Individual Cumulative Exposure Research Articles

Dose-response relationship between lung function and chest imaging response to silica exposures in artificial stone manufacturing workers

BackgroundOccupational exposure to artificial stone, a popular material used for countertops, can cause accelerated silicosis, but the precise relationship between silica dose and disease development is unclear.ObjectivesThis study evaluated the impact of silica exposure on lung function and chest imaging in artificial stone manufacturing workers.MethodsQuestionnaire and spirometry assessments were administered to workers in two plants. A high-exposure subset underwent further evaluation, including chest CT and DLco. Weighting factors, assigned as proxies for silica exposure, were based on work tasks. Individual cumulative exposures were estimated using area concentration measurements and time spent in specific areas. Exposure-response associations were analyzed using linear and logistic regression models.ResultsAmong 65 participants, the mean cumulative silica exposure was 3.61 mg/m3-year (range 0.0001 to 44.4). Each 1 mg/m3-year increase was associated with a 0.46% reduction in FVC, a 0.45% reduction in FEV1, and increased lung function abnormality risk (aOR = 1.27, 95% CI = 1.03–1.56). Weighting factors correlated with cumulative exposures (Spearman correlation = 0.59, p < 0.0001), and weighted tenure was associated with lung function abnormalities (aOR = 1.04, 95% CI = 1.01–1.09). Of 37 high-exposure workers, 19 underwent chest CT, with 12 (63%) showing abnormal opacities. Combining respiratory symptoms, lung function, and chest X-ray achieved 91.7% sensitivity and 75% specificity for predicting chest CT abnormalities.ConclusionLung function and chest CT abnormalities occur commonly in artificial stone workers. For high-exposure individuals, abnormalities on health screening could prompt further chest CT examination to facilitate early silicosis detection.

Associations of COVID-19 lockdown with birth weight in China.

During the special period of the global spread of COVID-19, pregnant women are sensitive groups to the impacts of COVID-19 epidemic. However, the effects of lockdown measures implemented in response to the COVID-19 on fetal birthweight remain unclear. This study investigated the associations of COVID-19 lockdown with birth weight in Chinese population. We collected 730,153 data of participants from hospitals of five cities in the south of China, we defined the time period of level I response (1/23-2/24/2020) as level I lockdown, and women who were pregnant during level I lockdown as the exposure group. Women who were pregnant during the same calendar month from 2015 to 2019 were defined as the unexposed group. We quantitatively estimate the individual cumulative exposure dose by giving different weights to days with different emergency response levels. Generalized linear regression models were used to estimate the association between COVID-19 lockdown exposure with birth weight and risk of low birth weight (<2,500 g) and macrosomia (>4,000 g). The birth weight of the exposed group is heavier than the unexposed group (3,238.52 vs. 3,224.11 g: adjusted β = 24.39 g [95% CI: 21.88, 26.91 g]). The exposed group had a higher risk of macrosomia (2.8% vs. 2.6%; adjusted OR = 1.17 [95% CI: 1.12, 1.22]). More obvious associations were found between COVID-19 lockdown and macrosomia in women who experienced the lockdown in their early pregnancy. Women who experienced the lockdown at their 4-7 weeks of pregnancy showed statistically significant heavier birth weight than unexposed group (after adjustment): β = 1.28 (95% CI: 1.11, 1.46) g. We also observed a positive association between cumulative exposure dose of COVID-19 lockdown in all pregnant women and birth weight, after divided into four groups, Q1: β = 32.95 (95% CI: 28.16, 37.75) g; Q2: β = 18.88 (95% CI: 14.12, 23.64) g; Q3: β = 19.50 (95% CI: 14.73, 24.28) g; Q4: β = 21.82 (95% CI: 17.08, 26.56) g. However, there was no statistically significant difference in the risk of low birth weight between exposed and unexposed groups. The COVID-19 lockdown measures were associated with a heavier birth weight and a higher risk of macrosomia. Early pregnancy periods may be a more susceptible exposure window for a heavier birth weight and a higher risk of macrosomia. We also observed a positive association between cumulative exposure dose of COVID-19 lockdown and birth weight. The government and health institutions should pay attention to the long-term health of the infants born during the COVID-19 lockdown period, and follow up these mothers and infants is necessary.

