Sergii Omel’chuk, Alina Syrota


Some studies have proven possible potentiating toxic effect of combined pesticides. The potentiating effect may be related to the impact of a certain substance on enzymatic activity of another one. Due to combined preparations popularity, the importance of evaluating probability of summation and synergetic or antagonizing action of the one-purpose substances becomes particularly important.

Aim of the research is to study peculiarities of histomorphological liver changes associated with combined effect of active substances with one-purpose action.

Methods. The authors have used toxicological, histochemical and statistical study methods. 45 rats have been used for the study. The liver specimens for histochemical analysis were selected immediately after dissection of the rats, from which the 5 micrometer sections were prepared, using freezing microtome. After leaving the sections in cold acetone, the histochemical reaction on determining the γ-glutamyl transpeptidase, a transformed hepatocyte marker, which forms nodules while proliferates, was conducted.

Results. The authors have established that the above-mentioned characteristics in animals which were administered the drug (benthiavalicarb-isopropyl+folpet) do not differ from negative control group. General specific area of nodules per сm2 and specific quantity of nodules per сm2 haven’t reliably changed, the control group exceeding these data by 18 % and 12 %, respectively.

Discussion. The study of the benthiavalicarb-isopropyl and folpet mixture effect on animals has not revealed liver tissue proliferation of the carcinogen-transformed cells and appearance of hyperplastic nodes, which express the γ-glutamyl transpeptidase, a histochemical marker of pre-tumor changes.

So, the fungicide (benthiavalicarb-isopropyl+folpet) has not induced multiplication or size increase of glutamyl transpeptidase nodules, which evidences about loss of the modifying effect of folpet on the benthiavalicarb-isopropyl carcinogenicity in this preparation formula.

The obtained results may be used when deciding on administration of combined fungicides with active substances of one-purpose action.


fungicides; γ-glutamyl transpeptidase; benthiavalicarb-isopropyl; folpet; histochemical analysis; N-nitrosodimethylamine; N-Nitroso-N-Metylurea; N-nitrosobis (2-hydroxypropyl) amine; rats; promotor activity

Full Text:



Stavnichenko, P. V., Antonenko, A. M., Bardov, V. G. (2017). Forecasting of development of acute poisonings in agricultural workers while using combined formulations based on difenoconazole. Medicni Perspektivi (Medical Perspectives), 22 (3), 116–121. doi:

Leadbeater, A., Gisi, U. (2009). The Challenges of Chemical Control of Plant Diseases. Recent Developments in Management of Plant Diseases, 3–17. doi:

Amr, S., Dawson, R., Saleh, D. A., Magder, L. S., St. George, D. M., El-Daly, M. et. al. (2014). Pesticides, Gene Polymorphisms, and Bladder Cancer Among Egyptian Agricultural Workers. Archives of Environmental & Occupational Health, 70 (1), 19–26. doi:

Omidakhsh, N., Bunin, G. R., Ganguly, A., Ritz, B., Kennedy, N., von Ehrenstein, O. S. et. al. (2017). Parental occupational exposures and the risk of childhood sporadic retinoblastoma: a report from the Children’s Oncology Group. Occupational and Environmental Medicine, 75 (3), 205–211. doi:

Depczynski, J. C. (2017). A population-based examination of cancer in New South Wales farm residents compared to rural non-farm and urban residents. University of Sydney. Available at:

Kim, K.-H., Kabir, E., Jahan, S. A. (2017). Exposure to pesticides and the associated human health effects. Science of The Total Environment, 575, 525–535. doi:

Benthiavalicarb-Isopropyl; pesticide tolerance (2006). Federal Register, 71 (170), 51998–52003. Available at:

De Albuquerque, N. C. P., Carrão, D. B., Habenschus, M. D., de Oliveira, A. R. M. (2018). Metabolism studies of chiral pesticides: A critical review. Journal of Pharmaceutical and Biomedical Analysis, 147, 89–109. doi:

Folpet; pesticide tolerance (2004). Federal Register, 69 (164), 52182–52192. Available at:

Ito, N., Shirai, T., Hasegawa, R.; Vainio, H., Magee, P. N., McGregor, D. B., McMichael, A. J. (Eds.) (1992). Medium term bioassays for carcinogens. Mechanism of carcinogenesis in riskidentification. The IARC Scientific Publications No. 93. Lyon: IARC, 353–388.

Sakthisekaran, D., Rajendran, P., Rengarajan, T., Nishigaki, I., Ekambaram, G. (2014). Potent chemopreventive effect of mangiferin on lung carcinogenesis in experimental Swiss albino mice. Journal of Cancer Research and Therapeutics, 10 (4), 1033. doi:

Wang, F., Zhu, Y., Zhou, L., Pan, L., Cui, Z., Fei, Q. et. al. (2015). Fluorescent In Situ Targeting Probes for Rapid Imaging of Ovarian-Cancer-Specific γ-Glutamyltranspeptidase. Angewandte Chemie International Edition, 54 (25), 7349–7353. doi:

McGlynn, K. A., Petrick, J. L., London, W. T. (2015). Global Epidemiology of Hepatocellular Carcinoma. Clinics in Liver Disease, 19 (2), 223–238. doi:

Bagliy, Ye. A., Nedopitanska, N. M., Lisovska, V. S., Reshavska, O. V. (2011). Vplyv avermektyniv na iniciyovani nitrozodietylaminom gepatocyty shhuriv. Suchasni problemy toksykologiyi, 1, 22–26.

U.S. EPA (2017). Chemicals Evaluated for Carcinogenic Potential. Available:



  • There are currently no refbacks.

Copyright (c) 2018 Sergii Omel’chuk, Alina Syrota

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

ISSN 2585-6634 (Online), ISSN 2585-6626 (Print)