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[Display omitted] Exposure to polycyclic aromatic hydrocarbons (PAHs) in the Chinese population was among the highest globally and associated with various adverse effects. This study examines the impact of China's two-phase clean air initiatives, namely the Air Pollution Prevention and Control Action Plan (APPCAP) in 2013–2017 and the Blue-Sky Defense War (BSDW) in 2018–2020, on PAH levels and human exposures in Beijing. To evaluate the effects of APPCAP, we measured 16 PAHs in 287 PM 2.5 samples collected in Beijing and 9 PAH metabolites in 358 urine samples obtained from 54 individuals who traveled from Los Angeles to Beijing between 2014 and 2018. The concentration of PM 2.5 -bound benzo[a]pyrene equivalents (BaPeq) decreased by 88.5% in 2014–2018 due to reduced traffic, coal, and biomass emissions. PAH metabolite concentrations in travelers' urine decreased by 52.3% in Beijing, correlated with changes in PM 2.5 and NO 2 levels. In contrast, no significant changes were observed in Los Angeles. To evaluate BSDW's effects, we collected 123 additional PM 2.5 samples for PAH measurements in 2019–2021. We observed sustained reductions in BaPeq concentrations attributable to reductions in coal and biomass emissions during the BSDW phase, but those from traffic sources remained unchanged. After accounting for meteorological factors, China's two-phase clean air initiatives jointly reduced Beijing's PM 2.5 -bound BaPeq concentrations by 96.6% from 2014 to 2021. These findings provide compelling evidence for the effectiveness of China's clean air actions in mitigating population exposure to PAHs in Beijing. [ABSTRACT FROM AUTHOR]

Based on toxicological evidence, children's exposure to phthalates may contribute to altered neurodevelopment and abnormal regulation of brain-derived neurotrophic factor (BDNF). We analyzed data from five aligned studies of the Human Biomonitoring for Europe (HBM4EU) project. Ten phthalate metabolites and protein BDNF levels were measured in the urine samples of 1148 children aged 6–12 years from Italy (NACII-IT cohort), Slovakia (PCB-SK cohort), Hungary (InAirQ-HU cohort) and Norway (NEBII-NO). Serum BDNF was also available in 124 Slovenian children (CRP-SLO cohort). Children's total, externalizing and internalizing behavioral problems were assessed using the Child Behavior Checklist at 7 years of age (only available in the NACII-IT cohort). Adjusted linear and negative binomial regression models were fitted, together with weighted quantile sum (WQS) regression models to assess phthalate mixture associations. Results showed that, in boys but not girls of the NACII-IT cohort, each natural-log-unit increase in mono-n-butyl phthalate (MnBP) and Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) was cross-sectionally associated with higher externalizing problems [incidence rate ratio (IRR): 1.20; 95% CI: 1.02, 1.42 and 1.26; 95% CI: 1.03, 1.55, respectively]. A suggestive mixture association with externalizing problems was also observed per each tertile mixture increase in the whole population (WQS—IRR = 1.15; 95% CI: 0.97, 1.36) and boys (IRR = 1.20; 95% CI: 0.96, 1.49). In NACII-IT, PCB-SK, InAirQ-HU and NEBII-NO cohorts together, urinary phthalate metabolites were strongly associated with higher urinary BDNF levels, with WQS regression confirming a mixture association in the whole population (percent change (PC) = 25.9%; 95% CI: 17.6, 34.7), in girls (PC = 18.6%; 95% CI: 7.92, 30.5) and mainly among boys (PC = 36.0%; 95% CI: 24.3, 48.9). Among CRP-SLO boys, each natural-log-unit increase in ∑DINCH concentration was associated with lower serum BDNF levels (PC: −8.8%; 95% CI: −16.7, −0.3). In the NACII-IT cohort, each natural-log-unit increase in urinary BDNF levels predicted worse internalizing scores among all children (IRR: 1.15; 95% CI: 1.00, 1.32). Results suggest that (1) children's exposure to di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) metabolites is associated with more externalizing problems in boys, (2) higher exposure to DINCH may associate with lower systemic BDNF levels in boys, (3) higher phthalate exposure is associated with higher urinary BDNF concentrations (although caution is needed since the possibility of a "urine concentration bias" that could also explain these associations in noncausal terms was identified) and (4) higher urinary BDNF concentrations may predict internalizing problems. Given this is the first study to examine the relationship between phthalate metabolite exposure and BDNF biomarkers, future studies are needed to validate the observed associations. [ABSTRACT FROM AUTHOR]

Acetyl tributyl citrate (ATBC) and acetyl triethyl citrate (ATEC) are widely used as plasticizers, but their metabolites as exposure biomarkers for biomonitoring, as well as approximate human metabolic pathways, are not well understood. This study addresses this knowledge gap by conducting suspect screening to propose specific metabolites in human urine as potential biomarkers of exposure and explore their kinetic profiles. Ten volunteers were administered deuterium labeled ATBC (ATBC-d3) and seven received ATEC or deuterium labeled ATEC (ATEC-d3), with urine samples collected over 48 h post-administration. Employing ultra-performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC-qTOF/MS), six metabolites of ATBC were consistently detected, including (OH)3-ATBC-d3, ADBC-d3, OH-ADBC-d3, DBC, OH-DBC, and OH-DBA. For ATEC, four metabolites were identified: ADEC-d3, AMEC-d3, OH-ADEC-d3, and DEC. Based on their high detection frequency, relative response, and specificity to their parent compounds, ADBC-d3 and OH-ADBC-d3 were identified as promising candidate biomarkers for ATBC exposure, while ADEC-d3 emerged as a suitable biomarker for ATEC. Estimated urinary elimination half-lives ranged from 1.0 to 9.9 h for ATBC metabolites and 1.6 to 3.0 h for ATEC metabolites. One-compartment kinetic modeling provided preliminary insights into metabolite kinetics. This research advances the understanding of ATBC and ATEC metabolism in humans, providing a foundation for future exposure assessments and toxicological studies. The identified biomarkers and preliminary metabolic profiles offer valuable starting points for biomonitoring and risk assessment of these alternative plasticizers.

Acetyl tributyl citrate (ATBC) and acetyl triethyl citrate (ATEC) are increasingly used as alternatives to phthalates in various products, including food packaging, medical devices, and personal care items, raising concerns about their potential health impacts. This study aimed to investigate the in vitro human metabolism of ATBC and ATEC and identify potential exposure biomarkers applicable in human biomonitoring. Pooled human liver microsomes were utilized to conduct in vitro metabolism assays of deuterium labeled ATBC (ATBC-d3) and ATEC, and ultra performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC-qToF/MS) was employed for analysis. Suspect screening workflow and confidence level assignment were applied for metabolite identification. Time-course analysis revealed rapid metabolism of both compounds, with estimated apparent half-lives of approximately 5 min for ATBC-d3 and less than 15 min for ATEC. Eleven metabolites were identified for ATBC-d3 and six for ATEC. The predominant chemical reactions observed were carboxylic ester hydrolysis, deacetylation, and hydroxylation. Based on their abundance and specificity, MB1 (hydroxylated) and MB11 (hydrolyzed and hydroxylated) were proposed as candidate exposure biomarkers for ATBC, and ME1 (hydrolyzed and deacetylated) for ATEC. The identified metabolites and proposed sequences of kinetic process enhance our understanding of the fate of these compounds in the human body, potentially informing future toxicological assessments and guiding the development of more comprehensive human biomonitoring strategies.

