Smoking habit in parents and exposure to environmental tobacco smoke in elementary school children of Milan.

INTRODUCTION: Children with smoking parents are potentially exposed to Environmental Tobacco Smoke (ETS). The aims of this study were: 1) to assess ETS exposure in Milan schoolchildren, by measuring urinary cotinine (COT-U), 2) to compare the parents' perception of children ETS exposure, with the actual ETS exposure measured by COT-U, 3) to explore the factors influencing COT-U, including smoking bans at home, the season, and children characteristics. METHODS: One-hundred school children (7-11 years) and their parents were recruited for the study in Spring 2018 (n = 81) and in Winter 2019 (n = 94), 75 children participated to both campaigns, for a sum of 175 observations. A questionnaire was submitted to parents to collect information about smoking habits in the house. COT-U was measured by LC-MS/MS in spot urine sample collected in the morning from children. RESULTS: Detectable COT-U levels were found in 42% and 57% of children, in spring and winter, in contrast with 17% and 13% of parents acknowledging ETS exposure. Children living with smokers or e-cigarette users (vapers) (30% of the participants) had higher COT-U levels than children not living with smokers or vapers (median 0.67, 0.46, and <0.1 µg/L in spring, and 0.98, 0.85, and 0.11 µg/L in winter, respectively). Increasingly higher COT-U levels were observed in children living in homes where smoking was completely banned, allowed in the external parts of the home, or allowed in some rooms. The multiple regression analysis confirmed the positive significant effect of living with smokers, a partial smoking ban and absence of smoking ban at home, the winter season, and BMI as determinants of COT-U. CONCLUSION: ETS exposure resulted in measurable urinary cotinine in children. Smoking parents underestimate exposure to ETS of their children. Living with smokers is a determinant of COT-U, only slightly mitigated by adopting partial smoking ban.

Minding the gap between cortisol levels measured with second-generation assays and current diagnostic thresholds for the diagnosis of adrenal insufficiency: a single-center experience.

PURPOSE: The current cut-offs for the diagnosis of adrenal insufficiency (AI) have been established using outdated immunoassays. We compared the cortisol concentrations measured with Roche Cortisol I (R1), the newly available Roche Cortisol II (R2), and liquid chromatography tandem mass spectrometry (LC-MS/MS), the gold standard procedure to measure steroids in patients undergoing the corticotropin (ACTH) test. METHODS: We enrolled 30 patients (age 47 ± 21 years) referred to undergo the ACTH test (1 or 250 µg). Cortisol was measured at 0, 30, and 60 min after stimulation with R1, R2, and LC-MS/MS. AI was diagnosed for R1-stimulated peak cortisol concentrations < 500 nmol/L. RESULTS: Mean cortisol concentrations measured with R2 and LC-MS/MS were comparable, while mean cortisol concentrations measured by R1 were higher than those of both R2 and LC-MS/MS (respectively, basal 411 ± 177, 287 ± 119, and 295 ± 119 nmol/L; at 30 min, 704 ± 204, 480 ± 132, and 500 ± 132 nmol/L; at 60 min, 737 ± 301, 502 ± 196, and 519 ± 201 nmol/L, p ≤ 0.01 for R1 vs. both R2 and LC-MS/MS at each point). Considering the 500 nmol/L cortisol peak cut-off, AI was diagnosed in 5/30 patients using R1 and in 12/30 using R2 (+ 140%). Based on the correlation between R1 and R2, the threshold of 500 nmol/L became 351 nmol/L (12.7 µg/dL) when cortisol was measured with R2, and 368 nmol/L (13.3 µg/dL) with LC-MS/MS. CONCLUSIONS: The use of more specific cortisol assays results in lower cortisol concentrations. This could lead to misdiagnosis and overtreatment when assessing AI with the ACTH test if a different cut-off for cortisol peak is not adopted.

Hair as a matrix to evaluate cumulative and aggregate exposure to pesticides in winegrowers.

