Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was performed at the Centre International de Toxicologie (C.I.T.) in accordance with the protocol agreed upon by Societe Francaise Hoechst (dated 21 September 1984), published in the Journal Officiel de la Republique Francaise (J.O.R.F., dated 24 October 1984) and the Principles of Good Labor Practice (GLP).

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
The study was performed in accordance with:
- the protocol agreed upon by Societe Francaise Hoechst (dated 21 September 1984), published in the Journal Officiel de la Republique Francaise (J.O.R.F., dated 24 October 1984), and
- the Procedures of the Centre International de Toxicologie, Evreux, France (C.I.T.).

Study results were calculated and interpreted according to Kay, J.H. et Calandra, J.C. (1962): Interpretation of Eye Irritation Tests. J. Soc. Cosm. Chem. 13, 281-289.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report):Allantoin
- Substance type: active substance
- Physical state: white powder
- Lot/batch No.: 0P.349
- Storage condition of test material: storage in plastic flask
- Other: pH of test substance suspended in 0.5% aqueous solution = 4.3

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Abbaye de Bellefontaine, Begrolles en Mauges, France
- Weight at study initiation: mean weight of 2.4 +/- 0.1 kg
- Housing:Kept in a conventional air-conditioned animal room, individual housing in polystyrene cages.
- Diet (e.g. ad libitum): ad libitum, certified pellet diet "Lapins entretien reference 112C", acquired from U.A.R., Villemoisson-sur-Orge, France.Animals received a preventive treatment for coccidiosis by administration of Mucoxid (R) solution at 140 mg/kg/day at a volume of 10 mL/kg to their drinking water for 5 days during the acclimatization period.
- Water (e.g. ad libitum): Tap water ad libitum.
- Acclimation period: at least 7 days.
- Only animals without ocular defects were used for the study.
ENVIRONMENTAL CONDITIONS
- Temperature (°C):T= 18 +/- 3°C
- Humidity (%):50 +/- 20%; (relative humidity)
- Air changes (per hr): air was non-recycled, filtered by absolute filters.
- Photoperiod (hrs dark / hrs light): 12 hrs each alternating

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: no control animals, but as only one eye per animal was treated with the test substance, the other remained untreated and served as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg of the test substance in its original form.

Duration of treatment / exposure:
Single introduction of test substance.
Observation period (in vivo):
Ocular reactions were evaluated after 1, 24, 48, 72 and 96 hours and 7 days after introduction of the test substance.
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No rinsing was performed after administration of the test substance.

SCORING SYSTEM:
Ocular reactions were evaluated according to the J.O.R.F. scoring system, published in the Journal Officiel de la Republique Francaise, dated 21 September 1984. Scoring bullets included:
- Conjunctival lesions and discharge (Chemosis, Discharge, Conjuntival enanthema)
- Iridic lesions
- Corneal lesions (Cornea, degree of opacity, area of opacity).
Statistic evaluation of results was performed according to Kay and Calandra (see Administrative Data). Individual, mean and maximum ocular irritation indexes were calculated.
The classification of the substance between "non-irritant" and "extremely irritant" was made basing on the maximum ocular irritation index.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 96h
Max. score:
0
Remarks on result:
other: No ocular reactions were observed in any of the animals at any time stage of the test.
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 96h
Max. score:
0
Remarks on result:
other: No ocular reactions were observed in any of the animals at any time stage of the test.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 96h
Max. score:
0
Remarks on result:
other: No ocular reactions were observed in any of the animals at any time stage of the test.
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 96h
Max. score:
0
Remarks on result:
other: No ocular reactions were observed in any of the animals at any time stage of the test.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 96h
Max. score:
0
Remarks on result:
other: No ocular reactions were observed in any of the animals at any time stage of the test.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 96h
Max. score:
0
Remarks on result:
other: No ocular reactions were observed in any of the animals at any time stage of the test.

Any other information on results incl. tables

No ocular reactions were observed after an introduction of 100 mg of test substance in 6 rabbits, at all of the time points.

The maximum irritation index was 0.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the scale of the EEC Directive 83/467/EEC, Allantoin was considered as non-irritant by ocular route in the rabbit.
Executive summary:

A single dose of 100 mg of the test substance in its original form was placed into the conjuntival sac of the left eye of 6 male New Zealand White rabbits. The eyes were not rinsed after introduction of the test substance. The ocular reactions were observed one hour after the introduction and on day 2, 3, 4, 5 and 8.

No ocular reactions were observed after an introduction of 100 mg of test substance in 6 rabbits, at any of the time points.

The maximum irritation index was 0.

According to the scale of the EEC Directive 83/467/EEC, Allantoin was considered as non-irritant by the ocular route in the rabbit.