Comparison of tris(2-ethylhexyl) phosphate and di(2-ethylhexyl) phosphoric acid toxicities in a rat 28-day oral exposure study.

Tris(2-ethylhexyl) phosphate (TEHP, CAS no. 78-42-2) is a plasticizer and a flame retardant, while di(2-ethylhexyl) phosphoric acid (DEHPA, CAS no. 298-07-7) is an oil additive and extraction solvent. Publicly-available information on repeated exposure to these two related organophosphate compounds is fragmentary. Hence, adult male and female Fischer rats were exposed to TEHP (300, 1000 and 3000 mg/kg body weight [BW]/day) or DEHPA (20, 60 and 180 mg/kg BW/day) by gavage for 28 consecutive days, to assess and compare their toxicities. Although significantly impaired BW gains and evidence of TEHP enzymatic hydrolysis to DEHPA were observed only in males, exposures to the highest TEHP and DEHPA doses often resulted in similar alterations of hematology, serum clinical chemistry and liver enzymatic activities in both males and females. The squamous epithelial hyperplasia and hyperkeratosis observed in the non-glandular forestomach of rats exposed to the middle and high DEHPA doses were most likely caused by the slightly corrosive nature of this chemical. Although tubular degeneration and spermatid retention were observed only in the testes of males exposed to the highest TEHP dose, numerous periodic acid-Schiff stained crystalline inclusions were observed in testis interstitial cells at all TEHP dose levels. No-observed-adverse-effect levels for TEHP and DEHPA are proposed, but the lower serum pituitary hormone levels resulting from TEHP and DEHPA exposures and the perturbations of testicular histology observed in TEHP-treated males deserve further investigation. Improved characterization of the toxicity of flame retardants will contribute to better informed substitution choices for legacy flame retardants phased-out over health concerns.

Assessment of urinary metabolite excretion after rat acute exposure to perfluorooctanoic acid and other peroxisomal proliferators.

Perfluorooctanoic acid (PFOA) is a persistent environmental contaminant. Activation of the peroxisome proliferator activated receptor alpha (PPARα) resulting from exposure to PFOA has been extensively studied in rodents. However, marked differences in response to peroxisome proliferators prevent extrapolation of rodent PPARα activation to human health risks and additional molecular mechanisms may also be involved in the biological response to PFOA exposure. To further explore the potential involvement of such additional pathways, the effects of PFOA exposure on urinary metabolites were directly compared with those of other well-known PPARα agonists. Male rats were administered PFOA (10, 33, or 100 mg/kg/d), fenofibrate (100 mg/kg/d), or di(2-ethylhexyl) phthalate (100 mg/kg/d) by gavage for 3 consecutive days and allowed to recover for 4 days, and overnight urine was collected. Greater urinary output was observed exclusively in PFOA-treated rats as the total fraction of PFOA excreted in urine increased with the dose administered. Assessment of urinary metabolites (ascorbic acid, quinolinic acid, 8-hydroxy-2'-deoxyguanosine, and malondialdehyde) provided additional information on PFOA's effects on hepatic glucuronic acid and tryptophan-nicotinamide adenine dinucleotide (NAD) pathways and on oxidative stress, whereas increased liver weight and palmitoyl-CoA oxidase activity indicative of PPARα activation and peroxisomal proliferation persisted up to day five after the last exposure.

Quantitative determination of free and total bisphenol A in human urine using labeled BPA glucuronide and isotope dilution mass spectrometry.

Bisphenol A (BPA) is a widely used industrial chemical in the manufacturing of polycarbonate plastic bottles, food and beverage can linings, thermal receipts, and dental sealants. Animal and human studies suggest that BPA may disrupt normal hormonal function and hence, potentially, have negative effects on the human health. While total BPA is frequently reported, it is recognized that free BPA is the biologically active form and is rarely reported in the literature. The objective of this study was to develop a sensitive and improved method for the measurement of free and total BPA in human urine. Use of a labeled conjugated BPA (bisphenol A-d6 ß-D-glucuronide) allowed for the optimization of the enzymatic reaction and permitted an accurate determination of the conjugated BPA concentration in urine samples. In addition, a (13)C12-BPA internal standard was used to account for the analytical recoveries and performance of the isotope dilution method. Solid-phase extraction (SPE) combined with derivatization and analysis using a triple quadrupole GC-EI/MS/MS system achieved very low method detection limit of 0.027 ng/mL. BPA concentrations were measured in urine samples collected during the second and third trimesters of pregnancy in 36 Canadian women. Total maternal BPA concentrations in urine samples ranged from not detected to 9.40 ng/mL (median, 1.21 ng/mL), and free BPA concentrations ranged from not detected to 0.950 ng/mL (median, 0.185 ng/mL). Eighty-six percent of the women had detectable levels of conjugated BPA, whereas only 22 % had detectable levels of free BPA in their urine. BPA levels measured in this study agreed well with data reported internationally.

