Identifying Greener and Safer Plasticizers: A 4-Step Approach

Abstract

The health and economic burden of endocrine disrupting chemicals, such as the plasticizer di(2-ethylhexyl) phthalate (DEHP), is prompting industry to develop alternatives. However, the absence of requirements for manufacturers to ensure the safety of these alternatives has led to the generation of replacements that may have similar or worse effects than the original chemicals. Consequently, there is increasing recognition by scientists, regulators and industry that proactive approaches are needed to develop safe chemical substitutes. We propose a 4-step approach for the design, characterization and toxicological testing of responsible alternative chemicals that we illustrate with our ongoing studies on DEHP replacements. Our approach is comprised of: (1) the design and characterization of alternative chemicals based on innovative chemical structures and environmental considerations; (2) large-scale in vitro cell-based high throughput and selective ex vivo studies to preselect the most innocuous alternatives; (3) an acute toxicity in vivo study to rule out overt toxicity of the selected candidates; and (4) an in utero and lactational exposure study comparing the effects of selected candidates to those currently in use, emphasizing commonly described phenotypes after exposure to the latter. Using this 4-step approach, we have identified 2 alternative chemicals displaying good plasticizing properties, better biodegradability, and less leaching than DEHP without any apparent toxicity in vivo. This process has thus far proven useful in the proactive identification of responsible chemical replacements for DEHP.

Replacement Bisphenols Adversely Affect Mouse Gametogenesis with Consequences for Subsequent Generations

“…The ability to rapidly enhance the properties of a chemical has tremendous potential for treating cancer, enhancing medical and structural materials, and controlling dangerous infectious agents. Importantly, this technology has paved the way for “green chemistry”, a healthier future achieved by engineering chemicals to ensure against hazardous effects (e.g., [67]). Currently, however, regulatory agencies charged with assessing chemical safety cannot keep pace with the introduction of new chemicals.…”

Effects of In Utero and Lactational Exposure to New Generation Green Plasticizers on Adult Male Rats: A Comparative Study With Di(2-Ethylhexyl) Phthalate

“…In previous studies, we used a 4-step approach to identify greener replacements for DEHP with desirable plasticizing properties, biodegradability, minimal leaching, and fewer deleterious effects. We identified 2 candidate compounds, 1,4butanediol dibenzoate (BDB) and dioctyl succinate (DOS), that did not cause significant physiological perturbations in several immortalized cell lines or after acute exposure in vivo (Albert et al, 2018;Boisvert et al, 2016;Nardelli et al, 2015). Recently, we demonstrated that in utero and lactational exposure to BDB and DOS did not produce the phenotypes described after exposure to DEHP from gestational day (GD) 8 to post-natal day (PND) 3, 8, or 21 (Nardelli et al, 2017).…”

Designing Green Plasticizers: Linear Alkyl Diol Dibenzoate Plasticizers and a Thermally Reversible Plasticizer

“…Three of the four compounds were as effective, or indeed, more effective than commercially-available DEHP in all but one tested material property. In combination with previous studies that showed rapid environmental degradability [21,24,30] and a low toxicity profile [26,27,28,29,35], 1,5-pentanediol dibenzoate in particular stands out as a good candidate green plasticizer to replace DEHP, in addition to 1,3-propanediol dibenzoate and 1,6-hexanediol dibenzoate. Further, while 1,4-butanediol dibenzoate is not a good candidate for a drop-in replacement of DEHP, due to its observed material hardening, this study suggests its use as a reversible heat-activated plasticizer or processing aid, with excellent plasticizer properties at mildly elevated temperatures.…”

“…Further, the proposed diol dibenzoate compounds could be good green candidates to replace phthalates, given previous work that identified their rapid biodegradation by soil bacteria [21,24,30]. Several toxicological in-vitro studies have also suggested a low hazard associated with these compounds [26,27,28,29,35], yet a more thorough toxicological analysis would likely be needed to confirm these findings.…”