Identification of UDP-glucuronosyltransferase (UGT) isoforms involved in the metabolism of Chlorophenols (CPs).

Chlorophenols (CPs) are a group of pollutants that pose a great threat to the environment, they are widely used in industrial and agricultural wastes, pesticides, herbicides, textiles, pharmaceuticals and plastics. Among CPs, pentachlorophenol was listed as one of the persistent organic pollutants (POPs) by the Stockholm convention. This study aims to identify the UDP-glucosyltransferase (UGT) isoforms involved in the metabolic elimination of CPs. CPs' mono-glucuronide was detected in the human liver microsomes (HLMs) incubation mixture with co-factor uridine-diphosphate glucuronic acid (UDPGA). HLMs-catalyzed glucuronidation metabolism reaction equations followed Michaelis-Menten or substrate inhibition type. Recombinant enzymes and chemical reagents inhibition experiments were utilized to phenotype the main UGT isoforms involved in the glucuronidation of CPs. UGT1A6 might be the major enzyme in the glucuronidation of mono-chlorophenol isomer. UGT1A1, UGT1A6, UGT1A9, UGT2B4 and UGT2B7 were the most important five UGT isoforms for metabolizing the di-chlorophenol and tri-chlorophenol isomers. UGT1A1 and UGT1A3 were the most important UGT isoforms in the catalysis of tetra-chlorophenol and pentachlorophenol isomers. Species differences were investigated using rat liver microsomes (RLMs), pig liver microsomes (PLMs), dog liver microsomes (DLMs), and monkey liver microsomes (MyLMs). All these results were helpful for elucidating the metabolic elimination and toxicity of CPs.

Effect modification by aging on the associations of nicotine exposure with cognitive impairment among Chinese elderly.

Active and passive exposure to tobacco smoke may increase risk of cognitive decline. However, effects of enhanced the aging process on the association of urinary nicotine metabolites with cognitive impairment remain unclear. In this study, 6657 Chinese older adults completed the physical examinations and cognitive tests. We measured urinary nicotine metabolite levels, mitochondrial DNA copy number (mtDNA-CN), and relative telomere length (RTL) and analyzed effects of urinary nicotine metabolites and their interaction with mtDNA-CN or RTL on cognitive impairment by generalized linear models and qg-computation, respectively. Each 1-unit increase in urinary 3-OHCot, 3-OHCotGluc, CotGluc, or NicGluc levels corresponded to a 1.05-, 1.09-, 1.04-, and 0.90-fold increased risk of cognitive impairment. Each 1-quantile increment in the mixture level of 8 nicotine metabolites corresponded to an increment of 1.40- and 1.34-fold risk of cognitive impairment in individuals with longer RTL or low mtDNA-CN. Urinary 3-OHCotGluc and RTL or mtDNA-CN exhibited an additive effect on cognitive impairment in addition to the mixture of 8 nicotine metabolites and mtDNA-CN. The findings suggested that aging process may increase the risk of tobacco-related cognitive impairment.

Non-linear dose-response relation between urinary levels of nicotine and its metabolites and cognitive impairment among an elderly population in China.

BACKGROUND: Active smoking and exposure to environmental tobacco smoke may be related to cognitive function decline. We assessed the associations of urinary levels of nicotine and its metabolites with cognitive function. METHODS: A total of 553 elder adults at high risk of cognitive impairment and 2212 gender- and age-matched individuals at low risk of cognitive impairment were selected at a ratio of 1: 4 from the remained individuals (n = 6771) who completed the baseline survey of the Shenzhen Ageing-Related Disorder Cohort, after excluding those with either Alzheimer's disease, Parkinson's syndrome or stroke as well as those with missing data on variables (including active and passive smoking status, Mini-Cog score). Urinary levels of nicotine and its metabolites and cognitive function for all individuals were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) and assessed using the Mini-Cog test, respectively. Associations of urinary levels of nicotine and its metabolites with cognitive function were analyzed by conditional logistic regression models. RESULTS: Individuals in the highest tertile of urinary OHCotGluc (OR: 1.52, 95%CI: 1.19-1.93) or NNO (OR: 1.50, 95%CI: 1.16-1.93) levels as well as in the second tertile of urinary ∑Nic level (OR: 1.43, 95%CI: 1.13-1.82) were at higher risk of cognitive impairment compared with those in the corresponding lowest tertile. Restricted cubic spline models revealed the non-linear dose-response relationships between urinary levels of OHCotGluc, NNO or ∑Nic and the risk of cognitive impairment. CONCLUSIONS: Urinary levels of OHCotGluc, NNO or ∑Nic exhibited a non-linear dose-response relationship with cognitive function in the urban elderly.

