Trifluoroacetyl chloride

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study report was not formally finalized because the laboratory activities were stopped shortly after finalization of the experimental phase.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

not specified

GLP compliance:

yes

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Trifluoroacetyl chloride

EC Number:

206-556-2

EC Name:

Trifluoroacetyl chloride

Cas Number:

354-32-5

Molecular formula:

C2ClF3O

IUPAC Name:

trifluoroacetyl chloride

Details on test material:

no data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

The animals were inspected for signs of illness at the beginning of the acclimatization period. No abnormalities were detected. 20 male and 20 female rats were used. Except during their stay in the exposure chamber the animals had free access to food and water. Animal room condition: 22°C, 30-70% relative humidity, 12 hour light/12 hour dark, ventilation frequency 16 times/hour, hygienic procedures according to standart operating procedure.

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

no data

Analytical verification of test atmosphere concentrations:

yes

Remarks:

During exposure the concentration of test material, the possible degradation products were measured on-line by infrared analysis. Concentrations were calculated on-line by Fourier Transform-Infrared analysis of multicomponent gas mixtures.

Duration of exposure:

ca. 4 h

Concentrations:

40 and 90 ppm

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

The purpose of this study was to compare the toxic potential of two batches of different production process of TFAC in rats and to confirm the LC 50 (78ppm). 20 male and 20 felmales Sprague Dawley derived rats were randomly distributed in groups of 5 and exposed once for 4h via inhalation to TFAC. 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. During this period the animals were observed for clinical symptoms and changes in body weights. All animals were necropsied. The animals were examined for changes of their external appearance and for macroscopical changes in the cervical area and the abdominal and thoracic cavities. The lungs (including the tracheas) were weighed.

Statistics:

no data

Results and discussion

Preliminary study:

no data

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

ca. 78 ppm

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Sex:

male/female

Dose descriptor:

other: mortality

Effect level:

ca. 40 ppm

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 1/10 male and 1/10 female were found dead at 2 and 3 days after exposure

Effect levels 3

Sex:

male/female

Dose descriptor:

LC100

Effect level:

ca. 90 ppm

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 8/10 male and 8/10 female were found dead between 1 and 6 days after exposure.

Mortality:

The mortalities were observed within the first week after exposure.
At 40 ppm: no mortality in the group E (TFAC from process 2); 2 mortalities for the group A (TFAC from process 1)
At 90 ppm: 4 males and 4 females died in the group B (TFAC from process 1); 4 males and 4 females died in the group D (TFAC from process 2).

Clinical signs:

other: All observed clinical signs are reported in the section " any other information on results" below.

Body weight:

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 TFAC of process 2 which showed a lower body weight gain.

Gross pathology:

no data

Other findings:

no data

Any other information on results incl. tables

All observed clinical signs

Group A (40 ppm, process 1), males: 1h post-exposure: apathy (animal 1), slight respiratory difficulties (animals 2,3,7,8), slight reduced respiratoty rates and alertness (all males), severe ptosis (all males), reduced fear reaction and locomotor activity (animals 3 and 7), severe reduced fear reaction (animals 3 and 8), abnormal body posture (animals 2 and 8). 1 day post-exposure: apathy, slight respiratory difficulties, severe reduced fear reaction, locomotor activity, slight piloerection (all animals), abnormal body posture (animals 2 and 8), ptosis (animals 2 and 8). 2 days post-exposure: slighty reduced respiratory rates, alertness, fear reaction and locomotor activity (all males), and ptosis (animal 1), abnormal body posture (animal 4 and 10) 3 days post-exposure: severe tremors (no. 1), slight respiratory difficulties, slight increased respiratory rates (all animals), abnormal body gate (no. 1) 5 days post-exposure: slight stereotypic behaviour (no. 3), slightly reduced alertness, fear reaction and locomotor activity (all males), and ptosis (no. 3 and 7), abnormal body posture (no. 4) 6 days post-exposure: slight abnormal posture (no. 6) 7 days post-exposure: slightly reduced fear reaction and slight ptosis (No. 3 and 7), slightly increased respiratory rate (No. 2,4 and 6), abnormal body posture (no. 2), slight vocalization (no. 6)

