Using primary organotypic mouse midbrain cultures to examine developmental neurotoxicity of silver nanoparticles across two genetic strains.

Micromass culture systems have been developed as three-dimensional organotypic in vitro alternatives to test developmental toxicity. We have optimized a murine-based embryonic midbrain micromass system in two genetic strains to evaluate neurodevelopmental effects of gold-cored silver nanoparticles (AgNPs) of differing sizes and coatings-20 nm AgCitrate, 110 nm AgCitrate, and 110 nm AgPVP. AgNPs are increasingly used in consumer, commercial, and medical products for their antimicrobial properties and observations of Ag in adult and fetal brain following in vivo exposures to AgNPs have led to concerns about the potential for AgNPs to elicit adverse effects on neurodevelopment and neurological function. Cytotoxicity was assessed at three time points of development by both nominal dose and by dosimetric dose. Ag dosimetry was assessed in cultures and the gold core component of the AgNPs was used as a tracer for determination of uptake of intact AgNPs and silver dissolution from particles in the culture system. Results by both nominal and dosimetric dose show cell death increased significantly in a dose-dependent manner at later time points (days 15 and 22 in vitro) that coincide with differentiation stages of development in both strains. When assessed by dosimetric dose, cultures were more sensitive to smaller particles, despite less uptake of Ag in smaller particles in both strains.

Macrocyclic and Other Non-Group 1 Gadolinium Contrast Agents Deposit Low Levels of Gadolinium in Brain and Bone Tissue: Preliminary Results From 9 Patients With Normal Renal Function.

OBJECTIVE: The purpose of this study was to determine whether gadolinium (Gd) is deposited in brain and bone tissues in patients receiving only non-Group 1 agents, either macrocyclic or linear protein interacting Gd-based contrast agents, with normal renal function. Group 1 agents are linear agents most associated with nephrogenic systemic fibrosis that the US Federal Drug Administration has defined as contraindicated in patients at risk for this disease. MATERIALS AND METHODS: This study was institutional review board approved and Health Insurance Portability and Accountability Act compliant for retrospective review of records and also had signed autopsy consent authorizing use of decedent's tissue in research studies. Tissue samples were collected from 9 decedents undergoing autopsy who had contrast-enhanced magnetic resonance imaging (MRI) with only single agent exposure to a non-Group 1 Gd-based contrast agent. Decedents with only noncontrast MRI or no MRI served as controls. Multiple brain areas, including globus pallidus and dentate nucleus, as well as bone and skin, were sampled and analyzed for Gd using inductively coupled plasma mass spectrometry. Gadolinium levels were compared between groups of decedents using the Mann-Whitney test and between brain and bone tissues of the same cases using the Wilcoxon signed-rank test. RESULTS: Of the 9 decedents, 5 received gadoteridol (ProHance; Bracco Diagnostics, Princeton, NJ), 2 received gadobutrol (Gadovist; Bayer Healthcare, Whippany, NJ), and 1 each had gadobenate (MultiHance; Bracco Diagnostics) and gadoxetate (Eovist; Bayer Healthcare). Gadolinium was found with all agents in all brain areas sampled with highest levels in globus pallidus and dentate. Bone levels measured 23 times higher (median) than brain levels (P = 0.008 for bone vs globus pallidus) and showed a significant correlation (r = 0.81, P = 0.022). In controls, Gd levels in the brain were at or below limits of measurement and were significantly lower compared with study cases (P = 0.005 for globus pallidus). CONCLUSION: Gadolinium deposition in normal brain and bone tissue occurs with macrocyclic and linear protein interacting agents in patients with normal renal function. Deposition of Gd in cortical bone occurs at much higher levels compared with brain tissue and shows a notable correlation between the two. Thus, the bone may serve as a surrogate to estimate brain deposition if brain Gd were to become a useful clinical or research marker.

Phthalate metabolite levels and menopausal hot flashes in midlife women.

