Cytotoxic Effects Induced by Combined Exposure of the Patulin, Ochratoxin A, and Acetamiprid to HK-2 and SK-N-SH Cell Lines

Patulin (PAT), ochratoxin A (OTA), and acetamiprid (ACM) are common food contaminants that frequently co-occur in agricultural products, raising concerns over their cumulative health risks. This study is the first to systematically assess the combined cytotoxic effects of PAT, OTA, and ACM using combination index (CI) and dose reduction index (DRI) models in HK-2 and SK-N-SH cells. All three compounds exhibited dose-dependent toxicity, with potency ranked as PAT > OTA > ACM. In HK-2 cells, PAT+OTA and OTA+ACM showed primarily antagonistic interactions, with synergism observed at low doses. PAT+ACM displayed exposure time-dependent additive effects, while the ternary mixture was mostly antagonistic, with OTA being the dominant contributor. In SK-N-SH cells, most combinations were antagonistic; however, OTA+ACM showed dose-dependent shifts, and the triple mixture transitioned from antagonism to synergism at higher concentrations. OTA and ACM were identified as the main toxicity drivers in all combinations. These findings highlight dose- and cell-specific interactions and underscore the importance of cumulative risk assessment of co-occurring mycotoxins and pesticides in food safety regulation.