Phosphoric acid, mixed esters with biphenyl-4,4'-diol and phenol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

of 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

of 2004

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

biphenyl-4,4'-diyl tetraphenyl bis(phosphate)

EC Number:

700-627-6

Cas Number:

17270-01-8

Molecular formula:

C36H28O8P2

IUPAC Name:

biphenyl-4,4'-diyl tetraphenyl bis(phosphate)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sprague Dawley rats, strain: Crl:CD (SD) IGS BR with appropriate range of bodyweight at study start.
- Source: Charles River UK Ltd., Margate, Kent, UK.
- Age at study start (day of dosing): 8 to 12 weeks.
- Weight at start (day of dosing): Females: minimum 205 g, maximum 243 g.
- Housing: Group housing with up to 4 animals in suspended solid-floor propylene cages.
- Bedding material: Woodflakes.
- Fasting period: Overnight immediately prior to dosing until 3-4 hours post administration.
- Diet (ad libitum, except for fasting period): Commercially available standard laboratory animal diet:
Certified Rat and Mouse Diet
- Water (ad libitum*): Mains drinking water
- Acclimation period: At least 5 days before start of dosing.

* Remark: The study report does not clearly state whether or not water was supplied during the fasting period.

ENVIRONMENTAL CONDITIONS

The animal room was maintained at target ranges of:
- Temperature (°C): 22 ± 3°C
- Relative Humidity (%): 30 to 70%
- Photoperiod: 12 h day / 12 h night
- Rate of air exchange: At least 15 changes/h

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Target dose of test material --- Concentration of test material in vehicle: 300 mg/kg bw --- 30 mg/mL
2000 mg/kg bw --- 200 mg/mL
- Amount (dose volume by gavage): 10 mL/kg bw
(individual dose volume was calculated based on individual fasted bodyweight at the time of dosing).

DOSAGE PREPARATION:
The test material, was freshly prepared as a solution in dimethyl sulphoxide (DMSO). DMSO was used as a vehicle, because the test material did not dissolve in distilled water or arachis oil BP.

RATIONALE FOR DOSE SELECTED:
The choice of the limit dose of 2000 mg/kg bw was appropriate in the main test, because doses of 300 mg/kg and 2000 mg/kg did not induce any deaths, clinical signs of toxicity, adverse effects on bodyweight or necropsy findings in sequential preliminary sighting studies with 1 female rat/dose.

Doses:

300 mg/kg bw (1 female)
2000 mg/kg bw (5 females)

No. of animals per sex per dose:

5 (females only)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Observation of clinical signs: 0.5, 1, 2 and 4 h post dosing on the day of administration (Day 0) and subsequently once daily for 14 days.
Weighing of each animal: Day 0 for dose calculation and on Days 7 and 14.
- Necropsy performed: yes, of all sighting and main study animals.

Statistics:

Not applicable, as there were no deaths

Results and discussion

Preliminary study:

There were no deaths, clinical signs of toxicity, adverse effects on bodyweight or necropsy findings in a preliminary sighting study at a dose of 300 mg/kg bw administered to 1 female rat.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths at 300 mg/kg (sighting) and at the limit dose of 2000 mg/kg

Mortality:

Single Dose at Mortality
300 mg/kg 0/1 (f)
2000 mg/kg 0/5 (f)

Clinical signs:

other: Clinical signs of systemic toxicity were not evident.

Gross pathology:

Necropsy of each animal at the end of the 14-day post treatment observation period did not reveal any macroscopic pathology findings.

Applicant's summary and conclusion

Conclusions:

In view of the oral LD50 > 2000 mg/kg bodyweight attained in the present study, its outcome does not necessitate any classification or labelling regarding acute oral toxicity according to EU regulations (REGULATION (EC) 1272/2008).