XXXVIII CICLO | Varalda Giorgia Maria

My research focuses on New Approach Methodologies (NAMs) to reduce animal testing in genotoxicity studies, integrating in vitro and in silico approaches for toxicological assessment.

I specialize in cellular genotoxicity, with expertise in micronucleus and chromosomal aberration assays, classical cytogenetics techniques, in situ hybridization, and human primary cell cultures as alternative models. My skills also include quantitative data analysis and interpretation for risk assessment.

Beyond my PhD, I gained international experience at the German Federal Institute for Risk Assessment, focusing on the toxicological evaluation of food contact materials and predictive models for chemical safety.

My research interests include regulatory toxicology, genotoxicity, applied cytogenetics and risk assessment, aiming to advance alternative methods for chemical safety and public health protection.

Emerging risks arise from newly identified hazards or unexpected increases in exposure to known hazards. This study applies New Approach Methodologies (NAMs) to assess the genotoxic potential of Bisphenol A alternatives (BPE), N-Nitrosamines, Phthalates (DEHP), and Neodecanoic Acid (NDA).
Cytome assays, immunofluorescence staining, and chromosome aberration analysis were conducted to evaluate their effects on genome stability. Results indicate that non-volatile nitrosamines do not raise genotoxic concerns. In contrast, DEHP and BPE induce aneuploidy, evidenced by increased micronuclei, chromosome missegregation, and mitotic spindle abnormalities. NDA exposure resulted in dose-dependent chromosomal damage, suggesting the potential for a threshold-based risk assessment.
A crucial distinction was made between mutagenic and aneugenic effects, as only the latter allows for the identification of a safe exposure threshold. These findings highlight the relevance of integrating genetic and metabolomic data within NAMs to improve hazard assessment while minimizing animal testing.
This study contributes to the refinement of genotoxicity testing strategies, supporting the development of regulatory frameworks that align with the 3Rs principle (Replace, Reduce, Refine) in toxicology. Future research will focus on confirming threshold mechanisms and integrating multi-omic data to enhance risk evaluation.