Chlorine is a toxic industrial chemical that has been used as a chemical weapon in recent armed conflicts. Confirming human exposure to chlorine has proven challenging, and there is currently no established method for analyzing human biomedical samples to unambiguously verify chlorine exposure. In this study, two chlorine-specific biomarkers: palmitoyl-oleoyl phosphatidylglycerol chlorohydrin (POPG-HOCl) and the lipid derivative oleoyl ethanolamide chlorohydrin (OEA-HOCl) are shown in bronchoalveolar lavage fluid (BALF) samples from spontaneously breathing pigs after chlorine exposure. These biomarkers are formed by the chemical reaction of chlorine with unsaturated phospholipids found in the pulmonary surfactant, which is present at the gas-liquid interface within the lung alveoli. Our results strongly suggest that lipid chlorohydrins are promising candidate biomarkers in the development of a verification method for chlorine exposure. The establishment of verified methods capable of confirming the illicit use of toxic industrial chemicals is crucial for upholding the principles of the Chemical Weapons Convention (CWC) and enforcing the ban on chemical weapons. This study represents the first published dataset in BALF revealing chlorine biomarkers detected in a large animal. Furthermore, these biomarkers are distinct in that they originate from molecular chlorine rather than hypochlorous acid. [Display omitted] • Detection of two phospholipid biomarkers, intact POPG-HOCl and its derivate OEA-HOCl, in BALF from pig after chlorine exposure • The chlorine specific biomarkers were detectable despite mild acute lung injury • These findings is one step closer the goal of a method for verification of chlorine exposure in humans [ABSTRACT FROM AUTHOR]

Based on toxicological evidence, children’s exposure to phthalates may contribute to altered neurodevelopment and abnormal regulation of brain-derived neurotrophic factor (BDNF). We analyzed data from five aligned studies of the Human Biomonitoring for Europe (HBM4EU) project. Ten phthalate metabolites and protein BDNF levels were measured in the urine samples of 1148 children aged 6–12 years from Italy (NACII-IT cohort), Slovakia (PCB-SK cohort), Hungary (InAirQ-HU cohort) and Norway (NEBII-NO). Serum BDNF was also available in 124 Slovenian children (CRP-SLO cohort). Children’s total, externalizing and internalizing behavioral problems were assessed using the Child Behavior Checklist at 7 years of age (only available in the NACII-IT cohort). Adjusted linear and negative binomial regression models were fitted, together with weighted quantile sum (WQS) regression models to assess phthalate mixture associations. Results showed that, in boys but not girls of the NACII-IT cohort, each natural-log-unit increase in mono-n-butyl phthalate (MnBP) and Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) was cross-sectionally associated with higher externalizing problems [incidence rate ratio (IRR): 1.20; 95% CI: 1.02, 1.42 and 1.26; 95% CI: 1.03, 1.55, respectively]. A suggestive mixture association with externalizing problems was also observed per each tertile mixture increase in the whole population (WQS—IRR = 1.15; 95% CI: 0.97, 1.36) and boys (IRR = 1.20; 95% CI: 0.96, 1.49). In NACII-IT, PCB-SK, InAirQ-HU and NEBII-NO cohorts together, urinary phthalate metabolites were strongly associated with higher urinary BDNF levels, with WQS regression confirming a mixture association in the whole population (percent change (PC) = 25.9%; 95% CI: 17.6, 34.7), in girls (PC = 18.6%; 95% CI: 7.92, 30.5) and mainly among boys (PC = 36.0%; 95% CI: 24.3, 48.9). Among CRP-SLO boys, each natural-log-unit increase in ∑DINCH concentration was associated with lower serum BDNF levels (PC: −8.8%; 95% CI: −16.7, −0.3). In the NACII-IT cohort, each natural-log-unit increase in urinary BDNF levels predicted worse internalizing scores among all children (IRR: 1.15; 95% CI: 1.00, 1.32). Results suggest that (1) children’s exposure to di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) metabolites is associated with more externalizing problems in boys, (2) higher exposure to DINCH may associate with lower systemic BDNF levels in boys, (3) higher phthalate exposure is associated with higher urinary BDNF concentrations (although caution is needed since the possibility of a “urine concentration bias” that could also explain these associations in noncausal terms was identified) and (4) higher urinary BDNF concentrations may predict internalizing problems. Given this is the first study to examine the relationship between phthalate metabolite exposure and BDNF biomarkers, future studies are needed to validate the observed associations.

Diesel exhaust (DE), Group 1 carcinogen, is an important source of air pollutants. Studies show that DE exposure associates with elevated incidences of respiratory and cardiovascular diseases. The toxic effects of DE are closely related to its components. Polycyclic aromatic hydrocarbons (PAHs) are one of the main toxic components in DE and are often used as human exposure biomarkers to DE. However, the exposure assessment of DE using PAHs as biomarkers could be interfered due to the other sources of PAHs. Therefore, identification of highly specific and reliable PAHs sourced biomarkers of DE exposure has become a hotspot of current research. New biomarkers of DE may play an important role in determining human exposure to DE and establishing dose-response relationship of DE exposure and health outcomes of interest. This paper focused on current progress in terms of PAHs sourced biomarkers of human exposure to DE with the following aims: (1) to clarify the types of PAHs sourced biomarkers to DE; (2) to explore the applicability and limitations of PAHs sourced biomarkers for DE exposure assessment in occupational exposure and environmental exposure analysis; and (3) to summarize the analysis methods for PAHs sourced exposure biomarkers in human urine samples and compare the advantages and disadvantages of different analytical methods.

[Display omitted] • Metabolites of ATBC and ATEC were suspect screened after human oral administration of ATBC-d 3 and ATEC-d 3 (ATEC). • Total 6 metabolites of ATBC and 4 metabolites of ATEC were commonly observed in the urine samples. • ADBC and OH-ADBC for ATBC, and ADEC for ATEC are considered the most suitable exposure biomarkers. • The kinetic properties of ATBC and ATEC metabolites were investigated, and their in vivo kinetic pathways in humans were predicted using one-compartment kinetic modeling. Acetyl tributyl citrate (ATBC) and acetyl triethyl citrate (ATEC) are widely used as plasticizers, but their metabolites as exposure biomarkers for biomonitoring, as well as approximate human metabolic pathways, are not well understood. This study addresses this knowledge gap by conducting suspect screening to propose specific metabolites in human urine as potential biomarkers of exposure and explore their kinetic profiles. Ten volunteers were administered deuterium labeled ATBC (ATBC-d 3) and seven received ATEC or deuterium labeled ATEC (ATEC-d 3), with urine samples collected over 48 h post-administration. Employing ultra-performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC-qTOF/MS), six metabolites of ATBC were consistently detected, including (OH) 3 -ATBC-d 3 , ADBC-d 3 , OH-ADBC-d 3 , DBC, OH-DBC, and OH-DBA. For ATEC, four metabolites were identified: ADEC-d 3 , AMEC-d 3 , OH-ADEC-d 3 , and DEC. Based on their high detection frequency, relative response, and specificity to their parent compounds, ADBC-d 3 and OH-ADBC-d 3 were identified as promising candidate biomarkers for ATBC exposure, while ADEC-d 3 emerged as a suitable biomarker for ATEC. Estimated urinary elimination half-lives ranged from 1.0 to 9.9 h for ATBC metabolites and 1.6 to 3.0 h for ATEC metabolites. One-compartment kinetic modeling provided preliminary insights into metabolite kinetics. This research advances the understanding of ATBC and ATEC metabolism in humans, providing a foundation for future exposure assessments and toxicological studies. The identified biomarkers and preliminary metabolic profiles offer valuable starting points for biomonitoring and risk assessment of these alternative plasticizers. [ABSTRACT FROM AUTHOR]

