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1.
Environ Sci Technol ; 58(15): 6499-6508, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38572580

RESUMO

A social housing estate in Denmark was designated for demolition due to exceedance of guidance values for polychlorinated biphenyls (PCBs) in indoor air. Here, we deployed precleaned silicone wristbands (n = 46) among demolition workers of these contaminated buildings during single workdays while conducting various work tasks. We established a method to analyze all 209 PCBs in wristbands to identify prominent congeners of exposure and evaluate differences between tasks. Wristbands were extracted using microwave-assisted extraction and then concentrated for gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis. Twenty-nine chromatographic peaks representing 37 congeners were detected in every wristband, and tetra-CBs were the dominant homologue group. PCB-66, -44, and -70 were the most abundant congeners measured in worker wristbands, none of which are included within the typical seven indicator or WHO 12 PCBs. Workers who cut PCB-containing sealants had wristbands with the highest PCB concentrations (geometric mean ∑209PCBs = 1963 ng/g wristband), which were followed by those handling concrete elements on the building roof. Additionally, wristbands captured a broader range of PCBs than has been previously measured in air and serum samples. Taken together, our results highlight the importance of total congener analysis in assessing current PCB exposure in demolition work and the utility of wristbands for assessing these exposures.


Assuntos
Bifenilos Policlorados , Humanos , Bifenilos Policlorados/análise , Monitoramento Ambiental , Espectrometria de Massas em Tandem , Silicones
2.
Ann Intern Med ; 176(11): 1476-1485, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37748181

RESUMO

BACKGROUND: Inadequate dose titration and poor adherence to basal insulin can lead to suboptimal glycemic control in persons with type 2 diabetes (T2D). Once-weekly insulin icodec (icodec) is a basal insulin analogue that is in development and is aimed at reducing treatment burden. OBJECTIVE: To compare the effectiveness and safety of icodec titrated with a dosing guide app (icodec with app) versus once-daily basal insulin analogues (OD analogues) dosed per standard practice. DESIGN: 52-week, randomized, open-label, parallel-group, phase 3a trial with real-world elements. (ClinicalTrials.gov: NCT04760626). SETTING: 176 sites in 7 countries. PARTICIPANTS: 1085 insulin-naive adults with T2D. INTERVENTION: Icodec with app or OD analogue (insulin degludec, insulin glargine U100, or insulin glargine U300). MEASUREMENTS: The primary outcome was change in glycated hemoglobin (HbA1c) level from baseline to week 52. Secondary outcomes included patient-reported outcomes (Treatment Related Impact Measure for Diabetes [TRIM-D] compliance domain score and change in Diabetes Treatment Satisfaction Questionnaire [DTSQ] total treatment satisfaction score). RESULTS: The estimated mean change in HbA1c level from baseline to week 52 was greater with icodec with app than with OD analogues, with noninferiority (P < 0.001) and superiority (P = 0.009) confirmed in prespecified hierarchical testing (estimated treatment difference [ETD], -0.38 percentage points [95% CI, -0.66 to -0.09 percentage points]). At week 52, patient-reported outcomes were more favorable with icodec with app than with OD analogues (ETDs, 3.04 [CI, 1.28 to 4.81] for TRIM-D and 0.78 [CI, 0.10 to 1.47] for DTSQ). Rates of clinically significant or severe hypoglycemia were low and similar with both treatments. LIMITATION: Inability to differentiate the effects of icodec and the dosing guide app. CONCLUSION: Compared with OD analogues, icodec with app showed superior HbA1c reduction and improved treatment satisfaction and compliance with similarly low hypoglycemia rates. PRIMARY FUNDING SOURCE: Novo Nordisk A/S.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Aplicativos Móveis , Adulto , Humanos , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Insulina Glargina/uso terapêutico
3.
Environ Res ; 222: 115354, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36709868

