Papers by Nayana Jayatilaka
Environmental Health, Apr 11, 2017
Background: Organophospate flame retardants (PFRs) are chemicals of emerging concern due to restr... more Background: Organophospate flame retardants (PFRs) are chemicals of emerging concern due to restrictions on polybrominated diphenyl ether flame retardant formulations. We describe the occurrence, variability, and predictors of urinary metabolites of PFRs among pregnant women. Methods: In 2014-2015, 59 women from Providence, RI provided up to 3 spot urine samples during pregnancy (~12, 28, and 35 weeks' gestation). We created a pooled urine sample per woman and measured nine relevant metabolites in individual and pooled samples. We used linear mixed models to calculate intraclass correlation coefficients (ICCs) across the 3 measurements and to assess sociodemographic and dietary predictors of PFRs. Results: The median (IQR) of bis-2-chloroethyl phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), and diphenyl phosphate (DPhP), the metabolites most frequently detected, from pooled samples were: 0.31 μg/L (0.17-0.54), 1.18 μg/L (0.64-2.19), 0.93 μg/L (0.72-1.97), respectively. We observed fair to good reproducibility for BCEP (ICC = 0.50), BDCPP (ICC = 0.60), and DPhP (ICC = 0.43), and excellent agreement between the urinary flame retardant metabolite concentrations averaged across pregnancy versus pooled urine sample concentrations for BCEP (ICC = 0.95), BDCPP (ICC = 0.89), and DPhP (ICC = 0.93). Adjusting for pertinent sociodemographic factors and gestational week of urine collection, each 1 kg increase in pre-pregnancy weight was associated with greater BCEP (1.1%; 95% CI: 0.1, 2.1), BDCPP (1.5%; 95% CI: 0.3, 2.7), and DPhP (0.5%; 95% CI: 0.0, 1.1). Dietary factors were generally not associated with urinary flame retardant metabolites. Conclusions: Urinary concentrations of BCEP, BDCPP, and DPhP were frequently detected among women in this pilot study and had fair reproducibility across pregnancy. Body size may be an important predictor of urinary flame retardant metabolite concentrations.
Journal of Physical Chemistry B, Jan 9, 2007
In sodium guanosine dihydrate single crystals, the guanine moiety is deprotonated at N1 due to gr... more In sodium guanosine dihydrate single crystals, the guanine moiety is deprotonated at N1 due to growth from high-pH (>12) solutions. EPR and ENDOR study of crystals x-irradiated at 10 K detected evidence for three radical forms. Radical R1,characterized by two proton and two nitrogen hyperfine interactions, was identified as the product of net hydrogenation at N7 of the N1deprotonated guanine unit. R1 exhibited an unusually distorted structure leading to net positive isotropic components of the hydrogen couplings. Radical R2, characterized by one proton and one nitrogen hyperfine coupling was identified as the primary electron loss product. This product is equivalent to that of deprotonation at N1 by the guanine cation and represents the first ENDOR characterization of that product. Radical R3, characterized by a single hydrogen hyperfine coupling, was identified as the product of net dehydrogenation at C1 of the ribose moiety. The identification of radicals R1-R3 was supported by DFT calculations on several possible structures using the B3LYP/ 6-311G(2df,p)//6-31G(d,p) approach. Radical R4, detected after warming the crystals to room temperature, was identified as the well-known product of net hydrogenation of C8 of the (N1deprotonated) guanine component. Radical R1, evidently formed by protonation of the primary electron addition product, was present as roughly 60% of the total radicals detected at 10 K. Radical R2 was present as roughly 27% of the total yield, and the concentration of R3 contributed the remaining 13%. R3 is evidently the product of oneelectron oxidation followed by deprotonation; thus, the balance of oxidation and reduction products is approximately equal within experimental uncertainty.
