Lactational exposure to phthalates in Southern Italy

BackgroundPhthalates, reproductive toxicants in animals, are synthetic chemicals with ubiquitous human exposures because of their extensive use, with potential detrimental health effects. Infants are considered to represent a population at increased risk, as they are exposed early in life to several different sources of exposure to phthalates.Objectives and methodsLittle information exists on phthalate exposure through breast milk from different geographic areas. By means of a LC/LC–MS/MS method we tested the presence of several different phthalate metabolites in breast milk from 62 healthy mothers living in Southern Italy.ResultsThe simple monoesters mono-isobutyl phthalate (MiBP) (median 18.8 μg/l) and mono(2-ethylhexyl) phthalate (MEHP) (median 8.4 μg/l) were present in all milk samples, whereas mono-n-butyl phthalate (MnBP) (median 1.5 μg/l) and mono-benzyl phthalate (MBzP) (median < 0.3 μg/l) were found in 64.5% and 43.5% of the samples, respectively. Among the oxidative metabolites of DEHP and DiNP only mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP) and monoisononyl phthalate with one hydroxyl group (OH-MiNP) were detectable in one and 13 samples (21%), respectively.ConclusionsThese findings indicate that exposure to phthalates through breast milk in Southern Italian infants is comparable to that of other countries, thus confirming that human milk may represent an additional potential source of phthalate exposure in a population at increased risk. However, different milk concentrations of MiBP may suggest a different pattern of usage of di-iso-butyl phthalate in Europe, as compared to USA, whereas for the first time, we detected an oxidative DiNP metabolite, whose significance remains unclear.     

Association between prenatal exposure to phthalates and the health of newborns

Phthalates are developmental and reproductive toxicants for the fetus in pregnant rodents, and the ability of phthalates to penetrate the placenta have been reported. The aims of this study were to evaluate the association between maternal urine excretion, the exposure of fetus to phthalates in amniotic fluid, and the health of newborns. Amniotic fluid and urine samples from pregnant women were collected to measure five phthalate monoesters using liquid chromatography/tandem mass spectrometry (LC/MS-MS) and the newborns' birth weight, gestational age, and anogenital distance (AGD) were collected. The median levels of three phthalate monoesters in urine and amniotic fluid were 78.4 and 85.2 ng/mL monobutyl phthalate (MBP); 24.9 and 22.8 ng/mL mono-(2-ethylhexyl) phthalate (MEHP); 19.8 and Not Detected monoethyl phthalate (MEP). We found a significant positive correlation only between creatinine adjusted urinary MBP and amniotic fluid MBP (R(2)=0.156, p<0.05) in all infants and, only in female infants, a significantly negative correlation between amniotic fluid MBP, AGD (R=-0.31, p<0.06), and the anogenital index adjusted by birth weight (AGI-W) (R=-0.32, p<0.05). Although the influence of prenatal di-n-butyl phthalate (DBP) exposure on the endocrinology and physiology of the fetus is still a puzzle, our data clearly show that in utero exposure to phthalates in general has anti-androgenic effects on the fetus.     

The effects of phthalates in the cardiovascular and reproductive systems: A review

Every year millions of tons of plastic are produced around the world and humans are increasingly exposed to them. This constant exposure to plastics has raised some concerns against human health, particularly when it comes to phthalates. These compounds have endocrine-disrupting properties, as they have the ability to bind molecular targets in the body and interfere with hormonal function and quantity. The main use of phthalates is to give flexibility to polyvinyl chloride (PVC) polymers. Phthalates are found in a variety of industrial and consumer products, and as they are not covalently bound to the plastic, phthalates contaminate the environment from which human exposure occurs. Studies in human and animal populations suggest a correlation between phthalate exposure and adverse health outcomes, particularly at the reproductive and cardiovascular systems, however there is much less information about the phthalate toxicity of the later. Thus, the main purpose of this review is to present the studies relating the effects already stated of phthalates on the cardiovascular and reproductive systems, and also present the link between these two systems.     

