Work

P30-01 Application of 3Rs Strategies for Existing Chemicals Substances Standard Registration in Taiwan: Case study of Silicon carbide

Year: 2025

Type: article

Abstract: Chemical safety remains an important issue for both human health and environmental protection. In Taiwan- the Chemicals Administration under the Ministry of Environment has adopted a registration system for existing chemical substances, referencing international regulatory frameworks such as the EU's SAICM, REACH and the CLP regulation. To align with global trends in animal welfare, Taiwan has also emphasized the application of the 3Rs principles (Reduction, Replacement, and Refinement) in chemical safety testing. In this context, our research explores the use of alternative testing strategies that integrate in vitro, in silico, and minimize in vivo methods for standard chemical registration. As a case study, we selected silicon carbide (SiC), a widely used substance in Taiwan's semiconductor and grinding industries. This was the first chemical substance evaluated through our platform and was used to assess the feasibility of applying integrated alternative testing strategies under Taiwan's registration framework. Our approach combined 2D and 3D in vitro cell-based assays, QSAR modeling, and minimized animal testing. When appropriate, we submitted tailored testing plans or applied for exemptions to meet data requirements without unnecessary use of animals. For toxicological evaluation, we applied several OECD Test Guidelines (TGs), including acute oral toxicity (TG 420), in vitro skin irritation using a 3D model (TG 439), and eye irritation via the short time exposure method (TG 491). Skin sensitization was assessed using the local lymph node assay (TG 442B) and alternative methods aligned with key events in the skin sensitization pathway (TG 442C/D/E). Genotoxicity was evaluated with the bacterial reverse mutation test (TG 471) and the in vitro micronucleus test (TG 487). We also conducted repeated dose 90-day oral toxicity (TG 408) and a two-generation reproductive toxicity study (TG 416). For ecotoxicity testing, we performed acute toxicity tests with Daphnia (TG 202), algal growth inhibition (TG 201), fish embryo toxicity (TG 236), and fish cell line (TG 249). The QSAR model was used to predict ready biodegradability (TG 301). Additional test plans and data submissions covered further OECD TGs, including 474, 417, 451, 209, 121, 211, 210, 220, 227, 216, 308, 307, 305, and 218, ensuring that all necessary endpoints for SiC safety assessment were addressed. This case study demonstrates the practical application of 3Rs-aligned strategies in Taiwan's regulatory context. The same approach has been extended to UVCBs (Substances of Unknown or Variable composition, Complex reaction products, or Biological materials), supporting manufacturers in meeting regulatory registration requirements. Overall, our methodology has enabled the completion of chemical registrations while reducing animal use by 50%, saving 50% in time, and lowering costs by up to 70% through joint registration efforts.

Source: Toxicology Letters

DOI: 10.1016/j.toxlet.2025.07.864