[Display omitted] • ATBC-d3 and ATEC metabolites identified after incubation with human liver microsomes. • 11 ATBC and 6 ATEC metabolites detected through suspect screening. • Specific metabolites of ATBC and ATEC proposed as exposure biomarkers. • Phase I metabolic pathways predicted using kinetic models and time-course data. Acetyl tributyl citrate (ATBC) and acetyl triethyl citrate (ATEC) are increasingly used as alternatives to phthalates in various products, including food packaging, medical devices, and personal care items, raising concerns about their potential health impacts. This study aimed to investigate the in vitro human metabolism of ATBC and ATEC and identify potential exposure biomarkers applicable in human biomonitoring. Pooled human liver microsomes were utilized to conduct in vitro metabolism assays of deuterium labeled ATBC (ATBC-d 3) and ATEC, and ultra performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC-qToF/MS) was employed for analysis. Suspect screening workflow and confidence level assignment were applied for metabolite identification. Time-course analysis revealed rapid metabolism of both compounds, with estimated apparent half-lives of approximately 5 min for ATBC-d 3 and less than 15 min for ATEC. Eleven metabolites were identified for ATBC-d 3 and six for ATEC. The predominant chemical reactions observed were carboxylic ester hydrolysis, deacetylation, and hydroxylation. Based on their abundance and specificity, MB1 (hydroxylated) and MB11 (hydrolyzed and hydroxylated) were proposed as candidate exposure biomarkers for ATBC, and ME1 (hydrolyzed and deacetylated) for ATEC. The identified metabolites and proposed sequences of kinetic process enhance our understanding of the fate of these compounds in the human body, potentially informing future toxicological assessments and guiding the development of more comprehensive human biomonitoring strategies. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are among the chemicals with proven impact on workers' health. The use of human biomonitoring (HBM) to assess occupational exposure to PAHs has become more common in recent years, but the data generated need an overall view to make them more usable by regulators and policymakers. This comprehensive review, developed under the Human Biomonitoring for Europe (HBM4EU) Initiative, was based on the literature available from 2008–2022, aiming to present and discuss the information on occupational exposure to PAHs, in order to identify the strengths and limitations of exposure and effect biomarkers and the knowledge needs for regulation in the workplace. The most frequently used exposure biomarker is urinary 1-hydroxypyrene (1-OH-PYR), a metabolite of pyrene. As effect biomarkers, those based on the measurement of oxidative stress (urinary 8-oxo-dG adducts) and genotoxicity (blood DNA strand-breaks) are the most common. Overall, a need to advance new harmonized approaches both in data and sample collection and in the use of appropriate biomarkers in occupational studies to obtain reliable and comparable data on PAH exposure in different industrial sectors, was noted. Moreover, the use of effect biomarkers can assist to identify work environments or activities of high risk, thus enabling preventive risk mitigation and management measures. [ABSTRACT FROM AUTHOR]

VX, a well-known organophosphorus nerve agent (OPNA), poses a significant threat to public safety if employed by terrorists. Obtaining complete metabolites is critical to unequivocally confirm its alleged use/exposure and elucidate its whole-molecular metabolism. However, the nitrogenous VX metabolites containing 2-diisopropylaminoethyl moiety from urinary excretion remain unknown. Therefore, this study applied a newly developed untargeted workflow platform to discover and identify them using VX-exposed guinea pigs as animal models. 2-(N,N -diisopropylamino)ethanesulfonic acid (DiPSA) was revealed as a novel nitrogenous VX metabolite in urine, and 2-(Diisopropylaminoethyl) methyl sulfide (DAEMS) was confirmed as another in plasma, indicating that VX metabolism differed between urine and plasma. It is the first report of a nitrogenous VX metabolite in urine and a complete elucidation of the VX metabolic pathway. DiPSA was evaluated as an excellent VX exposure biomarker. The whole-molecule VX metabolism in urine was characterized entirely for the first time via the simultaneous quantification of DiPSA and two known P-based biomarkers. About 52.1% and 32.4% of VX were excreted in urine as P-based and nitrogenous biomarkers within 24 h. These findings provide valuable insights into the unambiguous detection of OPNA exposure/intoxication and human and environmental exposure risk assessment. [Display omitted] • A novel nitrogenous VX metabolite (DiPSA) was revealed in urine. • DiPSA was evaluated as an excellent biomarker of VX exposure for the first time. • First characterization of whole-molecule VX metabolism in urine. • 32.4% of VX excreted as DiPSA and 52.1% as P-based metabolites in urine within 24 h. • First realizing unique confirmation of whole-molecule VX exposure from urine samples. [ABSTRACT FROM AUTHOR]

• Oral dose of di- n -butyl adipate (DnBA) to three volunteers. • Dose recoveries of four oxidized monoester metabolites 0.005−0.47 % (mean values). • Dermal application of sunscreen containing DnBA (n = 3): different metabolite ratios. • Excretion kinetics up to 48 h (oral) and 72 h (dermal). • Simple monoester and 3-hydroxy metabolite seem specific biomarkers of exposure. Di- n -butyl adipate (DnBA) is used as a plasticizer and in various consumer products (e.g. personal care products) replacing, in part, the endocrine disruptor di- n -butyl phthalate (DnBP). We provide quantitative in vivo data on human DnBA metabolism and excretion after oral dose (105−185 μg/kg bw) and dermal application to three volunteers each as a tool for exposure and risk assessment. Complete and consecutive urine samples were collected for two (oral) and four days (dermal), respectively, and analyzed for the metabolites mono- n -butyl adipate (MnBA), 3- and tentative 4-hydroxy-mono- n -butyl adipate (3OH-MnBA, 4OH-MnBA), and 3-carboxy-mono- n -propyl adipate (3cx-MnPrA), as well as the hydrolysis product adipic acid (AA) using stable isotope dilution quantification. Metabolites were excreted within 24 h after oral dose with one or two concentration maxima at 0.8–3.0 h (n = 3) and 4.8−6.3 h (n = 2). AA was the major but unspecific metabolite with urinary excretion fractions (F UE s) of 14−26 %. Mean F UE s (range) of 3cx-MnPrA, MnBA, 3OH-MnBA, and tentative 4OH-MnBA were low, but consistent between volunteers (0.47 % (0.35−0.63 %), 0.079 % (0.065−0.091 %), 0.012 % (0.006−0.016 %), and 0.005 % (0.002−0.009 %), respectively). MnBA and 3OH-MnBA seem to be suitable, specific exposure biomarkers for DnBA, whereas 3cx-MnPrA and 4OH-MnBA seem to originate also from other, unknown sources not related to DnBA. Compared to the oral study, metabolite excretion in the dermal study was delayed and MnBA excretion was somewhat higher compared to the oxidized metabolites. Based on urinary concentrations and the above excretion fractions, calculated uptakes in the dermal study did not exceed the adipate ester ADI of 5 mg/(kg bw*day). [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are among the chemicals with proven impact on workers’ health. The use of human biomonitoring (HBM) to assess occupational exposure to PAHs has become more common in recent years, but the data generated need an overall view to make them more usable by regulators and policymakers. This comprehensive review, developed under the Human Biomonitoring for Europe (HBM4EU) Initiative, was based on the literature available from 2008–2022, aiming to present and discuss the information on occupational exposure to PAHs, in order to identify the strengths and limitations of exposure and effect biomarkers and the knowledge needs for regulation in the workplace. The most frequently used exposure biomarker is urinary 1-hydroxypyrene (1-OH-PYR), a metabolite of pyrene. As effect biomarkers, those based on the measurement of oxidative stress (urinary 8-oxo-dG adducts) and genotoxicity (blood DNA strand-breaks) are the most common. Overall, a need to advance new harmonized approaches both in data and sample collection and in the use of appropriate biomarkers in occupational studies to obtain reliable and comparable data on PAH exposure in different industrial sectors, was noted. Moreover, the use of effect biomarkers can assist to identify work environments or activities of high risk, thus enabling preventive risk mitigation and management measures.

