Modeling of Human Exposure to In-Vehicle PM2.5 from Environmental Tobacco Smoke

Environmental tobacco smoke (ETS) is estimated to be a significant contributor to in-vehicle human exposure to fine particulate matter of 2.5 μm or smaller (PM_2.5). A critical assessment was conducted of a mass balance model for estimating PM_2.5 concentration with smoking in a motor vehicle. Recommendations for the range of inputs to the mass-balance model are given based on literature review. Sensitivity analysis was used to determine which inputs should be prioritized for data collection. Air exchange rate (ACH) and the deposition rate have wider relative ranges of variation than other inputs, representing inter-individual variability in operations, and inter-vehicle variability in performance, respectively. Cigarette smoking and emission rates and vehicle interior volume are also key inputs. The in-vehicle ETS mass balance model was incorporated into the Stochastic Human Exposure and Dose Simulation for Particulate Matter (SHEDS-PM) model to quantify the potential magnitude and variability of in-vehicle exposures to ETS. The in-vehicle exposure also takes into account near-road incremental PM_2.5 concentration from on-road emissions. Results of probabilistic study indicate that ETS is a key contributor to the in-vehicle average and high-end exposure. Factors that mitigate in-vehicle ambient PM_2.5 exposure lead to higher in-vehicle ETS exposure, and vice versa.     

A Conceptual Framework for the Interpretation of Biological Markers for Environmental Exposure Assessment

Human exposure to environmental contaminants occurs via air, water, soil, dust, food, and other environmental media. Given this multitude of sources, environmental exposure assessment is moving away from single route exposure assessment to more integrated measures of exposure. Biological markers are frequently advocated as appropriate exposure assessment tools since they provide a measure of internal dose integrated over all routes of exposure. However, contributing sources may be difficult to identify through use of biological markers, and thus, have had limited utility in the regulatory community. To explore the different perspectives on the use and application of biological markers for exposure assessors, epidemiologists, and regulatory personnel, we have developed a biological marker conceptual framework. This framework is developed as a paradigm for the interpretation of biological markers for environmental exposure assessment linking the exposure assessment and the health effects assessment perspectives regarding biological markers. Further, it incorporates issues of source-specific exposures, aggregate exposure assessment, route-specific contributions, and biological variation in response to exposure. This structure provides an approach to explore the current constraints in using biological markers to evaluate source-specific exposures. This framework is discussed in the context of currently available biological markers for lead, carbon monoxide, and toluene. Biological markers represent a complex tool to assess human exposures to environmental contaminants; the biological marker framework presents a structure for their interpretation recognizing that many of the determinants of exposure, bioavailablity, and toxicokinetics are still being evaluated. The conceptual framework presented here provides another tool for the researcher in assessing the utility of biological markers in exposure assessment and epidemiology.     

Further Comparisons of Empirical and Epidemiological Data with Predictions of the Integrated Exposure Uptake Biokinetic Model for Lead in Children

Observed blood lead levels for young children from several communities are compared with blood lead levels predicted for those communities using the USEPA's Integrated Exposure Uptake Biokinetic (IEUBK) Model. In contrast to the compari sons described elsewhere, the blood lead levels observed in the communities con sidered here are not well represented by the model's predictions. The model's predictions for Midvale, UT; Sandy, UT; Cincinnati, OH; and a recent data set for Palmerton, PA, show considerable deviation from observation both for the geometric mean blood lead level and the percent of blood lead levels above 10?µg/dL. Various adjustments in the model to consider play area soils, site specific geometric standard deviations and the time children spend away from their homes do not substantially improve the comparisons to observation. It is difficult to predict a priori the data sets for which the model will yield adequate predictions. This reduces the value of the model for use in communities where blood lead measurements have not been made, and suggests that caution should be exercised when using the model to set soil lead cleanup levels or to predict the result of remediation.     

