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. 2018 Dec 22:6:105-110.
doi: 10.1016/j.toxrep.2018.12.006. eCollection 2019.

Maximum tolerated doses and erythropoiesis effects in the mouse bone marrow by 79 pesticides' technical materials assessed with the micronucleus assay

Nataliya Ilyushina  1 , Marina Goumenou  2 , Polychronis D Stivaktakis  3 , Alexander I Vardavas  3 , Gleb Masaltsev  1 , Nataliya Averianova  1 , Olga Dmitricheva  1 , Yulia Revazova  1 , Aristidis M Tsatsakis  3 , Valerii Rakitskii  1
Affiliations

Maximum tolerated doses and erythropoiesis effects in the mouse bone marrow by 79 pesticides' technical materials assessed with the micronucleus assay

Nataliya Ilyushina et al. Toxicol Rep. .

Abstract

Effects of technical materials of pesticide active ingredients, belonging to various chemical classes, on erythropoiesis in mouse bone marrow were studied as part of the research on the pesticide mutagenic activity in micronucleus test. The purpose of the present study was to estimate the toxic action of the test substances on the target organ and the validity of the results of the micronucleus assay under conditions of erythropoiesis suppression. It was demonstrated that intragastrically administrated triazole pesticides reached bone marrow (target organ where micronucleus induction was assessed) and exerted an inhibitory effect on erythropoiesis. The effects of triazole pesticides were enhanced in the following order: difenoconazole ≤ tebuconazole < cyproconazole < flutriafol. Furthermore, an association between structural features of molecules and specific target organ activity of the test pesticides was observed. Based on the data on the general toxicity and the results of the evaluation of the effects on erythropoiesis, the maximum tolerated doses (MTDs) of 79 different technical materials of pesticides for CD-1 mice were determined.

Keywords: CI, confidence interval of the mean; Erythropoiesis; Es, total erythrocytes; MN test, micronucleus test; MTD, maximum tolerated dose; Maximum tolerated doses; Mice; Micronucleus test; NCE, normochromatic erythrocyte; PCE, polychromatic erythrocyte; Pesticides; Triazoles; mg/kg b.w., milligram per kilogram of body weight.

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Figures

None
Graphical abstract
Fig. 1
Fig. 1
Graphs illustrating suppression of erythropoiesis in bone marrow of CD-1 mice dosed with difenoconazole (97.9%), tebuconazole (98.4%), cyproconazole (94.0%), and flutriafol (97.6%). The Y axes: the mean ratio of PCEs to the sum of PCEs + NCEs (E). The X axes: doses of the respective pesticides administered to mice. The bars demonstrate 95% confidence intervals (CI) of the mean. In zero dose it is represented the ratio value for the negatice control.
Fig. 2
Fig. 2
Structural formulas of 4 triazole pesticides that cause suppression of erythropoiesis in CD-1 mice bone marrow.
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