The potential reproductive, developmental, immunological, growth and carcinogenetic effects of endocrine disruptors in humans and wildlife is of global concern. Scarce prior risk analyses of these multiple stressors in river watersheds existed. Therefore, this thesis developed an integrated risk assessment of endocrine disruptors at a section of the Lower Uruguay River with industrial (a bleached Kraft pulp mill), domestic (cities) and agricultural (soy crops) sources. A preliminary risk assessment prioritised oestrogens and further compounds of concern in the watershed, notably nonylphenol, glyphosate, endosulfan, chlorophenols, dioxins and furans, polyaromatic hydrocarbons, polychlorinated byphenyls, rosin acids and phytosterols. Models predicted their multimedia distribution, and food web interactions, and then tested. A three-tiered exposure assessment first rated the river status with eutrophication risks using artificial neural networks, while growth effects evidenced in Hyalella curvispina. Then, river sampling sites were determined by hydrodynamic modelling, tracking pollutant transport by clustering and observing reproductive effects in Ceriodapnia dubia. Finally, target compounds were analysed and endocrine disruption studied from gene to population levels. Biomonitoring with Astyanax fasciatus wildfish found no intersex, but smaller testes downstream the pulp mill and lower condition factor near municipal discharges. Spinal malformations were observed exposing Pimephales promelas to sediment elutriates. When exposed to pulp mill effluent, egg production decreased by half. Anti-oestrogenic or androgenic effects were suggested by the toxicogenomic biomarkers ESR1, ESR2, IGF-I and GHR. The oestrogenicity of a stream receiving municipal wastewater was demonstrated by effects like estradiol in ZP3, ESR1 and IGF-I expression, in agreement with the luciferase receptor-binding screen, and the occurrence of oestrogens and nonylphenol. Overall risks of endocrine disruptors were estimated with radar diagrams, pondering nonylphenol and endosulfan as of concern in the watershed.The risks of endocrine disruption to humans through fish and water ingestion were characterised as low, and from low to moderate to freshwater biota.