Ocular toxicity mechanism

The other major toxic effect of methanol is the ocular toxicity. Although formaldehyde might be formed locally in the retina, this seems unlikely, whereas formate is known to cause experimental ocular toxicity. The mechanism suggested involves inhibition by formate of cytochrome oxidase in the optic nerve. As the optic nerve cells have few mitochondria, they are very susceptible to this "histotoxic hypoxia,"... 

Today, the overwhelming majority of animal ocular toxicity studies are performed in the rabbit model, and the study of SM is no exception. New Zealand white rabbits have been used extensively with both liquid SM and vapor exposures (Amir et al, 2000, 2003 Bossone et al, 2002 Vidan et al, 2002 Babin et al, 2004). Other animal models have been employed, including those using bovine and rat corneas. Many articles appear on these in the Bulletin of Johns Hopkins Hospital, Vol. 82, 1948. Individual articles from this volume are cited in the mechanism of action section. 

In vitro methods will continue to mature and, little by little, replace animal tests. However, a great deal of work first remains to be done on in vivo toxicological mechanisms. Therefore in vitro methods are already being used both to reduce animal testing (screening) and to study the mechanisms involved in ocular toxicity (research). 

Bantseev, V. McCanna, D. Banh, A. Wong, W. W. Moran, K. L. Dixon, D. G. Trevithick, J. R. Sivak, J. G. Mechanisms of ocular toxicity using the in vitro bovine lens and sodium dodecyl sulfate as a ehemical model. Toxicol. Sci. 2003, 73, 98-107. 

CNTs have been studied for cancer therapies despite the fact that these have been shown to accumulate to toxic levels within the organs of diverse animal models and different cell lines (Fiorito et al., 2006 Tong and Cheng, 2007). The molecular and cellular mechanisms for toxicity of carbon nanotubes have not been fully clarified. Furthermore, toxicity must be examined on the basis of multiple routes of administration (i.e., pulmonary, transdermal, ocular, oral, and intravenous) and on multiple species mammals, lower terrestrial animals, aquatic animals (both vertebrates and invertebrates), and plants (both terrestrial and aquatic). A basic set of tests for risk assessment of nanomaterials has been put forward (Nano risk framework). 

These findings should have two consequences. First, the development of potential long-term ocular endotamponades should consider harmonising viscosity and density to avoid mechanically induced side effects. And secondly, the evaluation of the biocompatibility should include effects not directly related to classic toxic phenomena. 

This acidic characteristic may be only slightly outstanding indeed. But a high concentration of phenol can generate severe corrosion lesions. Once again, the toxicity of the phenolate ion completes the deletery mechanism of destruction of the ocular tissues. 

Methods for Reducing Toxic Effects. Limited information is available on treatments to alleviate the symptoms of tetryl exposure. These include treatment of the dermatitis with calamine lotion and/or zinc oxide preparations, treatment of dermatitis and ocular irritation with aluminum acetate or boric acid compresses, and treatment of hypersensitivity-like symptoms (including severe dermatitis and asthma-like symptoms) with epinephrine or antihistamines (Bain and Thomson I 954 Bergman 1952 Cripps 1917 Eddy 1943 Ruxton 1917 Smith 1916 Troup 1946 Witkowski et al. 1942). The data on the pharmacokinetics of tetryl are also limited (Zambrano and Mandovano 1956). In order to develop mitigating agents, further studies are needed on its kinetics and mechanisms of action. 

Enriquez de Salamanca, A., Diebold, Y., Calonge, M., Garcia-Vazquez, C., Callejo, S., Vila, A., and Alonso, M. J. (2006), Chitosan nanoparticles as a potential drug delivery system for the ocular surface Toxicity, uptake mechanism and in vivo tolerance, Invest. Ophthalmol. Vis. Sci., 47(4), 1416-1425. 

The mechanism of fluorescein staining of ocular epithelia has been subject to some conjecture. In earlier work it was suggested that staining occurred due to accumulation in intraepithelial spaces rather than direct staining of the cells. However, it has become clear that fluorescein can directly stain diseased human corneal cells and rabbit epithelial cells. Moreover, the hyperfluorescence that probably represents micropunctate clinical staining is likely due to optimum dye concentration and fluorescence within the cell rather than simple pooling. Cellular hyperfluorescence occurred from both mechanical abrasion and chemically induced toxicity, conditions that presumably promote an intracellular concentration that allows definitive clinical visualization. An issue that has received some attention is whether repeated... 

Topical anesthetic abuse, mostly unintentional, remains a persistent cause of keratitis and epithelial defects, leading to continuing ocular pain, visual impairment, and at worst enucleation (SEDA-21,134) (SEDA-22,140) (327). Mechanisms include direct toxicity of the local anesthetic or preservative and immunological causes. 

The exact mechanisms of MIC toxicity are not known, however, carbamylation of globin and other blood proteins have been speculated to contribute to MIC-induced toxicity. Acute exposure via inhalation of MIC vapors is known to cause irritation to the respiratory tract causing severe pulmonary edema and injury that can lead to death. It is also corrosive to the eyes causing severe corneal damage. Survivors of acute exposures may exhibit long-term respiratory and ocular effects. Direct skin contact of MIC in the liquid or gaseous form causes irritation of the skin. 

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