Role of telomere length in human carcinogenesis (Review).

Cancer is considered the most important clinical, social and economic issue regarding cause­specific disability­adjusted life years among all human pathologies. Exogenous, endogenous and individual factors, including genetic predisposition, participate in cancer triggering. Telomeres are specific DNA structures positioned at the end of chromosomes and consist of repetitive nucleotide sequences, which, together with shelterin proteins, facilitate the maintenance of chromosome stability, while protecting them from genomic erosion. Even though the connection between telomere status and carcinogenesis has been identified, the absence of a universal or even a cancer­specific trend renders consent even more complex. It is indicative that both short and long telomere lengths have been associated with a high risk of cancer incidence. When evaluating risk associations between cancer and telomere length, a disparity appears to emerge. Even though shorter telomeres have been adopted as a marker of poorer health status and an older biological age, longer telomeres due to increased cell growth potential are associated with the acquirement of cancer­initiating somatic mutations. Therefore, the present review aimed to comprehensively present the multifaceted pattern of telomere length and cancer incidence association.

Endocrine-Disrupting Chemicals and Persistent Organic Pollutants in Infant Formulas and Baby Food: Legislation and Risk Assessments.

Human milk is the healthiest option for newborns, although, under specific circumstances, infant formula is a precious alternative for feeding the baby. Except for the nutritional content, infant formulas and baby food must be pollutant-free. Thus, their composition is controlled by continuous monitoring and regulated by establishing upper limits and guideline values for safe exposure. Legislation differs worldwide, although there are standard policies and strategies for protecting vulnerable infants. This work presents current regulations and directives for restricting endocrine-disrupting chemicals and persistent organic pollutants in infant formulas. Risk assessment studies, which are limited, are necessary to depict exposure variations and assess the health risks for infants from dietary exposure to pollutants.

Antibiotics in Raw Meat Samples: Estimation of Dietary Exposure and Risk Assessment.

The extensive use of antibiotics in livestock farming poses increased concerns for human health as residues of these substances are present in edible tissues. The aim of this study was the determination of the levels of four groups of antibiotics (sulfonamides-SAs, tetracyclines-TCs, streptomycines-STr and quinolones-QNLs) in meat samples (muscles, livers and kidneys from beef, chicken and pork) and the estimation of the dietary exposure to antibiotics from meat consumption and the potential hazard for human health. Fifty-four samples of raw meat were randomly collected in 2018 from the Cretan market, Greece and analyzed both with an enzyme-linked immunosorbent assay (ELISA) and liquid chromatography-mass spectrometry (LC-MS). According to the results derived from the ELISA method, only 2% of the meat samples were free from antibiotics, 2% were detected with 4 antibiotics and the great majority of the samples (87%) were detected with 2 to 3 antibiotics. SAs presented the highest detection frequencies for all samples whereas TCs were not detected in any bovine sample. The highest median concentration was detected for STr in bovine muscles (182.10 µg/kg) followed by QNLs (93.36 µg/kg) in pork kidneys whereas the chicken samples had higher burdens of QNLs compared to the other meat samples. LC-MS analysis showed that oxytetracycline (OTC) was the most common antibiotic in all samples. The highest median concentration of all antibiotics was detected for doxycycline (DOX) (181.73 µg/kg in pork kidney) followed by OTC in bovine liver (74.46 µg/kg). Risk characterization was applied for each of the two methods; The hazard quotients (HQ) did not exceed 0.059 for the ELISA method and 0.113 for the LC-MS method for any group of antibiotics, whereas the total hazard indexes (HI) were 0.078 and 0.021, respectively. The results showed the presence of different groups of antibiotics in meat from the Cretan market and that the health risk to antibiotics is low. A risk assessment analysis conducted for meat consumption and corrected for the aggregated exposure revealed no risk for the consumers.

Determination of prenatal exposure to parabens and triclosan and estimation of maternal and fetal burden.