Effects of Ionizing Radiation Exposure on Cataract among Radiation Workers of Interventional Cardiology in Indonesia

Abstract Purpose The aim of this study was to determine the prevalence of radiation-induced cataracts and its correlation with radiation exposure dose and radiation protection equipment use among radiation workers of interventional cardiology. Methods This is a cross-sectional and retrospective case–control study. We included 180 subjects. The prevalence of radiation-induced cataracts was assessed using Scheimpflug analysis on the Pentacam-Oculus device. Individual cumulative radiation exposure dose and radiation protection equipment use were identified from questionnaires and personal dosimeters. Results The prevalence of radiation-induced cataracts was 16.7%. The median cumulative radiation dose was 0.8 (0.1–35.6) Gy. A positive correlation was found between cumulative radiation dose and lens density (R Spearman = 0.64). We found 83.9% of subjects used ceiling-suspended shields in 71 to 100% of their working period. However, most subjects (40.6%) did not wear protective eyewear. There was a statistically significant increasing risk of radiation-induced cataracts and unresponsive use of radiation protection equipment. Subjects using ceiling-suspended shield in only 31 to 50% of their working period increased their cataract risk by 10.8 times (95% confidence interval [CI]: 1.05–111.49, p = 0.044). Meanwhile, subjects using protective eyewear in only 51 to 70% of their working period increased their cataract risk by 8.64 times (p = 0.001). Subjects who did not wear protective eyewear had an odd ratio of 164.3 (95% CI: 19.81–1363) compared to those who did. Conclusion Radiation-induced cataracts among radiation workers of interventional cardiology depended on the radiation exposure dose and the use of radiation protection equipment.

145 Cumulative Occupational Exposure to Nanoparticles, Inflammatory Biomarkers and Respiratory Health in the Nanoexplore Cohort

Abstract Exposure to nanomaterials (NMs) may harm biological systems by altering the redox status and triggering inflammatory processes, which in turn may affect respiratory health. In the NanoExplore cohort of 141 workers, we observed a positive dose-response relationship between the short-term exposure to NMs and biomarkers of inflammation, measured in Exhaled Breath Condensate (EBC), but no relationship with lung function parameters (LFP). This study focuses on the association between cumulative exposure to NMs over the last 10 years and changes in LFP and the potential mediating role of airways inflammation. Individual cumulative exposure was estimated by multiplying the nanoparticle concentration, measured at workers’ workstations by DiSCmini, by the duration of worker’s employment at the corresponding workstation up to last 10 years. In EBC, we measured High-Sensitivity CRP (Hs-CRP), IL-1β, TNF-α, and IL-10 as biomarkers of inflammation. LFP were assessed according to ATS/ERS standards. Their association with cumulative exposure was examined using logistic regression models adjusted for tobacco consumption (in pack-years), among 136 workers with complete data (19-62 yrs., 70% males). We found that per unit increase in 10-year exposure, the risk of observing FEV1 values below the normal limit increases by 0.3% (95%CI: 1.000-1.005, p=0.049) and by 0.8% (95%CI: 1.000-1.015, p=0.039) with the exposure expressed as number of particles and lung deposited surface area, respectively. The ongoing mediation analysis will investigate the potential mediating role of inflammation in the association between cumulative exposure to NMs and lung function

Effects of coexposure to noise and mixture of toluene, ethylbenzene, xylene, and styrene (TEXS) on hearing loss in petrochemical workers of southern China.