RESUMO

BACKGROUND: Indoor air in buildings constructed with materials containing polychlorinated biphenyls (PCBs) may be contaminated with especially lower-chlorinated PCBs. So far, the cardiovascular consequences of living with such contamination are unknown. OBJECTIVES: To determine the risk of cardiovascular disease (CVD) following residential exposure to predominantly lower-chlorinated PCBs in indoor air. METHODS: The Health Effects of PCBs in Indoor Air (HESPAIR) cohort is register-based with 51 921 residents of two residential areas near Copenhagen: Farum Midtpunkt and Brøndby Strand Parkerne. Here, indoor air was contaminated with PCB in one third of the apartments due to construction with materials containing PCB. Individual PCB exposure was estimated based on register-based information on relocation dates and indoor air PCB measurements in subsets of the apartments. Information on CVD was retrieved from the Danish National Patient Register for the follow-up period of 1977-2018. We estimated adjusted hazard ratios using Cox regression with time-varying exposure. RESULTS: Cumulative residential exposure to airborne PCB was not associated with a higher overall risk for CVD (HR for highly exposed (≥3300 ng/m3 PCB × year): 1.02, 95% CI 0.94-1.10). This was also the case for most of the specific cardiovascular diseases, apart from acute myocardial infarction where a higher risk was observed for residents exposed to ≥3300 ng/m3 PCB × year compared to the reference group (HR 1.17, 95% CI 1.00-1.35). However, no exposure-response relationship was apparent and additional adjustment for education attenuated the risk estimate. DISCUSSION: In this, to our knowledge, first study ever to examine the risk of CVD following residential exposure to PCBs in indoor air, we observed limited support for cardiovascular effects of living in PCB-contaminated indoor air. Considering the prevalence of exposure to airborne PCBs and lack of literature on their potential health effects, these findings need to be corroborated in other studies.


Assuntos
Poluição do Ar em Ambientes Fechados , Doenças Cardiovasculares , Bifenilos Policlorados , Humanos , Bifenilos Policlorados/análise , Monitoramento Ambiental , Estudos de Coortes , Poluição do Ar em Ambientes Fechados/análise
4.
Environ Res ; 237(Pt 2): 117000, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37634693

RESUMO

BACKGROUND: Previous research indicates an association between higher-chlorinated polychlorinated biphenyls (PCBs) and type 2 diabetes (T2D). However, less is known about the extent to which PCB exposure in indoor air, composed primarily of lower-chlorinated PCBs, affects T2D risk. We assessed the association between indoor air exposure to PCBs in residential buildings and T2D incidence. METHODS: The register-based 'Health Effects of PCBs in Indoor Air' (HESPAIR) cohort comprises 51,921 Danish residents of two residential areas with apartments built with and without PCB-containing materials (reference apartments). We assessed exposure status by combining register-based information on relocation history with extrapolated values of exposure based on PCB-measurements in indoor air from subsets of the apartments. T2D cases were identified in the Danish registers during 1977-2018. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression analyses with time-varying exposure. RESULTS: We identified 2737 incident T2D cases during the follow-up. Exposure to ≥3300 ng/m3 PCB × year (3rd tertile of PCByear) was associated with higher risk of T2D (HR 1.15, 95% CI 1.02-1.30) compared with exposure to <300 ng/m3 PCB × year (reference). However, among individuals with lower cumulated PCByear, the risk was similar to residents with exposure <300 ng/m3 PCB × year (300-899 ng/m3 PCB × year: HR 0.98, 95% CI 0.87-1.11; 900-3299 ng/m3 PCB × year: HR 0.96, 95% CI 0.83-1.10). DISCUSSION: We observed a marginally higher risk of T2D, but there was no evidence of an exposure-response relationship. The results should be interpreted with caution until confirmed in other independent studies of PCB exposure in indoor air.

5.
J Appl Toxicol ; 42(1): 130-153, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34247391

RESUMO

Exposure to spray cleaning products constitutes a potential risk for asthma induction. We set out to review whether substances in such products are potential inducers of asthma. We identified 101 spray cleaning products for professional use. Twenty-eight of their chemical substances were selected. We based the selection on (a) positive prediction for respiratory sensitisation in humans based on quantitative structure activity relationship (QSAR) in the Danish (Q)SAR Database, (b) positive QSAR prediction for severe skin irritation in rabbits and (c) knowledge on the substances' physico-chemical characteristics and toxicity. Combining the findings in the literature and QSAR predictions, we could group substances into four classes: (1) some indication in humans for asthma induction: chloramine, benzalkonium chloride; (2) some indication in animals for asthma induction: ethylenediaminetetraacetic acid (EDTA), citric acid; (3) equivocal data: hypochlorite; (4) few or lacking data: nitriloacetic acid, monoethanolamine, 2-(2-aminoethoxy)ethanol, 2-diethylaminoethanol, alkyldimethylamin oxide, 1-aminopropan-2-ol, methylisothiazolinone, benzisothiazolinone and chlormethylisothiazolinone; three specific sulphonates and sulfamic acid, salicylic acid and its analogue sodium benzoate, propane-1,2-diol, glycerol, propylidynetrimethanol, lactic acid, disodium malate, morpholine, bronopol and benzyl alcohol. In conclusion, we identified an asthma induction potential for some of the substances. In addition, we identified major knowledge gaps for most substances. Thus, more data are needed to feed into a strategy of safe-by-design, where substances with potential for induction of asthma are avoided in future (spray) cleaning products. Moreover, we suggest that QSAR predictions can serve to prioritise substances that need further testing in various areas of toxicology.