Multimycotoxin analysis in urines to assess infant exposure: A case study in Cameroon

This study was conducted to investigate mycotoxin exposure in children (n = 220, aged 1.5–4.5 years) from high mycotoxin contamination regions of Cameroon and to examine the association between the mycotoxin levels (in total 18 analytes) and several socio-demographic factors and anthropometric characteristics. A cross-sectional study was conducted in six villages in Cameroon with 220 children. Mycotoxins and their metabolites were detected in 160/220 (73%) urine samples.There were significant differences in the mean contamination levels of ochratoxin A (p = 0.01) and β-zearalenol (p = 0.017) between the two agro-ecological zones investigated. Likewise significant differences were observed in the mean levels of aflatoxin M₁ (p = 0.001) across the weaning categories of these children. The mean concentration of aflatoxin M₁ detected in the urine of the partially breastfed children (1.43 ng/mL) was significantly higher (p = 0.001) than those of the fully weaned children (0.282 ng/mL).Meanwhile, the mean concentrations of deoxynivalenol (3.0 ng/mL) and fumonisin B₁ (0.59 ng/mL) detected in the urine of the male children was significantly (p value 0.021 for deoxynivalenol and 0.004 for fumonisin B₁) different from the levels detected in the urine of female children; 0.71 ng/mL and 0.01 ng/mL for deoxynivalenol and fumonisin B₁ respectively. In this study, there was no association between the different malnutrition categories (stunted, wasting and underweight) and the mycotoxin concentrations detected in the urine of these children.However, there is sufficient evidence to suggest that children in Cameroon under the age 5 are exposed to high levels of carcinogenic substances such as fumonisin B₁, aflatoxin M₁ and ochratoxin A through breastfeeding. To the best of our knowledge, this is the first report of its kind carried out in West Africa to determine multi-mycotoxin exposure in infants.     

Characterisation of human exposure pathways to perfluorinated compounds--comparing exposure estimates with biomarkers of exposure

Commercially used per- and polyfluorinated compounds (PFCs) have been widely detected in humans, but the sources of human exposure are not fully characterized. The objectives of this study were to assess the relative importance of different exposure pathways of PFCs in a group of Norwegians and compare estimated intakes with internal doses obtained through biomonitoring. Individual PFC intakes from multiple exposure sources for a study group of 41 Norwegian women were estimated using measured PFC concentrations in indoor air and house dust as well as information from food frequency questionnaires and PFC concentrations in Norwegian food. Food was generally the major exposure source, representing 67-84% of the median total intake for PFOA and 88-99% for PFOS using different dust ingestion rates and biotransformation factors of 'precursor' compounds. However, on an individual basis, the indoor environment accounted for up to around 50% of the total intake for several women. Significant positive associations between concentrations of PFCs in house dust and the corresponding serum concentrations underline the importance of indoor environment as an exposure pathway for PFCs. For breast-fed infants, breast milk was calculated to be the single most important source to PFCs by far. The estimated intakes were confirmed by comparing serum concentrations of PFOA and PFOS calculated using PK models, with the corresponding concentrations measured in serum. Even though food in general is the major source of exposure for PFCs, the indoor environment may be an important contributor to human exposure. This study provides valuable knowledge for risk assessment of PFCs and control strategies.     

Occupational exposure to pesticides and Parkinson's disease: A systematic review and meta-analysis of cohort studies

ObjectivesTo systematically review available cohort studies and estimate quantitatively the association between occupational exposure to pesticides and Parkinson's disease (PD).MethodsStudies were identified from a MEDLINE search through 30 November 2011 and from the reference lists of identified publications. Relative risk (RR) estimates were extracted from 12 studies published between 1985 and 2011. Meta-rate ratio estimates (mRR) were calculated according to fixed and random-effect meta-analysis models. Meta-analyses were performed on the whole set of data and separate analyses were conducted after stratification for gender, exposure characterisation, PD cases identification, geographic location, reported risk estimator and cohort study design.ResultsA statistically significant increased risk of PD was observed when all studies were combined (mRR = 1.28; 95% confidence interval [CI]: 1.03–1.59) but there was a high heterogeneity and inconsistency among studies. The highest increased risks were observed for studies with the best design, i.e. reporting PD diagnosis confirmed by a neurologist (mRR = 2.56; CI: 1.46–4.48; n = 4), for cohort studies reporting incidence of PD (mRR = 1.95; CI: 1.29–2.97; n = 3) as well as for prospective cohorts (mRR = 1.39; CI: 1.09–1.78; n = 6). A significant increased risk was also seen for banana, sugarcane and pineapple plantation workers (mRR = 2.05; CI: 1.23–3.42; n = 2).ConclusionsThe present study provides some support for the hypothesis that occupational exposure to pesticides increases the risk of PD.     

