Molecular toxicity

Pounds JG, Long GJ, Rosen JF. 1991. Cellular and molecular toxicity of lead in bone. Environ Health Perspect 91 17-32. 

The toxic effect on biocatalytic activity and stability in two-phase reaction system media can be divided into two effects. The first one, called the molecular-toxicity effect, is a direct toxic effect of the solvent molecules, which are dissolved in the aqueous phase and interact with the biocatalyst, particularly with whole cells. The second one, which is created by the presence of an interface between the aqueous and the organic solvent phase, is called the phase-toxicity effect [2, 24]. 

Organic solvents can interact with enzymes in several ways. There can be specific interactions between isolated solvent molecules and enzyme molecules. This kind of interaction also occurs in water containing dissolved solvent molecules. When a separate organic solvent phase is present, interfacial inactivation can also occur. This is sometimes called phase toxicity [55] to distinguish it from the molecular toxicity of isolated solvent molecules. Interfacial inactivation can be studied in detail by bubbling solvent through an aqueous enzyme solution under controlled conditions [56]. 

Kirsten, E., Sharma, M. L., Kun, E. (1978). Molecular toxicity of (-)-erythro-fluorocitrate selective inhibition of citrate transport in mitochondria and the binding of fluorocitrate to mitochondrial proteins. Mol. Pharmacol. 14 172-84. 

Screen series in vitro for cell molecular toxicity, ie.,... 

Recently, the hazardous effects of endocrine disruptors (environmental hormones) such as bisphenol A and nonylphenol on the human body have been reported, and led to the initiation of many studies concerning the detection and structural determination of these compounds present in tiny amounts [57]. As one of the QSAR analyses of environmental hormones, the relationship between their biological activity and chemical hardness has been reported [16]. By applying these analytical methods, the molecular toxicity and estrogen-like activity of environmental hormones have been found... 

Product information is presented for Amina T 100, a newly developed polymer from Creavis GmbH with antimicrobial action. Its crucial advantages lies in its macromolecular nature. In contrast to other polymers provided conventionally with biocides, there is no wash-out of low molecular toxic components. The starting materials are not antimicrobially active, and the antimicrobial action develops only in the polymer. Product properties are listed, its spectrum of activity is identified, and kinetics of reduction are charted. 

Mesenchymal stem cells isolated from murine bone marrow were applied in a study designed to evaluate the molecular toxicity of hydroxyapatite nanoparticles (Remya et al., 2014). Hydroxyapatite nanoparticles (50 nm) were used to study the cytotoxicity, nanoparticle uptake, effect on cytoskeletal arrangement, oxidative stress response and apoptotic behaviour with the confluent cells as per standard protocols. The results of the MTT assay indicated that hydroxyapatite nanoparticles do not induce cytotoxicity up to 800 pg ml-1. It was also observed that apoptosis related to oxidative stress and reactive oxygen species (ROS) production following nanoparticle treatment was comparable to that of the control (cells without treatment). Hence, it can be concluded that mesenchymal stem cell in vitro cultures can be used as a model to evaluate the potential toxicity of nanomaterials. 

It is found, in general, that if the relative toxicity of a number of poisons containing, for instance, a toxic sulfur atom is determined, the toxicity per gram atom of sulfur increases with the molecular weight of the sulfur compoimd, i.e., with the complexity of the chain or ring attached to the sulfur atom. This result would be expected from the dependence of molecular toxicity on the covering power of the poison. 

The degree to which normally nontoxic structures attached to a toxic sulfur atom may influence the molecular toxicity has been studied more systematically (Maxted and Evans, 36) by measuring the relative toxici-ties of a homologous series of alkyl thiols and sulfides in which simple hydrocarbon chains of varying lengths are linked to sulphur, a single chain of this nature being present in the thiols, and two in the sulfide. 

Fig. 11. Influence of molecular size on toxicity. The diagram, which refers to the relative toxicity of a series of ra-thiols and sulfides, shows the effect on the molecular toxicity of the attachment of one or of two normally nontoxic aliphatic chains, of increasing length, to a sulfur atom.

If, on the other hand, the two sulfur atoms, instead of occupying terminal positions, are adjacent to one another, little change in toxicity occurs thus, diethyl disulfide, (C2Hj)2S2, does not differ greatly in molecular toxicity from diethyl sulfide, (C2H6)2S, again in spite of its doubled sulfur content. 

Bar suggested that the toxicity in two-phase systems was caused by both the presence of a second phase (phase toxicity) and solvent molecules which dissolved in the aqueous phase (molecular toxicity). Basically, both mechanisms are governed by the same principle in that the solvent accumulates in the microbial membrane. In case of the direct contact between cells and pure solvent, the rate of entry of solvents in a membrane will be very high. If the solvent has to diffuse via the water phase, then the accumulation in membranes will be slower. This latter mechanism on the molecular toxicity has been investigated in more detail. In experiments with liposomes from E. coli, and ten representative organic solvents labeled by under aqueous-saturating levels, it was observed that the solvents accumulate... 

The levels of naphthenic acids in extraction waters are aeutely toxic to many aquatic biota [J36,147], Application of molecular toxicity methods, in which stress-inducible genes from E. coli are exposed to oil sands derived naphthenic acids, indicated that the main toxic response was indieative of eytotoxicity with osmotic stress and membrane disruption... 

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