During the menopausal transition, a woman's reproductive capacity declines, her hormone milieu changes, and her risk of hot flashes increases. Exposure to phthalates, which can be found in personal care products, can also result in altered reproductive function. Here, we investigated the associations between phthalate metabolite levels and midlife hot flashes. Eligible women (45-54 years of age) provided detailed information on hot flashes history and donated urine samples (n=195). Urinary phthalate metabolite levels were measured by HPLC-MS/MS. A higher total sum of phthalate metabolites commonly found in personal care products was associated with an increased risk of ever experiencing hot flashes (odds ratio (OR)=1.45; 95% confidence interval (CI)=1.07-1.96), hot flashes in the past 30days (OR=1.43; 95%CI=1.04-1.96), and more frequent hot flashes (OR=1.47; 95%CI=1.06-2.05). These data suggest that some phthalate exposures from personal care products are associated with menopausal hot flashes in women.

Urinary polycyclic aromatic hydrocarbon metabolites as biomarkers to woodsmoke exposure - results from a controlled exposure study.

Woodsmoke contains harmful components - such as fine particulate matter (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) - and impacts more than half of the global population. We investigated urinary hydroxylated PAH metabolites (OH-PAHs) as woodsmoke exposure biomarkers in nine non-smoking volunteers experimentally exposed to a wood fire. Individual urine samples were collected from 24-h before to 48-h after the exposure and personal PM2.5 samples were collected during the 2-h woodsmoke exposure. Concentrations of nine OH-PAHs increased by 1.8-7.2 times within 2.3-19.3 h, and returned to baseline approximately 24 h after the exposure. 2-Naphthol (2-NAP) had the largest post-exposure increase and exhibited a clear excretion pattern in all participants. The level of urinary OH-PAHs, except 1-hydroxypyrene (1-PYR), correlated with those of PM2.5, levoglucosan and PAHs in personal PM2.5 samples. This finding suggests that several urinary OH-PAHs, especially 2-NAP, are potential exposure biomarkers to woodsmoke; by contrast, 1-PYR may not be a suitable biomarker. Compared with levoglucosan and methoxyphenols - two other urinary woodsmoke biomarkers that were measured in the same study and reported previously - OH-PAHs might be better biomarkers based on sensitivity, robustness and stability, particularly under suboptimal sampling and storage conditions, like in epidemiological studies carried out in less developed areas.

Persistent Organic Pollutant Determination in Killer Whale Scat Samples: Optimization of a Gas Chromatography/Mass Spectrometry Method and Application to Field Samples.

Biologic sample collection in wild cetacean populations is challenging. Most information on toxicant levels is obtained from blubber biopsy samples; however, sample collection is invasive and strictly regulated under permit, thus limiting sample numbers. Methods are needed to monitor toxicant levels that increase temporal and repeat sampling of individuals for population health and recovery models. The objective of this study was to optimize measuring trace levels (parts per billion) of persistent organic pollutants (POPs), namely polychlorinated-biphenyls (PCBs), polybrominated-diphenyl-ethers (PBDEs), dichlorodiphenyltrichloroethanes (DDTs), and hexachlorocyclobenzene, in killer whale scat (fecal) samples. Archival scat samples, initially collected, lyophilized, and extracted with 70 % ethanol for hormone analyses, were used to analyze POP concentrations. The residual pellet was extracted and analyzed using gas chromatography coupled with mass spectrometry. Method detection limits ranged from 11 to 125 ng/g dry weight. The described method is suitable for p,p'-DDE, PCBs-138, 153, 180, and 187, and PBDEs-47 and 100; other POPs were below the limit of detection. We applied this method to 126 scat samples collected from Southern Resident killer whales. Scat samples from 22 adult whales also had known POP concentrations in blubber and demonstrated significant correlations (p < 0.01) between matrices across target analytes. Overall, the scat toxicant measures matched previously reported patterns from blubber samples of decreased levels in reproductive-age females and a decreased p,p'-DDE/∑PCB ratio in J-pod. Measuring toxicants in scat samples provides an unprecedented opportunity to noninvasively evaluate contaminant levels in wild cetacean populations; these data have the prospect to provide meaningful information for vital management decisions.

Susceptibility to quantum dot induced lung inflammation differs widely among the Collaborative Cross founder mouse strains.