Electronic nicotine delivery systems (ENDS), or e-cigarettes, are emerging tobacco products that produce aerosols by heating eliquids, which most often consist of propylene glycol and vegetable glycerin along with various flavoring compounds, bypassing the combustion that occurs in the use of traditional tobacco cigarettes. These products have seen a drastic increase in popularity in recent years both as smoking cessation devices as well as among younger generations, due in large part to the widespread perception among consumers that e-cigs are significantly less harmful to health than traditional tobacco cigarettes. Due to the novelty of ENDS as well as their rapidly increasing use, research into biomarkers of e-cig exposure and toxicity have lagged behind their popularity, leaving important questions about their potential toxicity unanswered. Research into potential biomarkers of acute and chronic e-cig use, and e-cigarette- or vaping-associated lung injury is necessary for informing both clinical and regulatory decision-making. We aim to provide an updated review of recent research into potential circulating, genomic, transcriptomic, and epigenetic biomarkers of exposure to and toxicity of e-cigs. We additionally highlight research areas that warrant additional study to gain a better understanding of health risks associated with ENDS use, as well as to provide validation of existing data and methods for measuring and analyzing e-cig-associated biomarkers in human and animal biofluids, tissues, and cells. This review also highlights ongoing efforts within the WNY Center for Research on Flavored Tobacco for research into novel biomarkers in extracellular vesicles that may be associated with short- and long-term ENDS use. [ABSTRACT FROM AUTHOR]

Although overexposure to manganese (Mn) is known to cause neurotoxic damage, effective exposure markers for assessing Mn loading in Mn-exposed workers are lacking. Here, we construct a Mn-exposed rat model to perform correlation analysis between Mn-induced neurological damage and Mn levels in various biological samples. We combine this analysis with epidemiological investigation to assess whether Mn concentrations in red blood cells (MnRBCs) and urine (MnU) can be used as valid exposure markers. The results show that Mn exposure resulted in neurotoxic damage in rats and that MnRBCs correlated well with neurological damage, showing potential as a novel Mn exposure biomarker. These findings provide a basis for health monitoring of Mn-exposed workers and the development of more appropriate biological exposure limits., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aflatoxin M 1 (AFM 1) is generally used as a biomarker in urine for the assessment of aflatoxin exposure in humans and animals. However, there is no approach for the rapid and on-site monitoring of AFM 1 level in urine. Here, we report a surface enhanced Raman scattering (SERS)-based lateral flow immunosensor built for such a purpose. Raman molecule 5,5-dithiobis-2-nitrobenzoic acid and anti-AFM 1 monoclonal antibody were conjugated with Au (core)@Ag (shell) nanoparticle to serve as SERS nanoprobe. AFM 1 -bovine serum albumin was conjugated with gold nanoparticle and then applied onto nitrocellulose membrane as a visible "GOLD" test line. Quantitation of AFM 1 was performed by the readout of Raman signal from the SERS nanoprobes captured on the test line. After optimizing experimental parameters, the detection limit of this immunosensor can achieve as low as 1.7 pg/mL of AFM 1 in urine, which is far below the recommended tolerable level (30 pg/mL) of AFM 1 in urine. The spiking experiment yielded 93.8%–111.3% recovery with coefficients of variation below 17% demonstrating high assay accuracy and precision. Moreover, this immunosensing assay is fast with an assay time below 20 min. Therefore, the developed immunosensor is a promising tool for the rapid assessment of aflatoxin exposure in the field. Image 1 • A surface enhanced Raman scattering-based lateral flow immunosensor was developed for AFM 1 in urine. • A visible "GOLD" test line was constructed to help the accurate location of test line in the immunosensor. • The detection limit was as low as 1.7 pg/mL of AFM 1 in urine. • The spiked recovery ratios were 93.8%–111.3% with coefficients of variation below 17%. • The detection time was less than 20 min. [ABSTRACT FROM AUTHOR]

Highlights • Human urinary excretion kinetics of 2-ethylhexyl salicylate (EHS) after oral dosage. • 7 metabolites identified, 3 metabolites unique to EHS investigated quantitatively. • Urinary excretion fractions for these 3 specific EHS metabolites. • ≥95% of these metabolites excreted within 24 h. • Exemplary calculation of metabolite-based daily EHS intakes for a pilot population. Abstract The UV filter 2-ethylhexyl salicylate (EHS) is used in sunscreens and other personal care products worldwide and has been found in a variety of environmental media. We aimed to provide human toxicokinetic data on EHS as a tool for risk assessment. For that purpose, we investigated metabolism and urinary metabolite excretion after a single oral EHS dose (57.4–75.5 μg/(kg body weight)) in three male volunteers. In a suspect screening, we tentatively identified seven EHS metabolites. Three EHS specific metabolites were quantitatively investigated: 2-ethyl-5-hydroxyhexyl 2-hydroxybenzoate (5OH-EHS), 2-ethyl-5-oxohexyl 2-hydroxybenzoate (5oxo-EHS), and 5-(((2-hydroxybenzoyl)oxy)methyl)heptanoic acid (5cx-EPS). These metabolites were excreted with urinary excretion fractions of 0.28% (range: 0.13−0.54%), 0.11% (0.06−0.20%), and 0.24% (0.14−0.41%), respectively. The elimination was fast: peak urinary concentrations were found 1.6–2.6 h after dose and ≥95% of the total amounts were excreted within 24 h. Elimination kinetics were biphasic, with mean elimination half-lives of 0.8 h (first phase) and 6.6 h (second phase) for 5OH-EHS, 0.8 h and 6.3 h for 5oxo-EHS, and 1.1 h and 5.9 h for 5cx-EPS. After dermal exposure (sunscreen application), we found a considerably delayed EHS elimination. Based on urinary metabolite levels we calculated EHS exposure levels for a small pilot population. [ABSTRACT FROM AUTHOR]

• Achieving generic detection of OPNA exposure by improving PGS and digestion method. • Removing matrix interference by adding NaCl to the washing buffer of PGS. • Reducing the aging of OPNA-BChE adducts by improving pH and time of pepsin digestion. • More sensitive and generic detection of OPNA exposure than pervious PGS methods. • Full describing adducted BChE levels versus five types of OPNA-exposed conc. in plasma. Organophosphorus nerve agent (OPNA) adducts to butyrylcholinesterase (BChE) can be applied to confirm exposure in humans. A sensitive method for generic detection of G- and V-series OPNA adducts to BChE in plasma was developed by combining an improved procainamide-gel separation (PGS) and pepsin digestion protocol with ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Residual matrix interferences from prior PGS purification of OPNA-BChE adducts from plasma were found to be a critical cause of significantly reduced UHPLC-MS/MS detection sensitivity. In our developed on-column PGS approach, the matrix interference was successfully removed by adding an appropriate concentration of NaCl to the washing buffer, and it could capture ≥92.5% of the BChE in plasma. The lower pH value and the longer digestion time in all previous pepsin digestion methods were found to be a key accelerated aging factor of several adducts such as tabun (GA)-, cyclohexylsarin (GF)-, and soman (GD)-BChE nonapeptide adducts, making them difficult to detect. The aging event of several OPNA-BChE nonapeptide adducts was so successfully addressed that the formic acid level in enzymatic buffer and digestion time were lowered to 0.05% (pH 2.67) and 0.5 h, respectively, and the post-digestion reaction was immediately terminated. The improved condition parameters were optimal for pepsin digestion of all types of OPNA-BChE adducts into their individual unaged nonapeptide adducts with the highest yields, expanding the applicability of the method. The method had a nearly one-fold decrease in sample preparation time through the reduction of digestion time and removal of ultrafiltration procedure after digestion. The limit of identification (LOI) were determined respectively as 0.13 ng mL−1, 0.28 ng mL−1, 0.50 ng mL−1, 0.41 ng mL−1 and 0.91 ng mL−1 for VX-, sarin (GB)-, GA-, GF-, and GD-exposed human plasma, being low exposure value compared to previously documented approaches. The approach was utilized to fully characterize the adducted (aged and unaged) BChE levels of five OPNAs in a series of their individual exposed concentration (1.00–400 nM) of plasma sample, and successfully detect OPNA exposure from all unknown plasma samples from OPCW's second and third biomedical proficiency tests. The OPNA-BChE adducts, their aged adducts, and unadducted BChE from OPNA-exposed plasma can simultaneously be measured using the method. The study provides a recommended diagnostic tool for generic verification of any OPNA exposure with high confidence by detecting its corresponding BChE adduct. [ABSTRACT FROM AUTHOR]

