Occupationally-exposed Individuals Research Articles

Misclassification of causes of death among a small all-autopsied group of former nuclear workers: Death certificates vs. autopsy reports.

The U.S. Transuranium and Uranium Registries performs autopsies on each of its deceased Registrants as a part of its mission to follow up occupationally-exposed individuals. This provides a unique opportunity to explore death certificate misclassification errors, and the factors that influence them, among this small population of former nuclear workers. Underlying causes of death from death certificates and autopsy reports were coded using the 10th revision of the International Classification of Diseases (ICD-10). These codes were then used to quantify misclassification rates among 268 individuals for whom both full autopsy reports and death certificates with legible underlying causes of death were available. When underlying causes of death were compared between death certificates and autopsy reports, death certificates correctly identified the underlying cause of death's ICD-10 disease chapter in 74.6% of cases. The remaining 25.4% of misclassified cases resulted in over-classification rates that ranged from 1.2% for external causes of mortality to 12.2% for circulatory disease, and under-classification rates that ranged from 7.7% for external causes of mortality to 47.4% for respiratory disease. Neoplasms had generally lower misclassification rates with 4.3% over-classification and 13.3% under-classification. A logistic regression revealed that the odds of a match were 2.8 times higher when clinical history was mentioned on the autopsy report than when it was not. Similarly, the odds of a match were 3.4 times higher when death certificates were completed using autopsy findings than when autopsy findings were not used. This analysis excluded cases where it could not be determined if autopsy findings were used to complete death certificates. The findings of this study are useful to investigate the impact of death certificate misclassification errors on radiation risk estimates and, therefore, improve the reliability of epidemiological studies.

Applicability of 'Toolkit for Safety Assessment' tool to interventional radiology using probabilistic risk assessment techniques.

Interventional radiology brings extensive benefits to patients. Nevertheless, certain procedures may result in high doses of radiation, leading to health risks to occupationally exposed individuals (OEIs). Therefore, a more comprehensive risk analysis is essential to ensuring safety and minimising radiation exposures for all OEIs. The Toolkit for Safety Assessment (TOKSA) tool performs risk assessments based on the concepts described in 'General Safety Requirements' Part 3 (Radiation Protection and Safety of Radiation Sources: International Basic Safety Standards) and Part 4 (Safety Assessment for Facilities and Activities). This tool was developed based on the 'Ibero-American Forum of Radiological and Nuclear Regulatory Agencies' risk models and can promote the use of the risk assessment processes by OEIs. The aim of this study was to experimentally analyse the applicability of the TOKSA tool in interventional radiology with the use/support of probabilistic risk assessment techniques. The results were used to reduce the risks associated with a hemodynamics room in a hospital in Belo Horizonte, Brazil.

Impact on dosimetry of occupationally exposed individuals on the patient management for PET/MRI studies: a comparison study with dosimetry on PET/CT

PET/MRI technology has expanded the boundaries of investigation in nuclear medicine, supported by the high sensitivity of solid-state PET detectors. Nonetheless, the coil positioning might lead to an increased exposure period of the worker to the injected patient. This procedure does not occur on PET/CT and, therefore, exposure period is reduced on such scanner. The aim of our study was to evaluate the dosimetry of two occupationally exposed individuals (OEI) working at the Center of Nuclear Medicine of Hospital das Clínicas of the University of Sao Paulo. We used thermoluminescent (TLD) dosimeters in pulse, whole-body and crystalline for PET/MRI and PET/CT procedures during five months of clinical and research routine. We also monitored the time for positioning/removing the patient on both scanners. For this study, OEI1 performed 76 PET/MRI studies and 102 PET/CT studies while OEI2 performed 26 and 56 PET/MRI and PET/CT studies, respectively. We found no evidence of differences for the whole-body dose values between both scanners (p = 0.22). The average time of patient management (positioning/removing the patient) was 14.38, and 3.81 minutes for PET/MRI and PET/CT, respectively. When the normalization by the number of PET/CT studies was applied, we found no statistical difference for effective and equivalent dose values. Our study encourages future investigations on nursing staff, which is a critical population that is exposed to ionizing radiation, mainly on dynamic studies, due to the synchronized injection with the protocol starting.

