3-methyl-3-(2,2,3,3,3-pentafluoropropoxy)methyl oxetane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 June 2018 - 10 July 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

482-280-8

EC Name:

-

Cas Number:

449177-94-0

Molecular formula:

C8H11F5O2

IUPAC Name:

3-methyl-3-[(2,2,3,3,3-pentafluoropropoxy)methyl]oxetane

Test material form:

liquid

Details on test material:

Lot No: 2231AM-68E
Expiry date: 01 January 2019
Storage conditions: room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK
- Females; nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks old
- Weight at study initiation: 167-191 g
- Fasting period before study: Overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing
- Housing: Housed in groups of four in suspended solid-floor polypropylene cages furnished with wood flakes.
- Diet and water: Free access to mains drinking water and food (2014C Teklad Global Rodent diet) was allowed throughout the study.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours of continuous dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
For the purpose of the study, the test item was freshly prepared as a solution in DMSO. DMSO was used because the test item did not dissolve/suspend in distilled water or arachis oil. No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation.

Doses:

In the absence of data relating to the toxicity of the test item, 300 mg/kg was chosen as the starting dose. A single animal was treated at 300 mg/kg which resulted in mortalilty. An additional animal was therefore treated at 50 mg/kg. In the absence of toxicity at a dose level of 50 mg/kg, an additional group of animals were treated.

No. of animals per sex per dose:

A total of 5 animals were therefore treated at a dose level of 50 mg/kg.

Control animals:

no

Details on study design:

- Clinical observations were made 30 minutes, 1, 2 and 4 hours after dosing and then daily for up to 14 days.
- Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14 or at death.
- Morbidity and mortality checks were made twice daily, early and late during normal working days and once daily at weekends and public holidays.

All animals were dosed once by gavage with the volume administered to each animal calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Suffcient time was allowed between each dose group to confirm the survival of the previously dosed animals.

Results and discussion

Preliminary study:

Not applicable

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 50 - < 300 mg/kg bw

Based on:

test mat.

Mortality:

At a dose level of 300 mg/kg, the animal was found dead two days after dosing.
At a dose level of 50 mg/kg, there were no deaths.

Clinical signs:

other: At a dose level of 300 mg/kg, signs of systemic toxicity noted were hunched posture, pilo-erection and noisy respiration. At a dose level of 50 mg/kg, no signs pf systemic toxicity were noted during the observation period.

Gross pathology:

No abnormalities detected in 4 females dosed at 50 mg/kg. In one female at 50 mg/kg, the kidneys were noted as dark.
At the dose level of 300 mg/kg, the macroscopic observations were as follows;
Liver: dark
Kidneys: dark
Stomach: gaseous
Gastric mucosa: hemorrhagic
Non-glandular region: henmorrhagic
Small and large intestine: clear colourless test item present

Any other information on results incl. tables

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

Dose Level (mg/kg)	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		1/2	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
300	1-0 Female	H	H	H	0	HP Rn	X	-	-	-	-	-	-	-	-	-	-	-	-

H= Hunched posture; P = Pilo-erection; Rn = Noisy respiration; 0= No signs of systemic toxicity; X = Animal found dead; - = No data, animal dead

Table 2 Individual Clinical Observations and Mortality Data - 50 mg/kg

Dose Level (mg/kg)	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		1/2	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
50	2-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-3 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

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 50-300 mg/kg body weight (Globally Harmonized Classification System - Category 3).

Executive summary:

A study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat. Following an initial test at dose levels of 300 mg/kg and 50 mg/kg, a further four fasted females was given a single oral dose of test item, as a solution in dimethyl sulfoxide at a dose level of 50 mg/kg body weight. Clinical signs and body weight development were monitored during the study.

The animal treated at a dose level of 300 mg/kg was found dead two days after dosing. No mortality and no signs of systemic toxicity were noted in the animals treated at a dose level of 50 mg/kg.

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