1H-Isoindol-1-one, 2,3-dihydro-3,3-bis(4-hydroxyphenyl)-2-phenyl-

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:

other: OECD 425 (2001) and US EPA OPPTS 870.1100 (2002); GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Remarks:

US EPA (40 CFR, Part 792) and OECD GLP

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

455-890-7

EC Name:

-

Cas Number:

6607-41-6

Molecular formula:

C26H19NO3

IUPAC Name:

455-890-7

Details on test material:

PPP-BP (CAS 6607-41-6; 2-Phenyl, 3-3-Bis (4-Hydroxy phenyl) Phthalimide)

Test animals

Species:

rat

Strain:

other: Outbred Albino (Rattus norvegicus)

Sex:

female

Details on test animals or test system and environmental conditions:

Five female outbred albino rats were received from Harlan, Inc. Indianapolis, IN. They weighed 204.5-209.6 g and were at least 49 days old. They were single housed upon arrival in polycarbonate cages with hardwood chip bedding. The animals were acclimated for at least 5 days prior to dosing. Tap water was provided ad libitum throughout the study and feed was provided ad libitum, with the exception of overnight prior to dosing. The temperature and humidity were maintained at 68±5°F and 30-70%, respectively. Room lights were on a 12-hour light/dark cycle.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

PPP-BP was suspended in USP Water for Injection (WFI) for dosing. The dosing volume did not exceed 1 mL/100 g body weight.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 females

Control animals:

no

Details on study design:

Food was withheld from the animals the night prior to dosing. Animals were administered a single dose of PPP-BP by oral gavage. After dosing, the animals were returned to their cages and supplied with feed and water ad libitum.

The first animal was dosed at 2000 mg/kg. As the animal survived, the limit test was continued at the dose of 2000 mg/kg and the main test was not conducted. Four animals were dosed sequentially so that a total of five animals were tested.

Careful clinical observations were made at least twice on the day of dosing. Special attention was given during the first four hours. The frequency was determined by the response of the animals to the treatment. Animals were observed daily for 14 days for clinical manifestations. Animals were weighed on Day 0, prior to dose administration, Day 7 and Day 14.

A gross necropsy was performed on all animals sacrificed at the end of the study.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

All animals survived the duration of the study.

Clinical signs:

No clinical signs of toxicity were observed in any animals over the course of the study.

Body weight:

All animals gained weight over the course of the study.

Gross pathology:

No unusual findings were found during necropsy for the animals euthanized at study termination

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Under the conditions of this study, PPP-BP was determined to have an acute oral LD50 of greater than 2000 mg/kg.

Executive summary:

The test substance suspended in water was given as a single 2000 mg/kg oral dose by gavage to 5 female rats. The rats were observed for 14 days for mortality and clinical signs, and body weights were recorded on Days 1, 7, and 14. There were no deaths during the observation period. No unusual clinical signs were observed All test organisms had expected body weight gain. Gross necropsy findings were normal. The acute oral LD50 was greater than 2000 mg/kg.