Dietary Exposure to United States Food and Drug Administration-Approved Synthetic Food Colors in Children, Pregnant Women, and Women of Childbearing Age Living in the United States.

The Food and Drug Administration (FDA) regulates artificial food colors (AFCs) in the United States. Exposure to AFCs has raised concerns about adverse behavioral effects in children. We quantified AFC exposure in women of childbearing age, pregnant women, and children and compared them to FDA and World Health Organization acceptable daily intakes (ADIs).

Ethylmalonic encephalopathy masquerading as meningococcemia.

Ethylmalonic encephalopathy (MIM #602473) is a rare autosomal recessive metabolic condition caused by biallelic variants in (MIM #608451), characterized by global developmental delay, infantile hypotonia, seizures, and microvascular damage. The microvascular changes result in a pattern of relapsing spontaneous diffuse petechiae and purpura, positional acrocyanosis, and pedal edema, hemorrhagic suffusions of mucous membranes, and chronic diarrhea. Here, we describe an instructive case in which ethylmalonic encephalopathy masqueraded as meningococcal septicemia and shock.

Standardized practices for RNA diagnostics using clinically accessible specimens reclassifies 75% of putative splicing variants.

Purpose: Genetic variants causing aberrant premessenger RNA splicing are increasingly being recognized as causal variants in genetic disorders. In this study, we devise standardized practices for polymerase chain reaction (PCR)-based RNA diagnostics using clinically accessible specimens (blood, fibroblasts, urothelia, biopsy).

Methods: A total of 74 families with diverse monogenic conditions (31% prenatal-congenital onset, 47% early childhood, and 22% teenage-adult onset) were triaged into PCR-based RNA testing, with comparative RNA sequencing for 19 cases.

Using High-Throughput Screening to Evaluate Perturbations Potentially Linked to Neurobehavioral Outcomes: A Case Study Using Publicly Available Tools on FDA Batch-Certified Synthetic Food Dyes.

There is growing evidence from human and animal studies indicating an association between exposure to synthetic food dyes and adverse neurobehavioral outcomes in children. However, data gaps persist for potential mechanisms by which the synthetic food dyes could elicit neurobehavioral impacts. We developed an approach to evaluate seven US FDA-batch-certified food dyes using publicly available high-throughput screening (HTS) data from the US EPA's Toxicity Forecaster to assess potential underlying molecular mechanisms that may be linked to neurological pathway perturbations.

Dig deeper when it does not make sense: Juvenile xanthomas due to sitosterolemia.

Sitosterolemia is an extremely rare autosomal recessive disease caused by mutations in either or , which encode for a sterol efflux transporter (sterolin) that pumps sterols out into the intestinal lumen or into bile. This leads to progressive accumulation of plant sterols in blood and tissues. Clinical presentation is variable and may include xanthoma, arthritis, thyroid dysfunction, premature atherosclerotic disease, splenomegaly, and hematologic manifestations.

Healthy Air, Healthy Brains: Advancing Air Pollution Policy to Protect Children's Health.

Evidence is growing on the adverse neurodevelopmental effects of exposure to combustion-related air pollution. Project TENDR (Targeting Environmental Neurodevelopmental Risks), a unique collaboration of leading scientists, health professionals, and children's and environmental health advocates, has identified combustion-related air pollutants as critical targets for action to protect healthy brain development. We present policy recommendations for maintaining and strengthening federal environmental health protections, advancing state and local actions, and supporting scientific research to inform effective strategies for reducing children's exposures to combustion-related air pollution.

An Integrated Approach Using Publicly Available Resources for Identifying and Characterizing Chemicals of Potential Toxicity Concern: Proof-of-Concept With Chemicals That Affect Cancer Pathways.

We developed an integrated, modular approach to predicting chemical toxicity relying on in vitro assay data, linkage of molecular targets to disease categories, and software for ranking chemical activity and examining structural features (chemotypes). We evaluate our approach in a proof-of-concept exercise to identify and prioritize chemicals of potential carcinogenicity concern. We identified 137 cancer pathway-related assays from a subset of U.

Project TENDR: Targeting Environmental Neuro-Developmental Risks The TENDR Consensus Statement.

Children in America today are at an unacceptably high risk of developing neurodevelopmental disorders that affect the brain and nervous system including autism, attention deficit hyperactivity disorder, intellectual disabilities, and other learning and behavioral disabilities. These are complex disorders with multiple causes—genetic, social, and environmental. The contribution of toxic chemicals to these disorders can be prevented.

Using ToxCast to Explore Chemical Activities and Hazard Traits: A Case Study With Ortho-Phthalates.

