Arsenic inorganic exposure, metabolism, genetic biomarkers and its impact on human health: A mini-review.

Inorganic arsenic species exist in the environment as a result of both natural sources, such as volcanic and geothermal activities, and geological formations, as well as anthropogenic activities, including smelting, exploration of fossil fuels, coal burning, mining, and the use of pesticides. These species deposit in water, rocks, soil, sediments, and the atmosphere. Arsenic-contaminated drinking water is a global public health issue because of its natural prevalence and toxicity. Therefore, chronic exposure to arsenic can have deleterious effect on humans, including cancer and other diseases. This work describes the mechanisms of environmental exposure to arsenic, molecular regulatory factors involved in its metabolism, genetic polymorphisms affecting individual susceptibility and the toxic effects of arsenic on human health (oxidative stress, DNA damage and cancer). We conclude that the role of single nucleotide variants affecting urinary excretion of arsenic metabolites are highly relevant and can be used as biomarkers of the intracellular retention rates of arsenic, showing new avenues of research in this field.

Detection of Bromochloro Alkanes in Indoor Dust Using a Novel CP-Seeker Data Integration Tool.

Bromochloro alkanes (BCAs) have been manufactured for use as flame retardants for decades, and preliminary environmental risk screening suggests they are likely to behave similarly to polychlorinated alkanes (PCAs), subclasses of which are restricted as Stockholm Convention Persistent Organic Pollutants (POPs). BCAs have rarely been studied in the environment, although some evidence suggests they may migrate from treated-consumer materials into indoor dust, resulting in human exposure via inadvertent ingestion. In this study, BCA-C14 mixture standards were synthesized and used to validate an analytical method. This method relies on chloride-enhanced liquid chromatography-electrospray ionization-Orbitrap-high resolution mass spectrometry (LC-ESI-Orbitrap-HRMS) and a novel CP-Seeker integration software package for homologue detection and integration. Dust sample preparation via ultrasonic extraction, acidified silica cleanup, and fractionation on neutral silica cartridges was found to be suitable for BCAs, with absolute recovery of individual homologues averaging 66 to 78% and coefficients of variation ≤10% in replicated spiking experiments (n = 3). In addition, a total of 59 indoor dust samples from six countries, including Australia (n = 10), Belgium (n = 10), Colombia (n = 10), Japan (n = 10), Thailand (n = 10), and the United States of America (n = 9), were analyzed for BCAs. BCAs were detected in seven samples from the U.S.A., with carbon chain lengths of C8, C10, C12, C14, C16, C18, C24 to C28, C30 and C31 observed overall, though not detected in samples from any other countries. Bromine numbers of detected homologues in the indoor dust samples ranged Br1-4 as well as Br7, while chlorine numbers ranged Cl2-11. BCA-C18 was the most frequently detected, observed in each of the U.S.A. samples, while the most prevalent degrees of halogenation were homologues of Br2 and Cl4-5. Broad estimations of BCA concentrations in the dust samples indicated that levels may approach those of other flame retardants in at least some instances. These findings suggest that development of quantification strategies and further investigation of environmental occurrence and health implications are needed.

Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) in human breast milk from Colombia: A probabilistic risk assessment approach.

Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs) are ubiquitous environmental contaminants. They were produced in relatively large volumes in the last century and are now subject to long-term monitoring and regulated under the United Nations Stockholm Convention (SC) on persistent organic pollutants (POPs). Though restricted, human exposure is still a concern and in some regions of the globe the information on the health risk is limited. Sixty breast milk samples from nursing mothers were collected between 2014 and 2015, residing in Bogota, Cartagena, and Medellin, which are industrialized cities in Colombia. This is the first comprehensive study to determine the concentrations in breast milk of PBDEs (n = 7), PCBs (n = 29), and OCPs (n = 28) in Colombia. The detection frequency of POPs, including BDE-47, CB-138, CB-153, CB-156, and CB-180, as well as several OCPs such as chloroneb, aldrins, HCHs, DDTs, and heptachlor, was found to be 100% in all samples tested. The mean concentrations of the analyzed legacy POPs were ∑3DDTs (423 ng/g lw) > chloroneb (50.1 ng/g lw) > ∑2permetrins (17.5 ng/g lw) > ∑2aldrins (16.7 ng/g lw) > 29 PCBs (15.04 ng/g lw) > ∑2chlordanes (CHLs) (11.2 ng/g lw) ≈ ∑3endosulfans (11.1 ng/g lw) > ∑2heptachlors (2.43 ng/g lw) > 7PBDEs (2.1 ng/g lw) > ∑4HCHs (0.58 ng/g lw). The results of this study suggest that the concentrations of DDTs were present in breast milk samples from Colombia at levels comparable to those found in previous studies conducted in other countries such as Brazil, Uruguay, Chile, and various Asian countries. The concentrations of PBDE and PCB congeners, as well as many pesticides, were found to be significantly correlated with each other. This suggests that these substances may have similar sources of exposure. The strength of the pair correlation among concentrations of POPs was assessed using Spearman's correlation coefficients, which varied from r = 0.62 for the association between BDE-47 and CB-153, to a high correlation of 0.99 for the correlation between γ-Chlordane and heptachlor. This suggests that these POPs may share similar sources, such as diet. An exposure assessment model obtained by Monte Carlo simulation showed that infants were exposed to low concentrations of POPs with exception of p,p'-DDE and Aldrin, in which 25th, 50th and 95th percentiles were greater than the threshold reference values of non-carcinogenic effects suggested by US-EPA regulations while the 90th percentile of pg TEQ/Kg-bw/day for dl-PCBs was above of the tolerable daily intake (TDI) proposed by the World Health Organization (WHO). Therefore, the health risk of infants exposed to OCPs and dl-PCBs should be exanimated continually through biomonitoring programs in the Colombian population.

An international investigation of chlorinated paraffin concentrations and homologue distributions in indoor dust.

In this study, very short-, short-, medium-, and long-chain chlorinated paraffins (vSCCPs, SCCPs, MCCPs and LCCPs, respectively) were measured in 40 indoor dust samples from four countries including Japan (n = 10), Australia (n = 10), Colombia (n = 10) and Thailand (n = 10). Homologues of the chemical formula CxH(2x+2-y)Cly ranging C6-36 and Cl3-30 were analysed using liquid chromatography coupled to Orbitrap high resolution mass spectrometry (LC-Orbitrap-HRMS) and integrated using novel custom-built CP-Seeker software. CPs were detected in all dust samples with MCCPs the dominant homologue group in all countries. Overall median ∑SCCP, ∑MCCP and ∑LCCP (C18-20) concentrations determined in dust samples were 30 µg/g (range; 4.0-290 µg/g), 65 µg/g (range; 6.9-540 µg/g) and 8.6 µg/g (range; <1.0-230 µg/g), respectively. Of the quantified CP classes, overall concentrations were generally highest in the samples from Thailand and Colombia, followed by Australia and Japan. vSCCPs with C≤9 were detected in dust from each country with an overall frequency of 48%, while LCCPs (C21-36) were present in 100% of samples. Estimated daily intakes (EDIs) calculated for SCCPs and MCCPs relating to ingestion of contaminated indoor dust were considered not to represent health risks based on currently available toxicological data using the margin of exposure (MOE) approach. To the authors' knowledge, this study provides the first data on CPs in indoor dust from Japan, Colombia and Thailand, and is among the first reports of vSCCPs in indoor dust, globally. These findings indicate that further toxicological data and the availability of appropriate analytical standards are needed to evaluate the potential for negative health outcomes deriving from exposure to vSCCPs and LCCPs.

Hydrocarbons in the atmospheric gas phase of a coastal city in Tunisia: Levels, gas-particle partitioning, and health risk assessment.

Many studies have focused on aliphatic hydrocarbons and polycyclic aromatic hydrocarbons (AHs and PAHs) in different environmental compartments, especially atmospheric particles (aerosols), due to their adverse effects on the environment and human health. However, much less information is currently available on the content of AHs and PAHs in the atmospheric gas phase, which is a major reservoir of volatile and photoreactive compounds. Here, for the first time, we assessed the levels, gas-particle partitioning, human health risks and seasonal variations of AHs and PAHs in the atmospheric gas-phase of Bizerte city (Tunisia, North Africa) over a one-year period (March 2015-January 2016). Σ34PAH concentration in the gas phase over the period ranged from 6.7 to 90.6 ng m-3 and on average was 2.5 times higher in the cold season than in the warm season. Σ28AH concentration in the gas phase over the period ranged from 14.0 to 35.9 ng m-3, with no clear seasonal variations. In the gas phase, hydrocarbons were dominated by low-molecular-weight (LMW) compounds, i.e. 3- and 4-ring for PAHs and < n-C24 for AHs. Gas-phase concentrations of PAHs and AHs accounted for up to 80 % of the total (gas + particle phases) atmospheric concentrations of PAHs and AHs. Further analysis of gas-particle partitioning showed that LMW hydrocarbons preferential accumulated in the gas phase, and that gas-particle partitioning was not in equilibrium but dominated by absorption processes into the aerosol organic matter. Benzo[a]pyrene toxic equivalency quotient (BaP-TEQ) in the gas phase represented on average 37 % of the total atmospheric BaP-TEQ concentration, which was always higher in the cold season. Atmospheric gas is a significant factor in the risks of cancer associated with inhalation of ambient air. The Monte Carlo simulation-based exposure assessment model predicted that outdoor air exposure to PAHs does not pose a cancer risk to infants, but the children, adolescent, and adult populations may face a lower cancer risk during the warm season and a higher risk in the cold season.