INTRODUCTION: Vineyard is a crop where a large number of pesticides are applied; exposure to pesticides may occur in farmers and the general population living close to the treated area. This work aimed to investigate hair as a matrix for the assessment of cumulative and aggregate exposure to pesticides in potentially exposed individuals. METHODS: Twenty agricultural workers (AW), 4 agricultural worker relatives (AR), and 5 research staff members (RS) were involved in the study. Hair samples were collected before and after the application season (PRE- and POST-EXP samples) to obtain 18 paired samples. Records with the name and the quantity of applied pesticides were obtained; twenty-seven pesticides were measured in hair by solvent extraction and LC-MS/MS. RESULTS: During the study season, AW applied 14 different pesticides with median amount ranging from 12 to 7200 g. The most popular pesticides were dimethomorph, penconazole, cyazofamid, fenamidone and quinoxyfen, applied from 94 to 69% of AW. In AW, in PRE-EXP samples the majority of used pesticides was detectable (with detection rates from 6 to 88%), with median concentrations of few pg/mg hair; in the POST-EXP samples the frequency of detected values increased (from 25 to 100%), with median concentrations up to two orders of magnitude higher. In AR, most pesticides were quantifiable only in POST-EXP samples and with lower concentration in comparison with AW; in RS, in both PRE- and POST-EXP samples only a few pesticides were quantifiable with very low levels. In AW, a linear correlation (r = 0.682 on log-transformed data, p < 0.01) was found between the total amounts of applied pesticides during the season and their concentration in hair. CONCLUSION: The study shows that the majority of assessed pesticides was incorporated into hair of AW and AR. The increased frequency of detection and level at the end of the season and the correlation between pesticide in hair and the amount of applied pesticides, reinforce the use of hair for quantitative biomonitoring of cumulative exposure to pesticides.

Annual, seasonal, and morning rush hour Land Use Regression models for black carbon in a school catchment area of Milan, Italy.

INTRODUCTION: The European Environment Agency has identified Northern Italy as one of the most polluted areas in Europe. Among air contaminants, black carbon (BC) has been identified as a sensitive marker of traffic related air pollution. This study aims to investigate the spatial distribution of BC in the catchment area of an elementary school of Milan, the biggest city in Northern Italy, using Land Use Regression (LUR) models and focusing especially on Morning Rush Hour (MRH). METHODS: Two recruitment campaigns were performed asking schoolchildren's parents and residents of the study area to host a monitoring site in their own dwellings. Finally, 34 monitoring sites and 1 reference site were sampled. BC was measured in two seasonal campaigns using eight micro-aethalometers. Six seasonal and annual LUR models were developed, 3 focused on MRH. RESULTS: Overall, median BC was 3247 and 1309 ng/m3 in the cold and warm season, respectively. In both seasons, there was a significant spatial variation between the monitoring sites. MRH values were higher than the daily values with median concentrations of 4227 and 2331 ng/m3, respectively. Developed LUR models showed that BC variability is well explained only by traffic variables; R2 ranged from 0.52 to 0.79 and from 0.65 to 0.81, for seasonal/annual and MRH LUR models respectively. DISCUSSION: LUR models based on traffic variables explain most of the measured BC distribution variability for both warm and cold season. MRH represents a critical moment for BC during all the year, with an increase of 1000 ng/m3 respective to the daily median value and differences in magnitude according to location. Our results highlight that the mobility issue is one of the most important challenges to reduce air pollution in the city of Milan and this is of particular concern for elementary schoolchildren that commute to school during MRH.

Association between Adiposity and disability in the Lc65+ Cohort.

