Toxicology relationships

Each substructure of a molecule contributes to its toxicity in a specific way and the QSAR equation describes this contribution. Models of this type have proven to be successful in the estimation of carcinogenicity, mutagenicity, rat, mouse, daphnia, and fathead minnow acute toxicity, and at establishing toxicological relationships across species boundaries. 

The basis for the toxicological relationship. Equation 4, was laid nearly 30 years ago by research on both rats and humans by Grob and Harvey ( ). This same relationship held true during the more recent rat dermal dose-response studies by Knaak et al, 1980 (,1, ... 

Practical Applications of Quantitative Structure-Activity Relationships (QSAR) in Environmental Chemistry and Toxicology W. Karcher, J. Devillers, Eds., Kluwer, Dordrecht (1990). 

Product Toxicology. The stmcture—toxicity relationships of organophosphoms compounds have been extensively researched and are relatively well understood (138—140). The phosphoms-based flame retardants as a class exhibit only moderate-to-low toxicity. NIOSH or EPA compilations and manufacturers safety data sheets show the following LD q values for rats, for representative commercial phosphoms flame retardants ... 

Biological characterization includes toxicological studies, dose relationships, routes of adininistration, identification of side effects, and absorption, distribution, metaboHsm, and excretion patterns. If the results are stiU acceptable, product formulation and dosage form are developed. The product should be pleasing to the patient and thus may contain flavoring and colorants. 

Natural and synthetic chemicals affect every phase of our daily Hves ia both good and noxious manners. The noxious effects of certain substances have been appreciated siace the time of the ancient Greeks. However, it was not until the sixteenth century that certain principles of toxicology became formulated as a result of the thoughts of Philippus Aureolus Theophrastus Bombastus von Hohenheim-Paracelsus (1493—1541). Among a variety of other achievements, he embodied the basis for contemporary appreciation of dose—response relationships ia his often paraphrased dictum "Only the dose makes a poison."... 

Dose—Response Relationships and Their Toxicological Significance... 

In the future, the preventive tole of toxicology will be emphasized. It will be increasingly important to develop early indicators to monitor longterm subtle exposures that predict deleterious effects that are known to have a causal relationship with occupational exposures. In addition to collection of blood and urine samples, also collection of cells from points of... 

Dose-response relationship 1 he toxicological concept that the toxicity of a substance depends not only on its toxic properties, but also on the amount of exposure or dose. 

For pharmacology there results a particularly close relationship with chemistry, and the work may lead quite naturally, with no special stress on practicality, to therapeutic application, or (in the case of adverse reactions) to toxicology. 

There is increasing interest in the relationship of the HS response to environmental toxicology. As induction of the HS response portends resistance to otherwise lethal stresses, many environmental hazards have the potential for inducing the HS response (Finnell et al., 1992). Activity of the dioxin receptor is affected by HS proteins (Nemoto et al., 1990 Pongratz et al., 1992) and it is likely that the HS... 

Davis, D. and Safe, S.H. (1990). Immunosuppressive activities of PCBs in C57BL/ 6N mice structure-activity relationships as Ah receptor agonists and partial agonists. Toxicology 63, 97-111. 

Hart, A.D.M. (1993). Relationships between behaviour and the inhibition of acetylcholinesterase in birds exposed to organophosphorous pesticides. Environmental Toxicology and Chemistry 12, 321-336. 

Kdnemaim, H. (1981). QSAR relationships in fish toxicity stndies. Part I Relationship of 50 industrial pollutants. Toxicology 19, 209-221. 

Wiemeyer, S.N., Bunck, C.M., and Stafford, C.J. (1993). Environmental contaminants in bald eagles—1980-1984—and further interpretations of relationships in productivity and shell thickness. Archives of Environmental Contamination and Toxicology 24, 213-244. 

Enslein, Kurt. Estimation of toxicological endpoints by structure-activity relationships. Pharmacol Rev 1984 36 (2, Suppl.) 131-5. 

Perkins R, Fang H, Tong W, Welsh WJ. Qnantitative structure-activity relationship methods perspectives on drng discovery and toxicology. Environ Toxicol Chem 2003 22 1666-79. 

One example of such constructive cross talk can be found in the growing literature on quantitative structure-pharmacokinetic relationships (QSPKR). Reports on how to predict pharmacokinetics from molecular information, or how to link pharmacokinetic parameters with molecular features, have appeared in both the pharmacokinetic [61] and the toxicological [62] literature. Others are extending this to pharmacodynamics as well [63], and the approaches look promising. 

Walker, J.D., Jaworska, J., Comer, M.H.I., Schultz, T.W., Deardon, J.C. (2003) Guidelines for Developing and Using Quantitative Structure Activity Relationships. Environmental Toxicology Chemistry, 22(8), 1653. 

Meylan, W.M. Howard, P.H. (2003) A Review of Quantitative Structure-Activity Relationship Methods for the Prediction of Atmospheric Qxidation of Qrganic Chemicals. Environmental Toxicology and Chemistry, 22(8), 1724—1732. 

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