Quantitative assessment of multiple pesticides in silicone wristbands of children/guardian pairs living in agricultural areas in South Africa

Little is known about personal and time-integrated exposure to past and current used pesticides in agricultural areas and within-family exposure similarities. We aimed to assess exposure to pesticides using silicone wristbands in child/guardian pairs living on farms and in villages within two agricultural areas in South Africa. Using silicone wristbands, we quantified 21 pesticides in child/guardian pairs in 38 households over six days in 2018. Levels (in ng/g wristband) of pesticides and their transformation products (12 current-use pesticides and nine organochlorine pesticides) were measured using GC-MS/MS. We assessed the correlation between pesticide levels and between household members using Spearman correlation coefficients (r(s)). Multivariable generalized least squares (GLS) models, using household id as intercept, were used to determine level of agreement between household members, exposure differences between children and guardians and exposure predictors (study area, household location [farm vs. village] and household pesticide use). We detected 16 pesticides with highest detection frequencies for deltamethrin (89%), chlorpyrifos (78%), boscalid (56%), cypermethrin (55%), and p,p'-DDT (48%). Most wristbands (92%) contained two or more pesticides (median seven (range one to 12)). Children had higher concentrations than guardians for four pesticides. Correlation between the pesticide levels were in most cases moderate (rs 0.30-0.68) and stronger in children than in guardians. Five pesticides showed moderate to strong correlation between household members, with the strongest correlation for boscalid (r(s) 0.84). Exposure differences between the two agricultural areas were observed for chlorpyri fas, diazinon, pmthiofos, cypermethrin, boscalid, p,p'-DDT and p,p'-DDE and within areas for cypermethrin. We showed that for several pesticides children had higher exposure levels than guardians. The positive correlations observed for child/guardian pairs living in the same household suggest non-occupational shared exposure pathways in these communities

Association of Altered Plasma Lipidome with Disease Severity in COVID-19 Patients

The severity of COVID-19 is linked to an imbalanced immune response. The dysregulated metabolism of small molecules and bioactive lipids has also been associated with disease severity. To promote understanding of the disease biochemistry and provide targets for intervention, we applied a range of LC-MS platforms to analyze over 100 plasma samples from patients with varying COVID-19 severity and with detailed clinical information on inflammatory responses (&gt;30 immune markers). This is the third publication in a series, and it reports the results of comprehensive lipidome profiling using targeted LC-MS/MS. We identified 1076 lipid features across 25 subclasses, including glycerophospholipids, sterols, glycerolipids, and sphingolipids, among which 531 lipid features were dramatically changed in the plasma of intensive care unit (ICU) patients compared to patients in the ward. Patients in the ICU showed 1.3–57-fold increases in ceramides, (lyso-)glycerophospholipids, diglycerides, triglycerides, and plasmagen phosphoethanolamines, and 1.3–2-fold lower levels of a cyclic lysophosphatidic acid, sphingosine-1-phosphates, sphingomyelins, arachidonic acid-containing phospholipids, lactosylceramide, and cholesterol esters compared to patients in the ward. Specifically, phosphatidylinositols (PIs) showed strong fatty acid saturation-dependent behavior, with saturated fatty acid (SFA)- and monosaturated fatty acid (MUFA)-derived PI decreasing and polystaturated (PUFA)-derived PI increasing. We also found ~4000 significant Spearman correlations between lipids and multiple clinical markers of immune response with |R| ≥ 0.35 and FDR corrected Q &lt; 0.05. Except for lysophosphatidic acid, lysophospholipids were positively associated with the CD4 fraction of T cells, and the cytokines IL-8 and IL-18. In contrast, sphingosine-1-phosphates were negatively correlated with innate immune markers such as CRP and IL-6. Further indications of metabolic changes in moderate COVID-19 disease were demonstrated in recovering ward patients compared to those at the start of hospitalization, where 99 lipid species were altered (6 increased by 30–62%; 93 decreased by 1.3–2.8-fold). Overall, these findings support and expand on early reports that dysregulated lipid metabolism is involved in COVID-19.</p

«Ахеменидская Авеста» через призму античных источников

The epidemiologic evidence for the carcinogenicity of lead is inconsistent and requires improved exposure assessment to estimate risk. We evaluated historical occupational lead exposure for a population-based cohort of women (n=74,942) by calibrating a job-exposure matrix (JEM) with lead fume (n=20,084) and lead dust (n=5383) measurements collected over four decades in Shanghai, China. Using mixed-effect models, we calibrated intensity JEM ratings to the measurements using fixed-effects terms for year and JEM rating. We developed job/industry-specific estimates from the random-effects terms for job and industry. The model estimates were applied to subjects' jobs when the JEM probability rating was high for either job or industry; remaining jobs were considered unexposed. The models predicted that exposure increased monotonically with JEM intensity rating and decreased 20-50-fold over time. The cumulative calibrated JEM estimates and job/industry-specific estimates were highly correlated (Pearson correlation=0.79-0.84). Overall, 5% of the person-years and 8% of the women were exposed to lead fume; 2% of the person-years and 4% of the women were exposed to lead dust. The most common lead-exposed jobs were manufacturing electronic equipment. These historical lead estimates should enhance our ability to detect associations between lead exposure and cancer risk in the future epidemiologic analyses

