Model for Screening-Level Assessment of Near-Field Human Exposure to Neutral Organic Chemicals Released Indoors

Screening organic chemicals for hazard and risk to human health requires near-field human exposure models that can be readily parametrized with available data. The integration of a model of human exposure, uptake, and bioaccumulation into an indoor mass balance model provides a quantitative framework linking emissions in indoor environments with human intake rates (<i>iR</i>s), intake fractions (<i>iF</i>s) and steady-state concentrations in humans (<i>C</i>) through consideration of dermal permeation, inhalation, and nondietary ingestion exposure pathways. Parameterized based on representative indoor and adult human characteristics, the model is applied here to 40 chemicals of relevance in the context of human exposure assessment. Intake fractions and human concentrations (<i>C</i>_U) calculated with the model based on a unit emission rate to air for these 40 chemicals span 2 and 5 orders of magnitude, respectively. Differences in priority ranking based on either <i>iF</i> or <i>C</i>_U can be attributed to the absorption, biotransformation and elimination processes within the human body. The model is further applied to a large data set of hypothetical chemicals representative of many in-use chemicals to show how the dominant exposure pathways, <i>iF</i> and <i>C</i>_U change as a function of chemical properties and to illustrate the capacity of the model for high-throughput screening. These simulations provide hypotheses for the combination of chemical properties that may result in high exposure and internal dose. The model is further exploited to highlight the role human contaminant uptake plays in the overall fate of certain chemicals indoors and consequently human exposure

Persistent Organohalogens in Paired Fish Fillet and Eggs: Implications for Fish Consumption Advisories

Fish consumption is associated with both health benefits from high-quality proteins, minerals, vitamins, and fatty acids and risks from contaminants in fish. Fish consumption advisories are issued by many government agencies to keep exposure to contaminants at a safe level. Such advisories are typically based on fillets and neglect consumption of other fish parts such as eggs by certain subpopulations. To evaluate potential for dietary exposure to toxic organic chemicals via fish eggs, we analyzed polybrominated diphenyl ethers (PBDEs), polychlorinated naphthalenes (PCNs), dioxin-like polychlorinated biphenyls (dlPCBs), and polychlorinated dibenzodioxins/furans (PCDD/Fs) in paired fillet and eggs of fish from a tributary to Lake Ontario, one of the North American Great Lakes. All wet weight based concentrations in fish eggs were statistically higher than in the paired fillet samples. In fish eggs, concentrations of Σ₁₄PBDEs, Σ₁₄PCNs, and Σ₁₂dlPCBs were 41–118, 0.3–1.7, and 30–128 ng/g wet weight (ww), respectively; Σ₃PCDD/Fs and total (dlPCB+ PCDD/Fs) toxic equivalents (TEQs) were 4–22 and 9–54 pg/g ww, respectively. In fillet samples, Σ₁₄PBDEs, Σ₁₄PCNs, and Σ₁₂dlPCBs were 4–116, 0.05–0.66, and 6–85 ng/g, respectively; Σ₃PCDD/Fs and TEQs were 2–10 and 3.4–31 pg/g ww, respectively. In contrast, the fillets had higher lipid normalized concentrations than the paired egg samples, suggesting that these chemicals did not reach equilibrium between the fillets and eggs. Accordingly, measured concentrations in eggs or empirical relationship with fillet rather than prediction from equilibrium partitioning model should be used to evaluate contaminant exposure via consumption of fish eggs. For fatty fish from the lower Great Lakes area, we suggest one fillet meal be reduced from the advised fish consumption frequency for consumptions of 207 ± 37, 39 ± 2, 105 ± 51, and 119 ± 9 g fish eggs of brown trout, Chinook salmon, Coho salmon, and rainbow trout, respectively

Cross-talk between Carboxypeptidase M and the Kinin B1 Receptor Mediates a New Mode of G Protein-coupled Receptor Signaling

