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A nationwide survey of the occurrence of melamine and its derivatives in archived sewage sludge from the United States

Zhu, Hongkai; Halden, Rolf U; Kannan, Kurunthachalam
Melamine-based resins are used extensively in laminates, plastics, coatings, glues, and dinnerware. Little is known, however, about the occurrence of melamine and its derivatives in the environment. In this study, a nationwide survey of melamine and its derivatives, namely ammeline, ammelide, and cyanuric acid, was conducted, using archived sewage sludge samples collected from 68 wastewater treatment plants in the United States (U.S.). The sum concentrations of four target compounds in sludge ranged from 34 to 1800 ng/g dry weight (dw), with a mean concentration of 240 ng/g dw; melamine (46%) and cyanuric acid (40%) collectively accounted for 86% of the total mass of analytes. No significant geographical variation in the concentrations of melamine and its derivatives in sewage sludge was found. The estimated emission of melamine and its derivatives via land-application of sludge was approximately 1600 kg/yr in the U.S. The hazard quotient values for melamine in sludge-amended soils ranged from 2.2 × 10-5 to 4.4 × 10-3, indicating that the current levels of melamine in sludge pose a minimal risk to the soil environment.
PMID: 30682756
ISSN: 1873-6424
CID: 4287442

How stable is oxidative stress level? An observational study of intra- and inter-individual variability in urinary oxidative stress biomarkers of DNA, proteins, and lipids in healthy individuals

Martinez-Moral, Maria-Pilar; Kannan, Kurunthachalam
Oxidative stress in humans is affected by the health and nutritional status as well as exposure to external environmental factors. To evaluate the effects of external factors, an assessment of baseline levels as well as diurnal variations in oxidative stress status of healthy individuals is needed. In this study, we examined intra- and inter-individual variability of oxidative stress biomarkers (OSBs) of lipids (malondialdehyde [MDA] and four F2-isoprostane isomers, namely, 8-isoprostaglandinF2α [8-PGF2α], 11β-prostaglandinF2α [11-PGF2α], 15(R)-prostaglandinF2α [15-PGF2α], and 8-iso,15(R)-prostaglandinF2α [8,15-PGF2α]); proteins (o,o'-dityrosine [diY]); and DNA (8-hydroxy-2'-deoxyguanosine [8-OHdG]) in urine from healthy individuals. The significance of creatinine correction, which is typically used to account for urinary dilution, on OSB concentrations was evaluated. Analysis of 515 urine samples, collected longitudinally from 19 healthy individuals daily for over a month, showed inter-individual coefficient of variation (CV) in concentrations from 112% for MDA to 272% for 15-PGF2α. Intra-individual CV in concentrations ranged from 29% for 8-OHdG to 149% for 15-PGF2α. MDA was the most abundant OSB found in urine. The intra- and inter-individual variability in F2-isoprostane concentrations were higher than the values calculated for diY, 8-OHdG, and MDA. All seven OSB concentrations were significantly correlated with each other and with creatinine. Creatinine normalization of OSB concentrations improved predictability in OSB concentrations over time. Our results suggest that 8-OHdG, showing the highest ICC (0.96), yielded more reproducible measurements with a low CV, and is the most suitable biomarker of OSB in spot urine samples. The measured concentrations and diurnal variability in urinary OSB levels in healthy individuals reported in this study are useful as a benchmark for future toxicological and epidemiological studies.
PMCID:6396322
PMID: 30572170
ISSN: 1873-6750
CID: 4287392

Inter-day and inter-individual variability in urinary concentrations of melamine and cyanuric acid

Zhu, Hongkai; Kannan, Kurunthachalam
Melamine is used extensively in household products, such as furniture, dinnerware, and food utensils. Several studies have shown that melamine adversely affects kidney function. Nevertheless, little is known about urinary melamine concentrations, and its temporal variability. In this study, 213 first-morning-void urine samples were collected from 19 volunteers for over a month to assess longitudinal variability in concentrations of melamine and its three structural analogues, i.e., cyanuric acid, ammeline, and ammelide. Target analytes were found in all urine samples at mean concentrations of 3.3, 16, 0.99, and 0.62 ng/mL, for melamine, cyanuric acid, ammelide, and ammeline, respectively. Cyanuric acid was the major compound found in all urine samples, accounting for 74-80% of the total concentrations, followed by melamine (12-20%), ammelide (4-6%), and ammeline (2-4%). Gender- and age-related differences in melamine concentrations were observed, although no such pattern was found for cyanuric acid. After adjusting for creatinine, melamine and cyanuric acid concentrations were moderately predictable with inter-day intraclass correlation coefficients (ICCs) in the range of 0.541-0.763. Nevertheless, substantial inter-individual variation in melamine levels existed even after creatinine adjustment, as evidenced by low ICCs (0.008-0.108). Cumulative daily intake of melamine and cyanuric acid was calculated on the basis of urinary concentrations and the mean values were found to be at least 10-fold below the current tolerable daily intake.
PMCID:6402796
PMID: 30572169
ISSN: 1873-6750
CID: 4287382

