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1.
Occupational exposure to hexavalent chromium. Part I. Hazard assessment of non-cancer health effects.
Hessel, EVS, Staal, YCM, Piersma, AH, den Braver-Sewradj, SP, Ezendam, J
Regulatory toxicology and pharmacology : RTP. 2021;:105048
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Abstract
Hexavalent chromium (Cr(VI)) compounds have been studied extensively and several agencies have described their toxicological profile. In the past, personnel of the Dutch Ministry of Defence may have been exposed to Cr(VI) during maintenance activities. To investigate if this exposure may have caused irreversible adverse health effects, the Dutch National Institute for Public Health and the Environment (RIVM) summarized all available knowledge from previous evaluations. This information was complemented with a scoping review to retrieve new scientific literature. All scientific evidence was evaluated in workshops with external experts to come to an overview of irreversible adverse health effects that could be caused by occupational exposure to Cr(VI) compounds. This review focuses on non-cancer health effects. It was concluded that occupational exposure to Cr(VI) can cause perforation of the nasal septum by chromium ulcers, chronic lung diseases, including asthma, rhinitis, pulmonary fibrosis and COPD, skin ulcers and allergic contact dermatitis in humans. It is currently insufficiently clear if Cr(VI) can cause irreversible diseases due to disturbances of the immune system (other than allergic contact eczema, allergic asthma and rhinitis and chronic lung diseases) or adverse effects on fertility or prenatal development in humans.
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Exposure to additives or multigrain flour is associated with high risk of work-related allergic symptoms among bakers.
Olivieri, M, Murgia, N, Spiteri, G, Biscardo, CA, Marchetti, P, Folletti, I, Verlato, G
Occupational and environmental medicine. 2021;(2):112-116
Abstract
OBJECTIVES Wheat flour exposure in bakers can elicit respiratory and skin symptoms. Scarce data are available on the prevalence of such conditions in bakers. We investigated the prevalence of work-related rhinitis, asthma-like symptoms and dermatitis in bakers according to job task and type of allergens involved. METHODS Of the 229 traditional bakeries in Verona area who were invited to participate in a cross-sectional survey, 211 (92%) accepted; 727 employees in these bakeries answered a modified version of a questionnaire on job tasks; allergen exposure within the bakery; and work-related nasal, asthma-like and skin symptoms during 2010-2014. Determinants of work-related nasal, asthma-like or skin disorders were separately evaluated using different logistic models. RESULTS The prevalence of work-related nasal and asthma-like symptoms was, respectively, 15.1% and 4.2% in bakery shop assistants, increasing to 25.7% and 9.5% in bakers using only wheat flour, and further to 31.8% and 13.6% in bakers using flour and additives, and then to 34.1% and 18.2% in bakers using flour with additives and multigrain (p<0.001). The risk of work-related asthma-like symptoms was more than doubled in bakers using additives without or with multigrain than in shop assistants (OR 2.3, 95% CI 1.0 to 5.5 and OR 3.4, 95% CI 1.1 to 10.8, respectively). Making bread with additives alone or with multigrain significantly increased the risk of work-related nasal symptoms in shop assistants, while the risk of skin symptoms was not significantly affected. CONCLUSIONS Bakers using additives alone or with multigrain are at a high risk of experiencing nasal and asthma-like symptoms.
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Genetic polymorphisms of metabolic enzyme genes associated with leukocyte mitochondrial DNA copy number in PAHs exposure workers.
