In vitro functional screening as a means to identify new plasticisers devoid of reproductive toxicity

Plasticisers are indispensable additives providing flexibility and malleability to plastics. Among them, several phthalates, including di (2-ethylhexyl) phthalate (DEHP), have emerged as endocrine disruptors, leading to their restriction in consumer products and creating a need for new, safer plasticisers. The goal of this project was to use in vitro functional screening tools to select novel non-toxic plasticisers suitable for further in vivo evaluation. A panel of novel compounds with satisfactory plasticiser properties and biodegradability were tested, along with several commercial plasticisers, such as diisononyl-cyclohexane-1,2-dicarboxylate (DINCH®). MEHP, the monoester metabolite of DEHP was also included as reference compound. Because phthalates target mainly testicular function, including androgen production and spermatogenesis, the authors used the mouse MA-10 Leydig and C18-4 spermatogonial cell lines as surrogates to examine cell survival, proliferation, steroidogenesis and mitochondrial integrity. The most promising compounds were further assessed on organ cultures of rat foetal and neonatal testes, corresponding to sensitive developmental windows. Dose-response studies revealed the toxicity of most maleates and fumarates, while identifying several dibenzoate and succinate plasticisers as innocuous on Leydig and germ cells. Interestingly, DINCH®, a plasticiser marketed as a safe alternative to phthalates, exerted a biphasic effect on steroid production in MA-10 and foetal Leydig cells. MEHP was the only plasticiser inducing the formation of multinucleated germ cells (MNG) in organ culture. Overall, organ cultures corroborated the cell line data, identifying one dibenzoate and one succinate as the most promising candidates. The adoption of such collaborative approaches for developing new chemicals should help prevent the development of compounds potentially harmful to human health.

Authors: Boisvert A, Jones S, Issop L, Erythropel HC, Papadopoulos V, Culty M. ;Full Source: Environmental Research. 2016 Jul 14; 150:496-512. doi: 10.1016/j.envres.2016.06.033. [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][Epub ahead of print] ;[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]