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
Study period:
No information is provided in the study report other than the completion date of September 15, 1977.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study was performed prior to the implementation of Good Laboratory Practice standards. It was, however, performed in accordance with the method described in 16 Code of Federal Regulations (CFR) Section 1500.42. The data are well documented and scientifically acceptable. See: U.S. Title 16: Commerical Practices, Part 1500-Hazardous Substances and Articles; Administrative and Enforcement Regulations, Section 1500.42 Test for eye irritants.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: 16 CFR Section 1500.42 Test for eye irritants
Deviations:
not applicable
Principles of method if other than guideline:
Title 16: Commercial Practices
PART 1500—HAZARDOUS SUBSTANCES AND ARTICLES; ADMINISTRATION AND ENFORCEMENT REGULATIONS
§ 1500.42 Test for eye irritants.
(a)(1) Six albino rabbits are used for each test substance. Animal facilities for such procedures shall be so designed and maintained as to exclude sawdust, wood chips, or other extraneous materials that might produce eye irritation. Both eyes of each animal in the test group shall be examined before testing, and only those animals without eye defects or irritation shall be used. The animal is held firmly but gently until quiet. The test material is placed in one eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test substance is dropped. The lids are then gently held together for one second and the animal is released. The other eye, remaining untreated, serves as a control. For testing liquids, 0.1 milliliter is used. For solids or pastes, 100 milligrams of the test substance is used, except that for substances in flake, granule, powder, or other particulate form the amount that has a volume of 0.1 milliliter (after compacting as much as possible without crushing or altering the individual particles, such as by tapping the measuring container) shall be used whenever this volume weighs less than 100 milligrams. In such a case, the weight of the 0.1 milliliter test dose should be recorded. The eyes are not washed following instillation of test material except as noted below.

(2) The eyes are examined and the grade of ocular reaction is recorded at 24, 48, and 72 hours. Reading of reactions is facilitated by use of a binocular loupe, hand slit-lamp, or other expert means. After the recording of observations at 24 hours, any or all eyes may be further examined after applying fluorescein. For this optional test, one drop of fluorescein sodium ophthalmic solution U.S.P. or equivalent is dropped directly on the cornea. After flushing out the excess fluorescein with sodium chloride solution U.S.P. or equivalent, injured areas of the cornea appear yellow; this is best visualized in a darkened room under ultraviolet illumination. Any or all eyes may be washed with sodium chloride solution U.S.P. or equivalent after the 24-hour reading.

(b)(1) An animal shall be considered as exhibiting a positive reaction if the test substance produces at any of the readings ulceration of the cornea (other than a fine stippling), or opacity of the cornea (other than a slight dulling of the normal luster), or inflammation of the iris (other than a slight deepening of the folds (or rugae) or a slight circumcorneal injection of the blood vessels), or if such substance produces in the conjunctivae (excluding the cornea and iris) an obvious swelling with partial eversion of the lids or a diffuse crimson-red with individual vessels not easily discernible.

(2) The test shall be considered positive if four or more of the animals in the test group exhibit a positive reaction. If only one animal exhibits a positive reaction, the test shall be regarded as negative. If two or three animals a positive reaction, the test is repeated using a different group of six animals. The second test shall be considered positive if three or more of the animals exhibit a positive reaction. If only one or two animals in the second test exhibit a positive reaction, the test shall be repeated with a different group of six animals. Should a third test be needed, the substance will be regarded as an irritant if any animal exhibits a positive response.

(c) To assist testing laboratories and other interested persons in interpreting the results obtained when a substance is tested in accordance with the method described in paragraph (a) of this section, an “Illustrated Guide for Grading Eye Irritation by Hazardous Substances” will be sold by the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402.1 The guide will contain color plates depicting responses of varying intensity to specific test solutions. The grade of response and the substance used to produce the response will be indicated.
GLP compliance:
no
Remarks:
This study was performed prior to the implementation of GLP standards.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The test material was in the form of a clear, viscous light brown liquid.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Six New Zealand White rabbits were received from Maryland Breeding Farms, Inc., Hewitt, N.J. The animals were individually housed and equilabrated in the laboratory prior to experimentation. Only animals which were determined to be free of ocular defects prior to compound administration were used in the study. No further information was provided in the study report on the test animals or environmental conditions.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
One-tenth milliliter of the test material at room temperature was instilled into one eye of each of the six rabbits. The animals received no further treatment.
Duration of treatment / exposure:
The test material was applied once.
Observation period (in vivo):
The eyes were examined and scored for ocular reactions (Draize et al., 1944) on days 1, 2, 3, 4, 7, 10, and 14 following compound administration or until the eyes were free of signs of irritation for two consecutive observations. A fluoroscein wash was used when necessary in scoring ocular abnormalities. The scoring scale used is based on Draize et al. (1944).

Reference: Draize et al. (1944) Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J. Pharm. Exp. Ther., Vol. 82, pp. 337-390.

Reference: Draize et al. (1944) Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J. Pharm. Exp. Ther., Vol. 82, pp. 337-390.
Number of animals or in vitro replicates:
6

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
n = 6
Time point:
other: 24 hours
Score:
>= 12
Max. score:
80
Reversibility:
fully reversible within: 10 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
n = 6
Time point:
other: 48 hours
Score:
>= 9
Max. score:
8
Reversibility:
fully reversible within: 10 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
n = 6
Time point:
other: 72 hours
Score:
>= 8
Max. score:
80
Reversibility:
fully reversible within: 10 days
Irritation parameter:
iris score
Basis:
mean
Remarks:
n = 6
Time point:
other: 24 hours
Score:
>= 2
Max. score:
10
Reversibility:
fully reversible within: 2 days
Irritation parameter:
iris score
Basis:
mean
Remarks:
n = 6
Time point:
other: 48 hours
Score:
>= 0
Max. score:
10
Remarks on result:
other: Normal
Irritation parameter:
iris score
Basis:
mean
Remarks:
n = 6
Time point:
other: 72 hours
Score:
>= 0
Max. score:
10
Remarks on result:
other: Normal
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
n = 6
Time point:
other: 24 hours
Score:
>= 10
Max. score:
20
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
n = 6
Time point:
other: 48 hours
Score:
>= 5
Max. score:
20
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
n = 6
Time point:
other: 72 hours
Score:
>= 1
Max. score:
10
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Corneal opacity and ulceration were noted in all six eyes. Iritis was noted in three of six eyes, persisting in one eye through day 2. All six eyes were assigned positive scores for conjunctival redness. One eye was free of all signs of irritation of day 3, three eyes on day 4 and two eyes on day 10.

Applicant's summary and conclusion

Conclusions:
DEDTA produced eye irritation following application to the anterior surface of the eye, which were fully reversible within 10 days of application.