Environmental health perspectives, Aug 17, 2016
Background: Organophospate flame retardants (PFRs) are chemicals of emerging concern due to restr... more Background: Organophospate flame retardants (PFRs) are chemicals of emerging concern due to restrictions on polybrominated diphenyl ether flame retardant formulations. We describe the occurrence, variability, and predictors of urinary metabolites of PFRs among pregnant women. Methods: In 2014-2015, 59 women from Providence, RI provided up to 3 spot urine samples during pregnancy (~12, 28, and 35 weeks' gestation). We created a pooled urine sample per woman and measured nine relevant metabolites in individual and pooled samples. We used linear mixed models to calculate intraclass correlation coefficients (ICCs) across the 3 measurements and to assess sociodemographic and dietary predictors of PFRs. Results: The median (IQR) of bis-2-chloroethyl phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), and diphenyl phosphate (DPhP), the metabolites most frequently detected, from pooled samples were: 0.31 μg/L (0.17-0.54), 1.18 μg/L (0.64-2.19), 0.93 μg/L (0.72-1.97), respectively. We observed fair to good reproducibility for BCEP (ICC = 0.50), BDCPP (ICC = 0.60), and DPhP (ICC = 0.43), and excellent agreement between the urinary flame retardant metabolite concentrations averaged across pregnancy versus pooled urine sample concentrations for BCEP (ICC = 0.95), BDCPP (ICC = 0.89), and DPhP (ICC = 0.93). Adjusting for pertinent sociodemographic factors and gestational week of urine collection, each 1 kg increase in pre-pregnancy weight was associated with greater BCEP (1.1%; 95% CI: 0.1, 2.1), BDCPP (1.5%; 95% CI: 0.3, 2.7), and DPhP (0.5%; 95% CI: 0.0, 1.1). Dietary factors were generally not associated with urinary flame retardant metabolites. Conclusions: Urinary concentrations of BCEP, BDCPP, and DPhP were frequently detected among women in this pilot study and had fair reproducibility across pregnancy. Body size may be an important predictor of urinary flame retardant metabolite concentrations.
Journal of Chromatography B, Jul 1, 2012
Atrazine [6-chloro-N-ethyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine] is the most widely used... more Atrazine [6-chloro-N-ethyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine] is the most widely used herbicide in the United States. In recent years, there has been controversy about atrazine's potential endocrine/reproductive and neurological adverse effects in wildlife and humans. The controversy triggered several environmental and epidemiologic studies, and it generated needs for sensitive and selective analytical methods for the quantification of atrazine, atrazine metabolites, and degradation or hydrolysis products. We developed a two-dimensional high performance liquid chromatography (2D-HPLC) method with isotope dilution tandem mass spectrometry detection to measure atrazine in urine, along with 11 atrazine metabolites and hydrolysis products, including 6chloro (Cl), 6-mercapto (Mer) and 6-hydroxy (OH) derivatives, and their desethyl, desisopropyl and diamino atrazine analogs (DEA, DIA and DAA, respectively). The 2D-HPLC system incorporated strong cation exchange and reversed phase separation modes. This versatile approach can be used for the quantitative determination of all 12 compounds in experimental animals for toxicological studies. The method requires only 10 μL of urine, and the limits of detection (LODs) range from 10 to 50 μg/L. The method can also be applied to assess atrazine exposure in occupational settings by measurement of 6-Cl and 6-Mer analogs, which requires only 100 μL of urine with LODs of 1-5 μg/L. Finally, in combination with automated off-line solid phase extraction before 2D-HPLC, the method can also be applied in non-occupational environmental exposure studies for the determination of 6-Cl and -6-Mer metabolites, using 500 μL of urine and LODs of 0.1-0.5 μg/L.
Environmental Health, Sep 11, 2020
Background: Organophosphate esters (OPEs)-used as flame retardants and plasticizers-are associate... more Background: Organophosphate esters (OPEs)-used as flame retardants and plasticizers-are associated with adverse pregnancy outcomes such as reduced fecundity and live births and increased preterm delivery. OPEs may interfere with growth and metabolism via endocrine-disruption, but few studies have investigated endocrinerelated outcomes. The objective of this pilot study (n = 56 mother-infant pairs) was to evaluate associations of OPEs with gestational weight gain (GWG), gestational age at delivery, infant anthropometry, and infant feeding behaviors. Methods: We quantified OPE metabolites (bis-2-chloroethyl phosphate [BCEP], bis (1,3-dichloro-2-propyl) phosphate [BDCPP], diphenyl phosphate [DPHP]) in pooled maternal spot urine collected throughout pregnancy (~12, 28, and 35 weeks' gestation). We obtained maternal sociodemographic characteristics from questionnaires administered at enrollment and perinatal characteristics from medical record abstraction. Trained research assistants measured infant weight, length, head and abdominal circumferences, and skinfold thicknesses at birth and 6 weeks postpartum. Mothers reported infant feeding behavior via the Baby Eating Behavior Questionnaire (BEBQ). Using multiple linear regression, we assessed associations of log 2-transformed maternal urinary OPE metabolites with GWG, gestational age at delivery, infant anthropometry at birth, weekly growth rate, and BEBQ scores at 6 weeks postpartum. We used linear mixed effects (LME) models to analyze overall infant anthropometry during the first 6 weeks of life. Additionally, we considered effect modification by infant sex.
ISEE Conference Abstracts
Background/Aim: Because of the phase-out of polybrominated diphenyl ethers (PBDEs), flame retarda... more Background/Aim: Because of the phase-out of polybrominated diphenyl ethers (PBDEs), flame retardant formulations containing mixtures of chlorinated and non-chlorinated organophosphates as well as o...
