Acute systemic toxicity via ocular exposure route is not a well understood aspect. Any material/drug/chemical that comes in contact with the eye can evade the first pass metabolism and enter the systemic circulation through the conjunctival blood vessels or via the nasolacrimal route. In this study, the effect of ocular irritant chemicals on the systemic toxicity was assessed in rabbit. Eyes of rabbits were exposed to known ocular irritant (cetyl pyridinium chloride, sodium salicylate, imidazole, acetaminophen, and nicotinamide) for 24？h and scored. After a period of 72？h, blood was collected from the animals for examining the hematological and biochemical parameters. The animals were then sacrificed and the eyes were collected for histopathology and cytokine analysis by ELISA. Splenocyte proliferation was assessed by tritiated thymidine incorporation assay. The liver and brain of the treated animals were retrieved for evaluating oxidative damage. The chemicals showed moderate to severe eye irritation. Inflammation was not evident in the histopathology but proinflammatory markers were significantly high. The splenocyte proliferation capacity was undeterred. And there was minimal oxidative stress in the brain and liver. In conclusion, acute exposure of ocular irritants was incapable of producing a prominent systemic side effect in the current scenario. 1. Introduction Toxic effects seen when chemicals/drug/materials are exposed in single or multiple doses over a period of 24？h are referred to as acute toxicity. Acute toxic effect of a chemical will be different from the prolonged exposure (subacute) to a chemical. Toxicity of a substance is affected by multifaceted parameters and is complex. Routes of exposure are one of the parameters that affect the toxicity of a substance and can cause a systemic effect. Intravenous administration of a substance elicits the most profound toxic effect; however the substance is susceptible to first pass metabolism in the liver. Other prominent routes of exposure include inhalation, intraperitoneal, subcutaneous, intramuscular, intradermal, oral, and topical. Ocular exposure of drugs or chemical is a relatively unexplored territory. Any chemicals that come in contact with the eye accidentally or by deliberate administration (ophthalmologic drug or cosmetics) can enter the systemic circulation through the rich network of conjunctival blood vessels or via the nasolacrimal route [1, 2]. Entry of drug through the above pathways ensures high plasma concentration of the substance due to evading of the first pass metabolism.
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