2-Propenoic acid, 2-fluoro-, methyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12/5/15 to 2/6/15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

methyl 2-fluoroprop-2-enoate

EC Number:

607-233-2

Cas Number:

2343-89-7

Molecular formula:

C4H5FO2

IUPAC Name:

methyl 2-fluoroprop-2-enoate

Test material form:

other: Light brown liquid

Details on test material:

- Name of test material (as cited in study report): 2-propenoic acid, 2-fluoro, methyl ester, EC Number: 607-233-2
- Physical state: Light brown liquid
- Analytical purity: 98.7 %
- Lot/batch No.: 03026-20140801
- Expiration date of the lot/batch: 27 August 2015
- Storage condition of test material: Approximately 4 °C in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harla Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 179.2 g (variation not exceeding ±20%)
- Fasting period before study: Overnight
- Housing: Suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): Free access to 1014C Teklad Global Rodent diet
- Water (e.g. ad libitum): Free access to main drinking water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): Fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark, twleve hours light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 5 mg/ml
- Amount of vehicle (if gavage):
- Justification for choice of vehicle: Arachis oil BP used as the test substance did not dissolve/suspend in distilled water

MAXIMUM DOSE VOLUME APPLIED: 50 mg/kg, 5 mg/ml.

Doses:

An initial sighting test was conducted aty 300 mg/kg. However, the test animal was killed for humane reasons due to the occurence of clinical signs of toxicity that exceeded the severity limit set forth in the UK Home Office Project Literature.

A dose of 50 mg/kg was than administeered. No mortality was recorded at this level.

No. of animals per sex per dose:

5 animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 30 minutes, 1, 2 and 4 hours after dosing, and then daily. Individual body weights were checked on Day 0, Day 7 and Day 14 or at death.
- Necropsy of survivors performed: Yes

Results and discussion

Preliminary study:

An intial dosing of 300 mg/kg was used in one rat, however this animal was killed for humane reasons one day after dosing due to it showing a severe toxicological effect.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 50 - <= 300 mg/kg bw

Based on:

act. ingr.

Mortality:

Outside of one death at the initial 300 mg/kg dose, no mortality was recorded.

Clinical signs:

other: Signs of systemic toxicity noted in the animal treated at a dose level of 300 mg/kg were prostration, pallor of the extremities, pilo-erection, emaciation, decreased respiratory rate, labored respiration and hypothermia. There were no signs of systemic to

Gross pathology:

Pale liver and pale kidneys were noted at necropsy of the animal treated at a dose level of 300 mg/kg. No abnormalities were noted at necropsy of animals treated at a dose level of 50 mg/kg.

Any other information on results incl. tables

Table 1 Individual Clinical Observations and Mortality Data - 300 mg/kg

Dose level	Animal number and sex	Effects noted after dosing (hours)				Effects noted during period after dosing
		0.5	1	2	4	1 day
300 mg/kg	1 -0 Female	0	0	0	0	Prostration,Pallor of the extremities, Pilo-erection, Emaciation, Decreased respiratory rate, Laboured respiration, Hypothermia. Animal killed for humane reasons.

Table 2 Individual Body Weights and Body Weight Changes - 300 mg/kg

Dose level	Animal number and sex	Body weight at day 0				Body weight at death
300 mg/kg	1 -0 Female	168 g				160 6 g

Table 3 Individual Necropsy Findings - 300 mg/kg

Does level	Animal number and sex	Time of death	Macroscopic Observations
300 mg/kg	1 -0 Female	Humanely killed Day 1	Liver: Pale, Kidneys: Pale

                                                                                                                                                                                                                                                                                       

Table 4 Individual Clinical Observations and Mortality Data - 50 mg/kg

Dose level	Animal number and sex	Effects noted after dosing (hours)				Effects noted during period after dosing (days)
		0.5	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
50 mg/kg	2 -0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
50 mg/kg	3 -0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
50 mg/kg	3 -1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
50 mg/kg	3 -2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
50 mg/kg	3 -3 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Table 5 Individual Body Weights and Body Weight Changes - 50 mg/kg

Dose level	Animal Number and Sex	Body weight at Day			Body Weight Gain During Week
		0	7	14	1	2
50 mg/kg	2 -0 Female	198	218	228	20	10
50 mg/kg	3 -0 Female	172	189	181	17	-8
50 mg/kg	3 -1 Female	170	170	200	0	30
50 mg/kg	3 -2 Female	178	174	181	-4	7
50 mg/kg	3 -3 Female	178	185	193	7	8

                                           

Table 6 Individual Necropsy Findings - 50 mg/kg

Dose level	Animal Number and Sex	Time of Death	Macroscopic Observatrions
50 mg/kg	2 -0 Female	Killed Day 14	No abnormalities detected
50 mg/kg	3 -0 Female	Killed Day 14	No abnormalities detected
50 mg/kg	3 -1 Female	Killed Day 14	No abnormalities detected
50 mg/kg	3 -2 Female	Killed Day 14	No abnormalities detected

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 50 - 300 mg/kg.

Executive summary:

Introduction

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat.

Methods

Following a sighting test at dose levels of 300 mg/kg and 50 mg/kg, a further group of four fasted females was given a single oral dose of test item, as a solution in arachis oil BP, at a dose level of 50 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results

Mortality. The animal treated at a dose level of 300 mg/kg was killed for humane reasons, 1 day after dosing, due to the occurrence of clinical signs of toxicity that exceeded the severity limit set forth in the UK Home Office Project Licence. There were no deaths noted at a dose level of 50 mg/kg.

Clinical Observations. Signs of systemic toxicity noted in the animal treated at a dose level of 300 mg/kg were prostration, pallor of the extremities, pilo-erection, emaciation, decreased respiratory rate, labored respiration and hypothermia. There were no signs of systemic toxicity at a dose level of 50 mg/kg.

Body Weight. Two animals showed body weight loss or no gain in body weight during the first week with expected gain in body weight during the second week. One other animal showed expected gain in body weight during the first week but body weight loss during the second week. Two animals showed expected gains in body weight over the study period.

Necropsy. Pale liver and pale kidneys were noted at necropsy of the animal treated at a dose level of 300 mg/kg. No abnormalities were noted at necropsy of animals treated at a dose level of 50 mg/kg.

Conclusion

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 50 - 300 mg/kg body weight (Globally Harmonized Classification System - Category 3).