Towards a paradigm shift in environmental health decision-making: a case study of oxybenzone

Background Technological advancements make lives safer and more convenient. Unfortunately, many of these advances come with costs to susceptible individuals and public health, the environment, and other species and ecosystems. Synthetic chemicals in consumer products represent a quintessential example of the complexity of both the benefits and burdens of modern living. How we navigate this complexity is a matter of a society’s values and corresponding principles. Objectives We aimed to develop a series of ethical principles to guide decision-making within the landscape of environmental health, and then apply these principles to a specific environmental chemical, oxybenzone. Oxybenzone is a widely used ultraviolet (UV) filter added to personal care products and other consumer goods to prevent UV damage, but potentially poses harm to humans, wildlife, and ecosystems. It provides an excellent example of a chemical that is widely used for the alleged purpose of protecting human health and product safety, but with costs to human health and the environment that are often ignored by stakeholders. Discussion We propose six ethical principles to guide environmental health decision-making: principles of sustainability, beneficence, non-maleficence, justice, community, and precautionary substitution. We apply these principles to the case of oxybenzone to demonstrate the complex but imperative decision-making required if we are to address the limits of the biosphere’s regenerative rates. We conclude that both ethical and practical considerations should be included in decisions about the commercial, pervasive application of synthetic compounds and that the current flawed practice of cost-benefit analysis be recognized for what it is: a technocratic approach to support corporate interests.

The Future Is Bright for Polyoxometalates

Polyoxometalates (POMs) are clusters of units of oxoanions of transition metals, such as Mo, W, V and Nb, that can be formed upon acidification of neutral solutions. Once formed, some POMs have shown to persist in solution, even in the neutral and basic pH range. These inorganic clusters, amenable of a variety of structures, have been studied in environmental, chemical, and industrial fields, having applications in catalysis and macromolecular crystallography, as well as applications in biomedicine, such as cancer, bacterial and viral infections, among others. Herein, we connect recent POMs environmental applications in the decomposition of emergent pollutants with POMs’ biomedical activities and effects against cancer, bacteria, and viruses. With recent insights in POMs being pure, organic/inorganic hybrid materials, POM-based ionic liquid crystals and POM-ILs, and their applications in emergent pollutants degradation, including microplastics, are referred. It is perceived that the majority of the POMs studies against cancer, bacteria, and viruses were performed in the last ten years. POMs’ biological effects include apoptosis, cell cycle arrest, interference with the ions transport system, inhibition of mRNA synthesis, cell morphology changes, formation of reaction oxygen species, inhibition of virus binding to the host cell, and interaction with virus protein cages, among others. We additionally refer to POMs’ interactions with various proteins, including P-type ATPases, aquoporins, cinases, phosphatases, among others. Finally, POMs’ stability and speciation at physiological conditions are addressed.

Ovine fetal testis stage-specific sensitivity to environmental chemical mixtures

Exposure of the fetal testis to numerous individual environmental chemicals is frequently associated with dysregulated development, leading to impaired adult reproductive competence. However, ‘real-life’ exposure involves complex mixtures of environmental chemicals (ECs). Here we test the consequences, for the male fetus, of exposing pregnant ewes to EC mixtures derived from pastures treated with biosolids fertiliser (processed human sewage). Fetal testes from continuously exposed ewes were either unaffected at Day 80 or exhibited a reduced area of testis immunostained for CYP17A1 protein at Day 140. Fetal testes from Day 140 pregnant ewes exposed transiently for 80 day periods during early (0-80 days), mid (30-110 days) or late (60-140 days) pregnancy, had fewer Sertoli cells and reduced testicular area stained for CYP17A1. Male fetuses from ewes exposed during late pregnancy also exhibited reduced fetal body, adrenal and testis mass, anogenital distance and lowered testosterone: collectively indicative of an anti-androgenic effect. Exposure limited to early gestation induced more testis transcriptome changes than observed for continuously exposed Day 140 fetuses. These data suggest that a short period of EC exposure does not allow sufficient time for the testis to adapt. Consequently, testicular transcriptomic changes induced during the first 80 days of gestation may equate with phenotypic effects observed at Day 140. In contrast, relatively fewer changes in the testis transcriptome in fetuses exposed continuously to ECs throughout gestation is associated with less severe consequences. Unless corrected by or during puberty, these differential effects would predictably have adverse outcomes for adult testicular function and fertility.