Many harmful factors existing simultaneously with noise are reported to induce hearing impairment, such as organic solvents. However, the existing hearing safety limits and current risk assessment for hearing loss rely on single noise exposure. It is urgent to clarify the combined effect of noise and other harmful factors on hearing loss. Petrochemical workers are always exposed to noise and organic solvents, mainly benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS), while the combined effect of their coexposure on hearing remains unclear. Herein we conducted a cross-sectional survey, measuring pure-tone audiometry of 1496 petrochemical workers in southern China. Participants exposed to BTEXS were 569, 524, 156, 452, and 177 respectively. Individual cumulative noise exposure (CNE) levels and BTEXS exposure were assessed. The average CNE was 93.27 ± 4.92dB(A)·years, and the concentrations of BTEXS were far below the occupational exposure limits of China. Logistic regression analyses showed that CNE was consistently positively associated with hearing loss (HL) and high-frequency hearing loss (HFHL) but not related to speech-frequency hearing loss (SFHL). Compared with participants in the lowest quartile of CNE, those in the highest quartile showed an OR of 5.229 (95% CI: 3.179, 8.598) for HFHL. Two-pollutant model analysis indicated that TEXS exposure was positively associated with HL (OR 1.679, 95%CI 1.086, 2.597), SFHL (OR 2.440, 95%CI 1.255, 4.744), and HFHL (OR 1.475, 95%CI 1.077, 2.020). However, no interactions were observed between CNE and TEXS coexposure on hearing loss. In our study, covariates including smoking and drinking status, body mass index (BMI), ear protection and personal protective equipment, and use of earphone/headphone were adjusted. In conclusion, coexposure to noise and low-level TEXS could induce more severe damage on hearing function than exposure to each alone, especially SFHL. Therefore, petrochemical workers simultaneously exposed to noise and TEXS, even at low-level, should be included in hearing protection programs.

Individual level spatial-temporal modelling of exposure potential of livestock in the Cove Wash watershed, Arizona

ABSTRACT Personal exposure studies suffer from uncertainty issues, largely stemming from individual behaviour uncertainties. Built on spatial-temporal exposure analysis and methods, this study proposed a novel approach to spatial-temporal modelling that incorporated behaviour classifications taking into account uncertainties, to estimate individual livestock exposure potential. The new approach was applied in a community-based research project with a Tribal community in the southwest United States to address questions on potential livestock exposure to abandoned uranium mines (AUMs). The study aimed to 1) classify Global Positioning System (GPS) data from livestock into three behaviour subgroups – grazing, travelling or resting; 2) calculate the daily cumulative exposure potential for livestock; 3) assess the performance of the computational method with and without behaviour classifications. Using Lotek Litetrack GPS collars, we collected data at a 20-min-interval for two flocks of sheep and goats during the spring and summer of 2019. Analysis and modelling of GPS data demonstrated no significant difference in individual cumulative exposure potential within each flock when animal behaviours with probability/uncertainties were considered. However, when daily cumulative exposure potential was calculated without consideration of animal behaviour or probability/uncertainties, significant differences among animals within a herd were observed, which does not match animal grazing behaviours reported by livestock owners. These results suggest that the proposed method including behaviour subgroups with probability/uncertainties more closely resembled the observed grazing behaviours. Results from the research may be used for future intervention and policy-making on remediation efforts in communities where grazing livestock may encounter environmental contaminants.

Das beruflich bedingte Harnblasenkarzinom – Die BK 1301-Matrix als Algorithmus und Entscheidungshilfe für eine Zusammenhangsbegutachtung

Work-related bladder cancer – The BK 1301 matrix as an algorithm and decision aid in the context of an assessment of an occupational disease The risk of developing bladder cancer can be influenced by various occupational and non-occupational risk factors. These need to be evaluated in the context of an assessment of an occupational disease according to no. 1301 (BK 1301: Mucosal changes, cancer and other neoplasms of the urinary tract (hereinafter referred to as “bladder cancer”) caused by aromatic amines) of the Annex to the Ordinance on Occupational Diseases. The BK 1301 matrix presented here for the assessment of the causal relationship in urinary bladder cancers after proven and relevant occupational exposure to carcinogenic aromatic amines was derived as a convention by a working group, based on the results of a workshop with more than 230 participants. It can be applied even in the absence of an individual cumulative exposure dose. The decision matrix is intended to support experts experienced in occupational medicine in the field of BK 1301 in the assessment procedure. It also provides an overview of relevant aspects of work-related bladder cancer for the purposes of accident insurance institutions and courts. The BK 1301 matrix includes occupational indicators such as exposure duration, exposure frequency and exposure intensity, as well as the age of onset, the latency period and competing non-occupational risk factors such as smoking behaviour. Based on the BK 1301 matrix, the relevant arguments favouring or refuting a causal occupational relationship in the individual case can be evaluated in detail by the occupational physician, resulting in a recommendation for or against recognition of the bladder cancer as an occupational disease. This notwithstanding, the decision as to whether an occupational disease is indeed present is ultimately an administrative act of the responsible accident insurance institution, which may be subject to review by the social courts. Keywords: expert opinion – occupational disease 1301 – bladder cancer – aromatic amines – matrix – convention

