Age- and Organ-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats.

Mitochondria play a central role in energy homeostasis and act as regulatory checkpoints for downstream metabolic responses and cell senescence processes during an entire life span. Acute or chronic environmental toxicant exposures have shown deleterious organ-specific human health issues at various life stages. Since mitochondria are a prime target for ensuing cellular bioenergetics responses and senescence, it is essential to understand mitochondrial bioenergetic responses in different organs over multiple life stages.

Age- and brain region-specific differences in mitochondrial bioenergetics in Brown Norway rats.

Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bioenergetic parameters in 5 brain regions (brain stem [BS], frontal cortex, cerebellum, striatum, hippocampus [HIP]) of 4 diverse age groups (1 month [young], 4 months [adult], 12 months [middle-aged], 24 months [old age]) to understand age-related differences in selected brain regions and their possible contribution to age-related chemical sensitivity. Mitochondrial bioenergetic parameters and enzyme activities were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5/group).

Carbaryl and 1-naphthol tissue levels and related cholinesterase inhibition in male Brown Norway rats from preweaning to senescence.

Studies incorporating both toxicokinetic and dynamic factors provide insight into chemical sensitivity differences across the life span. Tissue (brain, plasma, liver) levels of the N-methyl carbamate carbaryl, and its metabolite 1-naphthol, were determined and related to brain and RBC cholinesterase (ChE) inhibition in the same animals. Dose-response (3, 7.

Assessing nanoparticle risk poses prodigious challenges.

Risk assessment is used both formally and informally to estimate the likelihood of an adverse event occurring, for example, as a consequence of exposure to a hazardous chemical, drug, or other agent. Formal risk assessments in government regulatory agencies have a long history of practice. The precision with which risk can be estimated is inevitably constrained, however, by uncertainties arising from the lack of pertinent data.

Toluene effects on gene expression in the hippocampus of young adult, middle-age, and senescent Brown Norway Rats.

Differential susceptibility to environmental exposures across life stages is an area of toxicology about which little is known. We examined the effects of toluene on transcriptomic changes and oxidative stress (OS) parameters (e.g.

Serum biomarkers of aging in the Brown Norway rat.

Serum biomarkers to identify susceptibility to disease in aged humans are well researched. On the other hand, our understanding of biomarkers in animal models of aging is limited. Hence, we applied a commercially available panel of 58 serum analytes to screen for possible biomarkers of aging in 4, 12, and 24 month old Brown Norway rats.

Toluene effects on oxidative stress in brain regions of young-adult, middle-age, and senescent Brown Norway rats.

The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound, toluene. The objective was to test whether oxidative stress (OS) plays a role in the adverse effects caused by toluene exposure, and if so, if effects are age-dependent.

Engineered nanomaterials: exposures, hazards, and risk prevention.

Nanotechnology presents the possibility of revolutionizing many aspects of our lives. People in many settings (academic, small and large industrial, and the general public in industrialized nations) are either developing or using engineered nanomaterials (ENMs) or ENM-containing products. However, our understanding of the occupational, health and safety aspects of ENMs is still in its formative stage.

An observational assessment method for aging laboratory rats.

The rapid growth of the aging human population highlights the need for laboratory animal models to study the basic biologic processes of aging and susceptibility to disease, drugs, and environmental pollutants. Methods are needed to evaluate the health of aging animals over time, particularly methods for efficiently monitoring large research colonies. Here we describe an observational assessment method that scores appearance, posture, mobility, and muscle tone on a 5-point scale that can be completed in about 1 min.

Developmental exposure to a commercial PBDE mixture, DE-71: neurobehavioral, hormonal, and reproductive effects.

Developmental effects of polybrominated diphenyl ethers (PBDEs) have been suspected due to their structural similarities to polychlorinated biphenyls (PCBs). This study evaluated neurobehavioral, hormonal, and reproductive effects in rat offspring perinatally exposed to a widely used pentabrominated commercial mixture, DE-71. Pregnant Long-Evans rats were exposed to 0, 1.

Aging and susceptibility to toluene in rats: a pharmacokinetic, biomarker, and physiological approach.

Aging adults are a growing segment of the U.S. population and are likely to exhibit increased susceptibility to many environmental toxicants.

Characterizing uncertainty and variability in physiologically based pharmacokinetic models: state of the science and needs for research and implementation.

Physiologically based pharmacokinetic (PBPK) models are used in mode-of-action based risk and safety assessments to estimate internal dosimetry in animals and humans. When used in risk assessment, these models can provide a basis for extrapolating between species, doses, and exposure routes or for justifying nondefault values for uncertainty factors. Characterization of uncertainty and variability is increasingly recognized as important for risk assessment; this represents a continuing challenge for both PBPK modelers and users.

Neurobehavioral assessments of rats perinatally exposed to a commercial mixture of polychlorinated biphenyls.

Because of behavioral deficits associated with gestational exposure to PCBs in children, we sought to quantify neurobehavioral effects of perinatal exposure to Aroclor 1254(R) (A1254), a commercial mixture of PCBs, in rats. Pregnant Long-Evans rats were fed A1254 at doses of 0, 1.0, or 6.