Biphenyl-2-yl-(9,9-dimethyl-9H-fluoren-2-yl)-(9,9’-spirobifluoren-4-yl)-amine

Endpoint summary

Description of key information

The acute oral toxicity of a structural analogue substance was determined in a study according to OECD Guideline 423 under GLP conditions. The LD50 value was determined to be greater than 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 16, 2011 - February 03, 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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

Batch: OS11008922
Vehicle
Aqueous Methocel® K4M Premium solution was used as the vehicle.

Batch: DT170406
Released until: May 08, 2016
Batch (ZDP): 35/11 and 37/11
Released until (ZDP): October 21 and November 04, 2011


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
Directly before the administration the test material was prepared with aqueous Methocel® K4M Premium solution as the vehicle using an Ultra-Turrax device.

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 start of study: 9 weeks (f), 10 weeks (m)
- Weight at study initiation: 155 - 165g
- 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 (°C): 21 - 23°C
- Humidity (%): 51-75 %
- 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:

Methocel K4M Premium solution

Details on oral exposure:

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

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 (f) / 3 (m)

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:

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 clinical signs of toxicity were observed.

Body weight:

The body weight development of the rats was inconspicuous during the study.

Gross pathology:

The gross pathological examination revealed no organ alterations.

Objective

The objective of the present study was to identify potential toxic effects of the test item after single oral administration of 2000 mg/kg body weight to rats.

Study Design

This study was performed according to GLP and the methods applied are fully compliant with OECD TG 423. For this assay a starting dose of 2000 mg/kg body weight was selected.

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.

Results

No mortality occurred during the course of this 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.

Conclusion

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 after single oral administration in female rats.

Interpretation of results:

GHS criteria not met

Conclusions:

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.

Executive summary:

The test material was investigated for acute toxicity in rats in a limit test according to OECD Guideline 423. No signs of toxicity were seen in the rats (3 males, 3 females) after treatment with 2000 mg/kg bw of the test item. The body weight development of the rats was inconspicuous throughout the study. There were no deaths during the course of the study. The gross pathological examination revealed no organ alterations.

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.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

For this endpoint information from a structural similar compound is available. This study for this similar compound was performed according to GLP and the methods applied are fully compliant with OECD TG 423. See chapter 13 report for a more detailed justification.

Reason / purpose for cross-reference:

read-across source

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

Interpretation of results:

GHS criteria not met

Conclusions:

For this endpoint information from a structural similar compound is available. This study for this similar compound was performed according to GLP and the methods applied are fully compliant with OECD TG 423. See chapter 13 report for a more detailed justification.
From this justification it can be concluded that the oral LD50 value is higher than 2000 mg/kg after single oral administration in female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Guideline and GLP conform 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

Justification for classification or non-classification

Based on the provided data, the test item is not considered to be classified for acute oral toxicity according to Regulation (EC) No1272/2008.