Impact of membranetropic compounds on the sensitivity of mammalian erythrocytes to the posthypertonic shock action

The effect of cationic trifluoperazine (TFP) and nonionic decyl-β,D-glucopyranoside (DGP) on the sensitivity of human, rabbit and rat erythrocytes to the action of posthypertonic shock (PHS) at 0 °C was studied in this research. Trifluoperazine shows a high antihemolytic activity under conditions of PHS of human and animal erythrocytes at slight differences of values of effective concentrations. The value of antihemolytic activity of TFP for human and rabbit erythrocytes is ~ 60 %, and for rat cells the efficiency of this compound is approximately 1.4 times higher. The values of antihemolytic activity of DGP under PHS conditions of human and rat erythrocytes are comparable and amounts to 62 and 66 %, respectively. Significant differen­ces of this parameter (72 %) were found for rabbit cells compared with human erythrocytes. It was found that the size of plateau (the range of concentrations of amphiphilic compounds within the minimum level of erythrocyte hemolysis was observed) cationic TFP and nonionic DGP are significantly different. Thus, TFP has a narrow plateau (100–200 μmol/L), while DGP has a rather wide one (400–1600 μmol/L). In addition, a shift of the plateau concentrations of DGP to the region of higher values compared with TFP is observed, which is probably due to the fact that the value of the critical micelle concentration DGP is higher than TFP. Moreover, a shift of plateau concentrations of DGP to the region of higher values compared with TFP is observed, that is probably due to the fact that the value of the critical micelle concentration DGP is higher than TFP one. It was established that under PHS conditions of human erythrocyte, both compounds (TFP and DGP) show a commensurate antihemolytic activity. At the same time, for rabbit cells, DGP is more effective compared with TFP, and for rat erythrocytes, on the contrary, the efficiency of TFP is higher than DGP. This may be due to differences in the phospholipid composition of mammalian erythrocyte membranes. The results suggest that under PHS conditions the efficacy of membrane-tropic compounds is most likely due to their ability to incorporate into membrane to the defect formation areas, and thus significantly increase the critical hemolytic volume of cells, as a result, prevent their destruction.

Genotoxic properties of some organophosphate pesticides

С использованием теста Эймса и микроядерного теста in vivo на эритроцитах млекопитающих изучена генотоксичность некоторых фосфорорганических пестицидов, применяемых в сельском хозяйстве. Технические продукты хлорпирифоса и диазинона не проявляли генотоксичности ни в условиях in vitro, ни in vivo. Выявлены слабые мутагенные эффекты диметоата на штаммах бактерий. Некоторые технические продукты глифосата, диметоата, а также пиримифос-метил индуцировали цитогенетические нарушения у мышей линии CD-1. Наблюдаемые эффекты in vivo были низкими даже на уровне максимальных переносимых доз, поэтому все исследованные фосфорорганические пестициды могут быть отнесены к 3 или 4 классам опасности по критерию «мутагенность» согласно принятой в Российской Федерации классификации. The genotoxicity of some organophosphate pesticides applied in agriculture was studied using the Ames test and the mammalian erythrocyte micronucleus test in vivo. Technical grade active ingredients (TGAI) of chlorpyrifos and diazinon did not show genotoxicity either in vitro or in vivo. The weak mutagenic effects of dimethoate were revealed with bacterial strains. Some TGAIs of glyphosate, dimethoate, and pyrimifos-methyl induced cytogenetic abnormalities in CD-1 mice. The observed effects in vivo were low even at the maximum tolerated doses. Therefore, according to the pesticide hygienic classification adopted in the Russian Federation all studied organophosphate pesticides can be assigned a 3 or 4 class of hazard upon the criterion “mutagenicity”.

MODERN APPROACHES TO THE ASSESSMENT OF PESTICIDE MUTAGENICITY

Research on potential mutagenic pesticide activity is an important part of their toxicological and hygienic assessment. The present article provides international and Russian legal and normative documents, which regulate such investigations. There is presented a list of the principal Organization for Economic Cooperation and Development (OECD) protocols in the field of genetic toxicology which reflect protocols in force, newly adopted and canceled protocols along with the revised versions of existing documents. As an example, major changes of the research protocol for mutagenic properties of chemical compounds in mammalian erythrocyte micronucleus test in vivo are reviewed. The article also provides the minimal set of methods required for the evaluation of the pesticide-induced initial DNA damage, gene, chromosome and/or genome mutations. The article notes the need for the mutagenic assessment of generic pesticides to verify the equivalence of active ingredients and carry out further studies of the combined actions of pesticide mixtures/