OBJECTIVES: To examine the longitudinal association between body mass index (BMI) and waist circumference (WC) with mortality and incident disability in Lc65+ cohort. DESIGN: Population-based cohort of non-institutionalized adults with up to 8.9 years of follow-up. SETTING: City of Lausanne, Switzerland. PARTICIPANTS: 1,293 individuals aged 65 to 70 at baseline (58% women). MEASUREMENTS: BMI, WC and covariates were measured at baseline in 2004-2005. Vital status was obtained up to the 31st December 2013 and difficulty with basic activities of daily living (BADL) was reported in a self-administered questionnaire sent to participants every year. Main outcomes were total mortality and disability, defined as difficulty with BADL for ≥2 years or institutionalization. Cox regression was used with BMI/WC quintiles 2 as the reference. RESULTS: 130 persons died over a median follow-up of 8.47 years (crude mortality rate, men: 16.5/1,000 person-years, women: 9.7/1,000 person-years). In Cox regression adjusted for age, sex, education, financial situation, smoking and involuntary weight loss (IWL) at baseline, mortality was significantly associated with neither BMI nor WC, but there were trends towards non-significant J-curves across both BMI and WC quintiles. Disability (231 cases) tended to increase monotonically across both BMI and WC quintiles and was significantly associated with BMI quintile 5 (HR=2.44, 95% CI [1.65-3.63]), and WC quintiles 4 (HR=1.81 [1.15-2.85]) and 5 (HR=2.58, [1.67-4.00]). CONCLUSION: Almost half of the study population had a substantially increased HR of disability, as compared to the reference BMI/WC categories. This observation emphasizes the need for life-long strategies aimed at preventing excess weight, muscle loss and functional decline through adequate nutrition and regular physical activity, starting at early age and extending throughout life.

Urinary chromium is associated with changes in leukocyte miRNA expression in obese subjects.

BACKGROUND/OBJECTIVES: Epidemiological studies suggest a link between chromium (Cr) status and cardiovascular disease. Increased urinary excretion of Cr was reported in subjects with diabetes compared with non-diabetic controls and those with non-diabetic insulin resistance. Epigenetic alterations have been linked to the presence of Cr, and microRNA (miRNA) expression has been implicated in the pathogenesis of metabolic diseases and cardiovascular diseases (CVDs). We investigated the association between Cr excretion and miRNA expression in leukocytes from obese subjects. We also examined the relationship between altered miRNA expression and selected clinical parameters to further investigate mechanisms linking Cr to metabolic diseases and CVDs. SUBJECTS/METHODS: We analyzed urinary Cr in 90 Italian subjects using inductively coupled plasma-mass spectrometry. Peripheral blood miRNA levels were screened with TaqMan Low-Density Array Human MicroRNA A. Cr level-associated expression of miRNAs was detected with multivariate regression analyses, and the top 10 candidate miRNAs were selected for validation. We also used multivariate regression analyses to assess possible associations between validated miRNAs and glycated hemoglobin (A1c) and blood pressure (BP). The validated miRNAs were further investigated by functional analysis with Ingenuity Pathway Analysis software. RESULTS: Urinary Cr levels (mean: 0.35 µg/l; s.d.=0.24) ranged from 0.05 to 1.27 µg/l. In the screening phase, 43 miRNAs were negatively associated with Cr. Of the top 10 miRNAs selected for validation, nine (miR-451, miR-301, miR-15b, miR-21, miR-26a, miR-362-3p, miR-182, miR-183 and miR-486-3p) were downregulated in association with Cr (P-false discovery rate (FDR)<0.10). miR-451 expression was associated with A1c (ß=-0.06; P=0.0416), whereas miR-486-3p expression was associated both with diastolic (ß=2.1; P=0.004) and systolic BP (ß=3.3; P=0.003). CONCLUSIONS: These results indicate that miR-451 and miR-486-3p are involved in the link between Cr levels and metabolic diseases and CVDs.

Identification of Metabolites of the Fungicide Penconazole in Human Urine.

Penconazole (PEN) is a fungicide used in agriculture that has been classified as hazardous to humans and the environment. The objective of this work was to identify PEN urinary metabolites in humans and propose a biomarker for PEN exposure. Five urine samples were collected from agricultural workers who worked with and were exposed to PEN. Samples were analyzed by liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometry, with the source operating in the electrospray ionization mode. Metabolites previously identified in animal studies were searched as possible metabolites in humans. Candidate metabolites were first identified by multiple reaction monitoring following the protonated molecular ions that generated the protonated triazole moiety, which is expected to be present in all PEN metabolites; second, the isotopic patterns of the molecular ions were checked for consistency with the presence of two chlorine atoms; third, the full mass spectra were evaluated for consistency with the molecular structure. Seven different oxidized metabolites were found, both in the free and glucuronide conjugate forms. The major metabolite was the monohydroxyl-derivative PEN-OH (median molar fraction approximately 0.92 as a sum of free and glucuronide conjugated form). The product of further oxidation was the carboxyl-derivate PEN-COOH (median molar fraction approximately 0.03). After hydrolysis with ß-glucuronidase, the free compounds were quantified in the presence of deuterated PEN as an internal standard; PEN-OH levels ranged from 230 to 460 µg/L, and PEN-COOH levels ranged from 5.2 to 16.7 µg/L. We propose a pathway for PEN metabolism in humans and suggest PEN-OH, after hydrolysis of glucuronide conjugates, as a biomarker for monitoring human exposure to PEN.

