Experimental models of animal chronic pathology in assessing health risks for sensitive population groups

Abstract

The methodology for health risk assessment and hygienic standardization of chemicals often neglects such a vulnerable population group as people with chronic non-communicable diseases. According to the data provided by the WHO, the prevalence of such pathologies is high in many European countries; therefore, when a disease burden in a certain population is unaccounted for, this may result in lower accuracy of accomplished assessments. On the other hand, introduction of too conservative safe factors when hygienic standards are being developed for chemicals in various media leads to high uncertainty and excessive limitations. Our research goal was to provide scientific substantiation for a methodology for using experimental pathology models to improve reliability of hygienic standardization and accuracy of health risk assessments for sensitive population groups (people suffering from non-chronic communicable diseases) under exposure to naturally occurring chemicals. Another goal was to test this methodology by performing a case study on drinking water. The testing results indicate that a chronic 6-month exposure to model substances produced more apparent toxic effects on experimental animals with model pathologies (spontaneous hypertension and experimental histamine-induced nephropathy) in comparison with “healthy” animals. This allowed us to recommend using experimental models of congenital and induced animal pathology bearing in mind target organs for toxic effects produced by the analyzed chemicals to substantiate hygienic standards, health risks taken into account. This should be done at the stage when dose-dependent reactions are identified (determination of no-effect and / or threshold levels) in addition to studies performed on “healthy” animals. It is most appropriate to use this approach when the following conditions are met: 1) a research object is naturally occurring chemicals that are widely spread in the environment due to its natural formation; 2) pathologies of organs (systems) that are targets for biological effects produced by the tested chemicals are widely spread in a population (circulatory diseases, diseases of the excretory system, etc.).

Polymorphisms of xenobiotic metabolism enzyme genes cyp2e1, gstm1, gstt1, ephx1 as biomarkers of sensitivity to exposure to water disinfection byproducts (using chloroform as an example)

“…Учитывая новые данные об опасности тригалометанов, на международном уровне наметилась тенденция к ужесточению нормативов для содержания данной группы ППД в питьевой воде. Однако пересмотр национальных нормативов требует формирования надежной доказательной базы с учетом условий водопользования в республике и особенностей чувствительности популяции к экзогенным загрязнителям, что может быть достигнуто за счет применения ряда методических подходов [12].…”