Sulfur mustard (SM) is a chemical warfare agent that, upon topical application, damages skin and reaches internal organs through diffusion in blood. Two major toxic consequences of SM exposure are inflammation, associated with oxidative stress, and the formation of alkylated DNA bases. In the present study, we investigated the impact of exposure to SM on DNA repair, using two different functional DNA repair assays which provide information on several Base Excision Repair (BER) and Excision/Synthesis Repair (ESR) activities. BER activities were reduced in all organs as early as 4 h after exposure, with the exception of the defense systems against 8-oxo-guanine and hypoxanthine which were stimulated. Interestingly, the resulting BER intermediates could activate inflammation signals, aggravating the inflammation triggered by SM exposure and leading to increased oxidative stress. ESR activities were found to be mostly inhibited in skin, brain and kidneys. In contrast, in the lung there was a general increase in ESR activities. In summary, exposure to SM leads to a significant decrease in DNA repair in most organs, concomitant with the formation of DNA damage. These synergistic genotoxic effects are likely to participate in the high toxicity of this alkylating agent. Lungs, possibly better equipped with repair enzymes to handle exogenous exposure, are the exception. [ABSTRACT FROM AUTHOR]

Cytochrome P450 1A2 (CYP1A2) is an enzyme involved in the metabolic activation of certain carcinogens, and inducible by toxic substrates. To date, few studies have investigated in vivo CYP1A2 induction in humans and its relationship to polycylic aromatic hydrocarbons (PAHs) like benzo(a)pyrene (BaP). Non-smoking healthy male coke-oven workers (n = 30) were recruited as ‘exposure’ group, and non-smoking healthy office workers in the same city (n = 10) were selected as ‘control’ group, to test whether high inhalation exposure to PAHs can induce CYP1A2 activity in human livers. Significantly higher inhalation exposure of PAHs were found among the exposure group compared to the control. Inhalation BaP exposure concentration in the exposure group was more than 30 times higher than the control group ( p < 0.001). However, the exposure group did not exhale significant higher levels of 13 CO 2 / 12 CO 2 in breath samples ( p = 0.81), and no significant relationship was found between the inhaled BaP concentration and the 13 CO 2 / 12 CO 2 ratio ( p = 0.91). A significant association was found between the 13 CO 2 / 12 CO 2 exhalation and dietary BaP intake level. Hepatic CYP1A2 activity/induction level was not effected by inhaled BaP but was altered by ingestion of BaP. [ABSTRACT FROM AUTHOR]

From the 1950s to the 1970s, three Superfund sites discharged polychlorinated biphenyl (PCB)-contaminated waste upstream of the Mohawk Nation at Akwesasne, resulting in PCB contamination of groundwater, soil, and sediment in the surrounding area. Given the persistence of PCBs in the environment and in human tissues, there are continued concerns regarding PCB exposures and the potential for adverse health effects in the community. We developed an evidence map of PCB research at Akwesasne in order to characterize the available data and to highlight potential research needs. Human health and exposure biomarker studies were identified from a literature search based on population, exposure, comparator, and outcome (PECO) criteria. Data extracted from references that met the inclusion criteria after full-text review included study characteristics (e.g., sample size, study design, sampling years), details on PCB measurements (e.g., analytical method, number of congeners analyzed, method detection limits), and results (e.g., PCB levels and summary of study conclusions). We identified 33 studies, conducted between 1986 and 2013, that examined PCB exposure characteristics and health effects in residents of the Akwesasne Mohawk Nation. Organizing this literature into an evidence map including information on study cohort, congener groupings, exposure biomarker characteristics, and health effects allowed us to identify research gaps and to suggest future research priorities for the community. We identified current PCB exposure levels and PCB source characterization as major uncertainties, both of which could be addressed by new studies of PCB concentrations in environmental media. [Display omitted] • This evidence map describes human health research on PCBs at Akwesasne. • We identified 33 studies of PCB health effects and/or exposure characteristics. • We organized studies by cohort, PCB exposure measures, and health effects. • Major uncertainties are current PCB exposure levels and source characterization. [ABSTRACT FROM AUTHOR]

[Display omitted] • Simultaneous determination of selected pesticides and metabolites in human urine. • UHPLC/QTOFMS coupling perfectly adapted to targeted quantitative analysis. • Deconjugation step essential to measure the total concentration of certain substances. • Likely impact of the thawing/freezing cycles on the stability of certain substances. • Presence of pesticides in their metabolized form in French pregnant women's urine. An innovative method for the determination of pesticides of different uses and from different chemical families and/or their known metabolites in human urine was developed. The protocol includes an enzymatic hydrolysis followed by an off-line solid phase extraction (SPE) step and then a targeted quantitative analysis by ultra-high performance liquid chromatography coupled with hybrid quadrupole time-of-flight mass spectrometry (UHPLC/QTOFMS). Still rarely used for this purpose, this technique nevertheless offers excellent quantitative performance with high selectivity, but requires two separate injections for the same sample, one in the negative electrospray ionization mode (ESI-), and the other in the positive mode (ESI+). Two analytical methods were thus developed to cover 40 substances corresponding to 23 different pesticides plus nicotine and cotinine. The first method allows the determination of 15 biomarkers (SPE on a weak anion exchange polymeric support; ESI- mode) and the second 27 (SPE on a reverse phase polymeric support; ESI+ mode) with detection limits for a 2-mL urine sample varying from 0.02 to 25 μg.L−1. Replicate analysis of three pools of urine non-spiked and spiked at an intermediate level on about 20 different days showed most often excellent performance in terms of inter-day precision (<30%) and accuracy (between 80 and 125%), confirming that the UHPLC/QTOFMS coupling is perfectly adapted to a targeted quantitative analysis. The proposed methods were then applied to fifteen real urine samples, demonstrating the presence of pesticides, predominantly in metabolized form, in the urine of French pregnant women, and the capabilities of the proposed methods to detect them. They were finally applied to a study of the impact of thawing/freezing cycles on the conservation of the target substances, showing for the first time to our knowledge that the thawing/freezing cycles and the composition of urine samples could have an influence on the stability of some of the target substances. [ABSTRACT FROM AUTHOR]

