Baseline blood trihalomethanes,semen parameters and serum total testosterone: A cross-sectional study in China

Toxicological studies showed that trihalomethanes (THMs), the most abundant classes of disinfection by-products (DBPs) in drinking water, impaired male reproductive health, but epidemiological evidence is limited and inconsistent. This study aimed to examine the associations of baseline blood THMs with semen parameters and serum total testosterone in a Chinese population. We recruited 401 men seeking semen examination from the Reproductive Center of Tongji Hospital in Wuhan, China between April 2011 and May 2012. Baseline blood concentrations of THMs, including chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) were measured using SPME-GC/ECD method. Semen quality and serum total testosterone were analyzed. Multivariable linear regressions were used to assess the associations of baseline blood THM concentrations with semen parameters and serum total testosterone levels. We found that baseline blood THM concentrations were not associated with decrements in sperm motility, sperm straight-line and curvilinear velocity. However, moderate levels of BDCM (β = − 0.13 million; 95% CI: − 0.22, − 0.03) and DBCM (β = − 4.74%; 95% CI: − 8.07, − 1.42) were associated with decreased sperm count and declined sperm linearity compared with low levels, respectively. Suggestive dose–response relationships were also observed between elevated blood TCM or ∑ THMs (sum of TCM, BDCM, DBCM and TBM) concentration and decreased sperm concentration (both p for trend = 0.07), and between elevated blood DBCM concentration and decreased serum total testosterone (p for trend = 0.07). Our results indicate that elevated THM exposure may lead to decreased sperm concentration and serum total testosterone. However, the effects of THM exposure on male reproductive health still warrant further studies in humans.     

Sorption of trihalomethanes in foods

Trihalomethanes (THMs, namely, CHCl₃, CHCl₂Br, CHClBr₂ and CHBr₃) are disinfection by-products that are present in drinking water. These toxic chemicals are also present in meat, dairy products, vegetables, baked goods, beverages and other foods, although information regarding their concentrations and origin is very limited. This study investigates sorption of THMs occurring during rinsing and cooking of foods and the significance of food as an exposure source.Initial estimates of THM uptake were measured in experiments representing rinsing with tap water at 25 C using nine types of food, and for cooking in tap water at 90 C for fourteen other foods. A subset of foods was then selected for further study over a range of THM concentrations (23.7–118.7 μg/l), temperatures (25 C and 90 C), food concentrations (0.2–1.4, food weight: water weight), and contact times (5–240 min). Data were analyzed using regression and exponential models, and diffusion models were used to help explain the trends of THM uptake.Among vegetables, sorbed THM concentrations at 25 C were 213 to 774 ng/g for CHCl₃, 53 to 609 ng/g for CHCl₂Br, and 150–845 ng/g for CHClBr₂. Meats at 90 C tended to have higher concentrations, e.g., 870–2634 ng/g for CHCl₃. Sorbed concentrations increased with contact time and THM concentration, and decreased with food concentration in rinsing tests (using spinach, iceberg-head lettuce and cauliflower) and cooking tests (using tomato, potato, beef and miso–tofu soup). For most foods, THM uptake was diffusion limited and several hours were needed to approach steady-state levels. Swelling, hydrolysis and other physical and chemical changes in the food can significantly affect sorption. Screening level estimates for CHCl₃ exposures, based on experimental results and typical food consumption patterns, show that uptake via foods can dominate that due to direct tap water consumption, suggesting the importance of sorption and the need for further evaluation of THM intake due to foods.     

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.     

Preliminary study of children's exposure to PAHs and its association with 8-hydroxy-2′-deoxyguanosine in Guangzhou,China

