Studying NMDRs presents several challenges. First, traditional toxicological studies are often designed to detect monotonic effects, which means NMDRs can be overlooked. Experimental designs need to be adapted to include a wider range of doses, especially low doses that might be more relevant to human exposure. Additionally, the interpretation of NMDR data can be contentious, as the results may vary significantly between studies due to differences in experimental conditions, endpoints measured, and the biological systems used.