Phthalate exposure linked to high blood pressure in Chinese children.

BACKGROUND: Exposure to phthalate esters may be linked to the risk of high blood pressure (HBP), but limited evidence is available in Chinese children. OBJECTIVE: To investigate the associations between nine phthalate metabolites (mPAEs) and systolic/diastolic BP, pulse pressure (PP), mean arterial pressure (MAP), and the risk of HBP. METHODS: In this cross-sectional study, a total of 1044 primary school children (6-8 years old) were enrolled from Shenzhen, China, between 2016 and 2017. Nine mPAEs were analyzed from urine using ultra-performance liquid chromatography and tandem mass spectrometry. A multivariable linear regression model was used to explore the associations between phthalate exposure and systolic/diastolic BP, PP, and MAP. A binary logistic regression model was used to examine the associations between phthalate exposure and the risk of HBP. RESULTS: Monomethyl phthalate (MMP) concentrations were significantly higher in HBP children than normal BP children. MMP, monoisobutyl phthalate (MiBP), monobutyl phthalate (MnBP), mono(5-carboxy-2-ethylpentyl) phthalate, mono-[(2-carboxy methyl)hexyl] phthalate (MCMHP), the sum of four short-chain mPAEs (∑LMW), and the sum of all nine mPAEs (∑9mPAEs) were significantly positively associated with increases in systolic BP z-score, while only MMP was significantly positively associated with diastolic BP z-score. MMP, MiBP, MnBP, MCMHP, ∑LMW, and ∑9mPAEs were significantly associated with increases in PP, while MMP and MnBP were significantly associated with increases in MAP. MMP was significantly associated with the risk of HBP, with an odds ratio of 1.87 (95% CI: 1.23, 2.85). CONCLUSIONS: The present study suggests that dimethyl phthalate exposure increases the risk of HBP. And some types of phthalates are associated with elevations in systolic/diastolic BP z scores, PP, and MAP in Chinese children.

[Pollution Characteristics and Evaluation of Heavy Metal Pollution in Surface Soil Around a Municipal Solid Waste Incineration Power Plant].

To investigate and evaluate the pollution levels of heavy metals in the soil around a large Municipal Solid Waste Incineration power plant (MSWIPP), a total of 29 soil samples were collected around the MSWIPP and away from the power plant area. The contents of 10 selected heavy metals (Cr, Mn, Ni, Cu, Zn, As, Ag, Cd, Hg, and Pb) were analyzed. The results showed that the content of each heavy metal element did not exceed the values for Soil Environmental Quality of Risk Control Standard for Soil Contamination of Agricultural Land (GB15618-2018) and Development Land (GB 36600-2018). The mean contents of Mn, Cu, and As were higher than their respective background values of Anhui Province, where As was 1.03 times the background value, and Cu was 1.07 times. Compared with the control points, the contents of Cr, Ni, Cd, Cu, and As were lower than the control points, and the difference was statistically significant (P ≤ 0.05). The spatial distribution of Hg was more obvious in the soil around the power plant, and other heavy metals were not obvious and uniform. The content of Hg was the highest in the 500 m soil of perennial dominant downwind and sub-dominant downwind. With increasing distance from the power plant, the content gradually decreased and it was lower than the level of the control point. The pollution degree of heavy metal elements in the soil around the power plant and in the plant area was mild. The Nemero comprehensive pollution index (PI) was 1.1-1.2, and the control point had also mild pollution (PI was 1.5). The potential ecological risk was slight, and the comprehensive potential ecological risk index (RI) of various heavy metal elements was 60.2-67.7. The contribution rate of Hg and As to RI were large, and the control point had medium ecological risk (RI was 116.8). Based on the results of principal component analysis, accompanied with the content, spatial distribution characteristics, Pearson's correlation, and hierarchical cluster analysis results, three groups of heavy metals with different spatial distribution were identified:①Ni, Cr, As, and Mn originated from lithological sources; ②Cu, Zn, Ag, Cd, and Pb affected by both lithological and human sources (e.g. agricultural and traffic sources); ③Hg likely originated from the diffusion sedimentation of MSWI flue gas and its accumulation in the soil. The above results indicated that the unique pollution characteristics of Hg deserve serious attention in pollution monitoring in soils surrounding solid waste incinerator.