Quantum dots (QDs) are engineered semiconductor nanoparticles with unique physicochemical properties that make them potentially useful in clinical, research and industrial settings. However, a growing body of evidence indicates that like other engineered nanomaterials, QDs have the potential to be respiratory hazards, especially in the context of the manufacture of QDs and products containing them, as well as exposures to consumers using these products. The overall goal of this study was to investigate the role of mouse strain in determining susceptibility to QD-induced pulmonary inflammation and toxicity. Male mice from 8 genetically diverse inbred strains (the Collaborative Cross founder strains) were exposed to CdSe-ZnS core-shell QDs stabilized with an amphiphilic polymer. QD treatment resulted in significant increases in the percentage of neutrophils and levels of cytokines present in bronchoalveolar lavage fluid (BALF) obtained from NOD/ShiLtJ and NZO/HlLtJ mice relative to their saline (Sal) treated controls. Cadmium measurements in lung tissue indicated strain-dependent differences in disposition of QDs in the lung. Total glutathione levels in lung tissue were significantly correlated with percent neutrophils in BALF as well as with lung tissue Cd levels. Our findings indicate that QD-induced acute lung inflammation is mouse strain dependent, that it is heritable, and that the choice of mouse strain is an important consideration in planning QD toxicity studies. These data also suggest that formal genetic analyses using additional strains or recombinant inbred strains from these mice could be useful for discovering potential QD-induced inflammation susceptibility loci.

Ex vivo magnetic resonance imaging in South African manganese mine workers.

BACKGROUND: Manganese (Mn) exposure is associated with increased T1-weighted magnetic resonance imaging (MRI) signal in the basal ganglia. T1 signal intensity has been correlated with occupational Mn exposure but not with clinical symptomatology or neuropathology. OBJECTIVES: This study investigated predictors of ex vivo T1 MRI basal ganglia signal intensity in neuropathologic tissue obtained from deceased South African mine workers. METHODS: A 3.0 T MRI was performed on ex vivo brain tissue obtained from 19 Mn mine workers and 10 race- and sex-matched mine workers of other commodities. Basal ganglia regions of interest were identified for each subject with T1-weighted intensity indices generated for each region. In a pathology subset, regional T1 indices were compared to neuronal and glial cell density and tissue metal concentrations. RESULTS: Intensity indices were higher in Mn mine workers than non-Mn mine workers for the globus pallidus, caudate, anterior putamen, and posterior putamen with the highest values in subjects with the longest cumulative Mn exposure. Intensity indices were inversely correlated with the neuronal cell density in the caudate (p=0.040) and putamen (p=0.050). Tissue Mn concentrations were similar in Mn and non-Mn mine workers. Tissue iron (Fe) concentration trended lower across all regions in Mn mine workers. CONCLUSIONS: Mn mine workers demonstrated elevated basal ganglia T1 indices when compared to non-Mn mine workers. Predictors of ex vivo T1 MRI signal intensity in Mn mine workers include duration of Mn exposure and neuronal density.

Protection efficacy of gloves against components of the solvent in a sprayed isocyanate coating utilizing a reciprocating permeation panel.

OBJECTIVES: Determine protection effectiveness of 5-mil natural rubber latex (0.13-mm), 5-mil nitrile rubber (0.13-mm), and 13-mil butyl rubber (0.33-mm) glove materials against solvents present in a commonly used automotive clear coat formulation using a novel permeation panel. The latex and nitrile gloves were the type commonly used by local autobody spray painters. METHODS: Glove materials were tested by spraying an automotive clear coat onto an automated reciprocating permeation panel (permeation panel II). Temperature, relative humidity, and spray conditions were controlled to optimize clear coat loading homogeneity as evaluated by gravimetric analysis. Solvent permeation was measured using charcoal cloth analyzed by the National Institute for Occupational Safety and Health 1501 method. RESULTS: Natural rubber latex allowed 3-5 times the permeation of solvents relative to nitrile rubber for all 10 solvents evaluated: ethyl benzene, 2-heptanone, 1-methoxy-2-propyl acetate, o-xylene, m-xylene, p-xylene, n-butyl acetate, methyl isobutyl ketone, petroleum distillates, and toluene. There is a distinct behavior in solvent permeation before and after the coating dry time. Solvent permeation increased steadily before coating dry time and remained fairly constant after coating dry time. Butyl was not permeated by any of the solvents under the conditions tested. CONCLUSIONS: Commonly used 5-mil thick (0.13-mm) latex and nitrile gloves were ineffective barriers to solvents found in a commonly used clear coat formulation. Conversely, 13-mil (0.33-mm) butyl gloves were found to be protective against all solvents in the clear coat formulation.

