Brent D. Kerger

Measurement of volatile organic compounds inside automobiles

The objective of the current study was to evaluate the types and concentrations of volatile organic compounds (VOCs) in the passenger cabin of selected sedan automobiles under static (parked, unventilated) and specified conditions of operation (i.e., driving the vehicle using air conditioning alone, vent mode alone, or drivers window half open). Data were collected on five different passenger sedan vehicles from three major automobile manufacturers. Airborne concentrations were assessed using 90-min time-weighted average (TWA) samples under U.S. Environmental Protection Agency (USEPA) Method IP-1B to assess individual VOC compounds and total VOCs (TVOCs) calibrated to toluene. Static vehicle testing demonstrated TVOC levels of approximately 400–800 μg/m3 at warm interior vehicle temperatures (approximately 80°F), whereas TVOCs at least fivefold higher were observed under extreme heat conditions (e.g., up to 145°F). The profile of most prevalent individual VOC compounds varied considerably according to vehicle brand, age, and interior temperature tested, with predominant compounds including styrene, toluene, and 8- to 12-carbon VOCs. TVOC levels under varied operating conditions (and ventilation) were generally four- to eightfold lower (at approximately 50–160 μg/m3) than the static vehicle measurements under warm conditions, with the lowest measured levels generally observed in the trials with the drivers window half open. These data indicate that while relatively high concentrations of certain VOCs can be measured inside static vehicles under extreme heat conditions, normal modes of operation rapidly reduce the inside-vehicle VOC concentrations even when the air conditioning is set on recirculation mode.

Benzene Exposure Assessment for Use of a Mineral Spirits-Based Degreaser

This study examines benzene emissions from the use of a metal parts washer (degreaser) supplied with a mineral spirits solvent containing either 9 or 58 ppm benzene. Air samples were obtained during a one-hour session of relatively vigorous parts cleaning activity using a degreaser station equipped with wet brush and sprayer attachments and a compressed air hose. Two methods were utilized to assess airborne benzene levels: U.S. EPA TO-14 (summa stainless steel canister) and NIOSH 1501 (charcoal tube). Overall, both methods provided similar results, excepting detection limit differences. The first simulation was performed with recycled solvent (9 ppm benzene in solvent) showing average one-hour airborne benzene levels < or =33 ppbv in the workers breathing zone and directly above the parts cleaning tank. Average airborne benzene concentrations 18 inches away from the tank were below 2 ppbv during the 60-minute cleaning protocol. The second simulation with benzene-spiked recycled solvent (58 ppm benzene) showed airborne benzene levels averaging 500 ppbv measured over the 60-minute cleaning period in the workers breathing zone and directly above the tank, while average concentrations 18 inches from the tank perimeter were 63 ppbv. The data indicate that average and peak exposures to airborne benzene were roughly proportional to the solvent benzene content, although the brief peak exposures exhibited greater variance probably related to aerosol generation associated with the use of the brush and/or spraying attachment. Under this selected upper bound exposure simulation, we found that cleaning parts using a recycled mineral spirits-based solvent in an open warehouse setting did not result in exposures in excess of the current occupational exposure limit of 0.5 ppm averaged over 8 hours for solvent benzene content between 9 and 58 ppm.

Ammonia exposure and hazard assessment for selected household cleaning product uses.