BACKGROUND: Parabens (PBs) and triclosan (TCS) are generally used as antimicrobials mostly in personal care products. Their wide prevalence in daily products raised an acute need for the biomonitoring of these contaminants and the investigation of possible health impacts. MATERIAL AND METHODS: In this study we aimed to quantitatively determine PBs and TCS levels in urine and amniotic fluid samples using a liquid chromatography - mass spectrometry system (LC-MS). Ninety nine (99) pregnant women took part in this research. The samples were collected during the amniocentesis in the early second trimester of their pregnancy. Women of all ages, education, household income and profession were selected. The exposure and the burden of pregnant women and their infants were also evaluated. RESULTS: The most prevalent compound in urine, among the analyzed, was TCS with 74.7 % positive samples while in amniotic fluid methyl paraben (MePB) with 21.2 % positive samples. MePB was detected at higher concentrations in urine (mean: 378.5 ng/mL) followed by TCS (mean: 55.3 ng/mL), ethyl paraben (EtPB) (mean: 23.2 ng/mL) and butyl paraben (BuPB) (mean: 2.3 ng/mL) while benzyl paraben (BePB) was not detected in any urine sample. Concentrations in amniotic fluid samples were much lower. In particular, the mean concentrations were 6.6 ng/mL for MePB, 9.2 ng/mL for EtPB, 0.4 ng/mL for BuPB, 0.6 ng/mL for BePB and 1.8 ng/mL for TCS. The detected levels of all analytes in urine were correlated with those in amniotic fluid but no statistically significant results arose (p >n0.05). Negative associations were observed between amniotic fluid levels of MePB and maternal age (p = 0.05) while both urinary and amniotic levels of TCS were correlated with maternal BMI (p = 0.04). Somatometric characteristics of the infants showed no statistical significant associations with the detected levels of PBs and TCS. CONCLUSION: This study indicated a strong/possible association between exposure of pregnant women to TCS and higher/lower maternal body weight gain during pregnancy. The same trend was observed between amniotic fluid MePB levels and maternal age. However, no statistically significant associations were observed between neonatal somatometric characteristics or health status and PBs and TCS levels.

Phthalate metabolites concentrations in amniotic fluid and maternal urine: Cumulative exposure and risk assessment.

Phthalates are used in industry as plasticizers or additives in everyday products and they have been considered as endocrine disrupting chemicals. Maternal exposure during pregnancy has been associated with neonatal exposure, preterm birth and impacts in the reproductive and respiratory systems. The aim of this study is to determine six phthalate metabolites (mono isobutyl phthalate, miBP, mono n-butyl phthalate, mnBP, mono benzyl phthalate, mBzP, mono ethylhexyl phthalate, mEHP, mono 2-ethyl-5-hydroxyhexyl phthalate, mEHHP, mono 2-ethyl-5-oxohexyl-phthalate, mEOHP) in amniotic fluid and urine from 100 pregnant women. Participants answered questionnaires for the use of plastics and cosmetics, dietary habits, health effects, pregnancy problems, health and infant development. Positive amniotic fluid samples ranged from 1% to 21% and urine from 27% to 54%. The median levels for amniotic fluid were 2.3 µg/L - 10.7 µg/L and for urine 4.9 µg/L - 46.7 µg/L. The major results include significant correlations between urinary phthalates indicating their common sources of exposure, the frequent use of deodorant was significantly associated with higher urinary miBP (p = 0.050) and mnBP (p = 0.028) and a weak inverse association was found for the use of make-up products with mBzP (p = 0.053). The frequent use of plastic food containers was significantly associated with urinary mEHP (p = 0.026), and a positive trend was noticed for mEHP in amniotic fluid (p = 0.093). An association although weak was found between urinary mEHP and lower birth length (rs = 0.396, p = 0.062). No other associations were found for infant health problems or development. The daily intake of the total phthalates was calculated 5.4 µg/kg body weight/day which corresponds to hazard index 0.10 and exposure follows the declining trend that has been observed the last decades.

Biomonitoring of bisphenols A and S and phthalate metabolites in hair from pregnant women in Crete.

Phthalates, bisphenols A and S (BPA, BPS) are used as plasticizers and many of them are documented or suspected of being endocrine disruptors. Several studies indicate that exposure during pregnancy may affect the newborn's health and development. The aim of this cross-sectional study is the biomonitoring of seven phthalate metabolites, BPA and BPS in hair from 100 pregnant women in Crete. The most frequently detected compounds were monoethylhexyl phthalate (mEHP) (68%), mono isobutyl phthalate (miBP) (40%), BPA (37%), BPS (34%) and mono-n-butyl phthalate (mnBP) (28%). Phthalate metabolites were detected at medians from 19.5 to 44.4 pg/mg, BPA at 69.9 pg/mg and BPS at 3.5 pg/mg. Significant positive correlations between phthalate metabolites were found which indicated their common sources of exposure. The frequent use of plastics for food storage was strongly associated with mEHP (p = .013) and a weaker association was found for miBP (p = .063). The frequent use of cosmetics during or before pregnancy was associated with levels of phthalate metabolites in hair. More specifically, the use of hair spray before pregnancy was significantly correlated with monobenzyl phthalate (mBzP) (p = .041) and a trend was found for miBP (p = .066). The use of makeup products during pregnancy was strongly associated with miBP (p = .015) and the use of deodorant during pregnancy was inversely associated with mEHP (p = .021). Strong associations came up between mEHP and lower birth weight (Spearman correlation coefficient, r = -0.302, p = .021) and exposure to BPS was associated with increased body mass index of the participants (p = .036). Although data in literature on biomonitoring of the compounds in hair are limited, the findings of this study are promising and in agreement with existing data in hair or urine.