Protective Role of Genetic Variants in HSP90 Genes-Complex in COPD Secondary to Biomass-Burning Smoke Exposure and Non-Severe COPD Forms in Tobacco Smoking Subjects

Background: Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory disease characterized by airflow obstruction, commonly present in smokers and subjects exposed to noxious particles product of biomass-burning smoke (BBS). Several association studies have identified single-nucleotide polymorphisms (SNP) in coding genes related to the heat shock proteins family-genes that codify the heat shock proteins (Hsp). Hsp accomplishes critical roles in regulating immune response, antigen-processing, eliminating protein aggregates and co-activating receptors. The presence of SNPs in these genes can lead to alterations in immune responses. We aimed to evaluate the association of SNPs in the HSP90 gene complex and COPD. Methods: We enrolled 1549 participants, divided into two comparison groups; 919 tobacco-smoking subjects (cases COPD-TS n = 294 and, controls SWOC n = 625) and 630 chronic exposed to BBS (cases COPD-BBS n = 186 and controls BBES n = 444). We genotyped 2 SNPs: the rs13296 in HSP90AB1 and rs2070908 in HSP90B1. Results: Through the dominant model (GC + CC), the rs2070908 is associated with decreased risk (p < 0.01, OR = 0.6) to suffer COPD among chronic exposed BBS subjects. We found an association between rs13296 GG genotype and lower risk (p = 0.01, OR = 0.22) to suffer severe COPD-TS forms in the severity analysis. Conclusions: single-nucleotide variants in the HSP90AB1 and HSP90B1 genes are associated with decreased COPD risk in subjects exposed to BBS and the most severe forms of COPD in tobacco-smoking subjects.     

Coastal Vibrios: Identifying Relationships between Environmental Condition and Human Disease

Vibrio spp. cause frank and opportunistic infections of humans through exposure to seafood and seawater. Due to their natural occurrence in coastal environments, traditional indicator organisms, such as E. coli, do not predict their presence. This problem has complicated public health initiatives aimed at reducing the impact of illnesses from Vibrio spp. In the U.S., V. vulnificus has received extensive study due to the severity of its disease in humans. Its numbers increase with warmer summer temperature, and decline to nondetectable levels in colder winter months. In environments with salinities greater than 20 ppt, V. vulnificus numbers decline to levels that do not pose human health risks. A similar response to temperature has been observed for pathogenic strains of V. parahaemolyticus, where recent outbreaks of illness have been associated with El Niño weather conditions. In addition, temperature-induced plankton blooms have been linked to epidemic cholera in certain geographical regions of the world. New research shows that seawater temperature and salinity can be used to develop mathematical models of V. vulnificus incidence in coastal environments. Similar efforts might be extended to other Vibrio spp. to develop indicators that predict human health risk, as well as ecosystem integrity.     

Invertebrate Models of Kallmann Syndrome: Molecular Pathogenesis and New Disease Genes

Kallmann Syndrome is a heritable disorder characterized by congenital anosmia, hypogonadotropic hypogonadism and, less frequently, by other symptoms. The X-linked form of this syndrome is caused by mutations affecting the KAL1 gene that codes for the extracellular protein anosmin-1. Investigation of KAL1 function in mice has been hampered by the fact that the murine ortholog has not been identified. Thus studies performed in other animal models have contributed significantly to an understanding of the function of KAL1. In this review, the main results obtained using the two invertebrate models, the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster, are illustrated and the contribution provided by them to the elucidation of the molecular pathogenesis of Kallmann Syndrome is discussed in detail. Structure-function dissection studies performed in these two animal models have shown how the different domains of anosmin-1 carry out specific functions, also suggesting a novel intramolecular regulation mechanism among the different domains of the protein. The model that emerges is one in which anosmin-1 plays different roles in different tissues, interacting with different components of the extracellular matrix. We also describe how the genetic approach in C. elegans has allowed the discovery of the genes involved in KAL1-heparan sulfate proteoglycans interactions and the identification of HS6ST1 as a new disease gene.     