A pilot study of metabolites of organophosphorus flame retardants in paired maternal urine and amniotic fluid samples: potential exposure risks of tributyl phosphate to pregnant women.

Organophosphorus flame retardants (OPs) are of wide concern due to their presence in human urine and their considerable endocrine disruption and neuro-development toxicity. It has been confirmed that electronic waste (e-waste) dismantling activities have contributed to human exposure to OPs. However, assessments of OP exposure and the health risks for pregnant women and fetuses living in areas associated with e-waste dismantling have been impeded by a lack of data. In this study, six OP metabolites (mOPs) were measured in paired maternal urine and amniotic fluid samples collected from an e-waste dismantling area in Guangdong Province, China. All mOPs were detectable in maternal urine, whereas two were found in amniotic fluid. Dibutyl phosphate (DBP) was the predominant mOP in both maternal urine (geometric mean (GM): 2.9 ng ml-1) and amniotic fluid (1.3 ng ml-1); and diphenyl phosphate (DPHP) was the secondary one found (0.94 ng ml-1 in maternal urine, 0.12 ng ml-1 in amniotic fluid). The GM urinary concentrations of DBP and DPHP were two and seven times higher than those in amniotic fluid, respectively. The estimated daily intakes (EDIs) of triphenyl phosphate (TPHP) and tributyl phosphate (TnBP) by pregnant women were calculated from their daily urine excretion rate as fractions of OP metabolized to the corresponding metabolite (FUE). Our results showed high exposure levels to TPHP (median: 273 or 613 ng per kg bw per day) and TnBP (404 ng per kg bw per day) for pregnant women living in the e-waste associated area. Most importantly, 13% of mothers had EDITnBP levels that exceeded the reference dose (RfD: 2400 ng per kg bw per day), suggesting potential health risks from TnBP exposure for pregnant women living in areas associated with e-waste dismantling. This study, as a pilot study, presents the first measurements of mOPs in human amniotic fluid.

Urinary metabolites of organophosphate flame retardants in China: Health risk from tris(2-chloroethyl) phosphate (TCEP) exposure.

Organophosphate esters (OPs) are substitutes for polybrominated diphenyl ether (PBDE) flame retardants. China is the largest producer of OPs globally, with the production rate increasing at 15% annually. Since some OPs are neurodevelopmental and/or carcinogenic toxicants, human exposure is a concern. In this study, concentrations of eight OP metabolites (mOPs) were measured in human urine samples collected from 13 cities located in Northern, Eastern, Southern, and Southwestern China. All target mOPs were frequently detected with detection rates of 50% to 100%, indicating widespread human exposure to OPs. Bis(2-chloroethyl) phosphate (BCEP; median: 0.68 ng/mL), bis(1-chloro-2-propyl) phosphate (BCIPP; 0.30 ng/mL), diphenyl phosphate (DPHP; 0.30 ng/mL), and dibutyl phosphate (DBP; 0.29 ng/mL) were the dominant mOPs across all participants. Regional differences in concentrations (ΣmOPs varied from 0.86 to 3.7 ng/mL) and composition profiles (contribution of chlorinated mOPs to ΣmOPs varied from 35% to 95%) of mOPs were observed within China. In comparison to the concentrations reported worldwide, urinary DPHP and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) levels in China were lower, whereas BCEP and DBP levels were comparable or higher. The total daily intake (TDI) of tris(2-chloroethyl) phosphate (TCEP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) were estimated from daily urine excretion rate and the fraction of OP metabolized in human liver microsomes (TDIHLM) or S9 fraction (TDIS9). The intake estimates showed that Chinese residents were exposed to TCEP from 96.9 to 46,700 (or 52.2 to 25,200) ng/kg bw/day. Depending on the reference dose, we found that approximately 5% of the individuals exceeded the limit (i.e., 2200 ng/kg bw/day) for TCEP intake. To our knowledge, this is the first nationwide baseline survey to determine urinary levels of mOPs in Chinese residents.

Effect of E-waste Recycling on Urinary Metabolites of Organophosphate Flame Retardants and Plasticizers and Their Association with Oxidative Stress.

