Practical Framework for the Derivation of Health-Based Acute Exposure Guidance Values for Chemical Emergency Responses, Planning, and Prevention Programs.

Abstract

Tragic accidents in chemical manufacturing plants in the last century raised the need for regulatory frameworks to control hazards, prevent or reduce the risk of major accidents and to limit the consequences for human health and the environment. The derivation of health-based Acute Exposure Guidance Values (AEGVs) is pivotal for providing science/health-based landmarks, contributing to land-use planning, industrial plant design, and the development of chemical emergency response plans. Here, we describe a pragmatic procedure to derive reliable health-based values to comply with the provisions of the Directive 2012/18/EU (Seveso Directive III). The candidate substances selection considers their hazard classification, and existing AEGVs are used in a hierarchical proceeding. If needed, company-specific Acute Exposure Threshold Level-2 (AETL-2) values, preventing irreversible health effects or escape impairment, and AETL-3 values, preventing life-threatening effects or death, are derived based on the ACUTe EXposure project methodology. Since a substantial number of substances do not possess suitable experimental inhalation toxicity data, AEGV-related information of approximately 650 substances was extracted to derive generic AEGVs based on their classification for local corrosive or irritative effects. The values obtained support that a less severe classification category translates into higher AEGVs, and local corrosive toxicity appears to be a relevant driver for the AEGV derivation. In the absence of high acute toxicity, carcinogenic, mutagenic, or reproductive toxicity (CMR) properties, or organ-specific toxicity, generic AEGVs are useful to strengthen decisions for suitable points of departure in a weight of evidence approach and to confirm the plausibility of derived AETL values.