High-performance thin-layer chromatography (HPTLC)-bioassays are promising new methods for detecting bioactive chemicals in food packaging. Here, we test whether direct-acting genotoxic chemicals are detectable in food contact materials (FCM) using HPTLC-bioassays. First, an interactive worksheet lays out steps to calculate needed detection limits in (bio)analytical methods from regulatory limits, including thresholds of toxicological concern (TTC). Second, we show that the sensitivity of a HPTLC-genotoxicity assay to low doses of chemicals, including food contact chemicals, is greater than a standardized microtiter plate version and in vitro assays already reported. Third, using HPTLC, we detected genotoxicity in extracts of FCM, and not in simulated migrates of FCM. Applying the worksheet to calculate needed detection limits in FCM migrates, we observed that seven of ten genotoxic chemicals would be detectable with HPTLC if present at the regulatory 10 ppb limit and two of ten at TTC for adults. With development, HPTLC-bioassays might become the best option for supporting safety assessment of genotoxicants in food packaging.