There is scant information pertaining to airborne ammonia exposures from either spills or common household uses of ammonia-containing floor and tile cleaners or from spray-on glass cleaners. We assessed instantaneous and event-specific time-weighted average (TWA) exposures to airborne ammonia during spills and use (per label directions) of a household floor and tile cleaner and two spray-on window cleaners. Airborne ammonia levels measured at breathing zone height (BZH) above the spilled floor and tile cleaner product reached 500u2009p.p.m. within 5u2009min, while levels for spilled window cleaner were below 8u2009p.p.m. TWA exposures were assessed while tile walls and floors were cleaned in three different bathrooms of a residence, and during use of a spray-on glass cleaner while washing several large windows in an office setting. NIOSH Method 6015 was utilized with concurrent field measurements every 60u2009s using a Drager PAC III monitor with an electrochemical cell detector. Peak ammonia levels ranged from 16 to 28u2009p.p.m. and short-term TWA concentrations ranged from 9.4 to 13u2009p.p.m. during mixing (0.1% ammonia) and cleaning tiles in the three bathrooms. Ammonia exposures while using spray-on window cleaner were over 10-fold lower (TWA=0.65u2009p.p.m.). Use of the floor and tile cleaner mixed at 0.2% ammonia led to peak airborne ammonia levels within 3–5u2009min at 36–90u2009p.p.m., and use of full strength cleaner (3% ammonia) led to peak ammonia levels of 125 to >200u2009p.p.m. within 2–3u2009min. Spillage or intentional use of the full strength floor and tile cleaner led to airborne ammonia concentrations that exceed occupational short-term exposure limits, while spillage or use of the spray-on window cleaner did not approach potentially hazardous airborne ammonia levels and likely represents a minimal inhalation health hazard. We conclude that routine household uses of ammonia are unlikely to produce significant exposures when using standard cleaning solutions (0.1–0.2%), but spillage or use of concentrated ammonia solutions (e.g., 3%) in poorly ventilated areas can lead to potentially hazardous airborne ammonia exposures.

Review of cobalt toxicokinetics following oral dosing: Implications for health risk assessments and metal-on-metal hip implant patients

Abstract Cobalt (Co) can stimulate erythropoietin production in individuals at doses exceeding 25 mg CoCl2/day. Co has also been shown to exert effects on the thyroid gland, heart and nervous system at sufficient doses. The biological activity of Co is dictated by the concentration of free (unbound) ionic Co2+. Blood concentrations, as well as, urinary excretion rates of Co are reliable biomarkers for systemic Co exposure. A recent series of human volunteer Co-supplement studies simultaneously measured Co blood and urine concentrations, as well as, Co speciation in serum, and a number of biochemical and clinical parameters. It was found in these studies that peak Co whole blood concentration as high as 117 μg/L were not associated with changes in hematological parameters such as increased red blood cell (RBC) count, hemoglobin (Hgb) or hematocrit (Hct) levels, nor with changes in cardiac, neurological or, thyroid function. Using a Co biokinetic model, the estimated Co systemic tissue concentrations (e.g., liver, kidney, and heart) following 90-days of Co-dietary supplementation with ∼1 mg Co/day were found to be similar to estimated tissue concentrations in implant patients after 10 years of exposure at continuous steady state Co blood concentration of ∼10 μg/L. This study is the first to present modeled Co tissue concentrations at various doses following sub-chronic and chronic exposure. The modeled steady state tissue Co concentrations in combination with the data on adverse health effects in humans should help in the characterization of potential hazards associated with increased blood Co concentrations due to exposure to dietary supplements or cobalt-chromium (Co-Cr) containing implants.

Total cobalt determination in human blood and synovial fluid using inductively coupled plasma-mass spectrometry: method validation and evaluation of performance variables affecting metal hip implant patient samples

Inductively coupled plasma with mass spectrometric detection (ICP-MS) has been used for clinical analysis of cobalt (Co) due to its sensitivity and specificity; however, media-specific validation studies are lacking. This study provides data on performance variables affecting differences between selected analytical platforms (Perkin Elmer and Agilent), tissue sample preparation, storage, and interferences affecting measurements in whole blood, serum, and synovial fluid. The limits of detection (LOD) range from 0.2–0.5 µg/L in serum and synovial fluid, and 0.6–1.7 µg Co/L in whole blood. The Agilent platform with collision reaction cell is more sensitive, while the Perkin Elmer platform with dynamic reaction cell demonstrates more polyatomic interferences near the LOD for serum and whole blood. Split sample analysis showed good accuracy, precision, and reproducibility between serum Co measurements using acid digestion or detergent dilution preparations for persons with metal hip implants or following supplement intake. The results demonstrated reliability of the ICP-MS methodology across the two analytical platforms and between two commercial laboratories for Co concentrations above 5 µg Co/L, but digestion procedures and polyatomic interferences may affect measurements in some media at lower concentrations. These studies validate the described ICP-MS methodology for clinical purposes with precautions at low cobalt concentrations (<5 µg Co/L).

