Common Source Of Exposure Research Articles

Biomonitoring of bisphenols A and S and phthalate metabolites in hair from pregnant women in Crete

Phthalates, bisphenols A and S (BPA, BPS) are used as plasticizers and many of them are documented or suspected of being endocrine disruptors. Several studies indicate that exposure during pregnancy may affect the newborn's health and development. The aim of this cross-sectional study is the biomonitoring of seven phthalate metabolites, BPA and BPS in hair from 100 pregnant women in Crete. The most frequently detected compounds were monoethylhexyl phthalate (mEHP) (68%), mono isobutyl phthalate (miBP) (40%), BPA (37%), BPS (34%) and mono-n-butyl phthalate (mnBP) (28%). Phthalate metabolites were detected at medians from 19.5 to 44.4 pg/mg, BPA at 69.9 pg/mg and BPS at 3.5 pg/mg. Significant positive correlations between phthalate metabolites were found which indicated their common sources of exposure. The frequent use of plastics for food storage was strongly associated with mEHP (p = .013) and a weaker association was found for miBP (p = .063). The frequent use of cosmetics during or before pregnancy was associated with levels of phthalate metabolites in hair. More specifically, the use of hair spray before pregnancy was significantly correlated with monobenzyl phthalate (mBzP) (p = .041) and a trend was found for miBP (p = .066). The use of makeup products during pregnancy was strongly associated with miBP (p = .015) and the use of deodorant during pregnancy was inversely associated with mEHP (p = .021). Strong associations came up between mEHP and lower birth weight (Spearman correlation coefficient, r = −0.302, p = .021) and exposure to BPS was associated with increased body mass index of the participants (p = .036). Although data in literature on biomonitoring of the compounds in hair are limited, the findings of this study are promising and in agreement with existing data in hair or urine.

Dental X-Rays and the Risk of Thyroid Cancer and Meningioma: A Systematic Review and Meta-Analysis of Current Epidemiological Evidence.

Background: Exposure to moderate-to-high doses of ionizing radiation is the only established environmental risk factor for thyroid cancer and brain and central nervous system tumors. Considering the high lifetime prevalence and frequency of exposure to dental X-rays, the most common source of diagnostic radiation exposure in the general population, even a small associated increase in cancer risk would be of considerable public health importance. With the objective to inform clinical practice and guidelines, we synthesized the current epidemiological evidence on the association between dental X-rays and the risk of thyroid cancer, meningioma, and other cancers of the head and neck region. Methods: The Medline, Embase, and Web of Science databases were searched to identify eligible studies. Summary odds ratio/relative risk estimates and confidence intervals were extracted, and pooled risk ratios (RRs) for each cancer were calculated using random effects meta-analysis. Results: The literature search identified 5537 publications; of these, 26 studies including 10,868 cancer patients were included in the synthesis. The random effects meta-analyses, based on seven studies of thyroid cancer (six case/control, one cohort) and eight studies of meningioma (all case/control), showed that multiple (or repeated) exposures to dental X-rays were significantly associated with an increased risk of thyroid cancer (pooled RR = 1.87 [95% confidence interval, CI 1.11-3.15]) and meningioma (pooled RR = 1.53 [CI 1.26-1.85]). There was no association with glioma, and there were too few studies of other cancers of the head and neck region to conduct a meaningful meta-analysis. Conclusions: Based on a meta-analysis of retrospective case/control studies, these findings provide some support to the hypothesis that multiple (or repeated) exposures to dental X-rays may be associated with an increased risk of thyroid cancer and meningioma. These studies did not include individual organ doses and ages at exposure, and are subject to recall bias and other limitations. Furthermore, the thyroid exposure has decreased dramatically over time from the use of thyroid shields and improved technology/equipment. Prospective studies, based on dental X-ray records and patient follow-up, are needed to test the hypothesis further and clarify the possible cancer risk associated with dental radiography, as although the risk at the individual level, particularly with improved technology/equipment, is likely to be very low, the proportion of the population exposed is high. Considering that about one-third of the general population in developed countries is routinely exposed to one or more dental X-rays per year, these findings manifest the need to reduce diagnostic radiation exposure as much as possible.