Considerable exposure to the endocrine disrupting chemicals phthalates and bisphenol-A in intensive care unit (ICU) patients

Critical care medicine has largely benefited from plastic-containing medical devices. However, bisphenol-A (BPA) and phthalates present in the plastics can leach from such devices. We hypothesized that intensive care unit (ICU) patients are exposed to BPA and phthalates through (plastic) medical devices. Serum (n = 118) and urine (n = 102) samples of adult ICU patients (n = 35) were analyzed for total BPA and phthalate metabolites (PMs). Our results showed that adult ICU patients are continuously exposed to phthalates, such as di(2-ethylhexyl)phthalate (DEHP), as well as to BPA, albeit to a lesser extent. This exposure resulted in detectable high serum and urinary levels in almost every patient and at every studied time point. Moreover, these levels were significantly higher than in controls or compared to referenced literature. The chronology of exposure was demonstrated: pre-operative urinary and serum levels of the DEHP metabolites were often below the detection limit. Plastic-containing medical devices were the main source of DEHP exposure: post-operative patients on hemofiltration, extracorporeal membrane oxygenation or both showed serum levels 100-or 1000-fold higher than the levels in the general population reported in the literature. The serum and some of the urinary levels of the DEHP metabolites are the highest ever reported in humans; some at biologically highly relevant concentrations of ≥ 10–50 μM. Despite the continuously tightening regulations, BPA and DEHP appear to be still present in (some) medical devices. Because patient safety is a concern in the ICU, further research into the (possibly toxic and clinical) effects of these chemicals released from medical devices is imperiously necessary.     

A global assessment of phthalates burden and related links to health effects

Phthalates are ubiquitous environmental contaminants which are used in industry as plasticizers and additives in cosmetics. They are classified as Endocrine Disrupting Chemicals (EDCs) which impair the human endocrine system inducing fertility problems, respiratory diseases, childhood obesity and neuropsychological disorders. The aim of this review is to summarize the current state of knowledge on the toxicity that phthalates pose in humans based on human biomonitoring studies conducted over the last decade. Except for conventional biological matrices (such as urine and serum), amniotic fluid, human milk, semen, saliva, sweat, meconium and human hair are also employed for the estimation of exposure and distribution of pollutants in the human body, although data are not enough yet. Children are highly exposed to phthalates relative to adults and in most studies children's daily intake surpasses the maximum reference dose (RfD) set from US Environmental Protection Agency (US EPA). However, the global trend is that human exposure to phthalates is decreasing annually as a result of the strict regulations applied to phthalates.     

Urinary methyl tert-butyl ether and benzene as biomarkers of exposure to urban traffic

Methyl tert-butyl ether (MTBE) and benzene are added to gasoline to improve the combustion process and are found in the urban environment as a consequence of vehicular traffic. Herein we evaluate urinary MTBE (MTBE-U) and benzene (BEN-U) as biomarkers of exposure to urban traffic. Milan urban policemen (130 total) were investigated in May, July, October, and December for a total of 171 work shifts. Personal exposure to airborne benzene and carbon monoxide (CO), and atmospheric data, were measured during the work shift, while personal characteristics were collected by a questionnaire. A time/activity diary was completed by each subject during the work shift. Spot urine samples were obtained for the determination of MTBE-U and BEN-U. Median personal exposure to CO and airborne benzene were 3.3 mg/m(3) and 9.6 μg/m(3), respectively; median urinary levels in end-of-shift (ES) samples were 147 ng/L (MTBE-U) and 207 ng/L (BEN-U). The time spent on traffic duty at crossing was about 40% of work time. Multiple linear regression models, taking into account within-subject correlations, were applied to investigate the role of urban pollution, atmospheric conditions, job variables and personal characteristics on the level of biomarkers. MTBE-U was influenced by the month of sampling and positively correlated to the time spent in traffic guarding, CO exposure and atmospheric pressure, while negatively correlated to wind speed (R(2) for total model 0.63, P<0.001). BEN-U was influenced by the month and smoking habit, and positively correlated to urinary creatinine; moreover, an interaction between CO and smoking was found (R(2)=0.62, P<0.001). These results suggest that MTBE-U is a reliable marker for assessing urban traffic exposure, while BEN-U is determined mainly by personal characteristics.     