Assuntos
Cosméticos/toxicidade , Detergentes/toxicidade , Exposição Ocupacional/efeitos adversos , Sistema Respiratório/efeitos dos fármacos , Sabões/toxicidade , Animais , Asma , Humanos , Relação Quantitativa Estrutura-Atividade , Sistema Respiratório/fisiopatologia
6.
Diabetes Obes Metab ; 23(11): 2590-2594, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34338402

RESUMO

Subcutaneous semaglutide, at a 2.4 mg once-weekly maintenance dose, is approved in the United States for weight management in individuals with a body mass index (BMI) of 30 kg/m2 or higher, or with a BMI of 27 kg/m2 or higher and at least one obesity-related co-morbidity. To investigate the usability of the semaglutide pen-injector in individuals who met these criteria, we report post hoc analysis of the summative (human factors validation) usability testing and safety analysis involving patients with type 2 diabetes (an obesity-related co-morbidity) with the same pen-injector, limited to the 26 out of 30 patients with a BMI of 27 kg/m2 or higher (11 pen-injector-naïve, 15 pen-injector-experienced) and 15 non-pharmacist healthcare professionals (HCPs). Participants performed two simulated injections into an injection pad. No potentially serious use errors occurred. Mean subjective ease-of-use rating on a seven-point scale, where 1 = difficult and 7 = easy, was 6.9 for the second injection in all three groups. These results suggest that the semaglutide pen-injector is easy to use and not associated with serious use errors when used by pen-injector-naïve or pen-injector-experienced patients meeting the requirement for weight management with semaglutide treatment, and by non-pharmacist HCPs.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Injeções Subcutâneas , Design Centrado no Usuário , Interface Usuário-Computador
7.
Regul Toxicol Pharmacol ; 121: 104873, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33485927

RESUMO

Boron, often in the form of boric acid, is widely used as a flame retardant in insulation products, and although humans ingest boron through food, high exposure may lead to unwanted health effects. We assessed the toxicity of boric acid, borax and other forms of boron, after inhalation, dermal and oral exposure. After oral exposure, boron is absorbed over the gastrointestinal tract. Intact skin seems to pose a more effective barrier to boron than compromised skin. Boron excretion seems to mainly occur via the urine, although after skin exposure boron has been demonstrated in bile and gastrointestinal contents. Inhalation toxicity data are sparse, but one animal study showed reduced foetal weight after inhalation of cellulose that had a boric acid content of 20%. Skin exposure to boric acid has proven fatal in some cases, and the range of toxicity effects include abdominal as well as local effects on the skin. Fatalities from boric acid also have occurred after oral ingestion, and the endpoints in animals are weight loss and reproductive toxicity. Concerning genotoxicity studies, the overall picture indicates that boron-containing compounds are not genotoxic. There was no evidence of the carcinogenicity of boric acid in a 2-year study in mice.


Assuntos
Compostos de Boro/toxicidade , Administração Cutânea , Administração por Inalação , Administração Oral , Animais , Humanos , Exposição por Inalação , Testes de Mutagenicidade , Absorção Cutânea
8.
Acta Oncol ; 59(5): 588-595, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32048526