Sodium Arsenic Alters the Gene Expression of some Steroidogenic Genes in TM3 Leydig Cell

Arsenic is a broad-spectrum environmental contaminant with mutagenic, teratogenic and carcinogenic effects. Due to its widespread distribution in nature, drinking water is the most common source of arsenic exposure for the general population. In this study, we aimed to determine the effect of sodium arsenite on the viability and expression profile of steroidogenic genes in TM3 Leydig cells, responsible for testicular steroidogenesis. The TM3 Leydig cells were treated with sodium arsenic (384,8 µM or 7,6 mM) for 24 hours with LH (Luteinizing hormone) stimulation. The MTT assay was used for measuring cell viability, the expression level of key genes of the steroidogenesis was evaluated using RT-qPCR.The MTT assay showed that cell viability was decreased dose-dependently. RT-qPCR demonstrated that the expression level of CYP11A1, CYP17A1 were decreased as compared to the untreated control while StAR gene expression was found to be surprisingly high in the cell exposed to high-dose arsenic (p<0.05). The expression profile of two dehydrogenase; 17β-HSD and 3β-HSD was significantly reduced in high dose arsenic treated-group (p<0.05); but however, no statistical significance was found in low-dose. The RT-qPCR also showed that the expression SF-1 (Steroidogenic factor-1), a key regulator of adrenal and reproductive development, was significantly decreased in both low-dose and high-dose (p<0.05). Arsenic toxicity in Leydig cell leads to cell viability loss and cause a perturbation in key steroidogenic genes, reflecting the possible role of arsenic in infertility and male reproductive system disorders.

Metabolomic analysis reveals the mechanism of aluminum cytotoxicity in HT-29 cells.

BackgroundAluminum (Al) is toxic to animals and humans. The most common sources of human exposure to Al are food and beverages. The intestinal epithelium is the first barrier against Al-induced toxicity. In this study, HT-29, a human colon cancer cell line, was selected as an in vitro model to evaluate the Al-induced alteration in metabolomic profiles and explore the possible mechanisms of Al toxicity.MethodsMTT assay was performed to determine the half-maximal inhibitory concentration of Al ions. Liquid chromatography-mass spectrometry (LC-MS) was used for metabolomic analysis, and its results were further confirmed using quantitative reverse transcription polymerase chain reaction (RT-qPCR) of nine selected genes.ResultsAl inhibited the growth of the HT-29 cells, and its half-maximal dose for the inhibition of cell proliferation was found to be four mM. This dose was selected for further metabolomic analysis, which revealed that 81 metabolites, such glutathione (GSH), phosphatidylcholines, phosphatidylethanolamines, and creatine, and 17 metabolic pathways, such as the tricarboxylic acid cycle, pyruvate metabolism, and GSH metabolism, were significantly altered after Al exposure. The RT-qPCR results further confirmed these findings.ConclusionThe metabolomics and RT-qPCR results indicate that the mechanisms of Al-induced cytotoxicity in HT-29 cells include cellular apoptosis, oxidative stress, and alteration of lipid, energy, and amino acid metabolism.

Exploring the associations of serum concentrations of PCBs, PCDDs, and PCDFs with walking speed in the U.S. general population: Beyond standard linear models

