Consensus on the key characteristics of metabolism disruptors.

Metabolism-disrupting agents (MDAs) are chemical, infectious or physical agents that increase the risk of metabolic disorders. Examples include pharmaceuticals, such as antidepressants, and environmental agents, such as bisphenol A. Various types of studies can provide evidence to identify MDAs, yet a systematic method is needed to integrate these data to help to identify such hazards.

A toxic relationship: ultra-processed foods & plastics.

Background: Among the crises engulfing the world is the symbiotic rise of ultra-processed foods (UPFs) and plastics. Together, this co-dependent duo generates substantial profits for agri-food and petrochemical industries at high costs for people and planet. Cheap, lightweight and highly functional, plastics have ideal properties that enable business models to create demand for low-cost, mass-produced and hyper-palatable UPFs among populations worldwide, hungry, or not.

The Conflict between Regulatory Agencies over the 20,000-Fold Lowering of the Tolerable Daily Intake (TDI) for Bisphenol A (BPA) by the European Food Safety Authority (EFSA).

Background: The European Food Safety Authority (EFSA) recommended lowering their estimated tolerable daily intake (TDI) for bisphenol A (BPA) 20,000-fold to . BPA is an extensively studied high production volume endocrine disrupting chemical (EDC) associated with a vast array of diseases. Prior risk assessments of BPA by EFSA as well as the US Food and Drug Administration (FDA) have relied on industry-funded studies conducted under good laboratory practice protocols (GLP) requiring guideline end points and detailed record keeping, while also claiming to examine (but rejecting) thousands of published findings by academic scientists.

Obesogens: a unifying theory for the global rise in obesity.

Despite varied treatment, mitigation, and prevention efforts, the global prevalence and severity of obesity continue to worsen. Here we propose a combined model of obesity, a unifying paradigm that links four general models: the energy balance model (EBM), based on calories as the driver of weight gain; the carbohydrate-insulin model (CIM), based on insulin as a driver of energy storage; the oxidation-reduction model (REDOX), based on reactive oxygen species (ROS) as a driver of altered metabolic signaling; and the obesogens model (OBS), which proposes that environmental chemicals interfere with hormonal signaling leading to adiposity. We propose a combined OBS/REDOX model in which environmental chemicals (in air, food, food packaging, and household products) generate false autocrine and endocrine metabolic signals, including ROS, that subvert standard regulatory energy mechanisms, increase basal and stimulated insulin secretion, disrupt energy efficiency, and influence appetite and energy expenditure leading to weight gain.

European Medicines Agency Conflicts With the European Food Safety Authority (EFSA) on Bisphenol A Regulation.

The European Food Safety Authority (EFSA) has revised their estimate of the toxicity of bisphenol A (BPA) and, as a result, have recommended reducing the tolerable daily intake (TDI) by 20 000-fold. This would essentially ban the use of BPA in food packaging such as can liners, plastic food containers, and in consumer products. To come to this conclusion, EFSA used a systematic approach according to a pre-established protocol and included all guideline and nonguideline studies in their analysis.

Obesogens and Obesity: State-of-the-Science and Future Directions Summary from a Healthy Environment and Endocrine Disruptors Strategies Workshop.

On September 7 and 8, 2022, Healthy Environment and Endocrine Disruptors Strategies, an Environmental Health Sciences program, convened a scientific workshop of relevant stakeholders involved in obesity, toxicology, or obesogen research to review the state of the science regarding the role of obesogenic chemicals that might be contributing to the obesity pandemic. The workshop's objectives were to examine the evidence supporting the hypothesis that obesogens contribute to the etiology of human obesity; to discuss opportunities for improved understanding, acceptance, and dissemination of obesogens as contributors to the obesity pandemic; and to consider the need for future research and potential mitigation strategies. This report details the discussions, key areas of agreement, and future opportunities to prevent obesity.

Obesity II: Establishing causal links between chemical exposures and obesity.

Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens.

Obesity III: Obesogen assays: Limitations, strengths, and new directions.

There is increasing evidence of a role for environmental contaminants in disrupting metabolic health in both humans and animals. Despite a growing need for well-understood models for evaluating adipogenic and potential obesogenic contaminants, there has been a reliance on decades-old in vitro models that have not been appropriately managed by cell line providers. There has been a quick rise in available in vitro models in the last ten years, including commercial availability of human mesenchymal stem cell and preadipocyte models; these models require more comprehensive validation but demonstrate real promise in improved translation to human metabolic health.

Data integration, analysis, and interpretation of eight academic CLARITY-BPA studies.

