Toxicological and pharmacological actions

W.W. Carmichael, D.F. Biggs and P.R. Gorham, Toxicology and pharmacological action of Anabaena flos-aquae toxin, Science, 187 (1975) 542-544. 

Carmichael, W.W., Biggs, D.E., and Gorham P.R. 1975. Toxicology and pharmacological action of Anabaenaflos-aquae toxin. Science 187, 542-544. 

Toxicology The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH]... 

Clewell, H. (2005) Use of mode of action in risk assessment past, present, and future. Regulatory Toxicology and Pharmacology. 42, 3-14. 

The expectation of combined effects from mixture exposure is most often founded in the basic principles of toxicology and pharmacology (Loewe and Muischnek 1926a Bliss 1939 Plackett and Hewlett 1952). The first strictly pharmacological ideas formulated (Loewe and Muischnek 1926a) were supplemented by biometrical considerations. Later, Bliss (1939), a biologist and a biometrician, provided the first consistent framework, as depicted in Table 5.2 (Plackett and Hewlett 1952). In this framework, the main ideas focused on the presence or absence of interactions (commonly referred to as interactive and noninteractive joint action) with respect to responses observed in test organisms, and the presence of the same or a different mode of action. 

Toxicological Effects and Pharmacological Action In some cases only exaggerated pharmacological effects may be observed in the toxicological studies of the biopharmaceuticals. Sometimes these effects are difficult to distinguish from a compound-related toxicity. However, if the effect is related to the mechanism (predictable) and is reversible, it should not be considered as an adverse effect. 

Clement, J.G. (1981). Toxicology and pharmacology of hispyr-idinium oximes - insight into the mechanism of action vs. soman poisoning in vivo. Fundam. Appl. Toxicol. 1 193-202. 

A peer review panel was assembled for 1,1-dichloroethane. The panel consisted of the following members Dr. Benjamin Van Duuren, Institute of Environmental Medicine, New York University Medical Center Dr. James Bruckner, Department of Toxicology and Pharmacology, University of Georgia Dr. Theodore Mill, director. Physical Organic Chemistry Department, SRI International Dr. Nancy Tooney, Associate Professor, Department of Chemistry, Polytechnic University, Brooklyn, New York and Ms. Linda Massey, Private Toxicology Consultant, Santa Clara, California. These experts collectively have knowledge of 1,1-dichloroethane s physical and chemical properties, toxicokinetics, key health end points, mechanisms of action, human and animal exposure, and quantification of risk to humans. All reviewers were selected in conformity with the conditions for peer review specified in Section 104(i) (13) of the Comprehensive Environmental Response, Compensation, and Liability Act, as amended. 

Sonich-Mullin C, Fielder R, Wiltse J, et al. (2001) IPCS conceptual framework for evaluating a mode of action for chemical carcinogenesis. Regulatory Toxicology and Pharmacology 34 146-152. 

GENERAL TOXICOLOGY AND PHARMACOLOGY OF SULPHUR MUSTARD MECHANISMS OF ACTION... 

Clinical observations A careful clinical observation of each animal should be made at least once a day. Additional observations should be made daily with appropriate actions taken to minimise loss of animals to the study, e.g., necropsy or refrigeration of those animals found dead and isolation or sacrifice of weak or moribund animals. All toxicological and pharmacological signs should be recorded including time of onset, intensity, and duration. The time of death should also be noted. Individual records should be maintained for each animal. 

The applicant should provide justification for using the racemate. Where the interconversion of the enantiomers in vivo is more rapid than the distribution and elimination rates, then use of the racemate is justified. In cases where there is no such interconversion or it is slow, then differential pharmacological effects and fate of the enantiomers may be apparent. Use of the racemate may also be justified if any toxicity is associated with the pharmacological action and the therapeutic index is the same for both isomers. For preclinical assessment, pharmacodynamic, pharmacokinetic (using enantiospecific analytical methods) and appropriate toxicological studies of the individual enantiomers and the racemate will be needed. Clinical studies on human pharmacodynamics and tolerance, human pharmacokinetics and pharma-cotherapeutics will be required for the racemate and for the enantiomers as appropriate. 

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