Quantitation and Stability of Nicotine in Canadian Vaping Liquids.

Electronic cigarettes (e-cigarettes, vaping products) have become increasingly popular, with recent increases in use associated with closed systems delivering higher concentrations of nicotine. Most vaping products designed as an alternative to combustible cigarettes contain nicotine. A number of published studies have examined the reported concentrations of nicotine in vaping liquids (e-liquids) and found discrepancies between labelled and measured levels. Some discrepancy can also be explained by the lack of stability of nicotine in these types of products. Recently, a chemical analysis method for the quantitative determination of low and high levels of nicotine in vaping liquids was developed. This method uses dilution with acetonitrile prior to analysis with gas chromatograph mass spectrometry (GC-MS) in single ion monitoring mode (SIM). The developed method was validated using a laboratory-prepared vaping liquid as well as commercially available, nicotine-free products fortified with nicotine in the laboratory. The method detection limit (MDL) and the limit of quantitation (LOQ) for nicotine were calculated to be 0.002 mg/mL and 0.006 mg/mL, respectively. The newly developed method was applied to quantify nicotine in commercially available vaping liquids of various flavour profiles and across a wide range of nicotine concentrations, including those with nicotine salts. Furthermore, a subset of vaping liquids were analyzed to elucidate nicotine stability in various product subtypes. After a period of six months of accelerated storage to mimic one year, the overall mean percent of the original nicotine concentration remaining in the salt-based vaping products was 85% (minimum 64%, maximum 99%) while in the free-base nicotine products it was 74% (minimum 31%, maximum 106%). Nicotine stability in vaping liquids was found to be influenced by the nicotine form (pH) of formulation and its chemical composition. Non-targeted, qualitative analysis of chemical composition of vaping products showed that most constituents were identified and found to be remaining in the products following stability trials; however, three new compounds were tentatively identified in some vaping liquids at the end of the stability trials. Stability studies and the accurate quantitation of nicotine in vaping products can help inform product standards related to the safety, quality and utility of vaping products as a smoking cessation tool.

Determination of synthetic musk compounds in indoor house dust by gas chromatography-ion trap mass spectrometry.

A new method for the simultaneous determination of 11 synthetic musks and one fragrance compound in house dust was developed. The nitro musks included musk ketone (MK, 4-tert-butyl-3,5-dinitro-2,6-dimethylacetophenone), musk xylene (MX, 1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene), musk ambrette (1-tert-butyl-2-methoxy-4-methyl-3,5-dinitrobenzene) and musk moskene (1,1,3,3,5-pentamethyl-4,6-dinitroindane). The polycyclic musk compounds were 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-(γ)-2-benzopyran (HHCB), 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN), 4-acetyl-1,1-dimethyl-6-tert-butylindane, 6-acetyl-1,1,2,3,3,5-hexamethylindane, 5-acetyl-1,1,2,6-tetramethyl-3-isopropylindane, 6,7-dihydro-1,1,2,3,3-pentamethyl-4(5H)-indanon. The one macrocyclic musk was 1,4-dioxacycloheptadecane-5,17-dione. The bicyclic hydrocarbon fragrance compound (1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetramethylnaphthalen-2yl)ethan-1-one (OTNE) and HHCB-lactone (4,6,6,7,8,8-hexamethyl-1H,3H,4H,6H,7H, 8H-indeno[5,6-c]pyran-1-one), a degradation product of HHCB, were also analysed. NIST SRM 2781 (domestic sludge) and SRM 2585 (organic contaminants in house dust) were analysed for these target compounds. The method was applied for the analysis of 49 paired samples collected using two vacuum sampling methods: a sample of fresh or "active" dust (FD) collected using a Pullman-Holt vacuum sampler, and a household dust (HD) sample taken from the participants' vacuum cleaners. Method detection limits and recoveries ranged from 12 to 48 ng/g and 54 to 117 %, respectively. AHTN, HHCB, OTNE and HHCB-lactone were detected in all samples, with median concentrations of 552, 676, 252 and 453 ng/g for FD samples, respectively; and 405, 992, 212 and 492 ng/g for HD samples, respectively. MX and MK were detected with high frequencies but with much lower concentrations. The two sampling methods produced comparable results for the target analytes. Widely scattered concentration levels were observed for target analytes from this set of 49 house dust samples, suggesting a wide variability in Canadian household exposure to synthetic musks.