From Extrapolation to Precision Chemical Hazard Assessment: The Ecdysone Receptor Case Study

Hazard assessment strategies are often supported by extrapolation of damage probabilities, regarding chemical action and species susceptibilities. Yet, growing evidence suggests that an adequate sampling of physiological responses across a representative taxonomic scope is of paramount importance. This is particularly relevant for Nuclear Receptors (NR), a family of transcription factors, often triggered by ligands and thus, commonly exploited by environmental chemicals. Within NRs, the ligand-induced Ecdysone Receptor (EcR) provides a remarkable example. Long regarded as arthropod specific, this receptor has been extensively targeted by pesticides, seemingly innocuous to non-target organisms. Yet, current evidence clearly suggests a wider presence of EcR orthologues across metazoan lineages, with unknown physiological consequences. Here, we address the state-of-the-art regarding the phylogenetic distribution and functional characterization of metazoan EcRs and provide a critical analysis of the potential disruption of such EcRs by environmental chemical exposure. Using EcR as a case study, hazard assessment strategies are also discussed in view of the development of a novel “precision hazard assessment paradigm.

A Foliar Pigment-Based Bioassay for Interrogating Chloroplast Signalling Reveals that Chlorophyll Biosynthesis Requires Carotenoid Isomerisation.

Background: Plastid-derived metabolites can signal control over nuclear gene expression, chloroplast biogenesis, and chlorophyll biosynthesis. Norflurazon (NFZ) inhibition of carotenoid biosynthesis in seedlings can elicit a protoporphyrin retrograde signal that controls chlorophyll and chloroplast biogenesis. Recent evidence reveals that plastid development can be regulated by carotenoid cleavage products called apocarotenoids. The key steps in carotenoid biosynthesis and catabolism that generate apocarotenoid signalling metabolites in foliar tissues remains to be elucidated. Here, we established an Arabidopsis foliar pigment-based bioassay using detached rosettes to differentiate plastid signalling processes in young expanding leaves containing dividing cells with active chloroplast biogenesis, from fully expanded leaves containing mature chloroplasts. Results: We demonstrate that environmental (extended darkness and cold exposure) as well as chemical (norflurazon; NFZ) inhibition of carotenoid biosynthesis can reduce chlorophyll levels in young, but not older leaves following a 24 h of rosette treatment. Mutants that disrupted xanthophyll accumulation, phytohormone biosynthesis (abscisic acid and strigolactone), or enzymatic carotenoid cleavage, did not alter chlorophyll levels in young or old leaves. Perturbations in acyclic cis-carotene biosynthesis revealed that disruption of CAROTENOID ISOMERASE (CRTISO), but not ZETA-CAROTENE ISOMERASE (Z-ISO) activity, reduced chlorophyll levels in young but not older leaves of plants growing under a long photoperiod. NFZ-induced inhibition of PHYTOENE DESATURASE (PDS) activity triggered phytoene accumulation more so in younger relative to older leaves from both WT and the crtiso mutant, indicating a continued substrate supply from the methylerythritol 4-phosphate (MEP) pathway for carotenogenesis. NFZ treatment of WT and crtiso mutant rosettes reveal similar, additive, and opposite effects on individual pigment accumulation.Conclusion: The Arabidopsis foliar pigment-based bioassay was used to differentiate signalling events elicited by environmental, chemical, genetic, and combinations thereof, that control chlorophyll biosynthesis. Genetic perturbations that impaired xanthophyll biosynthesis and/or carotenoid catabolism did not affect chlorophyll biosynthesis. The lack of CAROTENOID ISOMERISATION generated a signal that rate-limited chlorophyll accumulation, but not phytoene biosynthesis in young Arabidopsis leaves exposed to a long photoperiod. Findings generated using this new foliar pigment bioassay implicate that carotenoid isomerisation and NFZ elicit different signalling pathways to control chlorophyll homeostasis in young emerging leaves.

High Throughput Phenotypic Screening of The Human Spermatozoon

Despite recent advances in male reproductive health research, there remain many elements of male (in)fertility where our understanding is incomplete. Consequently, diagnostic tools and treatments for men with sperm dysfunction, other than medically assisted reproduction, are limited. On the other hand, the gaps in our knowledge of the mechanisms which underpin sperm function have hampered the development of male non-hormonal contraceptives. The study of mature spermatozoa is inherently difficult. They are a unique and highly specialised cell type which does not actively transcribe or translate proteins and cannot be cultured for long periods of time or matured in vitro. One, large scale, approach to both increasing understanding of sperm function, and the discovery and development of compounds that can modulate sperm function, is to directly observe responses to compounds with phenotypic screening techniques. These target agnostic approaches can be developed into high-throughput screening platforms with the potential to drastically increase advances in the field. Here we discuss the rationale and development of high-throughput phenotypic screening platforms for mature human spermatozoa, and the multiple potential applications these present, as well as the current limitations and leaps in our understanding and capabilities needed to overcome them. Further development and use of these technologies could lead to the identification of compounds which positively or negatively affect sperm cell motility or function, or novel platforms for toxicology or environmental chemical testing among other applications. Ultimately, each of these potential applications is also likely to increase understanding within the field of sperm biology.