Studies have shown that persistent organic pollutants (POPs) can have various health effects. However, little is known about the effects of multiple chemicals with possible common sources of exposure on walking speed, a proxy index reflecting lower limb neuromuscular function and physical function. We simultaneously applied multiple linear and nonlinear statistical models to explore the complex exposure-response relationship between a mixture of 22 selected POPs and walking speed. A total of 14 polychlorinated biphenyls (PCBs), 3 polychlorinated dibenzo-p-dioxins (PCDDs), and 5 polychlorinated dibenzofurans (PCDFs) were measured in the serum of participants in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002. Walking speed was measured during a physical examination. Linear regression (LR), least absolute shrinkage and selection operator (LASSO), and group LASSO were used to evaluate the linearity of mixtures, while restricted cubic spline (RCS) regression, random forest (RF), and Bayesian kernel machine regression (BKMR) models were used to evaluate the nonlinearity of mixtures. Potential confounders were adjusted in the above models. A total of 436 subjects were included in our final analysis. The results of the LR model did not identify any POP exposure that was significantly associated with walking speed. The LASSO results revealed an inverse association of one PCDD congener and two PCDF congeners with walking speed, while the group LASSO analysis identified PCDFs at the exposure level and at the group level. In the RCS analysis, two PCB congeners presented significant overall associations with walking speed. The PCB congener PCB194 showed statistically significant effects on the outcome (P = 0.01) when a permutation-based RF was used. The BKMR analysis suggested that PCBs and PCDFs (probabilities = 0.887 and 0.909, respectively) are potentially associated with walking speed. Complex statistical models, such as RCS regression, RF and BKMR models, can detect the nonlinear and nonadditive relationships between PCBs and walking speed, while LASSO and group LASSO can identify only the linear relationships between PCDFs and walking speed. Fully considering the influence of collinearity in each method during modelling can increase the comprehensiveness and reliability of conclusions in studies of multiple chemicals.

Contact allergy and allergic contact dermatitis caused by lavender: A retrospective study from an Australian clinic.

Lavender is commonly used in aromatherapy and in a broad range of personal and household products. It has been identified as a contact sensitizer, and has been reported to cause allergic contact dermatitis (ACD). To report our experience with contact allergy and ACD caused by lavender, and to raise awareness of lavender as a potential contact allergen. A retrospective database review was performed of patients attending patch testing clinics at the Skin and Cancer Foundation, Victoria, Australia, from January 1, 1993 to December 31, 2017. Among the 2178 patients patch tested with lavender over this period, a total of 58 positive reactions were recorded in 49 individuals, giving a positive patch test prevalence for patients tested with lavender of 2.2%. Twenty-seven patients were diagnosed with ACD. The most common sources of exposure to lavender were personal care products and essential oils. Of the patients with ACD, 74% were tested with lavender absolute, with positive results in 90% of cases. Lavender is an uncommon cause of ACD but is important to consider, given the potential for exposure through the use of personal care items and essential oils.

Human exposures to veterinary pharmaceutical products reported to Australia’s largest poison information centre

Aim: To describe the epidemiology of veterinary pharmaceutical-related exposures based on telephone calls to Australia’s largest poisons information centre.Methods: A retrospective analysis of exposures to pharmaceutical products intended for animal use, managed by the New South Wales Poison Information Centre (NSWPIC, Australia’s largest poisons information centre) from 2014 to 2016 inclusive, was conducted. Case narratives were reviewed and coded for exposure-related circumstances and intended species. Descriptive statistics were generated and forest plots were produced to visualise the perceived severity of products.Results: From 2014 through 2016 NSWPIC received 2655 calls regarding exposure to veterinary pharmaceutical products: 11.72 human exposures to veterinary pharmaceuticals per 1000 PIC initial contact exposure calls (CI: 10.95–12.49) per year. The vast majority of exposures were with products intended for companion animals, particularly of the class “antiparasitic products, insecticides and repellents”, with the most common individual specified product being pimobendan, a phosphodiesterase inhibitor used as a cardiac inotrope and vasodilator in dogs. Immunologicals presented the greatest perceived severity, with livestock vaccinations eliciting substantial proportions of symptomatic exposures and those receiving hospitalisation. Exploratory behaviour, such as accessing packaging, was a common source of exposure within toddlers and children in particular.Conclusions: This overview of all exposures to veterinary pharmaceutical products has identified high-risk groups to target interventions to reduce the incidence of future exposures. The pet-owning population and those personnel administering immunologicals to livestock represent a substantial cohort of individuals at risk of harm during, and in the immediate time following, administration of veterinary pharmaceutical products to animals. It is important to review risk management plans for veterinary pharmaceutical products to ensure product safety is as stringent as human equivalents. The legislative requirements concerning child-resistant packaging and the scheduling of livestock vaccines require reconsideration.

Hand Wipes: A Useful Tool for Assessing Human Exposure to Poly- and Perfluoroalkyl Substances (PFASs) through Hand-to-Mouth and Dermal Contacts.