Halo and spillover effect illustrations for selected beneficial medical devices and drugs

BackgroundNegative news media reports regarding potential health hazards of implanted medical devices and pharmaceuticals can lead to a ‘negative halo effect,’ a phenomenon whereby judgments about a product or product type can be unconsciously altered even though the scientific support is tenuous. To determine how a ‘negative halo effect’ may impact the rates of use and/or explantation of medical products, we analyzed the occurrence of such an effect on three implanted medical devices and one drug: 1) intrauterine contraceptive devices (IUDs); 2) silicone gel-filled breast implants (SGBI); 3) metal-on-metal hip implants (MoM); and 4) the drug Tysabri.MethodsData on IUD use from 1965 to 2008 were gathered from the Department of Health and Human Services Vital and Health Statistics and peer-reviewed publications. Data regarding SGBI implant and explantation rates from 1989 to 2012 were obtained from the Institute of Medicine and the American Society of Plastic Surgeons. MoM implant and explantation data were extracted from the England and Wales National Joint Registry and peer-reviewed publications. Tysabri patient data were reported by Elan Corporation or Biogen Idec Inc. Data trends for all products were compared with historical recall or withdrawal events and discussed in the context of public perceptions following such events.ResultsWe found that common factors altered public risk perceptions and patterns of continued use. First, a negative halo effect may be driven by continuing patient anxiety despite positive clinical outcomes. Second, negative reports about one product can spill over to affect the use of dissimilar products in the same category. Third, a negative halo effect on an entire category of medical devices can be sustained regardless of the scientific findings pertaining to safety. Fourth, recovery of a product’s safety reputation and prevalent use may take decades in the U.S., even while these products may exhibit widespread use and good safety records in other countries.ConclusionsWe conclude that the ‘negative halo effect’ associated with a stigma, rather than an objective risk-benefit assessment of medical products can increase negative health outcomes for patients due to reduced or inappropriate product usage.

Total Aromatic Content in Petroleum Solvents Modifies Headspace Benzene Vapor Concentrations: Implications for Exposure Assessments

ABSTRACT This study evaluates how equilibrium vapor concentrations above petroleum solvent mixtures are affected by total aromatic content and the implications for estimating benzene vapor exposures. Headspace vapor concentrations over mixtures with liquid benzene content ranging from 0.001 to 1.0% and varying percentages of 1,2,4-trimethylbenzene and n-nonane were studied using a direct-injection gas chromatography/flame ionization detection method that showed good precision. The measured values were compared to predictions based on Raoults Law, with and without non-ideality corrections using activity coefficients. Ratios of vapor to liquid benzene concentrations decreased with increasing total aromatic content; that is, mixtures with 10% to 20% trimethylbenzene simulating non-hydrotreated mineral spirits had much lower ratios compared to the ≥99% aliphatic mixtures that simulate hydrotreated mineral spirits. Positive deviations from Raoults Law were greatest at liquid benzene concentrations less than 0.1%, particularly in the predominantly aliphatic mixtures. Correcting for non-ideality using activity coefficients resulted in predicted vapor concentrations that were closer to measured values. The data indicate that higher aromatic content and higher liquid benzene content suppress benzene vapor concentrations due to benzenes greater affinity for similar aromatic molecules in solution. Benzene exposure reconstructions should consider actual composition of the historic material with respect to aromatic content.