Li, X, Duan, X, Zhang, H, Ding, M, Wang, Y, Yang, Y, Yao, W, Zhou, X, Wang, W
Cancer reports (Hoboken, N.J.). 2021;(4):e1361
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Abstract
BACKGROUND Polycyclic aromatic hydrocarbons (PAHs) exposure had been reported to be a risk factor of mtDNAcn in our early study. However, the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs-Exposure workers has not been fully evaluated. AIM: The aim of the study was to explore the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs-Exposure. METHODS AND RESULTS We investigated the effects of metabolic enzymes' genetic polymorphisms on mtDNAcn among 544 coke oven workers and 238 office staffs. The mtDNAcn of peripheral blood leukocytes was measured using the Real-time quantitative polymerase chain reaction (PCR) method. PCR and restriction fragment length was used to detect five polymorphisms in GSTT1, GSTM1, GSTP1 rs1695, CYP2E1 rs6413432, and CYP2E1 rs3813867. The mtDNAcn in peripheral blood leukocytes was significantly lower in the exposure group than that in the control group (p < .001). The 1-OHPYR had an increasing trend with the genotypes AA→AG → GG of GSTP1 rs1695 in the control group. Generalized linear model indicated that the influencing factors of mtDNAcn were PAHs-exposure [β (95% CI) = -0.420 (-0.469, -0.372), p < .001], male [β (95% CI) = -0.058 (-0.103, -0.012), p = .013], and AA genotype for GSTP1 rs1695 [β (95% CI) = -0.051 (-0.095, -0.008), p = .020]. CONCLUSION The individuals carrying the AA genotype of GSTP1 rs1695 may have a lower mtDNAcn due to their weaker detoxification of PAHs.
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Microbiological and Toxicological Hazards in Sewage Treatment Plant Bioaerosol and Dust.
Szulc, J, Okrasa, M, Majchrzycka, K, Sulyok, M, Nowak, A, Ruman, T, Nizioł, J, Szponar, B, Gutarowska, B
Toxins. 2021;(10)
Abstract
Despite the awareness that work in the sewage treatment plant is associated with biological hazards, they have not been fully recognised so far. The research aims to comprehensively evaluate microbiological and toxicological hazards in the air and settled dust in workstations in a sewage treatment plant. The number of microorganisms in the air and settled dust was determined using the culture method and the diversity was evaluated using high-throughput sequencing. Endotoxin concentration was assessed with GC-MS (gas chromatography-mass spectrometry) while secondary metabolites with LC-MS/MS (liquid chromatography coupled to tandem mass spectrometry). Moreover, cytotoxicity of settled dust against a human lung epithelial lung cell line was determined with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and UHPLC-Q-ToF-UHRMS (ultra-high-performance liquid chromatography-quadrupole time-of-flight ultrahigh-resolution mass spectrometry) analysis was performed to determine the source of cytotoxicity. The total dust concentration in the sewage treatment plant was low and ranged from 0.030 mg m-3 to 0.044 mg m-3. The highest microbiological contamination was observed in sludge thickening building and screenings storage. Three secondary metabolites were detected in the air and sixteen in the settled dust. They were dominated by compounds typical of lichen and plants and Aspergillus, Penicillium and Fusarium genera mould. The settled dust from the sludge thickening building revealed high cytotoxicity to human lung epithelial cells A-549 (IC50 = 6.98 after 72 h). This effect can be attributed to a biocidal compound-didecyldimethylammonium chloride (DDAC-C10) and seven toxic compounds: 4-hydroxynonenal, carbofuran, cerulenin, diethylphosphate, fenpropimorph, naphthalene and onchidal. The presence of DDAC-C10 and other biocidal substances in the sewage treatment plant environment may bring negative results for biological sewage treatment and the natural environment in the future and contribute to microorganisms' increasing antibiotics resistance. Therefore, the concentration of antibiotics, pesticides and disinfectants in sewage treatment plant workstations should be monitored.
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The impact of the mechanical whole-body vibration experienced during military land transit on the physical attributes underpinning dismounted combatant physical performance: A randomised controlled trial.