"Consortium Linking Academic and Regulatory Insights on BPA Toxicity" (CLARITY-BPA) was a comprehensive "industry-standard" Good Laboratory Practice (GLP)-compliant 2-year chronic exposure study of bisphenol A (BPA) toxicity that was supplemented by hypothesis-driven independent investigator-initiated studies. The investigator-initiated studies were focused on integrating disease-associated, molecular, and physiological endpoints previously found by academic scientists into an industry standard guideline-compliant toxicity study. Thus, the goal of this collaboration was to provide a more comprehensive dataset upon which to base safety standards and to determine whether industry-standard tests are as sensitive and predictive as molecular and disease-associated endpoints.

Impacts of food contact chemicals on human health: a consensus statement.

Food packaging is of high societal value because it conserves and protects food, makes food transportable and conveys information to consumers. It is also relevant for marketing, which is of economic significance. Other types of food contact articles, such as storage containers, processing equipment and filling lines, are also important for food production and food supply.

Interventions to Address Environmental Metabolism-Disrupting Chemicals: Changing the Narrative to Empower Action to Restore Metabolic Health.

Metabolic disease rates have increased dramatically over the last four decades. Classic understanding of metabolic physiology has attributed these global trends to decreased physical activity and caloric excess; however, these traditional risk factors insufficiently explain the magnitude and rapidity of metabolic health deterioration. Recently, the novel contribution of environmental metabolism-disrupting chemicals (MDCs) to various metabolic diseases (including obesity, diabetes, and non-alcoholic fatty liver disease) is becoming recognized.

History of the Obesogen Field: Looking Back to Look Forward.

The Obesogen field developed from two separate scientific research areas, endocrine disruptors and the Developmental Origins of Health and Disease (DOHaD). Endocrine Disrupting Chemicals (EDCs) are exogenous chemicals or mixtures of chemicals that interfere with the action of hormones. Exposure to EDCs during early development (DOHaD) has been shown to increase susceptibility to a variety of diseases including infertility, asthma, breast and prostate cancer, early puberty, susceptibility to infections, heart disease, autoimmune disease, and attention deficit hyperactivity disorder/learning disability.

Timescales of developmental toxicity impacting on research and needs for intervention.

Much progress has happened in understanding developmental vulnerability to preventable environmental hazards. Along with the improved insight, the perspective has widened, and developmental toxicity now involves latent effects that can result in delayed adverse effects in adults or at old age and additional effects that can be transgenerationally transferred to future generations. Although epidemiology and toxicology to an increasing degree are exploring the adverse effects from developmental exposures in human beings, the improved documentation has resulted in little progress in protection, and few environmental chemicals are currently regulated to protect against developmental toxicity, whether it be neurotoxicity, endocrine disruption or other adverse outcome.

The developmental basis of disease: Update on environmental exposures and animal models.

At the Prenatal Programming and Toxicity (PPTox) Conference I in 2008, I presented an overview of the developmental origins of health and disease field focusing on environmental chemical exposures and disease outcomes. At that time, I noted that the field was getting off the ground with a focus on developmental exposure to a small number of endocrine disrupting chemicals (EDCs) and disease outcomes across the lifespan in animal models. In this update, I note that the DOHaD field has changed significantly over the last decade.

Environmental Obesogens: Mechanisms and Controversies.

Obesity is a worldwide pandemic in adults as well as children and adds greatly to health care costs through its association with type 2 diabetes, metabolic syndrome, cardiovascular disease, and cancers. The prevailing medical view of obesity is that it results from a simple imbalance between caloric intake and energy expenditure. However, numerous other factors are important in the etiology of obesity.

Meeting summary: the inaugural meeting of the US DOHaD society.

The US chapter of the International Developmental Origins of Health and Disease (DOHaD) Society recently held its inaugural meeting in Detroit, MI. US-based DOHaD researchers gathered both to create this new society chapter and share their latest research. The US DOHaD Society will provide a much-needed domestic forum for a broad range of DOHaD topics including nutrition, toxicology, stress, epidemiology, epigenetics, and more.

Correction to: Parma consensus statement on metabolic disruptors.

After publication of the article [1], it has been brought to our attention that the thirteenth author of this article has had their name spelt incorrectly. In the original article the spelling "Laura Rizzir" was used. In fact the correct spelling should be "Laura Rizzi".

Endocrine Disruptors and Health Effects in Africa: A Call for Action.

Background: Africa faces a number of unique environmental challenges. Unfortunately, it lacks the infrastructure needed to support the comprehensive environmental studies that could provide the scientific basis to inform environmental policies. There are a number of known sources of endocrine-disrupting chemicals (EDCs) and other hazardous chemicals in Africa.

Review of developmental origins of health and disease publications in environmental epidemiology.

The Developmental Origins of Health and Disease (DOHaD) scientific field investigates the influence of early life environmental stressors on later life health outcomes. Environmental chemical exposures are a particular focus area within this field. Although the DOHaD hypothesis originated in the 1990s, the data evaluating this hypothesis in environmental epidemiology has not been comprehensively summarized.