The indoor environment contributes considerably to human exposure to poly- and perfluoroalkyl substances (PFASs). This study estimated the human exposure to PFASs from the indoor environment through hand-to-mouth and dermal contacts using hand wipes. An analytical method was developed to determine 25 PFASs in hand wipe samples collected as a composite sample from both hands of 60 adults. Polyfluoroalkyl phosphate esters (PAPs) were the predominant PFASs in the hand wipe samples (medians between 0.21 and 0.54 ng per sample). Positive and significant correlations were observed between PAPs, perfluorooctanesulfonate (PFOS), and perfluorooctanoate (PFOA) in hand wipes. Low frequency of daily hand washing (≤8 times day-1) was associated with 30-50% higher concentrations of PFOS, PFOA, and 8:2diPAP in hand wipes. Further, significant correlations between paired hand wipes and house dust samples were observed for PFOS, PFOA, and 6:2diPAP. Also, a significant correlation between PFOS in hand wipes and EtFOSE in indoor air was found. This finding indicates either a common source of exposure or a transformation of EtFOSE to PFOS in the environment or on the hands. The contributions of direct and indirect exposure to perfluoroalkyl acids (PFAAs) showed that PFOA contributed the highest exposure to adults via hand-to-mouth and dermal contacts, followed by PFOS. The median of estimated daily intakes via hand-to-mouth and dermal contacts (for hands only) for PFOA were 0.83 and 0.50 pg·kg bw-1·day-1, respectively. This study gives a first indication that PFAS concentrations in hand wipes can be used as a proxy for the exposure to PFASs from indoor environments, but further studies are needed to confirm this.

Polycyclic Aromatic Hydrocarbons (PAHs) in Select Commercially Processed Meat and Fish Products in Finland and the Mutagenic Potential of These Food Items

Commercially processed meat and fish products are common sources of human exposure to chemical food mutagens. In this study, we investigated the mutagenic potential of 20 different commercially processed meat and fish products (7 product types with 2–3 lots of each), along with the presence of four principal polycyclic aromatic hydrocarbons (PAHs) (benzo[a]pyrene [BaP], benzo[b]fluoranthene [BbF], benzo[a]anthracene [BaA] and chrysene [CHR]) in them. Sample extraction was carried out by an accelerated solvent extraction method, while the concentrations of the 4 PAHs were determined by gas chromatography-tandem mass spectrometry (GC-MS/MS). The mutagenic potential of food extracts was assessed by the standard plate incorporation assay (Ames test) using two strains of Salmonella typhimurium (TA 100 and TA 98) both in the presence and the absence of metabolic activation (S9-mix). The results show that in the majority of food items investigated, PAH levels were below the limit of quantification (0.78 μg/kg), except for smoked fish (0.8–15 μg/kg for the 3 lots), one batch of which even exceeded the maximum limits for both the sum of the 4 PAHs (44 μg/kg vs. 30 μg/kg) and BaP (8.2 μg/kg vs. 5.0 μg/kg). Furthermore, all three batches of smoked fish were also found to be mutagenic on both strains of Salmonella, both in the presence and the absence of metabolic activation. Overall, the data from both assays were in a fairly good agreement with one another, suggesting that PAHs are major contributors to mutagenicity of processed food products and the set maximum levels for PAHs are usually protective against food mutagenicity, although food samples harboring PAHs at levels approaching the maximum limits may exhibit mutagenic potential. Since the number of samples investigated was relatively small, further studies are warranted to verify the conclusions.

Perfluorooctanoic Acid (PFOA): Environmental Sources, Chemistry, Toxicology, and Potential Risks

