CARCINOGENIC ACTIVITY OF A FEED ADDITIVE BASED ON HUMIC SUBSTANCES UPON REPEATED ORAL ADMINISTRATIO

Abstract

Humic acids are polyanionic in nature and bind ions by various mechanisms, both chemical and physical. Compared to inorganic adsorbents (zeolites), their adsorption capacity is seven to ten times higher. Due to the heterogeneous nature of humic substances, the toxicological assessment of one specific substance was considered insufficient for extrapolation to the group as a whole, although efforts were made to identify an appropriate model substance. The aim of the research was to establish the carcinogenic effect for oral administration of sodium humate solution (feed additive "Гумівет") using a micronucleus test. For the preparation of the oral form, brown coal from the Cherkasy deposit (Ukraine) with the following characteristics was used as raw material: humidity - 24.36%, ash content - 24.1%, organic matter - 51.5%. The prediction of the carcinogenic effect of oral administration of the feed additive "Гумівет" was carried out using the micronucleus test (a method for assessing genotoxicity by detecting micronuclei in mammalian bone marrow cells). Male and female white nonlinear mice with a body weight of 24.0-27.0 g were taken as an experimental model. In the first series of the experiment, the feed additive "Гумівет" (solution for oral administration) in doses of 0.80 and 4.0 ml/kg of body weight was administered intragastrically via a probe once only to male mice (n=6) with fixation of the cellular material 24 h after administration. In the second series, the tested feed additive was similarly administered to male and female mice (n=6) daily for 5 days. The fixation of the cellular material was carried out 24 h after the last administration. To conduct an experiment based on the principle of analogues, two control groups (positive and negative control) of 6 mice each were also formed. With a single administration of the feed additive “Гумівет” at the rate of 0.8 ml per kg of live weight, no changes in cytogenetic activity were detected, as evidenced by the absence of a significant increase in polychromatophilic erythrocytes. The positive obtained result indicates that the substance induces chromosomal damage and / or disruption of the mitotic apparatus of cells in experimental animals. The proportion of polychromatophilic erythrocytes from all erythrocytes should not normally exceed 0.2%. Analysis of the cytogenetic effect of the feed additive “Гумівет” with oral administration for five days showed that in mice from the positive control group (that received cyclophosphamide at a dose of 20 mg/kg of body weight) the proportion of polychromatophilic erythrocytes was (0.667-0.683)%.