Association of cumulative early medical factors with autism and autistic symptoms in a population-based twin sample

Although highly heritable, environment also contributes to the etiology of autism spectrum disorder (ASD), with several specific environmental factors previously suggested. A registry-linked population-based twin cohort of 15,701 pairs (586 individuals with an ASD diagnosis), was established within the Child and Adolescent Twin Study in Sweden. Participants were evaluated for autistic symptoms at age 9 using the Autism-Tics, ADHD and other Comorbidities parental interview. A series of binary cut-offs indicated whether participants scored over various ASD symptom percentiles. Three early medical factors previously associated with ASD, beyond familial confounding (low birth weight, congenital malformations and perinatal hypoxia), were summed up creating an individual cumulative exposure load. A series of unconditional logistic regressions between all individuals and conditional regressions within twin pairs were performed for each outcome and exposure level. Between all individuals increasing cumulative early exposure loads were associated with increasing risk of ASD diagnosis (OR 3.33 (95%CI 1.79–6.20) for three exposures) and autistic symptoms (ranging from OR 2.12 (1.57–2.86) for three exposures at the 55th symptom percentile cut-off to OR 3.39 (2.2–5.24) at the 95th). Within twin pairs, the association between three exposures and an ASD diagnosis remained similar, but not statistically significant (OR 2.39 (0.62–9.24)). Having a higher load of early cumulative exposure was consistently associated with autistic symptoms after adjusting for familial confounding and sex (OR 3.45 (1.66–7.15) to OR 7.36 (1.99–27.18)). This study gives support to the cumulative stress hypothesis of ASD, and the dimensional model regarding environmental exposures, after adjustment for familial confounding.

Characteristics and Determinants of the Presence of Respiratory Symptoms among Sewage Workers in Malaysia.

Background The purpose of this study was to determine the relationships of PM 2.5 and H2S exposure with the presence of work-related respiratory symptoms among sewage workers. Methods A cross-sectional study was conducted in eleven sewage plants located in the central region of Peninsular Malaysia. One hundred ninety-one sewage workers were assessed using the British Medical Research Council (BMRC) questionnaire. Area air sampling was performed in three different sewage plants to measure the following parameters: physical air quality and concentration of PM 2.5 and H2S. Result Chronic cough (34.0%) was reported as the most common symptom, followed by chronic phlegm (26.2%), shortness of breath (7.9%), and chest tightness (3.7%). There were five significant determinants of the presence of respiratory symptoms among the sewage workers: shift work (AOR 23.50, 95% CI: 1.90–616.52), working at a sludge treatment facility (STF) (AOR 25.46, 95% CI: 2.06–314.29), a longer duration of working years (AOR 1,21, 95% CI: 1.01–1.44), individual cumulative exposure to PM 2.5 (AOR 9.01, 95% CI: 1.98–83.33), and individual cumulative exposure to H2S (AOR 1.04, 95% CI: 1.01–1.07). The majority of STF and non-STF workers had higher exposure to PM 2.5 and H2S concentrations in the air than office workers. Conclusion Sewage workers working at non-STFs or STFs reported a significantly higher prevalence of work-related respiratory symptoms and exposure to PM 2.5 and H2S compared with office workers. Exposure-response relationships were also found in sewage workers' cumulative exposure to PM 2.5 and H2S and the presence of respiratory symptoms.

Adverse Childhood Experiences Distinguish Violent Juvenile Sexual Offenders' Victim Typologies.

