Sind Pyrethroide unbedenklich? Zur Bewertung experimenteller Befunde.

Pyrethroids are synthetic insecticides which world-wide increasingly replace DDT, Lindane, Organophosphate-pesticides etc. in fields like agriculture, hygienics, household, wear- and building industry. Being lipophilic and strongly neurotoxic substances, a considerable health risk has been predicted in regard of pyrethroid applications. On the other hand the published experimental data are often interpreted as proof of a small, calculable and, therefore, controllable risk. The present paper attempts to specify the reasons for these contrary judgements with regard to the pyrethroid effects. Since the arguments of both sides are based on the same experimental data, first the scientifically unquestioned evidence about effects and stability of the pyrethroids is acquired and critically reviewed. The different arguments are in turn discussed in details by means of this evidence. It was demonstrated that the scientific understanding of the pyrethroid effects is incomplete, as far as that the health risk cannot be considered as calculable. Impairments of health caused by pyrethroid effects, particularly known from scientific investigations carried out in China but also occurring with increasing incidence in Germany, can, therefore, not be excluded anymore. As practical consequences, moreover, an obligation to complete publication of pyrethroid intoxications and an extensive health education of the public about the risks associated with pyrethroid applications are demanded

Evidence for different mechanisms of action of the three pyrethroids, deltamethrin, cypermethrin, and fenvalerate, on the excitation threshold of myelinated nerve.

The effects of three α-cyano pyrethroids (deltamethrin, fenvalerate, and cypermethrin) on the electrophysiological function of single myelinated nerve fibers from Rana esculenta were investigated. The time course of pyrethroid-induced changes on the threshold interval, Vs − Vm (Vs: threshold voltage; Vm: membrane potential), as well as stationary membrane parameters determining this interval was measured on the same nerve preparation (membrane potential Vm, stationary transition voltage VTr, stationary sodium conductance). The results suggest that the mechanisms of changing the threshold interval are different for the three pyrethroids. Deltamethrin and cypermethrin increase this interval until inexcitability, deltamethrin by increasing the stationary sodium conductance and cypermethrin by blocking the sodium conductance. Fenvalerate, however, insignificantly affects the threshold interval because both Vm and Vs are shifted parallel by about the same amount in the same direction (depolarization). These qualitatively different effects of chemically related substances differentiate the pyrethroids from other classes of substances which are effective on the nerve function and suggests that the molecular mechanisms underlying the pyrethroid effects might have a unique quality

Determination of the net electric charge of a polyacrylamide molecule by Donnan potential measurements.

The net electric charge zpof a polyacrylamide molecule (Praestol, Mol. Wt. 3.4×106) in aqueous solution was determined for two pH values (7.2 and 10.0) by measuring the Donnan e.m.f. as function of the solutions NaCl content c <2.7 mM

Action of tocainide and mexiletine on the excitation threshold of myelinated nerves.

The antiarrhythmic drugs tocainide and mexiletine increase the excitation threshold and decrease the Na permeability (P(Na)) in nerves. Hodgkin-Huxley model calculations suggest that the P(Na) decrease is not sufficient to explain the threshold increase at low concentrations (<0.7 mM tocainide; < 0.1 mM mexiletine). On the other hand, a drug action on the membrane surface potential would be consistent with results of recent experiments. To clarify this point electrophysiological experiments on single nerve fibres (Rana esculenta) were carried out. Changes of the threshold interval (difference between membrane and threshold potential; V(m) - V(s)) were measured and compared with the corresponding changes of V(m) and V(s) (V(s) was measured by means of the transition voltage V(Tr)). The quantitatively good agreement between changes of V(m) - V(s) and those of V(Tr) suggests that at low concentrations tocainide and mexiletine decrease nerve excitability by acting mainly on the membrane surface charge. This possibility was supported by an independent electrophoresis experiment with myelin vesicles from the same nerve material

Shear dependence of the fibrin coagulation kinetics in vitro.

Fibrin thrombus formation, in vivo and in vitro, preferentially occurs in regions of retarded, recirculating flow which promote local variations of the distribution of blood components, e.g. thrombin, and shear rates. To better understand the effects of shear forces on the thrombin induced fibrin coagulation process the time course of fibrin formation in a fibrinogen/thrombin solution was studied for different shear rates γ̇ (0 s-1 ≤γ̇ ≤500 s-1) and thrombin concentrations c(thr) (0.1 units/ml≤c(thr)≤1.0 units/ml). The clotting curves at zero shear and the shear induced alterations of these curves could essentially be described in terms of a reaction kinetics defined by two rate coefficients k1, k2 which can be attributed to fibrinogen cleavage by thrombin and fibrin polymerisation, respectively. For c(thr)≥O0.5 units/ml and γ̇≥O15s-1 an additional mechanism, presumably fibrin breakage, had to be assumed. The rate coefficient k2 was markedly more affected by c(thr) and shear forces then was k1. The results fit well to the growth kinetics of fibrin thrombi formed in glas models of an arterial branching