X-chromosomal inactivation directly influences the phenotypic manifestation of X-linked protoporphyria.

X-linked protoporphyria (XLP), a rare erythropoietic porphyria, results from terminal exon gain-of-function mutations in the ALAS2 gene causing increased ALAS2 activity and markedly increased erythrocyte protoporphyrin levels. Patients present with severe cutaneous photosensitivity and may develop liver dysfunction. XLP was originally reported as X-linked dominant with 100% penetrance in males and females. We characterized 11 heterozygous females from six unrelated XLP families and show markedly varying phenotypic and biochemical heterogeneity, reflecting the degree of X-chromosomal inactivation of the mutant gene. ALAS2 sequencing identified the specific mutation and confirmed heterozygosity among the females. Clinical history, plasma and erythrocyte protoporphyrin levels were determined. Methylation assays of the androgen receptor and zinc-finger MYM type 3 short tandem repeat polymorphisms estimated each heterozygotes X-chromosomal inactivation pattern. Heterozygotes with equal or increased skewing, favoring expression of the wild-type allele had no clinical symptoms and only slightly increased erythrocyte protoporphyrin concentrations and/or frequency of protoporphyrin-containing peripheral blood fluorocytes. When the wild-type allele was preferentially inactivated, heterozygous females manifested the disease phenotype and had both higher erythrocyte protoporphyrin levels and circulating fluorocytes. These findings confirm that the previous dominant classification of XLP is inappropriate and genetically misleading, as the disorder is more appropriately designated XLP.

Identification and quantification of metabolites of the fungicide tebuconazole in human urine.

Tebuconazole (TEB) is a fungicide used in agriculture; the objective of this work was to identify and quantify TEB metabolites in human urine. Samples from seven vineyard workers exposed to TEB were submitted to liquid chromatography interfaced with a triple quadrupole mass spectrometer, equipped with an electron spray source, and a linear ion trap to gain a profile of candidate metabolites. Based on the presence of the ion m/z 70 in the MS/MS spectra, which corresponds to protonated triazole (a specific moiety of TEB), and the isotopic pattern of the molecular ions, typical of molecules with one chlorine atom, hydroxyl and carboxyl derivatives of TEB, that is, TEB-OH and TEB-COOH, were identified as major metabolites, both as free molecules and as glucuronide (Glc) conjugates. The mean molar fractions were 0.67, 0.13, 0.13, and 0.07 for TEB-O-Glc, TEB-OH, TEB-COO-Glc, and TEB-COOH. Urine samples were submitted to hydrolysis with ß-glucuronidase, and the free compounds were quantified in the presence of deuterated TEB (TEB-d6) as the internal standard (IS), by multiple reaction monitoring (MRM) mode. The assay was linear in the ranges of 0.2-600 µg/L and 0.1-240 µg/L for TEB-OH and TEB-COOH, respectively; precision, accuracy, and the limit of quantification (LOQ) were <3.1%, 98-103%, and 0.3 µg/L for both analytes. An evaluation of matrix effects showed that the use of TEB-d6 controlled these sources of bias. The urinary levels of TEB-OH and TEB-COOH in specimens collected from farmers exposed to TEB ranged from 10 to 473 and from 3 to 159 µg/L, respectively.

The role of salivary cortisol measured by liquid chromatography-tandem mass spectrometry in the diagnosis of subclinical hypercortisolism.