Diisocyanates are industrial chemicals which have a wide range of applications in developed and developing countries. They are notorious lung toxicants and respiratory sensitizers. However, the mechanisms behind their adverse effects are not adequately characterized. Autotaxin (ATX) is an enzyme producing lysophosphatidic acid (LPA), and the ATX-LPA axis has been implicated in lung related inflammatory conditions and diseases, including allergic asthma, but not to toxicity of environmental low-molecular-weight chemicals. We investigated effects of toluene diisocyanate (TDI) on ATX induction in human lung epithelial cell models, and we correlated LPA-levels in plasma to biomarkers of TDI exposure in urine collected from workers exposed to < 5 ppb (parts per billion). Information on workers' symptoms was collected through interviews. One nanomolar TDI robustly induced ATX release within 10 min in vitro. A P2X7- and P2X4-dependent microvesicle formation was implicated in a rapid ATX release and a subsequent protein synthesis. Co-localization between purinergic receptors and ATX was documented by immunofluorescence and confocal microscopy. The release was modulated by monocyte chemoattractant protein-1 (MCP-1) and by extracellular ATP. In workers, we found a dose–response relationship between TDI exposure biomarkers in urine and LPA levels in plasma. Among symptomatic workers reporting “sneezing”, the LPA levels were higher than among non-symptomatic workers. This is the first report indicating induction of the ATX-LPA axis by an environmental low-molecular-weight chemical, and our data suggest a role for the ATX-LPA axis in TDI toxicity. [ABSTRACT FROM AUTHOR]

RNAs are more susceptible to modifications than DNA, and chemical modifications in RNA have an effect on their structure and function. This study aimed to characterize chemical effects on total RNA in human A549 lung cells after exposure to elevated levels of major secondary air pollutants commonly found in urban locations, including ozone (O3), acrolein (ACR) and methacrolein (MACR). Enzyme-linked immunosorbent assays (ELISA) were used to measure levels of interleukin (IL)-8 in the growth media and 8-oxoguanine (8OG) levels in total cellular RNA, and lactate dehydrogenase (LDH) in the growth media was measured by a coupled enzymatic assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure levels of microRNA 10b (miR-10b). The study found that 1-h exposure to all tested pollutant mixtures consistently caused significant increases in the levels of 8OG in total RNA. In the case of 4 ppm O3 exposures, measured levels of IL-8, LDH and miR-10b each showed consistent trends between two independent trials, but varied among these three targets. After 1-h exposures to an ACR+MACR mixture, measured levels of IL-8, LDH and miR-10b showed variable results. For mixtures of O3+ACR+MACR, IL-8 measurements showed no change; miR-10b and LDH showed variable results. The results indicate that short-term high-concentration exposures to air pollution can cause RNA chemical modifications. Chemical modifications in RNAs could represent more consistent markers of cellular stress relative to other inflammation markers, such as IL-8 and LDH, and provide a new biomarker endpoint for mechanistic studies in toxicity of air pollution exposure. [ABSTRACT FROM AUTHOR]

The relationship between endocrine disrupting chemical (EDC) exposure and Precocious Puberty (PP) was investigated in this pilot study, involving girls with signs of PP (P) and pre-pubertal girls (C). Risk factors for PP were assessed through questionnaires, while 17β-oestradiol (E2) levels and oestrogenic activity were quantified on sera. The oestrogenic activity, expressed as E2 equivalent concentration (EEQ), was applied as EDC exposure biomarker. Questionnaires showed a low EDC knowledge, a high EDC exposure, and a potential relationship between some habits at risk for EDC exposure and PP. EEQs were similar between C and P; however, they were significantly higher in girls living in an urban environment than in girls living in a rural environment, suggesting a potential higher EDC exposure in cities. The results of this pilot study highlighted the need to raise awareness on EDCs and can be considered a starting point to clarify the relationship between EDC exposure and PP.

Background Exposomics is the cutting-edge concept of screening the environmental risk factors for disease. In the novel "top-down" approach, we estimate the molecular exposome by measuring all body fluid analytes in a case-controlled study. However, to detect diverse pollutants, a sufficient sample size and multiple analytical methods are required. This may lead to dramatically increased costs and research workload. Methods To help reduce complexity, we suggest a sample pooling strategy along with a scheme for combining both general unknown or multi-targeted screening with targeted analysis. The sample pooling method was tested using computer simulations. Results By comprehensively analysis of pooled samples, it is possible to identify environmental risk factors. Factors are initially screened in the pooled case and control population samples, then in the randomized grouped and pooled case and control subpopulation samples. In the sample grouping, five or more pools were suggested for groups having 30 individuals per pool. Conclusions This study suggests that sample pooling is a useful strategy for exposomics research, which provides a hypothesis-free method for pollutant risk screening. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the DDT, DDE, and 1-hydroxypyrene exposure levels of children living in communities located in southeastern Mexico. The study communities were Lacanja and Victoria in Chiapas state and Ventanilla in Oaxaca state. Children living in Lacanja had total blood DDT levels (mean ± SD, 29,039.6 ± 11,261.4 ng/g lipid) that were significantly higher than those of children in Victoria (10,220.5 ± 7,893.1 ng/g lipid) and Ventanilla (11,659.7 ± 6,683.7 ng/g lipid). With respect to the 1-hydroxypyrene levels in urine samples, the levels in Lacanja (4.8 ± 4.1 μg/L or 4.5 ± 3.9 μmol/mol creatinine) and Victoria (4.6 ± 3.8 μg/L or 3.9 ± 3.0 μmol/mol Cr) were significantly higher than levels found in Ventanilla (3.6 ± 1.4 μg/L or 2.5 ± 0.5 μmol/mol Cr). In conclusion, our data indicate high levels of exposure in children living in the communities studied in this work. The evidence found in this study could be further used as a trigger to revisit local policies on environmental exposures. [ABSTRACT FROM AUTHOR]

Abstract: Background: The effect of exposure to disinfection by-products (DBPs) during pregnancy on newborn''s birth weight has been commonly described in animal studies. However, epidemiological evidence was not consistent. Objectives: To investigate the relationship between exposure to DBPs and newborn''s birth weight in a Chinese population, we conducted a cross-sectional study in Wuhan, China. Methods: A total number of 398 women who had given birth to a live singleton with a gestational age between 37 to 42weeks were recruited from a local hospital between November 2008 and May 2009. Basic information for all mothers and newborns was obtained from clinic birth records. Among these subjects, 180 women also gave further information including maternal medical history, social status and water-use behaviors by a face-to-face interview. Urinary creatinine (Cr) adjusted trichloroacetic (TCAA) was used as an exposure biomarker. Results: No statically significant results were found in the linear regression for both 398 participants and 180 participants who finished questionnaires. However, both the crude and adjusted results showed that the mean birth weight of the subjects in the third and top quartiles of Cr-adjusted urinary TCAA concentrations was decreased compared with those in the lowest quartile. Subjects in the top quartiles had the lowest mean birth weight compared to those in other quartiles. In addition, a weak correlation was observed among 82 subjects between drinking water ingestion and urinary Cr-adjusted TCAA (r=0.23, P=0.04). Conclusion: Our findings suggested that elevated exposure to DBPs may affect fetal growth. The effect of exposure to DBPs during pregnancy on birth weight still warrants further investigations. [Copyright &y& Elsevier]