Assessing effects of germline exposure to environmental toxicants by high-throughput screening in C. elegans

Shin, Nara; Cuenca, Luciann; Karthikraj, Rajendiran; Kannan, Kurunthachalam; Colaiácovo, Monica P
Chemicals that are highly prevalent in our environment, such as phthalates and pesticides, have been linked to problems associated with reproductive health. However, rapid assessment of their impact on reproductive health and understanding how they cause such deleterious effects, remain challenging due to their fast-growing numbers and the limitations of various current toxicity assessment model systems. Here, we performed a high-throughput screen in C. elegans to identify chemicals inducing aneuploidy as a result of impaired germline function. We screened 46 chemicals that are widely present in our environment, but for which effects in the germline remain poorly understood. These included pesticides, phthalates, and chemicals used in hydraulic fracturing and crude oil processing. Of the 46 chemicals tested, 41% exhibited levels of aneuploidy higher than those detected for bisphenol A (BPA), an endocrine disruptor shown to affect meiosis, at concentrations correlating well with mammalian reproductive endpoints. We further examined three candidates eliciting aneuploidy: dibutyl phthalate (DBP), a likely endocrine disruptor and frequently used plasticizer, and the pesticides 2-(thiocyanomethylthio) benzothiazole (TCMTB) and permethrin. Exposure to these chemicals resulted in increased embryonic lethality, elevated DNA double-strand break (DSB) formation, activation of p53/CEP-1-dependent germ cell apoptosis, chromosomal abnormalities in oocytes at diakinesis, impaired chromosome segregation during early embryogenesis, and germline-specific alterations in gene expression. This study indicates that this high-throughput screening system is highly reliable for the identification of environmental chemicals inducing aneuploidy, and provides new insights into the impact of exposure to three widely used chemicals on meiosis and germline function.
PMCID:6375566
PMID: 30763314
ISSN: 1553-7404
CID: 4287472

Mass flows and removal of eight bisphenol analogs, bisphenol A diglycidyl ether and its derivatives in two wastewater treatment plants in New York State, USA

Xue, Jingchuan; Kannan, Kurunthachalam
Despite high production and usage of bisphenols including bisphenol A (BPA) as well as bisphenol A diglycidyl ether and its derivatives (BADGEs), little is known about the occurrence and fate of these substances in wastewater treatment plants (WWTPs) in the U.S. In this study, we investigated the occurrence, removal, mass flows, and fate of eight bisphenol analogues and six BADGEs based on the concentrations measured in influent, primary effluent, final effluent, and sludge from two WWTPs (WWTPA and WWTPB) in the Albany area of New York State, USA. BPA, bisphenol F, bisphenol S, and BADGE·2H2O were the predominant compounds found in influents of both WWTPs, at respective geometric mean (GM) concentrations of 90.0, 90.2, 31.2, and 6.48 ng/L in WWTPA, and 53.3, <MLOQ, 27.6, 2.25 ng/L in WWTPB. Incomplete removal of these compounds was observed in both WWTPs with the highest removal rate (52%) was found for BPA after the secondary treatment in WWTPA. The fraction of BPA sorbed to suspended particulate matter (SPM) was 6.83%. Mean daily mass loadings of total bisphenols and BADGEs ranged from 9.2 [∑(BADGEs) in WWTPB] to 226 mg/d/1000 inhabitants [∑(BPs) in WWTPA]. The environmental emission rates of total bisphenols and BADGEs through effluent discharges from WWTPs ranged from 13.7 [∑(BADGEs) in WWTPB] to 246 mg/d/1000 inhabitants [∑(BPs) in WWTPA]. Overall, bisphenols and BADGEs were not removed completely by activated sludge treatment. Furthermore, formation of bisphenols from the degradation of microplastics or other precursors such as alkylated bisphenols, in WWTPs is suggested.
PMID: 30121043
ISSN: 1879-1026
CID: 4287232

Distribution and partitioning of perfluoroalkyl carboxylic acids in surface soil, plants, and earthworms at a contaminated site