In this study, three chlorinated (Cl-mOPs) and five nonchlorinated (NCl-mOPs) organophosphate metabolites were determined in urine samples collected from participants living in an electronic waste (e-waste) dismantling area (n = 175) and two reference areas (rural, n = 29 and urban, n = 17) in southern China. Bis(2-chloroethyl) phosphate [BCEP, geometric mean (GM): 0.72 ng/mL] was the most abundant Cl-mOP, and diphenyl phosphate (DPHP, 0.55 ng/mL) was the most abundant NCl-mOP. The GM concentrations of mOPs in the e-waste dismantling sites were higher than those in the rural control site. These differences were significant for BCEP (p < 0.05) and DPHP (p < 0.01). Results suggested that e-waste dismantling activities contributed to human exposure to OPs. In the e-waste sites, the urinary concentrations of bis(2-chloro-isopropyl) phosphate (r = 0.484, p < 0.01), BCEP (r = 0.504, p < 0.01), dibutyl phosphate (r = 0.214, p < 0.05), and DPHP (r = 0.440, p < 0.01) were significantly increased as the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidative stress, increased. Our results also suggested that human exposure to OPs might be correlated with DNA oxidative stress for residents in e-waste dismantling areas. To our knowledge, this study is the first to report the urinary levels of mOPs in China and examine the association between OP exposure and 8-OHdG in humans.

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: 25.4µg/g Cre) were significantly higher (p<0.05) than those found in both rural (11.7µg/g Cre) and urban (10.9µg/g Cre) reference areas. The occupationally exposed e-waste workers (36.6µg/g Cre) showed significantly higher (p<0.01) urinary Σ10OH-PAHs concentrations than non-occupationally exposed people (23.2µg/g Cre) living in the e-waste recycling site. The differences in urinary Σ10OH-PAHs levels between smokers (23.4µg/g Cre) and non-smokers (24.7µg/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.

Brominated flame retardant emissions from the open burning of five plastic wastes and implications for environmental exposure in China.

Based on the most widely used plastics in China, five plastic wastes were selected for investigation of brominated flame retardant (BFR) emission behaviors during open burning. Considerable variations were observed in the emission factors (EF) of polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs) from the combustion of different plastic wastes. Distribution of BFR output mass showed that ΣPBDE was emitted mainly by the airborne particle (51%), followed by residual ash (44%) and the gas phase (5.1%); these values for ΣHBCD were 62%, 24%, and 14%, respectively. A lack of mass balance after the burning of the plastic wastes for some congeners (output/input mass ratios>1) suggested that formation and survival exceeded PBDE decomposition during the burns. However, that was not the case for HBCD. A comparison with literature data showed that the open burning of plastic waste is major source of PBDE compared to regulated combustion activities. Even for state-of-the-art waste incinerators equipped with sophisticated complex air pollution control technologies, BFRs are released on a small scale to the environment. According to our estimate, ΣPBDE release to the air and land from municipal solid waste (MSW) incineration plants in China in 2015 were 105 kg/year and 7124 kg/year. These data for ΣHBCD were 25.5 and 71.7 kg/year, respectively. Considering the fact that a growing number of cities in China are switching to incineration as the preferred method for MSW treatment, our estimate is especially important. This study provides the first data on the environmental exposure of BFRs emitted from MSW incineration in China.

Trace elements contamination and human health risk assessment in drinking water from Shenzhen, China.

The levels of seven essential trace elements (Mn, Co, Ni, Cu, Zn, Se, and Mo) and six non-essential trace elements (Cr, As, Cd, Sb, Hg, and Pb) in a total of 89 drinking water samples collected in Shenzhen, China were determined using inductively coupled plasma mass spectrometry (ICP-MS) in the present study. Both the essential and non-essential trace elements were frequently detectable in the different kinds of drinking waters assessed. Remarkable temporal and spatial variations were observed among most of the trace elements in the tap water collected from two tap water treatment plants. Meanwhile, potential human health risk from these non-essential trace elements in the drinking water for local residents was also assessed. The median values of cancer risks associated with exposure to carcinogenic metals via drinking water consumption were estimated to be 6.1 × 10(-7), 2.1 × 10(-8), and 2.5 × 10(-7) for As, Cd, and Cr, respectively; the median values of incremental lifetime for non-cancer risks were estimated to be 6.1 × 10(-6), 4.4 × 10(-5), and 2.2 × 10(-5) for Hg, Pb, and Sb, respectively. The median value of total incremental lifetime health risk induced by the six non-essential trace elements for the population was 3.5 × 10(-5), indicating that the potential health risks from non-carcinogenic trace elements in drinking water also require some attention. Sensitivity analysis indicates that the most important factor for health risk assessment should be the levels of heavy metal in drinking water.

