Tetrahydro-3-methylfuran

Endpoint summary

Description of key information

The oral Approximate Lethal Dose (ALD) is 5000 mg/kg, which is expected to equate to an LD50 between 3500-5000 mg/kg.
The inhalation Approximate Lethal Concentration (ALC) is >6700 PPM.
The dermal LD50 is >2000 mg/kg-bw based on read-across to the analog substance tetrahydrofuran.

Additional information

Tetrahydro-3-methylfuran (3-methyl-THF) has been adequately characterized for acute toxicity via oral, dermal and inhalation routes. In key and supporting studies, the acute oral toxicity of 3-methyl-THF is low following oral gavage or inhalation.  In rats, the oral Approximate Lethal Dose (ALD) is 5000 mg/kg (DuPont, 1969) and Approximate Lethal Concentration (ALC) is >6700 PPM (DuPont, 1985).  Following inhalation, clinical signs included a diminished startle response during exposure and heavy breathing was observed after inhalation and oral gavage. Rats exposed to 6700 ppm were limp and prostrate.  This low acute toxicity following oral administration or inhalation is supported by read-across to a closely related substance , Tetrahydrofuran (CAS# 109-99-9), in which, the oral LD50 was reported to 1650 mg/kg (Consumer Products Testing Company; 1978) and 2.3 mL/kg bw (1940 mg/kg bw [Kimura et al., 1971]) and the LC50 was reported to be >14.7 ppm (DuPont, 1996) .  Clinical signs included a diminished response to alerting stimulus after 2 hours of exposure by inhalation. In a key study conducted according to currently accepted guidelines and with full GLP compliance, treatment of male and female Wistar rats semi-occlusively with neat tetrahydrofuran at 2000 mg/kg bw for 24 hours produced no mortality or clinical signs of toxicity (BASF, 2009). The acute dermal LD50 value was > 2000 mg/kg bwt from this study. In addition, tetrahydro-2 -methylfuran is reported to have a measured acute dermal LD50 of 4500 mg/kg bwt (Deichmann, W.B.; 1969). In the absence of reliable data to the contrary, and the low acute toxicity following other routes of exposure, it can be concluded 3-methyl-THF is not acutely toxic following dermal exposure and the overall acute toxicity of 3-methyl-THF is low.

Justification for classification or non-classification

Acute oral toxicity

Based on the results of acute oral toxicity testing (ALD, rat = 5000 mg/kg-bw; estimated LD50 between 3500 - 5000 mg/kg-bw), the substance is not classified as toxic by the oral route under the EU DSD classification criteria (EU Directive 67/548/EEC) or the EU CLP classification criteria (Regulation (EC) 1272/2008).

Acute inhalation toxicity

Based on the results of acute inhalation toxicity testing (ALC, rat >6700 ppm; >23.6 mg/l), the substance is not classified as toxic by inhalation under the EU DSD classification criteria (EU Directive 67/548/EEC) or the EU CLP classification criteria (Regulation (EC) 1272/2008). However, given that rats exposed to 3200 ppm and rats exposed to 6700 ppm had a diminished startle response during exposure, and rats exposed to 3200 ppm staggered when they were released from restrainers after exposure, and rats exposed to 6700 ppm were limp and prostrate; all characteristic of narcotic effects, the substance should be classified as R67, Vapours may cause drowsiness and dizziness, under the DSD regulation and as Specific Target Organ Toxicity - Single Exposure (STOT-SE), Category 3, under the CLP regulation.

Acute dermal toxicity

Based on the results of acute dermal toxicity testing for the read-across substance (LD50, rat > 2000 mg/kg-bw) the substance is not classified as harmful or toxic in contact with skin under the EU DSD classification criteria (EU Directive 67/548/EEC) or under the EU CLP classification criteria (Regulation (EC) 1272/2008).