Zhu, Hongkai; Kannan, Kurunthachalam
A field study was conducted to elucidate distribution and partitioning of perfluoroalkyl carboxylic acids (PFCAs; C7-12) in a terrestrial ecosystem that was contaminated with industrial sources of release. Surface soil (0-6 cm), plants, and earthworms were collected from a field located within a 1-mile radius of a fluoropolymer industry that had been manufacturing fluorochemicals for over five decades. The mean concentrations of ∑PFCAs were 150, 420, 61, 68, and 430 ng/g dry weight (dw) in surface soil, earthworms, grass roots, grass leaves, and tree leaves, respectively. The measured concentrations were higher than those reported for corresponding matrices in other locations worldwide, suggesting that fluorochemical manufacturing operations have contributed to the contamination of this nearby land. Soil and plant tissues consisted mainly of perfluorooctanoic acid (PFOA; C8) (77.3-97.1% of the total PFCAs), whereas longer-chain PFCAs, such as perfluoroundecanoic acid (PFUnDA; C11: 17.6%) and perfluorododecanoic acid (PFDoDA; C12: 31.9%), accounted for relatively higher proportions in earthworms. Spatial distribution of PFCAs at this site suggested that both atmospheric deposition and groundwater recharge have contributed to the sources of contamination. Both earthworm- and grass-accumulated PFCAs from soil with biota-soil accumulation factors and root concentration factors increased with perfluorocarbon chain length. The translocation factors of PFCAs in grass decreased as the number of carbons in the fluorocarbon moiety increased. This field study is appropriate to improve our understanding of partitioning of PFCAs among soil, plants, and earthworms.
PMID: 30180370
ISSN: 1879-1026
CID: 4287262

Tissue-Specific Accumulation and Body Burden of Parabens and Their Metabolites in Small Cetaceans

Jeong, Yunsun; Xue, Jingchuan; Park, Kyum Joon; Kannan, Kurunthachalam; Moon, Hyo-Bang
Parabens have been of global concern due to their endocrine disrupting properties. However, few studies have reported tissue-specific distribution of parabens in wildlife. In this study, we measured parabens and their metabolites in organs and tissues (blubber, muscle, melon, stomach, kidney, liver, gonad, brain, uterus, and umbilical cord, total n = 94) of common dolphins ( Delphinus capensis) and finless porpoises ( Neophocaena asiaeorientalis), to investigate tissue-specific accumulation and body burden. Among the target compounds, methyl paraben (MeP) and para-hydroxybenzoic acid (4-HB) were detected in all organs. Compared to common dolphins, finless porpoises had significantly higher concentrations of MeP and 4-HB due to their near-shore habitat. Higher concentrations of MeP and 4-HB were found in the kidney, liver, and stomach than in other organs, indicating selective accumulation of parabens in certain organs. Significant correlations between MeP and 4-HB in liver/kidney suggested metabolic transformation of the former to the latter. Detection of parabens in brains, umbilical cords, and uteri suggests that these chemicals cross biological barriers such as the blood-brain and placental barriers. The body burdens of total parabens were in the ranges of 13000-90600 μg and 19800-81500 μg for common dolphins and finless porpoises, respectively.
PMID: 30518212
ISSN: 1520-5851
CID: 4287362

Metabolites of organophosphate esters in urine from the United States: Concentrations, temporal variability, and exposure assessment

