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

Acute Toxicity: dermal

Administrative data

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

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 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

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

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; C26H190N1O3); Purity: 99.8%

Test animals

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.

Administration / exposure

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.

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. 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.

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 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.