Ocular opacity

Serious side-effects have been associated with the important psychotherapeutic agent, chlorpromazine (358), almost since its introduction. High sensitivity to sunburn, pigmentation of the skin and ocular opacity are common phototoxic effects [ 196]. In a series of phenothiazines, the chloro-substituted compounds, particularly chlorpromazine, prochlorperazine and perphenazine, showed by far the greatest phototoxic activity [197, 198]. 

Hydroxychlorpromazine and chlorpromazine sulphoxide generated hydroxyl radicals when excited at 330 nm under either anaerobic or aerobic conditions. It is interesting that phenothiazine sulphoxides and 7-hydroxychlorpromazine have been associated with ocular opacity. It was suggested that the highly reactive hydroxyl radicals may be the cause of this. Chlorpromazine does not damage the eye [209]. 

Ocular Effects. Acute exposure to cyanogen gas produced eye irritation in volunteers (McNemey and Schrenk 1960). Similarly, chronic exposure to cyanide in the working environment caused eye irritation in exposed individuals (Blanc et al. 1985). In addition, exposure to potassium silver cyanide caused ocular opacity in exposed animals, but comeal opacity is also a sign of excessive exposure to soluble silver salts alone. However, when cyanide was applied to a rabbit s eye, keratitis developed regardless of the chemical form of cyanide used (Ballantyne 1983b). 

PO loading dose 400 mg tid x 15-30 days, then 200-400 mg qd (5-10 mg/l ) pneurrwnitis when dose >400 mg/d elevation of digoxin level, prolongation of prothrombin time (70-100%) with warfarin pultrwnary fibrosis, hepatitis, ocular opacities proarrhythmic monitor thyroid and liver function... 

For intermediate-duration studies, Fischer 344 rats were exposed to 0, 0.011, 0.041, or 0.143 ppm HDI in air for 6 hours per day for 66-69 days over a period of approximately 13 weeks. Animals were exposed to HDI in 2-cubic-meter chambers (whole body). All rats were sacrificed at week 14. Ocular opacity was observed in all groups of rats tested, including control animals, and did not exhibit a concentration-... 

Phenothiazine derivatives have found many applications in todays chemical industry they have been and are used primarily as dyestuffs, antioxidants and in pharmaceutical preparations. This application is due to the discovery of their neuroleptic activity (1 ) (e.g. Chlorpromazine), but allergic skin reactions and ocular opacity are known to occur during therapy. 

Melanosis manifested by skin pigmentation, ocular opacities, and pigmented retinopathy have been reported as side effects of long-term therapy. These observations make the potential interaction of chlorpromazine with melanin of practical and clinical significance. 

Both phototoxic and photoallergic reactions occurred in patients receiving low doses of chlorpromazine and several other phenothiazine tranquillizers (Zelickson and Zeller 1964). High dosage and prolonged treatment can produce severe dermatitis that is frequently accompanied by darkening of the skin due to the deposition of melanin in lower layers of the dermis. Such patients may also suffer retinal damage, ocular opacity, and loss of vision. 

Systemic Rabbit (New Zealand) once Ocular 0.1 (diffuse opacity of the corneal surface) Hart 1976... 

During the application of the various guidelines for ophthalmic, contact lens, and intraocular products, ocular examination and biomicro scopic examination of rabbit eyes are completed with objective reproducible grading for conjunctival congestion, conjunctival swelling, conjunctival discharge, aqueous (humor) flare, iris involvement, severity and area of corneal opacity or cloudiness, pannus, and intensity of fluorescein staining [39,103]. Other available methods... 

Rabbit Once Ocular 100 mg M (corneal opacity Iritis) Weeks etal. 1979... 

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. 

Ocular Effects. Inhalation and oral exposure of animals to hexachloroethane caused lacrimation and reddening of the eyes after oral exposure (NTP 1977, 1989), or closing of the eyes as an avoidance mechanism during inhalation exposure (Weeks et al. 1979). Overnight, direct contact of the eyes with crystalline hexachloroethane resulted in corneal opacity and iritis in rabbits, but recovery was complete 3 days later (Weeks et al. 1979). Direct eye contact with hexachloroethane at hazardous waste sites may result in an eye irritation. 

TABLE 17.5. Comparison between In Vivo Ocular Irritancy and Opacity Induced in Bovine Cornea... 

Gautheron, P.D. and Sina, J.F. (1990). The bovine corneal opacity, an in vitro assay of ocular irritancy. Toxicologist 10 258. 

Muir, C.K. (1985). Opacity of bovine cornea in vitro induced by surfactants and industrial chemicals compared with ocular irritancy in vivo. Toxicol. Lett. 24 157-162. 

Rabbit (albino) once Resp Ocular 2.5 F (rapid breathing) mg/kg 2.5 mg/kg F (corneal opacity, keratitis) Ballantyne 1983b KCN... 

Ocular Effects. Direct application of 5% phenol to the eyes of rabbits resulted in severe irritation, conjunctivitis, and comeal opacity (Murphy et al. 1982). No other reports of ocular effects in humans or animals were identified. Based on the limited data, ocular effects are unlikely to occur at the concentrations that occur in the environment or near hazardous waste sites. 

Ocular Effects. No studies were located regarding ocular effects in humans after exposure to 3,3 -dichlorobenzidine by any route. No adverse effects on the eye were noted when dichlorobenzidine (isomer unspecified, free base) was directly placed in the conjunctival sac of the eye of rabbits (Gerarde and Gerarde 1974). However, 0.1 mL 3,3 -dichlorobenzidine dihydrochloride (dihydro salt of 3,3 -dichloro-benzidine) in a 20% com oil suspension produced erythema, pus, and comeal opacity, giving a 76% score in the Draize test within an hour when placed in the conjunctival sac of the eye of the rabbit (Gerarde and Gerarde 1974). Apparently, the irritant effects of hydrochloric acid Ifom the salt-compoimd contributed... 

The LCso for 4 hours in male rats was 980 mg/m this exposure caused an increase in liver size and corneal opacity that diminished over time in survivors. Exposure of male rats to 8mg/m 6 hours/day for 10 of 12 days produced reversible liver weight changes, reversible increases in serum enzyme activities, and liver necrosis. No ocular changes occurred. No observable effects occurred at Img/mk... 

Opacities of the cornea and lens due to deposition of fine particulate matter are a common complication of chlorpromazine therapy but regress after drug withdrawal. The most serious ocular complication is pigmentary retinopathy associated with high-dose thioridazine administration it is an irreversible condition leading to decreased visual acuity and possibly blindness. 

Corneal opacities and other ocular defects may occur. 

Corneal edema, eye discharge, eye irritation, eye pain, increased intraocular pressure, ocular discomfort, punctate keratitis, reduced visual acuity, visual disturbance, vitreous floater, vitreous opacities... 

Isophorone is also irritating to the eyes of rabbits. Application of 0.02-0.1 ml of undiluted isophorone directly to the eye caused severe injury, corneal opacity, and necrosis (Carpenter and Smyth 1946 Hazleton Labs 1964 Truhaut et al. 1972) (see Table 2-3). Hazleton Labs (1964) found that the corneal damage was no longer present 14 days after exposure. No studies were located regarding dermal/ocular effects in animals following intermediate or chronic duration exposure to isophorone. 

Cataract opacity of the lens. It is sometimes visible from the initial examination but, more often, it appears secondarily. It is the consequence of the intensity and the depth of the ocular lesions. It is an element revealing a very bad final prognosis for the burned eye. 

---