Juvenile perpetrators account for over 25% of all sexual offenses, and over one-third of such offenses are against victims under the age of 18. Given empirical connections between adverse childhood experience (ACE) exposure and perpetration of violence, we create victim typologies based on the juveniles’ relationship to their victims among 5539 justice-involved adolescents who have committed violent against-person sexual felonies. Multinomial logistic regression is used to assess which covariates, including individual ACE exposures and cumulative traumatic exposures, are associated with victim typologies. This approach allows for better targeting of violence prevention efforts, as a more nuanced understanding of the increased likelihood to victimize specific victim groups lends to potential differences in treatment provision, beyond simplistic findings regarding ACE exposure increasing offending. Results indicate five classes of victim types, ranging from a low of 6.4%, with primarily strangers as victims, to 31.3%, with predominately acquaintances as victims, and only 12.9% with a diverse array of relationships to victims. Importantly, many demographic and individual risk factors, and specific traumatic exposures were related to victimizing one’s sibling, while cumulative trauma as measured by an ACE score decreased the likelihood of victimizing classmates, while increasing the likelihood of victimizing siblings and other relatives compared to victimizing acquaintances.

Factors Affecting Asbestosis Mortality Among Asbestos-Cement Workers in Italy.

This study was performed with the aim of investigating the temporal patterns and determinants associated with mortality from asbestosis among 21 cohorts of Asbestos-Cement (AC) workers who were heavily exposed to asbestos fibres. Mortality for asbestosis was analysed for a cohort of 13 076 Italian AC workers (18.1% women). Individual cumulative asbestos exposure index was calculated by factory and period of work weighting by the different composition of asbestos used (crocidolite, amosite, and chrysotile). Two different approaches to analysis, based on Standardized Mortality Ratios (SMRs) and Age-Period-Cohort (APC) models were applied. Among the considered AC facilities, asbestos exposure was extremely high until the end of the 1970s and, due to the long latency, a peak of asbestosis mortality was observed after the 1990s. Mortality for asbestosis reached extremely high SMR values [SMR: males 508, 95% confidence interval (CI): 446-563; females 1027, 95% CI: 771-1336]. SMR increased steeply with the increasing values of cumulative asbestos exposure and with Time Since the First Exposure. APC analysis reported a clear age effect with a mortality peak at 75-80 years; the mortality for asbestosis increased in the last three quintiles of the cumulative exposure; calendar period did not have a significant temporal component while the cohort effect disappeared if we included in the model the cumulative exposure to asbestos. Among heaviest exposed workers, mortality risk for asbestosis began to increase before 50 years of age. Mortality for asbestosis was mainly determined by cumulative exposure to asbestos.

A Pilot Biomonitoring Study of Cumulative Phthalates Exposure among Vietnamese American Nail Salon Workers.

Many California nail salon workers are low-income Vietnamese women of reproductive age who use nail products daily that contain androgen-disrupting phthalates, which may increase risk of male reproductive tract abnormalities during pregnancy. Yet, few studies have characterized phthalate exposures among this workforce. To characterize individual metabolites and cumulative phthalates exposure among a potentially vulnerable occupational group of nail salon workers, we collected 17 post-shift urine samples from Vietnamese workers at six San Francisco Bay Area nail salons in 2011, which were analyzed for four primary phthalate metabolites: mono-n-butyl-, mono-isobutyl-, mono(2-Ethylhexyl)-, and monoethyl phthalates (MnBP, MiBP, MEHP, and MEP, respectively; μg/L). Phthalate metabolite concentrations and a potency-weighted sum of parent compound daily intake (Σandrogen-disruptor, μg/kg/day) were compared to 203 Asian Americans from the 2011–2012 National Health and Nutritional Examination Survey (NHANES) using Student’s t-test and Wilcoxin signed rank test. Creatinine-corrected MnBP, MiBP, MEHP (μg/g), and cumulative phthalates exposure (Σandrogen-disruptor, μg/kg/day) levels were 2.9 (p < 0.0001), 1.6 (p = 0.015), 2.6 (p < 0.0001), and 2.0 (p < 0.0001) times higher, respectively, in our nail salon worker population compared to NHANES Asian Americans. Levels exceeded the NHANES 95th or 75th percentiles among some workers. This pilot study suggests that nail salon workers are disproportionately exposed to multiple phthalates, a finding that warrants further investigation to assess their potential health significance.