Microplastic Contamination in Soils: A Review from Geotechnical Engineering View

Microplastic contamination is a growing threat to marine and freshwater ecosystems, agricultural production, groundwater, plant growth and even human and animal health. Disintegration of plastic products due to mainly biochemical or physical activities leads to the formation and existence of microplastics in significant amounts, not only in marine and freshwater environments but also in soils. There are several valuable studies on microplastics in soils, which have typically focused on environmental, chemical, agricultural and health aspects. However, there is also a need for the geotechnical engineering perspective on microplastic contamination in soils. In this review paper, first, degradation, existence and persistence of microplastics in soils are assessed by considering various studies. Then, the potential role of solid waste disposal facilities as a source for microplastics is discussed by considering their geotechnical design and addressing the risk for the migration of microplastics from landfills to soils and other environments. Even though landfills are considered as one of the main geotechnical structures that contribute to the formation of considerably high amounts of microplastics and their contamination in soils, some other geotechnical engineering applications (i.e., soil improvement with tirechips, forming engineering fills with dredged sediments, soil improvement with synthetic polymer-based fibers, polystyrene based lightweight fill applications), as potential local source for microplastics, are also mentioned. Finally, the importance of geotechnical engineering as a mitigation tool for microplastics is emphasized and several important research topics involving geotechnical engineering are suggested.

An integrated host-microbiome response to atrazine exposure mediates toxicity in Drosophila

The gut microbiome produces vitamins, nutrients, and neurotransmitters, and helps to modulate the host immune system—and also plays a major role in the metabolism of many exogenous compounds, including drugs and chemical toxicants. However, the extent to which specific microbial species or communities modulate hazard upon exposure to chemicals remains largely opaque. Focusing on the effects of collateral dietary exposure to the widely used herbicide atrazine, we applied integrated omics and phenotypic screening to assess the role of the gut microbiome in modulating host resilience in Drosophila melanogaster. Transcriptional and metabolic responses to these compounds are sex-specific and depend strongly on the presence of the commensal microbiome. Sequencing the genomes of all abundant microbes in the fly gut revealed an enzymatic pathway responsible for atrazine detoxification unique to Acetobacter tropicalis. We find that Acetobacter tropicalis alone, in gnotobiotic animals, is sufficient to rescue increased atrazine toxicity to wild-type, conventionally reared levels. This work points toward the derivation of biotic strategies to improve host resilience to environmental chemical exposures, and illustrates the power of integrative omics to identify pathways responsible for adverse health outcomes.

Role of epidemiology in risk assessment: a case study of five ortho-phthalates

Background The association between environmental chemical exposures and chronic diseases is of increasing concern. Chemical risk assessment relies heavily on pre-market toxicity testing to identify safe levels of exposure, often known as reference doses (RfD), expected to be protective of human health. Although some RfDs have been reassessed in light of new hazard information, it is not a common practice. Continuous surveillance of animal and human data, both in terms of exposures and associated health outcomes, could provide valuable information to risk assessors and regulators. Using ortho-phthalates as case study, we asked whether RfDs deduced from male reproductive toxicity studies and set by traditional regulatory toxicology approaches sufficiently protect the population for other health outcomes. Methods We searched for epidemiological studies on benzyl butyl phthalate (BBP), diisobutyl phthalate (DIBP), dibutyl phthalate (DBP), dicyclohexyl phthalate (DCHP), and bis(2-ethylhexyl) phthalate (DEHP). Data were extracted from studies where any of the five chemicals or their metabolites were measured and showed a statistically significant association with a health outcome; 38 studies met the criteria. We estimated intake for each phthalate from urinary metabolite concentration and compared estimated intake ranges associated with health endpoints to each phthalate’s RfD. Result For DBP, DIBP, and BBP, the estimated intake ranges significantly associated with health endpoints were all below their individual RfDs. For DEHP, the intake range included associations at levels both below and above its RfD. For DCHP, no relevant studies could be identified. The significantly affected endpoints revealed by our analysis include metabolic, neurodevelopmental and behavioral disorders, obesity, and changes in hormone levels. Most of these conditions are not routinely evaluated in animal testing employed in regulatory toxicology. Conclusion We conclude that for DBP, DIBP, BBP, and DEHP current RfDs estimated based on male reproductive toxicity may not be sufficiently protective of other health effects. Thus, a new approach is needed where post-market exposures, epidemiological and clinical data are systematically reviewed to ensure adequate health protection.