ABSTRACT Attention regarding perfluoroalkyl and polyfluoroalkyl substances (PFAS) has increased in recent years, due to recognition of widespread environmental presence, recognition of a chemical structure that confers resistance to degradation, and reported health concerns. Historical common exposure sources include food, drinking water, occupational circumstances, and products in commerce (e.g., carpeting, clothing, paper products). Early-2000’s data showed perfluorooctanoic acid (PFOA) was present in blood samples from nearly all the U.S. general population (>99%). Alterations in industrial manufacturing processes, increased regulatory scrutiny, and advanced water treatment options have reduced the reported human body burden of PFAS in the U.S., including for PFOA. Human serum concentrations of PFOA, which do not identify the source(s) of exposure, have exhibited a substantial decrease (~63%) between the 1999–2000 and the 2013–2014 NHANES monitoring by the Centers for Disease Control and Prevention (CDC). With respect to both noncancer and potential cancer effects that may be associated with reported serum levels of PFOA, conclusions regarding an absence of effects, or insufficient information to suggest adverse effects, prevent a consistent conclusion about the occurrence and magnitude of human health effects. In the last several years, a number of state and federal agencies have developed health advisories or guideline values for drinking water exposure that are in the sub-ppb range. In 2016, a USEPA Health Advisory of 0.07 ppb was released, which stands in contrast to 2016 Health-based Values from Health Canada ranging from 0.2 ppb (PFOA) to 30 ppb, and a few other U.S. states with values even less than that of USEPA (e.g., MN, NJ, VT). Further work is necessary to distinguish in transparent fashion between drinking water levels that intentionally are set on a conservative basis to protect human health vs exposure levels that may be associated with tangible adverse effects.

Contact allergy to preservatives in Taiwan between 1996 and 2015

Background: Preservatives are widely used in personal and industrial products. Frequent and sustained exposure to preservatives can cause contact allergy. Objective: We investigated the prevalence of contact allergic reactions to common preservatives in Taiwan over a 20-year period. Methods: A retrospective analysis was conducted among patients with allergic contact dermatitis who underwent patch testing at our clinic between 1996 and 2015. Patients who showed positive reactions to preservatives were enrolled. The location of the reaction, likely source of the allergen, and patient occupation, sex, and age were recorded. Thirteen common preservatives, including methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), MI, formaldehyde (FA), paraben mix, and quaternium-15, were investigated. Results: Of 757 enrolled patients, 151 showed at least one positive reaction to preservatives. Allergy to MCI/MI (12.5%), the most frequent allergen in the standard series, showed a steeply increasing trend over time. FA (4.8%) and paraben mix (2.1%) were the next common allergens. Cosmetic products were the most common source of exposure (63.6%), while hairdressers and massage therapists were most commonly associated with occupational contact dermatitis. A sharp increase of sensitivity to MCI/MI was observed after 2006 and that of allergy to MI after 2013. Conclusions: In Taiwan, the prevalence of contact allergy to MCI/MI, MI, and parabens has increased in recent years. Individuals who are frequently exposed to cosmetic products should consider precautions against sensitization.

Blood Lead Surveillance and Exposure Sources Among Alaska Children.

Nationally, the child lead poisoning prevention strategy focuses on children in low-income communities living in old housing with lead paint. In Alaska, however, only about 3% of existing homes were built before 1950 and 38% were built during 1950-1979. As such, lead paint in old housing is a less frequent source of exposure for Alaska children with elevated blood lead levels (EBLLs). The Alaska Department of Health and Social Services collects and maintains data for all blood lead level (BLL) tests in the state and is responsible for following up on EBLLs. The Alaska Department of Health and Social Services conducts telephone interviews with parents of children with an EBLL to identify and remove possible sources of lead from the child's environment and prevent subsequent exposure. This review summarizes the surveillance data on BLLs in Alaska children for 2011-2015 and describes the most commonly identified possible sources of childhood lead exposure statewide since 2011. While the proportion of children in Alaska who received a BLL test during these years is low compared with other states and EBLL prevalence is low among children tested, several possible sources of exposure were identified among children with EBLLs, including nonpaint sources. This report summarizes the challenges of combatting childhood lead exposure in a rural state where housing is a less common exposure source and describes ongoing work to prevent childhood lead exposure in Alaska.

Political Ties and Predictable Returns

This paper demonstrates the importance of inter-firm political links, measured by common campaign contributions made by firm executives. Price movements of a firm’s stock are predictable based on stock price movements of connected firms. Cross-predictability is strongest among politically connected firms that operate in different states and sectors, suggesting that inter-firm political links are largely overlooked due to limited investor attention. To probe the underlying mechanism, I present evidence suggesting that common sources of political exposure across firms ex-ante cannot alone explain this relationship; instead, political ties play the key role, further synchronizing ex-post political agendas. Using the 2010 Citizens United v. FEC decision as an exogenous shock, I find that cross-predictability is weaker for firms that are restricted from actively engaging in political campaigns. Long-short stock portfolios based on political ties yield risk-adjusted returns of 4%-5% per annum.