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous air pollutants generated mainly from incomplete combustion such as automobile exhaust and cigarette smoke. Oxidative stress is believed to be involved in carcinogenesis, and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) was used as the biomarker to assess such DNA damage. The children's urinary PAH metabolite (OH-PAHs) level were explored in Guangzhou and their associations with 8-OHdG. Two groups of subjects were selected: (1) one group (n = 39, 6–7 years old) from an elementary school situated near a heavy traffic road (polluted area) and (2) another group (n = 35, 4–6 years old) from a kindergarten situated in a corner of the main campus of a big university (non-polluted area). Urinary 8-OHdG and nine urinary monohydroxylated PAH metabolites were measured, including 2-hydroxynaphthalene (2-OHN), 2-hydroxyfluorene (2-OHF), 2-, 3-, 4-, 9-hydroxyphenanthrene (2-, 3-, 4-, 9-OHPhe), 1-hydroxypyrene (1-OHP), 6-hydroxychrysene (6-OHChr) and 3-hydroxybenzo(a)pyrene (3-OHBaP). All other PAH metabolites were detected in urine samples from both children groups except for 6-OHChr and 3-OHBaP. Levels of 2-OHN, 2-OHF, 3-OHPhe, 9-OHPhe and 1-OHP were significantly different between two groups (P < 0.05, T-test). The elementary school children from the polluted area had higher urinary levels of 2-OHN, 2-OHF, 2-, 3-, 4-OHPhe and 1-OHP ((9.10 ± 7.39, 3.72 ± 2.91, 0.32 ± 0.50, 0.37 ± 0.28, 0.23 ± 0.29 and 0.64 ± 0.07 μmol/mol creatinine, respectively) than those from the control group. The results suggested that heavy traffic pollution led to higher PAH body burden. There existed no significant difference for urinary 8-OHdG concentration between two groups (p > 0.05, T-test), and no strong correlations between the individual OH-PAHs and 8-OHdG. However, the urinary 8-OHdG concentration in the elementary school children from the traffic polluted area was slightly higher than those in the non-polluted area (20.87 ± 14.42 μmol/mol creatinine vs. 16.78 ± 13.30 μmol/mol creatinine). It may be that the potential co-exposure of the children to other pollutants affects 8-OHdG concentration besides the PAHs.     

Associations between polycyclic aromatic hydrocarbon (PAH) exposure and oxidative stress in people living near e-waste recycling facilities in China

Emission of polycyclic aromatic hydrocarbons (PAHs) from e-waste recycling activities in China is known. However, little is known on the association between PAH exposure and oxidative damage to DNA and lipid content in people living near e-waste dismantling sites. In this study, ten hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and two biomarkers [8-hydroxy-2′-deoxyguanosine (8-OHdG) and malondialdehyde (MDA)] of oxidative stress were investigated in urine samples collected from people living in and around e-waste dismantling facilities, and in reference population from rural and urban areas in China. The urinary levels of ∑₁₀OH-PAHs determined in e-waste recycling area (GM: 25.4 μg/g Cre) were significantly higher (p < 0.05) than those found in both rural (11.7 μg/g Cre) and urban (10.9 μg/g Cre) reference areas. The occupationally exposed e-waste workers (36.6 μg/g Cre) showed significantly higher (p < 0.01) urinary Σ₁₀OH-PAHs concentrations than non-occupationally exposed people (23.2 μg/g Cre) living in the e-waste recycling site. The differences in urinary Σ₁₀OH-PAHs levels between smokers (23.4 μg/g Cre) and non-smokers (24.7 μg/g Cre) were not significant (p > 0.05) in e-waste dismantling sites, while these differences were significant (p < 0.05) in rural and urban reference areas; this indicated that smoking is not associated with elevated levels of PAH exposure in e-waste dismantling site. Furthermore, we found that urinary concentrations of Σ₁₀OH-PAHs and individual OH-PAHs were significantly associated with elevated 8-OHdG, in samples collected from e-waste dismantling site; the levels of urinary 1-hydroxypyrene (1-PYR) (r = 0.284, p < 0.01) was significantly positively associated with MDA. Our results indicate that the exposure to PAHs at the e-waste dismantling site may have an effect on oxidative damage to DNA among selected participants, but this needs to be validated in large studies.     

Urinary concentrations of organophosphate and carbamate pesticides in residents of a vegetarian community