Debenedictis, TA, Billing, D, Milanese, S, Furnell, A, Tomkinson, G, Thewlis, D
Journal of science and medicine in sport. 2021;(4):380-385
Abstract
OBJECTIVES The aim of this randomised controlled trial was to explore the impact of the mechanical WBV experienced during simulated military land transit on the physical attributes that underpin tasks performed by dismounted combatants. DESIGN This study used a parallel group randomised control trial design. METHODS Sixty participants were randomly assigned to one of four, 2-h laboratory-based simulations (restricted posture, sealed road, cross country or a control condition). A smaller sample of 16 Australian Defence Force infantry personnel served as a validation group and were exposed to the same conditions. Neither the restricted posture nor the control conditions were exposed to any WBV, but the former were secured in place using the built-in seat harness. Prior to, and following the assigned condition, participants performed a series of battlefield relevant physical performance tests including; drop jump, 20-m sprint, reactive agility, arm-hand steadiness, isometric mid-thigh pull, and sit-and-reach. RESULTS Medium decreases in the drop jump were observed for both the sealed road (effect size [ES]=0.53) and cross-country (ES=0.97) simulation conditions indicating a decrease in performance of the jump phase. A large decrease in 20-m sprint performance was observed in both the sealed road (ES=1.37) and cross-country (ES=0.88) exposure conditions. Additionally, a large decrease in 20-m sprint performance was observed for the restricted posture (ES=1.02) exposure condition. CONCLUSIONS These findings indicate that exposure to WBV experienced during motorised land transit has a negative influence on aspects of lower body explosive strength.
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Occupational heat exposure and the risk of chronic kidney disease of nontraditional origin in the United States.
Chapman, CL, Hess, HW, Lucas, RAI, Glaser, J, Saran, R, Bragg-Gresham, J, Wegman, DH, Hansson, E, Minson, CT, Schlader, ZJ
American journal of physiology. Regulatory, integrative and comparative physiology. 2021;(2):R141-R151
Abstract
Occupational heat exposure is linked to the development of kidney injury and disease in individuals who frequently perform physically demanding work in the heat. For instance, in Central America, an epidemic of chronic kidney disease of nontraditional origin (CKDnt) is occurring among manual laborers, whereas potentially related epidemics have emerged in India and Sri Lanka. There is growing concern that workers in the United States suffer with CKDnt, but reports are limited. One of the leading hypotheses is that repetitive kidney injury caused by physical work in the heat can progress to CKDnt. Whether heat stress is the primary causal agent or accelerates existing underlying pathology remains contested. However, the current evidence supports that heat stress induces tubular kidney injury, which is worsened by higher core temperatures, dehydration, longer work durations, muscle damaging exercise, and consumption of beverages containing high levels of fructose. The purpose of this narrative review is to identify occupations that may place US workers at greater risk of kidney injury and CKDnt. Specifically, we reviewed the scientific literature to characterize the demographics, environmental conditions, physiological strain (i.e., core temperature increase, dehydration, heart rate), and work durations in sectors typically experiencing occupational heat exposure, including farming, wildland firefighting, landscaping, and utilities. Overall, the surprisingly limited available evidence characterizing occupational heat exposure in US workers supports the need for future investigations to understand this risk of CKDnt.
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A clandestine culprit with critical consequences: Benzene and acute myeloid leukemia.
Shallis, RM, Weiss, JJ, Deziel, NC, Gore, SD
Blood reviews. 2021;:100736
Abstract
While most clinicians recognize adult therapy-related leukemias following cytotoxic chemotherapy and radiation, environmental regulatory agencies evaluate exposure to "safe levels" of leukemogenic compounds. Benzene represents the most notorious leukemogenic chemical. Used in the production of ubiquitous items such as plastics, lubricants, rubbers, dyes, and pesticides, benzene may be responsible for the higher risk of acute myeloid leukemia (AML) among automobile, janitorial, construction, and agricultural workers. It is possible that ambient benzene may contribute to many cases of "de novo" AML not arising out of germline predispositions. In this appraisal of the available literature, we evaluate and discuss the association between chronic, low-dose and ambient exposure to environmental benzene and the development of adult AML.
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Occupational exposure to pesticides in female tea garden workers and adverse birth outcomes.