Nonlinear low dose hematotoxicity of benzene; a pooled analyses of two studies among Chinese exposed workers

Background: Impairment of the hematopoietic system is one of the primary adverse health effects from exposure to benzene. We previously have shown that exposure to benzene at low levels (<1 ppm) affects the blood forming system and that these effects were proportionally stronger at lower versus higher levels of benzene exposure. This observation is potentially explained by saturation of enzymatic systems. Methods: Here we extend these analyses by detailed modeling of the exposure response association of benzene and its major metabolites (i.e. catechol, muconic acid, phenol, and hydroquinone) on peripheral white blood cell (WBC) counts and its major cell-subtypes (i.e. granulocytes, lymphocytes, and monocytes) using two previously published cross-sectional studies among occupationally exposed Chinese workers. Results: Supra-linear exposure response associations were observed between air benzene concentrations (range ∼ 0.1 – 100 ppm) and WBC counts and its cell-subtypes, with a larger than proportional decrease in cell counts at lower than at higher levels of benzene exposure. The hematotoxicity associations were largely similar in shape when the analyses were repeated with benzene urinary metabolites suggesting that enzymatic saturation is not a full explanation of the observed non-linearity with WBC endpoints. Discussion: We hypothesize that the flattening of the exposure response curve especially at higher benzene exposure levels may reflect a response by the bone marrow to maintain hematopoietic homeostasis. Toxicity to the bone marrow and an induced hyper-proliferative response could both contribute to risk of subsequently developing a hematopoietic malignancy. Additional work is needed to explore this hypothesis

Blood transcriptional and microRNA responses to short-term exposure to disinfection by-products in a swimming pool.

BACKGROUND: Swimming in a chlorinated pool results in high exposure levels to disinfection by-products (DBPs), which have been associated with an increased risk of bladder cancer. OBJECTIVES: By studying molecular responses at the blood transcriptome level we examined the biological processes associated with exposure to these compounds. METHODS: Whole-genome gene expression and microRNA analysis was performed on blood samples collected from 43 volunteers before and 2h after 40min swimming in an indoor chlorinated pool (PISCINAII study). Exposure to THMs was measured in exhaled breath. Heart rate and kcal expenditure were measured as proxies for physical activity. Associations between exposure levels and gene expression were assessed using multivariate normal models (MVN), correcting for age, body mass index and sex. A Bonferroni threshold at 5% was applied. RESULTS: MVN-models for the individual exposures identified 1778 genes and 23 microRNAs that were significantly associated with exposure to at least one DBP. Due to co-linearity it was not possible to statistically disentangle responses to DBP exposure from those related to physical activity. However, after eliminating previously reported transcripts associated with physical activity a large number of hits remained associated with DBP exposure. Among those, 9 were linked with bladder and 31 with colon cancer. Concordant microRNA/mRNA expressions were identified in association with DBP exposure for hsa-mir-22-3p and hsa-miR-146a-5p and their targets RCOR1 and TLR4, both related to colon cancer in association with DBP exposure. CONCLUSIONS: Short-term exposure to low levels of DBPs shows genomics responses that may be indicative of increased cancer risk

Exposure-Response Analyses of Asbestos and Lung Cancer Subtypes in a Pooled Analysis of Case-Control Studies

International audienceBACKGROUND:Evidence is limited regarding risk and the shape of the exposure-response curve at low asbestos exposure levels. We estimated the exposure-response for occupational asbestos exposure and assessed the joint effect of asbestos exposure and smoking by sex and lung cancer subtype in general population studies.METHODS:We pooled 14 case-control studies conducted in 1985-2010 in Europe and Canada, including 17,705 lung cancer cases and 21,813 controls with detailed information on tobacco habits and lifetime occupations. We developed a quantitative job-exposure-matrix to estimate job-, time period-, and region-specific exposure levels. Fiber-years (ff/ml-years) were calculated for each subject by linking the matrix with individual occupational histories. We fit unconditional logistic regression models to estimate odds ratios (ORs), 95% confidence intervals (CIs), and trends.RESULTS:The fully adjusted OR for ever-exposure to asbestos was 1.24 (95% CI, 1.18, 1.31) in men and 1.12 (95% CI, 0.95, 1.31) in women. In men, increasing lung cancer risk was observed with increasing exposure in all smoking categories and for all three major lung cancer subtypes. In women, lung cancer risk for all subtypes was increased in current smokers (ORs ~two-fold). The joint effect of asbestos exposure and smoking did not deviate from multiplicativity among men, and was more than additive among women.CONCLUSIONS:Our results in men showed an excess risk of lung cancer and its subtypes at low cumulative exposure levels, with a steeper exposure-response slope in this exposure range than at higher, previously studied levels. (See video abstract at, http://links.lww.com/EDE/B161.)