Wang, Yu; Li, Wenhui; Martínez-Moral, María Pilar; Sun, Hongwen; Kannan, Kurunthachalam
Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers in consumer products, which contributes to widespread exposure of humans. OPE diester metabolites in urine have been used as biomarkers of human exposure to these chemicals. Little is known, however, about occurrence and temporal variability in urinary concentrations of OPE metabolites in humans. In this study, 11 OPE metabolites were measured in 213 urine samples collected from 19 volunteers from Albany, New York, United States, at 3-day intervals for five weeks to investigate temporal variability in urinary concentrations. Diphenyl phosphate (DPHP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were the major OPE metabolites, detected in all urine samples at specific gravity (SG)-adjusted concentrations (geometric mean, GM) of 1060 and 414 pg/mL and creatinine (Cr)-adjusted concentration (GM) of 404 and 156 ng/g, respectively. Inter-day variability in urinary OPE metabolite concentrations in 19 individuals was evaluated by intraclass correlation coefficients (ICCs). The inter-day variability in Cr-adjusted OPE metabolite concentrations (ICC: 0.31-0.67) was lower than those of SG-adjusted (ICC: 0.19-0.71) and unadjusted urinary concentrations (ICC: 0.24-0.74). BDCIPP (ICC: 0.68) and bis(2-chloroethyl) phosphate (BCEP) (ICC: 0.67) concentrations showed a moderate-to-high reliability over the sampling period, whereas the other nine OPE metabolites exhibited a moderate reliability (ICC: 0.31-0.55). Urine samples were further stratified by gender, age, ethnicity, and body mass index (BMI). The concentrations of BDCIPP and DPHP were significantly lower in males with normal BMI (BMI: 18.5-25 kg/m2) than in females and other BMI categories (p < 0.01). Relatively high ICCs, indicating low inter-day variability, were observed for males (ICC: 0.35-0.71) of 30-40 years of age (ICC: 0.34-0.87) with normal BMI (ICC: 0.28-0.64). The daily exposure doses to OPEs were estimated from urinary concentrations of corresponding OPE metabolites. The estimated doses of triphenyl phosphate (TPHP) and triethyl phosphate (TEP), based on median urinary concentrations of their metabolites, were 19.4 and 24.0 ng/kg bw/day, and the exposure dose to ∑OPEs was estimated at 65.3 ng/kg bw/day. Overall, our results indicate a high ICC for Cr-adjusted urinary concentrations of 11 OPE metabolites in urine.
PMCID:6311423
PMID: 30449628
ISSN: 1873-6750
CID: 4287342

Examining Endocrine Disruptors Measured in Newborn Dried Blood Spots and Early Childhood Growth in a Prospective Cohort

Yeung, Edwina H; Bell, Erin M; Sundaram, Rajeshwari; Ghassabian, Akhgar; Ma, Wanli; Kannan, Kurunthachalam; Louis, Germaine M
OBJECTIVE:The goal of this study was to determine whether newborn concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and bisphenol A (BPA) are associated with early childhood growth. METHODS:A total of 1,954 singletons and 966 twins from the Upstate KIDS Study (born 2008-2010) were included in this study. Newborn dried blood spot concentrations of PFOS, PFOA, and BPA were quantified by liquid chromatography tandem mass spectrometry. Children's weight and height were reported from birth through 3 years of age. Repeated measures were modeled using generalized linear mixed models. RESULTS:[-0.17 to -0.051] per 1 standard deviation increase in log PFOS and PFOA, respectively) and not with early obesity among singletons. Inconsistent associations were observed for twins. BPA levels were higher among neonates with a neonatal intensive care unit stay (P < 0.001), making associations difficult to interpret. CONCLUSIONS:Perfluorinated alkyl substances did not exhibit obesogenic associations with early measures of childhood growth. Blood-based BPA measures are limited by the nonpersistent nature of the chemical, and unknown sources from hospital settings may present only transient exposures.
PMID: 30569634
ISSN: 1930-739x
CID: 3556712

Serum Cotinine versus Parent Reported Measures of Secondhand Smoke Exposure in Rural Appalachian Children

Yeramaneni, Samrat; Yolton, Kimberly; Kannan, Kurunthachalam; Dietrich, Kim N; Haynes, Erin N
Background/UNASSIGNED:Secondhand smoke (SHS) exposure in Appalachian children and associated adverse effects is understudied and not well documented. This study assessed the prevalence of SHS exposure in Appalachian children by parental self-report and internal biological measure. Methods/UNASSIGNED:SHS exposure was determined in children residing in rural Appalachian communities during their participation in the Communities Actively Researching Exposure Study between 2009 and 2013. Parents reported the number of smokers in the household and number of cigarettes smoked/day. Children ages 7-9 provided a serum sample for cotinine analysis. Parent reported measures and child serum cotinine measures of SHS exposure were compared with national and Appalachian-state estimates. Data analysis for the study was done in 2013. Results/UNASSIGNED:Approximately 37% parents reported at least one smoker in the home, yet 50% of children had a detectible level of cotinine in serum. The mean serum cotinine level in children was 0.7 + 1.6 ng/mL. In homes of at least one reported smoker, an average of 20 cigarettes were smoked//day. Compared to 7.6% children, aged 3-19 years, exposed to SHS nationally, 36.6% children in our study were exposed to SHS living in Appalachian counties. Implications/UNASSIGNED:Children living in rural Appalachian counties are significantly exposed to SHS exposure. Parental self-reports of smoking underestimates child exposure to SHS as measured by serum cotinine levels. Developing risk communication messages and implementing culturally appropriate interventions aimed at reducing tobacco dependence in rural Appalachian regions should be explored.
PMCID:6553863
PMID: 31179444
ISSN: 2641-7804
CID: 4287592