N-Formyllysine as a Biomarker of Formaldehyde Exposure: Formation and Loss of N-Formyllysine in Nasal Epithelium in Long-Term, Low-Dose Inhalation Studies in Rats.

Exposure to both endogenous and exogenous formaldehyde has been established to be carcinogenic, likely by virtue of forming nucleic acid and proteins adducts such as N-formyllysine. To better assess N-formyllysine as a biomarker of formaldehyde exposure, we studied accumulation of N-formyllysine adducts in tissues of rats exposed by inhalation to 2 ppm [CH]-formaldehyde for 7, 14, 21, and 28 days (6 h/day) and investigated adduct loss over a 7-day postexposure period using liquid chromatography-coupled tandem mass spectrometry. Our results showed formation of exogenous adducts in nasal epithelium and to some extent in trachea but not in distant tissues of lung, bone marrow, or white blood cells, with a 2-fold increase over endogenous N-formyllysine over a 3-week exposure period.

Formation, Accumulation, and Hydrolysis of Endogenous and Exogenous Formaldehyde-Induced DNA Damage.

Formaldehyde is not only a widely used chemical with well-known carcinogenicity but is also a normal metabolite of living cells. It thus poses unique challenges for understanding risks associated with exposure. N(2-)hydroxymethyl-dG (N(2)-HOMe-dG) is the main formaldehyde-induced DNA mono-adduct, which together with DNA-protein crosslinks (DPCs) and toxicity-induced cell proliferation, play important roles in a mutagenic mode of action for cancer.

Carbon capture and sequestration: an exploratory inhalation toxicity assessment of amine-trapping solvents and their degradation products.

Carbon dioxide (CO2) absorption with aqueous amine solvents is a method of carbon capture and sequestration (CCS) from flue gases. One concern is the possible release of amine solvents and degradation products into the atmosphere, warranting evaluation of potential pulmonary effects from inhalation. The CCS amines monoethanolamine (MEA), methyldiethanolamine (MDEA), and piperazine (PIP) underwent oxidative and CO2-mediated degradation for 75 days.

Formaldehyde-associated changes in microRNAs: tissue and temporal specificity in the rat nose, white blood cells, and bone marrow.

MicroRNAs (miRNAs) are critical regulators of gene expression, yet much remains unknown regarding their changes resulting from environmental exposures as they influence cellular signaling across various tissues. We set out to investigate miRNA responses to formaldehyde, a critical air pollutant and known carcinogen that disrupts miRNA expression profiles. Rats were exposed by inhalation to either 0 or 2 ppm formaldehyde for 7, 28, or 28 days followed by a 7-day recovery.

Dosimetry of N⁶-formyllysine adducts following [¹³C²H₂]-formaldehyde exposures in rats.

With formaldehyde as the major source of endogenous N⁶-formyllysine protein adducts, we quantified endogenous and exogenous N⁶-formyllysine in the nasal epithelium of rats exposed by inhalation to 0.7, 2, 5.8, and 9.

Formaldehyde and epigenetic alterations: microRNA changes in the nasal epithelium of nonhuman primates.

Background: Formaldehyde is an air pollutant present in both indoor and outdoor atmospheres. Because of its ubiquitous nature, it is imperative to understand the mechanisms underlying formaldehyde-induced toxicity and carcinogenicity. MicroRNAs (miRNAs) can influence disease caused by environmental exposures, yet miRNAs are understudied in relation to formaldehyde.

Cardiopulmonary response to inhalation of secondary organic aerosol derived from gas-phase oxidation of toluene.

The biological response to inhalation of secondary organic aerosol (SOA) was determined in rodents exposed to SOA derived from the oxidation of toluene, a precursor emitted from anthropogenic sources. SOA atmospheres were produced to yield 300 µg·m(-3) of particulate matter (PM) plus accompanying gases. Whole-body exposures were conducted in mice to assess both pulmonary and cardiovascular effects.

Dermal and ocular exposure systems for the development of models of sulfur mustard-induced injury.

Sulfur mustard (SM) is a chemical threat agent for which the effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present article details the techniques used to develop SM laboratory exposure systems for the development of animal models of ocular and dermal injury.

Inhalation exposure systems for the development of rodent models of sulfur mustard-induced pulmonary injury.

Sulfur mustard (SM) is a chemical threat agent for which its effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present manuscript details the techniques used to develop SM laboratory exposure systems for the development of animal models of pulmonary injury.

Generation and characterization of gasoline engine exhaust inhalation exposure atmospheres.

Exposure atmospheres for a rodent inhalation toxicology study were generated from the exhaust of a 4.3-L gasoline engine coupled to a dynamometer and operated on an adapted California Unified Driving Cycle. Exposure levels were maintained at three different dilution rates.