Determination of Bisphenol A in Paper Products by Synchronous Fluorescence Spectroscopy and Estimation of Daily Exposure

In this study, a simple and fast procedure was developed and validated for the determination of bisphenol A (BPA) in paper products using synchronous fluorescence spectroscopy. The method was used for the determination of BPA in thirteen types of paper products, including thermal receipt papers, lottery tickets, bus tickets, business cards, mailing envelopes, flyers, napkins, printing paper, food contact paper, kitchen rolls, toilet paper, newspapers, and magazines. BPA was found in 98% of thermal receipt papers (n = 341) at concentrations ranging from below the limit of quantification (LOQ) to 27.7 mg g−1 with a geometric mean of 14.6 mg g−1 and a median of 17.7 mg g−1. The detection rate for other paper products was 96%, with BPA concentrations ranging from below the LOQ to 379 µg g−1 and a median of 17.3 µg g−1. The estimated daily intake for the adjusted bodyweight of BPA (calculated at median concentrations) through dermal absorption from handling papers was 14.5 and 1070 ng day−1 for the general population and occupationally-exposed individuals, respectively. The proposed analytical method is simple, fast, and cost-effective for the determination of BPA in paper samples. Moreover, an estimated daily exposure of Brazilians to BPA through dermal absorption from handling different types of papers is shown.

Abstract 5038: Chrysotile asbestos fibers in tissue adjacent to laryngeal squamous cell carcinoma in cases with a history of occupational asbestos exposure

Abstract Asbestos describes a group of naturally occurring fibrous silicate mineral compounds. Its use dates back thousands of years but became widespread in the late 19th century through the late 20th century due to its favorable industrial properties, including its strength, flexibility and thermal properties, with peak use in the United States occurring in the 1970s. Asbestos has been associated with a number of chronic respiratory diseases, including malignancy, and was first linked to mesothelioma and lung cancer in the early to mid part of the 20th century. Despite the known health risks, asbestos is not universally banned and is still in use in many countries (including the United States), with an estimated 125 million occupationally-exposed individuals worldwide. In addition to mesothelioma and lung cancer, asbestos has also been implicated as a risk factor for squamous cancers involving the upper airway, in particular laryngeal and pharyngeal carcinoma, as indicated by recent meta-analyses; however, evidence for the latter associations is based solely on epidemiologic data from observational studies. The primary objective of this work was to attempt to strengthen the evidence via empirical demonstration of persistent asbestos fibers embedded in the tissue surrounding the tumor, thus providing a more definitive biological link between exposure and disease. Six HPV-negative laryngeal and pharyngeal squamous cell carcinoma cases were selected from a large population-based case-control study of head and neck cancer, plus one case with no occupational exposure history as a control. Briefly, detailed occupational history was available for 1,056 head and neck cancer cases enrolled through major teaching hospitals located in Boston, Massachusetts. Occupational data was reviewed to identify those with an occupational history of asbestos exposure. Tissue cores were obtained from adjacent non-neoplastic tissue in tumor blocks from the initial primary tumor resection from a subset of 6 cases with a history of occupational-asbestos exposure and 1 case with no reported occupational exposure (control). A count of asbestos fibers >5um was performed on the cores from each case at Duke University using a scanning electron microscope equipped with an energy dispersive x-ray analyzer (EDXA). Despite the low volume of input tissue, chrysotile asbestos fibers were identified in 3/6 of evaluated cases with a history of occupational asbestos exposure; all 3 cases had tumors originating in the larynx. This is the first study to demonstrate the presence of asbestos fibers in the larynx of cases with laryngeal squamous cell carcinoma, adding an additional line of physical evidence implicating asbestos as an etiologic factor for laryngeal squamous cell carcinoma. Citation Format: Stephanie K. Wronkiewicz, Victor Roggli, Damaris Kuhnell, Rondi A. Butler, Karl T. Kelsey, Scott M. Langevin. Chrysotile asbestos fibers in tissue adjacent to laryngeal squamous cell carcinoma in cases with a history of occupational asbestos exposure [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5038.

Toxicokinetics of benzo[a]pyrene in humans: Extensive metabolism as determined by UPLC-accelerator mass spectrometry following oral micro-dosing

Benzo[a]pyrene (BaP), is a known human carcinogen (International Agency for Research on Cancer (IARC) class 1). The remarkable sensitivity (zepto-attomole 14C in biological samples) of accelerator mass spectrometry (AMS) makes possible, with de minimus risk, pharmacokinetic (PK) analysis following [14C]-BaP micro-dosing of humans. A 46 ng (5 nCi) dose was given thrice to 5 volunteers with minimum 2 weeks between dosing and plasma collected over 72 h. [14C]-BaPeq PK analysis gave plasma Tmax and Cmax values of 1.25 h and 29–82 fg/mL, respectively. PK parameters were assessed by non- compartment and compartment models. Intervals between dosing ranged from 20 to 420 days and had little impact on intra-individual variation. DNA, extracted from peripheral blood mononuclear cells (PBMCs) of 4 volunteers, showed measurable levels (LOD ~ 0.5 adducts/1011 nucleotides) in two individuals 2–3 h post-dose, approximately three orders of magnitude lower than smokers or occupationally-exposed individuals. Little or no DNA binding was detectable at 48–72 h. In volunteers the allelic variants CYP1B1*1/*⁎1, *1/*3 or *3/*3 and GSTM1*0/0 or *1 had no impact on [14C]-BaPeq PK or DNA adduction with this very limited sample. Plasma metabolites over 72 h from two individuals (one CYP1B1*1/*1 and one CYP1B1*3/*3) were analyzed by UPLC-AMS. In both individuals, parent [14C]-BaP was a minor constituent even at the earliest time points and metabolite profiles markedly distinct. AMS, coupled with UPLC, could be used in humans to enhance the accuracy of pharmacokinetics, toxicokinetics and risk assessment of environmental carcinogens.

