Placental toxicity of alternative plasticizers: Current knowledge and future directions

Phthalates, a class of plasticizers, are known endocrine-disrupting chemicals that can negatively impact reproduction and development, including placental development and function. In response to growing concerns, various groups of chemicals, including but not limited to terephthalates, citrates, and cyclohexane dicarboxylic acids, have been developed as phthalate replacements. However, significant research gaps remain in understanding how these new chemicals affect humans. This review aims to synthesize existing research on how phthalate alternatives affect the placenta, a transient yet critical organ that supports fetal growth and development during pregnancy. Disruptions to placental structure and function can cause pregnancy complications and alter fetal programming. Herein, we review findings from biomonitoring, in vivo and in vitro experiments, as well as epidemiological studies to assess potential impacts. Although biomonitoring and house dust studies have identified the presence of alternative plasticizers, many identified chemical groups lack studies on their effects during pregnancy and on the placenta. Given the rising levels of these chemicals and their metabolites in urine and blood, further investigation into their mechanisms of toxicity is necessary. Notably, some alternatives may have the capability to alter pregnancy outcomes similar to traditional phthalates, such as by increasing the likelihood to develop conditions like gestational diabetes mellitus, although the majority of alternative plasticizers lack data. Understanding these impacts will inform public policy aimed at protecting maternal and fetal health, facilitate the development of safer consumer products, and prevent further emergence of regrettable replacements.