Aim. Studying the effect of generic pesticides cyproconazole (98 %) and two samples of epoxiconazole (epoxiconazole 1 — 95,75 % and epoxiconazole 2 — 98,7 %) on the reproductive system of male and female Wistar Han rats at the level of the organism when exposed during gametogenesis, identification and characterization of their hazard, as well as assessment of the risk of reproductive toxicity of these compounds. Materials and Methods. The test samples were administered daily (5 days a week) by oral gavage at doses of 0.2 and 2.0 mg/kg for cyproconazole and 0.5 and 2.0 mg/kg for epoxiconazoles during 11 weeks for males, and 10 weeks for females. Also, there were kept intact males and females, intended for crossover mating with experimental animals. After the end of the exposure, functional indicators of the state of the gonads and the ability of animals to reproduce offspring were studied. The duration and the frequency of each stage of the estrous cycle in female rats and the number of motile sperm, the total amount of sperm and the number of abnormal forms of germ cells of the male rats were studied. The reproductive function state in females was evaluated on day 20th of pregnancy. Thereby the number of corpora lutea in the ovaries, number of alive, dead and resorbed foetuses and embryos, the foetus weight, total weight of litters were registered. The studies were carried out in accordance with the recommendations of the Bioethics Commission and the Centre’s standard operating procedures, developed in accordance with the recommendations and requirements of Good Laboratory Practice (GLP). Conclusions. Test substances at a maximum dose of 2.0 mg/kg of body weight have reproductive toxicity and endocrine-disruptive effect, exerting a significant antiandrogenic effect on males and antiestrogenic effect on female rats. No-observed-adverse-effect-level (NOАEL) for gonadal and reproductive toxicity for male and female Wistar Han rats were established. They are 0.2 mg/kg body weight for cyproconazole and 0.5 mg/kg body weight for epoxiconazole. Key Words: azole fungicides, cyproconazole, epoxiconazole, reproductive toxicity, antiandrogenic and antiestrogenic effects, Wistar Han rats.
Aim of the research. Analysis of approaches to the assessment of neurotoxic effects of chemicals during ontogenesis. The dangerous tendency of the increase in the incidence of pathology of the nervous system in the child and the mother, who during pregnancy was exposed to neurotoxicants, necessitates the protection of the child’s body from such a negative effect of chemicals. One of the possible preventive ways to solve this problem is screening of xenobiotics before their widespread application, as well as identification of their ability to cause neurotoxic effects on the body during its development, and banning substances, neurotoxic effects of which on the development of progeny are proven. Materials and Methods. Detection of adverse effects at the stage of foetal development and then at the beginning of the functioning of a nervous system in the postnatal period requires complex experimental studies in laboratory animals, which are described in the recommendations of OECD guideline 426 (OECD Guideline for Testing of Chemicals; Guideline 426: Developmental Neurotoxicity Study, 2007). The OECD guideline 426 protocol provides for a wide range of methods for assessing sensory, motor, behavioural and cognitive functions. Conclusions. Analysis of data given in publications and methodological approaches to research and evaluation of neurotoxic effects of chemicals on the developing organism showed that to obtain representative results it is important to take into account all factors that may affect the result, select adequate informative tests and comply with all requirements. In Ukraine, international methodological approaches to the study of neurotoxic effects of pesticides on the body at the stage of development in the process of ontogenesis are applied at the L.I. Medved’s Research Center of Preventive Toxicology, Food and Chemical Safety, Ministry of Health, Ukraine (State Enterprise), Kyiv, Ukraine. Key Words: nervous system, neurotoxic effects, OECD guideline 426, neurobehavioral tests.
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