RESUMO

Background: Surveillance of childhood cancer incidence is informative for etiologic research and health policy. However, high-quality data covering several decades of virtually complete cancer diagnosis in children is sparse.Methods: Incident cases of childhood cancer (0-19 years at diagnosis), classified according to Birch and Marsden's International Classification of Childhood Cancer, first edition (ICCC-1), were identified in the Danish Cancer Registry and used to calculate age-standardized incidence rates (ASRs) and estimated annual percentage change (EAPC) separately for 1943-1977 (early period) and 1977-2014 (recent period).Results: During 1943-2014, 15,184 childhood cancer cases were reported. The ASR for any cancer was 13.0 per 100 000 person-years in the early period (EAPC 0.55%; 95% CI 0.30-0.80) and 17.7 per 100 000 person-years in the recent period (EAPC 1.16%; 95% CI 0.96-1.36). In both periods, the increasing trend was seen in both boys (EAPC 0.69%; 95% CI 0.43-0.96/EAPC 0.96%; 95% CI 0.75-1.17) and girls (EAPC 0.37%; 95% CI -0.01-0.75/EAPC 1.41%; 95% CI 1.11-1.72) and in children aged 0-14 years (EAPC 0.53%; 95% CI 0.26-0.80/EAPC 0.86%; 95% CI 0.64-1.08) and 15-19 years (EAPC 0.60%; 95% CI 0.19-1.02/EAPC 1.97%; 95% CI 1.67-2.28). Increasing trends were observed for all main diagnostic groups.Conclusions: The incidence of childhood cancer in Denmark has increased since the 1940s, especially since 1977 and in older children. In recent years the increase has been most pronounced among girls.


Assuntos
Neoplasias/epidemiologia , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Sistema de Registros/estatística & dados numéricos , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
9.
J Occup Environ Hyg ; 17(1): 15-29, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31815607

RESUMO

The purpose of the study was to compare measured air and surface concentrations after application of biocidal spray products with concentrations simulated with the ConsExpo Web spray simulation tool. Three different biocidal spray products were applied in a 20 m3 climate test chamber with well-controlled environmental conditions (22 ± 1 °C, 50 ± 2% relative humidity, and air exchange rate of 0.5 h-1). The products included an insect spray in a pressurized spray can, another insect spray product, and a disinfectant, the latter two applied separately with the same pumped spray device. The measurements included released particles, airborne organic compounds in both gas and particle phase, and surface concentrations of organic compounds on the wall and floor in front of the spraying position and on the most remote wall. Spraying time was a few seconds and the air concentrations were measured by sampling on adsorbent tubes at 9-13 times points during 4 hr after spraying. The full chamber experiment was repeated 2-3 times for each product. Due to sedimentation the concentrations of the particles in air decayed faster than explained by the air exchange rate. In spite of that, the non-volatile benzalkonium chlorides in the disinfectant could be measured in the air more than 30 min after spraying. ConsExpo Web simulated concentrations that were about half of the measured concentrations of the active substances when as many as possible of the default simulation parameters were replaced by the experimental values. ConsExpo Web was unable to simulate the observed faster decay of the airborne concentrations of the active substances, which might be due to underestimation of the gravitational particle deposition rates. There was a relatively good agreement between measured surface concentrations on the floor and calculated values based on the dislodgeable amount given in the selected ConsExpo Web scenarios. It is suggested to always supplement simulation tool results with practical measurements when assessing the exposure to a spray product.


Assuntos
Desinfetantes/análise , Exposição Ocupacional/estatística & dados numéricos , Aerossóis/análise , Humanos , Exposição por Inalação/estatística & dados numéricos , Inseticidas/análise , Modelos Estatísticos
10.
Gynecol Oncol ; 152(1): 208-217, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30415992

RESUMO

The tumor suppressor proteins p16 and p53 have been suggested to have prognostic value in some human papillomavirus (HPV)-associated cancers, however, this has been less well established for vulvar cancer. The aim of this review and meta-analysis was to examine the prognostic value of p16 and p53 expression status on survival after vulvar squamous cell carcinoma (VSCC). We conducted a thorough systematic literature search of multiple databases to identify studies examining survival after histolocally verified VSCC that were tested for p16 and/or p53. A total of 18 eligible studies were included. Using a fixed-effects model we calculated study-specific and pooled hazard ratios (HRs) of 5-year overall survival (OS). In the analyses of OS, we included 475 VSCC cases tested for p16 expression of which 38% were p16 positive. The pooled HRp16 was 0.40 (95% CI: 0.29-0.55). In addition, the majority of results from studies with adjusted analyses on the prognostic value of p16 indicated that p16 expression status could be an independent prognostic marker for OS in women diagnosed with VSCC, and the same pattern was seen for disease specific survival (DSS). We also included 310 VSCC cases tested for p53 expression of which 54% were p53 positive. The pooled HRp53 was 1.81 (95% CI: 1.22-2.68) indicating that p53 positive VSCC have a significantly lower 5-year OS compared to p53 negative. The results in relation to p53 reported from adjusted analyses OS and on DSS and disease free survival were more equivocal. This meta-analysis and review suggests that p53 and especially p16 expression status are of prognostic importance in women diagnosed with VSCC. This may be clinically important in the future design of targeted therapy and when planning the optimal follow-up strategy. Future studies should include the combined use of biomarkers such as p16, p53 and HPV status.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Inibidor p16 de Quinase Dependente de Ciclina/análise , Proteína Supressora de Tumor p53/análise , Neoplasias Vulvares/mortalidade , Carcinoma de Células Escamosas/química , Intervalo Livre de Doença , Feminino , Humanos , Prognóstico , Neoplasias Vulvares/química
11.
Part Fibre Toxicol ; 16(1): 21, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31182122