Mortality and mesothelioma incidence among chrysotile asbestos miners in Balangero, Italy: A cohort study.

We studied cancer mortality and mesothelioma incidence in 974 male workers employed at least 6 months at the Balangero mine (Italy), the largest chrysotile mine in Western Europe, active from 1917 to 1985. Vital status as of 31 May 2013, causes of deaths and mesothelioma incidence from 1990 were ascertained. Past exposure to asbestos by working area and calendar period was estimated, based on historical data of fibers concentrations. Individual cumulative exposure was assessed by applying estimates to the job history of cohort members. Standardized mortality ratios (SMRs) for selected causes and standardized incidence ratios for malignant mesothelioma (MM) were calculated based on regional reference rates. Poisson regression analysis was used to study MM and lung cancer risk by latency, duration, and cumulative exposure. Mortality was increased for all causes (SMR = 1.28; 95% confidence interval [CI] = 1.17-1.40), pleural cancer (SMR = 4.30; 95% CI = 1.58-9.37), asbestosis (SMR = 375.06; 95% CI = 262.68-519.23). An increase was also found for lung cancer (SMR = 1.14; 95% CI = 0.81-1.55) and peritoneal cancer (SMR = 3.25; 95% CI = 0.39-11.75). The risk of both pleural and peritoneal cancer mortality and of mesothelioma incidence increased with increasing cumulative exposure, duration, and latency. Poisson regression analyses showed an increase in mesothelioma risk with cumulative asbestos exposure and suggest a similar trend for lung cancer. Asbestosis mortality also increased with cumulative exposure. Among Balangero chrysotile miners and millers, the occurrence of malignant and nonmalignant asbestos-related diseases was increased by exposure, with dose-response relation. The study confirms the carcinogenicity of chrysotile asbestos, in particular for pleural mesothelioma.

Blood DNA methylation biomarkers of cumulative lead exposure in adults.

Background:Lead is a ubiquitous toxicant following three compartment kinetics with the longest half-life found in bones. Patella and tibia lead levels—validated measures of cumulative exposure—require specialized X-ray-fluorescence-spectroscopy available only in a few centers worldwide. We developed minimally-invasive biomarkers reflecting individual cumulative lead exposure using blood DNA methylation profiles—obtainable via Illumina450K or IlluminaEPIC bead-chip assays.Methods:We developed and tested two methylation-based biomarkers from 348 Normative Aging Study (NAS) elderly men. We selected methylation sites with strong associations with bone lead levels via robust regressions analysis and constructed the biomarkers using elastic nets. Results were validated in a NAS subset, reporting specificity and sensitivity.Findings:Participants were 73 years old on average (standard deviation, SD=6), with moderate lead levels of (mean±SD patella:27±18 μg/g; tibia:21±13 μg/g). Methylation-based biomarkers for lead in patella and tibia included 59 and 138 DNA methylation sites, respectively. Estimated lead levels were significantly correlated with actual measured values, (r=0.62 patella, r=0.59 tibia) and had low mean square error (MSE) (MSE=0.68 patella, MSE=0.53 tibia). Means and distributions of the estimated and actual lead levels were not significantly different across patella and tibia bones (p>0.05). Methylation-based biomarkers discriminated participants highly exposed (>median) to lead with a specificity of 74% and 73% for patella and tibia lead levels, respectively, with 70% sensitivity.Interpretation:DNA-methylation-based lead biomarkers are novel tools that can be used to reconstruct decades’ worth of individual cumulative lead exposure using only blood DNA methylation profiles and may help identify the consequences of cumulative exposure.

Mortality for Mesothelioma and Lung Cancer in a Cohort of Asbestos Cement Workers in BARI (Italy): Time Related Aspects of Exposure.