LB10. Changing Epidemiology of Hepatitis A Virus Infections–– United States, 2007–2017

BackgroundHepatitis A virus (HAV) is primarily spread fecal-orally and causes acute illness including fever, jaundice, and diarrhea. After introduction and widespread use of the hepatitis A vaccine in the United States, infection with HAV decreased and outbreaks typically associated with a common-source were uncommon.MethodCDC receives reports of hepatitis A infections from states through the National Notifiable Disease Surveillance System (NNDSS) and/or directly to the viral hepatitis outbreak response team. We analyzed NNDSS hepatitis A data for 2007–2016, and a combination of NNDSS data and cases directly reported to the CDC hepatitis A outbreak response team during 2017; excluding 2017 NNDSS data from the four states that directly reported outbreaks to the outbreak response team to eliminate the potential for double-counting cases.ResultDuring 2007–2011, a total of 10,619 hepatitis A cases were reported; 521 (5%) were associated with outbreaks. Of the 274 outbreak-associated cases for whom clinical data were reported, 102 (37%) were hospitalized and one (0.3%) died. Of the 407 outbreak-associated cases for whom risk exposure data were reported, 210 (52%) were associated with a common source. Comparatively, during 2012–2017, a total of 11,483 hepatitis A cases were reported; 2,323 (20%) were associated with outbreaks. Of the outbreak-associated cases for whom clinical data were reported, 1,306/2,162 (60%) were hospitalized and 43/2,178 (2%) died. Of the outbreak-associated cases for whom risk exposure data were reported, 379/2,188 (17%) were associated with a common source.ConclusionIn the United States, outbreaks of hepatitis A infections in the decade prior to 2017 were infrequent and typically associated with a common source. Reported cases associated with hepatitis A outbreaks are increasing, along with concurrent increases in hospitalizations and deaths among persons with outbreak-associated infections. Recent outbreaks indicate a decrease in cases associated with a common-source exposure. Decreasing the susceptible population through adherence to childhood vaccination recommendations and targeted vaccination of recommended at-risk groups can prevent future hepatitis A outbreaks of any transmission pattern.Disclosures All authors: No reported disclosures.

Exposure to polycyclic aromatic hydrocarbons in women living in the Chinese cities of BaoDing and Dalian revealed by hair analysis

Polycyclic aromatic hydrocarbons (PAH) are produced from incomplete combustion of organic matter and released as environmental contaminants from activities such as transports, wood combustion, coal-fired power plants. In numerous urban areas worldwide, the levels of PAH exposure are considered critical regarding public health issues. The possibility to detect PAH and PAH metabolites biologically incorporated in human hair was demonstrated and proposed as biomarkers of exposure. Nevertheless, the possibility to distinguish different levels of exposure between different populations is still needed to validate the relevance of hair analysis in epidemiological studies. In this work, hair samples were collected from 204 women from two cities in China based on one year Air Quality Index history from governmental data (Baoding as polluted city and Dalian less polluted city). 8 out of the 15 parent PAH and 7 out of the 56 metabolites analyzed in this study were detected in all the samples. The highest concentrations in hair were observed for phenanthrene (4.2 to 889 pg/mg) > fluoranthene (1.05 to 204 pg/mg) > pyrene (3.2 to 124 pg/mg) for parent PAH, and for 9-OH-fluorene (0.04 to 1.78 pg/mg) > 2-OH-naphthalene (0.68 to 811 pg/mg) > 1-OH-anthracene (0.24 to 10.9 pg/mg) for metabolites. 14 parent PAH and 15 metabolites presented a significantly higher concentration in the hair samples collected from Baoding, as compared to Dalian. The median concentration of parent PAH was from 1.5 to 2.8 times higher in the hair of the subjects from Baoding than in subjects from Dalian and that of PAH metabolites was from 1 to 2.3 times higher. The study of inter-chemical associations revealed similarities and differences between the two areas, suggesting common and different sources of exposure depending on PAH respectively. The results confirmed the relevance of hair analysis to identify qualitative and quantitative differences in PAH exposure between populations from different areas. This study is the first one to investigate both parent PAH and their metabolites in a biological matrix.