OBJECTIVE: The use of late-night salivary cortisol (LNSalC) for diagnosing subclinical hypercortisolism (SH) is debated. No data are available regarding the role of LNSalC as measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in SH diagnosis. The aim of this study was to evaluate the diagnostic accuracy of LNSalC measured by LC-MS/MS in SH. DESIGN: Cross-sectional prospective study of outpatients. METHODS: In 70 consecutive patients with adrenal incidentalomas (AI), without signs and symptoms of hypercortisolism, we diagnosed SH in the presence of at least two of the following: cortisol after 1 mg overnight dexamethasone suppression test (1  mg DST) >83  nmol/l, 24-h urinary free cortisol (UFC) >193  nmol/24  h, and morning ACTH <2.2  pmol/l. The LNSalC levels by LC-MS/MS at 2300  h (normal values <2.8  nmol/l) and the presence of hypertension, type 2 diabetes mellitus (T2DM), and osteoporosis (OP) were assessed. RESULTS: The increased LNSalC levels (>2.8  nmol/l) had an 83.3% specificity (SP) and a 31.3% sensitivity (SN) for predicting the biochemical diagnosis of SH. The increased LNSalC had an 85.2% SP and a 55.6% SN for predicting the presence of hypertension, T2DM, and OP, while the combination of LNSalC >1.4  nmol/l (cutoff with 100% SN) plus 1 mg DST >50  nmol/l had an 88.9% SN and an 85.2% SP (similar to SH criterion at enrollment). CONCLUSIONS: In AI patients, LNSalC measured by LC-MS/MS appears to be useful in combination with 1 mg DST for diagnosing SH, while it is not useful as a single criterion.

[Air and biomonitoring of occupational exposure to anesthetic gases in the health care workers of a large hospital in Milan]. / Il monitoraggio ambientale e biologico dell'esposizione professionale a gas anestetici presso le sale operatorie di un grande ospedale milanese.

In this study exposure to anesthetic gases in health care workers of a hospital of Milan was investigated. The evaluation focused on the period 2007-2010 and was performed by environmental monitoring (20 operating rooms and 54 samples) and biological monitoring (180 workers and 242 urine samples). Mean airborne exposure was 3:15 and 0.34 ppm for nitrogen protoxide (N2O) and sevorane; in end-of-exposure urine samples the concentration of N2O and hexafluoroisopropanol, metabolite of sevorane, were 4.85 mg/L and 0.21 mg/L, with 80 and 21% of values below the quantification limit. Sevorane monitoring exceeded or equaled the environmental limit value of 0.5 ppm and the biological exposure index in 17 and 11% of measures. There were no observed exceedances of the limit for N2O. The anesthetist and scrub nurse were tasks with greater exposure. There was a significant correlation between airborne halogenated gases and urinary hexafluoroisopropanol. The results of this study indicates that further efforts are needed to improve the hygienic conditions in the investigated hospital.

[Identification of biomarkers of short- and medium-term exposure in urine and hair of subjects exposed to terbuthylazine]. / Identificazione di indici biologici di esposizione a breve e medio termine nelle urine e nei capelli di soggetti esposti a terbutilazina.

Terbuthylazine (TBA) is a herbicide widely used for weed control in corn crop. In mammals it is completely metabolized and excreted in urine, mostly as desetilterbutilazina (DET). This work aims to evaluate the use of urine and hair as matrices for monitoring short- and medium-term exposure to TBA. Levels of TBA and DET have been evaluated in hair and urine samples of 12 exposed farmers, 14 rural residents, 17 urban residents. In hair TBA was quantified in all samples of farmers and rural residents, but not of urban residents. In urine DET was detected in post-application samples of farmers but not in rural and urban residents. These results suggest that TBA in hair can be used as an index of cumulative exposure to TBA, while DET in the urine can be used as an index of short-term exposure in farmers.

[Time course of excretion of tebuconazole and its metabolites in vineyard workers]. / Cinetica di escrezione del tebuconazolo e dei suoi metaboliti in viticoltori.