Relationships between House Characteristics and Exposures to Metal(loid)s and Synthetic Organic Contaminants Evaluated Using Settled Indoor Dust.

This study investigates associations between house characteristics and chemical contaminants in house dust, collected under the nationally representative Canadian House Dust Study (2007−2010). Vacuum samples (<80 µm fraction) were analysed for over 200 synthetic organic compounds and metal(loid)s. Spearman rank correlations between contaminant concentrations in dust and presence of children and pets, types of flooring, heating styles and other characteristics suggested a number of indoor sources, pointing to future research directions. Numerous synthetic organics were significantly associated with reported use of room deodorizers and with the presence of cats in the home. Hardwood flooring, which is a manufactured wood product, emerged as a source of metal(loid)s, phthalates, organophosphate flame retardants/plasticizers, and obsolete organochlorine pesticides such as ∑DDT (but not halogenated flame retardants). Many metal(loid)s were significantly correlated with flame-retardant compounds used in building materials and heating systems. Components of heating appliances and heat distribution systems appeared to contribute heat-resistant chemicals and alloys to settled dust. Carpets displayed a dual role as both a source and repository of dust-borne contaminants. Contaminant loadings (<80 µm fraction) were significantly elevated in heavily carpeted homes, particularly those located near industry. Depending on the chemical (and its source), the results show that increased dust mass loading may enrich or dilute chemical concentrations in dust. Research is needed to improve the characterisation of hidden indoor sources such as flame retardants used in building materials and heating systems, or undisclosed ingredients used in common household products, such as air fresheners and products used for companion animals.

Exposure of men living in the greater Montreal area to organophosphate esters: Association with hormonal balance and semen quality.

Exposure to organophosphate esters (OPEs) is extensive, yet few studies have investigated their association with hormone levels or semen quality. Here, we studied the association between urinary concentrations of OPEs and their metabolites with hormone levels and semen parameters in men (n = 117) predominantly in the 20-29 years age range who were recruited from the greater Montreal area between 2009 and 2012. Urine, serum, and semen samples were analyzed for OPEs, hormones, and semen quality, respectively. Bis(2-ethylhexyl) phosphate (BEHP), bis(2,4-di-tert-butylphenyl) hydrogen phosphate (B2,4DtBPP), tris(2-chloroisopropyl) phosphate (TCIPP), diphenyl phosphate (DPHP), bis (2-butoxyethyl) phosphate (BBOEP) and di-cresyl phosphate (DCPs) were detected in urine at a frequency ≥ 95%. The highest geometric mean concentration was observed for DPHP (18.54 ng/mL) and the second highest was B2,4DtBPP (6.23 ng/mL). Associations between a doubling in analyte concentrations in urine and hormone levels and semen quality parameters were estimated using multivariable linear regression. B2,4DtBPP levels were positively associated with total T3 (ß = 0.09; 95% CI: 0.01, 0.17). DPHP was inversely associated with estradiol (ß = -2.56; 95% CI: -5.00, -0.17), and TCIPP was inversely associated with testosterone (ß = -0.78; 95% CI: -1.40, -0.17). Concentrations of BCIPP were inversely associated with sperm concentrations (ß = -7.76; 95% CI: -14.40, -0.61), progressive motility (ß = - 4.98; 95% CI: -8.71, -1.09), and the sperm motility index (ß = -9.72; 95% CI: -17.71, -0.96). In contrast, urinary DPHP concentrations were positively associated with the sperm motility (ß = 4.37; 95% CI: 0.76, 8.12) and fertility indices (ß = 6.64; 95% CI: 1.96, 11.53). Thus, OPE detection rates were high and exposure to several OPEs was associated with altered hormone levels and semen parameters. The possibility that OPEs affect male reproduction warrants further investigation.

