Toxicological Sciences

https://academic.oup.com/toxsci

List of Papers (Total 3,878)

Dose Effects of Ammonium Perfluorooctanoate on Lipoprotein Metabolism in APOE*3-Leiden.CETP Mice

Epidemiological studies have reported positive associations between serum perfluorooctanoic acid (PFOA) and total and non-high-density lipoprotein cholesterol (non-HDL-C) although the magnitude of effect of PFOA on cholesterol lacks consistency. The objectives of this study were to evaluate the effect of PFOA on plasma cholesterol and triglyceride metabolism at various plasma...

Role of Macrophages in Acute Lung Injury and Chronic Fibrosis Induced by Pulmonary Toxicants

A diverse group of toxicants has been identified that cause injury to the lung including gases (eg, ozone, chlorine), particulates/aerosols (eg, diesel exhaust, fly ash, other combustion products, mustards, nanomaterials, silica, asbestos), chemotherapeutics (eg, bleomycin), and radiation. The pathologic response to these toxicants depends on the dose and duration of exposure and...

The GMO90+ Project: Absence of Evidence for Biologically Meaningful Effects of Genetically Modified Maize-based Diets on Wistar Rats After 6-Months Feeding Comparative Trial

The GMO90+ project was designed to identify biomarkers of exposure or health effects in Wistar Han RCC rats exposed in their diet to 2 genetically modified plants (GMP) and assess additional information with the use of metabolomic and transcriptomic techniques. Rats were fed for 6-months with 8 maize-based diets at 33% that comprised either MON810 (11% and 33%) or NK603 grains...

Human 3D Gastrointestinal Microtissue Barrier Function As a Predictor of Drug-Induced Diarrhea

Drug-induced gastrointestinal toxicities (GITs) rank among the most common clinical side effects. Preclinical efforts to reduce incidence are limited by inadequate predictivity of in vitro assays. Recent breakthroughs in in vitro culture methods support intestinal stem cell maintenance and continual differentiation into the epithelial cell types resident in the intestine. These...

Rationalizing Secondary Pharmacology Screening Using Human Genetic and Pharmacological Evidence

Safety-related drug failures remain a major challenge for the pharmaceutical industry. One approach to ensuring drug safety involves assessing small molecule drug specificity by examining the ability of a drug candidate to interact with a panel of “off-target” proteins, referred to as secondary pharmacology screening. Information from human genetics and pharmacology can be used...

Automated Morphological Feature Assessment for Zebrafish Embryo Developmental Toxicity Screens

Detection of developmental phenotypes in zebrafish embryos typically involves a visual assessment and scoring of morphological features by an individual researcher. Subjective scoring could impact results and be of particular concern when phenotypic effect patterns are also used as a diagnostic tool to classify compounds. Here we introduce a quantitative morphometric approach...

Employing Dietary Comparators to Perform Risk Assessments for Anti-Androgens Without Using Animal Data

This study investigated the use of androgen receptor (AR) reporter gene assay data in a non-animal exposure-led risk assessment in which in vitro anti-androgenic activity and exposure data were put into context using a naturally occurring comparator substance with a history of dietary consumption. First, several dietary components were screened to identify which selectively...

Today’s Challenges to De-Risk and Predict Drug Safety in Human “Mind-the-Gap”

Current gaps in drug safety sciences can result from the inability (1) to identify hazard across multiple target organs, (2) to predict and risk assess with certainty against drug safety liabilities for the major target organs, (3) to optimally manage and mitigate against drug safety liabilities, and (4) to apply principles of governance on the generation, integration, and use of...

Using Experimental Models to Assess Effects of Bisphenol A (BPA) and Phthalates on the Placenta: Challenges and Perspectives

The placenta is critical for all aspects of fetal development. Bisphenol A (BPA) and phthalates are endocrine disruptors with ubiquitous exposure in pregnant women—their effects on the placenta is an area of growing research interest. Therefore, our objectives were to (1) summarize research related to the effects BPA or phthalates on placental outcomes in animal and cell models...

Machine Learning of Toxicological Big Data Enables Read-Across Structure Activity Relationships (RASAR) Outperforming Animal Test Reproducibility

Earlier we created a chemical hazard database via natural language processing of dossiers submitted to the European Chemical Agency with approximately 10 000 chemicals. We identified repeat OECD guideline tests to establish reproducibility of acute oral and dermal toxicity, eye and skin irritation, mutagenicity and skin sensitization. Based on 350–700+ chemicals each, the...

A Ternary Mixture of Common Chemicals Perturbs Benign Human Breast Epithelial Cells More Than the Same Chemicals Do Individually

As a continuous source of hormonal stimulation, environmentally ubiquitous estrogenic chemicals, ie, xenoestrogens (XEs), are a potential risk factor for breast carcinogenesis. Given their wide distribution in the environment and the fact that bisphenol-A (BPA), methylparaben (MP), and perfluorooctanoic acid (PFOA) are uniformly detected in unselected body fluid samples, it must...

Development of the Concept for Stem Cell-Based Developmental Neurotoxicity Evaluation

Human brain development consists of a series of complex spatiotemporal processes that if disturbed by chemical exposure causes irreversible impairments of the nervous system. To evaluate a chemical disturbance in an alternative assay, the concept evolved that the complex procedure of brain development can be disassembled into several neurodevelopmental endpoints which can be...

The Role of Endocrine and Dioxin-Like Activity of Extracts of Petroleum Substances in Developmental Toxicity as Detected in a Panel of CALUX Reporter Gene Assays

Recent evidence suggests that the interaction of polycyclic aromatic hydrocarbons (PAHs), present in some petroleum substances (PS), with particular nuclear-hormone-receptors and/or the dioxin (aryl hydrocarbon receptor [AhR]) receptor, may play a role in the prenatal developmental toxicity (PDT) induced by these substances. To address this hypothesis, we evaluated the possible...

Developmental Exposure to Aluminum Chloride Irreversibly Affects Postnatal Hippocampal Neurogenesis Involving Multiple Functions in Mice

Aluminum (Al) is neurotoxic to adults and also to infants. In this study, we investigated the developmental exposure effect of AlCl3 on postnatal hippocampal neurogenesis. Pregnant mice were administered 0-, 900-, or 1800-ppm AlCl3 via drinking water from gestational day 6 to postnatal day (PND) 21, with their offspring examined on PND 21 and PND 77. On PND 21, GFAP...

Neuroendocrine Regulation of Air Pollution Health Effects: Emerging Insights

Air pollutant exposures are linked to cardiopulmonary diseases, diabetes, metabolic syndrome, neurobehavioral conditions, and reproductive abnormalities. Significant effort is invested in understanding how pollutants encountered by the lung might induce effects in distant organs. The role of circulating mediators has been predicted; however, their origin and identity have not...

Historical Highlights of Air Pollution Toxicology

Air pollution has a compelling history in the development of human cultures. Fossil fuels opened a new human cultural chapter of extraordinary technical and economic growth while bringing about noxious and unhealthful combustion byproducts to breathe. Toxicology saw its birth in the modern world with demonstrating the potential harmful effects of breathing smoke in its various...