Parent flame retardants and limits of detection and percent detected of associated urinary metabo... more Parent flame retardants and limits of detection and percent detected of associated urinary metabolites. Table S2. Urinary concentrations of flame retardant metabolites and coefficients of variation (CV) in 12 blinded replicates. Table S3. Medians and selected percentiles of urinary flame retardant metabolites in urine during pregnancy. Table S4. Intraclass correlation coefficients of pilot study participantsâ urinary flame retardant metabolite concentrations during pregnancy. Table S5. Intraclass correlation coefficients of average urinary flame retardant metabolite concentrations during pregnancy across pregnancy samples versus concentrations from a pooled urine sample among pilot study participants. Table S6. Spearman correlations among specific gravity standardized concentrations of flame retardant metabolites from the pooled urine samples. Table S7. Adjusted percent difference in urinary flame retardant metabolite concentrations as a function of sociodemographic predictors. Tabl...
Additional file 1: Table S1. Parent OPE, limits of detection and detection frequency of associate... more Additional file 1: Table S1. Parent OPE, limits of detection and detection frequency of associated urinary metabolites. Table S2. Maternal urinary OPE metabolite concentration was weakly associated with increased GWG. Table S3. Associations between urinary OPE metabolite concentration and weekly change in infant anthropometric measurement between birth and six weeks postpartum. Table S4. Linear mixed effects models for repeated measurements of infant anthropometrics at birth and six weeks postpartum. Table S5. Baby Eating Behavior Questionnaire (BEBQ) assessment of infant feeding behavior.
International Journal of Hygiene and Environmental Health, 2021
Triphenyl phosphate (TPP or TPhP) is commonly used as an additive plasticizer or organophosphate ... more Triphenyl phosphate (TPP or TPhP) is commonly used as an additive plasticizer or organophosphate flame retardant (OPFR)in consumer products including nail polish. We evaluated exposure to TPhP from 12 nail salon technicians working at four nail salons located in California over a period of two work days. Bulk samples of 15 nail polish and other nail products were collected. Study participants also provided two personal air samples, two hand wipe samples (preand post-shift on day two), and two urine samples (pre-shift day one and post-shift day two). The geometric mean (GM) of TPhP air sampling concentrations was 7.39 ng/m 3. Post-shift TPhP hand wipe concentrations (GM 1.35 μg/sample) were significantly higher (p = 0.024) than pre-shift hand wipe concentrations (GM 0.29 μg/sample). Diphenyl phosphate (DPP or DPhP), a urinary metabolite of TPhP used in this study as a biomarker of exposure, was detected in all post-shift urine samples and 75% of urine pre-shift samples. DPhP post-shift concentrations (GM 1.35 μg/g creatinine) were significantly higher than pre-shift concentrations (GM 0.84 μg/g creatinine; p = 0.012). In addition, DPhP post-shift concentrations were correlated with TPhP post-shift hand wipe concentrations, suggesting dermal contact may be a relevant exposure pathway for nail salon workers.
Environmental Epidemiology, 2019
Conclusion: We suggest that road traffic noise exposure in nurses with susceptibilities, such as ... more Conclusion: We suggest that road traffic noise exposure in nurses with susceptibilities, such as those with job strain, or living in urban areas, may lead to increased BMI, an adiposity marker.
Chemosphere, 2019
Chlorinated alkyl and non-chlorinated aryl organophosphate flame retardants (OPFRs) and some brom... more Chlorinated alkyl and non-chlorinated aryl organophosphate flame retardants (OPFRs) and some brominated flame retardants (FR) were introduced as replacements for polybrominated diphenyl ethers (PBDEs) after PBDEs phase-out in 2004 and 2013. Organophosphorous (OP) insecticides are mainly used in agricultural settings since the Food Quality Protection Act of 1996 phased-out most residential uses of OP insecticides in the United States.