Tebuconazole (TEB) is a fungicide widely used in vineyards. This work aimed at the identification of urinary metabolites of TEB for the biological monitoring of exposure, and to study their kinetics of excretion. Major urinary metabolites of TEB in rats are t-butyl-hydroxy-and-carboxy-tebuconazole (TEB-OH and TEB-COOH). TEB and these metabolites were determined in urine samples of 5 wine growers who collected each void before (24 hours), during and after (48 hours) TEB application. These chemicals were found in 95%, 100% and 100% of the samples with levels of < 1.5-13.4 microg/L for TEB, 5.2-749 microg/L for TEB-OH e 2.8-234 microg/l for TEB-COOH. TEB-OH is the major metabolite of TEB, its concentration increases at the end of exposure and peaks after 16-24 hours. TEB-COOH has similar pattern. TEB-OH and TEB -COOH are promising candidates for biological monitoring of TEB exposure; preliminary results suggest the day after the application as the best sampling time.

[Environmental and biological monitoring of exposure to PAHs in Taranto coke-oven workers and in two groups of the general population from Apulia]. / Monitoraggio ambientale e biologico dell'esposizione a IPA nei lavoratori della cokeria di Taranto e confronto con due gruppi della popolazione generale pugliese.

The exposure to PAHs was assessed by personal air sampling and urinary 1-hydroxypyrene (1-OHP) in 100 coke-oven workers (CW) of the Taranto plant and in subjects from the general population living close (NC, 18) and far away (FC, 15) from the plant. Median airborne benzo[a]pyrene (BaP) and 1-OHP levels were 152, 1.5, and 3.6 ng/m3 and 2.0, 0.5 and 0.6 microg/g creatinine in CW, NC, and FC, respectively. BaP exposure exceeded the German acceptable (70 ng/m3) and tolerable (700 ng/m3) limit risk based values in 82 and 11% of CW and the European target value for ambient air (1 ng/m3) in about 65% of NC and FC. 1-OHP levels exceed the proposed biological limit value for the coke-oven industry (4.4 microg/g crt) in 21% of CW and the Italian reference value (0.3 microg/g crt) in about 90% of NC and FC. The exposure resulted lower than in the past, but this study highlights that PAHs exposure from the coke plant still poses a health risk for workers and the general population.

[The assessment of risk for xylene exposure in a laboratory of anatomy: comparison between computational models and environmental and biological monitoring]. / La valutazione del rischio per esposizione a xilene in un laboratorio di anatomia patologica: confronto tra algoritmi matematici e monitoraggio ambientale e biologico.

Exposure to xylene in a pathology laboratory was evaluated using two algorithms: Stoffenmanager and Archi.me.de. The results were compared with those obtained by applying the environmental and biological monitoring of the exposure. The use of models required a period of self-learning and, for Stoffenmanager, knowledge of the English language. Information on the toxicity and safety of xylene, available from the medial and safety data sheets, and the conditions and amount of use, obtained through a survey and interviews with operators, have been imputed. Stoffenmanager estimated low the inhalation exposure and medium the dermal exposure, with a value of personal exposure during the work shift of 1.4 mg/m3. A.r.chi.me.d.e. estimated negligible the risk to health. These ratings are consistent with those obtained using the experimental approach. This result, combined with the simplicity and low cost, makes the algorithms very interesting tools for the assessment of chemical risk in the workplace.

Assessing variability and comparing short-term biomarkers of styrene exposure using a repeated measurements approach.

