Human Health Risk Assessment of Complexly Contaminated Sites: Limitations of Additive Risk Models and the Challenge of Complex Environmental Mixtures

Abstract

Human health risk assessment (HHRA) has become a central regulatory framework for evaluating contaminated soils and groundwater impacted by industrial activities, petroleum releases, hazardous waste disposal, and urban development. Contemporary cumulative HHRA methodologies commonly estimate carcinogenic and noncarcinogenic risks through additive aggregation of individual contaminant risks across multiple exposure pathways. Although these approaches provide practical and conservative tools for environmental regulation, they also rely on substantial assumptions regarding toxicological additivity, contaminant independence, and dose response behavior. Real-world contaminated sites frequently contain complex mixtures such as hydrocarbons, polycyclic aromatic hydrocarbons (PAHs), chlorinated solvents, metals, and transformation products which interactions remain incompletely understood. This review critically examines the conceptual and scientific limitations associated with additive cumulative HHRA frameworks for complexly contaminated sites. Particular attention is given to unresolved mixture toxicology, toxicokinetic and toxicodynamic interactions, exposure heterogeneity, and the distinction between regulatory screening thresholds and actual biological disease probability. Total petroleum hydrocarbons (TPH) are discussed as a representative example of unresolved environmental mixtures that challenge conventional fraction-based assessment methodologies. The paper argues that current cumulative HHRA models should be interpreted primarily as operational regulatory approximations designed to provide conservative protection rather than comprehensive mechanistic representations of human carcinogenesis under mixed environmental exposure conditions. Emerging advances in systems toxicology, exposomics, physiologically based pharmacokinetic modeling, and high-resolution analytical chemistry may support development of more biologically informed future risk assessment frameworks.