Geographic distribution of livestock-associated Staphylococcus aureus in the United States

Sampling for livestock-associated Staphylococcus aureus (LA-SA) in the United States is haphazard. The diversity of LA-S. aureus in the U.S. appears to be greater than in other countries. We review the epidemiology of LA-S. aureus in U.S. pigs, occupationally-exposed individuals, and environmental samples to assess the diversity and abundance of U.S. LA-S. aureus.

Estimation of dose distribution in occupationally exposed individuals to FDG-18F

The use of unsealed radiation sources in nuclear medicine can lead to important incorporation of radionuclides, especially for occupationally exposed individuals (OEIs) during production and handling of radiopharmaceuticals. In this study, computer simulation was proposed as an alternative methodology for evaluation of the absorbed dose distribution and for the effective dose value in OEIs. For this purpose, the Exposure Computational Model (ECM) which is named as FSUP (Female Adult Mesh - supine) were used. This ECM is composed of: voxel phantom FASH (Female Adult MeSH) in the supine position, the MC code EGSnrc and an algorythm simulator of general internal source. This algorithm was modified to adapt to specific needs of the positronic emission from FDG-18F. The obtained results are presented as absorbed dose/accumulated activity. To obtain the absorbed dose distribution it was necessary to use accumulative activity data from the in vivo bioassay. The absorbed dose distribution and the value of estimated effective dose in this study did not exceed the limits for occupational exposure. Therefore, the creation of a database with the distribution of accumulated activity is suggested in order to estimate the absorbed dose in radiosensitive organs and the effective dose for OEI in similar environment.

Cadmium and hypertension in exposed workers: A meta-analysis

In the general population, cadmium seems to be responsible for hypertension, atherosclerosis and an increase in acute coronary events. Therefore, the purpose of this meta-analysis was to analyze controlled studies conducted on cadmium and arterial pressure in occupationally-exposed workers. After analyzing all the relevant articles found in the literature, 6 publications were selected. A higher prevalence of hypertension and higher values of systolic and diastolic blood pressure were recorded in the exposed subjects. Cadmium in occupationally-exposed individuals appears to induce an increase in systolic and diastolic blood pressure and an increase in the prevalence of hypertension.

Molecular evidence of radiation hormesis at occupational exposure

The idea of favourable effects of low dose ionising radiation in biological systems has existed for many years and is the basis of radiation hormesis hypothesis. New evidence at subcellular levels might contribute to further clarify this problem. We used molecular epidemiological biomarkers (DNA/protein changes in peripheral blood; immunological changes in lymphocytes) in occupationally-exposed individuals (400 Nuclear Power Plant (NPP) workers). Two levels of investigations were studied: molecular (spontaneous and induced DNA repair by unscheduled DNA synthesis, induced protein synthesis, DNA damage) and cellular (lymphocyte subsets, immunofluorescent-stained mouse monoclonal antibodies). Potentially lethal damage is decreased in persons with mean annual dose ≤5 mSv. The highest repair capacity (after 2 Gy γ-rays) was also evaluated. Significant decreases of CD3+4+, CD4+25+, CD4+62L+ lymphocytes and CD4/CD8 ratio were observed at <200 mSv. Simultaneously, increased natural killer cells, CD57+8+, CD8+28+ and CD8+38 were recorded. Our study showed DNA repair capacity elevation following high dose irradiation and increased cellular resistance at annual doses twice lower than natural radiation background. We postulated that the positive dose correlation with CD4+25+ and CD57+8+ as well as the negative one with CD4+62L+, CD8+28+ and CD8+38+ could reflect adaptive processes and compensatory activated immune system due to the low dose irradiation.

Glutathione S-transferase-catalyzed conjugation of bioactivated aflatoxin B(1) in human lung: differential cellular distribution and lack of significance of the GSTM1 genetic polymorphism.

