Prevalence and reproductive toxicity of di-2-ethylhexyl terephthalate (DEHTP) and other substituted benzene carboxylic acid derivatives used as phthalate alternatives

Phthalate alternatives have emerged worldwide recently in response to concerns that traditional ortho-substituted phthalates alter and inhibit endocrine and reproductive functions and behave as endocrine disrupting chemicals (EDC). As a result, legacy plasticizers are being phased out of use, giving rise to alternative plasticizers. Human biomonitoring studies indicate that people are increasingly exposed to alternative plasticizers. However, recent studies suggest that alternative plasticizers may disrupt endocrine and reproductive functions. Foremost among these emerging substitutes are di-2-ethylhexyl terephthalate (DEHTP), a ring substitution isomer of the most common plasticizer phthalate di-2-ethylhexyl phthalate (DEHP), and tri-2-ethylhexyl trimellitate (TOTM), which has three ester side chains compared to DEHP and DEHTP's two. In this literature review, we provide a comprehensive overview of environmental monitoring and biomonitoring of DEHTP and other substituted benzene carboxylic acid derivatives used as phthalate alternatives, which together illustrate the widespread use of these compounds leading to human and environmental exposures as ubiquitous as phthalates. We also review reproductive toxicity findings in animals, in vitro, and human epidemiology. Overall, the availability of studies regarding the health impacts of alternative plasticizers is limited. Published literature suggests that these chemicals can disrupt hormone levels in rodents and zebrafish. This review underscores the urgent need for further research to characterize the long-term health impacts of these emerging chemicals and to prevent the regrettable substitution of one hazard for another.