Adverse Health Effects and Mercury Exposure in a Colombian Artisanal and Small-Scale Gold Mining Community.

The aim of this study was, first of all, to associate the mercury (Hg) concentrations and respiratory functions of the gold miners in the artisanal small-scale gold mining (ASGM) environment in San Martín de Loba, Colombia. We carried out a cross-sectional study using a survey whereby we collected basic demographic information, occupational medical history, and applied two validated questionnaires (Q16 and SF36). We measured Hg levels in all volunteers using direct thermal decomposition-atomic absorption spectrometry. Univariate and bivariate statistical analyses were carried out for all variables, performing logistic regression to assess the effect of ASGM on health outcomes. Volunteers enrolled (n = 124) were between the ages of 20 and 84 years (84% miners and 79% males). No changes were found in the systolic blood pressure, diastolic blood pressure, and heart rate from the ASGM miners, in crude and adjusted statistical analyses. ASGM miners increased 8.91 (95% confidence interval, 1.55-95.70) times the risk of having these than of having neurotoxic effects. Concentrations of total whole blood mercury (T-Hg) in all participants ranged from 0.6 to 82.5 with a median of 6.0 µg/L. Miners had higher T-Hg concentrations than non-miners (p-value = 0.011). Normal and abnormal respiratory spirometry patterns showed significant differences with the physical role and physical function of quality-of-life scales (the (p-value was 0.012 and 0.004, respectively). The spirometry test was carried out in 87 male miners, with 25% of these miners reporting abnormalities. Out of these, 73% presented a restrictive spirometry pattern, and 27%, an obstructive spirometry pattern. The ASGM population had higher Hg concentrations and worse neurotoxic symptomatology than non-miners of the same community.

Biochemical and Hematological Markers in Workers with Chronical Exposure to Lead and Cadmium in Colombia.

The aim of the present study was to find if workers chronically exposed to lead (Pb) and cadmium (Cd) presented changes in their general health and in the clinical parameters of the population under study. We carried out a cross-sectional survey in a sample of informal workers in Cartagena, Colombia. The population under study was composed of male informal workers (≥18 years of age), with experience in their job, selected from occupational settings with potential exposure to Pb and Cd (i.e., mechanics, battery and garbage recyclers, and welders). The median age was 45 years (interquartile range (IQR), 33−53). The median blood Pb level (BLL) was 2 µg/dL (IQR, 0.76−6.22), and the median of blood Cd level (BCL) was 1.22 µg/L (IQR, 0.33−2.01). The study found that 33% of high exposure jobs with BLL > 5 µg/dL (n = 57), whereas in 'control' workers, this was 15.3% (n = 9). The highest BLLs were found in battery recyclers (82.1%; n = 23), followed by mechanics (37.3%, n = 22). In the logistic regression model adjusted by age, time on the job, smoking and elevated BCL and BLL increased 3.2 times (95% CI, 1.1−9.7) in mechanics and 29.6 times (95% CI, 7.2−145.6) in battery recyclers. This study found negative changes in the health of workers with higher chronic exposure to lead in Cartagena, Colombia.

Polycyclic aromatic hydrocarbons (PAHs) in human breast milk from Colombia: Spatial occurrence, sources and probabilistic risk assessment.

