Next generation risk assessment of hair dye HC yellow no. 13: Ensuring protection from liver steatogenic effects.

Summary

Using an animal-free NGRA framework, the authors focused on hepatic steatosis as a key mode of action for a hair dye flagged by in silico tools. Human stem cell-derived hepatocytes showed gene expression changes across lipid metabolism pathways and triglyceride accumulation, enabling derivation of in vitro PoDs via PROAST to inform dermal safety margins.

Key Findings

• Adopted an AOP-guided NGRA focusing on hepatic steatosis for HC Yellow No. 13 due to in silico hepatotoxic alerts.
• In human stem cell-derived hepatocytes, measured expression of 11 lipid metabolism genes and triglyceride accumulation after 72 h exposure.
• Derived in vitro Points of Departure (PoDs) using PROAST to inform protective dermal exposure limits.

Clinical Implications

Supports safer formulation and regulatory submissions for hair dyes by quantifying steatogenic risk using human-relevant assays, enabling dermatologists and toxicologists to better counsel on product safety.

Limitations

• In vitro findings may not fully capture systemic metabolism and exposure dynamics.
• No confirmatory human exposure or epidemiological data presented.

Future Directions

Integrate in vitro-to-in vivo extrapolation (IVIVE) and dermal PBPK modeling to translate PoDs to consumer exposure scenarios; expand AOP endpoints to include mitochondrial dysfunction and inflammation pathways.