Dietary exposure to cadmium and risk of breast cancer in postmenopausal women: A systematic review and meta-analysis

BackgroundWith tobacco smoking, diet is the main source of cadmium (Cd) exposure in the general population. The carcinogenic and estrogenic activities of Cd make it a contaminant of potential concern for hormone-dependent cancers including breast cancer. Postmenopausal women represent the most appropriate population to investigate the possible impact of exogenous factors with potential estrogenic activity on breast cancer as, after menopause, their estrogenic influence is predominant.ObjectivesWe systematically reviewed available studies on the association between dietary exposure to Cd and breast cancer focusing on postmenopausal women. A meta-analysis combining the risk estimators was performed and potential sources of between studies heterogeneity were traced.MethodsStudies were searched from MEDLINE through 31 January 2015 and from the reference lists of relevant publications. Six eligible studies published between 2012 and 2014 were identified and relative risk estimates were extracted. Meta-rate ratio estimates (mRR) were calculated according to fixed and random-effect models. Meta-analyses were performed on the whole set of data and separate analyses were conducted after stratification for study design, geographic location, use of hormone replacement therapy (HRT), tumor estrogen receptor status (ER + or ER −), progesterone receptor status (PGR + or PGR −), body mass index (BMI), smoker status, zinc or iron intake.ResultsNo statistically significant increased risk of breast cancer was observed when all studies were combined (mRR = 1.03; 95% confidence interval [CI]: 0.89–1.19). Several sources of heterogeneity and inconsistency were identified, including smoker status, HRT use, BMI, zinc and iron intake. Inconsistency was also strongly reduced when only considering ER −, PGR −, tumors subgroups from USA and from Japan. The risks were, however, not substantially modified after stratifications. No evidence of publication bias was found.ConclusionThe present study does not provide support for the hypothesis that dietary exposure to Cd increases the risk of breast cancer in postmenopausal women. Misclassification in dietary Cd assessment in primary studies could have biased the results towards a finding of no association.     

Urinary polycyclic aromatic hydrocarbon metabolites as biomarkers of exposure to traffic-emitted pollutants

1-Nitro-pyrene has been considered a compound specific to diesel combustion emission, while 1- and 2-nitro-napthalene are mainly produced through photochemical conversion of naphthalene released to the atmosphere. Metabolites of these compounds may serve as biomarkers of exposure to traffic related pollutants. We collected urine samples from 111 healthy and non-smoking subjects within (i.e., during the Beijing Olympics) and outside (i.e., before and after the Olympics) a traffic control regime to improve Beijing's air quality. Urines were analyzed for the sum of 1&2-amino-naphthalene (metabolites of 1- and 2-nitro-naphthalene) and 1-amino-pyrene (a metabolite of 1-nitro-pyrene), using an HPLC-fluorescence method. Within the same time periods, PM_2.5 mass and constituents were measured, including elemental carbon, sulfate, nitrate, PAHs, carbon monoxide, nitrogen dioxide, sulfur dioxide, ozone, and particle number concentrations. The associations between the urinary metabolites and air pollutants were analyzed using linear mixed-effects models. From the pre- to during-Olympic period, 1&2-amino-naphthalene and 1-hydroxy-pyrene decreased by 23% (p = 0.066) and 16% (p = 0.049), respectively, while there was no change in 1-amino-pyrene (2% increase, p = 0.892). From during- to post-Olympic period, 1&2-amino-naphthalene, 1-amino-pyrene and 1-hydroxy-pyrene concentrations increased by 26% (p = 0.441), 37% (p = 0.355), and 3% (p = 0.868), respectively. Furthermore, 1&2-amino-naphthalene and 1-hydroxy-pyrene were associated with traffic related pollutants in a similar lag pattern. 1-amino-pyrene was associated more strongly with diesel combustion products (e.g. PN and elemental carbon) and not affected by season. Time-lag analyses indicate strongest/largest associations occurred 24–72 h following exposure. 1&2-amino-naphthalene and 1-hydroxy-pyrene can be used as a biomarker of exposure to general vehicle-emitted pollutants. More data are needed to confirm 1-amino-pyrene as a biomarker of exposure to diesel combustion emissions. Controlling creatinine as an independent variable in the models will provide a moderate adjusting effect on the biomarker analysis.     