Metallothioneins (MTs) are ubiquitous and inducible proteins characterized by low molecular mass (Mr 6-8 kDa), high Cys content (20-30%) but no aromatic or His residues, and strong affinity to binding toxic metals (Cd, Hg, Ag, Pb) in metal-thiolate clusters. Due to their induction by a variety of stimuli, MTs are considered suitable biomarkers in the medical and environmental fields. The protective role of MTs from Cd toxicity and lethality is well-established. Although MT assessment is a difficult task, the accurate measurement of MT is mandatory in order to assess its biomarker potential and to identify new outstanding biological roles. We have developed a highly specific, sensitive, and reliable method for total MT quantification in unheated extracts by reversed-phase high-performance liquid chromatography coupled to fluorescence detection (RP-HPLC-FD). A derivatization protocol with monobromobinane, a thiol-specific fluorogenic reagent, is required after heat-, SDS- EDTA- and DTT-treatment. SDS-polyacrylamide gel electrophoresis was used to confirm the identity of the mBBr-labeled MT peak resolved by RP-HPLC-FD. The method has been successfully used to quantify MT content in the digestive gland of various clam species from Southern Spanish sites with different metal levels, and also in the liver of fish injected with different Cd, Cu and Hg doses. MT levels obtained by RP-HPLC-FD in non-heated extracts were significantly higher when compared to those obtained by other well-established assays relying on solvent precipitation (spectrophotometry) or heating (differential pulse polarography) pre-purification steps. [ABSTRACT FROM AUTHOR]

Context: Since 1997 the Arctic Monitoring and Assessment Programme (AMAP) has produced integrated assessment reports on the status of and trends in environmental persistent organic pollutants (POPs) in the Arctic ecosystem. Three reports on biomonitoring POPs and their health risks for Arctic populations were published in 1998, 2002, and 2009. Issue: The present review summarizes data from Greenland on human monitoring of biomarkers of POP exposure and bioaccumulation and the determination of biomarkers for POP effects. The review focuses on hormone disruptive potentials and some genetic sensitivity biomarkers. The overview covers Greenlandic studies from 2000 to 2006. Lessons learned: The Greenland biomonitoring studies showed general geographical and gender differences of bioaccumulated serum POP levels, which were primarily related to diet and lifestyle. A high intake of traditional Greenlandic diet (eg seal, whale, polar bear, and seabirds) together with smoking caused higher blood concentrations of POPs. The highest POP values were found on the east coast of Greenland. The receptor effect studies showed a general inverse relationship between high serum POP concentration and estrogen receptor (ER) and Ah-receptor (AhR) transactivity; in addition for men in the two West Greenlandic districts, Nuuk and Sisimiut, a trend towards increased induced AR activity was found. An observed trend to an opposite direction between the dioxin-like AhR and ER activity supports the perception of that dioxins exert an antiestrogen effect. In conclusion, the actual mixtures of serum POPs in Greenlandic Inuit have an endocrine disrupting potential. Comparisons between European and Greenlandic male serum POP levels showed significantly higher levels in Inuit; however, in the same study Inuit had significantly lower sperm DNA damage. Further studies are required to elucidate whether the serum POP related effects on hormone receptors and/or AhR are explanatory factors. 'The Arctic dilemma' is that along with the intake of the Greenlandic traditional diet that contains POPs, there are also a number of important nutrients, such as trace elements/antioxidants and marine unsaturated fatty acids which have favorable effects on health. However, a number of studies suggest that an increase in Western food items in the diet can lead to other health risks, such as the metabolic syndrome and its sequels increase in weight, hypertension, diabetes type 2, cardiovascular disease, and cancer, including breast cancer. To elucidate these aspects further studies are required, including those into biomarkers for exposure and effects, epigenetic contexts and the determination of relevant genetic polymorphisms, case-control as well as generation studies. Finally, there is a need for the development of new biomarkers to study the potential POP effects that inhibit the immune system and affect the development of the central nervous system. [ABSTRACT FROM AUTHOR]

Correlations between drinking water and toenail arsenic concentrations have been demonstrated in previous studies, yet factors that may modify the exposure-biomarker association have not been adequately assessed. Using data from 500 controls enrolled in a bladder cancer study underway in Michigan, USA, the effects of demographic characteristics and nutritional measures on the biomarker response were evaluated. Drinking water and toenail samples were collected during a home visit and analyzed for arsenic and other elements. Participants reported dietary supplement intake habits and provided demographic data. Arsenic concentrations of drinking water and toenail samples were positively correlated. Of the nutritional measures evaluated, toenail iron concentration was a significant modifier of the exposure-biomarker association. No demographic characteristics or general measures of dietary intake affected the biomarker response. The results presented herein are critical for biomarker validation and prove promising for sound application of the arsenic toenail biomarker to future epidemiological investigations. [ABSTRACT FROM AUTHOR]

Mercury in hair is a generally accepted biomarker of methylmercury exposure, and permanent waving has been reported to affect the mercury concentration in hair. We conducted an experimental-field study to examine the changes in the mercury concentration in hair induced by treatments such as permanent waving, straightening and coloring. Hair samples were collected from 19 female subjects enrolled before and after hair treatment by a beautician during each visit to a beauty saloon. A total of 38 pair samples were cut in 1-cm segments from the proximal end up to 10 cm, and then as 2-cm segments up to the distal end thereafter. Each segment was analyzed for total mercury concentration by cold-vapor atomic absorption spectrometry. Permanent waving decreased mercury concentration for most of the segments except for the proximal two segments and the 8-9 cm segment from the proximal end. Nevertheless the average mercury concentration of 3-cm segments from the proximal end showed no signifi cant decrease by permanent waving. Since females usually have hair longer than 3 cm, hair samples subjected to permanent waving may give lower mercury exposure estimates when the full-length hair strands are analyzed. However, analyzing the proximal 3-cm segment of hair samples does not give lower mercury exposure estimates. Assuming that hair samples are collected from puerperal women around the time of delivery, the 3-cm segments represent fetal exposure to methylmercury during the third trimester when fetuses are most vulnerable to methylmercury exposure. Therefore, mercury concentrations in the proximal segment of maternal hair collected in the right time can be a good biomarker of fetal methylmercury exposure. [ABSTRACT FROM AUTHOR]

Abstract: The determination of biomarkers of acrylamide exposure in humans from general French population by measurement of hemoglogin adduct levels of acrylamide (AA) and glycidamide (GA) is presented. The analytical procedure included modified Edman degradation and LC–ESI-MS/MS analysis of the final derivatives using deuterated internal standards. Method performances were evaluated in terms of linearity, precision, accuracy, and sensitivity. The method was firstly assessed on rat blood samples and then applied to the study of background adducts levels of AA and GA in 68 human hemoglobin samples, showing mean levels of 33 and 23pmol/g globin for AA and GA adducts, respectively. [Copyright &y& Elsevier]

As cancer incidence is projected to increase for decades there is a need for effective preventive strategies. Fortunately, evidence continues to mount that altering dietary habits is an effective and cost-efficient approach for reducing cancer risk and for modifying the biological behavior of tumors. Predictive, validated and sensitive biomarkers, including those that reliably evaluate “intake” or exposure to a specific food or bioactive component, that assess one or more specific biological “effects” that are linked to cancer, and that effectively predict individual “susceptibility” as a function of nutrient-nutrient interactions and genetics, are fundamental to evaluating who will benefit most from dietary interventions. These biomarkers must be readily accessible, easily and reliably assayed, and predictive of a key process(es) involved in cancer. The response to a food is determined not only by the effective concentration of the bioactive food component(s) reaching the target tissue, but also by the amount of the target requiring modification. Thus, this threshold response to foods and their components will vary from individual to individual. The key to understanding a personalized response is a greater knowledge of nutrigenomics, proteomics and metabolomics. [ABSTRACT FROM AUTHOR]

