Ocular irritation

Irrespective of work conditions in different situations (e.g., chemical factories, heavy industries, metal/package industries), eye protection becomes an important aspect of human safety. Present-day industries use a variety of substances that are 

A number of industrial chemicals were screened using AFNOR protocols with rabbits as the test systems. Information on the appearance and irritancy potential of different chemicals (and the classification thereof) offers valuable clues to the worker to avoid skin injury (Table 16-4). Certain drugs normally used by humans can cause adverse effects on eyes. The types of ocular disturbance are blurring of vision and diplopia, impairment of visual acuity, yellow vision (xanthopsia), corneal opacities, and lenticular opacities and drugs producing or precipitating the formation of cataract, which have been implicated with the use of candidate drugs. 

For instance, blurring of vision and diplopia are caused by the use of imipramine, iproniazid, chlorpromazine, thioridazine, and promethazine. Impairment of visual acuity is caused by chlorpropamide, tolbutamide, alcohol, chlorpromazine, phenylbutazone, indomethacin, chloroquine, sulfonamides, ethambutol, chloramphenicol, isonex, clioquinol, quinine, streptomycin, and paraaminosalicylate. Yellow vision (xanthopsia) has been traced to the use of sulfonamides, streptomycin, methaqualone, barbiturates, chlorothiazide, 

TABLE 16-3 AFNOR Scale of Ocular Irritancy and the Interpretation  

Acute Ocular Day 7 Individual Mean Ocular Irritancy 

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Tests have shown that citric acid is not corrosive to skin but is a skin and ocular irritant (50). Eor these reasons it is recommended that individuals use appropriate personal protection to cover the hands, skin, eyes, nose, and mouth when in direct contact with citric acid solutions or powders. 

Internal Reports Skin Corrosion Potential ofEiquid Citric Acid S0%,Jan. 19, 1979, Dermal Irritation of Citric Acid in the Rabbit, Dec. 20, 1990, Ocular Irritation of Citric Acid in the Rabbit, May 14, 1991, Miles Inc., Elkhart, Ind. 

Methods of testing for eye and skin irritation potential have been reviewed (137). The official FHSA procedure for evaluating ocular irritation potential of detergent products is a modified Drai2e rabbit eye test (138). Some controversy surrounds this method at present, and a search for a procedure less injurious to test animals is in progress. In general, the order of irritation is cationic > anionic > nonionic (139). 

The water solubiUty of glutaric acid fosters its toxicity. Glutaric acid is a known nephrotoxin. Renal failure has been documented ia rabbits adruinistered sodium glutarate subcutaneously (124). Dibasic ester (Du Pont), which contains primarily dimethyl glutarate, has low acute toxicity by inhalation and by ingestion, and is moderately toxic via dermal absorption. The acid is both a dermal and ocular irritant of humans. The ester is a severe skin irritant and may cause a rash ia humans (120). 

Ribavirin is given by inhalation and can cause worsening of respiratory status, hypotension, and ocular irritation, including erythema (redness of skin), conjunctivitis, and blurred vision. 

The most common adverse reactions associated with the NSAIDs include transient burning and stinging upon instillation and other minor ocular irritation. 

These drug are contraindicated in individuals with known hypersensitivity to an individual drug or any components of the drug. The NSA.ID flurbiprofen is contraindicated in patients with herpes simplex keratitis. Diclofenac and ketorolac are contraindicated in patients who wear soft contact lenses (may cause ocular irritation). 

The ocular irritation caused by cosmetic ingredients has been evaluated by the determination of the amount of histamine contained in tears. Contact of surfactants and the eye tissue cause an immediate dose-dependent release of histamine through direct cytotoxic damage of cell membranes. This method has been tested with sodium lauryl sulfate with volunteers [187]. 

Limited information was available regarding ocular irritation by endosulfan. An unspecified amount of a 20% aqueous suspension of endosulfan instilled in the eyes of rabbits did not produce any ocular irritation or congestion (Gupta and Chandra 1975). 

Hj antihistamines are the most commonly prescribed medications for AR. Hj antihistamines bind to and stabilize the Hj histamine receptor, thereby inhibiting mast cell and basophil mediator release and resulting in reduction of sneezing, itching, rhinorrhea, and ocular irritation. Antihistamines do not prevent histamine release, nor do they bind to already-released histamine. For this reason, maintenance therapy is considered optimal. However, antihistamines are also effective when taken on an as-needed basis.4,11,12 Antihistamines only minimally... 