Liver tumor potency indicators for technical toxaphene and congeners simulating weathered toxaphene

ABSTRACT Technical toxaphene (TT) is a liver tumor promoter in B6C3F1 mice but not in F344 rats. To further evaluate dose-response relationships for weathered toxaphene, B6C3F1 mouse hepatocytes were treated with TT alone, five selected persistent congeners (p-26, p-50, p-62, Hx-Sed, and Hp-Sed), or two selected congener mixtures (simulating weathered toxaphene) and dose-response relationships were characterized for cytotoxicity and gap junction intercellular communication (GJIC) inhibition. Phenobarbital was included as a positive control for mouse liver tumor promotion and GJIC inhibition and dose ranges were calibrated to define benchmark dose concentrations. Each treatment group exhibited significant cytotoxicity and GJIC inhibition for at least one sex (M/F) after 3 and/or 24 h of treatment. Maximum GJIC inhibition was observed at certain noncytotoxic concentrations with sex-specific differences in relative potency estimated as the effective concentration at 20% inhibition (EC20); however, no significant EC20 differences were observed between the treatment groups. Analysis of mixture interactions at the EC20 showed that GJIC inhibition of the two weathered toxaphene mixtures was significantly less than additive compared to that for the component congeners. These findings suggest that the persistent toxaphene congener mixtures tested are not more tumorigenic than the parent insecticide mixture.

Headspace and small-chamber studies of airborne diacetyl release from selected food flavoring mixtures: activity coefficients and air modeling implications

Laboratory studies were conducted to evaluate airborne release of diacetyl from selected mixtures simulating butter flavorings added to foods. The test materials included diacetyl (97% purity); 0.015%, 0.15%, 1.5%, and 3.0% diacetyl in a water/propylene glycol mixture; 1.5% diacetyl in deionized water or soybean oil; and 3% or 6% diacetyl in a commercial steam distillate from milk fermentation known as “butter starter distillate.” Diacetyl was quantified by gas chromatography with flame ionization detection. Expected concentration-dependent emission patterns based on liquid diacetyl content were demonstrated, but were significantly altered by mixture composition. Soybean oil and deionized water more readily released diacetyl when compared with starter distillate, propylene glycol solutions, and pure diacetyl. Measured diacetyl concentrations under static headspace and dynamic flow-chamber conditions were compared to estimated concentrations utilizing Raoults law with published and fitted activity coefficient corrections for each mixture, indicating that published coefficients often understated the measured concentrations. It is concluded that headspace (static) and small-chamber (dynamic) measurements of airborne diacetyl provide data to assist in validating model-estimated airborne diacetyl concentrations by using mixture-specific activity coefficients. Implications of these empirical data for validating exposure estimates for diacetyl based on near-field/far-field modeling in workplace settings are discussed.

Proposed reference dose for toxaphene carcinogenicity based on constitutive androstane receptor-mediated mode of action

ABSTRACT Toxaphene is a liver tumor promoter in B6C3F1 mice but not in F344 rats or hamsters. Recent studies demonstrate that key events leading to the mouse liver tumor response for toxaphene are mediated by activation of the constitutive androstane receptor (CAR). Benchmark dose modeling was conducted on available data for five endpoints in B6C3F1 mouse liver tissue or cultured liver cells (tumor response, cytotoxicity, proliferation, gap junction intercellular communication inhibition, and CAR-mediated CYP2B10 induction) and for CAR activation in human HepG2 cells, all reported in previous studies. The available evidence supports a nonlinear CAR-mediated mode of action (MOA) for toxaphene-induced mouse tumors including demonstration of a J-shaped dose-response pattern for human CAR activation, indicating that linear risk extrapolation at low doses is not supported for this MOA. Based on analysis of benchmark dose lower confidence limits at 10% response (BMDL10) and no observed effect levels (NOELs) for potential key events in the mouse liver tumor MOA for toxaphene, an RfD of 0.13 mg/kg-d is proposed based on a the BMDL10 for human CAR activation in human HepG2 cells. This value is below candidate RfD values based on BMDL10 estimates for both mouse liver tumors and mouse hepatocyte proliferation and therefore can be considered protective for human risk of liver tumor promotion and other CAR-mediated adverse health effects based on available data.