After the completion of the exploitation of ore deposits, atmospheric migration of sulfur compounds remains an urgent ecological and hygienic problem. The aim of the study was to obtain scientifically sound ideas about the danger of waste from the extraction and processing of sulfide ores of non-ferrous and precious metals accumulated in mining regions for the environment and public health based on the methodology of integrated modeling. The emission of sulfur compounds was studied on a full-scale model of the Ursky dump of barite–pyrite bulk (Ursk settlement, Kemerovo Region), the nature of their combined action was studied in a model experiment on Wistar rats. According to the simulation results, the main components of harmful emissions from the Ursky dump include dimethyl sulfide, dimethyl sulfoxide and sulfur dioxide, the concentrations of which in the air exceeded the normative ones by 129–170, 119–127 and 1,7 times. When exposing experimental animals with a two-component mixture of dimethyl sulfide and dimethyl sulfoxide, a partial summation of the neuro- and hepatotoxic effects of the components was noted, while a three-component mixture of dimethyl sulfide, dimethyl sulfoxide and sulfur dioxide potentiated the irritating effect. The dependences of the qualitative and quantitative characteristics of the biological effects of the isolated mixtures on the sum of the concentrations of their components and time are investigated. The proven algorithm for modeling the effects of the impact of a sulfide-containing dump on the environment and public health makes it possible to expand the possibilities of environmental expertise of environmental protection measures and assessment of risks to public health in mining regions.