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Description of key information

Acute toxicity: oral: Waiving
Acute toxicity: dermal: Waiving
Acute toxicity: inhalation: NOAEC = 300 mg/m3 (vapors) based on local irritation effect of the nasal cavity epithelium.

Key value for chemical safety assessment

Additional information

Acute oral: In accordance with column 2 of REACH Annex VII, the acute oral study (required in section 8.5.1) does not need to be conducted as the substance is a strong acid (pH=0.45; alkali reserve= 35g NaOH/100g substance; see §4.20) and classified as corrosive.

In an acute oral toxicity study in rats ( Kheilo and Kremneva, 1964; secondary literature), LD0, LD10 and LD100 values of 250, 500 and 1000 mg/kg bw were obtained, respectively. Based on these results a LD50 value between 500 and 1000 mg/kg bw could be determined. Although this LD50 would result in a classification as Acute Oral Tox, Cat 4, it should be noted that the toxic mode of action of TFA is due to its corrosive nature and not because of true systemic toxicity after oral adminstration. For this reason a classification for Acute Oral Toxicity is not considered warrented.

Acute dermal: In accordance with column 2 of REACH Annex VIII, the acute dermal study (required in section 8.5.3) does not need to be conducted as the substance is a strong acid (pH=0.45; alkali reserve= 35g NaOH/100g substance; see § 4.20) and classified as corrosive.

Acute inhalation:

An extended acute inhalation toxicity study was performed similarly to the OECD guideline No. 403, including three concentrations of exposure for NOAEC determination, and relevant additional examinations including broncho-alveolar lavage (BAL) analysis, upper respiratory tract histopathology including the lung analysis, and histopathology of the liver, the kidneys, the testis and the thymus. This study was conducted in compliance with the GLP.

In a preliminary study, male and female Wistar rats (3 animals/sex/concentration) were exposed to vapours of TFA (0; 30 or 300 mg/m3) according to a nose only exposure. At 30 mg/m3, no significant differences were observed in the evaluated parameters (clinical signs, body weight, BAL) between controls and exposed animals, males or females. Effects after BAL were observed in male and female rats exposed to 300 mg/m3. Indeed, in male animals ALP was increased which showed in the ANOVA as an interaction of the factor sexe. The total protein dosage was increased in the highest tested concentration (300 mg/m3). Cellular parameters showed an increase in neutrophils in the broncho-alveolar lavage fluid of male animals of group animal treated with 300 mg/m3 reflected in significant group and sex factors in the ANOVA (p<0.05), a tendency for an interaction. No other parameters were affected. As male animals seemed more sensitive to the effects of exposure to trifluoroacetic acid, they were used for the main study. Based on these results, the concentrations for the main study were chosen to be 30, 100 and 300 mg/m3. Furthermore, it was assumed that at this highest concentration of 300 mg/m3, histopathological findings would be observed.

In the main study, the exposure method was unchanged compared to the preliminary study. Two groups of 5 males/concentration were therefore exposed to TFA vapours at concentrations of 0; 30; 100 or 300 mg/m3 for 4 hours. The animals of the first group/concentration were sacrificed and necropsied one day after the end of the exposure, while the animals of the second group/concentration were sacrificed after a 14-day observation period. This second group was designed in order to study the reversibility of the effects which would be observed at day 1.

Clinical signs were observed, body weight (at day 0, 1, 3, 7, and 14) was measured, gross pathology (at the sacrifice or death of animal) and histopathology were analysed. In addition a broncho-alveolar lavage was performed on the animals of the both groups in order to analyse biochemical parameters such as the total protein content, the alkaline phosphatase (ALP), the lactate Deshydrogenase (LDH), the N-acetylglucosaminidase (NAG) and the gamma-glutamyltransferase (gamma-GT). Furthermore thetotal white blood cellnumber was determined in the BAL.

No mortality nor clinical signs or effect on body weight gain were observed at the tested concentrations during the study. The macroscopic examination of the testes and the thymus performed both one day after exposure and after the 14-day recovery period, could not establish any treatment-related changes. All changes observed were common findings for rats of this strain and age.

At the microscopic level, the examination revealed treatment-related histopathological changes at the second and third levels of the rat nasal cavity within the day following the end of exposure. The histopathological lesions consisted of a very slight focal degeneration of the respiratory epithelium lining the dorsal part of the septum. It was considered as the consequence of irritating local effects of the TFA vapours. This lesion was only observed at the highest tested concentration (300 mg/m3) in 4/5 animals for the second level of the nasal cavity and in 1/5 animal for the third level. Furthermore, this irritating local effect was reversible as there was no irritation of the nasal cavity (all levels considered) in the animals necropsied 14 days after treatment. The histopathological analyses revealed no effect of TFA vapours on the trachea, larynx, lungs, kidneys, liver and testes. Furthermore, no treatment-related differences were recorded between the control group and the TFA exposed groups in any of the biochemical and cellular parameters after the broncho-alveolar lavage on both day 1 and 14 recovery periods.

In conclusion, TFA induced no mortality at the tested concentrations (up to 300 mg/m3). However, at the highest concentration, TFA induced local irritation of the nasal cavity epithelium of the rats. This effect is reversible since no irritation of the nasal cavity was noted in the animals necropsied at the end of the observation period. The NOAEC for local effects based on the nasal cavity epithelium irritation is therefore 300 mg/m3.

Due to the corrosive properties (pH 0.45, 10% solution), an additional hazard statement as 'corrosive to the respiratory tract' (EUH071) is applied for TFA.

Justification for classification or non-classification

Trifluoroacetic acid is classified according to Annex VI of Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008: Trifluoroacetic acid is reported under the Index No 607-091-00-1 and is classified as Acute Toxicity Category 4 (H332, Harmful if inhaled). Due to the corrosive properties (pH 0.45, 10% solution), an additional hazard statement as 'corrosive to the respiratory tract' (EUH071) is applied for TFA.