Trans-2-{4-[difluoro(3,4,5-trifluorophenoxy)methyl]-3,5-difluorophenyl}-5-(trans-4-propylcyclohexyl)-1,3-dioxane

Endpoint summary

Description of key information

Acute oral LD50 > 2000 mg/kg bw (reference 7.2.1 -1)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 10, 2011 - January 24, 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted on December 17th, 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Council Regulation (EC) No. 440/2008 laying down test methods pursuant to Regulation (EC) No. 1907/2006 of the European Parliament and the council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Kißlegg
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 10 weeks (males) and 9 weeks (females)
- Weight at study initiation: The mean initial body weight at the start of study was 158 g (range from 151 to 172 g)
- Fasting period before study: 17 hours before until up to 4 hours after treatment
- Housing: separately in type III Makrolon cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 - 23°C
- Humidity: 51 - 75%
- Photoperiod: 12 hour light - 12 hour dark regime

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

Methocel K4M Premium solution

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 g/L
- Amount of vehicle: 10 mL/kg
- Justification for choice of vehicle: well tolerated and established standard vehicle

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 (m) / 3 (f)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: day 1, 2, 4, 6, 8, 11, 13 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

Standard statistical methods have been applied for data processing.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

All rats survived the observation period.

Clinical signs:

No signs of toxicity were detected in the 3 male and 3 female rats after treatment with 2000 mg/kg of test item.

Body weight:

One female rat showed a reduction of body weight on day 6 of the experimental part. The body weight development of all other rats was inconspicuous throughout the study.

Gross pathology:

The gross pathological examination revealed no organ alterations.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the result of this study, it is concluded that the test item has no acute oral toxic potential and that the LD50 value is higher than 2000 mg/kg after single oral administration in rats.

Executive summary:

The test material was tested for acute toxicity in rats after single oral administration of 2000 mg/kg body weight in accordance with OECD TG 423. For regulatory requirements, prior to testing, an in vitro study was performed to assess the irritation potential by means of the Human Skin Model Test and no irritating potential could be detected. No signs of toxicity were seen in the rats (3 males, 3 females) after treatment with 2000 mg/kg of the test item. One female rat showed a reduction of body weight on day 6 of the experimental part. The body weight development of all other rats was inconspicuous throughout the study. There were no deaths during the course of the study. The gross pathological examination revealed no organ alterations. In conclusion and based on the result of this study, it is concluded that the test item has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg after single oral administration in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant study.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

The test material was tested for acute toxicity in rats after single oral administration of 2000 mg/kg body weight in accordance with OECD TG 423. For regulatory requirements, prior to testing, an in vitro study was performed to assess the irritation potential by means of the Human Skin Model Test and no irritating potential could be detected.No signs of toxicity were seen in the rats (3 males, 3 females) after treatment with 2000 mg/kg of the test item. One female rat showed a reduction of body weight on day 6 of the experimental part. The body weight development of all other rats was inconspicuous throughout the study. There were no deaths during the course of the study.The gross pathological examination revealed no organ alterations. In conclusion and based on the result of this study, it is concluded that the test item has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg after single oral administration in rats.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on actue toxicity, the test item does not require classification according to Regulation (EC) No 1272/2008 (CLP), as amended for the twelfth time in Regulation (EU) 2019/521.