In vivo toxicology

Petry, T.W., Wolfgang, G.H., Jolly, R.A., Ochoa, R. and Donarski, W.J. (1992). Antioxidant-dependent inhibition of diquat-induced toxicity in vivo. Toxicology 74, 33-43. 

In the last 30 years, the use of in vitro tools for toxicological studies and evaluation has become relevant and the number of scientific works and techniques has increased day by day. One of the most important advantages of in vitro systems is their ability to serve as model for the central events in the in vivo toxicological process, and a depth evaluation of the intrinsic cellular toxicity can provide useful information for toxicological safety evaluation. 

S. Bailey in Physicochemical Drug Properties Associated with In Vivo Toxicological Outcomes, 15th RSC-SCI Medicinal Chemistry Symposium, September 9, 2009, Cambridge, UK. 

Stacey, N.H., K-L.Wong, and C.D. Klaassen. 1983. Protective effects of chromium on the toxicity of cadmium in vivo. Toxicology 28 147-153. 

Scheuhammer, A.M. 1987b. Erythrocyte delta-aminolevulinic acid dehydratase in birds. II. The effects of lead exposure in vivo. Toxicology 45 165-175. 

For the present, the utilization of in vivo toxicological models is imperative for responsible risk assessment of new chemical entities. At the same time, the use of the many in vitro models currently available can serve as valuable adjuncts to these in vivo assessments, not only reducing the number of animals used in risk assessment, but providing unique information and possibilities for scientists involved in the drug discovery and development process. 

Maduh EU, Nealley EW, Song H, et al. 1995. A protein kinase C inhibitor attenuates cyanide toxicity in vivo. Toxicology 100 129-137. 

Niknahad H, O Brien PJ. 1996. Antidotal effect of dihydroxyacetone against cyanide toxicity in vivo. Toxicology and Applied Pharmacology 138 186-191. 

The other change that needed to be made in the synthesis of RSR 13 for in vivo administration was the method of purification. RSR 13 is used in vivo as the sodium salt. I prepared the first batch for in vivo toxicology by triturating RSR 13 sodium salt with acetone to remove any vestiges of water. However, the first industrial scale-up procedure called for crystallization of the salt from ethanol-water. The ethanol-water crystals were not as soluble as the acetone triturated method and could not be formulated at a reasonable volume. We performed the crystal structure determination of the ethanol-water crystals and found that it was a heptahydrate (Figure 17.5) [50]. The problem for large-scale production of RS R13 was solved eventually by the industrial producers of RSR 13. 

The third health effect bioassay employed utilizes acute toxicity in whole animals (rats). Since the major objective of the Level 1 biological testing procedure is to identify toxicology problems at minimal cost, a two-step approach is taken to the initial acute in vivo toxicology evaluation of unknown compounds. The first is based on a... 

The initial formulation for most drugs is to allow basic in vivo toxicology, pharmacology and biopharmaceutical assessments to be conducted. Aqueous solutions for injection are optimum for this application since the entire dose is administered at a single time point and the problem of bioavailability does not arise. It is important that these formulations are considered carefully, particularly for drugs that are poorly water soluble, because potentially useful compounds may be rejected inadvertently. These early formulations are also crucial because they set an in vivo benchmark for the drug s future performance. 

Hughes, J.D., Blagg, J., Price, D.A., Bailey, S., DeCrescenzo, G.A., Devraj, R.V., Ellsworth, E., Fobian, Y.M. et al. (2008) Physiochemical drug properties associated with in vivo toxicological outcomes. Bioorganic and Medicinal Chemistry Letters, 18 (17), 4872-4875. 

Another concurrent factor not considered in the risk analysis was the toxicology of residual amounts of the disinfectant species including hypochlorous acid and chloramines related to chlorine that would normally be present as residuals in chlorinated water. The in vivo toxicology of hypochlorite now indicates the formation of haloforms and halonitriles and thus additional risks (34). 

Naganuma A, Tanaka T, Maeda K, et al. 1983. The interaction of selenium with various metals in vitro and in vivo. Toxicology 29 77-86. 

VI. In vivo toxicology toxicokinetics toxicity testing Animal Determine toxicokinetic profile of oligos Determine toxicological effects of ohgos in a GLP (Good Laboratory Practice) setting... 

Abel, S. and Gelderblom, W. C. (1998). Oxidative damage and fumonisin Bj-induced toxicity in primary rat hepatocytes and rat liver in vivo. Toxicology 131(2-3), 121-131. 

Sawyer, T.W., Risk, D. (1999). Effect of lowered temperature on the toxicity of sulphur mustard in vitro and in vivo. Toxicology 134 27-37. 

Sogorh, M.A., Alvarez-Escalante, Carrera, V., Vilanova, E. (2007). An in vitro approach for demonstrating the critical role of serum alhumin in the detoxification of the carhamate carharyl at in vivo toxicologically relevant concentrations. Arch. Toxicol. 81 113-9. 

A variety of in vitro and in vivo toxicological studies have examined the potential health effects of CFA. Most of these studies have concluded that iron release from CFA can generate free radicals, and therefore can trigger DNA damage and toxicity (Smith et al, 1998, 2000 Veranth et al., 2000 van Maanen et al, 1999 Chen et al, 1990). Hence, the deleterious effects from inhalation exposure to CFA may be linked to its content of leachable iron, its alkali content, and the amounts of soluble salts that can dissolve to generate acid and thereby enhance iron release. However, the chemical reactions between CFA and lung and macrophage fluids, and the potential health effects of leachable metals and metalloids other than iron must be studied further. 

Methods of Assessing Cholinesterase Inhibition. The increased use of cholinesterase-inhibiting insecticides has stimulated research in many areas of scientific endeavor. One such area has been concerned with the in vivo toxicological properties of cholinesterase inhibitors. However, the area of concern here is in the field of analytical chemistry where cholinesterases are used as a tool for the quantitative determination of unknown amounts of inhibitors (8). Such procedures are frequently used for the analysis of certain pesticide residues and can be categorized into the following types of methods ... 

GLP toxicology safety pharmacology, genetic toxicology, in vivo toxicology/ histopathology, mechanistic studies, non-rodent telemetry... 

Hughes JD, BlaggJ, Price DA, et al. Physiochemical drug properties associated with in vivo toxicological outcomes. BioorgMed Chem Lett. 2008 18(17) 4872-4875. 

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