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

Eye irritation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

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

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) Phthalimidine; Purity: 99.8%

Test animals / tissue source

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.

Test system

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

Results and discussion

In vivo

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.