4'-Ethyl-2,3-difluorbiphenyl-4-boronic acid

Endpoint summary

Description of key information

OECD 423: 300 -2000 mg/kg bw

The subsequent evaluation on the necessity of a acute test via a second route was done in accordance with Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7a: Endpoint specific guidance, Version 6.0, July 2017, p 374f.

A DermWin calculation shows a dermally absorbed dose of 4.8*10^-5 to 0.00049 mg/cm2/event. Based on the very low dermally absorbed rate and the absence of systemic effects after (sub)acute oral administration, a study on acute dermal toxicity is not required.

Furthermore, based on the lack of systemic toxicity after (sub)acute oral adminsitration, it is more than evident that an acute study on inhalation would not show any different outcome. Therefore, and due to animal welfare reasons a study on acute inhalation is not required.

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:

May 02 - Nov 05, 2018

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)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 weeks at start of treatment
- Weight at study initiation: 166 g (range from 156 to 173 g)
- Fasting period before study: no
- Housing: grouped
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.9 – 24.5°C
- Humidity (%): 44.4 – 62.4%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: 0.25% aqueous hydroxypropylcellulose (Methocel® K4M Premium solution, 2.5 g/L distilled water)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 g/L
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: well tolerated and established standard vehicle

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- 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.

Doses:

300 and 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: before treatment (day 1) and on day 2, 4, 6, 8, 11, 13 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, gross pathology

Statistics:

Standard statistical methods have been applied for data processing.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Three out of six rats treated with 2000 mg/kg died on day 1 after the last observation. No mortality was seen after treatment with 300 mg/kg during the course of this study.

Clinical signs:

other: One rat treated with 300 mg/kg showed locomotor disturbance 3 hours after treatment until the last observation time point on day 1. No clinical signs of toxicity were observed in all other rats treated with 300 mg/kg. All rats treated with 2000 mg/kg show

Gross pathology:

No organ alterations were identified during the gross pathological examination.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The information for this endpoint study record was obtained from an experimental study. The OECD GLP criteria were met and the methods applied are fully compliant with OECD TG 423. The test material shows an oral LD50 between 300 and 2000 mg/kg bw and must thus be classified as acute toxicity hazard category 4 (300-2000 mg/kg bw).

Executive summary:

The information for this endpoint study record was obtained from an experimental study. The OECD GLP criteria were met and the methods applied are fully compliant with OECD TG  423. The test material shows an oral LD50 between 300 and 2000 mg/kg bw and must thus be classified as acute toxicity hazard category 4 (300-2000 mg/kg bw).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Quality of whole database:

OECD Guideline and GLP conform

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The test material shows an oral LD50 between 300 and 2000 mg/kg bw and must thus be classified as acute toxicity hazard category 4 (300-2000 mg/kg bw) according to the EU Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures, as amended for the 10th time in Regulation (EU) No 2017/776. The test item is neither classified for acute dermal toxicity and acute toxicity after inhalation according to Regulation (EC) No 1272/2008.