Ocular chemical exposures

Saini and Sharma [30] reported a series of 145 chemical eye injuries in 102 patients treated at a major referral center in India between 1984 and 1991 [30]. Bilateral injuries were seen in 42.1% of patients. Acids and alkalis accounted for 80% of chemical ocular injuries in this series. Two-thirds of the injuries occurred in young people working in laboratories and factories. Roper-Hall Grade III and IV injuries were seen in 52 eyes (35.9%). In total, 102 eyes (70.3%) recovered with a visual acuity of 6/60 or better. Ten eyes (6.9%) had no light perception. Phthis bulbi (a deformed eyeball with no light perception) occurred in 71.4% of the seven deliberate chemical assault victims but in only 3.6% of the accidental ocular chemical exposures. The final visual acuity was better in the eyes with less severe grades of chemical injuries on presentation [30],... 

No international or national databases were found that specifically collect data on ocular chemical injuries. There are individual publications detailing bums in general or chemical biuns (including eye and/or skin bums) in a region or country and case series from bum centers, hospitals, or groups of hospitals. Occupational bum data are usually regional in nature or are case series. National Poison Center databases such as the US American Association of Poison Centers National Poison Data System (NPDS) collect data on the annual number of eye exposures, but do not contain specific information... 

PURPOSE AND RATIONALE This test uses the ex vivo model of comeal organ culture previously discussed combined with surface biotinylation technique. The comeal epithelium functions as a barrier that separates the internal ocular tissues from the external environment and is therefore vulnerable to chemical insult (Gipson and Sugrue 1994). The joint assessment of comeal organ culture and surface biotinylation is a measure of ocular toxicity that is intended to reveal disrupted tight junction barriers following chemical exposure. 

Comeal organ culture combined with objectively quantifiable assays for comeal epithelial barrier disruption reduces the high variability associated to the subjectively scored Draize Test. The FITC-Dextran retention has been studied as a quantitative evaluation of the comeal epithelial barrier (Lopez et al. 1991) following chemical exposure of bcnzal konium chloride (BAC), Polyquad, and Thimerosal. Sodium dodecyl sulfate (SDS) has also been tested for disruption of the tight junctions via FITC-Dextran retention assay. However, as an objective outcome measure for ocular toxicity, the scoring system is not yet quantitatively comparable for assessment of ocular irritancy to multiple test products. This limitation is similar to surface biotinylation assays. As fluorometry is utilized more extensively in varied laboratories with numerous test chemicals a standardized scoring system can be elicited similar to the familiar Draize Test. 

DNA binding of AP-1 and NFkB is concentration-dependent and corresponds to Draize scores for ocular irritancy. Test chemical exposure time and probelabeling efficiency may introduce variance to results. Despite the variance, detection of altered expression and/or activation of stress-response transcription factors like AP-1 and NFkB can serve as an early marker for subsequent deteriorative outcomes (Ramesh et al. 1999) of ocular toxicity. 

Of the bum injury patients admitted to a specialized Regional Bum Center in Toronto, Ontario, Canada, over an 8-year period, the 24 chemically injured patients made up 2.6 % of the total [29], Occupationally related chemical exposures accounted for 75 % of these injuries, and the involved chanicals included hydrofluoric acid, sulfuric add, black liquor (a heated mixture of sodium carbonate, sodium hydroxide, sodium sulfide, sodium thiosulfate, and sodium sulfate), lyes (alkaline corrosives), phenol, and potassium permanganate. Complications were seen in 58 % of chemically injured patients, including chemical ocular injuries, wound infections, tendon exposures, toe amputation, and systemic toxicity. Of these 24 patients, 14 required extensive surgical debridement and skin grafting. One patient with a 98 % TBSA chemical skin injury died. Of those patients who had typical decontamination measures such as removal of contaminated clothing... 

In a US study of compensable work-related ocular injuries, the incidence of eye burns was 23.4 per 10,000 employees [9]. The majority of these were associated with chemical exposures. 

In mammals, the toxicity of nickel is a function of the chemical form of nickel, dose, and route of exposure. Exposure to nickel by inhalation, injection, or cutaneous contact is more significant than oral exposure. Toxic effects of nickel to humans and laboratory mammals are documented for respiratory, cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, dermal, ocular, immunological, developmental, neurological, and reproductive systems (NAS 1975 Nielsen 1977 USEPA 1980, 1986 WHO 1991 USPHS 1993). 

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). 

Dermal/Ocular Effects. No studies were located regarding dermal/ocular effects in humans. Acute-duration dermal exposure caused skin necrosis in rabbits however, effects were reversible within 2 weeks (Duprat and Gradiski 1978). Nasal irritation resulted from 15 minute exposure to vapor concentrations of 155 ppm (de Ceaurriz et al. 1988). No dermal/ocular effects were seen following intermediate- or chronic-duration dermal exposure in rabbits. Based on acute effects in rabbits, hexachlorobutadiene may pose some risk to humans following skin contact with the chemical-depending on the area exposed. Inhalation of vapors may cause irritation of the nasal mucosa. 