G protein-coupled receptor (GPCR) signaling is affected by formation of GPCR homo-or heterodimers, but GPCR regulation by other cell surface proteins is not well understood. We reported that the kinin B1 receptor (B1R) heterodimerizes with membrane carboxypeptidase M (CPM), facilitating receptor signaling via CPM-mediated conversion of bradykinin or kallidin to des-Arg kinin B1R agonists. Here, we found that a catalytically inactive CPM mutant that still binds substrate (CPM-E264Q) also facilitates efficient B1R signaling by B2 receptor agonists bradykinin or kallidin. This response required co-expression of B1R and CPM-E264Q in the same cell, was disrupted by antibody that dissociates CPM from B1R, and was not found with a CPM-E264Q-B1R fusion protein. An additional mutation that reduced the affinity of CPM for C-terminal Arg and increased the affinity for C-terminal Lys inhibited the B1R response to bradykinin (with C-terminal Arg) but generated a response to Lys(9)-bradykinin. CPM-E264Q-mediated activation of B1Rs by bradykinin resulted in increased intramolecular fluorescence resonance energy transfer (FRET) in a B1R FRET construct, similar to that generated directly by a B1R agonist. In cytokine-treated human lung microvascular endothelial cells, disruption of B1R-CPM heterodimers inhibited B1R-dependent NO production stimulated by bradykinin and blocked the increased endothelial permeability caused by treatment with bradykinin and pyrogallol (a superoxide generator). Thus, CPM and B1Rs on cell membranes form a critical complex that potentiates B1R signaling. Kinin peptide binding to CPM causes a conformational change in the B1R leading to intracellular signaling and reveals a new mode of GPCR activation by a cell surface peptidase

Semivolatile Organic Contaminants in the Hawaiian Atmosphere

An air sampling campaign on the Island of Hawaii aimed to assess background concentrations of semivolatile organic compounds (SVOCs) over the Central Northern Pacific and to explore their distribution along an altitudinal transect. XAD-resin-based passive air samplers were deployed from May to September 2011 at six sites along a transect from the northeastern coast to the Mauna Loa Observatory and at three other island sites. By crossing the trade wind inversion, the transect comprised the marine boundary layer and free troposphere. At the two ends of the transect, flow-through samplers simultaneously sampled air at monthly resolution. Elevated levels of dieldrin, chlordane- and DDT-related pesticides, polycyclic aromatic hydrocarbons (PAHs), and polybrominated diphenyl ethers (PBDEs) at two urban sites indicated contributions from local sources. The composition of chlordane and DDT-related residues indicated recent emissions. PAHs concentrations that decline more rapidly with increasing elevation than those for PBDEs are consistent with faster atmospheric degradation of PAHs. SVOC levels on Mauna Loa were generally at the lower end of concentration ranges reported for remote sites, including the Arctic. However, in contrast to the Arctic, long-range atmospheric transport is deemed less important than human-induced material flow as the source of SVOCs to the island’s atmosphere

Carboxypeptidase M augments kinin B1 receptor signaling by conformational crosstalk and enhances endothelial nitric oxide output

The G protein-coupled receptors (GPCRs) are the largest class of membrane proteins that play key roles in transducing extracellular signals to intracellular proteins to generate cellular responses. The kinin GPCRs, named B1 (B1R) and B2 (B2R), are responsible for mediating the biological responses to kinin peptides released from the precursor kininogens. Bradykinin (BK) or kallidin (KD) are agonists for B2Rs, whereas their carboxypeptidase (CP)-generated metabolites, des-Arg(9)-BK or des-Arg(10)-KD, are specific agonists for B1Rs. Here, we review the evidence for a critical role of membrane-bound CPM in facilitating B1R signaling by its ability to directly activate the receptor via conformational crosstalk as well as generate its specific agonist. In endothelial cells, the CPM/B1R interaction facilitates B1R-dependent high-output nitric oxide under inflammatory conditions

