increased, socio-economic burden

The key event "increased, socio-economic burden" represents a non-traditional Adverse Outcome (AO) that serves a specific purpose: to extend the biological plausibility of an AOP into its broader societal and economic implications. We propose here to label this special AO as a Cost Outcome (CO). The addition of a CO to an AOP leads to the creation of a new framework referred to as a COP (Cost Outcome Pathway). A Cost Outcome does not change the working framework of the AOPs, but adds an extra level of organisation.

Unlike conventional AOs, which typically reflect toxicological or clinical endpoints (e.g., impaired fertility, cancer, mortality), this socio-economic AO captures the downstream impacts of those outcomes on healthcare systems, labor markets, and societal well-being. As such, this event should not be used in isolation, but rather should always follow a conventional AO within the AOP structure. It functions as a terminal extension to highlight how established adverse health effects translate into measurable economic and social consequences, supporting regulatory relevance and policy decision-making.

This socio-economic adverse outcome can be further decomposed into more specific consequences, such as:

• Loss of income or productivity (e.g., due to morbidity or premature death)
• Increased healthcare costs (e.g., hospitalization, long-term treatment)
• Costs of monitoring and risk management (e.g., environmental surveillance, medical screening programs)
• Social costs (e.g., reduced educational attainment, increased social assistance needs)
• Intangible costs (e.g., reduced quality of life, psychological distress)

These component-level outcomes can be used to support a more granular and context-specific assessment of the 'increased, socio-economic burden', depending on the nature of the conventional AO and the regulatory question at hand.

Socio-economic burden refers to the overall impact that a particular issue such as a disease (cancer, obesity), environmental hazard, or social condition (lower IQ) has on both the economic resources and the social well-being of individuals, communities, and societies at large. This burden encompasses direct costs (e.g., medical expenses, infrastructure damage), indirect costs (e.g., productivity loss, reduced educational attainment), and intangible costs (e.g., psychological distress, social exclusion).

• Direct Costs: These are measurable expenses directly related to the issue, such as healthcare expenditures, social service costs, compensary education and monitoring.

• Indirect Costs: These refer to productivity losses due to morbidity, premature mortality, absenteeism or lower IQ. Method such as the human capital approach is commonly used to estimate these costs.

• Intangible Costs: These include reduced quality of life, psychological distress, and social stigma. Tools such as quality-adjusted life years (QALYs) and disability-adjusted life years (DALYs) are used to assess the burden on individuals' well-being.

Regulatory significance of the socio-economic burden refers to the extent to which the quantification and understanding of economic and socio-economic costs influence public policy, regulatory frameworks, and resource allocation. When the economic burden of an issue (such as a disease, environmental hazard, or social determinant) is demonstrated to be substantial, it can serve as a compelling rationale for government intervention.

This information can inform policymakers about the adverse effects of various exposures, such as environmental pollutants or socio-economic stressors. By structuring the associated socio-economic burden, it provides evidence-based insights that can guide regulatory action, risk assessment, and preventive strategies aimed at mitigating harm and protecting public health.

Policymakers have a vested interest not only in protecting public health and well-being, but also in reducing the economic burden associated with preventable exposures. Effective regulation can thus serve a dual purpose: safeguarding the population while simultaneously alleviating financial pressures on healthcare systems, social services, and the broader economy.

From the human perspective, diseases such as cancer or obesity (or recently Covid-19) do not represent the end point of a toxicity pathway (AOP), but rather the beginning of a broader set of socio-economic consequences. These conditions often lead to a cascade of burdens, including direct costs (such as medical treatment, care and reduced salary), indirect costs (such as productivity loss and long-term disability), and intangible costs (such as psychological distress and diminished quality of life). As such, the full impact of these diseases extends well beyond clinical outcomes, underscoring the need for comprehensive public health and regulatory responses.

• Global status report on noncommunicable diseases, WHO
• Global Burden of Diseases, IHME

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