Toxicodynamics

Abstract: Environmental pollution has become a concerning matter to human beings. Flint water crisis in the USA pointed out that pollution by heavy metal is getting worse day by day, predominantly by Lead, Cadmium, Mercury and Arsenic. Despite of not having any biological role in flora and fauna, they exhibit detrimental effect following exposure (acute or chronic). Even at low dose, they affect brain, kidney and heart. Oxidative stress has been termed as cause and effect in heavy metal-induced kidney toxicity. In treatment strategy, different chelating agent, vitamins and minerals are included, though chelating agents has been showed different fatal drawbacks. Interestingly, plants and plants derived compounds had shown possible effectiveness against heavy metals induced kidney toxicity. This review will provide detail information on toxicodynamics of Pb, Cd, Hg and As, treatment strategy along with the possible beneficiary role of plant derived compound to protect kidney.

Abstract: The pyrethroid insecticides are extremely toxic to fish, with 96—h LC50 values generally below 10 μg/L and i.p. and i.v. LD50 values below 20 mg/kg. Corresponding LD50 values in mammals and birds are in the range of several hundred to several thousand milligrams per kilogram. This review examines pyrethroid toxicokinetics and toxicodynamics in fish as critical factors associated with species selectivity. Studies with permethrin, cypermethrin and fenvalerate have established that rates of metabolism and elimination in rainbow trout are significantly lower than those reported for birds and mammals. Comparatively low lethal brain pyrethroid concentrations and nonneural aspects of pyrethroid intoxication in fish suggest that variations in toxicodynamics are also crucial in evaluating pyrethroid selectivity.

Abstract: Mechanistic studies on membrane toxicity are reviewed and linked to effects observed in-vivo. Time-resolved spectroscopy on energy-transducing membranes is an in-vitro test method that provides information on the toxicodynamics of membrane toxicity, namely baseline toxicity and uncoupling. Without blurring effects of the toxicokinetic phase, the intrinsic potency of membrane toxicants can directly be determined thus allowing the development of a classification system to distinguish between baseline toxicity and uncoupling. Toxicity data of known baseline toxicants and of substituted phenols from literature are reevaluated in light of the information obtained from the mechanistic test system. Exposure-based effect data (aqueous effect concentrations) of substituted phenols (baseline toxicants and uncouplers) from various aquatic organisms (bacteria, protozoa, algae, daphnids, fish) are compared to the corresponding effect concentrations expected from baseline toxicity. The results of the comparison support the view that the membrane is the primary target site for acute toxicity of substituted phenols in aquatic organisms. The classification into baseline toxicants and uncouplers based upon the criteria derived from the mechanistic test system is correct. Nevertheless, the acute toxicity in-vivo cannot be correlated quantitatively to the mechanistic data presumably because bioaccumulation is not directly proportional to intrinsic toxicity and the metabolic transformation is variable within the test set of substituted phenols. The pH-dependence of acute toxicity is mainly determined by the pH-dependence of bioccumulation, the internal effect concentrations are virtually independent on external pH. The internal effect concentrations, also called lethal body burdens or critical body residues, which are taken from the literature or calculated from aqueous effect concentrations and bioconcentration factors, are related to membrane concentrations using a simple three-compartment equilibrium partitioning model. The modeled membrane concentrations of non-polar and polar narcotics turn out to be statistically indistinguishable, which is consistent with the findings from the mechanistic test system. The toxic ratios, i.e., the excess toxicity of uncouplers in relation to their baseline toxicity, agree for most compounds upon comparison of the mechanistic test system with the aquatic organisms thus confirming that uncoupling is the dominant mode of action responsible for lethality.

Abstract: Chemical form (i.e., species) can influence metal toxicokinetics and toxicodynamics and should be considered to improve human health risk assessment. Factors that influence metal speciation (and examples) include: (1) carrier-mediated processes for specific metal species (arsenic, chromium, lead and manganese), (2) valence state (arsenic, chromium, manganese and mercury), (3) particle size (lead and manganese), (4) the nature of metal binding ligands (aluminum, arsenic, chromium, lead, and manganese), (5) whether the metal is an organic versus inorganic species (arsenic, lead, and mercury), and (6) biotransformation of metal species (aluminum, arsenic, chromium, lead, manganese and mercury). The influence of speciation on metal toxicokinetics and toxicodynamics in mammals, and therefore the adverse effects of metals, is reviewed to illustrate how the physicochemical characteristics of metals and their handling in the body (toxicokinetics) can influence toxicity (toxicodynamics). Generalizing from mercury,...