Few population studies have measured urinary levels of pesticides in individuals with vegan, vegetarian, or organic diets. The objectives of this study were to evaluate whether a vegan/vegetarian diet was associated with increased exposure to organophosphate and carbamate pesticides, and to evaluate the impact of organic consumption on pesticide exposure in vegans and vegetarians. In the current pilot study conducted in 2013–2014, we collected spot urine samples and detailed 24 h recall dietary data in 42 adult residents of Amirim, a vegetarian community in Northern Israel. We measured urinary levels of non-specific organophosphate pesticide metabolites (dialkylphosphates, (DAPs)) and specific metabolites of the current-use pesticides chlorpyrifos (3,5,6-trichloro-2-pyridinol (TCPy)), propoxur (-isopropoxyphenol (IPPX)), and carbaryl (1-naphthol). Six DAP metabolites were detected in between 67 and 100% of urine samples, with highest geometric mean concentrations for dimethylphosphate (19.2 μg/g). Creatinine-adjusted median concentrations of total DAPs and of TCPy were significantly higher in Amirim residents compared to the general Jewish population in Israel (0.29 μmol/g compared to 0.16, p < 0.05 for DAPs and 4.32 μg/g compared to 2.34 μg/g, p < 0.05 for TCPy). Within Amirim residents, we observed a positive association between vegetable intake and urinary TCPy levels (rho = 0.47, p < 0.05) and lower median total dimethyl phosphate levels in individuals reporting that > 25% of the produce they consume is organic (0.065 μmol/L compared to 0.22, p < 0.05). Results from this pilot study indicate relatively high levels of urinary organophosphate pesticide metabolite concentrations in residents of a vegetarian community, a positive association between vegetable intake and urinary levels of a chlorpyrifos specific metabolite, and lower levels of total dimethyl phosphate in individuals reporting higher intake of organic produce. Results suggest that consumption of organic produce may offer some protection from increased exposure to organophosphate pesticide residues in vegetarians.     

Predictors of exposure to organophosphate pesticides in schoolchildren in the Province of Talca,Chile

BackgroundFew data exist in Latin America concerning the association between organophosphate (OP) urinary metabolites and the consumption of fruits and vegetables and other exposure risk variables in schoolchildren.MethodsWe collected samples of urine from 190 Chilean children aged 6–12 years, fruits and vegetables, water and soil from schools and homes, and sociodemographic data through a questionnaire. We measured urinary dialkylphosphate (DAP) OP metabolites and OP pesticide residues in food consumed by these 190 children during two seasons: December 2010 (summer) and May 2011 (fall). We analyzed the relationship between urinary DAP concentrations and pesticide residues in food, home pesticide use, and residential location.ResultsDiethylalkylphosphates (DEAP) and dimethylalkylphosphates (DMAP) were detected in urine in 76% and 27% of the samples, respectively. Factors associated with urinary DEAP included chlorpyrifos in consumed fruits (p < 0.0001), urinary creatinine (p < 0.0001), rural residence (p = 0.02) and age less than 9 years (p = 0.004). Factors associated with urinary DMAP included the presence of phosmet residues in fruits (p < 0.0001), close proximity to a farm (p = 0.002), home fenitrothion use (p = 0.009), and season (p < 0.0001).ConclusionsUrinary DAP levels in Chilean school children were high compared to previously reported studies. The presence of chlorpyrifos and phosmet residues in fruits was the major factor predicting urinary DAP metabolite concentrations in children.     

Daily intake of bisphenol A and triclosan and their association with anthropometric data,thyroid hormones and weight loss in overweight and obese individuals

Bisphenol A (BPA) and triclosan (TCS) were determined in urine of Belgian overweight and obese (n = 151) and lean (n = 43) individuals. After the first urine collection (0 M), obese patients started a diet program or have undergone bariatric surgery. Hereafter, three additional urine samples from obese patients were collected after 3 (3 M), 6 (6 M) and 12 (12 M) months. Both compounds were detected in > 99% of the samples. BPA had median concentrations of 1.7 and 1.2 ng/mL in obese and lean groups, respectively, while TCS had median concentrations of 1.5 and 0.9 ng/mL in the obese and lean groups, respectively. The obese group had higher urinary concentrations (ng/mL) of BPA (p < 0.5), while no significant differences were found for TCS between the obese and lean groups. No time trends between the different collection moments were observed. The BPA concentrations in the obese group were negatively associated with age, while no gender difference or relationship with body mass index was observed. For TCS, no relationships with gender, BMI, or age were found. The temporal variability of BPA and TCS was assessed with calculation of the intraclass correlation coefficient, Spearman rank correlation coefficients, and surrogate category analysis. We observed evidence that single spot urine samples might be predictive of exposure over a longer period of time. Dietary intakes of BPA and TCS did not differ significantly among the time points considered after obese individuals started losing weight (6 and 12 months). Multiple linear regression analyses after adjusting for age and weight loss revealed negative associations between urinary TCS and serum FT4 in the 0 M and 3 M female obese individuals and positive associations between urinary BPA and serum TSH in the lean group.     

