CARBENDASIM CARCINOGENICITY: AN EXPERIMENTAL TWO-YEAR STUDY IN WISTAR RATS

Lisovska V. S., Nedopytanska N. M., Reshavska O. V., Bagliy Y. A.

PATHOMORPHOLOGY

Scentific article

Objective. Carbendazim is one of the widely used benzimidazole fungicides. It mechanism of action is to inhibit polymerization of microtubules of the mitotic spindle in fungal cells and damage the cell division. A similar effect on mammalian and human cells is not ruled out. Well known reproductive and developmental toxicity of carbendazime, but the question of its carcinogenicity has not yet been clarified. Carbendazim cause liver tumours in mice and classified by EPA (1989) as “possible human carcinogen” and not classified in one of the carcinogenicity categories in EC. In Ukraine are 27 registered fungicides containing the active ingredient carbendazim, mainly generic, so the question of its carcinogenicity is still relevant. Object and methods. In our study, the carcinogenic effect of carbendazim technical 98 % were investigated by chronic 24-month experiment in Wistar rats. Male and female rats aged between 1.5 and 2.0 months were assigned randomly to experimental and control groups, each group consisted of 70 rats of each sex. Rats receiving carbendazim at a dose of 5, 25, or 75 mg/kg body weight by gavage. All rats were observed daily for general physical condition and weekly were recorded body weights and the palpable neoplasms. Died and sacrificed (in according to study plan) animals have been necropsied and tissue samples were collected for histopathology. Statistically was evaluated such direct indicators of carcinogenic effect as the tumor rate, latent period and survival of animals with tumors. Results. According to the obtained results in our study, benign neoplasms prevailed among tumors in all groups and were usual occurring neoplasm, characteristic to Wistar rats. The incidence of malignant neoplasia across the treatment and control groups was similar. Treatment-related tumours included neoplasms of mammary gland, thyroid gland and pituitary in femals and testis tumours in male without clear dose dependence. There was low but significant increased tumours of thyroid gland in the 5 mg/kg female group, mammary gland in the 5 and 25 mg/kg groups, pituitary in the 75 mg/kg and leydig cells tumours in the 25 mg/kg male group. Thus, the most frequently tumors were in the organs of the endocrine and reproductive system. The tumor rate of this localization in males was 9 %, 12 %, 6 % in minimal, middle and high dose opposite 5 % in the control, and in females – 21 %, 19 %, 18 % and 10 %, respectively. Conclusion. Under the conditions of 2-year studies, there was evidence of carcinogenic activity of carbendazime in rats based on increased incidences of hormone-dependent tumors without clear dose dependence and reduction of their latent period. Thus, the obtained data indicate a weak carcinogenic effect of carbendazim, most likely, an epigenetic mechanism. Non-linear dose reactions have been clearly established for aneunogens, which also does not exclude the way the oncogenic effect is realized.

carbendazim, carcinogenesis, tumors, Wistar rats.

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«Bulletin of problems biology and medicine» Issue 1 (155), 2020 year, 321-328 pages, index UDK 616-006:632.95.024:59.08

10.29254/2077-4214-2020-1-155-321-328