Kumar, SN, Vaibhav, K, Bastia, B, Singh, V, Ahluwalia, M, Agrawal, U, Borgohain, D, Raisuddin, S, Jain, AK
Journal of biochemical and molecular toxicology. 2021;(3):e22677
Abstract
Pesticides are globally used to eliminate pests from crops and plants. The increased use of pesticides has posed a serious threat to human health. This study evaluates the effects of pesticide exposure on pregnancy outcomes in tea garden workers (TGW). The acetylcholinesterase (AChE) activity was measured in the maternal blood, placenta, and cord blood of TGW and housewives (HWs). The placental structure and expression of hypoxia-inducible factor (HIF)-1α were also analyzed in TGW and HW groups delivering low birth weight (LBW) and normal birth weight (NBW) babies. A significantly decreased AChE activity was observed in maternal blood and cord blood in TGW as compared with HW in the LBW group. However, it did not change significantly in the NBW group (p < .05). The adjusted regression analysis of birth outcomes (birth weight, head circumference, infant's length, and ponderal index) revealed a significant and positive association with the levels of AChE activity in maternal blood, placenta, and cord blood in TGW (p < .05). The histological analysis showed significantly higher placental syncytial knots, chorangiosis, fibrinoid deposition, necrosis, and stromal fibrosis in the LBW group of TGW. Microinfarction, increased fibrinoid deposition, and atypical villi characteristics, such as mushroom-like structures, were observed during scanning electron microscopy along with increased HIF-1α expression in placental tissues of TGW exposed to pesticides. Results suggest that occupational pesticide exposure during pregnancy may decrease AChE activity and cause in utero pathological changes accompanied by an increased HIF-1α expression, which also contributes to placental insufficiency and fetal growth restriction.
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Methoxyflurane toxicity: historical determination and lessons for modern patient and occupational exposure.
Allison, SJ, Docherty, PD, Pons, D, Chase, JG
The New Zealand medical journal. 2021;(1534):76-90
Abstract
AIM: Historically methoxyflurane was used for anaesthesia. Evidence of nephrotoxicity led to abandonment of this application. Subsequently, methoxyflurane, in lower doses, has re-emerged as an analgesic agent, typically used via the Penthrox inhaler in the ambulance setting. We review the literature to consider patient and occupational risks for methoxyflurane. METHOD Articles were located via PubMed, ScienceDirect, Google Scholar, Anesthesiology journal and the Cochrane Library. RESULTS Early studies investigated pharmacokinetics and considered the resulting effects to pose minimal risk. Pre-clinical rodent studies utilised a species not vulnerable to the nephrotoxic fluoride metabolite of methoxyflurane, so nephrotoxicity was not identified until almost a decade after its introduction, and was initially met with scepticism. Further evidence of nephrotoxicity led to abandonment of methoxyflurane use for anaesthesia. Subsequent research suggested there are additional risks potentially relevant to recurrent patient or occupational exposure. Specifically, greater than expected fluoride production after repeated low-dose exposure, increased fluoride production due to medication-caused hepatic enzyme induction, fluoride deposition in bone potentially acting as a slow-release fluoride compartment, which suggests a risk of skeletal fluorosis, and hepatotoxicity. Gestational risk is unclear. CONCLUSIONS Methoxyflurane poses a potentially substantial health risk in high (anaesthetic) doses, and there are a number of pathways whereby repeated exposure to methoxyflurane in lower doses may pose a risk. Single analgesic doses in modern use generally appear safe for patients. However, the safety of recurrent patient or occupational healthcare-worker exposure has not been confirmed, and merits further investigation.
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Efficacy of hydroxychloroquine for post-exposure prophylaxis to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among adults exposed to coronavirus disease (COVID-19): a structured summary of a study protocol for a randomised controlled trial.
