NIOSH, 2004; Woods & Seevers, 1954).

Justification for classification or non-classification

In accordance with Annex VI, classification under CLP should be at minimum Category 4 for oral and dermal exposure (H302 and H312) and Category 3 for inhalation exposure (H331).

For acute oral and dermal toxicity, based on the available LD50 data reviewed in this dossier, furfuryl alcohol warrants classification under Category 3 for acute exposure via the oral and dermal routes (as Toxic if swallowed H301, Toxic in contact with skin H311).

For inhalation LC50 values of 1.17 mg/L (aerosol) and 1.35 mg/L (vapour) were obtained. These concentrations are close to the Saturated Vapour Concentration (SVC) of 2.1 mg/L at 20C. The criteria for classification state "An LC50 well below the SVC will be considered for classification according to the criteria for vapours: whereas an LC50 close to or above the SVC will be considered for classification according to the criteria for mists (see also OECD GD 39)". Furfuryl alcohol must be classified according to the criteria for mists. Therefore furfuryl alcohol warrants classification under Category 4 for acute inhalation toxicity, H332 Harmful if inhaled.

However, in accordance with the minimum legal classification of Annex VI, classification should be at minimum Category 3 for inhalation exposure. Therefore, the applicable classification is Acute Inhalation Category 3, H331 Toxic if inhaled.