Phthalates and diet: a review of the food monitoring and epidemiology data.

Phthalates are associated with a variety of health outcomes, but sources that may be targeted for exposure reduction messaging remain elusive. Diet is considered a significant exposure pathway for these compounds. Therefore, we sought to identify primary foods associated with increased exposure through a review of the food monitoring survey and epidemiological data. A search in PubMed and Google Scholar for keywords "phthalates" and "diet" "food" "food stuffs" "dietary intake" "food intake" and "food concentration" resulted in 17 studies measuring phthalate concentrations in United States (US) and international foods, three epidemiological association studies, and three interventions. We report on food groups with high (≥300 µg/kg) and low (<50 µg/kg) concentrations and compare these to foods associated with phthalate body burden. Based on these data, we estimated daily intakes of di-2-ethylhexyl phthalate (DEHP) of US women of reproductive age, adolescents and infants for typical consumption patterns as well as healthy and poor diets. We consistently observed high DEHP concentrations in poultry, cooking oils and cream-based dairy products (≥300 µg/kg) across food monitoring studies. Diethyl phthalate (DEP) levels were found at low concentrations across all food groups. In line with these data, epidemiological studies showed positive associations between consumption of meats, discretionary fat and dairy products and DEHP. In contrast to food monitoring data, DEP was found to be associated with intake of vegetables in two studies. DEHP exposure estimates based on typical diets were 5.7, 8.1, and 42.1 µg/kg-day for women of reproductive age, adolescents and infants, respectively, with dairy as the largest contributor to exposure. Diets high in meat and dairy consumption resulted in two-fold increases in exposure. Estimates for infants based on a typical diet exceeded the Environmental Protection Agency's reference dose of 20 µg/kg-day while diets high in dairy and meat consumed by adolescents also exceeded this threshold. The review of the literature demonstrated that DEHP in some meats, fats and dairy products is consistently found in high concentrations and can contribute to exposure. Guidance on future research in this area is provided that may help to identify methods to reduce dietary phthalate exposures.

Accuracy of prenatal smoking data from Washington State birth certificates in a population-based sample with cotinine measurements.

PURPOSE: To assess the accuracy of smoking data in contemporary U.S. birth certificates. METHODS: We compared data on prenatal smoking as reported on Washington State birth certificates to cotinine measured in archived newborn screening dried blood spots for 200 infants born in 2007 (100 randomly selected from births to self-reported nonsmokers and 100 born to self-reported smokers). We estimated the sensitivity of the birth certificate data to identify prenatal smokers and the precision with which self-identified third trimester smokers report smoking levels. RESULTS: Infants born to two (2%) mothers who reported they did not smoke during the pregnancy had whole blood cotinine concentrations consistent with active smoking by the mother (sensitivity 85%). Sensitivity of the birth certificate to identify reported smokers who continued to smoke throughout pregnancy was similar (89%). Among self-identified third trimester smokers whose infants' specimens were collected shortly after delivery, Spearman rho between infant cotinine and maternal-reported cigarettes/day in the third trimester was 0.54. CONCLUSIONS: Birth certificates may represent a viable option for assessing prenatal smoking status, and possibly smoking cessation and level among smokers, in epidemiologic studies sufficiently powered to overcome a moderate amount of exposure measurement error.

Testing of glove efficacy against sprayed isocyanate coatings utilizing a reciprocating permeation panel.

