Tetrahydrofuran

Endpoint summary

Description of key information

The acute oral toxicity of tetrahydrofuran has been determined in adequate studies in the rat following oral, inhalation and dermal administrations.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

1 650 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LC50

Value:

14 700 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute Toxicity: Oral

The acute oral toxicity of tetrahydrofuran has been determined to be low in key and supporting studies in the rat.  In a key study conducted in male and female Wistar rats, mortality was observed at all administered dose levels ranging from 0.50 to 4.00 g/kg bwt. The calculated LD50 value in this latter study was 1.65 g/kg bwt. Clinical signs observed prior to death included depression, ranging from slight to severe. Although not consistently observed, pathological findings included fibrous tissue encasing the heart and lungs; reddening of the pyloric and intestinal mucosa; lung consolidation; thickening of the stomach wall; and test material present in the stomach (highest dose). In a supporting study, the LD50 values for tetrahydrofuran in rats of various ages were reported: in newborn rats, an accurate LD50 could not be determined and was reported as < 1.0 ml/kg bwt; in 14-day-old rats, the LD50 was 2.3 ml/kg bwt; in young adult rats, the LD50 was 3.6 ml/kg bwt; and in older rats, the LD50 was 3.2 ml/kg bwt.

Acute Toxicity: Inhalation

The acute inhalation toxicity of tetrahydrofuran has been determined to be low in key and supporting studies conducted in the rat. In a key study, no mortality was reported in either male or female CD rats following a single, 6-hour exposure at vapor concentrations of 0, 500, 2500 or 5000 ppm. The principle acute effect noted was a concentration-dependent sedation. An acute 6-hour LC50 > 5000 ppm (> 14.7 mg/l) can be assigned in this study.  In a supporting study, male and female Sprague-Dawley rats were exposed to concentrations as high as 127,346 ppm (375.2 mg/l) displayed significant mortality at 30- and 60-minute exposure periods. A LC50 value of 375 mg/l (127,346 ppm) for a 30-minute exposure was reported in this study. Clinical signs of toxicity in this latter study included narcosis, respiratory irritation, and lack of a pain reflex. Pathology noted included acute dilation of the right ventricle of the heart, congestive heart failure, and distended liver. In another supporting study, male and female CD rats were exposed to vapor concentrations of tetrahydrofuran as high as 20,500 ppm for 6-hour exposure periods. There was no mortality reported in this study. Clinical signs included rapid respiration, pawing, scratching, chewing, closing of the eyes and decreased or no response to sound. Mild body weight loss occurred 24 hours post-exposure, followed by normal weight gains. In male rats, an approximate non-narcotic concentration was 15.9 mg/l. For female rats, the corresponding concentration was 16.8 mg/l. The LC50 (6 -hour) in this latter study was in excess of 60.6 mg/l.

Acute Toxicity: Dermal

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 bwt for 24 hours produced no mortality or clinical signs of toxicity. The acute dermal LD50 value was > 2000 mg/kg bwt from this study.

Justification for classification or non-classification

Acute oral toxicity

Based on the results of acute oral toxicity testing, tetrahydrofuran is classified as Xn;R22 (Harmful if swallowed) under the EU DSD classification criteria (EU Directive 67/548/EEC). It is assigned an Acute Toxicity Category 4 rating (Harmful if swallowed) under the EU CLP classification criteria (EU Regulation 1272/2008).

Acute inhalation toxicity

Based on the clear presence of CNS depression in animal studies, tetrahydrofuran is classified as R67 (Vapours may cause drowsiness and dizziness) under the EU DSD classification criteria. Based on the presence of upper respiratory tract irritation in animal studies, tetrahydrofuran would be classified as Xi;R37 (Irritating to respiratory system) under the EU DSD classification criteria. Tetrahydrofuran would be rated STOT SE 3, based on either CNS depression or upper respiratory tract irritation according to the EU CLP classification criteria.

Acute dermal toxicity

Based on the results of the key study (rat dermal LD50 >2000 mg/kg), tetrahydrofuran would not be classified under the EU DSD classification criteria. Similarly, tetrahydrofuran would not receive classification under the EU CLP classification criteria.