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.

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.

Evaluating adverse effects of environmental agents in food: a brief critique of the US FDA's criteria.

Background: In the US, the Food and Drug Administration (US FDA) is charged with protecting the safety of food from both pathogens and chemicals used in food production and food packaging. To protect the public in a transparent manner, the FDA needs to have an operational definition of what it considers to be an "adverse effect" so that it can take action against harmful agents. The FDA has recently published two statements where, for the first time, it defines the characteristics of an adverse effect that it uses to interpret toxicity studies.

Fluoride exposure and hypothyroidism in a Canadian pregnancy cohort.

Background: While fluoride can have thyroid-disrupting effects, associations between low-level fluoride exposure and thyroid conditions remain unclear, especially during pregnancy when insufficient thyroid hormones can adversely impact offspring development.

Objectives: We evaluated associations between fluoride exposure and hypothyroidism in a Canadian pregnancy cohort.

Methods: We measured fluoride concentrations in drinking water and three dilution-corrected urine samples and estimated fluoride intake based on self-reported beverage consumption.

Gestational thyroid hormone concentrations and risk of attention-deficit hyperactivity disorder in the Norwegian Mother, Father and Child Cohort Study.

Background: Maternal thyroid function plays an important role in foetal brain development; however, little consensus exists regarding the relationship between normal variability in thyroid hormones and common neurodevelopmental disorders, such as attention-deficit hyperactivity disorder (ADHD).

Objective: We sought to examine the association between mid-pregnancy maternal thyroid function and risk of clinically diagnosed ADHD in offspring.

Methods: We conducted a nested case-control study in the Norwegian Mother, Father and Child Cohort Study.

Accuracy of Predicting One-Repetition Maximum from Submaximal Velocity in The Barbell Back Squat and Bench Press.

This study examined the accuracy of predicting a free-weight back squat and a bench press one-repetition maximum (1RM) using both 2- and 4-point submaximal average concentric velocity (ACV) methods. Seventeen resistance trained men performed a warm-up and a 1RM test on the squat and bench press with ACV assessed on all repetitions. The ACVs during the warm-up closest to 1.

Endothelial Cell Protein Targeting by Myeloperoxidase-Derived 2-Chlorofatty Aldehyde.

Neutrophils are important cellular mediators of injury and repair in diseases including ischemic heart disease, atherosclerosis, and sepsis. Myeloperoxidase-derived (MPO)-oxidants released from neutrophils are potential mediators of endothelial injury in disease. MPO-derived HOCl attacks plasmalogen phospholipid to liberate 2-chlorofatty aldehyde (2-ClFALD).

Endocrine disrupting chemicals and thyroid hormone action.

Thyroid hormones (predominantly thyroxine, T4, and triiodothyronine, T3) are essential for normal development and for adult physiology. There are several challenges, however, that make identifying chemicals that produce adverse effects by interfering with the thyroid system difficult. First, individual variability in serum concentrations of thyroid hormones represent only about 10% of the population reference range that is considered to be "normal.

Thresholds and Endocrine Disruptors: An Endocrine Society Policy Perspective.

The concept of a threshold of adversity in toxicology is neither provable nor disprovable. As such, it is not a scientific question but a theoretical one. Yet, the belief in thresholds has led to traditional ways of interpreting data derived from regulatory guideline studies of the toxicity of chemicals.

Urinary Phthalate Biomarkers and Bone Mineral Density in Postmenopausal Women.

Context: Phthalates are endocrine-disrupting chemicals that could disrupt normal physiologic function, triggering detrimental impacts on bone.

Objective: We evaluated associations between urinary phthalate biomarkers and BMD in postmenopausal women participating in the prospective Women's Health Initiative (WHI).

Methods: We included WHI participants enrolled in the BMD substudy and selected for a nested case-control study of phthalates and breast cancer (N = 1255).

Distinct Functions of Acyl/Alkyl Dihydroxyacetonephosphate Reductase in Peroxisomes and Endoplasmic Reticulum.

