Acute Eye Irritation Test

Eye irritation is the production of reversible changes in the eye following the application of a test chemical to the anterior surface of the eye. Eye corrosion is the production of irreversible tissue damage in the eye following application of a test chemical to the anterior surface of the eye. 

In the evaluation of a chemical s toxic characteristics, determination of the irritant/corrosive effects on the eyes of mammals is an important parameter. Data obtained from this test indicate hazards likely to arise from exposure of the eyes and associated mucous membranes to the toxic chemical under test. 

Test System Although a variety of animals have been used for acute eye irritation tests, the adult albino rabbit is the preferred species. The animals should 

Chemicals that are strongly acidic or alkaline in nature (i.e., with a pH of 2 or less 11.5 or greater) need not be tested because of their probable corrosive properties. Chemicals that demonstrate definite corrosion or severe irritation in a dermal study need not be further tested for eye irritation. It may be presumed that such chemicals produce similarly severe effects in the eyes. 

To test a chemical contained in a pressurized aerosol container, the eye should be held open and the test chemical administered in a single burst of about 1 second from a distance of 10 cm directly in front of the eye. The dose may be estimated by weighing the container before and after use. Care should be taken not to damage the eye. Pump sprays should not be used but instead, the liquid should be expelled and 0.1 mL collected and instillated into the eye as described for liquids. 

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Much toxicological data are available on this red pigment acute oral toxicity in mice, 90-day subchronic toxicological study, acute dermal irritation and corrosion, acute eye irritation and corrosion, anti-tumor effectiveness, micronucleus test in mice, AMES test Salmonella typhimurium reverse mutation assay), estimation of antibiotic activity, and results of estimation of five mycotoxins. A new patent on Arpink Red was filed in 2001 with claims of anti-cancer effects of the anthraquinone derivatives and apphcations in the food and pharmaceutical fields. 

In the OECD test guideline for acute eye irritation/corrosion (OECD TG 405), the following definitions are provided ... 

In the EU test guidelines for acute dermal irritation/corrosion (Annex V B.4) and for acute eye irritation/corrosion (Annex V B.5), the dehnitions for dermal and eye irritation/corrosion are identical to those provided in the respective OECD test guidelines (Section 4.5.1.1). 

The base set of data is designed to provide fundamental information regarding acute toxicity by the oral route and/or intended dose route (Table 1). Skin and eye irritation testing should be conducted irrespective of the route of use of the candidate excipient. These data are intended to protect researchers during the research and production life of the material. 

Ocular irritation tests are significantly different from the other local tissue irritation tests on a number of grounds. For the pharmaceutical industry, eye irritation testing is performed when the material is intended to be put into the eye as a means or route of application for ocular therapy. There are a number of special tests applicable to pharmaceuticals or medical devices that are beyond the scope of this discussion since they are not intended to assess potential acute effects or irritation. In general, however, it is desired that an eye irritation test be both sensitive and accurate in predicting the potential to cause irritation in humans. Failing to identify human ocular irritants (lack of sensitivity) is to be avoided, but of equal concern is the occurrence of false positives. 

Primary Irritation. Dispersed as smoke, aerosol, or in solution, agents will contaminate skin and eyes and may cause acute inflammatory reactions at these sites. Therefore, there is a requirement to know if contact with the skin and eye will have a local tissue injuring potential and how formulation may affect the reaction. Supplemental to standard eye irritation tests it is of practical value to undertake in vivo studies on the influence of the agent on corneal thickness by pachymetry and on lOP by tonometry (Ballantyne et al., 1977a Myers et al., 1998 Ballantyne, 1999b). 

RBM (1992b) Acute eye irritation study in New Zealand White rabbits treated with test article MTBE. Istituto di Ricerche Biomediche Antoine Marxer RBM S.p.A, Rome, Italy... 

Acute oral, dermal, and inhalation studies on rats or other mammals Skin and eye irritation tests on rabbits... 

Safety/Toxicity Acute and chronic toxicity, cytotoxicity, estrogenicity, eye irritation tests, toxicity to insects, mutagenicity, oral toxicity, phototoxicity, teratogenicity, topical toxicity ... 

The conventional test for the irritant and corrosive potential of chemicals is the rabbit eye test, which was developed by Draize et al. (1944), and has become the international standard assay for acute eye irritation and corrosion (EC B.5, Directive 2004/73/EC OECD TG 405, 2002). The test material is applied to the conjunctival sac of the animal s eye and subsequent grading of ocular lesion is established cornea opacity, iris lesion, redness of conjunctivae, and oedema of conjunctivae (chemosis). 

OECD, 2002, Test Guideline 405, Acute Eye Irritation/Corrosion. 

Health and Safety Factors. Results of acute oral toxicity studies of 2-pyrrohdinone on white rats and guinea pigs show the LD q to be 6.5 ml,/kg. Skin patch tests on 200 human subjects indicate that 2-pyrrohdinone is a skin kritant, but there is no indication of sensitising action. It is a mild eye irritant (79). 

Primary Irritancy Studies. These studies are employed to determine the potential of materials to cause local inflammatory effects in exposed body surfaces, notably skin and eye, following acute or short-term repeated exposure. In general, the approach involves applying the test material to the surface of the skin or eye, and observing for signs of inflammation, their duration, and resolution. Reviews have been written about the conduct of primary eye irritation (58,86,87) and primary skin irritation studies (88,89). 

Enslein, K. An overview of structure-activity relationships as an alternative to testing in animals for carcinogenicity, mutagenicity, dermal and eye irritation, and acute oral toxicity. Toxicol Industrial Health 1988 4 479-98. 

Toxicological properties Acute toxicity (by two routes of admission) Skin irritation Eye irritation Skin sensitization 28 days subacute toxicity Ames test In vitro metaphase analysis (or mouse micronucleus test)... 

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