The diet is the main route that polycyclic aromatic hydrocarbons (PAHs) enter the body and measuring breast milk is one of the best ways to understand the maternal body burden and can be passed on to infants. In this study, it was determinate the concentrations of 23 PAHs in 60 milk samples taken from 3 cities in Colombia and to determine the potential routes of exposure and risk to human health. On average, concentration for the ∑PAHs across all locations was 186.6 ng g-1, lipid mass (LM), with city means of 260.1, 175.7, and 123.9 ng g-1 LM for Cartagena, Bogota and Medellin, respectively. Monte Carlo simulations were used to estimate the hazard quotient (HQ) and incremental lifetime cancer risk (ILCR) for infant dietary exposure to PAHs. HQs were below the safe thresholds (HQ = 1) while ILCRs were greater than the reference value equal to 10-6 (mg kg-1day-1). Dietary source assessment indicated that fish is a significant source of PAHs, with mothers that consumed fish at least once per week having ∼2.5 times greater PAH milk concentrations than other groups. While a disparity was also observed among consumers of exclusively marine (∑PAHs 198.5 ng g-1 LM) or freshwater fish (∑PAHs 85.7 ng g-1 LM). However, geographical considerations can be significant in this finding.

As3MT and GST Polymorphisms Influencing Arsenic Metabolism in Human Exposure to Drinking Groundwater.

The urinary arsenic metabolites may vary among individuals and the genetic factors have been reported to explain part of the variation. We assessed the influence of polymorphic variants of Arsenic-3-methyl-transferase and Glutathione-S-transferase on urinary arsenic metabolites. Twenty-two groundwater wells for human consumption from municipalities of Colombia were analyzed for assessed the exposure by lifetime average daily dose (LADD) (µg/kg bw/day). Surveys on 151 participants aged between 18 and 81 years old were applied to collect demographic information and other factors. In addition, genetic polymorphisms (GSTO2-rs156697, GSTP1-rs1695, As3MT-rs3740400, GSTT1 and GSTM1) were evaluated by real time and/or conventional PCR. Arsenic metabolites: AsIII, AsV, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were measured using HPLC-HG-AFS. The influence of polymorphic variants, LADD and other factors were tested using multivariate analyses. The median of total arsenic concentration in groundwater was of 33.3 µg/L and the median of LADD for the high exposure dose was 0.33 µg/kg bw/day. Univariate analyses among arsenic metabolites and genetic polymorphisms showed MMA concentrations higher in heterozygous and/or homozygous genotypes of As3MT compared to the wild-type genotype. Besides, DMA concentrations were lower in heterozygous and/or homozygous genotypes of GSTP1 compared to the wild-type genotype. Both DMA and MMA concentrations were higher in GSTM1-null genotypes compared to the active genotype. Multivariate analyses showed statistically significant association among interactions gene-gene and gene-covariates to modify the MMA and DMA excretion. Interactions between polymorphic variants As3MT*GSTM1 and GSTO2*GSTP1 could be potential modifiers of urinary excretion of arsenic and covariates as age, LADD, and alcohol consumption contribute to largely vary the arsenic individual metabolic capacity in exposed people.

Organophosphate esters in indoor dust from 12 countries: Concentrations, composition profiles, and human exposure.

A total of 20 organophosphate triesters (OPEs), including seven alkyl-OPEs, three chlorinated (Cl)-OPEs, seven aryl-OPEs, and three oligomeric-OPEs were measured in 341 house dust samples collected from 12 countries during the period 2010-2014. OPEs were ubiquitous in indoor dust, and the total concentrations of OPEs (∑OPEs; sum of 20 OPEs) ranged from 49.4 to 249,000 ng/g dry weight (dw). Generally, Cl-OPEs were the predominant compounds (51% of total) in indoor dust samples, with a median concentration of 800 ng/g, followed by alkyl-OPEs (31%), aryl-OPEs (17%), and oligomeric-OPEs (1%), with median concentrations of 480, 270, and 21.9 ng/g, respectively. ∑OPE concentrations in indoor dust from more industrialized countries (South Korea: median, 31,300; Japan: 29,800; and the United States: 26,500 ng/g dw) were one or two orders of magnitude higher than those from less industrialized countries (Greece: 7140, Saudi Arabia: 5310, Kuwait: 4420, Romania: 4110, Vietnam: 1190, China: 1120, Colombia: 374, India: 276, and Pakistan: 138 ng/g dw). Statistically significant positive correlations (0.114 < r < 0.748, p < 0.05) were found among the concentrations of 16 OPEs in dust samples, indicating similar sources of these compounds. The median estimated daily intakes of ΣOPEs via dust ingestion for children and adults were in the ranges of 0.29-64.8 and 0.07-14.9 ng/kg bw/day, respectively.