Epidemiological studies suggest that aflatoxin B(1) (AFB(1)), a mycotoxin produced by certain Aspergillus species, may play a role in human respiratory cancers in occupationally-exposed individuals. AFB(1) requires bioactivation to the corresponding exo-8,9-epoxide for carcinogenicity, and glutathione S-transferase (GST)-catalyzed conjugation of the epoxide with glutathione (GSH) is a critical determinant of susceptibility to AFB(1). Of the purified human GST enzymes studied, the polymorphic hGSTM1-1 has the highest activity towards AFB(1) exo-epoxide. The influence of the GSTM1 polymorphism on AFB(1)-GSH formation, as well as the abilities of cytosols from preparations enriched in different isolated lung cell types to conjugate AFB(1)-epoxides, were examined. In whole-lung cytosols from patients undergoing clinically indicated lobectomy, GSTM1 genotype correlated with GSTM1 phenotype as determined by [(3)H]trans-stilbene oxide conjugation: GSTM1-positive = 295 +/- 31 pmol/mg/h (n = 6); GSTM1-negative = 92.8 +/- 23.3 pmol/mg/h (n = 4) (P < 0.05). In contrast, conjugation of microsome-generated [(3)H]AFB(1)-epoxides with GSH was low and variable between patients, and did not correlate with GSTM1 genotype: GSTM1-positive = 11.9 +/- 8.1, 111 +/- 66 and 510 +/- 248 fmol/mg/h (n = 6); GSTM1-negative = 15.3 +/- 16.7, 167 +/- 225 and 540 +/- 618 fmol/mg/h (n = 4) (for 1, 10 and 100 microM [(3)H]AFB(1), respectively). GSH conjugates of AFB(1) exo-epoxide and the much less mutagenic stereoisomer AFB(1) endo-epoxide were produced in a ratio of approximately 1:1 in cytosols from both whole lung and isolated cells. Total cytosolic AFB(1)-epoxide conjugation was significantly higher in fractions enriched in alveolar type II cells (3.07 +/- 1.61 pmol/mg/h) than in unseparated lung cells (0.143 +/- 0.055 pmol/mg/h) or fractions enriched in alveolar macrophages (0. 904 +/- 0.319 pmol/mg/h; n = 4) (P < 0.05). Furthermore, AFB(1)-GSH formation and percentage of alveolar type II cells in different cell fractions were correlated (r = 0.78, P < 0.05). These results demonstrate that human lung GSTs exhibit very low conjugation activity for both AFB(1)-8,9-epoxide stereoisomers, and that this activity is heterogeneously distributed among cell types, with alveolar type II cells exhibiting relatively high activity. Of the GSTs present in human peripheral lung which contribute to AFB(1) exo- and endo-epoxide detoxification, hGSTM1-1 appears to play at most only a minor role.

Increase in Hair Lead, but not Blood Lead Content of Occupationally-Exposed Workers

This study attempted to investigate whether increased hair lead concentrations due to environmental exposure are accompanied by parallel increases in blood lead concentrations. A sample set consisting of both occupationally-exposed individuals and persons from the general population was investigated. The lead content of scalp and pubic hair from the general population (n=189), traffic police personnel (n=27) and battery workers (n=22) were analysed. The hair samples were taken from the nape of the neck by cutting 23 cm closest to the scalp and cleaned using a washing procedure developed in our laboratory. The effectiveness of the washing procedure was partly determined by examining the scanning electron micrographs of the hair samples. Venous samples of blood were taken from each volunteer's arm.

The Impact of Exercise and Intersubject Variability on Dose Estimates for Dichloromethane Derived from a Physiologically Based Pharmacokinetic Model

The Impact of Exercise and Intersubject Variability on Dose Estimates for Dichloromethane Derived from a Physiologically Based Pharmacokinetic Model. Dankovic, D. A., and Bailer, A. J. (1994). Fundam. Appl. Toxicol. 22, 20-25.Andersen et al. and Reitz et al. have developed physiologically based pharmacokinetic models for the human metabolism of methylene chloride (dichloromethane; DCM) and have advanced the hypothesis that the carcinogenicity of DCM is related to target organ metabolism of DCM by glutathione S-transferase (GST). The models included physiological parameters appropriate for humans at rest and metabolic parameters based on average rates of DCM metabolism. Increasing the model parameters describing cardiac output, alveolar ventilation, and blood flows to tissues from resting values to values consistent with light work conditions, and assuming a 25 ppm exposure for an 8-hr work day, increases the estimated GST-metabolized dose for human liver by a factor of 2.9 compared to the GST-metabolized dose estimate of Reitz et al. These modifications also increase the GST-metabolized dose to the lung by 2.4-fold. If the model is also modified to reflect individual variation in DCM metabolism (in addition to the modifications for light work conditions), the estimated GST-metabolized dose for estimated by Reitz et al. The GST-metabolized dose to the lung ranges from 0 to as much as 3.6-fold greater than the dose estimated by Reitz et al. These results indicate that some occupationally-exposed individuals may receive GST-metabolized doses several-fold greater than the Reitz et al. human dose estimates.