Calibration and Application of a Passive Air Sampler (XAD-PAS) for Volatile Methyl Siloxanes

Because the atmosphere is key to understanding the environmental behavior of volatile methyl siloxanes (VMS), a variety of reliable air sampling methods are needed. The purpose of this study was to calibrate and evaluate an existing, polystyrene–divinylbenzene copolymeric resin-based passive air sampler (XAD-PAS) for VMS. Sixteen XAD-PAS were deployed for 7–98 days at a suburban site in Toronto, Canada, while the VMS concentration in air was monitored by an active sampling method. This calibration and a subsequent field test further allowed for investigation of the temporal and spatial variability of VMS in the region. Uptake in the XAD-PAS of octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and three linear VMS was linear throughout the whole deployment period. Sampling rates were between 0.4 and 0.5 m³/day. The XAD-PAS measured ∑VMS concentrations ranged from nondetects in rural areas (<i>n</i> = 3), to 169 ± 49 ng/m³ in the urban region (<i>n</i> = 21), to levels above 600 ng/m³ at sewage treatment plants (<i>n</i> = 2). Levels and composition of VMS within the urban area were remarkably uniform in space. Levels, but not composition, were highly variable in time and weakly correlated with temperature, wind speed, and wind direction

Representative respiratory tracings.

<p>Representative respiratory tracings of airway pressure(Paw), esophageal pressure (Pes), intragastric pressure (Pgas),transpumonary pressure (PL),Airflow、abdominal muscles surface electromyography (EMGab)and diaphragmatic esophageal surface electromyography (EMGdi) in BIPAP_SB,BIPAP_AP group in representative animals. BIPAP_SB = biphasic positive airway pressure with SB; BIPAP_AP = biphasic positive airway pressure with abdominal muscles paralysis.</p

Chitosan/Phytic Acid Polyelectrolyte Complex: A Green and Renewable Intumescent Flame Retardant System for Ethylene–Vinyl Acetate Copolymer

We describe the preparation and characterization of a green and renewable polyelectrolyte complex (PEC) containing phosphorus, nitrogen and carbon elements, based on the ionic complexation between chitosan and phytic acid. Introduction of this PEC to ethylene–vinyl acetate copolymer (EVA) leads to an improvement of the flame retardancy. As for the EVA/PEC composites with 20.0 wt % of PEC (EVA/20PEC), the char residue at 600 °C is 12 wt % higher than that of the pristine EVA under nitrogen atmosphere. Compared to the pristine EVA, the peak heat release rate and total heat release of EVA/20PEC show 249 W g^–1 and 5.6 kJ g^–1 decreases, respectively. The char residue of EVA/20PEC is full and compact, demonstrating excellent intumescent effect. Introduction of this PEC also contributes to a slight increase of the Young’s modulus while maintains the excellent ductility. This work provides a new approach for the development of environmentally friendly intumescent flame retardant system

Histopathological examination.

<p>Representative appearances and photomicrographs of hematoxylineosin–stained lung sections (magnification ×200) from control group (A, n = 6), BIPAP_SB = biphasic positive airway pressure with SB (B, n = 6), and BIPAP_AP = biphasic positive airway pressure with abdominal muscles paralysis (C, n = 6).The control group had minimal alveolar congestion, and inflammatory cell infiltration. The BIPAP_AP group showed mild thickening of the alveolar walls, alveolar congestion, and hemorrhage. In the BIPAP_SB group, inflammatory cell infiltration, thickening of the alveolar walls, alveolar congestion, and more prominent hemorrhagic areas were observed.</p

Time course of the EELV.

<p>Time course of the end- expiratory lung volume (EELV) in experimental groups (n = 6 per group). BIPAP_SB = biphasic positive airway pressure with SB; BIPAP_AP = biphasic positive airway pressure with abdominal muscles paralysis; SB = spontaneous breathing; *P < 0.05, vs. other groups.</p