The aim of this work is to compare several short-term biomarkers of styrene exposure, namely urinary styrene (StyU), mercapturic acids (M1+M2), mandelic acid (MA), phenylglyoxylic acid (PGA), phenylglycine (PHG), and 4-vinylphenol conjugates (VP), for use as biomarkers of exposure in epidemiologic studies. A repeated measurements protocol (typically 4 measurements per worker over 6 weeks) was applied to measure airborne styrene (StyA) and urinary biomarkers in 10 varnish and 8 fiberglass reinforced plastic workers. Estimated geometric mean personal exposures to StyA were 2.96mg/m(3) in varnish workers and 15.7mg/m(3) in plastic workers. The corresponding levels of StyU, M1+M2, MA, PGA, MA+PGA, PHG and VP were 5.13microg/L, 0.111, 38.2, 22.7, 62.6, 0.978, and 3.97mg/g creatinine in varnish workers and 8.38microg/L, 0.303, 146, 83.4, 232, 2.85 and 3.97mg/g creatinine in plastic workers. Within-worker (sigma(wY)(2)) and between-worker (sigma(bY)(2)) variance components were estimated from the log-transformed data as were the corresponding fold ranges containing 95% of the respective lognormal distributions of daily levels ((w)R(0.95)) and subject-specific mean levels ((b)R(0.95)). Estimates of (w)R(0.95) (range: 4-26) were generally smaller than those of (b)R(0.95) (range: 5-790) for both environmental and biological markers; this indicates that exposures varied much more between workers than within workers in these groups. Since attenuation bias in an estimated exposure-response relationship increases with the variance ratio lambda=sigma(wY)(2)/sigma(bY)(2), we estimated values of lambda for all exposure measures in our study. Values of lambda were typically much less than one (median=0.220) and ranged from 0.089 for M1+M2 in plastic workers to 1.38 for PHG in varnish workers. Since values of lambda were 0.147 and 0.271 for StyA in varnish workers and plastic workers, respectively, compared to 0.178 and 0.210 for MA in the same groups, our results suggest that either air measurements or conventional biomarker measurements (urinary MA) would be comparable surrogates for individual exposures in epidemiologic studies.

Leisure activities and the risk of dementia in the elderly: results from the Three-City Study.

OBJECTIVE: There is accumulating evidence that involvement in leisure activities may be related to risk of dementia; however, there is no consensus concerning the underlying mechanism of this association. Hypothesizing that leisure activities may contribute to cognitive reserve (CR), we examined the association between leisure activities and risk of incident dementia and its subtypes within a general population sample, categorizing leisure activity as stimulating, passive, physical, and social. The possibility that these associations may be driven by other proxies of CR was also examined. METHODS: Analyses were carried out on 5,698 dementia-free participants aged 65 and over included in the Three-City cohort study in Dijon and Montpellier (France) in 1999-2001. Hazard ratios (HR) were calculated for incident dementia and its subtypes (mixed/vascular dementia and Alzheimer disease) in relation to category of leisure activity. RESULTS: Stimulating leisure activities were found to be significantly associated with a reduced risk of dementia (n = 161, HR = 0.49, 95% confidence interval [CI]: 0.31; 0.79) and Alzheimer disease (n = 105, HR = 0.39, 95% CI: 0.21; 0.71) over the 4-year follow-up 1) independently of other proxies of CR, 2) after adjusting for vascular risk factors, depressive symptoms, and physical functioning, and 3) independently of other leisure activities. Furthermore, no significant association was found with other leisure activities and dementia after controlling for the potential confounders. CONCLUSION: Our findings support the hypothesis that cognitively stimulating leisure activities may delay the onset of dementia in community-dwelling elders.

A novel headspace solid-phase microextraction method using in situ derivatization and a diethoxydiphenylsilane fibre for the gas chromatography-mass spectrometry determination of urinary hydroxy polycyclic aromatic hydrocarbons.

An innovative and simple headspace solid-phase microextraction method using a novel diethoxydiphenylsilane fibre based on in situ derivatization with acetic anhydride was optimized and validated for the gas chromatography-mass spectrometry determination of some monohydroxy metabolites of polycyclic aromatic hydrocarbons, namely 1-hydroxynaphthalene, 2-hydroxynaphtalene, 9-hydroxyfluorene, 2-hydroxyfluorene and 1-hydroxypyrene at trace levels in human urine. Enzymatic hydrolysis was applied before derivatization, whereas extraction conditions, i.e. the effects of time and temperature of extraction and salt addition were investigated by experimental design. Regression models and desirability functions were applied to find the experimental conditions providing the highest global extraction response. These conditions were found in correspondence of an extraction temperature of 90 degrees C, an extraction time of 90 min and 25% NaCl added to urine samples. The capabilities of the developed method were proved obtaining limit of quantitations in the 0.1-2 microg/l range, thus allowing the bio-monitoring of these compounds in human urine. A good precision was observed both in terms of intra-batch and inter-batch repeatability with RSD always lower than 14%. Recoveries ranging from 98(+/-3) to 121(+/-1)% and extraction yields higher than 72% were also obtained. Finally, the analysis of urine specimens of coke-oven workers revealed analytes' concentrations in the 2.2-164 microg/l range, proving the exposure to PAHs of the involved workers.