Occurrence of legacy and replacement plasticizers, bisphenols, and flame retardants in potable water in Montreal and South Africa.

The occurrence of thirty-nine contaminants including plasticizers, bisphenols, and flame retardants in potable water from Montreal and South Africa was analyzed to determine their presence and concentrations in different water sources. In Montreal, five bottled water (BW) brands and three drinking water treatment plants (DWTP) were included. In South Africa, water was sampled from one urban DWTP located in Pretoria, Gauteng, and one rural DWTP located in Vhembe, along with water from the same rural DWTP which had been stored in small and large plastic containers. A combination of legacy compounds, typically with proven toxic effects, and replacement compounds was investigated. Bisphenols, Dechlorane-602, Dechlorane-603, and s-dechlorane plus (s-DP) were not detected in any water samples, and a-dechlorane plus (a-DP) was only detected in one sample from Pretoria at a concentration of 1.09 ng/L. Lower brominated polybrominated diphenyl ethers (PBDE)s were detected more frequently than higher brominated PBDEs, always at low concentrations of <2 ng/L, and total PBDE levels were statistically higher in South Africa than in Montreal. Replacement flame retardants, organophosphate esters (OPEs), were detected at statistically higher concentrations in Montreal's BW (68.56 ng/L), drinking water (DW) (421.45 ng/L) and Vhembe (198.33 ng/L) than legacy PBDEs. Total OPE concentrations did not demonstrate any geographical trend; however, levels were statistically higher in Montreal's DW than Montreal's BW. Plasticizers were frequently detected in all samples, with legacy compounds DEHP, DBP, and replacement DINCH being detected in 100 % of samples with average concentrations ranging from 6.89 ng/L for DEHP in Pretoria to 175.04 ng/L for DINCH in Montreal's DW. Total plasticizer concentrations were higher in Montreal than in South Africa. The replacement plasticizers (DINCH, DINP, DIDA, and DEHA) were detected at similar frequencies and concentrations as legacy plasticizers (DEHP, DEP, DBP, MEHP). For the compounds reported in earlier studies, the concentrations detected in the present study were similar to other locations. These compounds are not currently regulated in drinking water but their frequent detection, especially OPEs and plasticizers, and the presence of replacement compounds at similar or higher levels than their legacy compounds demonstrate the importance of further investigating the prevalence and the ecological or human health effects of these compounds.

Investigation of the migration of bisphenols from baby bottles and sippy cups.

Bisphenol A (BPA) is used as a monomer in a number of consumer products, including baby bottles and sippy cups. Some jurisdictions around the world (including Canada) have regulated the production, advertising or selling polycarbonate baby bottles with BPA. Following the ban, makers have opted for alternative materials to BPA [named BPA analogues, BPAAs], which may not be as safe as promoted. The objective of this project was to conduct a migration study in baby bottles and sippy cups, and analyze 16 BPAAs, as a follow-up on the BPA migration study conducted by Health Canada in 2009. Baby bottles (20 brands) and sippy cups (13 brands) were tested for migration of BPAAs. The most commonly detected analytes in baby bottles were BPS, BPA, BPF, BPAF, BPM and BPTMC with detection frequency (DF) of more than 50%. In sippy cups, only BPA, BPS and BPF were frequently detected. The mean concentration of BPA in baby bottle leachate was 31.5 ng/L in water simulant whereas a 1.4-fold increase was seen in 50% EtOH simulant. Similarly, a 1.4-fold increase was seen in the mean concentration of BPS in 50% EtOH simulant, when compared to the mean concentration of 2.33 ng/L in water simulant. Increasing median concentration was observed for BPA as the ethanol content of the simulant increased (water<10% EtOH<50% EtOH). The concentration of BPS and BPA was higher in sippy cups than that in their matched brand of baby bottles with the 50% EtOH simulant. Although most of the target analytes were detected in baby bottles, their concentrations were low and no migration was observed for any of the analytes with increasing incubation time. Therefore, it is likely that known BPA analogues are not present in the polymers used in the manufacture of most of the baby bottle brands sold in Canada.

Synthetic Musk Compounds in Human Biological Matrices: Analytical Methods and Occurrence-A Review.