Associations between blood persistent organic pollutants and 25-hydroxyvitamin D3 in pregnancy

Persistent organic pollutants (POPs) are suggested to contribute to lower vitamin D levels; however, studies in humans are scarce and have never focused on pregnancy, a susceptibility period for vitamin D deficiency. We investigated whether serum levels of POPs were associated with circulating 25-hydroxyvitamin D3 [25(OH)D3] concentration in pregnancy. Cross-sectional associations of serum concentrations of eight POPs with plasma 25(OH)D3 concentration were analyzed in 2031 pregnant women participating in the Spanish population-based cohort INfancia y Medio Ambiente (INMA) Project. Serum concentrations of POPs were measured by gas chromatography and plasma 25(OH)D3 concentration was measured by high-performance liquid chromatography in pregnancy (mean 13.3 ± 1.5 weeks of gestation). Multivariable regression models were performed to assess the relationship between blood concentrations of POPs and 25(OH)D3. An inverse linear relationship was found between serum concentration of PCB180 and circulating 25(OH)D3. Multivariate linear regression models showed higher PCB180 levels to be associated with lower 25(OH)D3 concentration: quartile Q4 vs. quartile Q1, coefficient = − 1.59, 95% CI − 3.27, 0.08, p trend = 0.060. A non-monotonic inverse relationship was found between the sum of predominant PCB congeners (PCB 180, 153 and 138) and 25(OH)D3 concentration: coefficient (95% CI) for quartile Q2 vs. Q1 [− 0.50 (− 1.94, 0.94)], quartile Q3 vs. Q1 [− 1.56 (− 3.11, − 0.02)] and quartile Q4 vs. Q1 [− 1.21 (− 2.80, 0.38)], p trend = 0.081. No significant associations were found between circulating 25(OH)D3 and serum levels of p,p′-DDE, p,p′-DDT, HCB, and ß-HCH. Our results suggest that the background exposure to PCBs may result in lower 25(OH)D3 concentration in pregnant women.     

Increased levels of phthalates in very low birth weight infants with septicemia and bronchopulmonary dysplasia

Very low birth weight infants (VLBW; birth weight < 1500 g) are exposed to potentially harmful phthalates from medical devices during their hospital stay. We measured urinary phthalate concentrations among hospitalized VLBW infants participating in a nutritional study. Possible associations between different phthalates and birth weight (BW), septicemia and bronchopulmonary dysplasia (BPD) were evaluated. Forty-six VLBW infants were enrolled in this randomized controlled nutritional study. The intervention group (n = 24) received increased quantities of energy, protein, fat, essential fatty acids and vitamin A, as compared to the control group (n = 22). The concentrations of 12 urinary phthalate metabolites were measured, using high-performance liquid chromatography coupled to tandem mass spectrometry, at 3 time points during the first 5 weeks of life. During this study, the levels of di (2-ethylhexyl) phthalate (DEHP) metabolites decreased, whereas an increasing trend was seen regarding metabolites of di-iso-nonyl phthalate (DiNP). Significantly higher levels of phthalate metabolites were seen in infants with lower BW and those diagnosed with late onset septicemia or BPD. A significant positive correlation between the duration of respiratory support and DEHP metabolites was observed (p ≤ 0.01) at 2.9 weeks of age. Birth weight was negatively associated with urinary phthalate metabolite concentrations. Infants with lower BW and those diagnosed with septicemia or BPD experienced prolonged exposure from medical equipment containing phthalates, with subsequent higher levels of phthalate metabolites detected. Clinical Trial Registration no.: NCT01103219.     