Barnabas, RV, Brown, E, Bershteyn, A, Miller, RS, Wener, M, Celum, C, Wald, A, Chu, H, Wesche, D, Baeten, JM, et al
Trials. 2020;(1):475
Abstract
OBJECTIVES Primary Objective • To test the efficacy of Hydroxychloroquine (HCQ) (400 mg orally daily for 3 days then 200 mg orally daily for an additional 11 days, to complete 14 days) to prevent incident SARS-CoV-2 infection, compared to ascorbic acid among contacts of persons with SARS-CoV-2 infection Secondary objectives • To determine the safety and tolerability of HCQ as SARS-CoV-2 Post-exposure Prophylaxis (PEP) in adults • To test the efficacy of HCQ (400 mg orally daily for 3 days then 200 mg orally daily for an additional 11 days, to complete 14 days) to prevent incident SARS-CoV-2 infection 2 weeks after completing therapy, compared to ascorbic acid among contacts of persons with SARS-CoV-2 infection • To test the efficacy of HCQ to shorten the duration of SARS-CoV-2 shedding among those with SARS-CoV-2 infection in the HCQ PEP group • To test the efficacy of HCQ to prevent incident COVID-19 TRIAL DESIGN This is a randomized, multi-center, placebo-equivalent (ascorbic acid) controlled, blinded study of HCQ PEP for the prevention of SARS-CoV-2 infection in adults exposed to the virus. PARTICIPANTS This study will enroll up to 2000 asymptomatic adults 18 to 80 years of age (inclusive) at baseline who are close contacts of persons with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 or clinically suspected COVID-19 and a pending SARS-CoV-2 PCR test. This multisite trial will be conducted at seven sites in Seattle (UW), Los Angeles (UCLA), New Orleans (Tulane), Baltimore (UMB), New York City (NYU), Syracuse (SUNY-Upstate), and Boston (BMC). Inclusion criteria Participants are eligible to be included in the study only if all of the following criteria apply: 1.Men or women 18 to 80 years of age inclusive, at the time of signing the informed consent2.Willing and able to provide informed consent3.Had a close contact of a person (index) with known PCR-confirmed SARS-CoV-2 infection or index who is currently being assessed for COVID-19 Close contact is defined as: a.Household contact (i.e., residing with the index case in the 14 days prior to index diagnosis or prolonged exposure within a residence/vehicle/enclosed space without maintaining social distance)b.Medical staff, first responders, or other care persons who cared for the index case without personal protection (mask and gloves)4.Less than 4 days since last exposure (close contact with a person with SARS-CoV-2 infection) to the index case5.Access to device and internet for Telehealth visits6.Not planning to take HCQ in addition to the study medication Exclusion criteria Participants are excluded from the study if any of the following criteria apply: 1.Known hypersensitivity to HCQ or other 4-aminoquinoline compounds2.Currently hospitalized3.Symptomatic with subjective fever, cough, or shortness of breath4.Current medications exclude concomitant use of HCQ5.Concomitant use of other anti-malarial treatment or chemoprophylaxis, including chloroquine, mefloquine, artemether, or lumefantrine.6.History of retinopathy of any etiology7.Psoriasis8.Porphyria9.Known bone marrow disorders with significant neutropenia (polymorphonuclear leukocytes <1500) or thrombocytopenia (<100 K)10.Concomitant use of digoxin, cyclosporin, cimetidine, amiodarone, or tamoxifen11.Known moderate or severe liver disease12.Known long QT syndrome13.Severe renal impairment14.Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of the study drugs or planned use during the study period INTERVENTION AND COMPARATOR Households will be randomized 1:1 (at the level of household), with close contact participants receiving one of the following therapies: •HCQ 400 mg orally daily for 3 days then 200 mg orally daily for an additional 11 days •Placebo-like control (ascorbic acid) 500 mg orally daily for 3 days then 250 mg orally daily for 11 days MAIN OUTCOMES The primary outcome of the study is the incidence of SARS-CoV-2 infection through day 14 among participants who are SARS-CoV-2 negative at baseline by randomization group. RANDOMISATION Participants will be randomized in a 1:1 ratio to HCQ or ascorbic acid at the level of the household (all eligible participants in 1 household will receive the same intervention). The randomization code and resulting allocation list will be generated and maintained by the Study Statistician. The list will be blocked and stratified by site and contact type (household versus healthcare worker). BLINDING (MASKING): This is a blinded study. HCQ and ascorbic acid will appear similar, and taste will be partially masked as HCQ can be bitter and ascorbic acid will be sour. The participants will be blinded to their randomization group once assigned. Study team members, apart from the Study Pharmacist and the unblinded statistical staff, will be blinded. Laboratory staff are blinded to the group allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size for the study is N=2 000 participants randomized 1:1 to either HCZ (n=1 000) and ascorbic acid (n=1 000). TRIAL STATUS Protocol version: 1.2 05 April 2020 Recruitment is ongoing, started March 31 and anticipated end date is September 30, 2020. TRIAL REGISTRATION ClinicalTrials.gov, Protocol Registry Number: NCT04328961 Date of registration: April 1, 2020, retrospectively registered FULL PROTOCOL The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.