Extensive use of synthetic musk compounds (SMs) in numerous consumer and personal care products has resulted in direct human exposures via dermal absorption, inhalation of contaminated dust and volatilized fragrances, and oral ingestion of contaminated foods and liquids. SMs and their metabolites are lipophilic, hence commonly detected in various biological matrices such as blood, breast milk, and adipose tissue. Appropriate analytical techniques are needed to detect and quantify SMs in biological matrices to assess their potential effects on human health. Different methods to process and analyze SMs in biological matrices, including sample-pretreatment, solvent extraction, cleanup, and instrumental analysis, are presented in this review. The concentration levels of selected musk compounds in biological samples from different countries/regions are summarized. Finally, research gaps and questions pertaining to the analysis of SMs are identified and suggestions made for future research studies.

Vitamin E Acetate Determination in Vaping Liquids and Non-targeted Analysis of Vaping Emissions of Diluents of Concern, Vitamin E Acetate and Medium-Chain Triglycerides Oil.

During the summer of 2019, cases of lung injury associated with vaping emerged in North America, including among individuals who reported exclusive use of nicotine vaping liquids. Once vitamin E acetate was identified as a potential causative agent a quantitative method based on a simple sample dilution, separation by gas chromatography and analysis by triple quadrupole mass spectrometry (GC MSMS) was developed. Method detection limit (MDL) and limit of quantification (LOQ) were determined at 0.159 µg/mL and 0.505 µg/mL, respectively. The analysis was performed on a subset of 203 commercially sourced nicotine containing vaping liquids of various flavour profile and nicotine range (nicotine free-59 mg/mL) from an internal inventory. The target analyte, Vitamin E Acetate, was not detected in any samples analyzed, as expected, given the reported detection in literature and high association of the chemical with cannabis and not nicotine containing vaping products.

Challenges associated with quantification of selected urinary biomarkers of exposure to tobacco products.

Tobacco use, of which cigarette smoking is the most common, is a global health concern and is directly linked to over 7 million premature deaths annually. Measurement of the levels of tobacco-related biomarkers in biological matrices reflects human exposure to the chemicals in tobacco products. Nicotine, nicotine metabolites, anatabine, and anabasine are specific to tobacco and nicotine containing products. However, as nicotine and its metabolites are ubiquitous in the environment, background contamination during sample preparation can occur, making the quantification of target analytes challenging. The main purpose of the present study was to examine quality control measures needed in the determination of urinary nicotine, nicotine metabolites, anatabine, and anabasine. Urine samples (n = 75) and NIST standard reference materials SRM 3671 and SRM 3672 were analysed. A one-step extraction procedure using cold acetone was used in this study, which involved no additional clean up. The blank matrices investigated included synthetic urine prepared with HPLC-grade water, synthetic urine prepared with Milli-Q water, and bovine urine. By adopting strategies for minimizing the background levels, very low detection limits for all the target analytes ranging from 0.025 ng/mL for 3-hydroxycotinine to 0.634 ng/mL for nicotine, were achieved. Recoveries ranged between 67% and 118% with RSD values below 20%. Intra-day and inter-day precisions were in the range of 1.1-11.7% and 4.8-25.2%, respectively. The levels of all target analytes were higher in daily smokers than in non-smokers, with the largest difference observed for 3-hydroxycotinine. No difference was observed in the levels of target analytes between individuals who were former smokers, who never smoked or who were exposed to environmental tobacco smoke (ETS), except for total nicotine equivalents (TNE), which was significantly higher in non-smokers exposed to environmental tobacco smoke compared with study participants who never smoked. The results obtained from SRM 3671 and SRM 3672 could inform a potential certification of additional biomarkers of exposure to tobacco products in those standard reference materials.

Open Characterization of Vaping Liquids in Canada: Chemical Profiles and Trends.

