Objective. Analyse and summarize modern data on the degree of hazard of chlorpyrifos when used in accordance with the intended purpose, substantiate the expediency of limiting the scope and extent of use of insecticide in the human living environment. Materials and methods. Analytical review of scientific publications has been performed using the abstract database of libraries and the text database of medical and biological publications PubMed. Results. Based on the conducted analytical review of scientific publications, data on the degree of hazard of chlorpyrifos have been summarized, the requirements regarding the expediency of the prohibition of the use of chlorpyrifos and chlorpyrifos-based preparations as insecticidal agents in the human living environment, first of all, in everyday life, in maternity departments, in medical institutions, in child day care centres and educational institutions have been substantiated.

Metolachlor and currently its biological active isomer S–metolachlor is one of the most widely used herbicides in the world. Chronic experiments in rats have found hepatocarcinogenic effect of metolachlor, and epidemiological studies have found positive relationship between enzyme exposure to metolachlor and prevalence of liver cancer. Possibility of the influence of harmful impurities contained in technical products on the detected effects is emphasized. Objective is to study promotor effect of S–metolachlor generics with different hepatotoxicity in carcinogenesis of liver in rats induced by nitrosodiethylamine (NDEA) and analyse possibility of its realisation in human. Materials and Methods. Experiments were performed in male Wistar Han rats on hepatocarcinogenesis model “NDEA — hepatectomy”. Two specimens of S–metolachlor generics were studied; and their ratio of S/R enantiomers was 87/13 % with different hepatotoxicity. Substances were administered intragastrically in the doses of 1.5,15 and 150 mg/kg body weight for 8 weeks. Animals of the negative control group received water, and positive control — phenobarbital. Promotor effect was evaluated by the standardised parameters of the total area and number of hepatocyte foci expressing γ-glutamyl transpeptidase (GTP). Results. No clinical signs of the toxic action of S–metolachlor on the rat body induced to carcinogenesis by NDEA were found. Increase in the number and total area of γ-GTP positive foci in the liver of animals on tumorogenic dose of both specimens of S–metolachlor as well as phenobarbital was found. Mean area of focus in the liver of rats on more toxic specimen was lower. The threshold of promotor action of S–metolachlor on hepatocarcinogenesis has been established at the level of γ 15 mg/kg body weight. Analysis of literature data on the mechanism of hepatotoxic action of metolachlor allowed to make a conclusion aboutphenobarbital-like mechanism of promotor action that is realised through constitutive androstane receptor (CAR). This mechanism is species-specific for rodents; therefore, the results of epidemiological studies on the possibility of liver cancer in human cannot be confirmed experimentally. Conclusion. Tumorogenic dose of S–metolachlor generics with different degree of hepatotoxicity shows promotor effect in NDEA induced carcinogenesis in rat liver. Hepatotoxicity of S–metolachlor inhibits growth of γ-GTP positive foci. The threshold of hepatocarcinogenesis promotion has been established at the level of γ 15 mg/kg body weight. The mechanism of the observed effect is not relevant for human. Key Words: S–metolachlor, hepatocarcinogenesis initiated by nitrosodiethylamine, Wistar Han rats, γ-glutamyltranspeptidase.

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Throughout life, the human body is exposed to multiple environmental carcinogens that may stimulate carcinogenesis in different organs. Critical place among these carcinogens belongs to nitroso compounds. Triadimefon belongs to the chemical class of triazoles that are widely used as fungicides in pesticides and medicinal products. Objective is to investigate the effect of triadimefon on the development of preneoplastic lesions of the tissues and tumours in carcinogenesis induced in different organs by nitroso compounds. Materials and Methods. Experiments were performed in male Wistar Han rats in which nitroso compounds - N-nitrosodiethylamine, N-methylnitrosourea, N-nitrosobis(2-hydroxypropyl) amine induced multi-organ carcinogenesis according to the N.Ito. protocol. Triadimefon at the doses: 16.0 and 80.0 mg/kg body weight that corresponded to the no-observed-effect and observed effect level by carcinogenic effect were administered intragastrically on a daily basis for 20 weeks. Clinical studies were conducted throughout the experiment. The general condition of animals, their body weight and body weight gain were assessed. After necropsy, gross examination, including aberrant multiple crypts of the colonic mucosa, and histological examinations were conducted. Nodules positive for γ-glutamyl transpeptidase (γ-GTP) were determined by histochemistry in the hepatic tissue. Results. No clinical signs of toxic action of triadimefon in rat body induced by nitroso compounds to carcinogenesis were established. No specific organotrophic action of triadimefon was found by changes in the internal organ weight, except for liver. High dose resulted in the increase of liver weight, as well as in the number and size of γ-GTP positive nodules suggesting an increase in the pool of transformed hepatocytes. Histological examination of internal organs allowed detecting proliferative processes that are criterial markers of carcinogenicity of chemical substances upon their study in multi-organ model. The tendency to the increase in the rate of dose-dependent thyroid adenoma has been established. Increase in the rate of epithelium hyperplasia of oesophagus and forestomach, prostatic gland, as well as the total rate of benign tumours in different organs of animals on the tumour-inducing dose of triadimefon was found. The rate of malignancies in these animals do not differ from the control. Conclusion. The tumour-inducing dose of triadimefon shows weak promotor effect on the development of preneoplastic lesions of tissues of the thyroid gland, liver, oesophagus and forestomach, prostatic gland, as well as on the development of benign tumours in rats induced by carcinogenic nitroso compounds. No-observed-effect level of triadimefon by oncogenic effect established in chronic experiments ensures its safety upon exposure in the body of rats initiated by carcinogenic nitroso compounds. Regulations developed on this parameters ensure oncological safety of its use in human.