Toxicity ocular

The effects that L has on the eyes are similar to those of SM with the addition of immediate irritation. This immediate effect results in a reflex blepharospasm that limits exposure and caused early reviewers to conclude that L had less effect than SM. The pathology of L induced ocular injury has been described by a number of early reviews of the defence litera-ture, but much of the original source data are unobtainable. The reviews however describe a destructive ocular lesion from small amounts of liquid L instilled into rabbit eyes. A 0.1 mg drop caused perforation of the cornea in 75% of animals treated and corneal haze in the remainder. Gates et al. report US defence sources as determining that doses of 0.01-0.02 mg per eye of liquid L will cause permanent damage to rabbit eyes equivalent to that caused by 0.1-0.2 mg of SM. The same sources report that a nominal Ct of 2800 mg min m of L is required to produce moderate corneal damage in dogs and a Ct of 5500 mg min m is required for a destructive lesion. These 

Cts are high compared with those of SM that cause effects in humans (see Chapter 5). 

No studies of the effect of L on human eyes, or reference to them, have been located. 

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The toxicity of a few boric acid esters has been summarized (30). In general the toxicities are directiy related to the toxicity of the alcohol or phenol produced on hydrolysis. Methyl borate has an oral rat LD q of 6.14 mL/kg in a range finding test (31) and the percutaneous LD q for the rabbit of 1.98 mL/kg. In eadier work (32), the oral LD q for the rat was 2.82 mL/kg the intraperitoneal LD q was 3.2 mL/kg. It has been shown that the mouse is more susceptible to these compounds than the rat. Methyl borate was found to be moderately irritating in an ocular toxicity test using rabbits (31,32) but only mildly irritating to skin (31). 

Anand M, Gopal K, Mehrotra S, et al. 1987. Ocular toxicity of organochlorinated pesticides in rabbits. Journal Toxicol-Cut and Ocular Toxicol 6 161-171. 

J. (1985). Ocular toxicity of intravitreally injected liposomal amphotericin B in rhesus monkeys. Am. J. Ophthalmol., 100, 259-263. 

Albino rabbits have been the primary species used to test ocular toxicity and irritation of ophthalmic... 

Pavlidis NA, Petris C, Briassoulis E, Klouvas G, Psilas C, Rempapis J, Petroutsos G (1992) Clear evidence thatlong-term, low-dose tamoxifen treatment can induce ocular toxicity a prospective study of 63 patients. Cancer 69(12) 2961-2964... 

Gorin MB, Day R, Costantino JP, Fisher B, Redmond CK, Wickerham L, et al. (1998) Long-term tamoxifen citrate use and potential ocular toxicity. Am J Ophthalmol 126 338... 

Sinow, J. and Wei, E. (1973). Ocular toxicity of paraquat. Bull. Environ. Contam. Toxicol. 9 163-168. 

Various parts of the ophthalmological examination are shown in Table 20.14. The most important common ophthalmological test to evaluate patients for the occurrence of chronic drug-induced toxicity is slit-lamp examination. Specific types of drugs with known potential for ocular toxicity may require that special attention be directed to other evaluations shown in Table 20.14. Most drugs that are to be taken... 

These tests are of minimal value in determining ocular toxicity and are not recommended for routine use in ophthalmological examination to detect drug toxicities. 

Offord EA, Sharif NA, Mace K, Tromvoukis Y, Spillare EA, Avanti O, Howe WE, Pfeifer AM. Immortalized human corneal epithelial cells for ocular toxicity and inflammation studies. Invest Ophthalmol Vis Sci 40 1091-1101 (1999). 

Schneider AI, Maier-Reif K, Graeve T. The use of an in vitro cornea for predicting ocular toxicity. In Vitro Toxicol 10 309-318 (1997). 

Q74 Prilocaine should be avoided in patients receiving co-amoxiclav. Prilocaine may cause ocular toxicity v/hen used for ophthalmic procedures. 

Prilocaine is a local anaesthetic of low toxicity, which should be avoided in severe or untreated hypertension, severe heart disease and in patients using drugs that may cause methaemoglobinaemia. Prilocaine may cause ocular toxicity, which has been reported with the use of the product in excessively high doses during ophthalmic procedures. 

ICCVAM has evaluated alternative test methods for acute oral toxicity, genetic toxicity, biologies, immunotoxicity, dermal corrosion and irritation, ocular toxicity, developmental toxicity, pyrogeni-city, and endocrine disrupter effects (ICCVAM 2007). As examples, alternative test systems for dermal corrosion and irritation are described in the following text. 

Mild burning of the eyes after acute exposure to either trow-1,2-dichloroethylene vapor or aerosol was reported by two subjects in a 1936 self-experimentation study. However, dichloroethylene has been used in combination with ether as a general anesthetic in at least 2000 cases with no evidence of ocular toxicity ... 

Ocular toxicity of ethylene chlorohydrin and ethylene glycol in rabbits eyes. Toxicol Appl Pharmacol 1972... 

Epithelial keratitis that has not responded clinically to topical idoxuridine, or when ocular toxicity or hypersensitivity to idoxuridine has occurred. In a smaller number of patients resistant to topical vidarabine, trifluridine was also effective. 

If there are no signs of improvement after 7 days, or if complete re-epithelialization has not occurred after 14 days, consider other forms of therapy. Avoid continuous administration for periods exceeding 21 days because of potential ocular toxicity. 

Its most important adverse effects are visual disturbances. This ocular toxicity is dose dependent and has an incidence of lower than 1 % at low doses but can reach 5% at high dose regimens. Ocular toxicity manifests itself as retrobulbar neuritis usually after the second month of use. If therapy is discontinued immediately it is mostly reversible but not always. During the treatment visual function should periodically be tested. Age under 8 years is a relative contraindication as visual symptoms are difficult to monitor. 

Ovarian enlargement is the most common side effect of clomiphene use. The occurrence of multiple births following ovulation induction with clomiphene is 4 to 9% 90% of these multiple births are twins. Since clomiphene is teratogenic, therapy should be discontinued if there is a chance that conception has occurred. Rarely, irreversible ocular toxicities have been reported with clomiphene use. 

Ocular toxicity especially retinopathy may occur and may progress even after drug is discontinued. 

Ocular toxicity may occur if used longer than 21 days. 

Ocular toxicity Instillation of 0.5 or 1.0 mg into the rabbit conjunctival sac produced mild to moderate conjunctivitis that lasted a week. If the eyes were washed out with water a few minutes after dosing, the conjunctivitis lasted 24 h. 

Intravenous cidofovir is effective for the treatment of CMV retinitis and is used experimentally to treat adenovirus infections. Intravenous cidofovir must be administered with high-dose probenecid (2 g at 3 hours before the infusion and 1 g at 2 and 8 hours after), which blocks active tubular secretion and decreases nephrotoxicity. Cidofovir dosage must be adjusted for alterations in the calculated creatinine clearance or for the presence of urine protein before each infusion, and aggressive adjunctive hydration is required. Initiation of cidofovir therapy is contraindicated in patients with existing renal insufficiency. Direct intravitreal administration of cidofovir is not recommended because of ocular toxicity. 

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