RESUMO

BACKGROUND: Short-term controlled exposure to diesel exhaust (DE) in chamber studies have shown mixed results on lung and systemic effects. There is a paucity of studies on well-characterized real-life DE exposure in humans. In the present study, 29 healthy volunteers were exposed to DE while sitting as passengers in diesel-powered trains. Exposure in electric trains was used as control scenario. Each train scenario consisted of three consecutive days (6 h/day) ending with biomarker samplings. RESULTS: Combustion-derived air pollutants were considerably higher in the passenger carriages of diesel trains compared with electric trains. The concentrations of black carbon and ultrafine particles were 8.5 µg/m3 and 1.2-1.8 × 105 particles/cm3 higher, respectively, in diesel as compared to electric trains. Net increases of NOx and NO2 concentrations were 317 µg/m3 and 36 µg/m3. Exposure to DE was associated with reduced lung function and increased levels of DNA strand breaks in peripheral blood mononuclear cells (PBMCs), whereas there were unaltered levels of oxidatively damaged DNA, soluble cell adhesion molecules, acute phase proteins in blood and urinary excretion of metabolites of polycyclic aromatic hydrocarbons. Also the microvascular function was unaltered. An increase in the low frequency of heart rate variability measures was observed, whereas time-domain measures were unaltered. CONCLUSION: Exposure to DE inside diesel-powered trains for 3 days was associated with reduced lung function and systemic effects in terms of altered heart rate variability and increased levels of DNA strand breaks in PBMCs compared with electric trains. TRIAL REGISTRATION: ClinicalTrials.Gov ( NCT03104387 ). Registered on March 23rd 2017.


Assuntos
Poluentes Atmosféricos/análise , Sistema Cardiovascular/efeitos dos fármacos , Dano ao DNA , Pulmão/efeitos dos fármacos , Material Particulado/análise , Emissões de Veículos/análise , Poluentes Atmosféricos/toxicidade , Biomarcadores/sangue , Biomarcadores/urina , Sistema Cardiovascular/fisiopatologia , Monitoramento Ambiental , Gasolina , Voluntários Saudáveis , Humanos , Pulmão/fisiopatologia , Material Particulado/toxicidade , Ferrovias , Emissões de Veículos/toxicidade
12.
Int J Cancer ; 142(6): 1158-1165, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29090456

RESUMO

High-risk human papillomavirus (HPV) infection is essential in the carcinogenesis of a substantial part of anogenital and oropharyngeal cancers and has additionally been shown to be a possible predictive marker for survival, especially in oropharyngeal cancer. Studies examining the influence of HPV status on survival after vulvar cancer have been conflicting and limited by small study populations. Therefore, the aim of this review and meta-analysis was to examine whether HPV status influences survival after vulvar cancer, which, to our knowledge, has not been done before. We conducted a systematic search of PubMed, Cochrane Library and Embase to identify studies examining survival after histologically verified and HPV tested vulvar cancer. A total of 18 studies were eligible for inclusion. Study-specific and pooled HRs of the 5-year OS and DFS were calculated using a fixed effects model. The I2 statistic was used to describe heterogeneity. The studies included a total of 1,638 women with HPV tested vulvar cancers of which 541 and 1,097 were HPV-positive and HPV-negative, respectively. Fifteen studies included only squamous cell carcinomas. We found a pooled HR of 0.61 (95% CI: 0.48-0.77) and 0.75 (95% CI: 0.57-1.00) for 5-year OS and DFS, respectively. Across study heterogeneity was moderate to high (OS: I2 = 51%; DFS: I2 = 73%). In conclusion, women with HPV-positive vulvar cancers have a superior survival compared to women with HPV-negative, which could be of great clinical interest and provides insight into the differences in the natural history of HPV-positive and negative vulvar cancers.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/mortalidade , Neoplasias Vulvares/mortalidade , Sobreviventes de Câncer/estatística & dados numéricos , Carcinoma de Células Escamosas/virologia , DNA Viral/isolamento & purificação , Intervalo Livre de Doença , Feminino , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Neoplasias Vulvares/virologia
13.
Br J Cancer ; 116(3): 398-404, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28081550