Arsenic exposure, profiles of urinary arsenic species, and polymorphism effects of glutathione-s-transferase and metallothioneins.

This study assessed the effects of polymorphic variants of gutathione-S-transferase and metallothioneins on profiles of urinary arsenic species. Drinking groundwater from Margarita and San Fernando, Colombia were analyzed and the lifetime average daily dose (LADD) of arsenic was determined. Specific surveys were applied to collect demographic information and other exposure factors. In addition, GSTT1-null, GSTM1-null, GSTP1-rs1695 and MT-2A-rs28366003 genetic polymorphisms were evaluated, either by direct PCR or PCR-RFLP. Urinary speciated arsenic concentrations were determined by HPLC-HG-AFS for species such as AsIII, AsV, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and total urinary As (TuAs). Primary methylation index (PMI) and secondary methylation index (SMI) were also calculated as indicators of the metabolic capacity. Polymorphisms effects were tested using multivariate analysis, adjusted by potential confounders. The As concentrations in groundwater were on average 34.6 ± 24.7 µg/L greater than the WHO guideline for As (10 µg/L). There was a correlation between As concentrations in groundwater and TuAs (r = 0.59; p = 0.000). Urinary inorganic arsenic (%InAs) was associated with GSTP1, LADD, GSTP1*Age, GSTP1*alcohol consumption (r2 = 0.43; likelihood-ratio test, p = 0.000). PMI was associated with sex (r2 = 0.20; likelihood-ratio test, p = 0.007). GSTP1 (AG + GG) homozygotes/heterozygotes could increase urinary %InAs and decrease the PMI ratio in people exposed to low and high As from drinking groundwater. Therefore, the explanatory models showed the participation of some covariates that could influence the effects of the polymorphisms on these exposure biomarkers to As.

Linear and Nonlinear Calibration Methods for Predicting Mechanical Properties of Polypropylene Pellets Using Raman Spectroscopy.

A nondestructive and faster methodology to quantify mechanical properties of polypropylene (PP) pellets, obtained from an industrial plant, was developed with Raman spectroscopy. Raman spectra data were obtained from several types of samples such as homopolymer PP, random ethylene-propylene copolymer, and impact ethylene-propylene copolymer. Multivariate calibration models were developed by relating the changes in the Raman spectra to mechanical properties determined by ASTM tests (Young's traction modulus, tensile strength at yield, elongation at yield on traction, and flexural modulus at 1% secant). Several strategies were evaluated to build robust models including the use of preprocessing methods (baseline correction, vector normalization, de-trending, and standard normal variate), selecting the best subset of wavelengths to model property response and discarding irrelevant variables by applying genetic algorithm (GA). Linear multivariable models were investigated such as partial least square regression (PLS) and PLS with genetic algorithm (GA-PLS) while nonlinear models were implemented with artificial neural network (ANN) preceded by GA (GA-ANN). The best multivariate calibration models were obtained when a combination of genetic algorithms and artificial neural network were used on Raman spectral data with relative standard errors (%RSE) from 0.17 to 0.41 for training and 0.42 to 0.88% validation data sets.

Synthetic Phenolic Antioxidants and Their Metabolites in Indoor Dust from Homes and Microenvironments.

Synthetic phenolic antioxidants (SPAs), including 2,6-di-tert-butyl-4-hydroxytoluene (BHT), are extensively used in food, cosmetic and plastic industries. Nevertheless, limited information is available on human exposures, other than the dietary sources, to SPAs. In this study, occurrence of 9 SPAs and their metabolites/degradation products was determined in 339 indoor dust collected from 12 countries. BHT was found in 99.5% of indoor dust samples from homes and microenvironments at concentrations that ranged from < LOQ to 118 µg/g and 0.10 to 3460 µg/g, respectively. This is the first study to measure BHT metabolites in house dust (0.01-35.1 µg/g) and their concentrations accounted for 9.2-58% of the sum concentrations (∑SPAs). 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO), 2,6-di-tert-butyl-4-(hydroxymethyl)phenol (BHT-OH), 2,6-di-tert-butyl-1,4-benzoquinone (BHT-Q) were the major derivatives of BHT found in dust samples. The concentrations of gallic acid esters (gallates) in dust from homes and microenvironments ranged from < LOQ to 18.2 and < LOQ to 684 µg/g, respectively. The concentrations and profiles of SPAs varied among countries and microenvironments. Significantly elevated concentrations of SPAs were found in dust from an e-waste workshop (1530 µg/g). The estimated daily intake (EDI) of BHT via house dust ingestion ranged from 0.40 to 222 ng/kg/d (95th percentile).