Urinary polycyclic aromatic hydrocarbons and monohydroxy metabolites as biomarkers of exposure in coke oven workers.

OBJECTIVES: To assess exposure to polycyclic aromatic hydrocarbons (PAHs) using 13 unmetabolised PAHs (U-PAHs) and 12 monohydroxy metabolites (OHPAHs) in urine, and to compare the utility of these biomarkers. METHODS: 55 male Polish coke oven workers collected urine spot samples after a workshift. U-PAHs (naphthalene, acenaphtylene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benzo[a]anthracene, chrysene, benzo[k]fluoranthene, benzo[b]fluoranthene, benzo[a]pyrene) were determined by automatic solid phase micro-extraction followed by gas chromatography/mass spectrometry (GC/MS). OHPAHs (1- and 2-hydroxynaphthalene, 2- and 9-hydroxyfluorene, 4-, 9-, 3-, 1- and 2-hydroxyphenanthrene, 1-hydroxypyrene, 6-hydroxychrysene, 3-hydroxybenzo[a]pyrene) were determined, after liquid/liquid extraction and derivatisation, by GC/MS. RESULTS: U-PAHs from naphthalene to chrysene were found in 100% of samples, and heavier U-PAHs in 7-22% of samples. OHPAHs up to 1-hydroxypyrene were found in 100% of samples, while 6-hydroxychrysene and 3-hydroxybenzo[a]pyrene were always below the quantification limit. Median naphthalene, phenanthrene, pyrene, chrysene and benzo[a]anthracene levels were 0.806, 0.721, 0.020, 0.032 and 0.035 microg/l, while hydroxynaphthalenes, hydroxyphenanthrenes and 1-hydroxypyrene levels were 81.1, 18.9 and 15.4 microg/l. For each chemical, the ratio between U-PAH and the corresponding OHPAH ranged from 1:26 to 1:1000. Significant correlations between logged values of U-PAHs and OHPAHs, between U-PAHs, and between OHPAHs were found, with Pearson's r ranging from 0.27 to 0.97. CONCLUSION: Current analytical techniques allow specific and simultaneous measurement of several urinary determinants of PAHs in humans. The results of these measurements support the use of U-PAHs as biomarkers of exposure and suggest the spectrum of chemicals to be investigated, including carcinogenic chrysene and benzo[a]anthracene, should be widened.

Biological monitoring and questionnaire for assessing exposure to ethylenebisdithiocarbamates in a multicenter European field study.

This study deals with pesticide exposure profile in some European countries with a specific focus on ethylenebisdithiocarbamates (EBDC). In all, 55 Bulgarian greenhouse workers, 51 Finnish potato farmers, 48 Italian vineyard workers, 42 Dutch floriculture farmers, and 52 Bulgarian zineb producers entered the study. Each group was matched with a group of not occupationally exposed subjects. Exposure data were gained through self-administered questionnaires and measuring ethylenethiourea (ETU) in two spot urine samples collected, respectively, before the beginning of seasonal exposure (T0), and after 30 days, at the end of the exposure period (T30). Controls underwent a similar protocol. Study agriculture workers were involved in mixing and loading pesticides, application of pesticide mixture with mechanical or manual equipments, re-entry activities, and cleaning equipments. Chemical workers were involved in synthesis, quality controls, and packing activities. The number of pesticides to whom these subjects were exposed varied from one (zineb production) to eight (potato farmers). The use of personal protective devices was variegate and regarded both aerial and dermal penetration routes. EBDC exposure, assessed by T30 urinary ETU, was found to follow the order: greenhouse workers, zineb producers, vineyard workers, potato farmers, floriculture farmers with median levels of 49.6, 23.0, 11.8, 7.5, and 0.9 microg/g creatinine; the last group having ETU at the same level of controls (approximately 0.5 microg/g creatinine). Among agriculture workers, pesticide application, especially using manual equipment, seems to be the major determinant in explaining internal dose. Although the analysis of self-administered questionnaires evidenced difficulties especially related to lack and/or poor quality of reported data, biological monitoring confirms to be a powerful tool in assessing pesticide exposure.