The production and release of chemicals from human activities are on the rise. Understanding how the aquatic environment is affected by the presence of an unknown number of chemicals is lacking. We employed the chemical activity concept to assess the combined effects of hydrophobic organic contaminants on the phyto-plankton species Rodomonas salina. Chemical activity is additive, and refers to the relative saturation of a chemical in the studied matrix. The growth of R. salina was affected by chemical activity, following a chemical activity-response curve, resulting in an Ea50 value of 0.078, which falls within the baseline toxicity range observed in earlier studies. The chlorophyll a content exhibited both increases and decreases with rising chemical activity, with the increase possibly linked to an antioxidant mechanism. Yet, growth inhibition provided more sensitive and robust responses compared to photosynthesis-related endpoints; all measured endpoints correlated with increased chemical activity. Growth inhibition is an ecologically relevant endpoint and integrates ther-modynamic principles such as membrane disruption. Our study utilized passive dosing, enabling us to control exposure and determine activities in both the medium and the algae. The concept of chemical activity and our results can be extended to other neutral chemical groups as effects of chemical activity remain independent of the mixture composition.