Boron exposure through drinking water during pregnancy and birth size

BackgroundBoron is a metalloid found at highly varying concentrations in soil and water. Experimental data indicate that boron is a developmental toxicant, but the few human toxicity data available concern mostly male reproduction.ObjectivesTo evaluate potential effects of boron exposure through drinking water on pregnancy outcomes.MethodsIn a mother-child cohort in northern Argentina (n = 194), 1–3 samples of serum, whole blood and urine were collected per woman during pregnancy and analyzed for boron and other elements to which exposure occurred, using inductively coupled plasma mass spectrometry. Infant weight, length and head circumference were measured at birth.ResultsDrinking water boron ranged 377–10,929 μg/L. The serum boron concentrations during pregnancy ranged 0.73–605 μg/L (median 133 μg/L) and correlated strongly with whole-blood and urinary boron, and, to a lesser extent, with water boron. In multivariable-adjusted linear spline regression analysis (non-linear association), we found that serum boron concentrations above 80 μg/L were inversely associated with birth length (B − 0.69 cm, 95% CI − 1.4; − 0.024, p = 0.043, per 100 μg/L increase in serum boron). The impact of boron appeared stronger when we restricted the exposure to the third trimester, when the serum boron concentrations were the highest (0.73–447 μg/L). An increase in serum boron of 100 μg/L in the third trimester corresponded to 0.9 cm shorter and 120 g lighter newborns (p = 0.001 and 0.021, respectively).ConclusionsConsidering that elevated boron concentrations in drinking water are common in many areas of the world, although more screening is warranted, our novel findings warrant additional research on early-life exposure in other populations.     

Biomonitoring of the general population living near a modern solid waste incinerator: A pilot study in Modena,Italy

Background and goalsAs part of the authorization process for the solid waste incinerator (SWI) in Modena, Italy, a human biomonitoring cross-sectional pilot study was conducted to investigate the degree to which people living and working in the proximity of the plant were exposed to SWI emissions.MethodsBetween May and June 2010, 65 subjects living and working within 4 km of the incinerator (exposed) and 103 subjects living and working outside this area (unexposed) were enrolled in the study. Blood, serum and urinary metals (Pb, Cd, Cu, Zn, Hg, Mn, Ni), urinary benzene, toluene, xylene (BTEX), S-phenylmercapturic acid (SPMA), and urinary polycyclic aromatic hydrocarbons (PAHs) were analysed. Information about lifestyle, anthropometric characteristics, residence, and health status was collected by a self-administered questionnaire. Exposure to particulate matter (PM) emitted from the SWI was estimated using fall-out maps from a quasi-Gaussian dispersion model. A multiple linear regression analysis investigated the relationship between biomarkers and the distance of a subject's place of residence from the SWI plant or the exposure to PM.ResultsUrinary BTEX and SPMA and blood, serum and urinary metals showed no differences between exposed and unexposed subjects. PAHs were higher in exposed than in unexposed subjects for phenanthrene, anthracene, and pyrene (median levels: 9.5 vs. 7.2 ng/L, 0.8 vs. < 0.5 ng/L and 1.6 vs. 1.3 ng/L, respectively, p < 0.05). Multiple linear regression analysis showed that blood Cd and Hg and urinary Mn, fluorene, phenanthrene, anthracene and pyrene were inversely correlated to the distance of a subject's residence from the SWI. Urinary Mn, fluorene and phenanthrene were directly correlated to PM exposure.ConclusionsThis study, although not representative of the general population, suggests that specific biomarkers may provide information about the degree of exposure the subjects working and living in the proximity of the SWI plant may have to emissions from that facility.     

Maternal urinary bisphenol A levels and infant low birth weight: A nested case–control study of the Health Baby Cohort in China

BackgroundExposure to bisphenol A (BPA), a known endocrine disruptor, has been demonstrated to affect fetal development in animal studies, but findings in human studies have been inconsistent.ObjectivesWe investigated whether maternal exposure to BPA during pregnancy is associated with an increased risk of infant low birth weight (LBW).MethodsA total 452 mother-infant pairs (113 LBW cases and 339 matched controls) were selected from the participants enrolled in the prospective Health Baby Cohort (HBC) in Wuhan city, China, during 2012–2014. BPA concentrations were measured in maternal urine samples collected at delivery, and the information of birth outcomes was retrieved from the medical records. A conditional logistic regression was used to evaluate the relationship between urinary BPA levels and LBW.ResultsMothers with LBW infants had significantly higher urinary BPA levels (median: 4.70 μg/L) than the control mothers (median: 2.25 μg/L) (p < 0.05). Increased risk of LBW was associated with higher maternal urinary levels of BPA [adjusted odds ratio (OR) = 3.13 for the medium tertile, 95% confidence interval (CI): 1.21, 8.08; adjusted OR = 2.49 for the highest tertile, 95% CI: 0.98, 6.36]. The association was more pronounced among female infants than among male infants, with a statistical evidence of heterogeneity in risk (p = 0.03).ConclusionsPrenatal exposure to higher levels of BPA may potentially increase the risk of delivering LBW infants, especially for female infants. This is the first case–control study to examine the association in China.     

