esterification product of 2-hydroxypropane-1,3-diyl-bis(2-methylprop-2-enoate) and 3-hydroxypropane-1,2-diyl-bis(2-methylprop-2-enoate) and diphosphorus pentoxide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November-December 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted under GLP conditions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Severe signs of irritation were observed following the administration of the test item to the first animal. The remaining two animals were therefore not treated for animal welfare reasons.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

GLYPHO

IUPAC Name:

GLYPHO

Details on test material:

- Name of test material (as cited in study report:GLYPHO
- Substance type: Yellowish liquid
- Physical state: Liquid
- Lot/batch no.:AH2/170
- Expiration date of the lot/batch:01-Feb-2002
- Storage condition of test material:In the original container, in the refrigerator (range of 2-8 degrees C), away from direct sunlight.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source:Elevage Scientifique des Dombes
F-01400 Chatillon sur Chalaronne / France
- Age at study initiation: 10-11 weeks (female number 74 only)
- Housing: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood and haysticks for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance ad libitum (batch no. 92/01)
- Water (e.g. ad libitum):Community tap water from Fullinsdorf, ad libitum.
ENVIRONMENTAL CONDITIONS
- Temperature (°C):17-23 degrees C
- Humidity (%):30-70%
- Air changes (per hr):10-15
- Photoperiod (hrs dark / hrs light):12/12
IN-LIFE DATES: From:19 November 2001 To: 23 November 2001

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.1 mL per animal.
- Concentration (if solution): NEAT
VEHICLE
- Amount(s) applied (volume or weight with unit):None

Duration of treatment / exposure:

Single application with planned observations at 24, 48, and 72 hours.

Observation period (in vivo):

As the test article was suspected to produce irritancy a single animal (female number 74) was treated first. The animal was examined at 1 and 24 hours after instillation and severe ocular irriation was observed. Based on these findings the animal was prematurely sacrificed on test day 4 and the remaining two animals were not treated.

Number of animals or in vitro replicates:

3; experiment terminated for humane reasons with only one animal treated.

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24-72 hours

Score:

ca. 2 - ca. 3

Reversibility:

not reversible

Irritant / corrosive response data:

A possible reversibility of the corneal opacity was not expected, therefore, the test item can be considered to possess a corrosive potential.

Any other information on results incl. tables

Eye reactions consisted of grade 3.00 corneal opacity, grade 2.00 iris lesions, grade 0.00 redness of the conjunctivae and grade 2.00 chemosis of the conjunctivae. Opacity, affecting the whole area of the cornea, was observed in the treated eye at 1-hour reading and was still evident at termination of the test. Light reflex was absent throughout the 72 hour observation period.

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information

Conclusions:

Based on the results of this study and the calculated pH (1.72 in 10% solution), the test article is an ocular corrosive.

Executive summary:

The primary eye irritation/corrosion potential of the test article was evaluated in New Zealand White Rabbits. This study was conducted in compliance with Swiss GLP (2000) and OECD GLP (1997). The test method was based on OECD 405 (1987) and Directive 92/69 EEC, B.5 (1992). Only 1 female rabbit was initially tested as the test article was suspected to produce irritancy. At a concentration of 10% test article in water, the pH was found to be 1.72. The test material (0.1 mL) was administered as received to the conjunctival sac of one eye of the rabbit by gently pulling the lower eyelid away from the eye. The lids were held together for approximately one second after administration to insure adequate distribution of the test material. The contralateral eye of the animal served as the control. The treated eye of the rabbit was examined for irritation of the cornea, iris and conjunctiva at 1, 24, 48 and 72 hours postdose using the Draize technique. Sodium fluorescein dye procedures were not used to improve the evaluation of the cornea. Body weight was recorded at pretest, the day of treatment, and at termination. Ocular discharge was not scored, thus professional judgment was used to score discharge. There were no signs of systemic toxicity or abnormal changes in body weight. The individual mean values (24-72 hours) were 3.0 for corneal opacity, 2.0 for iritis, 0.0 for conjunctival redness, and 2.0 for conjunctival chemosis. Since corneal opacity was not expected to clear, the animal was euthanized in extremis on Day 4, and the other two animals were not treated with the test article. The light reflex was absent throughout the 72-hour observation period. Moderate watery discharge (score: 2) and slight watery discharge (scores: 1) were observed at 1 hour postdose and at 24, 48, and 72 hours postdose, respectively. The highest Primary Irritation Index was 80/110 at 1 hour postdose. No corrosion of the cornea was observed. However, since corneal opacity was not expected to reverse,The test article can be considered to possess a corrosive potential. Based on the results of this study and the calculated pH (1.72 in 10% solution), the test article is an ocular corrosive.