Increases in the global use of plastics
have caused concerns regarding
potential adverse effects on human health. Plastic products contain
hundreds of potentially toxic chemical additives, yet the exact chemicals
which drive toxicity currently remain unknown. In this study, we employed
nontargeted analysis and in vitro bioassays to identify
the toxicity drivers in plastics. A total of 56 chemical additives
were tentatively identified in five commonly used plastic polymer
pellets (i.e., PP, LDPE, HDPE, PET, and PVC) by employing suspect
screening and nontargeted analysis. Phthalates and organophosphates
were found to be dominant in PVC pellets. Triphenyl phosphate and
2-ethylhexyl diphenyl phosphate accounted for a high amount (53.6%)
of the inhibition effect of PVC pellet extract on human carboxylesterase
1 (hCES1) activity. Inspired by the high abundances of chemical additives
in PVC pellets, six different end-user PVC-based products including
three widely used PVC water pipes were further examined. Among them,
extracts of PVC pipe exerted the strongest PPARγ activity and
cell viability suppression. Organotins were identified as the primary
drivers to these in vitro toxicities induced by the
PVC pipe extracts. This study clearly delineates specific chemical
additives responsible for hCES1 inhibition, PPARγ activity,
and cell viability suppression associated with plastic.