OBJECTIVES: Modify a permeation panel to evaluate dermal protective clothing for resistance to sprayed coatings with minimal variability in spray paint loading across the test panel. Determine isocyanate protection effectiveness of natural rubber latex (5 mil or 0.13mm), nitrile rubber (5 mil or 0.13mm), and butyl rubber (13 mil or 0.33mm) glove materials against a commonly used automotive clear coat formulation. The latex and nitrile gloves were the type used by the local autobody spray painters. METHODS: Glove materials were tested by spraying paint onto an automated reciprocating permeation panel (permeation panel II). Temperature, relative humidity, and spray conditions were controlled to optimize paint loading homogeneity as evaluated by gravimetric analysis. Isocyanate permeation was measured using 1-(2-pyridyl)-piperazine-coated fiber-glass filters analyzed by a modified version of the OSHA 42/PV2034 methods. RESULTS: Latex exhibited a higher permeation rate compared with nitrile for isocyanates (1,6-hexamethylene diisocyanate (HDI) and isophorone diisocyanate monomers) and both materials presented permeation at all of the time points suggesting a fast isocyanate breakthrough. Butyl material exhibited no permeation or breakthrough for isocyanates under the tested conditions. The spray application at 69±8°F was optimally homogeneous at 45±0.5mg weight of dry clear coat per 5cm(2). CONCLUSIONS: The permeation panel II is a reliable method to assess dermal protective clothing performance against polymerizing coatings. Commonly used 5-mil (0.13-mm) latex and nitrile gloves were determined to be ineffective barriers against the isocyanates found in a commonly used clear-coat formulation while butyl gloves were protective.

Occurrence of trivalent monomethyl arsenic and other urinary arsenic species in a highly exposed juvenile population in Bangladesh.

Following reports of high cytotoxicity and mutagenicity of monomethyl arsonous acid (MMA(III)) and early reports of urinary MMA(III) in arsenic-exposed individuals, MMA(III) has often been included in population studies. Use of urinary MMA(III) as an indicator of exposure and/or health risk is challenged by inconsistent results from field studies and stability studies, which indicate potential artifacts. We measured urinary arsenic species in children chronically exposed to arsenic in drinking water, using collection, storage, and analysis methods shown to conserve MMA(III). MMA(III) was easily oxidized in sample storage and processing, but recoveries of 80% or better in spiked urine samples were achieved. Attempts to preserve the distribution of MMA between trivalent and pentavalent forms using complexing agents were unsuccessful and MMA(III) spiked into treated urine samples actually showed lower stability than in untreated samples. In 643 urine samples from a highly exposed population from the Matlab district in Bangladesh stored for 3-6 months at ≤-70 °C, MMA(III) was detected in 41 samples, with an estimated median value of 0.3 µg/l, and levels of MMA(III) above 1 µg/l in only two samples. The low urinary concentrations in highly exposed individuals and known difficulties in preserving sample oxidation state indicate that urinary MMA(III) is not suitable for use as an epidemiological biomarker.

A sensitive LC-MS/MS method for measurement of organophosphorus pesticides and their oxygen analogs in air sampling matrices.

A rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed for determination of levels of the organophosphorus (OP) pesticides chlorpyrifos (CPF), azinphos methyl (AZM), and their oxygen analogs chlorpyrifos-oxon (CPF-O) and azinphos methyl-oxon (AZM-O) on common active air sampling matrices. XAD-2 resin and polyurethane foam (PUF) matrices were extracted with acetonitrile containing stable-isotope labeled internal standards (ISTD). Analysis was accomplished in Multiple Reaction Monitoring (MRM) mode, and analytes in unknown samples were identified by retention time (±0.1 min) and qualifier ratio (±30% absolute) as compared to the mean of calibrants. For all compounds, calibration linearity correlation coefficients were ≥0.996. Limits of detection (LOD) ranged from 0.15-1.1 ng/sample for CPF, CPF-O, AZM, and AZM-O on active sampling matrices. Spiked fortification recoveries were 78-113% from XAD-2 active air sampling tubes and 71-108% from PUF active air sampling tubes. Storage stability tests also yielded recoveries ranging from 74-94% after time periods ranging from 2-10 months. The results demonstrate that LC-MS/MS is a sensitive method for determining these compounds from two different matrices at the low concentrations that can result from spray drift and long range transport in non-target areas following agricultural applications. In an inter-laboratory comparison, the limit of quantification (LOQ) for LC-MS/MS was 100 times lower than a typical gas chromatography-mass spectrometry (GC-MS) method.

