In a viewpoint article published on July 25, 2022, in the journal of Environmental Science & Technology, Evgenios Agathokleous from Nanjing University of Information Science & Technology, China, and 38 co-authors from universities and other research institutions worldwide urge for the consideration of subthreshold effects (i.e., below the no-observed-adverse-effect-level, NOAEL) in chemical risk assessment.
The authors argue that risk assessment frameworks currently in place are still based on outdated scientific knowledge from the 20th century broadly assuming a linear dose-response relationship of chemicals and often only include high doses which are not necessarily environmentally realistic. However, with technological progress low-dose and hormetic effects can and have been measured. Hormetic effects are characterized by low-dose stimulation and high-dose inhibition, thus resulting in a J-shaped or an inverted U-shaped dose respPreview Changes (opens in a new tab)onse.
Agathokleous et al. describe that such effects have been demonstrated upon exposure to several environmental contaminants including micro- and nanoplastics as well as organic flame retardants. Besides, pathways regulating cancer would often follow a hormetic function. Accordingly, the authors think that “there is an urgent need for regulatory authorities around the world to be inclusive of the most up-to-date science by (re)considering (i) potential subthreshold responses, (ii) nonlinear dose−response models able to detect subthreshold responses, and (iii) abandoning the default use of linear dose−response models for all risk assessments.” In practice that would mean selecting the most suitable model describing the response of a chemical instead of expecting a specific dose-response model “a priori.” Only if such an accurate risk assessment process is implemented can appropriate action be taken, Agathokleous and co-authors emphasized further. In addition to regulatory agencies, scientists should also set a higher priority in researching effects of lower and environmentally realistic doses.
The scientists also discuss that current regulatory frameworks would, for the most part, not consider subthreshold responses but some efforts exist. For instance, the European Food Safety Authority’s (EFSA) scientific committees have acknowledged subthreshold effects and nonlinear responses of the endocrine disrupting chemicals (EDC) bisphenol A (BPA, CAS 80-05-7) and bis(2-ethylhexyl phthalate) (DEHP, CAS 117-81-7) and emphasized to address such responses in risk assessment.
Mid 2020, the non-governmental organization Chem Trust called to consider EDCs as non-threshold chemicals by default (FPF reported) and the European Committee of the Regions (CoR) to apply the non-threshold principle to all EDCs across EU laws while also requesting to ban bisphenols and phthalates in food contact materials (FPF reported). According to the EU Chemicals Strategy for Sustainability, the European Commission will “extend the generic approach to risk management to ensure that consumer products…do not contact chemicals that cause cancers, gene mutations, affect the reproductive or the endocrine system” (FPF reported).
Reference
Agathokleous E. et al (2022). “Rethinking Subthreshold Effects in Regulatory Chemical Risk Assessments.” Environmental Science & Technology. DOI: 10.1021/acs.est.2c02896
