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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 February - 14 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

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute 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: N/A

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test item formulated using proylene glycol within 4 h of dosing.
- 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 the formulation was 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. 8-9 weeks old
- Weight at study initiation: ± 20 % of the sex mean
- Fasting period before study: No
- Housing: Individually housed in polycarbonate cages (Type III, height 15 cm) containing purifed sawdust as bedding (SAWI, Jelu Werk, Rosenburgh, Germany).
- Diet (e.g. ad libitum): Standard pelleted laboratory animal feed (from Altorim (code VRF 1)) provided ad libitum.
- Water (e.g. ad libitum): Tap water provided ad libitum.
- Acclimation period: 5 days

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

IN-LIFE DATES: From: To: Not reported

Administration / exposure

Type of coverage:

occlusive

Vehicle:

propylene glycol

Details on dermal exposure:

TEST SITE
- Area of exposure: Back
- % coverage: 10
- Type of wrap if used: Surgical gauze (Surgy 1D) covered with aluminium foil and Coban flexible bandage. Dressings on females were further fixed with Micropore tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes- water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg bodyweight
- Concentration (if solution): Not reported
- Constant volume or concentration used: Not reported
- For solids, paste formed: N/A

VEHICLE
- Amount(s) applied (volume or weight with unit): Not reported
- Concentration (if solution): Not reported
- Lot/batch no. (if required): Not reported
- Purity: Not reported

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

no

Details on study design:

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

Statistics:

Not performed

Results and discussion

Preliminary study:

Not conducted

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured

Clinical signs:

lethargy (hypoactivity)

Body weight:

lower than 10% body weight loss

Remarks:

Slightly body weigh loss was noted in 2 females between day 1 and 8.

Gross pathology:

No abnormalities were noted.

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 /5	0 / 5	0 / 10	N/A	5 / 5	5 / 5	10 / 10

N/A not applicable

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

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

Executive summary:

In an acute dermal toxicity study (OECD 402) groups of young adult Wistar rats (male and female) were dermally exposed to test item in ethylene glycol for 24 hours to 10 % of the total skin area at a single dose 2000 mg/kg bw.  Animals then were observed for 14 days.

No mortality was observed in the limit test.

Clinical signs of toxicity were observed in all individuals including lethargy, tremor, hunched posture, chromodacryorrhoea, ptosis, quick breathing and/or piloerection were noted among the animals between Day 1 - 9.  In one female hunched posture was noted until Day 13.  In a second female chromodacryorrhoea was noted between Day 9 - 12.  In another female chromodacryorrhoea was noted from Day 9 on wards.  General erythema, scales, scabs and/or swelling were seen in the treated skin-area of the animals during the observation period.  Reduced body weight gain was observed in the males between Day 1 - 8 and among females through the whole study period.  Slight body weight loss was observed in some females between Day 1 – 8.  No macroscopic abnormalities were observed in the post mortem examination.