Isopropyl trifluoroacetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From April 22nd to June 22nd 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

September 22nd, 2015

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Isopropyl trifluoroacetate

EC Number:

206-922-1

EC Name:

Isopropyl trifluoroacetate

Cas Number:

400-38-4

Molecular formula:

C5H7F3O2

IUPAC Name:

propan-2-yl 2,2,2-trifluoroacetate

Test material form:

liquid

Details on test material:

Name: Isopropyl trifluoroacetate

Test animals

Species:

rat

Strain:

other: CRL:(WI)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 10 weeks old
- Weight at study initiation: 206 - 234 g
- Fasting period before study: yese
- Housing: Type II polypropylene/polycarbonate
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: yes, at least 18 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.2 – 24.0°C
- Humidity (%): 33 – 73 %
- Air changes (per hr): 15 – 20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: From: April 7th, 2016 To: May 17th, 2016

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Lot/batch no. (if required): SZBF3070V

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: The test item was freshly formulated at a concentration of 200 mg/mL in the vehicle, in the Pharmacy of CiToxLAB Hungary Ltd. on the day of administration. The formulation container was magnetic stirred continuously up to the end of dose administration procedures.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The initial dose level was selected by the Study Director to be that which is most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 per group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed:
* clinical signs: Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
* necropsy: Macroscopic examination was performed on all animals. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.

Statistics:

Not applicable

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Isopropyl trifluoroacetate did not cause mortality at a dose level of 2000 mg/kg bw.

Clinical signs:

other: At the dose level of 2000 mg/kg bw incoordination was observed in 6/6 animals on the day of treatment, decreased activity in 4/6 animals during the first three days after treatment, distended abdomen on Day 2 in 1/6 animal were noted. 2/6 animals showed p

Gross pathology:

No macroscopic observations were seen in animals dosed at 2000 mg/kg bw terminated on Day 14.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Under the conditions of this study, the acute oral LD50 value of the test item Isopropyl trifluoroacetate was found to be above 2000 mg/kg bw in female CRL:(WI) rats.

Executive summary:

The single-dose oral toxicity of Isopropyl trifluoroacetate was performed according to the acute toxic class method (OECD 423 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.Tris) in CRL:(WI) rats.

Two groups of 3 female CRL:(WI) rats were treated with the test item at a dose level of 2000 mg/kg bw (Group 1 and Group 2).

A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after the treatment. The test item was formulated in dimethyl sulfoxide (DMSO) at a concentration of 200 mg/mL at a dose volume of 10 mL/kg bw.

Initially, three females (Group 1) were treated at a dose level of 2000 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group, therefore no further testing was required according to OECD 423 and Commission Regulation (EC) NO 440/2008 of 30 May 2008, B.1.Tris.

Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days -1, 0 and 7 and before necropsy. All animals were subjected to a necropsy and a macroscopic examination.

The results of the study were summarized as follows:

Mortality: Isopropyl trifluoroacetate did not cause mortality at a dose level of 2000 mg/kg bw.

Clinical Observations: At the dose level of 2000 mg/kg bw incoordination was observed in 6/6 animals on the day of treatment, decreased activity in 4/6 animals during the first three days after treatment, distended abdomen on Day 2 in 1/6 animal were noted. 2/6 animals showed piloerection up to Day 5 after treatment and hunched back was observed in 6/6 animals up to Day 5 after treatment. Body Weight and Body Weight Gain There were no effects on body weights or body weight gains that could be attributed to treatment with of Isopropyl trifluoroacetate.

Macroscopic Findings: No macroscopic observations were seen in animals dosed at 2000 mg/kg bw terminated on Day 14.

Conclusion: Under the conditions of this study, the acute oral LD50 value of the test item Isopropyl trifluoroacetate was found to be above 2000 mg/kg bw in female CRL:(WI) rats.