Rethinking Subthreshold Effects in Regulatory Chemical Risk Assessments

A great number of dose–response studies indicate that hormesis is a common phenomenon, occurring in numerous organisms exposed to singular or combined environmental stressors, such as pharmaceuticals, heavy metals, micro/nanoplastics, organic flame retardants, pesticides, and rare earths. (1−6) While biological responses to low exposure levels are often beneficial, exposure to doses below the no-observed-adverse-effect-level (NOAEL; hereafter subthreshold doses) does not always translate to beneficial responses. (2,4) For example, subthreshold contaminant doses can enhance the virulence of phytopathogenic microbes and promote the resistance of crop pests with significant implications for crop production. (2,7,8) Subthreshold contaminant exposures can also stimulate infectious animal/human pathogens and promote their resistance to antibiotics and other drugs, threatening long-term sustainability. Importantly, the hormetic function of common pathways that regulate cancer progress indicate that current regulatory standards may not protect adequately against cancer risks. (9−11)