Of 1,720 persons with occupational bum injuries in the US State of North Carolina, the most common event was exposure to corrosive substances [18]. Of bum injury patients from all causes, 361 patients (69.6%) also had eye bums [18]. Ocular bums comprise about 7-18% of ocular trauma presenting to emergency departments in the USA and eye injuries account for about 3 % of total occupational injuries [6]. Most of these (approximately 84%) are chemical bums. About 15-20% of patients with facial bums also have ocular bums. The ratio of acid/alkali chemical ocular bums is 1 1-1 4 [6]. 

Cartotto et al. [34] reported a series of patients treated at the bum center in Toronto, Ontario, Canada [34], Of the total 24 chemical bum cases, there were 8 chemical eye splashes. Five of these eight patients were decontaminated at the scene (presumably with water). The three chemical eye splash patients who did not receive immediate decontamination developed severe ocular injuries. However, three of the five who had immediate decontamination developed comeal erosions and one patient with eye exposure to black liquor developed a very deep comeal erosion leading to blindness [34]. 

As mentioned earlier, nickel carbonyl is a volatile intermediate in the Mond process for nickel refining. This compound also is used for vapor plating of nickel in the semiconductor industry, and as a catalyst in the chemical and petrochemical industries. The toxicity of the compound has been known for many years Exposure of laboratory animals to the compound has induced a number of ocular anomalies, including aiioplidialiiiiaandinicrophtlialmia, and has been shown to be a carcinogenic for rats. 

Based on adverse ocular effects observed in humans and animals exposed to chemicals structurally-related to CDDs and animals (monkeys) exposed to 2,3,7,8-TCDD itself, it is reasonable to assume that CDDs will cause similar effects under similar exposure conditions. 

Chromium(IV) dioxide is a tetravalent chromium compound with limited industrial application. It is used to make magnetic tape, as a catalyst in chemical reactions, and in ceramics (Hartford 1979). Because of its limited industrial uses, the potential for human exposure is less for chromium dioxide than for the more industrially important chromium(VI) and chromium(ni) compounds. A single chronic inhalation study in rats exposed to 15.5 mg chromium(IV)/m3 as chromium dioxide reported no respiratory, cardiovascular, gastrointestinal, hematological, hepatic, renal, or dermal/ocular effects (Lee et al. 1989). 

PURPOSE AND RATIONALE This test uses an ex vivo model of corneal organ culture, preferentially porcine, to obtain information of the possible ocular toxicity of various chemicals. This test is used as an alternative to the Draize Test to minimize or replace the use of live animal testing of ocular irritancy (Symposium, Proceeding 1996). The test allows for determination of reversibility of corneal injury following exposure to chemicals, drugs or cosmetics (Xu etal. 2004). 

The dose of chemicals applied to filter paper may be modified to view concentration-dependent parameters of test substances. By establishing the dose response to ocular irritancy, comparisons can be made to the mild, moderate and severe grading systems previously validated (Stokes 2003). An alternative exposure of test chemicals may be performed by direct application of test solution dropwise onto the center surface of the comeal (Xu et al. 2000). The test solution then dissolves into the culture media. 

The Navy proposes to set a SEAL 1 of 10 ppm and a SEAL 2 of 20 ppm for hydrogen sulfide. These levels are based on eye irritation reported at concentrations ranging from 5 to 30 ppm, particularly with coexposure to other chemicals or eye irritants that could lower the threshold for irritation. The Navy notes that evacuation should be considered if eye irritation becomes unbearable at hydrogen sulfide concentrations between SEAL 1 and SEAL 2, and that continued exposure could result in more permanent ocular changes, including keratoconjunctivitis and vesiculation of the corneal epithelium. 

Research should be conducted in experimental animals to determine the lowest concentration that causes serious effects, such as severe eye irritation or damage. Data are limited on the exposure that result in eye irritation, particularly for the concentrations, conditions, and durations associated with the transition from irritation to irreversible eye damage. More data quantifying the effects of other chemicals in lowering the threshold for ocular toxicity also are needed. Research should also be conducted to elucidate the dose-response curve for cytochrome oxidase inhibition with increasing hydrogen sulfide concentrations (i.e., 15 ppm and above). 

A previously developed PBPK-PD model for the CWNA surrogate DFP was parameterized to simulate the concentration and effects of low-level chemical warfare agents (CWAs) in the guinea pig after exposure by inhalation and subcutaneous injection. The model code was written to account for absorption of CWAs from multiple sites (respiratory tract - lower and upper, dermal, ocular) after... 

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