Registration Dossier

Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Safepharm Laboratories Ltd.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material: Nicotinamide

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: 12 to 16 weeks
- Weight at study initiation: 2.54 - 2.97 kg
- Housing: The animals were individually housed in suspended metal cages.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: Minimum acclimatisation period of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 20
- Humidity (%): 43 - 48
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: Fro
- From: 25 April 1990
- To: 3 May 1990

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 g
Duration of treatment / exposure:
The right eye of each animal was treated. The left eye remained untreated and was used for control purposes.
Observation period (in vivo):
1, 24, 48 and 72-hour and 7 days after exposure
Number of animals or in vitro replicates:
3 female animals. Immediately before the start of the test, both eyes of the three provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Animals showing evidence of ocular lesions were rejected and replaced.
Details on study design:
SCORING SYSTEM:
- Draize J.H. 1959, Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics"
- Kay J.H. and Calandra J.C., J. Soc. Cosmet. Chern., 1962 13 281-289

TOOL USED TO ASSESS SCORE:
- Standard ophthalmoscope.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 1 hour
Score:
19.7
Max. score:
21
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 24 hours
Score:
34.3
Max. score:
41
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 48 hours
Score:
27.7
Max. score:
39
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 72 hours
Score:
17.7
Max. score:
39
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 7 days
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
2.7
Max. score:
3
Reversibility:
not specified
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
2.3
Max. score:
3
Reversibility:
not specified
Irritant / corrosive response data:
The individual scores are presented. A dulling of the normal lustre of the corneal surface was noted in two treated eyes one hour after treatment. Diffuse corneal opacity was noted in all treated eyes at subsequent 24, 48 and 72-hour observations. Iridial inflammation was noted in all treated eyes one hour after treatment and at the 24 and 48-hour observations and in one treated eye at the 72-hour observation.
Moderate to severe conjunctival irritation was noted in all treated eyes one hour after treatment and at the 24-hour observation. Moderate conjunctival irritation continued to be noted in two treated eyes at the 48-hour observation and in one treated eye at the 72-hour observation.
Minimal conjunctival irritation was noted in one treated eye at the 48- hour observation and in another treated eye at the 72-hour observation.
Two treated eyes appeared normal seven days after treatment. The remaining animal was sacrificed for humane reasons following the 72-hour observation.
The test material produced a maximum group mean score of 34.3 and was classified as a moderate irritant (class 5 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results obtained in this study, group mean scores calculated (maximum group mean score of 34.3) and scoring according Kay and Calandra (1962) the test item was considered moderately irritant.
Executive summary:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The study followed EU Method B.5 and OECD Guideline 405 (Acute Eye Irritation / Corrosion).

A single application of the test material to the non-irrigated eye of three rabbits produced a dulling of the normal lustre of the corneal surface, diffuse corneal opacity, iridial inflammation and moderate to severe conjunctival irritation. The test material produced a maximum group mean score of 34.3 and was classified as a moderate irritant (Class 5 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.