Toxicokinetics of dioxins and other organochlorine compounds in Japanese people: Association with hepatic CYP1A2 expression levels

Concentrations of persistent organochlorine compounds (OCs) including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) in the liver and adipose tissue of Japanese cadavers were measured, and their toxicokinetics were examined in association with hepatic cytochrome P450 (CYP) 1A protein expression levels. Total 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) were 66 ± 74 and 65 ± 57 pg/g lipid weight (mean ± S.D.) in the liver and adipose tissue, respectively. Total PCBs (sum of 62 congeners targeted), p,p′-dichlorodiphenyl-dichloroethylene (p,p′-DDE) and β-hexachlorocyclohexane (β-HCH) were detected at concentrations over 1 μg/g lipid in both tissues of some specimens. For most of the dioxin-like congeners, total PCBs, p,p′-DDE, oxychlordane, α- and β-HCH, hexachlorobenzene (HCB), and tris(4-chlorophenyl)methane (TCPMe), age-dependent increases in concentrations were found in the adipose tissue of males. No such age-dependent trend was observed in the liver, suggesting that there are different mechanisms underlying the hepatic concentrations of OCs. Immunoblot analyses indicated detectable expression of hepatic CYP1A2 protein, whereas no CYP1A1 protein was detected. The CYP1A2 expression levels were positively correlated with concentrations (on wet weight basis) of 2,3,4,7,8-P₅CDF, the dominant TEQ-contributed congeners in the liver, indicating the induction of this CYP. Hepatic CYP1A2 protein levels were strongly correlated with the liver to adipose concentration (L/A) ratios of PCDD/F congeners with more than 5 chlorine atoms. Together with higher concentrations of the congeners in the liver than in the adipose tissue, the observation on L/A ratios of highly chlorinated PCDD/Fs suggests that induced hepatic CYP1A2 protein is involved in their sequestration in this human population, as observed in model animals (rodents). Nonetheless, the magnitude of hepatic sequestration (L/A ratio) of PCDD/Fs in this human population was lower than in other mammals and birds, reported previously. This study emphasizes the fact that toxicokinetics of some OCs can be affected at least partly by CYP1A2 protein levels in humans. For the extrapolation of their toxicokinetics from model animals to humans, knowledge on the induction and sequestration potencies of CYP1A is necessary.     

Pharmacokinetics of bisphenol A in humans following a single oral administration

BackgroundHuman exposures to bisphenol A (BPA) are widespread. The current study addresses uncertainties regarding human pharmacokinetics of BPA.ObjectiveTo reduce uncertainties about the metabolism and excretion of BPA in humans following oral administration.MethodsWe exposed six men and eight women to 100 μg/kg bw of deuterated BPA (d6-BPA) by oral administration and conducted blood and urine analysis over a three day period. The use of d6-BPA allowed administered d6-BPA to be distinguished from background native (unlabeled) BPA. We calculated the rate of oral absorption, serum elimination, half-life, area under the curve (AUC), urinary excretion, and metabolism to glucuronide and sulfate conjugates.ResultsMean serum total (unconjugated and conjugated) d6-BPA C_max of 1711 nM (390 ng/ml) was observed at T_max of 1.1 ± 0.50 h. Unconjugated d6-BPA appeared in serum within 5–20 min of dosing with a mean C_max of 6.5 nM (1.5 ng/ml) observed at T_max of 1.3 ± 0.52 h. Detectable blood levels of unconjugated or total d6-BPA were observed at 48 h in some subjects at concentrations near the LOD (0.001–0.002 ng/ml). The half-times for terminal elimination of total d6-BPA and unconjugated d6-BPA were 6.4 ± 2.0 h and 6.2 ± 2.6 h, respectively. Recovery of total administered d6-BPA in urine was 84–109%. Most subjects (10 of 14) excreted > 90% as metabolites within 24 h.ConclusionsUsing more sensitive methods, our study expands the findings of other human oral pharmacokinetic studies. Conjugation reactions are rapid and nearly complete with unconjugated BPA comprising less than 1% of the total d6-BPA in blood at all times. Elimination of conjugates into urine largely occurs within 24 h.     

