4,4'-[2,2,2-trifluoro-1-(trifluoromethyl)ethylidene]diphenol; bisphenol AF

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 February - 02 March 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study was conducted in accordance with International guidelines and in accordance with GLP. All guideline validity criteria were met.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-[2,2,2-trifluoro-1-(trifluoromethyl)ethylidene]diphenol

Cas Number:

1478-61-1

Molecular formula:

C15H10F6O2

IUPAC Name:

4,4'-[2,2,2-trifluoro-1-(trifluoromethyl)ethylidene]diphenol

Test material form:

solid

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature in the dark
- Stability under test conditions: Not reported
- Solubility and stability of the test substance in the solvent/vehicle: Not reported
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: Not reported

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test item formulated in propylene glycol within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level.
- Preliminary purification step (if any): N/A
- Final dilution of a dissolved solid, stock liquid or gel: Not reported
- Final preparation of a solid: N/A

FORM AS APPLIED IN THE TEST (if different from that of starting material): Liquid

OTHER SPECIFICS: Homogeneity of formulation confirmed by visual inspection.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: ca. 9 weeks
- Weight at study initiation: Did not exceed ± 20 % of the sex mean
- Fasting period before study: Yes - 20 h prior to dosing (max.) and for 3-4 h after dosing.
- Housing: 3 animals housed per Macrolon cage (Type IV, height 15 cm) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenburg, Germany).
- Diet (e.g. ad libitum): Standard pelleted laboratory animal diet (from Altromin (Code VRF 1)) provided ad libitum.
- Water (e.g. ad libitum): Tap water provided ad-libitum.
- Acclimation period: Minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3 ºC
- Humidity (%): 30 - 70 %
- Air changes (per hr): ca. 15.
- Photoperiod (hrs dark / hrs light): 12:12 light:dark

IN-LIFE DATES: From: To: Not reported

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Not reported
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: Guideline recommended
- Lot/batch no. (if required): Not reported
- Purity: Not reported

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

DOSAGE PREPARATION (if unusual): Test item formulated in propylne glycol within 4 hours prior to dosing. Homogeneity of formulation confirmed by visual inspection.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Not reported

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for mortality were made twice daily. Bdy weights were recorded on Day 1 (pre-dose) and Day 8 and 15. Clinical signs were recorded once daily.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights and necropsy.

Statistics:

Not performed

Results and discussion

Preliminary study:

N/A

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed

Clinical signs:

lethargy (hypoactivity)

Body weight:

lower than 10% body weight loss

Remarks:

Slight body weight loss in individuals animals was noted between day 1 and 8 (1 male -12% and 1 female -8%).

Gross pathology:

No abnormalities were observed.

Any other information on results incl. tables

Table 2:       Number of animals dead (and with evident toxicity) (and time range within which mortality occured)

Nominal dose (mg/kg bw)	Mortality (No. dead / total)			Time range of deaths (hours)	Clinical signs (No. / total)
	Male	Female	Combined		Male	Female	Combined
2000	0 /3	0 / 3	0 / 6	N/A	3 / 3	2 / 3	5 / 6

N/A not applicable

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of the test item in Wistar rats exceeded 2000 mg/kg bw.

Executive summary:

In an acute oral toxicity study (OECD 423) groups of fasted, 9 week old, Wistar rats (3 male, 3 female) were given a single oral dose of  test item in propylene glycol at a single dose of 2000 mg/kg bw and observed for 14 days.

No mortality was observed in the limit test.

Clinical signs of toxicity were observed in 2 /3 females, namely hunched posture between Days 1 - 3 and 7 - 9.  Clinical signs of toxicity were also observed in all of the males rats including lethargy, hunched posture, chromodacryorrhoea, rales and/or piloerection between Days 1 - 7. Salivation was also observed in all male rats however this is commonly seen after treatment by oral gavage and was therefore not considered to be of toxicologial relevance. No macroscopic abnormalities were observed in the post mortem examination.