Group B (90 ppm, process 1) males: 1h post-exposure: respiratory difficulties (no. 17), decreased alertness (no. 15), decreased locomotor activity (no. 11), abnormal body gait (no. 15), ptosis (no. 14, 17, 18, 19, 12), vocalization (no. 19), abnormal gait (no. 12, 14) 1 day post-exposure: respiratory difficulties (all amles), decreased fear reaction (no. 17), decreased locomotor activity (no. 17), abnoramal gait (no. 17, 15, 19 and all females), ptosis (no. 13) 2 days post-exposure: respiratory difficulties (no. 11, 19, 13 and all females), increased respiratory rates (no. 13, 11, 19 and all females) 3 days post-exposure: respiratory difficulties (no. 13 and 19). 4 days post-exposure: increased respiratory rate (no. 19), decreased fear reaction and locomotor activity (no. 13, 19), abnormal body gait (no. 19). 5 days post-exposure: decreased fear reaction (no. 13, 19, 20), decreased locomotor activity (no. 13), abnormal body gate (no. 19). 6 days post-exposure: decreased fear reaction and decreased locomotor activity (no. 13), abnormal body posture and ptosis (no. 20). The urine of animal 19 contained blood.

Group D (90 ppm, process 2), males: 1h post-exposure: respiratory difficulties (no. 31, 37, 38, 39), decreased fear reaction (no. 36, 37, 39), decreased locomotor activity (no. 31, 33, 36, 37, 38, 39, 40), abnormal body posture (no. 31, 33, 36, 38, 39, 40). 1 day post-exposure: tremors (no. 36, 40), respiratory difficulties (no. 35, 31, 33, 37, 39 and all females), increased respiratory rates (no. 35, 31, 33, 37, 39), ptosis (left eye only, no. 39). 2 days post-exposure: respiratory difficulties ( all animals), increased respiratory rates (all animals), ptosis (no. 31). 3 days post-exposure: abnormal body posture (no. 39), ptosis (no. 39), apathy (no. 40), stereotypic behaviour, respiratory difficulties, increased respiratory rates, straub tail and ptosis (no. 40). 4 days post exposure: increased respiratory rates (no. 39, 40), abnormal body posture (no. 39), piloerection (no. 39, 40), reduced locomotor activity (no. 40). 5 days post-exposure: increased respiratory rates (no. 39, 40), abnormal body posture and piloerection (no. 39).

Group E (40 ppm, process 2) males: 1h post-exposure: respiratory difficulties (no. 43, 45, 50), reduced fear reaction (no. 42, 46, 49), abnormal gait (no. 42, 43, 45, 46, 47, 48, 50), ptosis (no. 43, 45), noisy breathing (no. 45), abnormal posture (no. 46). 1 day post-exposure: ptosis (no. 12 and 46). 2 days post-exposure: increased respiratory rates (no. 49), reduced fear reaction (no. 42, 46, 49), reduced locomotor activity (no. 45, 49), abnormal body posture (no. 42, 45, 46, 49), piloerection (no. 45), ptosis (all males and no. 42, 46), vocalization (no. 41). 3 days post-exposure: abnormal gait (no. 47), piloerection (no. 45, 47, 49), abnormal body posture (no. 42), urine incontinence (no. 46, 48, 50). 8 days post-exposure: vocalization (no. 48,50)

Applicant's summary and conclusion

Interpretation of results:

Category 1 based on GHS criteria

Conclusions:

The 4-hour LC50 of Trifluoroacetyl chloride was considered to be between 40 and 90 ppm.

Executive summary:

The acute inhalation toxicity of trifluoroacetyl chloride (TFAC) in the rat was investigated in a GLP study similar to OECD Testing Guideline 403. The objective 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). 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. ln the animals that died within three days after exposure, the macroscopic findings included changes in the respiratory tract (oedema, emphysema) together with increases in lung weights. Haemorrhagic spots were observed on the surface of the kidneys in the one animal found dead at day 6. At the end of the 14-day observation period, increased lung weights were observed in the males exposed to product of both groups and in the females exposed to high purity grade product group. Whether this increase was sequelae of sublethal pulmonary oedema or resulting from tissue repair reaction was not established. No macroscopic observations were made in the survivors at terminal necropsy. The slope of the concentration mortality relationship is very steep. The difference between both groups (no mortality versus 2/10 fatalities at 40 ppm and equal mortality at 90 ppm) is regarded as not significant. ln addition, the slight effects on respiratory rates do not permit to distinguish a difference between the technical grade and the high purity grade products. The 4-hour LC50 of Trifluoroacetyl chloride was therefore considered to be between 40 and 90 ppm for both groups, resulting in the classification as fatal if inhaled (Category 1).