Phthalates and risk of endometriosis.

BACKGROUND: Phthalates are ubiquitous environmental chemicals with endocrine disruptive properties. The impact of these chemicals on endocrine-related disease in reproductive-age women is not well understood. OBJECTIVE: To investigate the relationship between urinary phthalate metabolite concentrations and the risk of a hormonally-driven disease, endometriosis, in reproductive-age women. METHODS: We used data from a population-based case-control study of endometriosis, conducted among female enrollees of a large healthcare system in the U.S. Pacific Northwest. We measured urinary phthalate metabolite concentrations on incident, surgically-confirmed cases (n=92) diagnosed between 1996 and 2001 and population-based controls (n=195). Odds ratios (OR), and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusting for urinary creatinine concentrations, age, and reference year. RESULTS: The majority of women in our study had detectable concentrations of phthalate metabolites. We observed a strong inverse association between urinary mono-(2-ethyl-5-hexyl) phthalate (MEHP) concentration and endometriosis risk, particularly when comparing the fourth and first MEHP quartiles (aOR 0.3, 95% CI: 0.1-0.7). Our data suggested an inverse association between endometriosis and urinary concentrations of other di-2-ethylhexyl phthalate (DEHP) metabolites (mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)) and ∑DEHP, however, the confidence intervals include the null. Our data also suggested increased endometriosis risk with greater urinary concentrations of mono-benzyl phthalate (MBzP) and mono-ethyl phthalate (MEP), although the associations were not statistically significant. CONCLUSIONS: Exposure to select phthalates is ubiquitous among female enrollees of a large healthcare system in the U.S. Pacific Northwest. The findings from our study suggest that phthalates may alter the risk of a hormonally-mediated disease among reproductive-age women.

The glutathione synthesis gene Gclm modulates amphiphilic polymer-coated CdSe/ZnS quantum dot-induced lung inflammation in mice.

Quantum dots (QDs) are unique semi-conductor fluorescent nanoparticles with potential uses in a variety of biomedical applications. However, concerns exist regarding their potential toxicity, specifically their capacity to induce oxidative stress and inflammation. In this study we synthesized CdSe/ZnS core/shell QDs with a tri-n-octylphosphine oxide, poly(maleic anhydride-alt-1-tetradecene) (TOPO-PMAT) coating and assessed their effects on lung inflammation in mice. Previously published in vitro data demonstrated these TOPO-PMAT QDs cause oxidative stress resulting in increased expression of antioxidant proteins, including heme oxygenase, and the glutathione (GSH) synthesis enzyme glutamate cysteine ligase (GCL). We therefore investigated the effects of these QDs in vivo in mice deficient in GSH synthesis (Gclm +/- and Gclm -/- mice). When mice were exposed via nasal instillation to a TOPO-PMAT QD dose of 6 µg cadmium (Cd) equivalents/kg body weight, neutrophil counts in bronchoalveolar lavage fluid (BALF) increased in both Gclm wild-type (+/+) and Gclm heterozygous (+/-) mice, whereas Gclm null (-/-) mice exhibited no such increase. Levels of the pro-inflammatory cytokines KC and TNFα increased in BALF from Gclm +/+ and +/- mice, but not from Gclm -/- mice. Analysis of lung Cd levels suggested that QDs were cleared more readily from the lungs of Gclm -/- mice. There was no change in matrix metalloproteinase (MMP) activity in any of the mice. However, there was a decrease in whole lung myeloperoxidase (MPO) content in Gclm -/- mice, regardless of treatment, relative to untreated Gclm +/+ mice. We conclude that in mice TOPO-PMAT QDs have in vivo pro-inflammatory properties, and the inflammatory response is dependent on GSH synthesis status. Because there is a common polymorphism in humans that influences GCLM expression, these findings imply that humans with reduced GSH synthesis capabilities may be more susceptible to the pro-inflammatory effects of QDs.

Unexpected results in a randomized dietary trial to reduce phthalate and bisphenol A exposures.