RESUMO

BACKGROUND: Childhood cancer survivors can experience learning problems resulting in lower-than-expected attained education as adults. It is unclear whether learning problems manifest already during adolescence. METHODS: We analysed nationwide Danish registries on school grades for Danish children during 2001-2014. Applying a matched design we compared grades of childhood cancer survivors to children without cancer at ninth grade. We estimated grade differences by subject and its correlation to cancer site and age at diagnosis. The available statistical precision allowed for an analysis of more rare cancer sites. RESULTS: The total study population was 793 332 children (mean age 15.24 years and 49.7% girls), of whom 1320 were childhood cancer survivors. Lower rank grades were seen in children with cancer in all school subjects but differed substantially according to cancer site. Most affected were survivors of central nervous system (CNS) tumours, neuroblastoma, lymphoma, leukaemia, other malignant neoplasm and germ-cell tumours. Survivors from other cancer types did not obtain lower grades. Lower rank grades were associated with young age at diagnosis. CONCLUSIONS: The effect of childhood cancer differed substantially between cancer sites. The largest effect was among survivors of CNS tumours and leukaemia diagnosed at a young age, suggesting an association with radiation therapy. However, the majority of cancer survivors fare well. Increasing awareness on children affected by cancer and special accommodations may help maximise the learning potential of those most affected.


Assuntos
Escolaridade , Neoplasias/reabilitação , Instituições Acadêmicas/estatística & dados numéricos , Sobreviventes/estatística & dados numéricos , Adolescente , Idade de Início , Neoplasias do Sistema Nervoso Central/epidemiologia , Dinamarca/epidemiologia , Feminino , Humanos , Leucemia/epidemiologia , Masculino , Neoplasias/epidemiologia , Neoplasias/psicologia , Sistema de Registros , Sobreviventes/psicologia
15.
Toxicol Lett ; 400: 9-15, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38977139

RESUMO

Polycyclic aromatic compounds (PAHs) are formed during incomplete combustion and firefighters are inadvertently at risk of being exposed to these and other hazardous compounds. Exposure to PAHs is often estimated by measuring their hydroxylated metabolites (OH-PAH) in urine. Here, an online-SPE LC-MS-MS method was set up for eight OH-PAHs thus increasing sample throughput and minimizing manual handling. The method was validated over a 5-month period and showed good reproducibility with intra- and inter-day variation of 2.4-8.1 % and 1.6-6.5 %, respectively, of low-level samples and accuracy (91.6-104.8 %) for a standard reference material. The method was applied to urine samples from conscripts training to become firefighters to determine the optimal sampling time for this training activity before a large intervention study. In total, six conscripts sampled urine 6-8 times over a 40-hr period during a 3-day training course. All eight metabolites were detected in ≥ 97 % of the samples and showed peak excretion 4-6 hrs after the training corresponding to 8-10 hrs after first exposure. Samples taken the morning after the exercise contained low levels of most metabolites. Consequently, 4-6 hrs post exposure is recommended as the optimal sampling time for quantification of PAH exposure and monitoring of potential differences in exposure.


Assuntos
Bombeiros , Exposição Ocupacional , Hidrocarbonetos Policíclicos Aromáticos , Espectrometria de Massas em Tandem , Humanos , Hidrocarbonetos Policíclicos Aromáticos/urina , Espectrometria de Massas em Tandem/métodos , Exposição Ocupacional/análise , Masculino , Reprodutibilidade dos Testes , Cromatografia Líquida/métodos , Hidroxilação , Extração em Fase Sólida , Fatores de Tempo , Adulto Jovem , Monitoramento Biológico/métodos , Adulto , Espectrometria de Massa com Cromatografia Líquida
16.
Environ Health ; 12: 116, 2013 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-24373585

