Assessment of the impact of pharmaceutical residues on living organisms is a very complex subject. Apart from taking into account the toxicity of individual compounds, environmental factors should also be taken into account. In this paper, attempts were made to assess the impact of coexisting inorganic ions and changes in pH on the toxicity of ten selected pharmaceuticals. Two bioassays were used to measure the estrogenic and androgenic effects (XenoScreen YES/YAS – Saccharomyces cerevisiae) and acute toxicity (Microtox® – Vibrio fischeri).The Microtox® test gave the most definitive outputs concerning the determination of interaction type between drugs and chemical species. Synergism was proven for almost all drugs and chemical species, and only two cases of antagonism were found. Significant drug/pH interactions were rare.Regarding the XenoScreen YES/YAS bioassay, when estrogenic and androgenic agonistic effects (YES+ and YAS+, respectively) were studied, many cases of well-expressed synergism for all inorganic ions with limited number of drugs (diazepam, fluoxetine, estrone, chloramphenicol for the YES+ test and diazepam, progesterone, androstenedione, and estrone for the YAS+ test) were found. Antagonism was also proven for the YES+ test, especially for diclofenac and androstenedione interacting with cations. On the other hand, the YES- and YAS- tests (estrogenic and androgenic, respectively, antagonistic effects) did not indicate cases of synergetic interaction except for the couples Br−/diazepam and NH4+/ketoprofen. Antagonistic drug/ion interactions were detected only with diclofenac and fluoxetine. It is interesting that well-expressed (antagonism or synergism) drug/pH interactions were rare.Both tests were found utilizable in performing studies on impact of ions/pH fluctuations on drugs mixtures' toxicity confirming in most cases synergic impact of parameters studied on toxicity. The approach proposed in the paper seems to be proven as a reliable tool in assessing impact of abiotic factors on toxicity and endocrine potential of complex mixtures of pharmaceuticals' mixtures.