Urinary metals and metal mixtures in Bangladesh: Exploring environmental sources in the Health Effects of Arsenic Longitudinal Study (HEALS)

IntroductionEnvironmental exposure to toxic metals and metalloids is pervasive and occurs from multiple sources. The Health Effects of Arsenic Longitudinal Study (HEALS) is an ongoing prospective study predominantly focused on understanding health effects associated with arsenic exposure from drinking water. The goal of this project was to measure a suite of elements in urine to better understand potential exposure patterns and to identify common environmental sources of exposure among this semi-rural Bangladeshi population. MethodsIn a random sample of 199 adult HEALS participants (50% female), the concentrations of 15 urinary elements (As, Ba, Cd, Co, Cs, Cu, Mn, Mo, Ni, Pb, Se, Sr, Tl, W, Zn) were assessed by Inductively-Coupled Plasma Mass Spectrometry (ICP-MS) to assess commonalities with sociodemographic characteristics and potential sources of exposure. We used principal component analysis (PCA) with varimax normalized rotations, and hierarchical cluster analysis (CA), using Ward's method with Euclidean distances, to evaluate these relationships. ResultsPCA and CA showed similar patterns, suggesting 6 principal components (PC) and 5 clusters: 1)PC: Sr-Ni-Cs/ CA: Sr-Ni-Co; 2) Pb-Tl/Pb-Tl-Se-Cs; 3) As-Mo-W/As-Mo-W; 4) Ba-Mn/Ba-Mn; 5) Cu-Zn/Cu-Zn-Cd; and 6) Cd. There was a strong significant association between the As-Mo-W PC/cluster and water arsenic levels (p < 0.001) and between the Cd PC and betel nut use (p = 0.003). The Sr-Ni-Cs PC was not related to any of the socio-demographic characteristics investigated, including smoking status and occupation. The first PC, Sr-Ni-Cs, explained 21% of the variability; the third PC, As-Mo-W, explained 12.5% of the variability; and the sixth PC, Cd, explained 10% of the variability. Day laborers appeared to have the highest exposure. ConclusionsGroundwater and betel nut use are likely important sources of metal and metalloid exposure in this population. These findings will guide future exposure assessment research in Bangladesh and future epidemiologic research investigating the degree to which metal mixtures play a role in disease development.

Urinary trace metals individually and in mixtures in association with preterm birth

One in ten infants born in the United States is born preterm, or prior to 37 weeks gestation. Exposure to elevated levels of metals, such as lead and arsenic, has been linked to higher risk of preterm birth (PTB), but consequences of lower levels of exposure and less studied metals are unclear. We examined the associations between 17 urinary trace metals individually and in mixtures in relation to PTB. The LIFECODES birth cohort enrolled pregnant women at <15 weeks gestation at Brigham and Women's Hospital in Boston. We selected cases of PTB (n = 99) and unmatched controls (n = 291) and analyzed urine samples for a panel of trace metals (median: 26 weeks gestation). We used logistic regression models to calculate the odds ratio (OR) for PTB and subtypes of PTB based on presentation at delivery. Subtypes included spontaneous and placental PTB. We used elastic net (ENET) regularization to identify individual metals or pairwise interactions that had the strongest associations with PTB, and principal components analysis (PCA) to identify classes of exposures associated with the outcome. We observed increased odds of PTB (OR: 1.41, 95% Confidence Interval [CI]: 1.12, 1.78) in association with an interquartile range difference in urinary copper (Cu). We also observed an increased OR for selenium (OR: 1.33, 95% CI: 0.98, 1.81). ENET selected Cu as the most important trace metal associated with PTB. PCA identified 3 principal components (PCs) that roughly reflected exposure to toxic metals, essential metals, and metals with seafood as a common source of exposure. PCs reflecting essential metals were associated with increased odds of overall and spontaneous PTB. Maternal urinary copper in the third trimester was associated with increased risk of PTB, and statistical analyses for mixtures indicated that after accounting for correlation this metal was the most important statistical predictor of the outcome.

