101 Health-based nanomaterial guidance value (HNGV) for occupational exposure to spheroidal biodurable engineered nanomaterials of relatively low substance-specific toxicity

Abstract Exposure to engineered nanomaterials (ENMs) at the workplace can adversely affect human health via inhalation. Occupational exposure limits (OELs) for specific ENMs remain scarce due to a lack of nano-specific data and consensus on the most appropriate dose metric for exposure assessment. In 2022, recommendations were provided on how to derive Health-based Nano Reference Values (HNRVs) for different categories of ENMs (Visser et al Nanoimpact). We updated these recommendations based on new insights and information and changed the name into Health-based Nanomaterial Guidance Values (HNGVs) to distinguish from existing pragmatic Nano Reference Values. Using an expert consultation approach, we derived an HNGV for spheroidal biodurable ENMs with relatively low substance-specific toxicity. Benchmark ENMs were selected based on criteria such as low dissolution rate in physiologically relevant media and absence of substance-specific toxicity. For these ENMs, several human health endpoints were evaluated and pulmonary inflammation was selected as the critical effect. Persistent inflammation is considered an important driver for chronic adverse nanoparticle effects and keeping exposures below levels causing neutrophil influx will protect against effects such as lung fibrosis and lung cancer. Subsequently, no-observed-adverse-effect-concentrations (NOAECs) or lowest-observed-adverse-effect-concentrations (LOAECs) were derived from in vivo studies to provide a range of Derived No Effect Levels (DNELs). Based on a weighing of the studies contributing to the range, we recommend an HNGV value for an 8-h working day. This HNGV can be practically assessed at the workplace for ENMs that have a clear chemical signature such as metal-based ENMs, and may be more challenging for carbonaceous materials.