Plasmalogens are a subclass of ether glycerophospholipids characterized by a vinyl-ether bond at the -1 position of the glycerol backbone. Plasmalogen biosynthesis is initiated in peroxisomes. At the third step of plasmalogen synthesis, alkyl-dihydroxyacetonephosphate (DHAP) is enzymatically reduced to 1-alkyl--glycero-3-phospate by acyl/alkyl DHAP reductase (ADHAPR), whose activity is found in both peroxisomes and microsomes.

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.

The gene encodes plasmanylethanolamine desaturase which introduces the characteristic vinyl ether double bond into plasmalogens.

A significant fraction of the glycerophospholipids in the human body is composed of plasmalogens, particularly in the brain, cardiac, and immune cell membranes. A decline in these lipids has been observed in such diseases as Alzheimer's and chronic obstructive pulmonary disease. Plasmalogens contain a characteristic 1--alk-1'-enyl ether (vinyl ether) double bond that confers special biophysical, biochemical, and chemical properties to these lipids.

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.

Maternal, cord, and three-year-old child serum thyroid hormone concentrations in the Health Outcomes and Measures of the Environment study.

Purpose: Maternal thyroid function during pregnancy may influence offspring thyroid function, though relations between maternal and child thyroid function are incompletely understood. We sought to characterize relations between maternal, cord and child thyroid hormone concentrations in a population of mother-child pairs with largely normal thyroid function.

Methods: In a prospective birth cohort, we measured thyroid hormone concentrations in 203 mothers at 16 gestational weeks, 273 newborns and 159 children at 3 years among participants in the Health Outcomes and Measures of the Environment (HOME) Study.

Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification.

Endocrine-disrupting chemicals (EDCs) are exogenous chemicals that interfere with hormone action, thereby increasing the risk of adverse health outcomes, including cancer, reproductive impairment, cognitive deficits and obesity. A complex literature of mechanistic studies provides evidence on the hazards of EDC exposure, yet there is no widely accepted systematic method to integrate these data to help identify EDC hazards. Inspired by work to improve hazard identification of carcinogens using key characteristics (KCs), we have developed ten KCs of EDCs based on our knowledge of hormone actions and EDC effects.

The Use and Misuse of Historical Controls in Regulatory Toxicology: Lessons from the CLARITY-BPA Study.

For many endocrine-disrupting chemicals (EDCs) including Bisphenol A (BPA), animal studies show that environmentally relevant exposures cause harm; human studies are consistent with these findings. Yet, regulatory agencies charged with protecting public health continue to conclude that human exposures to these EDCs pose no risk. One reason for the disconnect between the scientific consensus on EDCs in the endocrinology community and the failure to act in the regulatory community is the dependence of the latter on so-called "guideline studies" to evaluate hazards, and the inability to incorporate independent scientific studies in risk assessment.

CLARITY-BPA: Bisphenol A or Propylthiouracil on Thyroid Function and Effects in the Developing Male and Female Rat Brain.

The CLARITY-BPA experiment, a large collaboration between the National Institute of Environmental Health Sciences, the National Toxicology Program, and the US Food and Drug Administration, is designed to test the effects of bisphenol A (BPA) on a variety of endocrine systems and end points. The specific aim of this subproject was to test the effect of BPA exposure on thyroid functions and thyroid hormone action in the developing brain. Timed-pregnant National Center for Toxicological Research Sprague-Dawley rats (strain code 23) were dosed by gavage with vehicle control (0.

Thyroid hormones and neurobehavioral functions among adolescents chronically exposed to groundwater with geogenic arsenic in Bangladesh.

Groundwater, the major source of drinking water in Bengal Delta Plain, is contaminated with geogenic arsenic (As) enrichment affecting millions of people. Children exposed to tubewell water containing As may be associated with thyroid dysfunction, which in turn may impact neurodevelopmental outcomes. However, data to support such relationship is sparse.