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

Endpoint summary

Description of key information

An acute dermal irritation / corrosion study was performed (2004) in rabbits in accordance with OECD 404. The study was GLP compliant (OECD/EPA). The test substance did not elicit any signs of erythema or edema and was concluded to be non-irritant to skin. 
An acute eye irritation / corrosion study was performed (2004) in rabbits in accordance with OECD 405. The study was GLP compliant (OECD/EPA). The substance elicited very mild signs of irritation (conjunctival redness and chemosis) at one hour post-instillation. However, the irritation was considered to be 'mechanical' [physical] in nature.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD 404 (2002) and US EPA OPPTS 870.2500 (1998); GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes

Remarks:

US EPA TSCA GLPs (40 CFR, Part 792); OECD GLPs

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Male and female New Zealand White rabbits, at least 10 weeks of age, weighing 2.39 to 2.79 kg were obtained from Millbrook Breeding Labs, Amherst, MA. The animals were acclimated for at least five days and individually housed in suspended stainless-steel cages. They were provided food and tap water ad libitum. Room temperature was 68 +/- 5°F and the relative humidity ranged between 30-70%. Room lights were on a 12-hour light/dark cycle.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

Approximately 24 hours prior to dosing, the application sites were prepared by clipping the skin of the trunk free of hair (not less than 10% of the body surface was clear for the application of the test substance). One half gram of the test substance, moistened with 1.0 mL of sterile water was applied to a small area of the skin (approximately 6 cm2).

Duration of treatment / exposure:

Each application area was covered with a gauze patch and secured with non-irritating tape. Initially, three test patches were applied sequentially to a single animal and removed after three minutes, one hour and then four hours of contact to assess for possible corrosion. Once it was determined that a four-hour exposure could humanely be allowed, a single test patch was applied to two additional animals for a four hour exposure period.

Observation period:

Dermal scores were recorded at 1, 24, 48 and 72 hours after patch removal. Daily clinical observations included all toxicologic and pharmacologic signs. Animals were weighed at Day 0 prior to dose administration and at the end of the observation period (Day 3).

Number of animals:

3

Details on study design:

Erythema and Edema formation were observed/scored based upon the Draize definitions:

Irritation parameter:

other: Erythema and Eschar Formation

Basis:

mean

Time point:

other: 24 hours

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 hours

Score:

0

Max. score:

4

Irritation parameter:

other: Erythema and Eschar Formation

Basis:

mean

Time point:

other: 48 hours

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 48 hours

Score:

0

Max. score:

4

Irritation parameter:

other: Erythema and Eschar Formation

Basis:

mean

Time point:

other: 72 hours

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 72 hours

Score:

0

Max. score:

4

Irritant / corrosive response data:

No signs of erythema or edema were present at the 1 hour, 24, 48 or the 72 hour observation points in the initial test or the confirmatory test.

None of the control sites of any animal at any of the observation periods showed signs of erythema or edema.

Other effects:

All animals gained weight over the course of the study. No overt signs of toxicity were evident in any of the animals during the course of the study.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Under the conditions of this study, PPP-BP is considered to be a non-irritant.

Executive summary:

The test substance was evaluated for the potential for acute skin irritation in 3 young adult New Zealand white rabbits. A dose of 0.5 g test substance with 1.0 mL water was applied to the intact skin site under a semiocclusive dressing for 3 minutes, 1 hour and 4 hours. The application site was then washed and observations made at 1, 24, 48 and 72 hours after removal of the test substance. All organisms gained weight over the course of the study. No overt signs of toxicity were evident in any of the organisms during the course of the study. There were no signs of irritation at any time point.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD 405 (2002) and US EPA OPPTS 870.2400 (1998); GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes

Remarks:

US EPA TSCA GLPs (40 CFR, Part 792) and OECD GLPs

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Male and female New Zealand White rabbits, at least 10 weeks of age, weighing 2.51 to 2.64 kg were obtained from Millbrook Breeding Labs, Amherst, MA. The animals were acclimated for at least five days and individually housed in suspended stainless-steel cages. They were provided food and tap water ad libitum. Room temperature was 68 +/- 5°F and the relative humidity ranged between 30-70%. Room lights were on a 12-hour light/dark cycle.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Within the 24 hours prior to dosing, the eyes of the animals selected for the test were examined to insure that the eyes were free of abnormality, damage and disease, scored according to the Grades for Ocular Lesions and scored by Fluorescein Staining (details provided below). The animals were dosed in the left eye at a volume of 0.1 mL (~50 mg).

