In a study published on July 15, 2016 in the peer-reviewed journal Environmental Research, Annie Boisvert and colleagues from McGill University, Canada, report on the results of an in vitro screening performed for a panel of novel plasticizers being developed with the aim to replace toxic phthalates.

Eighteen representatives of four chemical families, dibenzoates, succinates, maleates, and fumarates, were tested, along with several commercial plasticizers. The latter included 1,2-cyclohexane dicarboxylic acid di-isononyl ester (DINCH®), a plasticizer marketed as a safe alternative to phthalates and widely used in polyvinyl chloride toys and childcare products in Europe. In vitro tests focused on testicular function, as this endpoint is most strongly affected by several phthalates. Mouse MA-10 Leydig and C18-4 spermatogonial cell lines, as well as primary cultures of rat fetal and neonatal testes, were used to assess the effects on cell survival, proliferation, mitochondrial integrity, and hormone-induced steroid production (steroidogenesis). Compounds with low toxicity profiles were further prioritized based on three “plasticizer properties” criteria, namely their ability to provide flexibility to polyvinyl chloride polymers, their leaching behavior, and biodegradability.

DINCH® did not affect cell viability and proliferation, but inhibited steroidogenesis in both cell lines and primary cultures. Maleates and fumarates significantly impaired cell viability and proliferation, and inhibited steroidogenesis in cell lines and primary cultures. Most of dibenzoates and succinates did not cause a significant toxicity or inhibition of steroidogenesis, but, surprisingly, most of these compounds stimulated steroid production instead. This was true also for the two molecules proposed by the authors as the most promising alternative plasticizer candidates, 1,4-butanediol dibenzoate (BDB) and di-n-octyl diester of succinic acid (DOS), selected after additionally weighing in their “plasticizer properties.” Although the authors reasoned that stimulation of steroidogenesis is certainly less adverse than inhibition caused by phthalates, it has to be pointed out that the consequences of such an effect for the male reproductive health are currently incompletely understood.


Boisvert, A. et al. (2016). “In vitro functional screening as a means to identify new plasticizers devoid of reproductive toxicity.Environmental Research 150: 496-512.