Chemical and toxicological characterization of sediments along a Colombian shoreline impacted by coal export terminals.

Extraction, transport and utilization of coal spread out coal dust. Nowadays, Colombia is an important producer of this mineral in South America, being the Santa Marta area one of the largest coal exporting ports in the country. The aim of this work was to assess the pollutants levels and toxicity of shoreline sediments from this place. 16 PAHs and 46 elements were measured in nine locations during dry and rainy seasons. HepG2 cells were exposed to 1% sediment extracts and mRNA expression evaluated for selected genes. PAHs levels were greater during the rainy season. The highest ∑PAHs (89.9 ng g(-1)) appeared at a site located around 300 m far from the coast line at close proximity to the area where coal is loaded into cargo vessels for international shipments, being naphthalene the most abundant PAH. At Santa Marta Bay port, ∑PAHs were 62.8 ng g(-1) and 72.8 ng g(-1) for dry and rainy seasons, respectively, with greatest levels for fluoranthene. Based on sediment standards, most stations have poor condition regarding Cr, but moderate contamination on Cu, Pb and Zn. Sediments from the port and coal transport sites, the most polluted by PAHs and metals, induced CYP1A1 and NQO1 during the dry season. Data showed the sediments from this shoreline have bioactive chemicals that determine their toxicological profile.

A comparative assessment of human exposure to tetrabromobisphenol A and eight bisphenols including bisphenol A via indoor dust ingestion in twelve countries.

Tetrabromobisphenol A (TBBPA) and eight bisphenol analogues (BPs) including bisphenol A (BPA) were determined in 388 indoor (including homes and microenvironments) dust samples collected from 12 countries (China, Colombia, Greece, India, Japan, Kuwait, Pakistan, Romania, Saudi Arabia, South Korea, U.S., and Vietnam). The concentrations of TBBPA and sum of eight bisphenols (Æ©BPs) in dust samples ranged from <1 to 3600 and from 13 to 110,000 ng/g, respectively. The highest TBBPA concentrations in house dust were found in samples from Japan (median: 140 ng/g), followed by South Korea (84 ng/g) and China (23 ng/g). The highest ∑BPs concentrations were found in Greece (median: 3900 ng/g), Japan (2600 ng/g) and the U.S. (2200 ng/g). Significant variations in BPA concentrations were found in dust samples collected from various microenvironments in offices and homes. Concentrations of TBBPA in house dust were significantly correlated with BPA and ∑BPs. Among the nine target chemicals analyzed, BPA was the predominant compound in dust from all countries. The proportion of TBBPA in sum concentrations of nine phenolic compounds analyzed in this study was the highest in dust samples from China (27%) and the lowest in Greece (0.41%). The median estimated daily intake (EDI) of ∑BPs through dust ingestion was the highest in Greece (1.6-17 ng/kg bw/day), Japan (1.3-16) and the U.S. (0.89-9.6) for various age groups. Nevertheless, in comparison with the reported BPA exposure doses through diet, dust ingestion accounted for less than 10% of the total exposure doses in China and the U.S. For TBBPA, the EDI for infants and toddlers ranged from 0.01 to 3.4 ng/kg bw/day, and dust ingestion is an important pathway for exposure accounting for 3.8-35% (median) of exposure doses in China.

A survey of cyclic and linear siloxanes in indoor dust and their implications for human exposures in twelve countries.