Duration of treatment / exposure:

The test substance was instilled into the left eye by gently pulling the lower lid away from the eye to form a cup into which the test substance was placed. The upper and lower lids were gently held together for approximately one second to prevent the loss of the test substance. The test material was rinsed from the eye with USP water for injection 2 hours after dosing due to test material still remaining in the eye. The right eye remained untreated and served as a control.

Observation period (in vivo):

The eyes were examined at 1, 24, 48 and 72 hours after treatment and scored according to the Grades for Ocular Lesions provided below. In addition, after recording the scores at 24 hours, the eyes were further examined with the aid of fluorescein and scored as described below. Animals were observed daily for clinical signs of toxicity. Animals were weighed at study start (Day 0) and completion (Day 3).

Number of animals or in vitro replicates:

3

Irritant / corrosive response data:

No corneal or iris involvement was observed in the test eyes of any animal at any time point. All three animals demonstrated mild conjunctival redness and chemosis at the 1-hour scoring interval. As these findings were no longer apparent after rinsing, they are most likely due to mechanical irritation of the test substance. No fluorescein staining was present in the test eyes at any time point during the study.

Other effects:

All animals gained weight and no systemic signs of toxicity were observed during the course of the study. No irritation was observed in the control eyes at any scoring interval.

Summary of Results for the Treated (Left) Eyes
Animal No.	Effects at one hour
	Cornea		Iris	Conjunctiva		Fluor Exam
	O	A	V	R	C	IS	A
44210	0	0	0	1	1	n/a	n/a
44211	0	0	0	1	1	n/a	n/a
44212	0	0	0	1	1	n/a	n/a
Effects at 24 hours
44210	0	0	0	0	0	0	0
44211	0	0	0	0	0	0	0
44212	0	0	0	0	0	0	0
Effects at 48 hours
44210	0	0	0	0	0	0	0
44211	0	0	0	0	0	0	0
44212	0	0	0	0	0	0	0
Effects at 72 hours
44210	0	0	0	0	0	0	0
44211	0	0	0	0	0	0	0
44212	0	0	0	0	0	0	0
O: Opacity; A: Area Involved V: Iritis Value R: Redness; C: Chemosis; Fluor: Fluorescein; IS: Intensity of staining; A: Area Involved n/a: not applicable

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Under the conditions of this study, the administration of PPP-BP to the ocular tissue of New Zealand White rabbits resulted in very mild signs of irritation (conjunctival redness and chemosis) in the treated eyes only at the 1-hour timepoint; this irritation was most likely mechanical in nature. No other signs of irritation were noted in the test eyes and no signs of irritation were present in any of the control eyes. Therefore, PPP-BP is considered to be a very mild mechanical eye irritant.

Executive summary:

The test substance was evaluated for acute eye irritation in 3 young adult New Zealand white rabbits. The test substance aliquot was administered to 1 eye of each test organism. The untreated eye served as a control. The conjunctiva, iris, and cornea of each treated eye were evaluated and scored according Grades for Ocular Lesions numerical scale over 72 hours. Mild redness and chemosis was observed one hour after instillation probably mechanical in nature. All irritation had reversed by 24 hours. No corneal damage or iridial inflammation was observed. The test substance was considered to be slightly irritating.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation

The test substance was evaluated for the potential for acute skin irritation in 3 young adult New Zealand white rabbits. A dose of 0.5 g test substance with 1.0 mL water was applied to the intact skin site under a semiocclusive dressing for 3 minutes, 1 hour and 4 hours. The application site was then washed and observations made at 1, 24, 48 and 72 hours after removal of the test substance. There were no signs of irritation at any time point. The test substance was considered to be non-irritant.

 

Eye Irritation

The test substance was evaluated for acute eye irritation in 3 young adult New Zealand white rabbits. The test substance aliquot was administered to 1 eye of each test organism. The conjunctiva, iris, and cornea of each treated eye were evaluated and scored according Grades for Ocular Lesions numerical scale over 72 hours. Mild redness and chemosis was observed one hour after instillation probably mechanical in nature. All irritation had reversed by 24 hours. No corneal damage or iridial inflammation was observed. The test substance was considered to be slightly irritating.

Based on the available information, the test substance is not irritant to skin and has a very low order of irritation to eyes.

Justification for selection of skin irritation / corrosion endpoint:
GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Justification for selection of eye irritation endpoint:
GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

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

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

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

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