2-Propenoic acid, 2-[[1,1,2-trifluoro-2-(1,1,2,2,3,3,3-heptafluoropropoxy)ethyl]thio]ethyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021-04-20 to 2021-06-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 17, 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-{[1,1,2-trifluoro-2-(1,1,2,2,3,3,3-heptafluoropropoxy)ethyl]sulfanyl}ethyl prop-2-enoate

EC Number:

864-951-0

Cas Number:

2170099-74-6

Molecular formula:

C10H8F10O3S

IUPAC Name:

2-{[1,1,2-trifluoro-2-(1,1,2,2,3,3,3-heptafluoropropoxy)ethyl]sulfanyl}ethyl prop-2-enoate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River GmbH, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9 wks
- Weight at study initiation: 160 g
- Fasting period before study: from about 17 to 20 hours before start of treatment until 4 hours after administration
- Housing:
During acclimation phase: 3 rats per treatment group were group-housed in type IV Makrolon cages with a shelter on softwood bedding material (ABEDD LTE E-001, ABEDD LAB&VET Service GmbH, Austria). Play tunnels (Ref. 14153, Plexx BV, Netherlands) were placed in the cages as additional enrichment

After treatment: single housed in type III Makrolon cages with a shelter and a play tunnel on softwood bedding material overnight.

Because no clinical symptoms were seen at the end of observation day 1, and the body weight gain was only slightly influenced in the rats treated with 300 mg/kg the rats were group-housed again in type IV Makrolon cages until the end of the observation period.

- Diet: maintenance diet ad libitum (V1534, ssniff Spezialdiäten GmbH, Germany)
- Water: tap water ad libitum (community water supply)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.9 - 23.9
- Humidity (%): 41.1 - 62.9
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.25% aqueous hydroxypropylcellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 g/L for 300 mg/kg bw dose (2000 mg/kg bw was administered undiluted)
- Justification for choice of vehicle: a well-tolerated and established standard vehicle

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD
- Rationale for the selection of the starting dose: The toxic potential of the test item could not be estimated. Therefore, the study was started in 3 females with 300 mg/kg.

Doses:

300, 2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations daily, weighing before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15
- Necropsy of survivors performed: yes
- Clinical signs including body weight: yes
- Other examinations performed: histopathology, only in case of macroscopic findings

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the course of this study.

Clinical signs:

other: No clinical signs of toxicity were observed in the rats treated with 300 mg/kg bw. All rats treated with 2000 mg/kg bw showed a decreased spontaneous activity 3 hours after treatment up to 5 or 6 hours after treatment.

Gross pathology:

At gross pathology, animals were unremarkable except for one rat treated with 2000 mg/kg which exhibited a diffuse red discoloration of the thymus. At histopathology, this finding correlated to moderate acute multifocal hemorrhages. These acute hemorrhages represent a sporadically occurring agonal change and are therefore not considered to be treatment related.

Any other information on results incl. tables

Table 1 body weight

 

Animal No.	Sex	Dose [mg/kg]	Body weight in g on day								Body weight gain in g
			1	2	4	6	8	11	13	15	Day 1 to 15
1	Female	300	155	175	13C	175	132	185	182	189	+34
2	Female	300	149	163	161	164	164	169	169	173	+24
3	Female	300	148	161	168	167	175	177	130	184	+36
4	Female	300	152	171	170	172	173	174	182	188	+36
5	Female	300	149	164	168	167	171	169	173	175	+26
6	l emale	300	146	162	165	167	172	165	175	176	+30
7	Female	2000	172	184	196	191	202	201	206	210	+38
8	Female	2000	177	188	202	211	210	206	219	219	+42
9	Female	2000	168	176	183	187	193	20Ü	200	207	+39
10	Female	2000	164	174	179	184	188	199	199	198	+34
11	Female	2000	166	173	184	186	191	196	196	202	+36
12	Female	2000	176	186	195	196	203	207	208	210	+34

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance has a low acute toxic potential under the conditions of the present study, and the LD50 value is higher than 2000 mg/kg after single oral administration to female rats.

Executive summary:

The objective of the present study was to identify potential toxic effects of the test item after single oral administration to rats in a stepwise procedure in accordance with OECD guideline 423. The study was started with 300 mg/kg in 3 female rats, continued with further 3 females treated with 300 mg/kg. As no mortality was seen after treatment with 300 mg/kg, further 6 females were treated with 2000 mg/kg. Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the Observation period, all surviving rats were sacrificed and subjected to a detailed necropsy.

No mortality occurred during the course of this study. No clinical signs of toxicity were observed in the rats treated with 300 mg/kg. All rats treated with 2000 mg/kg showed a decreased spontaneous activity 3 hours after treatment up to 5 or 6 hours after treatment. The body weight development was inconspicuous throughout the study. The gross pathological examination revealed a diffuse red discoloration of the thymus in one rat treated with 2000 mg/kg which correlated to moderate acute multifocal hemorrhages at histopathology. This Observation represents an agonal change and is therefore not considered to be treatment related.

The test item has a low acute toxic potential under the conditions of the present study, and the LD50 value is higher than 2000 mg/kg after single oral administration to female rats.