Siloxanes are used widely in a variety of consumer products, including cosmetics, personal care products, medical and electrical devices, cookware, and building materials. Nevertheless, little is known on the occurrence of siloxanes in indoor dust. In this survey, five cyclic (D3-D7) and 11 linear (L4-L14) siloxanes were determined in 310 indoor dust samples collected from 12 countries. Dust samples collected from Greece contained the highest concentrations of total cyclic siloxanes (TCSi), ranging from 118 to 25,100ng/g (median: 1380), and total linear siloxanes (TLSi), ranging from 129 to 4990ng/g (median: 772). The median total siloxane (TSi) concentrations in dust samples from 12 countries were in the following decreasing order: Greece (2970ng/g), Kuwait (2400), South Korea (1810), Japan (1500), the USA (1220), China (1070), Romania (538), Colombia (230), Vietnam (206), Saudi Arabia (132), India (116), and Pakistan (68.3). TLSi concentrations as high as 42,800ng/g (Kuwait) and TCSi concentrations as high as 25,000ng/g (Greece) were found in indoor dust samples. Among the 16 siloxanes determined, decamethylcyclopentasiloxane (D5) was found at the highest concentration in dust samples from all countries, except for Japan and South Korea, with a predominance of L11; Kuwait, with L10; and Pakistan and Romania, with L12. The composition profiles of 16 siloxanes in dust samples varied by country. TCSi accounted for a major proportion of TSi concentrations in dust collected from Colombia (90%), India (80%) and Saudi Arabia (70%), whereas TLSi predominated in samples collected from Japan (89%), Kuwait (85%), and South Korea (78%). Based on the measured median TSi concentrations in indoor dust, we estimated human exposure doses through indoor dust ingestion for various age groups. The exposure doses ranged from 0.27 to 11.9ng/kg-bw/d for toddlers and 0.06 to 2.48ng/kg-bw/d for adults.

Occurrence of perchlorate in indoor dust from the United States and eleven other countries: implications for human exposure.

Perchlorate is a widespread environmental contaminant and potent thyroid hormone disrupting compound. Despite this, very little is known with regard to the occurrence of this compound in indoor dust and the exposure of humans to perchlorate through dust ingestion. In this study, 366 indoor dust samples were collected from 12 countries, the USA, Colombia, Greece, Romania, Japan, Korea, Pakistan, Kuwait, Saudi Arabia, India, Vietnam, and China, during 2010-2014. Dust samples were extracted by 1% (v/v) methylamine in water. Analyte separation was achieved by an ion exchange (AS-21) column and analysis was performed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The overall concentrations of perchlorate in dust were in the range of 0.02-104µg/g (geometric mean: 0.41µg/g). The indoor dust samples from China contained the highest concentrations (geometric mean: 5.38µg/g). No remarkable differences in perchlorate concentrations in dust were found among various microenvironments (i.e., car, home, office, and laboratory). The estimated median daily intake (EDI) of perchlorate for toddlers through dust ingestion in the USA, Colombia, Greece, Romania, Japan, Korea, Pakistan, Kuwait, Saudi Arabia, India, Vietnam, and China was 1.89, 0.37, 1.71, 0.74, 4.90, 7.20, 0.60, 0.80, 1.55, 0.70, 2.15, and 21.3ng/kgbodyweight (bw)/day, respectively. Although high concentrations of perchlorate were measured in some dust samples, the contribution of dust to total perchlorate intake was <5% of the total perchlorate intake in humans. This is the first multinational survey on the occurrence of perchlorate in indoor dust.

Near-infrared chemical imaging slope as a new method to study tablet compaction and tablet relaxation.

Near-infrared chemical imaging (NIR-CI) spectra of lactose monohydrate tablets were acquired and the spectral slope from each pixel in the data hypercube was used to assess tablet compaction and relaxation. Tablets were prepared at compaction pressures of 100, 300, and 500 MPa using un-lubricated and magnesium stearate lubricated lactose monohydrate. Results show that NIR slope distribution is a function of applied compaction forces and magnesium stearate lubrication. The distribution of NIR slope values was studied using histograms and statistical parameters. The mean slope value yields a linear calibration curve that predicts tablet compaction pressure as a function of spectral slope. The NIR-CI slope measurements were also used to study tablet relaxation, which occurs as tablets release some of the stored energy from compression. The NIR-CI slope method provides a qualitative description of the relaxation process and provides quantitative information describing relaxation through time.

An assessment of sources and pathways of human exposure to polybrominated diphenyl ethers in the United States.