Exposure to lead increases the risk of meningioma and brain cancer: A meta-analysis

ObjectiveTo analyze the relationship between environmental lead exposure and various types of brain tumors.MethodsSearch databases PubMed, Web of Science, Embase and Chinese National Knowledge Infrastructure (CNKI) as of July 1, 2019. Stata 15.0 software was used for analysis.ResultsIn the case control, lead exposure was associated with gliomas and meningiomas 0.82 (95 % CI: 0.69, 0.95) and 1.06 (95 % CI: 0.65, 1.46). In the cohort study, lead exposure was associated with brain cancer and meningiomas 1.07 (95 % CI: 0.95, 1.19) and 1.06 (95 % CI: 0.94, 1.17). The risk of childhood brain tumors associated with parental lead exposure was 1.17 (95 % CI: 0.99, 1.34).ConclusionsLead may be a risk factor for meningiomas and brain cancers. However, the glioma results suggest that lead may be a protective factor, which needs to be further studied.     

Focus: Sex and Gender Health: Tobacco Smoking and the Resting Maternal Brain: A Preliminary Study of Frontal EEG

Tobacco smoking has been attributed to a wide range of detrimental health consequences for both women and their children. In addition to its known physical health effects, smoking may also impact maternal neural responses and subsequent caregiving behavior. To begin investigating this issue, we employed electroencephalography (EEG) to examine resting neural oscillations of tobacco-smoking mothers (n = 35) and non-smoking mothers (n = 35). We examined seven EEG frequency bands recorded from frontal electrode sites (delta, theta, alpha, alpha₁, alpha₂, beta, and gamma). While no between-group differences were present in high-frequency bands (alpha₂, beta, gamma), smokers showed greater spectral power in low-frequency bands (delta, theta, alpha, alpha₁) compared to non-smokers. This increased power in low-frequency bands of tobacco-smoking mothers is consistent with a less aroused state and may be one mechanism through which smoking might affect the maternal brain and caregiving behavior.     

Evaluation of Three Measures of Exposure Concentration: A Case Study of Surface Sediment Concentrations in the Passaic River

Arithmetic and lognormal means historically have been used as estimates of exposure concentration for both human health and ecological risk assessment. Past risk assessment guidance has emphasized the need to include all available informa tion, particularly regarding the spatial and temporal aspects of data and exposure. One estimate of exposure concentration that includes spatial information is the 95% upper confidence limit (UCL) of the area weighted mean. An area weighted mean is calculated using weightings based on the ratio of the area associated with a sample location and the total area of the study area. Currently, U.S. Environmental Protection Agency (USEPA) risk assessment guidance recommends the use of the 95% UCL of the arithmetic mean as the most appropriate measure of exposure concentration for soil and sediment in human health and ecological risk assess ments. The purpose of this study was two fold: (1) to evaluate the use of the 95% UCL of the area weighted mean vs. the 95% UCL of the arithmetic mean for the lognormal distribution and the normal distribution using a large data set from a recent riverine sediment characterization study, and (2) to evaluate the potential associated with the different approaches for reduction in surface sediment exposure concentrations for 2,3,7,8 TCDD and coplanar polychlorinated biphenyls (PCBs) for several subsets of the data. The results of this evaluation indicated that there was no significant reduction in exposure concentrations of the study area surface sediments after any of the selected higher concentration data points had been removed from the various data subsets. In addition, this evaluation indicated that, due to its dependence on the variance of the data, the 95% UCL of the arithmetic mean for a lognormal distribution produced subset exposure concentrations that were higher than the calculated concentrations of the full data set and produced the smallest percent changes in concentration compared to the other two measures. Based on this analysis, the 95% UCL of the area weighted mean was determined to be the most stable and appropriate estimator of exposure concentration for surface sediments.     