Decision rule approach applied to estimate occupational lead exposure in a case-control study of kidney cancer.

We developed a systematic, data-driven approach to estimate metrics of occupational exposure to lead to aid in epidemiologic analyses in a case-control study of kidney cancer. Probability of exposure to ten lead sources was assigned using decision rules developed from an extensive literature review and expert judgement. For jobs with >50% probability of exposure, we assigned source-specific frequency based on subjects' self-reported task frequencies or means of subjects' job-groups and source-specific intensity estimates of blood lead (μg/dL). In our study, 18.7% of employed person-years were associated with high (≥80%) probability of exposure to any lead source. The most common medium (>50%) or high probability source of lead exposure was leaded gasoline (2.5% and 11.5% of employed person-years, respectively). The median blood lead attributed to occupational exposure was 3.1 μg/dL. These rules can aid in future studies after population-specific adaption for geographic differences and different exposure scenarios.

Occupational allergic contact dermatitis caused by colophonium.

Colophonium is a common contact allergen that is present not only in household products but also in occupational settings. To describe the sources of occupational exposure to colophonium and the occupations at risk of colophonium allergy. We reviewed patch test files from the years 2002 to 2017 at the Finnish Institute of Occupational Health for patients with allergic reactions to colophonium and abietic acid. We analysed the patch test, occupation and exposure data of 39 patients diagnosed with occupational allergic contact dermatitis (OACD) caused by colophonium. Of the patients examined for suspected occupational dermatitis, 4.6% (n = 118) reacted positively to colophonium. The majority of the OACD patients worked in the wood industry, as machinists, or were involved in soldering or agriculture. The most common occupational sources of exposure were coniferous wood and wood-derived materials, followed by glues, metalworking fluids, and soldering materials. Colophonium is not always mentioned in safety data sheets (SDSs), and the sources of colophonium exposure are often materials for which there are no SDSs. OACD caused by colophonium is quite common and occurs in a variety of occupations. SDSs provide poor information for exposure assessment. Patch testing with the patient's own materials was often useful in establishing the diagnosis.

Current strategies in the safety assessment of monoclonal antibodies

Naphthalene occurs together with polycyclic aromatic hydrocarbons (PAHs) at industrial workplaces and is ubiquitous in the environment. For biological monitoring of naphthalene exposures, up to now mainly 1- and 2-naphthol in urine have been used. Recently, we proposed 1,2-dihydroxynaphthalene (1,2-DHN) and the 1- and 2-naphthylmercapturic acid (1- and 2-NMA) as new urinary biomarkers to characterise a naphthalene exposure.In this study, in a collective of nine occupationally exposed workers handling with creosote the naphthalene metabolites 1,2-DHN, 1- and 2-NMA as well as 1- and 2-naphthol were analysed in order to evaluate the suitability of the different parameters for their application in biomonitoring studies. Additionally, air sampling was conducted to characterise the exposure in task related exposure situations at different workplaces.In the analysed 51 urine samples, 1,2-DHN was the main metabolite with concentrations ranging from 2.3 to 886 μg/g creatinine (crea) (median 34 μg/g crea). For the sum of 1- and 2-naphthol, concentrations in the range of 2.6–174 μg/g crea (median 15 μg/g crea) were observed. 1-NMA concentrations were in the range of < LOD-2.4 μg/g crea (61% > LOD), while 2-NMA was not detected in the analysed urine samples. The biomarkers 1,2-DHN, 1- and 2-naphthol as well as 1-NMA showed significant correlations, which pointed out to naphthalene as the common exposure source. The poor correlations between naphthalene in the air and the biomarkers in urine may be a result of the varying exposure situations and may indicate not solely inhalative, but additional dermal uptake.1,2-DHN was the most sensitive and, together with 1-NMA, the most specific parameter of the biological monitoring of naphthalene exposure at workplaces. Further studies with this parameter are needed for individuals at different workplaces as well as for persons of the general population without occupational PAH exposure to characterise 1,2-DHN levels as well as to establish their relationship with the naphthalene exposure.