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

Endpoint summary

Description of key information

An acute oral toxicity study was performed (2004) in female rats in accordance with OECD 425 (up-and-down procedure). The study was GLP compliant (OECD/EPA). The oral LD50 was > 2000 mg/kg bw. 
An acute dermal toxicity study was performed (2004) in male and female rabbits in accordance with OECD 402. The study was GLP compliant (OECD/EPA). The dermal LD50 was > 2000 mg/kg bw.
An acute inhalation toxicity study in rodents was not performed as acute oral and dermal toxicity studies fulfill this endpoint.

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

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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

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.

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The test substance was examined according to OECD guideline 425 and GLP to provide information on potential acute toxicity

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Value:

mg/m³

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: OECD 402 (1987) and EPA OPPTS 870.1200 (1998); GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Remarks:

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

Test type:

other:

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female New Zealand White rabbits were received from Millbrook Breeding Labs, Amherst, MA. The animals weighed 2.00-2.45 kg and were 12-15 weeks old and were individually housed upon arrival in stainless steel suspended cages with hardwood chip bedding The animals were acclimated for at least 5 days prior to dosing. Water and feed were provided ad libitum. The temperature and humidity were maintained at 68±5°F and 30-70%, respectively. Room lights were on a 12-hour light/dark cycle.

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

The application site, not less than 10% of the body surface, was prepared approximately 24 hours prior to dosing by clipping the skin of the trunk free of hair. PPP-BP was dosed as received from the Sponsor. The PPP-BP was slightly moistened with 1.5 mL of USP Water for Injection and introduced under gauze patches (two single layers thick) and applied directly to the skin of 10 animals. The animals were immobilized and the patches were secured in place by wrapping the entire trunk of the animal with an impervious bandage. Test sites were secured to prevent the animals from ingesting the test substance. After the completion of the 24-hour exposure period, the wrapping was removed and the skin was gently wiped and rinsed with USP Water for Injection to remove any test substance still remaining.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5/sex

Control animals:

not required

Details on study design:

Five animals/sex were dosed at 2000 mg/kg (limit test). The animals were observed frequently during the first day and then a careful clinical examination was made at least once a day through 14 days. The test site of each animal was also observed for signs of erythema and edema after the exposure period according to the Draize Scale for Scoring Skin Reactions. Animals were weighed at Day 0 (prior to dose administration), Day 7 and Day 14. Changes in body weights were calculated and recorded. A gross necropsy was performed on all animals whether found dead in extremis (dead no longer than 12 hours) or sacrificed by an injectable barbiturate at the end of the study.

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. All animals displayed normal skin reactions 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.

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 dermal LD50 of greater than 2000 mg/kg.

Executive summary:

The test substance suspended in water was applied with an occlusive dressing to the clipped backs of male and female rabbits at a dose of 2000 mg/kg of body weight. The test substance was removed after 24 hours, with further observation for 14 days. There were no deaths or other clinical signs of toxicity during the observation period. All animals gained weight normally. Gross necropsy findings were normal. The acute dermal LD50 was greater than 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The test substance was examined according to OECD guideline 402 and GLP to provide information on potential acute toxicity

Additional information

In two separate studies the acute oral and acute dermal toxicity LD50 was determined.

For oral: 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. There were no deaths during the observation period and gross necropsy findings were normal. The acute oral LD50 (rat) was >2000 mg/kg bw.

For dermal: The test substance suspended in water was applied with an occlusive dressing to the clipped backs of male and female rabbits at a dose of 2000 mg/kg of body weight, removed after 24 hours with observation for 14 days. There were no deaths or other clinical signs of toxicity during the observation period. The acute dermal LD50 (rabbit) was >2000 mg/kg bw.

Based on the available information, the test substance has a low order of acute oral and dermal toxicity, with an LD50 of greater than 2000 mg/kg bw by either route. Inhalation is not a relevant route of exposure.

Justification for selection of acute toxicity – oral endpoint
GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Justification for selection of acute toxicity – dermal endpoint
GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Justification for classification or non-classification

The test substance does not meet classification criteria under EU Directive 67/548/EEC for acute toxicity.

The test substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity.