Phthalate plasticizers are incorporated into plastics to make them soft and malleable, but are known to leach out of the final product into their surroundings with potential detrimental effects to human and ecological health. The replacement of widely-used
phthalate plasticizers, such as di-ethylhexyl
phthalate (
DEHP), that are of known toxicity, by the commercially-available alternative Tris(2-ethylhexyl) tri-mellitate (
TOTM) is increasing. Additionally, several newly designed "green"
plasticizers, including di-heptyl
succinate (DHPS) and di-octyl
succinate (DOS) have been identified as potential replacements. However, the impact of
plasticizer exposure from medical devices on patient recovery is unknown and, moreover, the safety of
TOTM, DHPS, and DOS is not well established in the context of patient recovery. To study the direct effect of clinically based chemical exposures, we exposed C57bl/6 N male and female mice to
DEHP,
TOTM, DOS, and DHPS during recovery from cardiac surgery and assessed survival, cardiac structure and function, immune cell infiltration into the cardiac
wound and activation of the NLRP3
inflammasome. Male, but not female, mice treated in vivo with
DEHP and
TOTM had greater cardiac dilation, reduced cardiac function, increased infiltration of neutrophils, monocytes, and macrophages and increased expression of
inflammasome receptors and effectors, thereby suggesting impaired recovery in exposed mice. In contrast, no impact was detected in female mice and male mice exposed to DOS and DHPS. To examine the direct effects in cells involved in wound healing, we treated human THP-1 macrophages with the
plasticizers in vitro and found
DEHP induced greater NLRP3 expression and activation. These results suggest that replacing current
plasticizers with non-
phthalate-based
plasticizers may improve patient recovery, especially in the male population. In our assessment, DHPS is a promising possibility for a non-toxic biocompatible
plasticizer.