Influence of impactor operating flow rate on particle size distribution of four jet nebulizers.

When a nebulizer is evaluated by the Andersen Cascade Impactor (ACI), the flow rate is generally maintained at 28.3 L/min, as recommended by the manufacturer. However, the nebulizer flow rate that a patient inhales is only around 18 L/min.

Disposition and clearance of tungsten after single-dose oral and intravenous exposure in rodents.

Tungsten (W) has been nominated for study to the National Toxicology Program (NTP) because of reported associations between concentrations of W in drinking water and childhood leukemia. The disposition of W (administered as sodium tungstate dihydrate in water) in plasma, liver, kidneys, uterus, femur, and intestine of rodents (Sprague-Dawley rats and C57BL/6N mice) was characterized after exposures by oral gavage (1, 10, or 100 mg/kg) or intravenous (1 mg/kg) administration. Each tissue (or plasma) was collected and analyzed by inductively coupled plasma mass spectrometry at 1, 2, 4, or 24 h after dose administration.

Identification of urinary metabolites of orally administered N,N-dimethyl-p-toluidine in male F344 rats.

The metabolism of orally administered N,N-dimethyl-p-toluidine (DMPT) in male F344 rats was investigated. The rat urinary metabolite profile was determined by analytical reverse-phase high performance liquid chromatography (HPLC). Four radiolabeled peaks were observed, isolated, and purified by solid-phase extraction (SPE) and preparative HPLC methods.

Disposition of orally and intravenously administered methyltetrahydrofuran in rats and mice.

The disposition of [14C]methyltetrahydrofuran (14C-MTHF) in rats and mice was determined by following changes in the radioactivity in tissue and excreta with time after dosing. MTHF administered orally (1, 10, or 100 mg/kg) or intravenously (1 mg/kg) to either rats or mice was rapidly metabolized and excreted with <8% (mice) or 8-22% (rats) of the dose remaining in the body after 24 h (1 and 10 mg/kg doses) or 72 h (100 mg/kg dose). Based on recovery of radioactivity in excreta (other than feces) and tissues (other than the gastrointestinal [GI] tract), absorption of orally administered MTHF was essentially complete (93-100%).

Measurement of plasma or urinary metabolites and Hprt mutant frequencies following inhalation exposure of mice and rats to 3-butene-1,2-diol.

Studies were performed to determine if the detoxification pathway of 1,3-butadiene (BD) through 3-butene-1,2-diol (BD-diol) is a major contributor to mutagenicity in BD-exposed mice and rats. First, female and male mice and rats (4-5 weeks old) were exposed by nose-only for 6h to 0, 62.5, 200, 625, or 1250 ppm BD or to 0, 6, 18, 24, or 36 ppm BD-diol primarily to establish BD and BD-diol exposure concentrations that yielded similar plasma levels of BD-diol, and then animals were exposed in inhalation chambers for 4 weeks to BD-diol to determine the mutagenic potency estimates for the same exposure levels and to compare these estimates to those reported for BD-exposed female mice and rats where comparable blood levels of BD-diol were achieved.

Medical nebulizer performance: effects of cascade impactor temperature.

Background: During operation of a jet nebulizer, the temperature of the nebulizer outlet could decrease by more than 10 degrees C, depending on the nebulizer type and operating conditions, such as driving flow rate and fill volume. The droplet size distribution generated from the nebulizer can be measured by a cascade impactor. However, when the cascade impactor is operated at ambient room temperature, the droplets could evaporate because of the temperature difference between the nebulizer outlet and the body of the impactor.

Concentration and particle size of airborne toxic algae (brevetoxin) derived from ocean red tide events.

Red tides in the Gulf of Mexico are formed by blooms of the dinoflagellate Karenia brevis, which produces brevetoxins (PbTx). Brevetoxins can be transferred from water to air in the wind-powered whitecapped waves during red tide episodes. Inhalation exposure to marine aerosol containing PbTx causes respiratory problems.

Analysis of butadiene urinary metabolites by liquid chromatography-triple quadrupole mass spectrometry.

1,3-Butadiene (BD) is a monomer produced in petrochemical production facilities and from several combustion sources. The United States Environmental Protection Agency has defined BD as a probable human carcinogen. Methods for assessing exposure and internal dose are therefore of critical interest, and one technique is the measurement of urinary metabolites.

Chronic self-administration of nicotine in rats impairs T cell responsiveness.

Chronic exposure of rodents to nicotine via subcutaneously or intracerebroventricularly implanted miniosmotic pumps affects T cell function. However, this method of continuous nicotine administration does not replicate the self-motivated administration of nicotine in human smokers. To determine whether nicotine impairs the immune system under conditions pertinent to human smokers, we investigated the T cell responsiveness of male Lewis rats self-administering (SA) nicotine (0.