Exposure to MRI-related magnetic fields and vertigo in MRI workers

OBJECTIVES: Vertigo has been reported by people working around magnetic resonance imaging (MRI) scanners and was found to increase with increasing strength of scanner magnets. This suggests an association with exposure to static magnetic fields (SMF) and/or motion-induced time-varying magnetic fields (TVMF). This study assessed the association between various metrics of shift-long exposure to SMF and TVMF and self-reported vertigo among MRI workers. METHODS: We analysed 358 shifts from 234 employees at 14 MRI facilities in the Netherlands. Participants used logbooks to report vertigo experienced during the work day at the MRI facility. In addition, personal exposure to SMF and TVMF was measured during the same shifts, using portable magnetic field dosimeters. RESULTS: Vertigo was reported during 22 shifts by 20 participants and was significantly associated with peak and time-weighted average (TWA) metrics of SMF as well as TVMF exposure. Associations were most evident with full-shift TWA TVMF exposure. The probability of vertigo occurrence during a work shift exceeded 5% at peak exposure levels of 409 mT and 477 mT/s and at full-shift TWA levels of 3 mT and 0.6 mT/s. CONCLUSIONS: These results confirm the hypothesis that vertigo is associated with exposure to MRI-related SMF and TVMF. Strong correlations between various metrics of shift-long exposure make it difficult to disentangle the effects of SMF and TVMF exposure, or identify the most relevant exposure metric. On the other hand, this also implies that several metrics of shift-long exposure to SMF and TVMF should perform similarly in epidemiological studies on MRI-related vertigo

Exposure-response analyses for soluble platinum-salt exposed workers and sensitisation: a retrospective cohort study among newly exposed workers using routinely collected surveillance data

OBJECTIVES: Soluble platinum salts are well known respiratory sensitising agents leading to work related sensitisation in the work environment. No quantitative exposure response relation has been described for soluble platinum salts. The objective of this study was to explore exposure response relations for soluble platinum salt exposed workers. METHOD: A retrospective cohort study was conducted using routinely collected health surveillance data and soluble platinum exposure data. Workers who newly entered between 1 January 2000 and 31 December 2010 were included and the relation between measured soluble platinum exposure and sensitisation (as determined by skin prick testing) was analysed in more than 1000 refinery workers from 5 refineries from whom a total of more than 1700 personal exposure measurements were available. Exposure response relations were analysed in survival analysis considering changes in exposure over time. Associations were explored for present exposure, cumulative exposure and average exposure. The exposure was lagged by 0.5, 1.0, 1.5, etc. year with a maximum of 5 years. RESULTS: A clear exposure response relation was observed, most strongly for present platinum salt exposure. Exposure lagging showed that exposure preceding sensitisation with maximally 1-2 years was most strongly associated with sensitisation risk. The exposure response relationship was modified by smoking and atopy, but relative risks for smoking and atopy were only modestly elevated. CONCLUSIONS: The precision of estimate of the exposure-response relationship derived from this dataset appears superior to previous epidemiologic studies conducted on platinum salt sensitisation and may as a result have possible utility to occupational exposure standard setting

Estimation of the exposure response relation between benzene and acute myeloid leukemia by combining epidemiological, human biomarker, and animal data

Background Chemical risk assessment can benefit from integrating data across multiple evidence bases, especially in exposure-response cure (ERC) modelling when data across the exposure range is sparse. Methods We estimated the ERC for benzene and acute myeloid leukemia (AML), by fitting linear and spline-based Bayesian meta-regression models that included summary risk estimates from non-AML and non-human studies as prior information. Our complete dataset included six human AML studies, three human leukemia studies, ten human biomarker studies, and four experimental animal studies. Results A linear meta-regression model with intercept best predicted AML risks after cross-validation, both for the full dataset and AML studies only. Risk estimates in the low exposure range (<40 ppm yrs) from this model were comparable, but more precise, when the ERC was derived using all available data than when using AML data only. Allowing for between-study heterogeneity, RRs and 95% prediction intervals [95%PI] at 5 ppm years were 1.58 [1.01, 3.22]) and 1.44 [0.85, 3.42], respectively. Conclusions Integrating the available epidemiological, biomarker, and animal data resulted in more precise risk estimates for benzene exposure and AML, although the large between-study heterogeneity hampers interpretation of these results. The harmonization steps required to fit the Bayesian meta-regression model involve a range of assumptions that need to be critically evaluated, as they seem crucial for successful implementation. Impact By describing a framework for data-integration and explicitly describing the necessary data harmonization steps, we hope to enable risk assessors to better understand the advantages and assumptions underlying a data integration approach