Diet is a primary source of exposure for high-molecular-weight phthalates and bisphenol A (BPA), but little is known about the efficacy of various interventions to reduce exposures. We conducted a randomized trial with 10 families to test the efficacy of a 5-day complete dietary replacement (Arm 1; n=21) versus written recommendations to reduce phthalate and BPA exposures (Arm 2; n=19). We measured phthalate and BPA concentrations in urine samples at baseline, intervention, and post-intervention periods. We used Wilcoxon paired signed-rank tests to assess change in concentrations across time and multi-level mixed effects regression models to assess differences between Arms 1 and 2. Urinary di(2-ethylhexyl) phthalate (DEHP) metabolite concentrations increased unexpectedly from a median of 283.7 nmol/g at baseline to 7027.5 nmol/g during the intervention (P<0.0001) among Arm 1 participants, and no significant changes were observed for Arm 2 participants. We observed a statistically significant increase in total BPA concentration between baseline and intervention periods in Arm 1 but no significant changes in Arm 2. Arm 1 food ingredient testing for DEHP revealed concentrations of 21,400 ng/g in ground coriander and 673 ng/g in milk. Food contamination with DEHP led to unexpected increases in urinary phthalate concentrations in a trial intended to minimize exposure. In the absence of regulation to reduce phthalate and BPA concentrations in food production, it may be difficult to develop effective interventions that are feasible in the general population. An estimate of DEHP daily intake for children in the dietary replacement Arm was above the US Environmental Protection Agency oral reference dose and the European Food Safety Authority's tolerable daily intake, suggesting that food contamination can be a major source of DEHP exposure.

Transport of a solvent mixture across two glove materials when applied in a paint matrix.

The transport of mixed paint solvents through natural rubber latex (4 mil) and nitrile rubber (5 mil) gloves was evaluated after spray application of the paint formulation directly on the glove surface. Glove materials and thicknesses were those selected by the majority of spray painters in the local automobile repair industry. A flat panel containing glove specimens mounted in multiple permeation cells permitted evaporation of solvents from the applied paint and incorporated a solid sorbent receiving medium for measuring glove membrane transport. The panel was sprayed in a paint booth to simulate use conditions. Charcoal cloth under the glove adsorbed transported solvents, which were quantified by gas chromatography. For each solvent component, results were expressed as mass transported through the glove relative to the mass applied, per unit area, during 30 min after spray application. The paint formulation contained ketones, acetates, and aromatics. Natural rubber latex allowed 6-10 times the transport of solvents relative to nitrile rubber for all eight solvent components: methyl ethyl ketone, toluene, styrene, ethyl benzene, xylene isomers, and 2-heptanone. m-Xylene showed the largest difference in transport between the two glove materials. This solvent also had the highest transport for each material. The results indicate that nitrile rubber gloves offer somewhat greater chemical resistance to all eight solvents studied compared with natural rubber latex gloves, regardless of the chemical properties of the individual solvent components. However, it must be emphasized that neither of the glove materials, in the thicknesses used in this study, provide adequate protection when exposed by direct spray painting. Simulation of realistic spray conditions may offer a source of useful information on the performance of chemical protective gloves because it accounts for solvent evaporation and the effect of paint polymerization after application on glove transport.

Short term serum pharmacokinetics of diammine silver fluoride after oral application.

BACKGROUND: There is growing interest in the use of diammine silver fluoride (DSF) as a topical agent to treat dentin hypersensitivity and dental caries as gauged by increasing published research from many parts of the world. While DSF has been available in various formulations for many years, most of its pharmacokinetic aspects within the therapeutic concentration range have never been fully characterized. METHODS: This preliminary study determined the applied doses (3 teeth treated), maximum serum concentrations, and time to maximum serum concentration for fluoride and silver in 6 adults over 4 h. Fluoride was determined using the indirect diffusion method with a fluoride selective electrode, and silver was determined using inductively coupled plasma-mass spectrometry. The mean amount of DSF solution applied to the 3 teeth was 7.57 mg (6.04 µL). RESULTS: Over the 4 hour observation period, the mean maximum serum concentrations were 1.86 µmol/L for fluoride and 206 nmol/L for silver. These maximums were reached 3.0 h and 2.5 h for fluoride and silver, respectively. CONCLUSIONS: Fluoride exposure was below the U.S. Environmental Protection Agency (EPA) oral reference dose. Silver exposure exceeded the EPA oral reference dose for cumulative daily exposure over a lifetime, but for occasional use was well below concentrations associated with toxicity. This preliminary study suggests that serum concentrations of fluoride and silver after topical application of DSF should pose little toxicity risk when used in adults. CLINICAL TRIALS REGISTRATION: NCT01664871.

