Rachael completed her undergraduate degree in chemistry in 2009 at the University of Leeds under the supervision of Dr Richard Foster, and remained there to complete a masters degree in chemical biology, followed by a PhD which focused on the design, chemical synthesis and biological screening of fenretinide analogues as a therapeutic for the childhood cancer, Ewing’s sarcoma.
Upon completion of her PhD, Rachael joined Lhasa in 2015 where her work has primarily focused on the development of expert knowledge-based toxicity alerts for multiple toxicological endpoints, including mutagenicity, chromosome damage, skin sensitisation and carcinogenicity. Since 2017, Rachael has taken leadership of knowledge development for Derek Nexus, working closely with members and regulators to develop new knowledge and robust in silico predictions from both public and proprietary data. Rachael is also the lead scientist for Lhasa’s ICHM7 solution, and over the last 18 months has been heavily involved in collaborations that aim to address the ongoing challenges of nitrosamine impurities in APIs.
Mutagenicity data is a core component of the safety assessment data required by regulatory agencies for acceptance of new drug compounds, with the OECD-471 bacterial reverse mutation (Ames) assay most widely used as a primary screen to assess drug impurities for potential mutagenic risk. Previous literature reports indicated that the Ames test might not be sensitive enough to detect the mutagenic potential of N-nitrosamines in order to accurately predict a risk of carcinogenicity. To explore this hypothesis, public Ames and rodent carcinogenicity data pertaining to the N-nitrosamine class of compounds was collated for analysis. Here we present how variations to the OECD 471-compliant Ames test, including type of metabolic activation, solvent type and preincubation/plate incorporation methods, may impact the predictive performance for carcinogenicity. An understanding of optimal conditions for testing of N-nitrosamines may improve both the accuracy and confidence in the ability of the Ames test to identify potential carcinogens.View Details