US EPA's Toxicity Forecaster (ToxCastTM) is a tool with potential use in evaluating safer consumer products, conducting chemical alternatives analyses, prioritizing chemicals for exposure monitoring, and ultimately performing screening-level risk assessments. As a case study exploring a potential use of ToxCast, we evaluated ToxCast results for ortho-phthalates focused on the well-established toxicological endpoints of some members of this class. We compared molecular perturbations measured in ToxCast assays with the known apical toxicity endpoints of o-phthalates reported in the open literature to broadly reflect on the predictive capability of the high-throughput screening (HTS) assays.

Children's Environmental Health: Beyond National Boundaries.

Children are especially vulnerable to environmental pollution, a major cause of disease, death, and disability in countries at every level of development. This article reviews threats to children, including air and water pollution, toxic industrial chemicals, pesticides, heavy metals, and hazardous wastes. Global climate change is expected to exacerbate many of these issues.

Impact of environmental chemicals on lung development.

Background: Disruption of fundamental biologic processes and associated signaling events may result in clinically significant alterations in lung development.

Objectives: We reviewed evidence on the impact of environmental chemicals on lung development and key signaling events in lung morphogenesis, and the relevance of potential outcomes to public health and regulatory science .

Data Sources: We evaluated the peer-reviewed literature on developmental lung biology and toxicology, mechanistic studies, and supporting epidemiology.

Inhalation of an essential metal: development of reference exposure levels for manganese.

Exposures to high levels of manganese by ingestion or inhalation can damage the central nervous system. However, the capacity of environmental manganese to cause neurotoxicity is of most concern following inhalation exposure. Reference exposure levels (RELs) are values developed by California EPA's Office of Environmental Health Hazard Assessment (OEHHA) to protect the general public from periodic and continual exposures to airborne toxicants.

Development of TEFs for PCB congeners by using an alternative biomarker--thyroid hormone levels.

Polychlorinated biphenyls (PCBs) are ubiquitous toxic contaminants. Health risk assessment for this class of chemicals is complex: the current toxic equivalency factor (TEF) method covers dioxin-like (DL-) PCBs, dibenzofurans, and dioxins, but excludes non-DL-PCBs. To address this deficiency, we evaluated published data for several PCB congeners to determine common biomarkers of effect.

The effects of fine particle components on respiratory hospital admissions in children.

Background: Epidemiologic studies have demonstrated an association between acute exposure to ambient fine particles and both mortality and morbidity. Less is known about the relative impacts of the specific chemical constituents of particulate matter<2.5 microm in aerodynamic diameter (PM2.

Focusing on children's inhalation dosimetry and health effects for risk assessment: an introduction.

Substantial effort has been invested in improving children's health risk assessment in recent years. However, the body of scientific evidence in support of children's health assessment is constantly advancing, indicating the need for continual updating of risk assessment methods. Children's inhalation dosimetry and child-specific adverse health effects are of particular concern for risk assessment.

The association between exposure to environmental tobacco smoke and breast cancer: a review by the California Environmental Protection Agency.

Background: The California Environmental Protection Agency (Cal/EPA) recently completed a health effects assessment of exposure to environmental tobacco smoke (ETS) which resulted in California listing ETS as a Toxic Air Contaminant in January 2006. As part of the assessment, studies on the association between exposure to ETS and breast cancer were reviewed.

Methods: Twenty-six published reports (including 3 meta-analyses) evaluating the association between ETS exposure and breast cancer were reviewed.

Development of a chronic inhalation reference level for respirable crystalline silica.

Chronic inhalation exposure of workers to crystalline silica can result in silicosis. The general public can also be exposed to lower levels of crystalline silica from quarries, sand blasting, and entrained fines particles from surface soil. We have derived an inhalation chronic reference exposure level for silica, a level below which no adverse effects due to prolonged exposure would be expected in the general public.

Acute toxicity and cancer risk assessment values for tert-butyl acetate.

tert-Butyl acetate (TBAc) is an industrial chemical with potential uses as a degreaser and in architectural coatings. Limited chronic toxicity data exist for TBAc. However, acute inhalation exposure data are available for TBAc.

Development of acute inhalation reference exposure levels (RELs) to protect the public from predictable excursions of airborne toxicants.

Uniform guidelines have been developed for the derivation of 1-h acute inhalation reference exposure levels (RELs) applicable to the general public exposed routinely to hazardous substances released into the environment. Existing acute exposure guidance values developed by other organizations have been examined, and strengths and weaknesses in these existing guidelines have been identified. The results of that examination have led to the development of a reproducible and resource-intensive methodology to calculate acute inhalation RELs for 41 prioritized chemicals.

Differences between children and adults: implications for risk assessment at California EPA.

The California legislature enacted a law requiring the California Environmental Protection Agency (Cal/EPA) Office of Environmental Health Hazard Assessment (OEHHA) to evaluate whether our risk assessment methodologies are adequately protective of infants and children. In addition both OEHHA and the California Air Resources Board must examine whether the Ambient Air Quality Standards set for criteria air pollutants and the health values developed for air toxics are adequately protective of infants and children. We have initiated a program to look at potential differences in response to toxicants between children and adults.