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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
Study period:
1938-1946
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline-similar study reported in sufficient detail to enable confident assessment of the method and interpretation of the results and published in a peer-reviewed journal

Data source

Reference
Reference Type:
publication
Title:
Chemical burns of the rabbit cornea
Author:
Carpenter CP, Smyth HF Jr
Year:
1946
Bibliographic source:
Am J Ophthalmol 29: 1363-72

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Grade the severity of eye burns from a large number of chemicals and translate each injury into a numerical score.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
other: normal, albino

Test system

Vehicle:
other: propylene glycol or water
Controls:
not specified
Amount / concentration applied:
0.005 mL undiluted, 5% solution and 15% solution
Duration of treatment / exposure:
18-24 hours
Number of animals or in vitro replicates:
Usually 5
Details on study design:
Rabbit eyes were selected on the basis of absence of grossly visible staining by the 5% aqueous solution of fluorescein sodium, flushed with distilled water for 20 seconds after application. After a 2-hr interval to allow the eye to return to normal, 0.005 mL of the undiluted material is applied to the center of the cornea while the lids are retracted. About one minute later, the lids are released. Eighteen to 24 hours later, the eye is examined in strong diffuse daylight, then stained with fluorescein, and the injury scored. Additional applications of the test material are made until the chemical can be assigned to a specific grade (see Table 2) . If large volumes are applied, lids are held closed for one minute before the animal is released.The individual numerical scores of each eye (see Table 1) were added together and then divided by the number of eyes (usually 5) to obtain the score of the injury caused by treatment. A total of 180 chemicals were arranged according to injury grades.

Results and discussion

In vivo

Results
Irritation parameter:
other: grade 8
Basis:
mean
Remarks:
15% solution scores over 5.0; 5% solution not over 5.0
Remarks on result:
other: A score of 5.0 corresponds to necrosis, visible only after staining and covering about three-fourths of the surface of the cornea; or a more severe necrosis covering a smaller area.
Irritant / corrosive response data:
Succinic anhydride was assigned grade 8 on the basis that 0.005 mL and 15% solutions yielded scores of over 5.0 and the 5% solution was not over 5.0.

Any other information on results incl. tables

Table 3. Injury grades of some chemicals when applied to the rabbit eye

 Grade 8 (0.005 mL and 15% solution yield scores of over 5.0, 5% solution not over 5.0)   
 Caproic acid  Phenyl methyl ketone
 *Di-2 -ethylhexyl amine Soap (granulated white) 
 Di-n-hexyl amine Succinic acid 
 *Dimethyl sulfate Succinic anhydride 
 *Ethylene diamine  Tetramethyl ethylene diamine
 *Formaldehyde  Trimethyl adipic acid
 Lactic acid  
 Grade 10 (1% solution yields score of over 5.0)   
 *Maleic anhydride  *Sodium hydroxide
    * Compounds known to have caused severe human eye injury

Applicant's summary and conclusion

Interpretation of results:
corrosive
Remarks:
Migrated informationCriteria used for interpretation of results: expert judgment
Conclusions:
Succinic anhydride caused severe injury to rabbit eyes when applied undiluted and as a 15% solution for an 18- 24 hour exposure; a 5% solution did not cause this eye damage grade.Succinic acid was graded in the same effect group.Maleic anhydride caused severe injury to rabbit eyes when applied as a 1% solution for an 18- 24 hour exposure.
Executive summary:

Undiluted succinic anhydride (0.005 mL) was applied to the center of the cornea of approximately 5 albino rabbits while the lids were retracted. Lids were released after one minute. Larger volumes of 5% and 15% succinic anhydride solutions were also applied and lids were held closed for one minute before the animal was released. Eighteen to 24 hours later, the eye was examined, stained and scored such that each injury was translated into a numerical score developed by the authors. The individual numerical scores of each eye were added together and then divided by the number of eyes to obtain the score of the injury caused by treatment. These scores were then arranged according to injury grades developed by the authors. Undiluted and 15% succinic anhydride yielded an injury score of over 5.0 and the 5% solution yielded an injury score not over 5.0. The authors described succinic anhydride as grade 8, which causes severe injury to rabbit eyes.

Another cyclic anhydride also tested in this scheme for eye injury. Maleic anhydride was scored as grade 10 for injury to the rabbit eye and a solution of 1% yielded an injury score of over 5.0.

Sufficient information is available on succinic anhydride and a separate eye irritation study is not proposed and cannot be justified based upon animal welfare considerations.