Polybrominated diphenyl ethers (PBDEs) are ubiquitous in the indoor environment, owing to their use in consumer products ranging from electronics to mattresses, furniture, and carpets. People are exposed to PBDEs through inhalation of indoor air and ingestion, and dermal absorption of dust particles present in the air. In this study, concentrations of PBDEs were determined in indoor air and house dust collected from homes in Albany, New York, USA. Based on the measured concentrations of PBDEs in indoor air and dust, we estimated daily exposure dose (DED) of PBDEs. In addition, we used previously published PBDE concentrations reported for breast milk from Massachusetts, USA [Johnson-Restrepo, B., Addink, R., Wong, C., Arcaro, K., Kannan, K., 2007. Polybrominated diphenyl ethers and organochlorine pesticides in human breast milk from Massachusetts. USA. J. Environ. Monitor. 9, 1205-1212] and foodstuffs collected from Texas and Florida, USA [Schecter, A., Päpke, O., Harris, T.R., Tung, K.C., Musumba, A., Olson, J., Birnbaum, L., 2006. Polybrominated diphenyl ether (PBDE) levels in an expanded market basket survey of U.S. food and estimated PBDE dietary intake by age and sex. Environ. Health Perspect. 114, 1515-1520, Johnson-Restrepo, B., Kannan, K., Addink, R., Adams, D.H., 2005b. Polybrominated diphenyl ethers and polychlorinated biphenyls in a marine foodweb of coastal Florida. Environ. Sci. Technol. 39, 8243-8250], in an estimation of dietary exposure to PBDEs. The exposure assessment was performed for five age groups: infants (<1yr), toddlers (1-5yr), children (6-11yr), teenagers (12-19yr), and adults (20yr). The dust ingestion and air inhalation factors that we used were the US Environmental Protection Agency's (EPA) exposure factors, while the daily food intake rates (g/day) were derived from the US Department of Agriculture's (USDA) food intake surveys. The total DED of PBDEs was calculated by summation of the exposures from diet, indoor air, and house dust. The average estimated DED of PBDEs was the highest for breastfed infants (86.4ng/kg-bw/day), contributed primarily (91%) from the consumption of breast milk. The average DED of PBDEs for toddlers, children, teenagers, and adults was respectively, 13.3, 5.3, 3.5, and 2.9ng/kg-bw/day. Ingestion and dermal absorption of house dust are the major pathways of PBDE exposure in toddlers, children, teenagers, and adults accounting for, on average, 56-77% of the total PBDE intake.

Oral microemulsions of paclitaxel: in situ and pharmacokinetic studies.

The overall goal of this study was to develop cremophor-free oral microemulsions of paclitaxel (PAC) to enhance its permeability and oral absorption. The mechanism of this enhancement, as well as characteristics of the microemulsions relevant to the increase in permeability and absorption of the low solubility, low permeability PAC was investigated. Phase diagrams were used to determine the macroscopic phase behavior of the microemulsions and to compare the efficiency of different surfactant-oil mixtures to incorporate water. The microemulsion region on the phase diagrams utilizing surfactant-myvacet oil combinations was in decreasing order: lecithin: butanol: myvacet oil (LBM, 48.5%)>centromix CPS: 1-butanol: myvacet oil (CPS, 45.15%)>capmul MCM: polysorbate 80: myvacet oil (CPM, 27.6%)>capryol 90: polysorbate 80: myvacet oil (CP-P80, 23.9%)>capmul: myvacet oil (CM, 20%). Oil-in-water (o/w) microemulsions had larger droplet sizes (687-1010 nm) than the water-in-oil (w/o) microemulsions (272-363 nm) when measured using a Zetasizer nano series particle size analyzer. Utilizing nuclear magnetic resonance spectroscopy (NMR), the self-diffusion coefficient (D) of PAC in CM, LBM and CPM containing 10% of deuterium oxide (D(2)O) was 2.24x10(-11), 1.97x10(-11) and 0.51x10(-11) m(2)/s, respectively. These values indicate the faster molecular mobility of PAC in the two w/o microemulsions (CM and LBM) than the o/w microemulsion--CPM. The in situ permeability of PAC through male CD-IGS rat intestine was 3- and 11-fold higher from LBM and CM, respectively, than that from the control clinical formulation, Taxol (CE, cremophor: ethanol) in a single pass perfusion study. PAC permeability was significantly increased in the presence of the pgp/CYP3A4 inhibitor cyclosporine A (CsA). This enhancement may be attributed to the pgp inhibitory effect of the surfactants, oil and/or the membrane perturbation effect of the surfactants. The oral disposition of PAC in CM, LBM and CPM compared to CE was studied in male CD-IGS rats after a single oral dose (20 mg/kg). The area-under-the-curve of PAC in CM was significantly larger than LBM, CPM and CE. Oral microemulsions of PAC were developed that increased both the permeability and AUC of PAC as compared to CE.