RESUMO

BACKGROUND: Exposure to particulate air pollution increases respiratory and cardiovascular morbidity and mortality, especially in elderly, possibly through inflammation and vascular dysfunction. METHODS: We examined potential beneficial effects of indoor air filtration in the homes of elderly, including people taking vasoactive drugs.Forty-eight nonsmoking subjects (51 to 81 years) in 27 homes were included in this randomized, double-blind, crossover intervention study with consecutive two-week periods with or without the inclusion of a high-efficiency particle air filter in re-circulating custom built units in their living room and bedroom. We measured blood pressure, microvascular and lung function and collected blood samples for hematological, inflammation, monocyte surface and lung cell damage markers before and at day 2, 7 and 14 during each exposure scenario. RESULTS: The particle filters reduced the median concentration of PM2.5 from approximately 8 to 4 µg/m3 and the particle number concentration from 7669 to 5352 particles/cm3. No statistically significant effects of filtration as category were observed on microvascular and lung function or the biomarkers of systemic inflammation among all subjects, or in the subgroups taking (n = 11) or not taking vasoactive drugs (n = 37). However, the filtration efficacy was variable and microvascular function was within 2 days significantly increased with the actual PM2.5 decrease in the bedroom, especially among 25 subjects not taking any drugs. CONCLUSION: Substantial exposure contrasts in the bedroom and no confounding by drugs appear required for improved microvascular function by air filtration, whereas no other beneficial effect was found in this elderly population.


Assuntos
Poluentes Atmosféricos/toxicidade , Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Filtração , Pulmão/efeitos dos fármacos , Material Particulado/toxicidade , Idoso , Idoso de 80 Anos ou mais , Poluentes Atmosféricos/análise , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Cidades , Estudos Cross-Over , Dinamarca , Método Duplo-Cego , Feminino , Testes Hematológicos , Humanos , Inflamação/sangue , Inflamação/etiologia , Pulmão/fisiologia , Masculino , Pessoa de Meia-Idade , Material Particulado/análise , Testes de Função Respiratória
17.
Toxicology ; 495: 153612, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37558157

RESUMO

Exposure to spray-formulated products for car cabin detailing is a potential risk for asthma induction. With a focus on the asthma-related endpoints sensitisation and irritation of the lungs, we performed an occupational risk assessment based on requirements in the EU Chemical Agents Directive. We identified 71 such spray products available in Denmark. We identified ingredient substances in safety data sheets and screened for harmonised classifications of respiratory sensitisation and airway irritation. For respiratory sensitisation, we also applied quantitative structure-activity relationship (QSAR). We modelled the exposure during 15 min of work inside a car cabin, and determined the risk ratio of the products by further applying occupational exposure limits - mainly derived no-effect levels (DNELs) from the European Chemicals Agency (ECHA) set on respiratory irritation. Four substances had a harmonised classification for respiratory irritation (bronopol, 2-phenoxyethanol, 2-methoxypropanol, and butan-1-ol). Seven substances were positive in the QSAR model for respiratory sensitisation (monoethanolamine, bronopol, glycerol, methyl salicylate, benzoic acid, ammonium benzoate, and sodium benzoate). Two vinyl treatment products had a risk ratio > 1 based on the level of sodium benzoate and its DNEL set on respiratory irritation. Two products had risk ratios of 0.69 and 0.73, respectively, based on 2-methyl-2 H-isothiazol-3-one and its acute DNEL set on respiratory irritation. In conclusion, 10 substances that may pose a risk for asthma induction were identified in the products. Two of the 71 products had a risk ratio > 1, meaning they may pose an asthma-induction risk in the modelled exposure scenario and using respiratory irritation DNELs from ECHA.


Assuntos
Asma , Relação Quantitativa Estrutura-Atividade , Humanos , Automóveis , Benzoato de Sódio , Asma/induzido quimicamente , Medição de Risco
18.
Int J Hyg Environ Health ; 247: 114056, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36395656