A review on human exposure to brominated flame retardants--particularly polybrominated diphenyl ethers

Brominated flame retardants (BFRs) have been and are still heavily used as additive or reactive chemicals in polymers and textiles. Only a few of the BFRs have been assessed in human subjects with a major data set on internal exposures to polybrominated diphenyl ethers (PBDEs). Increasing PBDE levels have been observed in mothers' milk from Sweden as well as in blood from Germany and Norway. The levels are in general lower than PCB levels. However, the PBDE concentrations found in the North Americans are considerably higher compared to European subjects. The PBDEs are dominated by 2,2',4,4'-tetrabromodiphenyl ether (BDE-47). Decabromodiphenyl ether (BDE-209) is reported both in the general population and in occupationally exposed persons showing the bioavailability of this high molecular weight compound. While the lower and medium brominated diphenyl ethers are persistent, BDE-209 has a fairly short half-life of approximately 2 weeks. Tetrabromobisphenol A (TBBPA) is readily eliminated in humans showing a half-life of about 2 days. Still, TBBPA is accumulated in humans but a continuous exposure to this BFR is required to maintain a certain level in the human subject. TBBPA has not been detected in the general population but in people exposed at work. The current review addresses human exposure routes and levels of BFRs.     

Association of modeled long-term personal exposure to ultrafine particles with inflammatory and coagulation biomarkers

BackgroundLong-term exposure to fine particulate matter has been linked to cardiovascular disease and systemic inflammatory responses; however, evidence is limited regarding the effects of long-term exposure to ultrafine particulate matter (UFP, < 100 nm). We used a cross-sectional study design to examine the association of long-term exposure to near-highway UFP with measures of systemic inflammation and coagulation.MethodsWe analyzed blood samples from 408 individuals aged 40–91 years living in three near-highway and three urban background areas in and near Boston, Massachusetts. We conducted mobile monitoring of particle number concentration (PNC) in each area, and used the data to develop and validate highly resolved spatiotemporal (hourly, 20 m) PNC regression models. These models were linked with participant time-activity data to determine individual time-activity adjusted (TAA) annual average PNC exposures. Multivariable regression modeling and stratification were used to assess the association between TAA-PNC and single peripheral blood measures of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor-necrosis factor alpha receptor II (TNFRII) and fibrinogen.ResultsAfter adjusting for age, sex, education, body mass index, smoking and race/ethnicity, an interquartile-range (10,000 particles/cm³) increase in TAA-PNC had a positive non-significant association with a 14.0% (95% CI: − 4.6%, 36.2%) positive difference in hsCRP, an 8.9% (95% CI: − 0.4%, 10.9%) positive difference in IL-6, and a 5.1% (95% CI: − 0.4%, 10.9%) positive difference in TNFRII. Stratification by race/ethnicity revealed that TAA-PNC had larger effect estimates for all three inflammatory markers and was significantly associated with hsCRP and TNFRII in white non-Hispanic, but not East Asian participants. Fibrinogen had a negative non-significant association with TAA-PNC.ConclusionsOur findings suggest an association between annual average near-highway TAA-PNC and subclinical inflammatory markers of CVD risk.     

