Introduction to “The Trouble with Plastics” special issue

Plastics surround us. If we move our gaze to what we use in our daily lives, there are plastics in many guises. We rely on them and would be hard pressed to live without them. Our cell phones, ear buds, credit cards, clothes, shoes, car parts, grocery bags, packaging, food containers, glasses, laboratory ware, water bottles, cigarette butts, linings metal cans, pens, medical tubing, laboratory supplies, fishing gear, toys, baby bottles, sippy cups, pacifiers, all are made up of plastics. The manufacture, use, and disposal of plastics release many long-lasting chemicals into the environment that accumulate and negatively affect flora and fauna, as well as humans. As much as we need plastics, we also need to be aware of how they impact the environment, our health, and that of our children and their children. The authors for this special issue have tackled the "trouble with plastics" from several points of view (Figure 1). We will learn many of the ways in which plastics negatively impact our health and induce birth defects, some that may not manifest until later life. These findings should motivate us to consider with some urgency what we can do to minimize or avoid the negative impact of plastics. Dr. Darbre (Darbre, in this issue) provides an overview of the many chemicals lurking in plastics. Bisphenol A and phthalates are added to plastics, leach from them, and disrupt many hormone systems. We breath them in, eat them, and absorb them through our skin. When we are exposed to these insidious endocrine-disrupting chemicals at a vulnerable "window of susceptibility" in utero or during early life, consequences may arise later in life in the form of reproductive difficulties, metabolic disorders, thyroid dysfunction, immune dysregulation, adverse neurobehavioral outcomes, or cancer. Dr. Darbre urges further studies to fill the many gaps in our understanding regarding how these ubiquitous chemicals affect our health and that of generations to come. Dr. Duttaroy and team (Basak et al., in this issue) lay out an extensive review of the compounds related to plastics that can, even at low concentrations, affect the development of animal models and likely that of humans. These include "bisphenols (BPA, BPS, BPF), bis(2-ethylhexyl) phthalate, and dibutyl phthalate (DBP)" and also "polybrominated diphenyl ethers (PBDE) and tetrabromobisphenol A (TBBPA)." Plastics-derived endocrine-disrupting compounds and their alternate "safer" substitutes are showing similar adversity on reproductive development in several studies. Animal studies expose that mechanisms of action of these chemicals that leach from plastics can disturb early embryonic and placental development. Evidence is accumulating that these chemicals act through long-lasting epigenetic effects that may explain transgenerational effects. The U.S. Food and Drug Administration (FDA) banned BPA in baby bottles and sippy cups in 2012. We can congratulate ourselves for reducing our exposure to BPAs, yet its replacements, bisphenol-F (BPF) and bisphenol-S (BPS), may be worse! As the evidence mounts for the negative effects of these chemicals, intriguing questions come to mind. Could the rising levels of these compounds in humans account for the decline in sperm count and the rapid rise in obesity and metabolic disease? Dr. Montor and his team (Segovia-Meurdoza et al., in this issue; Solleiro-Villavicencio et al., in this issue) supply us with the astonishing statistics about the plastic patches covering our planet. These plastic patches or islands are deep, and debris often sinks to the bottom of the ocean. Various animals ingest plastics, and they are ingested in turn up the food chain, eventually reaching large predators including humans. Aside from aesthetic considerations, these patches pose a threat to life in the oceans and to our health in many ways. The two papers from this group also expand on the effects of BPA, phthalates, and other chemicals that are associated with plastics that affect the neuroendocrine (Solleiro-Villavicencio et al., in this issue) and the immune (Segovia-Meurdoza et al., in this issue) systems. While these systems are discussed separately, they overlap in their functions and affect many organs and systems in our bodies. Our "complex regulatory neuroendocrine network" expresses receptors that BPA and phthalates can bind to and initiate disruptive responses and/or inhibit normal responses even at low concentrations. The links between exposure to these chemicals in utero and early life and neurobehavioral and cognitive dysfunction are also disturbing. The authors also warn that, in studies of the immune system, "… many reports do not consider that the immune response must be studied by challenging the immune components, so there is little information about BPA effects on the immune response during disease." This means that immune system deficiencies caused by BPA and phthalates exposure might be missed by studying basal conditions and that BPA and phthalate effects could be worse or more widespread than we suspect. Dr. Posnack and colleagues (Ramadan et al., in this issue) alert us to the inadvertent hospital-based chemical exposures through the use of plastic medical products, which can lead to cardiovascular consequences. Notably, phthalate concentrations accumulate over time in stored red blood cell units with di(2-ethylhexyl)phthalate (DEHP) levels increasing over time. Cardiopulmonary bypass is known to precipitate an inflammatory response, yet it is still unclear whether phthalate and bisphenol chemicals from the tubing circuitry may contribute to these effects. These distressing facts suggest that vulnerable pediatric populations are at increased risk for chemical exposures through lines and other medical devices. Dr. Atay and colleagues (Atay et al., in this issue) describe how BPA affects early chicken embryo development. Key events at these stages are the closure of the neural tube and formation of somites. Both were disrupted by BPA exposure, and the overall growth of the embryo lagged. The puzzle here is that BPA is thought to act as an endocrine disruptor targeting steroid hormone receptors [estrogen receptor (ER), estrogen-related receptor (ERR), and androgen receptor (AR)] (Asencio-Hernández, Kieffer, & Delsuc, 2016) that are known to be expressed during gonad development but have not been reported in the neural tube or somites at this early stage. However, there is a report that these receptors are expressed in the extraembryonic membranes (Kumar, Lohrentz, Gahr, & Groothuis, 2019), suggesting an indirect effect through these membranes rather than a direct effect of BPA on the embryo. Atay et al. report the novel finding that AR and ER mRNAs are expressed on extraembryonic membranes (EMs) before the embryo begins its own hormone production, identifying a novel substrate for action of maternal hormones on the embryo. Finished plastic products that end up in the environment, as well as chemicals released from plastics, are known to negatively affect human and animal health. This special issue provides insight into a number of known and potential health impacts of chemicals in plastics. The ongoing saga of BPA and bisphenol replacements can also be followed in an in-progress special issue of Toxicology, to which articles continue to be added: https://www.sciencedirect.com/journal/toxicology/special-issue/10DGCJPVNJZ. The global problem of plastic manufacture, use, and disposal continues to receive much-needed attention from regulatory bodies and consumer groups worldwide, incorporating new technologies. The authors declare no conflict of interest.