Toxic action mechanism

The mechanism of toxic action involved in the algorithm loop of Fig. 4 is associated with the critical biological effect of the toxicant at the molecular or cellular level. The main classes of toxic action mechanisms are as follows nonpolar narcosis, polar narcosis, weak acid respiratory uncoupling, formation of free radicals, electrophilic reactions, and toxic action by specific (receptor-mediated) mechanisms. 

Successful predictive models in toxicology exist - however, they are of a rather local nature. Effects considered in toxicology can be caused by different mechanisms. Efforts to get away from a class perspective to one that is more consistent regarding modes of toxic action are still a subject of ongoing research. 

Health and Safety Factors. Carbonyl sulfide is dangerously poisonous, more so because it is practically odorless when pure. It is lethal to rats at 2900 ppm. Studies show an LD q (rat, ip) of 22.5 mg/kg. The mechanism of toxic action appears to iavolve breakdowa to hydrogea sulfide (36). It acts principally on the central nervous system with death resulting mainly from respiratory paralysis. Little is known regarding the health effects of subacute or chronic exposure to carbonyl sulfide a 400-p.g/m max level has been suggested until more data are available (37). Carbon oxysulfide has a reported inhalation toxicity in mice LD q (mouse) = 2900 ppm (37). 

Cardiac glycosides have a small ratio of toxic to therapeutic concentration. Possible adverse effects are nausea, vomiting, abdominal pain, diarrhoea, fatigue, headache, drowsiness, colour vision disturbances, sinus bradycardia, premature ventricular complexes, AV-block, bigeminy, atrial tachycardia with AV-Block, ventricular fibrillation. There are several mechanisms relevant for their toxic action (Table 2). 

Truhaut R, Gak JC, Graillot C. 1974. [Organochlorine insecticides Research work on their toxic action, its modalities and mechanisms. Part 1 Comparative study of the acute toxicity on the hamster and the rat.] Eur J Toxicol Environ Hyg 7 159-166. (French)... 

The mechanism of toxic action of some important organic pollutants is described and related, where possible, to ecotoxicological effects. 

Neither of these mechanisms of toxic action is susceptible to the kind of QSAR analysis referred to earlier, the employment of which depends on knowledge of the structure of particular binding sites. 

Croni MT et al. (2000) Structure-toxicity relationships for aliphatic compounds encompassing a variety of mechanisms of toxic action to Vibrio fischeri. SAR QSAR Environ Res 11(3-4) 301-312... 

The mechanism of the toxic action of diisopropyl methylphosphonate is unclear. Therefore, therapies that could interfere with its mechanism are unknown. 

It appeared to the author some years ago that, irrespective of the mechanism of the toxic action of DDT, there might be a correlation of structure and toxicity in analogous compounds. Hammett (13) has shown that the rate and equilibrium constants of over 50 side-chain reactions of meta and para substituted aromatic compounds may be correlated with the so-called substituent constant a, according to the equation log k — log k0 = pa, where k and k0 are rate (or equilibrium) constants for substituted and unsubstituted compounds, respectively, p is the reaction constant giving the slope of the linear relationship, and a is the substituent constant, which is determined by the nature and... 

Brieger H, Rieders F, Hodes WA. 1951. Acrylonitrile spectrophotometric determination, acute toxicity and mechanism of action. Arch Ind Health Occup Toxicol 6 128-140. 

Information concerning the mechanism of toxic action is incomplete... 

Hopf2 concludes that although insect nerve tissues produce substances that simulate acetylcholine and a cholinesterase which is inhibited by organo-phosphorus insecticides, these substances (in locusts at any rate) are not antagonized by atropine. Furthermore, tubocurarine does not poison insects, although it is active in warm-blooded animals and affects the neuromuscular junctions (see pp. 36, 37). In short, different physiological mechanisms appear to be at work in insects. In particular, it seems that acetylcholine, when injected into a variety of insects, has no marked toxic action. It seems then that, in some... 

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