[1,1':3',1''-Terphenyl]-2'-ol, 5',5''''-(2,2,2-trifluoro-1-methylethylidene)bis-

Endpoint summary

Description of key information

OECD 423: LD50 (oral) > 2000 mg/kg bw (BASF SE, 2008)
OECD 402: LD50 (dermal) > 2000 mg/kg bw (BASF SE, 2015)

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: study according to guideline and GLP

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Remarks:

testing lab.

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, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 10 – 11 weeks
- Weight at study initiation: animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: single housing in Makrolon cages, type III
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 24°C
- Humidity (%): 20 – 80%
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 3 and 20 g/100 ml
- Justification for choice of vehicle: Olive oil Ph.Eur./DAB had to be used to ensure homogeneity.

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg (gavage)

DOSAGE PREPARATION:
The test-substance preparation was produced for each test group shortly before administration by stirring with a high speed homogenizer (Ultra-Turrax) and a magnetic stirrer. The homogeneity of the test-substance preparation during application was provided by stirring with a magnetic stirrer.

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

300 mg/kg: 3 animals; 2000 mg/kg: 6 animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Individual body weight determination shortly before administration (day 0), weekly thereafter and on the last day of observation.
Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals.
A check for any dead or moribund animal was made twice each workday and once on weekends and on public holidays.
- Necropsy of survivors performed: yes
Necropsy with gross-pathology examination on the last day of the observation period after sacrificed by CO2-inhalation in a chamber with increasing concentrations over time.
- No histological examinations were performed.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

None

Clinical signs:

other: Clinical observation - 2000 mg/kg test group: reduced feces was observed on study day 1 after administration - 300 mg/kg test group: impaired general state, dyspnoea, and piloerection Findings were observed from hour 2 through to hour 5 after administrat

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals examined on the last day of observation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

A Klimisch 1 study according to guideline and GLP

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: study according to guideline and GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nosan No. 8147

GLP compliance:

yes (incl. QA statement)

Remarks:

Bioassay

Test type:

standard acute 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
- Age at study initiation: males approx. 8 weeks, females approx. 12 weeks
- Weight at study initiation: males 227.2g, females 204.2 g
- Housing: single
- Diet: VRF1(P) diet ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal and dorsolateral parts of the trunk
- % coverage: at least 10
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing with warm water
- Time after start of exposure: at removal of the dressing (24h after application)

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw (4.44 ml/kg bw)
- Concentration (if solution): 45g/100ml

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individual body weights were determined shortly after application, weekly thereafter and on the last day of observation
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, assessment of skin reactions

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: none

Gross pathology:

No macroscopic pathologic abnormalities

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

A Klimisch 1 study according to guideline and GLP

Additional information

An acute oral toxicity study was conducted according to OECD testing guideline 423 (Acute Oral Toxicity – Acute Toxic Class Method; BASF SE, 2008). Therefore, female rats were treated in groups of 3 with either 300 mg/kg or 2000 mg/kg Ligand TFME-DPP. Treatment with 2000 mg/kg was repeated with a second group of 3 female rats, thus increasing animal numbers in this group to 6. No mortality occurred in the 14-day observation period following substance administration. Clinical signs in the low dose group were impaired general state, dyspnea, and piloerection; reduced feces on the day following administration was observed in the high dose level group. No macroscopic pathologic abnormalities were noted at the final examination. Therefore, the LD50, oral, in the rat was determined to be >2000 mg/kg.

An acute dermal toxicity study was conducted according to OECD testing guideline 402 as Limit test (BASF SE, 2015). Therefore, 5 males and 5 females were treated with 2000 mg/kg Ligand TFME-DPP on the clipped skin for 24 hours (covered by semi-occlusive dressing). During the observation period of 14 days, no mortalities occurred and no signs of systemic toxicity or local skin effects were observed. A weight stagnation was observed in 3 animals, however this finding is generally known to occur as a possible consequence of the dermal application procedure, therefore, it is considered to be treatment-, but not substance-related. Thus, the LD50, dermal, in the rat was determined to be >2000 mg/kg.

Justification for selection of acute toxicity – oral endpoint
study according to guideline and GLP

Justification for selection of acute toxicity – dermal endpoint
study according to guideline and GLP

Justification for classification or non-classification

Since the current data do not fulfill the classification criteria according to Regulation (EU) 1272/2008 and Regulation 67/548/EEC, a non-classification for Ligand TFME-DPP is warranted.