In this cohort mortality study we used an exposure index to evaluate individual cumulative exposure as proxy of asbestos dose and we evaluated change in cancer mortality pattern after long time since the end of exposure. We calculated standardized mortality ratios (SMRs) for several causes of death stratified by latency, cumulative exposure, and time since last exposure (TSLE). Latency: we observed a peak and then a decrease in SMR for lung, pleural, and peritoneal cancer. Cumulative Exposure: We observed a peak and then a decrease in SMR for lung and pleural cancer, not for peritoneal cancer. TSLE: Pleural cancer SMR peaked at 20 to 29 years, then decreased, peritoneal cancer SMR reached a plateau after 20 years and lung cancer mortality was in excess in each class. We found different patterns in mortality in the main asbestos-related tumors.

Use of phthalate-containing prescription drugs and the risk of gastric cancer: a Danish nationwide case-control study

Background: Phthalates are used as excipients in some drug products, and up to a 50-fold increased urinary excretion of phthalate metabolites compared to non-users has been demonstrated in users of such products. In vitro studies have demonstrated that phthalates stimulate mechanisms involved in gastric cancer development. We therefore examined the association between cumulative phthalate exposure from drug products and the risk of gastric adenocarcinomas.Methods: Using the Danish Cancer Registry, we identified all patients with incident gastric adenocarcinoma from 2008 to 2015 (n = 1525). Cancer cases were matched to 10 controls. Linking information retrieved from nationwide Danish registries, we determined individual cumulative phthalate exposure to the ortho-phthalates diethyl phthalate (DEP), dibutyl phthalate (DBP) and enteric phthalate polymers from prescription drugs. The association between cumulative phthalate exposure and gastric adenocarcinoma was estimated using conditional logistic regression, adjusting for socioeconomical status and drugs or comorbidities known or suspected to modify the risk of gastric adenocarcinoma.Results: No association was seen for the risk of gastric adenocarcinomas among individuals with high cumulative exposure to ortho-phthalates (exceeding 500 mg) (ORadj 1.22, 95% CI: 0.84–1.77). Likewise, no associations were observed individually for DEP (ORadj 1.06 95% CI: 0.63–1.76) or DBP (ORadj 1.32 95% CI: 0.78–2.23). Cumulative exposure to enteric phthalate polymers exceeding 10,000 mg, did not reveal an association with gastric adenocarcinoma (ORadj 0.79, 95% CI: 0.54–1.16) and no association was seen for individual compounds. Additionally, no dose-response pattern was observed across exposure strata (p = .39, test for trend).Conclusion: We did not find an increased risk of gastric adenocarcinoma among Danish users of phthalate-containing drug products. Our study is limited by a low number of cases exposed to high cumulative doses of phthalates.

Blood DNA Methylation Biomarkers of Cumulative Lead Exposure in Adults

Lead is a ubiquitous toxicant following three compartment kinetics with the longest half-life found in bones. Patella and tibia lead levels—validated measures of cumulative exposure—require specialized X-ray-fluorescence-spectroscopy available only in a few centers worldwide. We developed minimally invasive biomarkers reflecting individual cumulative lead exposure using blood DNA methylation profiles—obtainable via Illumina 450K or IlluminaEPIC bead-chip assays. We developed and tested two methylation-based biomarkers from 348 Normative Aging Study (NAS) elderly men. We selected methylation sites with strong associations with bone lead levels via robust regressions analysis and constructed the biomarkers using elastic nets. Results were validated in a NAS subset, reporting specificity, and sensitivity. Participants were 73 years old on average (standard deviation, SD = 6), with moderate lead levels of (mean ± SD patella: 27 ± 18 µg/g; tibia:21 ± 13 µg/g). Methylation-based biomarkers for lead in patella and tibia included 59 and 138 DNA methylation sites, respectively. Estimated lead levels were significantly correlated with actual measured values, (r = 0.62 patella, r = 0.59 tibia) and had low mean square error (MSE) (MSE = 0.68 patella, MSE = 0.53 tibia). Means and distributions of the estimated and actual lead levels were not significantly different across patella and tibia bones (p > 0.05). Methylation-based biomarkers discriminated participants highly exposed (>median) to lead with a specificity of 74 and 73% for patella and tibia lead levels, respectively, with 70% sensitivity. DNA methylation-based lead biomarkers are novel tools that can be used to reconstruct decades’ worth of individual cumulative lead exposure using only blood DNA methylation profiles and may help identify the consequences of cumulative exposure.

