Registration Dossier

Administrative data

Description of key information

The reported acute LC50 values are relatively consistent and show no particular sex- or species related sensitivity. The 4 hr LC50 can be estimated to be about 30000ppm (123000 mg/m3) in the rat, although no Reliability 2 study report is available. A Reliability 2 study is available in the hamster, which reported a 4 hr LC50 value of 28500 ppm (116508 mg/m3). The primary toxic effect is kidney damage (proximal tubule necrosis) observed in the rat at concentrations around 3700 ppm (15100 mg/m3) for 4 hours in absence of any clinincal sign of toxicity.

Key value for chemical safety assessment

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
Value:
116 508 mg/m³

Additional information

In accordance with section 2 of REACH Annex XI acute oral and dermal studies do not need to be conducted as the substance is a gas.

A number of acute toxicity studies have been conducted on TFE by inhalation. The reported LC50 values are relatively consistent and show no particular sex- or species-related sensitivity. Sakharova and Tolgskaya (1977) reported 4 hr LC50 values around 30000 ppm for the mouse, rat and guinea pig. Du Pont determined a 4 hr LC50 of approximately 40000 ppm in the rat (Du Pont, 1959) and 28500 ppm in the hamster (Nash et al, 1980). General toxicity such as sedation was seen at concentrations greater or equal to 20000 ppm in these studies.

None of the studies in the rat were Reliability 2 due to methodological deficiencies, principally the lack of a 14-day post exposure period. The study in the hamster, however, was conducted with an appropriate protocol, including a full 14-day post-exposure period. Most of the deaths reported in this study occurred post-exposure. This study was selected as the key study for the acute toxicity end-point.

Kidney damage occurred in rats exposed to levels as low as 3700 ppm for 4 hours. Histological examination showed degeneration of the epithelium of kidney tubules upon cessation of exposure (at 3700 ppm) and renal tubular fibrosis after a 14 day recovery period. This was considered as irreversible damage (Sarver and Trochimowicz, 1977).

In male rats, necrosis of the proximal tubules in the kidney was observed without any liver damage after exposure to 6000 ppm for 6 hours. Based on nephrotoxicity as judged by urine analysis (changes in alkaline phosphatase and g-glutamyl-transpeptidase levels) at concentrations greater than or equal to 3000 ppm, the no-observed-adverse effect level (NOAEL) on the kidney was 2000 ppm (Odum and Green, 1984).

Justification for classification or non-classification

The 4 hr LC50 in the hamster of 116508 mg/m3 for TFE is above the upper regulatory limit for classification for acute toxicity by inhalation of 20000 mg /m3. Therefore the substance does not need to be classified for acute toxicity according to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation EC No. 1272/2008.

Based on the data from the acute toxicity studies, TFE would not warrant classification for non-lethal target organ effects following a single exposure according to EU Directive 67/548/EEC because significant nephrotoxicity was only observed in the rat following 4 hour exposure to concentrations in excess of 20 mg/l.

However, based on the same data, classification in STOT-SE Cat 2 is warranted according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation EC No. 1272/2008, because significant nephrotoxicity has been observed in the rat following 4-hour exposure to concentration of 3700 ppm. Hazard statement H371 should therefore be assigned to the label for this property.

It should be noted that exposure to these high levels of TFE will not occur in practice due to the explosive nature of the gas and the consequent implementation of area alarms set at 100 ppm in all manufacturing and polymerization plants.