Registration Dossier

Administrative data

Endpoint:
eye irritation
Remarks:
other: ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
22 November 1988 to 23 December 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP compliant study conducted to a non-standard ex vivo method but sufficiently well reported to be judged as reliable with restrictions.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Isolated Eye Test (Price & Andrews, 1985)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
From Appendix A:
Batch an other numbers SNC No. 1986: 88009
Toxicology reference No. St88/253Source: Shell Nederland Raffindarerij BV Rotterdam
Date received: 18 Oct 1988
Appearance: clear colourless liquid
Analysis: 94.51-97.51% cis isomer with 1.5% trans isomer
Density: 1.224 g/mL @ 15.2 ºC
Date released: 18 Nov 1988
Storage: dark at ambient temperature
Stability: stable for the duration of the study (no changes from 21 Nov 1988 to 19 Jan 1989

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
New Zealand White rabbits were obtained from a commercial supplier (Froxfield SPF Rabbits). Their bodyweight was between 3.0 and 4,0 kg and their age 3 to 5 months at the time of receipt. They were allowed to become accustomed to their new environment for at least two weeks before any experimentation commenced, The animals were singly housed in hanging, stainless cages with perforated dimple or wire-mesh flooring. Each cage measured 67 cm x 43 cm x 45 cm. A pelleted diet (Standard Rabbit Diet, S.Q.C., Special Diet Services Ltd.) and water from the public supply were provided ad libitum. There were no excursions of animal room environmental conditions beyond target values of 15° to 20°C and 30% to 70% R.H. that were considered to have influenced the outcome of the study. Lighting (fluorescent tube) was automatically controlled to provide a 12 hour day and 12 hour night. Animals assigned to the study were identified by cage-labels displaying the animal number, experiment number and treatment regime and by uniquely numbered ear-tags.

Three rabbits were killed by intravenous injection of sodium pentobarbitone and their eyes excised prior to the determination of eye irritation potential.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 mL of undiluted test material
Duration of treatment / exposure:
10 seconds
Observation period (in vivo):
5 hr
Number of animals or in vitro replicates:
3 (6 eyes were used for this ex vivo study)
Details on study design:
Three rabbits were killed by intravenous injection of sodium pentobarbitone and their eyes excised. The eyes were held in clamps designed to secure the eye in the desired orientation without deformation. Each clamp plus eye was mounted in a chamber held at approximately 32°C by means of a circulating water jacket. The eyes were superfused with warm saline which dripped across the frontal surface of the eye, After one hour's equilibration, the corneal thickness of the excised eyes was measured using a pachymeter attachment to a Zeiss photo-slit lamp ophthalmic microscrope and the values compared with previously determined in vivo, values. The n vivo and ex vivo, values showed no significant differences and there was no corneal staining upon application of fluorescein, confirming that the eyes had not been damaged during the dissection procedure. The saline drip was diverted and 0.1 ml of undiluted cis-l,3-dichloropropene was applied to each eye. After about 10 seconds each eye was irrigated with approximately 5 ml of warm saline, The corneal thickness of each eye was measured at hourly intervals after dosing for a total of 5 hours.

After the 4 hour reading, fluorescein was applied to each eye and the degree of staining noted. The mean corneal thickness at each observation time was calculated and used to grade the eye irritancy potential of the test material.

Results and discussion

In vivo

Results
Irritation parameter:
other: mean corenal thickness
Basis:
mean
Remarks on result:
other: ex vivo results

Any other information on results incl. tables

Effect on isolated rabbit eyes (n=3, 2 per animal)

time mean % corneal thickness
0 h 100.0
1 h 110.7
2 h 116.0
3 h 122.8
4 h 130.3
5 h 140.8

Application of 0.1 ml of undiluted test substance to each of 6 isolated eye preparations resulted in increase of corneal thickness by more than 20% (group mean value) within 3 hours of treatment. Corneal uptake of fluorescein was apparent in all preparations following application of the dye to the corneal surface 4 hours after treatment.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the ex vivo application of test material to rabbit eyes and resulting corneal thickening, cis-1,3 -dichloropropene is considered to be a potential eye irritant. It is predicted that the application of the test material to the eye, in vivo would result in significant ocular damage persisting 21 days after treatment.
Executive summary:

A GLP-compliant ex vivo eye irritation study has been conducted in accordance with a non-standard method (Price & Andrews, 1985). Based on the ex vivo application of test material to rabbit eyes and resulting corneal thickening, cis-1,3 -dichloropropene is considered to be a potential eye irritant.. It is predicted that the application of the test material to the eye, in vivo would result in significant ocular damage persisting 21 days after treatment.