Effect of Occupational Exposure to Cyanuric Chloride on Respiratory Morbidity: Cross-Sectional Analyses of Respiratory Symptoms and Longitudinal Analyses of Lung Function Parameters.

The study aimed to investigate the relationship between occupational exposure to cyanuric chloride and respiratory morbidity. The cohort comprises former and active workers at three European production sites. Individual cumulative exposure, exposure duration, and long-term average concentration were estimated. In the longitudinal analyses, generalized equation estimates (GEEs) models were used to estimate the risks. To determine a threshold value for cumulative exposure, hockey-stick models were fitted. A sensitization to cyanuric chloride, without an effect on lung function, has been observed. For the total cohort, both the single models and the multimodel analyses provided hints of lung function loss resulting from long-term exposure to cyanuric chloride. With respect to the estimated average loss from a representative model, a cumulative exposure of 0.3 mg/m-years (0.2 to 0.4 mg/m-years) yielded the best model fit. A shift reference value (time-weighted average, 8 hours) of 0.06 mg/m could be derived. For future research, a larger database of exposure measurements and continuing health monitoring will be valuable.

Exposures to Air Pollution and Risk of Acute-onset Placental Abruption: A Case-crossover Study.

Despite abruption's elusive etiology, knowledge of triggers that precede it by just a few days prior to delivery may help to understand the underpinnings of this acute obstetrical complication. We examine whether air pollution exposures immediately preceding delivery are associated with acute-onset abruptions. We applied a bidirectional, time-stratified, case-crossover design to births with an abruption diagnosis in New York City, 2008-2014. We measured ambient fine particulate matter (PM2.5) and nitrogen dioxide (NO2). We fit distributed lag nonlinear models based on conditional logistic regression to evaluate individual exposure and cumulative exposures over lags 0-7 days before abruption, adjusted for temperature and relative humidity (similar lags to the main exposures). We identified 1,190 abruption cases. We observed increased odds of abruption for exposure to PM2.5 (per 10 μg/m) on lag day 3 (odds ratio [OR] 1.19, 95% confidence interval [CI] = 0.98, 1.43), lag day 4 (OR 1.21, 95% CI = 1.01, 1.46), and lag day 5 (OR 1.17, 95% CI = 1.03, 1.33). Similarly, the odds of abruption increased with exposure to NO2 (per 5 ppb) on lag day 3 (OR 1.16, 95% CI = 0.98, 1.37), lag day 4 (OR 1.19, 95% CI = 1.02, 1.39), and lag day 5 (OR 1.16, 95% CI = 1.05, 1.27). Exposures to PM2.5 and NO2 at other lags, or cumulative exposures, were not associated with abruption of acute onset. This case-crossover study showed evidence of an association between short-term ambient air pollution exposures and increased abruption risk of acute onset.

Mortality Among Hardmetal Production Workers: German Historical Cohort Study.

The aim of this study was to investigate a cohort in German hardmetal industry, especially relationship between exposures to cobalt, with and without tungsten, and risks of total and cause-specific mortality. The cohort comprises blue-collar workers at three German plants who were employed in hardmetal processing. Individual cumulative exposures and long-term average concentrations were estimated for cobalt, nickel, tungsten, respirable, and inhalable dust. Standardized mortality ratios (SMRs) were calculated for external comparisons. Time-dependent multivariable Cox models were performed for internal analyses. Elevated SMRs were found for all-cause, heart diseases, and nonmalignant respiratory diseases mortality, but not for lung cancer. Internal analyses did not show increased risks for any endpoints, and no exposure-response relationship was indicated. This study does not provide evidence for elevated lung cancer risks. Methodologic limitations, incomplete ascertainment of death causes in particular, impede conclusions about exposure effects.