Research Publications (Food Safety)

There has been limited toxicity testing of cigarillos, including comparison to cigarettes. This study compared the smoke chemistry and the cytotoxic and genotoxic potential of 10 conventional cigarettes and 10 cigarillos based on the greatest market share. Whole smoke and total particulate matter (TPM) were generated using the Canadian Intense and International Organization for Standardization puffing protocols.

The biological half-life (t1/2) of methylmercury (MeHg) shows considerable individual variability (t1/2 < 30 to > 120 days), highlighting the importance of mechanisms controlling MeHg metabolism and elimination. Building on a prior physiologically based pharmacokinetic (PBPK) model, we elucidate parameters that have the greatest influence on variability of MeHg t1/2 in the human body.

Regulatory agencies have derived noncancer toxicity values for 2,3,7,8-tetrachlorodibenzo-p-dioxin based on reduced sperm counts relying on single studies from a large body of evidence. Techniques such as meta-regression allow for greater use of the available data while simultaneously providing important information regarding the uncertainty associated with the underlying evidence base when conducting risk assessments.

Chemical modifications of proteins, DNA, and RNA moieties play critical roles in regulating gene expression. Emerging evidence suggests the RNA modifications (epitranscriptomics) have substantive roles in basic biological processes. One of the most common modifications in mRNA and noncoding RNAs is N6-methyladenosine (m6A).

Methods to assess environmental exposure to hazardous chemicals have primarily focused on quantification of individual chemicals, although chemicals often occur in mixtures, presenting challenges to the traditional risk characterization framework. Sampling sites in a defined geographic region provide an opportunity to characterize chemical contaminants, with spatial interpolation as a tool to provide estimates for non-sampled sites.

Over the last 2 decades, the zebrafish (Danio rerio) has emerged as a stellar model for unraveling molecular signaling events mediated by the aryl hydrocarbon receptor (AHR), an important ligand-activated receptor found in all eumetazoan animals. Zebrafish have 3 AHRs—AHR1a, AHR1b, and AHR2, and studies have demonstrated the diversity of both the endogenous and toxicological functions of the zebrafish AHRs.

Congenital heart disease (CHD), the leading birth defect worldwide, has a largely unknown etiology, likely to result from complex interactions between genetic and environmental factors during heart development, at a time when the heart adapts to diverse physiological and pathophysiological conditions. Crucial among these is the regulation of cardiomyocyte development and postnatal maturation, governed by dynamic changes in DNA methylation.

The plastic component bisphenol A (BPA) impairs reproductive organ development in various experimental animal species. In birds, effects are similar to those caused by other xenoestrogens. Because of its endocrine disrupting activity, BPA is being substituted with other bisphenols in many applications.

Bisphenols are endocrine disrupting chemicals to which humans are ubiquitously exposed to. Prenatal bisphenol A exposure can lead to insulin resistance. However, the metabolic effects of other emerging bisphenols, such as bisphenol S (BPS) and bisphenol F (BPF), are less understood.

Amoxicillin-clavulanate is the most common cause of idiosyncratic drug-induced liver injury (DILI). Drug-specific CD4+ T cells have been detected in patients with DILI, suggestive of an immune etiology. Furthermore, genetic associations including the human leucocyte antigen (HLA) DRB1*15:01-DQB1*06:02 haplotype influence susceptibility. Amoxicillin forms protein adducts that are postulated to activate T cells, by conjugating with lysine residues.

Studies have shown that mammalian testes, in particular the Sertoli cells, are highly susceptible to exposure of environmental toxicants, such as cadmium, perfluorooctanesulfonate, phthalates, 2,5-hexanedione and bisphenol A. However, important studies conducted by reproductive toxicologists and/or biologists in the past have been treated as toxicology reports per se.

In 2019, lung cancer was estimated to be the leading cause of cancer deaths in humans. Polycyclic aromatic hydrocarbons (PAHs) are known to increase the risk of lung cancer. PAHs are metabolized by the cytochrome P450 (CYP)1A subfamily, comprised of the CYP1A1 and 1A2 monooxygenases. These enzymes bioactivate PAHs into reactive metabolites that induce mutagenic DNA adducts, which can lead to cancer.