Development of a permeation panel to test dermal protective clothing against sprayed coatings.

OBJECTIVES: Design, construct, and characterize an apparatus to evaluate dermal protective clothing for resistance to polymerizing materials. Specifically, we evaluated the permeation of the most common glove material used in automotive collision repair (0.10-0.13 mm or 4-5 mil latex) with representative isocyanate-containing clear coats. Our ultimate goal is to make informed recommendations on dermal protective materials to prevent isocyanate exposures and reduce the likelihood of occupational illness in automotive collision repair and other industries. METHODS: A novel permeation panel was developed to assess dermal protective clothing. With this apparatus, up to eight test materials may be evaluated under typical-spray application conditions. Solid collection media comprised of 1-(2-pyridyl)-piperazine (2-PP)-coated fiberglass filters or colorimetric SWYPE™ pads were placed behind test materials to capture permeants. The 2-PP-coated filters were subsequently analyzed using a modified OSHA42/PV2034 method. Color change in the SWYPEs provided an immediate field estimate of breakthrough time. In addition, Teflon filters were mounted proximal to the permeation cells to measure the mass of clear coat applied to the panel and to evaluate loading homogeneity. This study evaluated the permeation of isocyanates through 0.10-0.13 mm latex glove material at a fixed time (30 min post-spraying) and over a time course (6-91 min post-spraying). RESULTS: Monomers 1,6-hexamethylene diisocyanate (HDI) and isophorone diisocyanate (IPDI) permeated through (0.10-0.13 mm) latex glove material under typical glove use conditions (30 min). The latex glove material exhibited immediate breakthrough, with a permeation rate of 2.9 ng min(-1) cm(-2). The oligomeric forms of HDI and IPDI did not permeate the latex glove material. The spray application at 71 ± 5 °F was fairly homogeneous (33.7 ± 8 mg weight of dry clear coat per 5 cm(2)). CONCLUSIONS: The permeation panel is a viable method to assess dermal protective clothing performance against polymerizing materials. Thin (0.10-0.13 mm) latex gloves were determined to be ineffective barriers to the isocyanates commonly found in clear coats. Because this type of glove is used frequently in auto body shops, the potential for isocyanate exposure is of concern. Permeation tests with other dermal protective clothing materials and other clear coat formulations are needed to make recommendations about alternative materials.

Relation of whole blood carboxyhemoglobin concentration to ambient carbon monoxide exposure estimated using regression.

Exposure to carbon monoxide (CO) and other ambient air pollutants is associated with adverse pregnancy outcomes. While there are several methods of estimating CO exposure, few have been evaluated against exposure biomarkers. The authors examined the relation between estimated CO exposure and blood carboxyhemoglobin concentration in 708 pregnant western Washington State women (1996-2004). Carboxyhemoglobin was measured in whole blood drawn around 13 weeks' gestation. CO exposure during the month of blood draw was estimated using a regression model containing predictor terms for year, month, street and population densities, and distance to the nearest major road. Year and month were the strongest predictors. Carboxyhemoglobin level was correlated with estimated CO exposure (rho = 0.22, 95% confidence interval (CI): 0.15, 0.29). After adjustment for covariates, each 10% increase in estimated exposure was associated with a 1.12% increase in median carboxyhemoglobin level (95% CI: 0.54, 1.69). This association remained after exclusion of 286 women who reported smoking or being exposed to secondhand smoke (rho = 0.24). In this subgroup, the median carboxyhemoglobin concentration increased 1.29% (95% CI: 0.67, 1.91) for each 10% increase in CO exposure. Monthly estimated CO exposure was moderately correlated with an exposure biomarker. These results support the validity of this regression model for estimating ambient CO exposures in this population and geographic setting.