Modeling Human Exposure to Phthalate Esters: A Comparison of Indirect and Biomonitoring Estimation Methods

Humans are potentially exposed to phthalate esters (PEs) through ingestion, inhalation, and dermal contact. Studies quantifying exposure to PEs include “biomarker studies” and “indirect studies.” Biomarker studies use measurements of PE metabolites in urine to back-calculate exposure to the parent diester, while indirect studies use the concentration of the PE in each medium of exposure and the rate of intake of that medium to quantify intake of the PE. In this review, exposure estimates from biomarker and indirect studies are compiled and compared for seven PEs to determine if there are regional differences and if there is a preferred approach. The indirect and biomarker methods generally agree with each other within an order of magnitude and discrepancies are explained by difficulties in accounting for use of consumer products, uncertainty concerning absorption, regional differences, and temporal changes. No single method is preferred for estimating intake of all PEs; it is suggested that biomarker estimates be used for low molecular weight PEs for which it is difficult to quantify all sources of exposure and either indirect or biomarker methods be used for higher molecular weight PEs. The indirect methods are useful in identifying sources of exposure while the biomarker methods quantify exposure.     

Acetyl-coenzyme A synthase: the case for a Ni<Subscript>p</Subscript><Superscript>0</Superscript>-based mechanism of catalysis

Acetyl-CoA synthase (also known as carbon monoxide dehydrogenase) is a bifunctional Ni-Fe-S-containing enzyme that catalyzes the reversible reduction of CO₂ to CO and the synthesis of acetyl-coenzyme A from CO, CoA, and a methyl group donated by a corrinoid iron-sulfur protein. The active site for the latter reaction, called the A-cluster, consists of an Fe₄S₄ cubane bridged to the proximal Ni site (Ni_p), which is bridged in turn to the so-called distal Ni site. In this review, evidence is presented that Ni_p achieves a zero-valent state at low potentials and during catalysis. Ni_p appears to be the metal to which CO and methyl groups bind and then react to form an acetyl-Ni_p intermediate. Methyl group binding requires reductive activation, where two electrons reduce some site on the A-cluster. The coordination environment of the distal Ni suggests that it could not be stabilized in redox states lower than 2+. The rate at which the [Fe₄S₄]²⁺ cubane is reduced is far slower than that at which reductive activation occurs, suggesting that the cubane is not the site of reduction. An intriguing possibility is that Ni_p²⁺ might be reduced to the zero-valent state. Reinforcing this idea are Ni-organometallic complexes in which the Ni exhibits analogous reactivity properties when reduced to the zero-valent state. A zero-valent Ni stabilized exclusively with biological ligands would be remarkable and unprecedented in biology.Electronic Supplementary Material Supplementary Material is available in the online version of this article at     

Collection and Dissemination of Exposure Data Throughout the Chemical Value Chain: A Case Study from a Global Consumer Product Industry

The human and environmental safety of chemicals in formulated consumer products has for decades been important for product manufacturers and ingredient suppliers. However, prior to the mid-1990s, the underlying product safety data were largely not publicly available. The U.S. Environmental Protection Agency's Chemical Right-to-Know Program and a related program of the Organization of Economic Cooperation and Development have since been the catalysts for the broad dissemination of standardized hazard datasets for thousands of high production volume (HPV) chemicals in commerce around the globe. The formulated consumer products industry took the additional step of developing and summarizing the science around exposure to their products, largely cleaning products and personal care products, in order to be able to characterize and communicate the safety of their products. Perhaps even more significant was the collection and circulation of information surrounding the habits and practices of product use, and ingredient concentrations in products. The objective of this article is to detail the methods used for collection of this information by the American Cleaning Institute (ACI), and the process by which hazard and exposure information may be used in screening-level risk assessments. These data and methods appear in a number of ACI's publications (http://www.aciscience.org).     

