Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
other information
Study period:
Nov to Dec 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well reported GLP Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of test material in study report: LZ937.00
Batch No. 624
crystalline solid; purity: 99.3%

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Duration of treatment / exposure:
24 h
Observation period (in vivo):
28 days
Number of animals or in vitro replicates:
3 males

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24 h, 48 h and 72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 28 d
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24 h, 48 h and 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24 h, 48 h and 72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24 h, 48 h and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 9 d
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24 h, 48 h and 72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 h
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24 h, 48 h and 72 h
Score:
0.66
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24 h, 48 h and 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 9 d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24 h, 48 h and 72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 6 d
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24 h, 48 h and 72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 9 d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24 h, 48 h and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 6 d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24 h, 48 h and 72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24 h, 48 h and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 d
Other effects:
A thick white patch covering the lower third of the cornea was noted in Animal 1 from study days 9-28.

Any other information on results incl. tables

Results of the study:

 animal  sex  body weight  Observation  1 h 24 h  48 h  72 h   6 d  9 d  12 d  15 d  19 d 23 d 26 d   28 d
 1  m  2.78 kg  corneal opacity (degree)  2 2
       corneal opacity (area  4F  4F 4F  3F  1F  1F  1F  1F  1F  1F  1F  1F 
       iris  1 1 1  0  0  0
       conjunctivae, redness  2  0  0  0  0
       conjunctivae, chemosis  3 1  0  0  0
       discharge  2 2*  2* 0
 2  m  2.7  corneal opacity (degree)  1
       corneal opacity (area)  1F 1F  0F  -
       iris  1
       conjunctivae, redness  2
       conjunctivae, chemosis  2
       discharge  1 - - - -
 3 2.8   corneal opacity (degree)  1 -
      corneal opacity (area)  3F 3F  2F 0F  - -
       iris  1
       conjunctivae, redness  2 - - - -
       conjunctivae, chemosis  2 -
      discharge  2

F = stained with fluorescin

* = thick white discharge

Applicant's summary and conclusion

Executive summary:

0.1 ml of the pulverised test substance was administered into the conjunctival sac of in each case one rabbit eye of 3 males. The grade of ocular reaction was recorded after 1, 24, 42 and 72 h. Observations were extended up to day 28, in order to fully evaluate reversibility of reactions.

In this eye irritation study methyl 3-aminocrotonate was slightly eye irritating to the eyes of two animals but resulted in irreversible changes (an easily discernible translucent area of the cornea (score 2) from 1 h after instillation up to day 28) in one animal. Therefore,

methyl 3-aminocrotonate has to be classified as a seriously eye damaging agent.