RESUMO

Applications of polychlorinated biphenyls (PCBs) in buildings and their persistence in indoor environments have led to cases of current and highly elevated exposure in humans, despite the global cease of production decades ago. Personal exposure to PCBs was assessed among residents in a social housing estate in Denmark containing both contaminated (n = 67) and non-contaminated (n = 23) apartments. Samples and estimated daily intakes (EDIs) were assessed for 15 PCB congeners, and body burden, which was limited by the dietary data availability, was compared across 7 indicator PCBs, with its sum (PCBsum7) often applied in European regulation of PCBs. Median PCBsum7 EDI across measured pathways for exposed residents was 101 ng· (kg bodyweight)-1· day-1, with the majority of exposure (60%) coming from inhalation of contaminated indoor air. Calculated from both PCBs measured in indoor air and on hand wipes, dermal absorption estimates showed comparable results and served as a secondary exposure pathway, accounting for 35% of personal exposure and considering selected assumptions and sources of physical-chemical parameters. Estimates revealed that diet was the primary PCB source among the reference group, accounting for over 75% of the PCBsum7 EDI across exposure routes. When evaluating overall EDIs across the two study groups and including dietary estimates, PCB exposure among exposed residents was around 10 times higher than the reference group. Solely within the exposed population, pathway-specific body burdens were calculated to account for exposure across years of residence in contaminated apartments, where lower chlorinated PCBs were dominant in indoor air. Among these dominant congeners, estimated body burdens of PCB-28 and -52 were significantly correlated with measured serum (rs = 0.49, 0.45; p < 0.001). This study demonstrates that inhalation and dermal absorption serve as dominant exposure pathways for residents of apartments contaminated with predominantly lower chlorinated PCBs and suggest that predictions of body burden from indoor environment measurements may be comparable to measured serum PCBs.


Assuntos
Poluição do Ar , Bifenilos Policlorados , Humanos , Carga Corporal (Radioterapia) , Peso Corporal , Mãos
19.
Chemosphere ; 345: 140449, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37839747

RESUMO

In a recent estimate, 96 million tons of hazardous waste were produced in the European Union, most of which were handled among the member states. Organophosphate esters (OPEs) are applied as flame retardants and plasticizers and are present in many products, e.g., electronics, which end up in the hazardous waste stream upon disposal. Given the growing body of information suggesting potential adverse health effects of OPEs, waste recycling workers who handle hazardous waste could potentially be at risk of elevated exposure to these chemicals. Using silicone wristbands, we evaluated OPE exposure among waste recycling workers who handled hazardous waste and compared their exposure to that of administrative workers from the same waste companies. Wristbands were extracted and analyzed for six OPEs, which were all detected in >75% of wristbands. Overall, the sum of tris(2-chloroisopropyl) phosphate (∑TCIPP) isomers was the most abundant OPE across all wristbands collected within the study. In general, the sum of tri(methyl phenyl) phosphate isomers (∑TMPP) was elevated for all waste workers (10ß = 7.9), whereas tri-n-butyl phosphate (TnBP), tris(1,3-dichloroisopropyl) phosphate (TDCIPP), and ∑TMPP were 3-12 times higher among those specifically handling electronic and hazardous waste compared to the administrative workers (p < 0.05). Repeated wristband measurements from the same worker had fair to good consistency in OPE concentrations (intraclass correlation coefficients = 0.54-0.77), except for the two most volatile chlorinated OPEs. Taken together, our results suggest that waste recycling workers who handle electronic and hazardous waste have significantly elevated exposure to OPEs, and efforts to reduce these exposures should be considered.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Retardadores de Chama , Humanos , Silicones , Organofosfatos , Fosfatos , Retardadores de Chama/análise , Resíduos Perigosos , Ésteres , Dinamarca , Monitoramento Ambiental
20.
Int J Hyg Environ Health ; 252: 114220, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37429119

RESUMO

Cleaning work using spray products has been associated with adverse respiratory effects but little is known of the exposure concentrations. The purpose of this study was to characterize aerosol generation at spray scenarios in a controlled climate chamber. Spraying on vertically and horizontally oriented surfaces, as well as spraying on a cloth, was investigated. Furthermore, the effect of nozzle geometry was tested. The average mass generation rates of six pressurized spray cans and 13 trigger sprays were about 1.7 g/s and did not differ significantly, but the average values of the individual sprays had large variations (0.5-3.1 g/s). The time required to halve the air concentration of aerosol particles, the half-life time, was determined for all spray products. The average half-life time of the total particle mass concentration (TPMC) of the pressurized spray cans was 0.5 h versus 0.25 h for trigger sprays. Gravimetrically determined airborne fractions of pressurized spray cans tended to be higher than those of trigger sprays. However, airborne fractions based on the measured peak TPMC were up to three orders of magnitude smaller. A comparison of different trigger spray nozzles when spraying the same product showed that the TPMC can be up to 18 times higher for the largest emitting nozzle. The distance of the nozzle to a cloth should be 1 cm to significantly reduce the concentration of the generated aerosols. ConsExpo modeling predicted the measured peak TPMC well but less well the decay.


Assuntos
Clima , Desinfecção , Tamanho da Partícula , Aerossóis
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