Variable forms of soluble guanylyl cyclase: protein-ligand interactions and the issue of activation by carbon monoxide

1 , the resting Fe(II) state is mainly 6-coordinate and low-spin, and the CO adduct has vibrational frequencies characteristic of a histidine-heme-CO complex in a hydrophobic environment. In contrast, the protein sGC₂ is 5-coordinate, high-spin in the resting state, and the CO adduct has perturbed vibrational frequencies indicative of a negatively polarizing residue in the binding pocket. The differences may result from the need to reconstitute sGC₁ or different isolation procedures for sGC₁ versus sGC₂. However, both sGC₁ and sGC₂ are activated by the same mechanism, namely displacement of the proximal histidine ligand upon NO binding, and neither one is activated by CO. If CO is an activator in vivo, some additional molecular component is required. Received: 11 February 1999 / Accepted: 17 September 1999     

Impact of the Spanish Smoking Law on Exposure to Second-Hand Smoke and Respiratory Health in Hospitality Workers: A Cohort Study

Background

A smoke-free law came into effect in Spain on 1st January 2006, affecting all enclosed workplaces except hospitality venues, whose proprietors can choose among totally a smoke-free policy, a partial restriction with designated smoking areas, or no restriction on smoking on the premises. We aimed to evaluate the impact of the law among hospitality workers by assessing second-hand smoke (SHS) exposure and the frequency of respiratory symptoms before and one year after the ban.

Methods and Finding

We formed a baseline cohort of 431 hospitality workers in Spain and 45 workers in Portugal and Andorra. Of them, 318 (66.8%) were successfully followed up 12 months after the ban, and 137 nonsmokers were included in this analysis. We obtained self-reported exposure to SHS and the presence of respiratory symptoms, and collected saliva samples for cotinine measurement. Salivary cotinine decreased by 55.6% after the ban among nonsmoker workers in venues where smoking was totally prohibited (from median of 1.6 ng/ml before to 0.5 ng/ml, p<0.01). Cotinine concentration decreased by 27.6% (p = 0.068) among workers in venues with designated smoking areas, and by 10.7% (p = 0.475) among workers in venues where smoking was allowed. In Portugal and Andorra, no differences between cotinine concentration were found before (1.2 ng/ml) and after the ban (1.2 ng/ml). In Spain, reported respiratory symptom declined significantly (by 71.9%; p<0.05) among workers in venues that became smoke-free. After adjustment for potential confounders, salivary cotinine and respiratory symptoms decreased significantly among workers in Spanish hospitality venues where smoking was totally banned.

Conclusions

Among nonsmoker hospitality workers in bars and restaurants where smoking was allowed, exposure to SHS after the ban remained similar to pre-law levels. The partial restrictions on smoking in Spanish hospitality venues do not sufficiently protect hospitality workers against SHS or its consequences for respiratory health.     

Exposure to Second-Hand Smoke and the Risk of Tuberculosis in Children and Adults: A Systematic Review and Meta-Analysis of 18 Observational Studies

Background

According to WHO Global Health Estimates, tuberculosis (TB) is among the top ten causes of global mortality and ranks second after cardiovascular disease in most high-burden regions. In this systematic review and meta-analysis, we investigated the role of second-hand smoke (SHS) exposure as a risk factor for TB among children and adults.

Methods and Findings

We performed a systematic literature search of PubMed, Embase, Scopus, Web of Science, and Google Scholar up to August 31, 2014. Our a priori inclusion criteria encompassed only original studies where latent TB infection (LTBI) and active TB disease were diagnosed microbiologically, clinically, histologically, or radiologically. Effect estimates were pooled using fixed- and random-effects models. We identified 18 eligible studies, with 30,757 children and 44,432 adult non-smokers, containing SHS exposure and TB outcome data for inclusion in the meta-analysis. Twelve studies assessed children and eight studies assessed adult non-smokers; two studies assessed both populations. Summary relative risk (RR) of LTBI associated with SHS exposure in children was similar to the overall effect size, with high heterogeneity (pooled RR 1.64, 95% CI 1.00–2.83). Children showed a more than 3-fold increased risk of SHS-associated active TB (pooled RR 3.41, 95% CI 1.81–6.45), which was higher than the risk in adults exposed to SHS (summary RR 1.32, 95% CI 1.04–1.68). Positive and significant exposure–response relationships were observed among children under 5 y (RR 5.88, 95% CI 2.09–16.54), children exposed to SHS through any parent (RR 4.20, 95% CI 1.92–9.20), and children living under the most crowded household conditions (RR 5.53, 95% CI 2.36–12.98). Associations for LTBI and active TB disease remained significant after adjustment for age, biomass fuel (BMF) use, and presence of a TB patient in the household, although the meta-analysis was limited to a subset of studies that adjusted for these variables. There was a loss of association with increased risk of LTBI (but not active TB) after adjustment for socioeconomic status (SES) and study quality. The major limitation of this analysis is the high heterogeneity in outcomes among studies of pediatric cases of LTBI and TB disease.

