Trifluoroacetyl chloride

Endpoint summary

Description of key information

Acute oral toxicity: Waiving
Acute dermal toxicity: Waiving
Acute inhalation toxicity: The 4-hour LC50 of Trifluoroacetyl chloride was considered to be between 40 and 90 ppm. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

> 40 - < 90 ppm air

Physical form:

inhalation: gas

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

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 trifluoroacetyl chloride (TFAC) is classified as corrosive (see §7.3.1).

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 TFAC is classified as corrosive (see § 7.3.1).

Acute inhalation

A waiver is appropriate for this endpoint as the substance is corrosive and exposure will result in rapid tissue destruction. However two acute inhalation studies are available on trifluoroacetyl chloride. Both acute inhalation study reports have not been formally finalised because the laboratory activities were stopped shortly after finalization of the experimental phase, and it is not possible to obtain an official statement for finalisation because the laboratory has been closed. Even if not finalised, these acute inhalation toxicity studies provide useful information on the acute toxicity profile of the substance as described below.

The first study was performed in 1995 according to GLP. The purpose of this study was to compare the toxicity potential of two batches of different production process of Trifluoroacetyl chloride in rats (i.e. a technical grade and a high purity grade). The method applied was similar to the OECD Testing Guideline No 403. Five males and five females Sprague Dawley rats were exposed per concentration and per batch for 4 hours via inhalation to Trifluoroacetyl chloride. Target concentrations for both batches were 40 and 90 ppm. The animals were exposed in a cylindrical nose-only exposure chamber of polypropylene. After termination of exposure the animals were observed for 14 days for clinical symptoms and changes in body weights. All surviving animals were necropsied and examined.

Mortalities were observed within the first week after exposure. At 40 ppm, no mortality was observed in the group exposed to the high purity grade of product, whereas 2 mortalities were observed for the technical grade product. At 90 ppm 4 males and 4 females died in both groups. All animals showed a marked body weight loss during the first 3 days. At the end of the observation period the weight gains of the survivors resumed up to normal values except for the animals exposed to 90 ppm of high purity grade product which showed a lower body weight gain. The 4-hour LC50 of TFAC was therefo considered to be between 40 and 90 ppm for both groups. 

The acute inhalation toxicity of trifluoroacetyl chloride (TFAC) in the rat was furher investigated in another GLP study. The objective of this study was to investigate the toxic potential of Trifluoroacetyl chloride in male rats after acute inhalation exposure for various combinations of exposure times and exposure concentrations. As the objective of this study was not to determine an acute LC50, the design of this study did not follow the OECD Testing Guideline 403. Fifteen groups of 4 male rats were exposed nose-only to a test atmosphere containing the substance at target concentrations of 140 ppm (30, 45, 60 and 90 minutes), 280 ppm (7.5, 15, 30, 45 and 60 minutes), 560 ppm (7.5, 15 and 30 minutes), 1120 ppm (15 and 30 minutes) and 2240 ppm (30 minutes). All animals were observed for clinical symptoms and for body weight changes up to 14 days after exposure. Hereafter, the surviving animals were killed and necropsied. Subsequently the lungs were removed, weighed and examined microscopically.
Treatment related mortalities were observed in the groups exposed to 2240 ppm for 30 minutes, to 280 ppm for 45 minutes and to 140 ppm for 90 minutes. The mortalities in the 2240 ppm group occurred during or shortly after exposure. ln this group a significant reduction of the respiratory rate was observed. This reaction is interpreted as being caused by the exposure to a corrosive compound. Except for one animal the lung weights of the decedents clearly increased when compared with the lung weights of the survivors. These increased lung weights correlate well with the presence of pulmonary oedema, which was observed at macro- and microscopy. Reversible sublethal symptoms were observed in the groups exposed to 1120 ppm for 15 and 30 minutes and to 280 ppm for 60 minutes. No clinical symptoms were observed in the groups exposed to 140 ppm up to 60 minutes, in the groups exposed to 280 ppm for 7.5, and 30 minutes and in the groups exposed to 560 ppm for 15 and 30 minutes.
For the exposure atmosphere dry air was used to avoid hydrolysis of trifluoroacetyl chloride in the test atmosphere during exposure. Nevertheless, hydrolysis of the test material in the humid air of the respiratory tract is likely to occur resulting in the formation of trifluoroacetic acid and hydrogen chloride. The reactive properties of trifluoroacetic acid and its hydrolysis products are regarded to be the cause of the clinical symptoms, including mortalities, pulmonary oedema and consequently increased lung weights and reduced weight gains. 

Based on the results of these studies, even if not formally finalised, the available acute inhalation toxicity studies show that Trifluoroacetyl chloride is to be classified in the most severe acute toxicity category of the GHS.

Justification for classification or non-classification

The acute inhalation toxicity studies available on Trifluoroacetyl chloride demonstrate that the substance is fatal if inhaled and that the corrosive properties are the primary cause of the clinical symptoms. Based on the available data, Trifluoroacetyl chloride is to be classified as acute inhalation toxicity category 1, H330: Fatal if inhaled.