Substantial decline of polychlorinated biphenyls serum levels 10 years after public health interventions in a population living near a contaminated site in Northern Italy

IntroductionPolychlorinated biphenyls (PCBs) are persistent pollutants classified among endocrine disruptors and human carcinogens. In an urban area in Northern Italy (Brescia), a chemical factory producing PCBs from 1938 to 1984 caused soil and food pollution. Since the discovering of the environmental pollution in the area in 2001, various public health interventions have been implemented to avoid human contamination.MethodsTwo independent surveys were carried out in 2003 and 2013 using the same study design and methods. A random sample of the adult general population living in four areas of the town with different soil contamination level was enrolled in both surveys. Investigation included serum levels of 24 PCB congeners and of other common clinical-chemical parameters and questions about residential and occupational history as well as current and past diet and consumption of locally produced food. 537 subjects were tested in the 2003 and 488 in the 2013 survey.ResultsTotal PCB serum levels showed a strong correlation with age (Spearman r = 0.71 in 2003 and r = 0.80 in 2013), but not with gender. Consumers of food produced in the most polluted area had higher total PCB serum levels (median 15.6 and 4.7 ng/ml in 2003 and 2013, respectively) than non-consumers (4.1 and 2.3 ng/ml) and consumers of food produced in non-polluted areas (6.5 and 1.9 ng/ml), with increasing trend of PCB serum levels with cumulative local food intake. PCB serum levels from 2003 to 2013 survey declined by around half in all age groups, especially among the youngest people. The total PCB reduction was found to be due to a combination of a birth cohort effect (− 41% every 10 years) and survey period effect (− 18% in 2013 versus 2003), with medium chlorinated CB congeners showing the most relevant reduction (− 30%) between the two surveys. High chlorinated CBs were more strongly associated with birth cohort (− 46% every 10 years): in the 2013 survey they represented 58% of total PCBs in 60–79 years old while they were 37% among the under 40s with a median value 20 times higher in the oldest than in the youngest (3.1 versus 0.16 ng/ml).ConclusionsPCBs serum levels declined from the 2003 to 2013 survey though they are still high in the elderly mainly because of past intake of locally produced contaminated food. Present findings suggest that PCBs food chain contamination and human absorption have been interrupted successfully in the area since discovery of the pollution in 2001.     

Urinary biomarkers of flame retardant exposure among collegiate U.S. gymnasts

Flame retardants are widely used in polyurethane foam materials including gymnastics safety equipment such as pit cubes and landing mats. We previously reported elevated concentrations of flame retardants in the air and dust of a U.S. gymnastics training facility and elevated PentaBDE in the serum of collegiate gymnasts. Our objective in this pilot study was to compare urinary biomarkers of exposure to other flame retardants and additives of polyurethane foam including tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), triphenyl phosphate (TPHP) and 2-ethylhexyl- 2,3,4,5-tetrabromobenzoate (EH-TBB) in samples collected from 11 collegiate gymnasts before and after a gymnastics practice (n = 53 urine samples total). We identified a 50% increase in the TPHP biomarker (p = 0.03) from before to after practice, a non-significant 22% increase in the TDCIPP biomarker (p = 0.14) and no change for the EH-TBB biomarker. These preliminary results indicate that the gymnastics training environment can be a source of recreational exposure to flame retardants. Such exposures are likely widespread, as we identified flame retardants in 89% of foam samples collected from gyms across the U.S.     

Human exposure pathways to organophosphate triesters — A biomonitoring study of mother–child pairs