Conclusions

We found that SHS exposure is associated with an increase in the relative risk of LTBI and active TB after controlling for age, BMF use, and contact with a TB patient, and there was no significant association of SHS exposure with LTBI after adjustment for SES and study quality. Given the high heterogeneity among the primary studies, our analysis may not show sufficient evidence to confirm an association. In addition, considering that the TB burden is highest in countries with increasing SHS exposure, it is important to confirm these results with higher quality studies. Research in this area may have important implications for TB and tobacco control programs, especially for children in settings with high SHS exposure and TB burden.     

Exposure Assessment of Pharmaceuticals and Their Metabolites in the Aquatic Environment: Application to the French Situation and Preliminary Prioritization

Low levels of pharmaceuticals have been detected in many countries in surface waters. As a wide range of pharmaceuticals can reach aquatic environments, a selection of molecules to survey is the first step before implementing a monitoring program. We used a simple equation to calculate Predicted Environmental Concentrations (PECs), adapted from the European Medicine Agency model used for the Environmental Risk Assessment (ERA) of human pharmaceutical. Excretion fractions for pharmaceuticals were determined for 76 compounds. Using year 2004 French drug consumption data, we determined aquatic PECs for 112 parent molecules and several metabolites. Considering excretion fractions of pharmaceuticals can lead to drastically reduce predicted concentrations reaching the aquatic environment and help to target environmentally relevant pharmaceuticals and metabolites. Calculated PECs using the described methodology are consistent with French field measurements. The simple model for calculating PECs can be used as a valuable estimation of the exposure. Risk quotient ratios were also calculated. Due to the lack of ecotoxicological data, the use of PEC/PNEC ratios is not enough informative to prioritize pharmaceuticals likely to pose a risk for surface waters. Alternative ways to prioritize risk to pharmaceuticals, combining PEC, pharmacological, and ecotoxicological data available from the literature, should be implemented.     

Health Risk Assessment of Petrol Station Workers in the Inner City of Bangkok,Thailand, to the Exposure to BTEX and Carbonyl Compounds by Inhalation

The occupational health risk of petrol station workers from exposure to BTEX and carbonyl compounds via inhalation was estimated in the inner city of Bangkok. Personal sampling was performed within the workers’ breathing zone using 2,4 dinitrophenylhydrazine cartridges and charcoal glass tubes connected to a personal air pump during eight working hours at six petrol stations. BTEX and carbonyl compounds were quantitatively analyzed by GC/FID and HPLC/UV, respectively. Of all detectable BTEX and carbonyl compounds, the levels of the four most prevalent compounds (benzene, ethylbenzene, formaldehyde, and acetaldehyde) were used to assess the lifetime cancer risk and 95% confidence interval of the risk levels were found to be totally higher than acceptable criteria for benzene (1.82 × 10^–4–2.50 × 10^–4), formaldehyde (7.81 × 10^–6–1.04 × 10^–5), ethylbenzene (4.11 × 10^–6–5.52 × 10^–6), and acetaldehyde (1.39 × 10^–6–2.45 × 10^–6). Thus, petrol station workers in the inner city of Bangkok have a potentially high cancer risk through inhalation exposure. With respect to the noncarcinogenic agents, toluene, m,p-xylene, o-xylene, and propionaldehyde, all non-cancer health risk were within hazard quotients of 1 and of acceptable risk.