Currently, there is a lack of comprehensive data on the diversity of chemicals present in vaping liquids. To address this gap, a non-targeted analysis of 825 vaping liquids collected between 2017 and 2019 from Canadian retailers was conducted. Prior to mass spectrometry analysis, samples were diluted 1:500 v/v with methanol or acetonitrile. Chemical compound separation and analysis was carried out using gas chromatography and triple quadrupole mass spectrometry (GC-MS/MS) systems operated in the full scan mode and mass range of 35-450 m/z. Mass spectrum for each sample was obtained in electron ionization at 70 eV and processed. Non-targeted identification workflow included use of automated mass spectral deconvolution and identification system (AMDIS), where required, as well as a number of commercially available spectral libraries. In order to validate identities, an in-house database of expected compounds previously detected in vaping liquids was used along with genuine analytical standards for compounds of interest. This resulted in a dataset of over 1,500 unique detected chemicals. Approximately half of these chemical compounds were detected only once in a single product and not in multiple products analyzed. For any sample analyzed, on average, 40% of the chemical constituents appeared to have flavouring properties. The remainder were nicotine and related alkaloids, processing, degradation or indirect additives, natural extractives and compounds with unknown roles. Data published here from the project on the Open Characterization of vaping liquids is unique as it offers a detailed understanding of products' flavour chemical profiles, the presence and frequency of chemicals of potential health concern, as well as trends and changes in products' chemical complexity over a three-year period. Non-targeted chemical surveillance such as this present valuable tools to public health officials and researchers in responding to emergent issues such as vaping associated lung injury or informing chemical based strategies which may be aimed at addressing product safety or appeal.

Simultaneous quantitation of parabens, triclosan, and methyl triclosan in indoor house dust using solid phase extraction and gas chromatography-mass spectrometry.

An integrated analytical method for the simultaneous determination of five parabens (methyl-, ethyl-, propyl-, butyl-, and benzyl-), triclosan, and methyl triclosan in indoor house dust was developed based on gas chromatographic-mass spectrometric technique (GC/MS). Analytes were extracted from dust samples by sonication. After sample cleanup by solid-phase extraction (SPE), the extracts were derivatized with N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) and then analyzed by gas chromatography coupled with ion trap mass spectrometry operated in multiple reaction monitoring (MRM) mode. For quantitation, isotope-labelled internal standards were used for each corresponding target analyte. Only 0.05 g of dust sample was needed for the analysis. Method detection limits ranged from 6.5 to 10 ng/g, and absolute recoveries from 74% to 92%. The developed method demonstrated good repeatability and reproducibility, with relative standard deviations (RSDs) less than 16% for all the analytes. The analytes were determined in dust samples collected using two vacuum sampling methods from 63 Canadian homes: a sample of fresh or "active" dust (FD) collected using a Pullman-Holt vacuum sampler, and a composite sample taken from the household vacuum cleaner (HD). Methyl paraben, propyl paraben, and triclosan were detected in all HD and FD samples. HD samples yielded median values for methyl paraben, propyl paraben, and triclosan of 1080, 463, and 378 ng/g, respectively, which were comparable to the FD sample medians of 1120, 618 and 571 ng/g. Ethyl paraben was detected at frequencies of 89% in FD and 73% in HD samples, with median values of 52 and 25 ng/g, respectively. Butyl paraben was detected at frequencies of 44% in FD and 75% in HD samples, with median values of <10 and 59 ng/g, respectively. Benzyl paraben and methyl triclosan were not detected in any of the samples collected by either method. Samples collected according to the fresh dust protocol agreed with the household vacuum samples 90% of the time. Widely scattered concentration levels were observed for target analytes from this preliminary set of 63 Canadian samples, which suggests a wide variability in Canadian household exposures to these chemicals.

A review of the analysis of biomarkers of exposure to tobacco and vaping products.

Quantification of exposure to different chemicals from both combustible cigarettes and vaping products is important in providing information on the potential health risks of these products. To assess the exposure to tobacco products, biomarkers of exposure (BOEs) are measured in a variety of biological matrices. In this review paper, current knowledge on analytical methods applied to the analysis of biomarkers of exposure to tobacco products is discussed. Numerous sample preparation techniques are available for the extraction and sample clean up for the analysis of BOEs to tobacco and nicotine delivery products. Many tobacco products-related exposure biomarkers have been analyzed using different instrumental techniques, the most common techniques being gas and liquid chromatography coupled with mass spectrometry (GC-MS, GC-MS/MS and LC-MS/MS). To assess exposure to emerging tobacco products and study exposure in dual tobacco users, the list of biomarkers analyzed in urine samples has been expanded. Therefore, the current state of the literature can be used in preparing a preferred list of biomarkers based on the aim of each study. The information summarized in this review is expected to be a handy tool for researchers involved in studying exposures to tobacco products, as well as in risk assessment of biomarkers of exposure to vaping products.