Investigating exposure to endocrine disruptors via hair analysis of pregnant women.

The aim of this study was the monitoring of the levels of parabens (PBs) and triclosan (TCS) in head hair samples of women collected during the first months of their pregnancy. Personal details concerning somatometric and demographic characteristics, dietary habits, use of personal care products and the medical and obstetrical history of the pregnant women as well as infants' somatometric characteristics and health condition were recorded through relevant questionnaires. Ninety five hair samples were collected, extracted by solid-liquid extraction and analysed using a liquid chromatography-mass spectrometry system (LC-MS). Analysis revealed high percentage of positive samples for all tested compounds (90-100% except from BePB (15.8%)). The mean concentration levels were 4501.2 pg/mg (17.6-27,437.0 pg/mg) for MePB; 510.1 pg/mg (11.0-4224.5 pg/mg) for EtPB; 22.9 pg/mg (2.1-66.6 pg/mg) for BePB; 237.1 pg/mg (1.8-2513.7 pg/mg) for BuPB and 245.0 pg/mg (8.8-8070.2 pg/mg) for TCS. Statistical analysis of both analytical results and questionnaires' data showed that the frequent use of personal care and hygiene products, such as makeup, hairspray and sunscreens, is correlated with higher levels of PBs in hair of the pregnant women. Additionally, positive correlation was observed between the BePB levels in hair and the infants' height. Finally, no other correlation was observed between endocrine disruptors' levels in maternal hair and infants' somatometric characteristics or health condition. Our study is the first one that determined PBs and TCS levels in hair samples, simultaneously. At the same time, correlation of the detected levels with the use of personal care products was accomplished, leading to significant association of BePB levels in hair of pregnant women with infants' height.

Estimation of daily intake and risk assessment of organophosphorus pesticides based on biomonitoring data - The internal exposure approach.

Human exposure to pesticides can be estimated through different approaches. The approach adopted in this study is based on internal dose measures. Studies published during 2001 and 2017 were collected from PubMed and Scopus databases, filtered and organized. The intake of parent compounds is estimated based on the urinary excretion of different OP metabolites applying a mathematical model previously used for similar purposes. Once defined an Estimated Daily Intake (EDI), risk assessment is performed through comparison with specific guideline values and hazard index (HI) is calculated to assess cumulative health risk. The EDI was expressed as malathion, diazinon, parathion, phorate and dimethoate equivalents. Differences in exposure between pregnant women, general population, children and farmers are highlighted and exposures are presented by country and sampling year. Higher exposure to OPs was calculated for farmers, followed by children whereas pregnant women were less exposed. Median HQ values for children ranged between 0.016 and 0.618, for pregnant women 0.005-0.151, for general population 0.008-0.206 and for farmers 0.009-0.979. Combined exposure to dimethoate and phorate was the worst-case scenario. The annual distribution of the urinary DAPs showed that exposure to OPs since 1998 tends to be stable for both children and adults.

Biomonitoring of bisphenol A, triclosan and perfluorooctanoic acid in hair samples of children and adults.

Bisphenol A (BPA), triclosan (TCS) and perfluorooctanoic acid (PFOA) are endocrine disruptors linked with negative health effects such as developmental, reproductive and cardiovascular toxicity. The aim of this study was to determine simultaneously the concentration of BPA, TCS and PFOA in hair from children and adults and examine possible associations between biomonitoring data and age, gender, dietary habits and body mass index. Methanolic extraction was applied and the compounds were determined by liquid chromatography-mass spectrometry. Low levels of exposure to PFOA were detected for children and adults at concentrations below limit of quantification. The mean concentration of BPA in children and adults was 20.6 and 16.6 pg mg-1 , while for TCS 275.2 and 687.0 pg mg-1 , respectively. Children were highly exposed to BPA relative to adults (P = .011) although adults had greater exposure to TCS (P = .003). Hair from girls had a greater burden of BPA (P = .06) compared to boys. Moreover, higher TCS levels were depicted for females in both examined groups (children P = .200 and adults P = .213) compared to males, but no statistical differences were observed. Significant differences were also observed between age groups (P = .0007) for TCS. No correlations were found between BPA or TCS levels and body mass index or dietary habits for both children and adults. Children have a greater exposure to BPA compared to adults, whereas exposure of adults to TCS seems to be higher than that in children and elderly people. Exposure to BPA occurs mainly via ingestion whereas exposure to TCS mainly via dermal absorption.

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.