In Vivo Mutagenicity Testing of Arylboronic Acids and Esters

Melisa J. Masuda-Herrera1, Krista L. Dobo2, Michelle O. Kenyon2, Julia D. Kenny3, Sheila M. Galloway4, Patricia A. Escobar4, M. Vijayaraj Reddy4, Robert A. Jolly5, Alejandra Trejo-Martin1, Caren Brown6, Marie Mckeon6, Megan Young6, Shannon Bruce6, Kamala Pant6, Aparajita Dutta6, Rohan Kulkarni6, Joel P. Bercu1

1 Gilead Sciences
2 Pfizer Global Research & Development
3 GlaxoSmithKline
4 Merck & Co. Inc.
5 Eli Lilly and Company
6 Millipore Sigma BioReliance® Toxicology

Environmental and Molecular Mutagenesis
Volume 60, Issue 9, December 2019, Pages 766-777

Arylboronic acids and esters are routinely used in the pharmaceutical industry as intermediaries during the synthesis of drugs. An unintended consequence of using arylboronic acids and esters is that impurities are sometimes left over during the process of drug synthesis. Based on previous studies, arylboronic acids and esters are often positive in the in vitro Ames bacterial reverse mutation assay. Due to this positive in vitro Ames result, the level of impurities based on these intermediaries must be kept to a very low level during drug synthesis and must be monitored closely for genotoxicity. It is also worth mentioning that keeping these impurities at very low levels is both complex and expensive for pharmaceutical companies.  

For this study, researchers evaluated 8 arylboronic compounds using Litron’s MutaFlow (Pig-a) Kit, Litron’s in vivo MicroFlow Kit for micronucleus detection, and also the in vivo comet assay. The results for all of the studies were negative. This work demonstrates that the risk of mutagenicity due to arylboronic compounds is quite low.