A Selective and Sensitive Gas Chromatography-Tandem Mass Spectrometry Method for Quantitation of Synthetic Musks in Human Serum.

BACKGROUND: Synthetic musk compounds are widely used as fragrances in many consumer products; however, information on human exposure and health effects is limited. Also, analytical methods for their quantification in biological matrices are limited. OBJECTIVE: In this study, an integrated method was developed and validated for the analysis of selected synthetic musk compounds in human serum. METHOD: The method is based on liquid-liquid extraction (LLE), sample clean-up by solid-phase extraction (SPE), and separation and detection by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). RESULTS: The method demonstrated good recoveries (86-105%) and high sensitivity, with low method detection limits (MDLs) ranging from 0.04 to 0.17 µg/L. The method was applied to the analysis of 10 synthetic musk compounds in 40 serum samples collected from Canadian women aged 20-44 years (20 individual samples collected in 2014 and 20 pooled samples collected in 2006). The most commonly detected compound was Galaxolide (HHCB), with median concentrations of 0.59 µg/L in samples collected in 2006, and 0.34 µg/L for samples collected in 2014. Musk ketone (MK) was not detected in any of the samples collected in 2006, but was detected in 60% of the samples collected in 2014 with a median concentration of 0.29 µg/L. Tonalide (AHTN) was detected in only one sample above its MDL (0.12 µg/L). CONCLUSIONS: This is the first study in Canada to report levels of synthetic musks in human. The data generated from this study has been used in risk screening assessment by Environment and Climate Change Canada and Health Canada.

Short-chain and medium-chain chlorinated paraffins in Canadian house dust and NIST SRM 2585.

A method for the analysis of short-chain and medium-chain chlorinated paraffins (SCCPs and MCCPs) in house dust was developed. The method is based on sonication extraction, sample cleanup by solid phase extraction (SPE), and separation and detection by gas chromatography coupled with mass spectrometry (GC/MS) operated in electron capture negative ion (ECNI) chemical ionization mode. The method is sensitive, with method detection limits (MDLs) down to 0.22 µg/g for SCCPs and 0.55 µg/g for MCCPs. The overall recoveries of the method were 104 (± 11)% and 108 (± 16)% for SCCPs and MCCPs, respectively. The method was successfully applied to the analysis of SCCPs and MCCPs in NIST standard reference material (SRM 2585, organic contaminants in house dust) and a subset of house dust samples collected under the Canadian House Dust Study (CHDS). Average concentrations of SCCPs and MCCPs in SRM 2585 (n = 12 replicates) were 7.58 (± 0.43) µg/g for SCCPs and 16.4 (± 2.1) µg/g for MCCPs, respectively. A comparison was made between CP concentrations in paired dust samples collected using two different methods from the same homes: fresh or "active" dust (FD) collected by technicians and a sample taken from the household vacuum cleaner (HD). Spearman rank analysis showed a significant positive correlation (p < 0.01) between FD and HD samples for both MCCPs and SCCPs. CPs were detected in every house dust sample (n = 48 HD samples), with median (range) concentrations of 6.2 (4.0 - 57) µg/g and 19 (5.9-901) µg/g for SCCPs and MCCPs, respectively. Widely scattered CP levels and 100% detection frequency in this preliminary set of 48 HD samples suggest a wide variability in Canadian household exposures to CPs.

Are cell phones an indicator of personal exposure to organophosphate flame retardants and plasticizers?

BACKGROUND: Exposure to organophosphate ester (OPE) flame retardants and plasticizers is widespread and is of concern due to their toxicity. OBJECTIVES: To investigate relationships between and within OPE concentrations in air, dust, hands, electronic product wipes and urinary metabolites with the goal of identifying product sources and exposure pathways. METHODS: Women in Toronto and Ottawa, Canada, provided a urine sample, two sets of hand wipes, access to their homes for air and dust sampling, and completed a questionnaire. OPE concentrations were obtained for air and floor dust in the bedroom (n = 51) and most used room (n = 26), hand wipes (n = 204), and surface wipes of handheld (n = 74) and non-handheld electronic devices (n = 125). All air, dust and wipe samples were analyzed for 23 OPE compounds; urine samples (n = 44) were analyzed for 8 OPE metabolites. RESULTS: Five-8 OPEs were detected in >80% of samples depending on the sample type. OPE median concentrations in hand wipes taken 3 weeks apart were not significantly different. Palms had higher concentrations than the back of hands; both were significantly correlated. Concentrations of 9 OPEs were significantly higher in surface wipes of handheld than non-handheld electronic devices. Six OPEs in hand wipes were significantly correlated with cell phone wipes, with two to four OPEs significantly correlated with tablet, laptop and television wipes. Multiple regression models using hand wipes, cell phone wipes and dust explained 8-33% of the variation in creatinine-adjusted urinary metabolites; air concentrations did not have explanatory power. OPEs in cell phone wipes explained the greatest variation in urinary metabolites. CONCLUSIONS: Handheld electronic devices, notably cell phones, may either be sources or indicators of OPE exposure through hand-to-mouth and/or dermal uptake.