Inorganic arsenic (iAs) is a recognized environment-related factor for bladder cancer (BCa). Arsenic (+3 oxidation state) methyltransferase (AS3MT) gene might influence BCa by regulating iAs metabolism. The aim of the present study was to explore whether AS3MT polymorphisms could affect BCa susceptibility.

Polychlorinated biphenyls (PCBs) are ubiquitously detected and have been linked to metabolic diseases. Gut microbiome is recognized as a critical regulator of disease susceptibility; however, little is known how PCBs and gut microbiome interact to modulate hepatic xenobiotic and intermediary metabolism. We hypothesized the gut microbiome regulates PCB-mediated changes in the metabolic fingerprints and hepatic transcriptome.

Drug-induced liver injury is a major reason for drug candidate attrition from development, denied commercialization, market withdrawal, and restricted prescribing of pharmaceuticals. The metabolic bioactivation of drugs to chemically reactive metabolites (CRMs) contribute to liver-associated adverse drug reactions in humans that often goes undetected in conventional animal toxicology studies.

Toxicological Sciences, 164(2), 2018, 527–538

Cadmium (Cd) is a heavy metal and an environmental pollutant. However, the full spectrum of its neurotoxicity and the underlying mechanisms are not completely understood. Our previous studies demonstrated that Cd exposure impairs adult hippocampal neurogenesis and hippocampus-dependent memory in mice. This study aims to determine if these adverse effects of Cd exposure can be mitigated by genetically and conditionally enhancing adult neurogenesis.

The aryl hydrocarbon receptor (AHR) mediates developmental toxicity of several xenobiotic classes including polycyclic aromatic hydrocarbons. Using embryonic zebrafish, we previously identified 4 polycyclic aromatic hydrocarbons that caused a novel phenotype among AHR ligands—growth of a lateral, duplicate caudal fin fold.

Toxicological Sciences 113(1), 127–137 (2010), https://doi.org/10.1093/toxsci/kfp259

In the original publication, the following errors were present in the MATERIALS AND METHODS section, subheading Selection of Dose Levels: In the sentence “The estimated exposure of the children ranged from 0.03 to 8.92 mg/kg body weight (bw) per day”, the unit was incorrectly written as “milligrams” instead of “micrograms”. The correct estimated exposure for Italian children was 0.03 to 8.92 μg/kg body weight (bw) per day.

Epidemiological evidence links polychlorinated biphenyls (PCBs) to skeletal toxicity, however mechanisms whereby PCBs affect bone are poorly studied. In this study, coplanar PCB 126 (5 μmol/kg) or corn oil vehicle was administered to N = 5 and 6 male and female, wild type (WT) or AhR −/− rats via intraperitoneal injection. Animals were sacrificed after 4 weeks. Bone length was measured; bone morphology was assessed by microcomputed tomography and dynamic histomorphometry.

Methylmercury (MeHg) is a well-known neurotoxicant; however, its role in metabolic diseases has been gaining wider attention. We have previously shown that MeHg causes metabolic alterations in Caenorhabditis elegans, leading to decreased nicotinamide adenine dinucleotide cofactor, mitochondrial dysfunction, and oxidative stress.

An increasing number of compounds in our diet and environment are being identified as estrogenic, causing serious and detrimental effects on human, animal, and ecosystem health. Time- and cost-effective biological tools to detect and screen these compounds with potential high-throughput capabilities are in ever-growing demand.

Bisphenol A (BPA) is a plasticizer with endocrine disrupting properties particularly relevant for children health. Recently BPA has been associated with metabolic dysfunctions but no data are yet available in specific, long-term studies. This study aimed to evaluate BPA modes of action and hazards during animal juvenile life-stage, corresponding to childhood.

Emerging data indicate that structural analogs of bisphenol A (BPA) such as bisphenol S (BPS), tetrabromobisphenol A (TBBPA), and bisphenol AF (BPAF) have been introduced into the market as substitutes for BPA. Our previous study compared in vitro testicular toxicity using murine C18-4 spermatogonial cells and found that BPAF and TBBPA exhibited higher spermatogonial toxicities as compared with BPA and BPS.