The ESTIV Members AreaNext generation risk assessment for occupational chemical safety:
A real world example with sodium-2-hydroxyethane sulfonate
We hope you will join us for the next installment of the ESTIV-ASCCT webinar series on Thursday, July 24, 2025. Please see below for the complete abstract and event details.
| When: Thursday, July 24, 2025 11:00 am – 12:00 pm ET / 15:00 – 16:00 UTC Featuring: Adam Wood, MRes, Risk Assessor at Unilever Steve Gutsell, PhD, Head of Regulatory Science for Chemical Safety at Unilever. A brief Q&A session will follow each presentation. Abstracts: Next Generation Risk Assessment (NGRA) is an exposure-led approach to safety assessment that uses New Approach Methodologies (NAMs). Application of NGRA has been largely restricted to assessments of consumer use of cosmetics and is not currently implemented in occupational safety assessments, e.g. under EU REACH. Contrastingly, a large number of worker/occupational safety assessments are underpinned by toxicological studies using experimental animals, hence occupational safety assessment represents an area that would benefit from increasing application of NGRA to safety decision making. Adapting previous NGRA workflows, we developed an occupational specific NGRA workflow, before testing the feasibility of this to make real-world safety decisions with a case study chemical; sodium 2-hydroxyethane sulphonate (sodium isethionate or SI). Exposures were first estimated using a standard occupational exposure model following a comprehensive life cycle assessment of SI and considering factory-specific data. Outputs of this model were then used to estimate internal exposures using a Physiologically Based Kinetic (PBK) model, which was constructed with SI specific Absorption, Distribution, Metabolism and Excretion (ADME) data. PBK modelling indicated a worst-case plasma maximum concentration (Cmax) of 0.8 μM across the SI life cycle. SI bioactivity was assessed in a battery of NAMs relevant to systemic, reproductive, and developmental toxicity; a cell stress panel, high throughput transcriptomics in three cell lines (HepG2, HepaRG and MCF-7 cells), pharmacological profiling and specific assays relating to developmental toxicity (Reprotracker and devTOX quickPredict). Points of Departure (PoDs) for SI ranged from 104 to 5044 µM. Cmax values obtained from PBK modelling of occupational exposures to SI were compared with PoDs from the bioactivity assays to derive Bioactivity Exposure Ratios (BERs) which demonstrated the safety for workers exposed to SI under current levels of factory specific risk management. In summary, the tiered and iterative workflow developed here represents an opportunity for integrating non animal approaches for a large subset of substances for which systemic worker safety assessment is required. Such an approach could be followed to ensure that animal testing is only conducted as a “last resort” e.g. under EU REACH. REGISTER NOW! |