Serum levels of perfluoroalkyl compounds in human maternal and umbilical cord blood samples.

Perfluoroalkyl compounds (PFCs) are end-stage metabolic products from industrial flourochemicals used in the manufacture of plastics, textiles, and electronics that are widely distributed in the environment. The objective of the present study was to quantify exposure to perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorodecanoic acid (PFDeA), perfluorohexane sulfonate (PFHxS), perfluoroheptanoic acid (PFHpA), and perfluorononanoic acid (PFNA) in serum samples collected from pregnant women and the umbilical cord at delivery. Pregnant women (n=101) presenting for second trimester ultrasound were recruited and PFC residue levels were quantified in maternal serum at 24-28 weeks of pregnancy, at delivery, and in umbilical cord blood (UCB; n=105) by liquid chromatography-mass spectrometry. Paired t-test and multiple regression analysis were performed to determine the relationship between the concentrations of each analyte at different sample collection time points. PFOA and PFOS were detectable in all serum samples analyzed including the UCB. PFOS serum levels (mean+/-S.D.) were significantly higher (p<0.001) in second trimester maternal serum (18.1+/-10.9 ng/mL) than maternal serum levels at delivery (16.2+/-10.4 ng/mL), which were higher than the levels found in UCB (7.3+/-5.8 ng/mL; p<0.001). PFHxS was quantifiable in 46/101 (45.5%) maternal and 21/105 (20%) UCB samples with a mean concentration of 4.05+/-12.3 and 5.05+/-12.9 ng/mL, respectively. There was no association between serum PFCs at any time point studied and birth weight. Taken together our data demonstrate that although there is widespread exposure to PFCs during development, these exposures do not affect birth weight.

Analysis of Bisphenol A, Alkylphenols, and Alkylphenol Ethoxylates in NIST SRM 2585 and Indoor House Dust by Gas Chromatography-Tandem Mass Spectrometry (GC/MS/MS).

Background: Ingestion of house dust has been demonstrated to be an important exposure pathway to several contaminants in young children. These compounds include bisphenol A (BPA), alkylphenols (APs), and alkylphenol ethoxylates (APEOs). Analysis of these compounds in house dust is challenging because of the complex composition of the sample matrix. Objective: The objective was to develop a simple and sensitive method to measure BPA, APs, and APEOs in indoor house dust. Methods: An integrated method that involved solvent extraction using sonication, sample cleanup by solid-phase extraction, derivatization by 2,2,2-trifluoro-N-methyl-N-(trimethylsilyl)acetamide, and analysis by GC coupled with tandem MS was developed for the simultaneous determination of BPA, APs, and APEOs in NIST Standard Reference Material (SRM) 2585 (Organic contaminants in house dust) and in settled house dust samples. Results: Target analytes included BPA, 4-tert-octylphenol (OP), OP monoethoxylate, OP diethoxylate, 4-n-nonylphenol (4nNP), 4nNP monoethoxylate (4nNP1EO), branched nonylphenol (NP), NP monoethoxylate, NP diethoxylate, NP triethoxylate, and NP tetraethoxylate. The method was sensitive, with method detection limits ranging from 0.05 to 5.1 µg/g, and average recoveries between 82 and 115%. All target analytes were detected in SRM 2585 and house dust except 4nNP and 4nNP1EO. Conclusions: The method is simple and fast, with high sensitivity and good reproducibility. It is applicable to the analysis of target analytes in similar matrixes, such as sediments, soil, and biosolids. Highlights: Values measured in SRM 2585 will be useful for future research in method development and method comparison.