Benchmark Dose Modeling Approaches for Volatile Organic Chemicals Using a Novel Air-Liquid Interface In Vitro Exposure System.

Inhalation is the most relevant route of volatile organic chemical (VOC) exposure; however, due to unique challenges posed by their chemical properties and poor solubility in aqueous solutions, in vitro chemical safety testing is predominantly performed using direct application dosing/submerged exposures. To address the difficulties in screening toxic effects of VOCs, our cell culture exposure system permits cells to be exposed to multiple concentrations at air-liquid interface (ALI) in a 24-well format. ALI exposure methods permit direct chemical-to-cell interaction with the test article at physiological conditions.

Diesel exhaust inhalation increases cardiac output, bradyarrhythmias, and parasympathetic tone in aged heart failure-prone rats.

Acute air pollutant inhalation is linked to adverse cardiac events and death, and hospitalizations for heart failure. Diesel engine exhaust (DE) is a major air pollutant suspected to exacerbate preexisting cardiac conditions, in part, through autonomic and electrophysiologic disturbance of normal cardiac function. To explore this putative mechanism, we examined cardiophysiologic responses to DE inhalation in a model of aged heart failure-prone rats without signs or symptoms of overt heart failure.

Whole and particle-free diesel exhausts differentially affect cardiac electrophysiology, blood pressure, and autonomic balance in heart failure-prone rats.

Epidemiological studies strongly link short-term exposures to vehicular traffic and particulate matter (PM) air pollution with adverse cardiovascular (CV) events, especially in those with preexisting CV disease. Diesel engine exhaust is a key contributor to urban ambient PM and gaseous pollutants. To determine the role of gaseous and particulate components in diesel exhaust (DE) cardiotoxicity, we examined the effects of a 4-h inhalation of whole DE (wDE) (target PM concentration: 500 µg/m(3)) or particle-free filtered DE (fDE) on CV physiology and a range of markers of cardiopulmonary injury in hypertensive heart failure-prone rats.

Acute toluene exposure and rat visual function in proportion to momentary brain concentration.

Acute exposure to toluene was assessed in two experiments to determine the relationship between brain toluene concentration and changes in neurophysiological function. The concentration of toluene in brain tissue at the time of assessment was estimated using a physiologically based pharmacokinetic model. Brain neurophysiological function was measured using pattern-elicited visual evoked potentials (VEP) recorded from electrodes located over visual cortex of adult male Long-Evans rats.

A dosimetric analysis of the acute behavioral effects of inhaled toluene in rats.

Knowledge of the appropriate metric of dose for a toxic chemical facilitates quantitative extrapolation of toxicity observed in the laboratory to the risk of adverse effects in the human population. Here, we utilize a physiologically based toxicokinetic (PBTK) model for toluene, a common volatile organic compound (VOC), to illustrate that its acute behavioral effects in rats can be quantitatively predicted on the basis of its concentration in the brain. Rats previously trained to perform a visual signal detection task for food reward performed the task while inhaling toluene (0, 1200, 1600, 2000, and 2400 ppm in different test sessions).

Evaluating the NMDA-glutamate receptor as a site of action for toluene, in vivo.

Acute exposure to toluene and other volatile organic solvents results in neurotoxicity characterized by nervous system depression, cognitive and motor impairment, and alterations in visual function. In vitro, toluene disrupts the function of N-methyl-D-aspartate (NMDA)-glutamate receptors, indicating that effects on NMDA receptor function may contribute to toluene neurotoxicity. NMDA-glutamate receptors are widely present in the visual system and contribute to pattern-elicited visual-evoked potentials (VEPs) in rodents, a measure that is altered by toluene exposure.