Ocular irritation or soreness Blurry vision Contact lens intolerance Diurnal fluctuation Symptoms that worsen later in the day... 

Anti-inflammatory agents may be used in conjunction with artificial tears. The only approved agent is cyclosporine emulsion. Administered topically, it is thought to act as a partial immuno-modulator suppressing ocular inflammation, but the exact mechanism is unknown. Cyclosporine emulsion increases tear production in some patients. Fifteen minutes should elapse after instillation of cyclosporine before artificial tears are instilled.31 Use of topical corticosteroids for short periods (e.g., 2 weeks) may suppress inflammation and ocular irritation symptoms. No topical corticosteroid is approved for this indication, however.30... 

Based on these data, it is not likely that acute exposure of humans to environmental levels of polyalphaolefin hydraulic fluids will result in ocular irritation. There is insufficient information to determine if long-term exposure to polyalphaolefin hydraulic fluids will result in ocular irritation in humans. 

As a part of the Federal Hazardous Substances Act (FHSA), a modified Draize test was adopted [63-65] as the official method for evaluation of acute ocular irritancy [66]. It is a pass/fail determination that remains in effect today. Two refinements have been accepted as alternatives (a) the test which uses a small volume more consistent with the capacity of the inferior con-... 

Current guidelines for toxicity evaluation of ophthalmic formulations involve both single and multiple applications, dependent on the proposed clinical use [39]. The multiple applications may extend over a 9-month period and incorporate evaluations of ocular irritation and toxicity, systemic toxicity, and determinations of systemic exposure (toxicokinetics). In many cases the systemic exposure from an ocular route is less than by parenteral administration, information that will assist in determining whether additional studies may be needed to establish systemic safety of the ophthalmic preparation. U.S. and international guidance documents are available [71,72], and regulations and tests have been summarized for ophthalmic preparations [39,73,74],... 

Surfactants. The use of surfactants is greatly restricted in formulating ophthalmic solutions. The order of surfactant toxicity is anionic > cationic >> nonionic. Several nonionic surfactants are used in relatively low concentrations to aid in dispersing steroids in suspensions and to achieve or to improve solution clarity. Those principally used are the sorbitan ether esters of oleic acid (Polysorbate or Tween 20 and 80), polymers of oxyethylated octyl phenol (Tyloxapol), and polyoxyl 40 stearate. The lowest concentration possible is used to perform the desired function. Their effect on preservative efficacy and their possible binding by macromolecules must be taken into account, as well as their effect on ocular irritation. The use of surfactants as cosolvents for an ophthalmic solution of chloramphenicol has been described [271]. This com-... 

The anhydrous petrolatum base may be made more miscible with water through the use of an anhydrous liquid lanolin derivative. Drugs can be incorporated into such a base in aqueous solution if desired. Poly-oxyl 40 stearate and polyethylene glycol 300 are used in an anti-infective ointment to solubilize the active principle in the base so that the ointment can be sterilized by aseptic filtration. The cosmetic-type bases, such as the oil-in-water (o/w) emulsion bases popular in dermatology, should not be used in the eye, nor should liquid emulsions, owing to the ocular irritation produced by the soaps and surfactants used to form the emulsion. 

Ocular irritation has also been noted after animals were exposed to hydrogen sulfide. Epiphora was noted in Fischer-344 rats exposed to 400 ppm, but not 200 ppm, of hydrogen sulfide for 4 hours (Lopez et al. 1988b). Eye irritation was noted in guinea pigs exposed to 20 ppm of hydrogen sulfide for 20 days,... 

Lefebvre M, Yee D, Fritz D, et al. 1991. Objective measures of ocular irritation as a consequence of hydrogen sulphide exposure. Vet Hum Toxicol 33 564-566. 

Respiratory distress nasal and ocular irritation some deaths in 4-5 days pulmonary edema bronchial degeneration excess blood in heart, liver, and kidney... 

Contact with crystalline hexachloroethane (100 mg caused swelling, iritis, corneal opacity, and discharge when placed in rabbit eyes overnight. All signs of ocular irritation were reversed 72 hours later (Weeks et al. 1979). This LOAEL for ocular effects in rabbits is reported in Table 2-3. 

Clinical signs of ocular irritation (lacrimation, hyperemia of the conjunctiva) were observed throughout a 24-week study in rabbits exposed to 3,000 ppm -hexane (Lungarella et al. 1984). These effects were the result of direct contact of -hcxanc vapor with the eye. 

Ocular irritation is significantly different from the other local tissue irritation tests on a number of grounds. For the pharmaceutical industry, eye irritation testing is... 

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