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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

Constituent 1
Chemical structure
Reference substance name:
2-Propenoic acid, 2-[[1,1,2-trifluoro-2-(1,1,2,2,3,3,3-heptafluoropropoxy)ethyl]thio]ethyl ester
Cas Number:
2170099-74-6
Molecular formula:
C10H8F10O3S
IUPAC Name:
2-Propenoic acid, 2-[[1,1,2-trifluoro-2-(1,1,2,2,3,3,3-heptafluoropropoxy)ethyl]thio]ethyl ester
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:
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.
Body weight:
The body weight development was inconspicuous throughout the study (please refer to table below).
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.

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