Among the scientific interests of cancer epidemiology is the identification of both environmental and genetic factors associated with cancer development. Observational designs requiring sophisticated methodology are applied to control for potential confounding factors. The enormous biotechnological potential developed in the last two decades has allowed the integration of a plethora of new biomarkers in epidemiological studies to better define the exposure and “neoclassic” outcomes, as well as incorporating genetic susceptibility factors in both classical and new epidemiological designs. The integration of scopes, objectives, data and tools coming from different disciplines also benefits epidemiology, thus evolving into “systems epidemiology”. In this manuscript, we review the basic concepts of study designs and data analysis and introduce readers to the more innovative aspects that are now being applied in epidemiological studies. [ABSTRACT FROM AUTHOR]

Abstract: Organophosphorus and carbamate insecticides inhibit the carboxylesterases found in plasma. Therefore, these carboxylesterases might be used as biomarkers of exposure to these insecticides. This work initiates the characterization of the phenylacetate (PA) and 1-nafthylacetate (NA) hydrolyzing activities (PAase and NAase) in the plasma of 11 different wild bird species and aims to determine their suitability as biomarkers of exposure. PAase activity values, expressed as μmol product/30min/mL plasma, ranged between 38±2.3 (black vulture) and 27±0.85 (barn owl), while NAase values ranged between 6.0±5.2 (griffon vulture) and 38±0.85 (barn owl). In all assayed species, NAase was between 1.1 and 2.8 times higher than the corresponding PAase. PAase and NAase of chicken white stork were 1.6 and 1.7 times higher, respectively, than the corresponding activities of adult individuals. Nocturnal raptors, eagle owl and barn owl, exhibited PAase and NAase between 1.3 and 8.0 times higher than activities exhibited by diurnal raptors (Montagu''s harrier, common buzzard, booted eagle, Spanish imperial eagle, black kite, griffon vulture and black vulture). Data presented in this work suggest that plasma PAase and NAase of the studied birds might be used as biomarkers of exposure to organophosphorus and carbamate insecticides, although further studies of inhibition of these activities are still needed. [Copyright &y& Elsevier]

Abstract: Hemoglobin adducts (Hb-MDX) of monomeric methylenediphenyl diisocyanate (MDI) are often interpreted as indirect evidence of hydrolysis of the diisocyanate moiety to the respective amine (diphenylmethane-4,4′-diamine, 4,4′-MDA) which constitutes the rationale of using this biomarker as an internal dosimeter of exposure to putatively formed MDA. In contrast, more recently published data suggest that following inhalation the high concentration of glutathione (GSH) present in lungs favor an adduct formation with GSH and/or peptides/proteins rather than hydrolysis. The focus of this study was to test this alternate hypothesis, viz. whether Hb-MDX can also be formed by the GSH bis-adduct of monomeric MDI. The synthesized mMDI-GSH bis-adduct was administered to rats by single intratracheal instillation. Additional groups were dosed by gavage and intraperitoneal injection. Biomarkers of exposure were determined in blood (plasma protein and hemoglobin adducts) and urine after harsh alkaline and acid hydrolysis, respectively. Data from previous single inhalation exposure studies with aerosols of MDI and 4,4′-MDA in rats served as reference. As to whether N-acetylation plays any modifying role to yield these mMDI-specific biomarkers was addressed in similarly head-only exposed dogs, a species with no appreciable N-acetylation capacity whereas rats are strong N-acetylators. The results obtained suggest that biomarkers in blood from controlled exposures above current workplace standards of mMDI appear not to be suitable for reliable assessments of past exposures. The biomarkers typically used to assess past exposures to MDI were also identified following exposure to the MDI-GSH bis-adduct. Their yield was low but quite similar for MDI aerosol and the MDI-GSH bis-adduct, whilst that of MDA was distinctively higher. The findings of this study are supportive of a conceptual pathway that the MDI-derived biomarkers of exposure are formed through MDI-GSH adducts rather than MDA. Data from dogs support the findings from rats and show that N-acetylation does not appear to be an essential modifying factor. It is concluded that the yield of MDI-related markers of exposure is relatively low and dependent on the exposure dose (and route). MDA originating from hydrolyzed serum protein or hemoglobin appear to be confounded by false-positive background levels which are surmised to be associated with the method of hydrolysis. The determination of urinary biomarkers might be a useful tool to identify recent exposures (by any route). Due methodological uncertainties associated with the harsh hydrolysis of biological specimens may be reduced substantially when using incremental pre- to post-shift changes rather than relying solely on absolute data. [Copyright &y& Elsevier]

Abstract: The implementation of eco-toxicological assessment in South America is presently limited due to significant scientific information gaps concerning native species and their potential use as biomarkers. Recently, a common southern hemisphere fish species, Astyanax fasciatus, has been pointed out as a potential bio-indicator to anthropogenic pollution. This is a small, abundant, Neotropical characid, which is widely distributed from Central America south, to the Rio de la Plata Basin of western Uruguay. Our study found a statistically significant increase of coproporphyrin, uroporphyrin and protoporphyrin concentrations in hepatic tissues of A. fasciatus collected from a stream segment with high anthropogenic disturbance (due mainly to agricultural derivatives and motor vehicle transportation activities). Although the area studied showed differences in up and downstream limno-chemical parameters, these differences were not related to the increase of hepatic porphyrin concentrations. Based on the results of our study, we conclude that A. fasciatus is a good bio-indicator of exposure to environmental contaminants, and we propose that this abundant fish species be considered as a sentinel organism for monitoring potential disturbances to freshwater ecosystems. [Copyright &y& Elsevier]

Exposure misclassification is a major obstacle to obtain accurate dose-response relationships. In order to solve this problem, the impact of hair treatment on total mercury in hair was assessed in Japanese women. A cross-sectional study was carried out among 327 women at age 24–49 years to determine hair mercury levels and estimate daily mercury intakes from seafood by using a food frequency questionnaire. Hair mercury levels in the women and daily mercury intake ranged from 0.11 to 6.86 (median 1.63) μg/g and from 0.77 to 144.9 (median 15.0) μg/day, respectively. The hair mercury was positively correlated with the daily mercury intake (p<0.001). When the women were divided into two subgroups based on artificial hair-waving, hair coloring/dyeing, residence (non-fishing and fishing areas), and working status, a significant difference in the hair mercury level was observed between the women with and without artificial hair-waving only (p<0.001). The multiple regression analysis showed that the log-transformed hair mercury level was significantly related to the log-transformed daily mercury intake (standardized regression coefficient βs=0.307) and artificial hair-waving (βs=−0.276); but not to hair coloring/dyeing, residence, working status or age. Permanent hair treatment was estimated to reduce total mercury in hair by approximately 30%, after adjusting for daily mercury intake and other possible factors. These findings suggest that hair mercury is not the best biomarker of methylmercury exposure when a study population includes women with artificial hair-waving. [ABSTRACT FROM AUTHOR]

To clarify etiology of lung cancer in nonsmoker females, various studies have been done. Particularly, host factors and environmental tobacco smoking (ETS) of females have been emphasized. However, traditional epidemiological data showed controversial results of sex or gender differences in lung cancer susceptibility and suggest presence of some confounders. One of them is that most of epidemiology studies are based on self-reports for ETS. To prevent misestimate effects of ETS via the self-report, exposure monitoring of ETS is required. On the other hand, focusing on genetic polymorphisms in metabolic enzymes and DNA repair, molecular epidemiological studies have been done in nonsmoker females. Therefore, this review considered: 1. gender differences in lung cancer; 2. effects of passive smoking on lung cancer; 3. exposure monitoring of ETS including genetic risks of lung cancer to clarify etiology of lung cancer in the nonsmoker females with molecular epidemiological discussion. [ABSTRACT FROM AUTHOR]