4-chloromethyl-4''-ethyl-2'-fluoro-[1,1':4',1''-terphenyl]

Endpoint summary

Description of key information

The LD50 value is higher than 2000 mg/kg bw in female rats after single oral administration of the test item (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:

2017-09-20 to 2017-10-18

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:

2001-12-17

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at start of study: 9 weeks
- Weight at study initiation: 164 – 175 g
- Fasting period before study: about 17 to 20 hours before until up to 4 hours after treatment
- Housing: acclimation: 3 animals group houses in type IV Makrolon cages, starting one day before treatment: separately in type III Makrolon cages with wire grid over softwood granules until 4 h after administration or until signs of toxicity subsided
- Diet: ad libitum, exception see above, maintenance diet (V1534, ssniff Spezialdiäten GmbH, Germany)
- Water: ad libitum, tap water, changed at least 3 times per week
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.8 - 23.2
- Humidity (%): 45.9 - 59.5
- Air changes (per hr): not specified but fully air conditioned room
- Photoperiod (hrs dark / hrs light): 12 hour light - 12 hour dark regime

IN-LIFE DATES: From: day 1 To: day 15

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

0.25 % aqueous hydroxypropylcellulose (Methocel® K4M Premium)

Details on oral exposure:

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

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The test item preparation was made directly before administration. Appropriate amounts of the test item were suspended in the vehicle using a spatula, a mini shaker (Vortex Genie 2, Scientific Industries lnc, New York, USA), Ultra-Turrax device (Ultra-Turrax T25, IKA-Werke GmbH & Co. KG, Staufen, Germany) and a magnetic stirrer. The test item preparation was administered within less than 1 hour after preparation.

CLASS METHOD
- Rationale for the selection of the starting dose: Due to the chemical properties of the test item, mortality was not expected at the highest starting dose of 2000 mg/kg bw. Therefore, the study was started with 2000 mg/kg bw in three female rats and continued with further three females at 2000 mg/kg bw.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 (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 (before treatment), 2, 4, 6, 8, 11, 13 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

No statistical analysis was done.

Preliminary study:

not applicable

Key result

Sex:

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:

other: No clinical signs of toxicity were observed.

Body weight:

other body weight observations

Remarks:

There were no effects on the body weight development throughout the study.

Gross pathology:

The gross pathological examination revealed no organ alterations.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 value is higher than 2000 mg/kg bw in female rats after single oral administration of the test item.

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. Therefore, a study according to OECD TG 423 was conducted. The study was started with 2000 mg/kg bw in 3 female rats and continued with further 3 females treated with 2000 mg/kg bw. 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 the study. No clinical signs of toxicity were observed. The body weight development was inconspicuous throughout the study. The gross pathological examination revealed no organ alterations. Based on the results, the test item has no acute toxic potential under the conditions of the present study, and the LD₅₀ value is higher than 2000 mg/kg bw after single oral administration in female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

The guideline and GLP conform study is of sufficient quality to address the endpoint.

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

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. Therefore, a study according to OECD TG 423 was conducted. The study was started with 2000 mg/kg bw in 3 female rats and continued with further 3 females treated with 2000 mg/kg bw. 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 the study. No clinical signs of toxicity were observed. The body weight development was inconspicuous throughout the study. The gross pathological examination revealed no organ alterations. Based on the results, the test item has no acute toxic potential under the conditions of the present study, and the LD50 value is higher than 2000 mg/kg bw after single oral administration in female 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 acute toxicity, the test item does not require classification for acute toxicity via the oral route according to Regulation (EC) No 1272/2008 (CLP).