Bisphenol A in supermarket receipts and its exposure to human in Shenzhen, China.

Paper receipt has been documented as one major source of bisphenol A (BPA) for human exposure but little has been done by researchers to elaborate the potential health risk caused by handling paper receipt up to date. In the present study, BPA was analyzed in 42 supermarket receipts collected from Shenzhen, China. BPA was detected in all samples at concentrations ranging from 2.58 to 14.7mgg(-1). In most cases, the total amount of BPA on the receipt was at least one thousand times the amount found in the epoxy lining of a food can, another controversial use of the chemical. The estimated daily intakes (EDI) of BPA via handling of supermarket receipt ranged from 2 to 347µgday(-1) (mean, 40.4µgday(-1)) for a supermarket cashier and from 0.24 to 3.98µgday(-1) (mean, 0.69µgday(-1)) for general population. Based on the cumulative probability distribution of the calculated daily exposure to BPA via handling supermarket receipt, the EDI at the 0.1th and 1th percentile for supermarket cashier and general population, were already larger than 100ng (kgbw)(-1)day(-1), while at the 0.2th and 71th percentile, the EDI for both populations reached 1000ng (kgbw)(-1)day(-1). Considering the adverse endocrine disruptive effects of BPA and the dosage exposure level (from tens to hundreds ng (kgbw)(-1)day(-1)), human exposure to BPA in Shenzhen deserves more attention. Sensitivity analysis result showed that the handling time and frequency of supermarket receipts are the most important variables that contributed to most of the total variance of exposure.

Food as a main route of adult exposure to PBDEs in Shenzhen, China.

The present study measured eight PBDE congeners' (BDE-28, 47, 99, 100, 153, 154, 183, and 209) exposure via ingestion of indoor dust and soil, inhalation, and food consumption. Contributions to PBDEs exposure from different media revealed that indoor dust (dust suspended in air) was not an important exposure route for PBDE congeners for adults in Shenzhen, China. Food consumption contributed more to daily intake of Σ(8)BDE, especially for lower-brominated PBDE congeners. Based on calculated average total daily intake, hazard quotients were determined to estimate the non-cancer risks of PBDE exposure. Meanwhile, cancer risk was also estimated assuming that the oral cancer slope factors of all PBDE congeners are equipotent as BDE-209. The hazard quotients ranged from 1.2×10(-5) (BDE-209) to 2.0×10(-2) (BDE-47), suggesting a low deleterious risk with regard to PBDEs. The cancer risk value ranged from 1.1×10(-24) to 5.5×10(-21) implying that the total risks due to exposure to PBDEs via all exposure routes are extremely low for adults.

Increased urinary 8-hydroxy-2'-deoxyguanosine levels in workers exposed to di-(2-ethylhexyl) phthalate in a waste plastic recycling site in China.

BACKGROUND: Di-(2-ethylhexyl) phthalate (DEHP) is a common plasticizer used in industrial and diverse consumer products. Animal studies indicate DEHP caused developmental, reproductive, and hepatic toxicities. However, human studies of the potential effects of DEHP are limited. METHODS: The exposed site with a history of over 20 years of waste plastic recycling was located in Hunan Province, China. The reference site without known DEHP pollution source was about 50 km far away from the exposed site. In this study, 181 workers working in plastic waste recycling and 160 gender-age matched farmers were recruited. DEHP concentrations in water and cultivated soil samples, serum thyroid-stimulating hormone, malondialdehyde (MDA), superoxide dismutase (SOD), urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and micronuclei frequency in human capillary blood lymphocytes were analyzed. RESULTS: Mean levels of DEHP were greater in environment at the recycling site than at reference site (industry wastewater for the exposed: 42.43 µg/l; well water: 14.20 vs. 0.79 µg/l, pond water: 135.68 vs. 0.37 µg/l, cultivated soil: 13.07 vs. 0.81 mg/kg, p < 0.05 for all). The workers had higher median levels of MDA (3.80 vs. 3.14 nmol/ml) and urinary 8-OHdG (340.37 vs. 268.18 µmol/mol creatinine) and decreased SOD activities (112.15 vs. 123.82 U/ml) than the reference group (p < 0.01 for all). Multivariate analysis revealed that the history of working in waste plastic recycling was an independent risk factor for the increased urinary 8-OHdG levels in the male workers (p < 0.01). CONCLUSIONS: The occupational DEHP exposure might contribute to oxidative deoxyribonucleic acid damage in the male workers.