Pesticides exposure in Pakistan: a review

This is the first systematic review of studies done since 1960, and to give an integrated picture of pesticides exposure to humans, animals, plants, waters, soils/sediments, atmosphere etc. in Pakistan. Authors have extracted data from different departments, published literature in research journals and National reports. Although the wide-spread usage of pesticides in Pakistan has controlled the pests, but like other countries, it has started causing environmental problems in the area. In some areas of Punjab and Sindh groundwater has been found contaminated and is constantly being under the process of contamination due to pesticide use. There is considerable evidence that farmers have overused and misused pesticides especially in cotton-growing areas. It is evident from the biological monitoring studies that farmers are at higher risk for acute and chronic health effects associated with pesticides due to occupational exposure. Furthermore, the intensive use of pesticides (higher sprays more than the recommended dose) in cotton areas involves a special risk for the field workers, pickers, and of an unacceptable residue concentration in cottonseed oil and cakes. The authors have also discussed the merits and demerits of different studies. The review will set the future course of action of different studies on pesticide exposure in Pakistan. Data limitations are still the major obstacle towards establishing clear environmental trends in Pakistan. The authors suggest that a reliable monitoring, assessment and reporting procedures shall be implemented in accordance with appropriate environmental policies, laws and regulations in order to minimize the pesticides exposure.     

Spirometric tests to assess the prevalence of childhood asthma at Portuguese rural areas: influence of exposure to high ozone levels

The study here reported aimed to: i) evaluate the prevalence of childhood asthma at a Portuguese rural area with high ozone concentrations through lung function tests, validating the previously estimated one assessed through questionnaires (similar to those of the ISAAC); ii) compare the achieved prevalence with the one reported at an unexposed area (with low ozone concentrations), aiming to evaluate the influence of exposure to high ozone levels; and iii) determine potential risk factors. Ninety-five of the original 478 children that completed the questionnaires, mentioned to have at least one of asthma symptoms (wheeze, dyspnea or cough) and were therefore evaluated by spirometry. FEV(1) was in average 89.7% for asthmatics and 102.8% for non-asthmatics. For the studied sample the risk was higher for girls with a tendency to be higher from 8 to 10 years old. Lifetime prevalence of childhood asthma at the exposed area was 9.2%. Children living at the exposed area had 3 times higher risk of having asthma than those living at the unexposed area. Considering that ozone concentrations were the main difference between both areas, it can be suggested that ozone pollution increased asthma prevalence. Nevertheless, it should be remarked that further studies should be done to confirm these results.     

Selenium and exposure to fibrogenic mineral dust: A mini-review

Individuals exposed to fibrogenic mineral dust may exhibit an impaired antioxidant system and produce high levels of reactive oxygen and nitrogen species through immune cells, contributing to the perturbation of immune cell function, inflammation, fibrosis and lung cancer. The lung diseases which are caused by inhalation of fibrogenic mineral dust, known as pneumoconioses, develop progressively and irreversibly over decades. At the moment there is no known cure. The trace element selenium has potent antioxidant and anti-inflammatory properties mediated mainly through selenoproteins. Research has demonstrated that selenium has the ability to protect against cardiovascular diseases; to kill cancer cells in vitro and reduce cancer incidence; and to immunomodulate various cellular signaling pathways. For these reasons, selenium has been proposed as a promising therapeutic agent in oxidative stress associated pathology that in theory would be beneficial for the prevention or treatment of pneumoconioses such as silicosis, asbestosis, and coal worker's pneumoconiosis. However, studies regarding selenium and occupational lung diseases are rare. The purpose of this study is to conduct a mini-review regarding the relationship between selenium and exposure to fibrogenic mineral dust with emphasis on epidemiological studies. We carried out a systematic literature search of English published studies on selenium and exposure to fibrogenic mineral dust. We found four epidemiological studies. Reviewed studies show that selenium is lower in individuals exposed to fibrogenic mineral dust. However, three out of the four reviewed studies could not confirm cause-and-effect relationships between low selenium status and exposure to fibrogenic mineral dust. This mini-review underscores the need for large follow-up and mechanistic studies for selenium to further elucidate its therapeutic effects.