The worldwide ban of several formulations of brominated flame retardants has caused an increase in the production of organophosphorus flame retardants (PFRs) to meet the existing fire regulations for a wide range of household products. This biomonitoring study surveys the occurrence of the metabolites from PFRs and related plasticizers (dialkyl and diaryl phosphates; DAPs) in urine from a Norwegian mother–child cohort (48 mothers and 54 children). Concentrations of DAPs were higher in the children than in their mothers (Wilcoxon signed-rank test p = 0.001). Median urinary concentrations of diphenyl phosphate (DPHP) were 1.1 and 0.51 ng/mL in children and mothers, respectively, followed by bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) with medians of 0.23 and 0.12 ng/mL, respectively. Detection frequencies for bis(2-butoxyethyl) phosphate (BBOEP) in urine from children and mothers were 32 and 1%, respectively (median < 0.18 ng/mL), and for di-n-butyl phosphate (DNBP) 15 and 8%, respectively (median < 0.12 ng/mL). The concentrations of DPHP and BDCIPP in urine from children were significantly correlated with those found for their parent compounds in air and dust from the households (Spearman's rank correlations 0.30 < R_s < 0.36; p < 0.05). For mothers, only the urinary concentration of BDCIPP was correlated to its precursor in dust from the households (R_s = 0.40; p < 0.01), which might indicate higher impact of the household environment on children than mothers. A diurnal variability study of the mothers' urinary concentrations of DPHP and BDCIPP showed lower concentrations at time periods when women were likely to be outside the household. In contrast, no relevant associations between organophosphate metabolites in urine and food consumption data obtained through a 24 hour recall were seen. This suggests that the residential environment is a more important exposure pathway to PFRs than the diet.     

Organophosphate pesticide exposure and perinatal outcomes in Shanghai,China

Although pesticide use is widespread in China, little is known about levels of exposure to organophosphate pesticides in the population and its potential adverse health effects. We investigated levels of organophosphate exposure in pregnant women and the association between organophosphate exposure and perinatal outcomes in Shanghai, China, by enrolling 187 healthy pregnant women between September 2006 and January 2007. Pesticide exposure was assessed by a questionnaire administered to the mothers in the hospital after delivery as well as by analyses of maternal urinary nonspecific metabolites of organophosphate pesticides (dimethyl and diethyl phosphates). Information on birth weight and length was collected from medical records. Geometric means of metabolites were 25.75 μg/L for dimethylphosphate (DMP); 11.99 μg/L for dimethylthiophosphate (DMTP); 9.03 μg/L for diethylphosphate (DEP); and 9.45 μg/L for diethyldithiophosphate (DETP). We found that a log unit increase in urinary DEP was associated with a decrease in gestational duration in girls by 1.79 weeks. [ß_adjusted = − 1.79 weeks per log₁₀ unit increase; 95% confidence interval (CI), −2.82 to − 0.76; p = 0.001]. These data suggest that high pesticide level might adversely affect duration of gestation although this association was not present among boys. No associations for any of the organophosphate exposure measures were present for birth weight and length, suggesting that organophosphate pesticides may have no effects on fetal growth. Given that maternal urine pesticide levels in Shanghai were much higher than those reported in developed countries, more studies on the effects of in utero organophosphate exposure on fetal growth and child neurodevelopment are warranted.     

Hazard quotient profiles used as a risk assessment tool for PFOS and PFOA serum levels in three distinctive European populations

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) blood levels are commonly used as biomarkers of human environmental exposure to these compounds. Many biomonitoring studies indicate 100% detection for PFOS and PFOA thus justifying a concern of possible risk for the most exposed individuals.This study addresses the predictive value of hazard quotients (HQs) calculated on the basis of serum PFOS and PFOA in male and female populations of reproductive age in Greenland, Poland and Ukraine.Overall, 2026 results of PFOS and PFOA serum concentrations (589 males, 1437 females) were obtained from the INUENDO database. HQs were calculated from the actual biomonitoring results and literature-based animal data linking toxicological outcomes and critical PFOS/PFOA serum levels. HQs for serum PFOS were calculated based on Points of Departure (PoD) at 13 μg mL^− 1 (cynomolgus monkeys, 183 days, changes in THS and T₃) and for PFOA at 7.1 μg mL^− 1 serum (male rats, 90 days, hepatocellular necrosis, increased liver weight). Uncertainty factors were applied to reflect interspecies differences and human variability. Serum HQs were expressed as a ratio relative to the point of departure for each PFOS and PFOA. Only in the three cases of males in Greenland were there serum PFOS levels showing HQ values exceeding 1, so indicating that such serum levels may be of concern. The mean serum concentration of PFOS was significantly higher in male than in female populations. Despite significant differences between HQ profiles for PFOS and PFOA in donors from Greenland, Poland and Ukraine, the concentrations of these perfluoroalkylated compounds do not indicate a cause for concern, except for the three aforementioned cases from Greenland.This study demonstrates that the HQ approach can help to interpret human biomonitoring data and thus serve as a valuable tool in further risk assessment priority settings and may also be used as a basis for taking decisions in risk management.