Journal of Occupational and Environmental Hygiene, 2019
Tris(1-chloro-2-propyl) phosphate (TCPP, also referenced as TCIPP), a flame retardant used in spr... more Tris(1-chloro-2-propyl) phosphate (TCPP, also referenced as TCIPP), a flame retardant used in spray polyurethane foam insulation, increases cell toxicity and affects fetal development. Spray polyurethane foam workers have the potential to be exposed to TCPP during application. In this study, we determined exposure to TCPP and concentrations of the urinary biomarker bis(1-chloro-2-propyl) phosphate (BCPP) among 29 spray polyurethane foam workers over 2 work days. Work was conducted at residential or commercial facilities using both open-cell (low density) and closed-cell (high density) foam. Study participants provided two personal air samples (Day 1 and Day 2), two hand wipe samples (Pre-shift Day 2 and Postshift Day 2), and two spot urine samples (Pre-shift Day 1 and Post-shift Day 2). Bulk samples of cured spray foam were also analyzed. Sprayers were found to have significantly higher TCPP geometric mean (GM) concentration in personal air samples (87.1 lg/m 3), compared to helpers (30.2 lg/m 3 ; p ¼ 0.025). A statistically significant difference was observed between TCPP pre-and post-shift hand wipe GM concentrations (p ¼ 0.004). Specifically, TCPP GM concentration in post-shift hand wipe samples of helpers (106,000 ng/sample) was significantly greater than pre-shift (27,300 ng/sample; p < 0.001). The GM concentration of the urinary biomarker BCPP (23.8 lg/g creatinine) was notably higher than the adult male general population (0.159 lg/g creatinine, p < 0.001). Urinary BCPP GM concentration increased significantly from Pre-shift Day 1 to Post-shift Day 2 for sprayers (p ¼ 0.013) and helpers (p ¼ 0.009). Among bulk samples, cured open-cell foam had a TCPP GM concentration of 9.23% by weight while closed-cell foam was 1.68%. Overall, post-shift BCPP urine concentrations were observed to be associated with TCPP air and hand wipe concentrations, as well as job position (sprayer vs. helper). Spray polyurethane foam workers should wear personal protective equipment including air-supplied respirators, coveralls, and gloves during application.
Environment international, 2018
Use of organophosphate flame retardants (OPFRs) including tris(1,3-dichloro-2-propyl) phosphate, ... more Use of organophosphate flame retardants (OPFRs) including tris(1,3-dichloro-2-propyl) phosphate, triphenyl phosphate, tris(1-chloro-2-propyl) phosphate, and tris-2-chloroethyl phosphate, in consumer products is on the rise because of the recent phase out of polybrominated diphenyl ether (PBDE) flame retardants. Some of these chemicals are also used as plasticizers or lubricants in many consumer products. To assess human exposure to these chlorinated and non-chlorinated organophosphates, and non-PBDE brominated chemicals in a representative sample of the U.S. general population 6years and older from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). We used solid-phase extraction coupled to isotope dilution high-performance liquid chromatography-tandem mass spectrometry after enzymatic hydrolysis of conjugates to analyze 2666 NHANES urine samples for nine biomarkers: diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis-(1-chloro-2-propyl...
Analytical and bioanalytical chemistry, 2017
Polybrominated diphenyl ethers (PBDEs), produced as flame retardants worldwide, have been phased-... more Polybrominated diphenyl ethers (PBDEs), produced as flame retardants worldwide, have been phased-out in many countries, and chlorinated and non-chlorinated organophosphates and non-PBDE brominated formulations (e.g., Firemaster 550 (FM550)) have entered the consumers' market. Recent studies show that components of organophosphate esters and FM550 are frequently detected in many products common to human environments. Therefore, urinary metabolites of these compounds can be used as human exposure biomarkers. We developed a method to quantify nine compounds in 0.4 mL urine: diphenyl phosphate (DPhP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis-(1-chloro-2-propyl) phosphate, bis-2-chloroethyl phosphate, di-p-cresylphosphate, di-o-cresylphosphate (DoCP), di-n-butyl phosphate, dibenzyl phosphate (DBzP), and 2,3,4,5-tetrabromobenzoic acid. The method relies on an enzymatic hydrolysis of urinary conjugates of the target analytes, automated off-line solid phase extraction, reversed...
Environmental Science & Technology, 2014
The variability and predictors of urinary concentrations of phthalate metabolites in preschool-ag... more The variability and predictors of urinary concentrations of phthalate metabolites in preschool-aged children have not been thoroughly examined. Additionally, the impact of temporal changes in the use and restriction of phthalates in children's products has not been assessed. Our objective was to identify demographic, behavioral, and temporal predictors of urinary phthalate metabolite concentrations in young children. Between 2004 and 2011, we collected up to five urine samples from each of 296 children participating in a prospective birth cohort during annual study visits at ages 1− 5 years. We used linear mixed models to calculate intraclass correlation coefficients (ICCs), a measure of within-individual reproducibility, and identify demographic predictors of urinary phthalate metabolites. We used multivariable linear regression to examine cross-sectional relationships between food packaging or personal care product use and phthalate metabolites measured at age 5 years. Across annual measurements, monoethyl phthalate exhibited the least variation (ICC = 0.38), while di-2-ethylhexyl phthalate (ΣDEHP) metabolites exhibited the most variation (ICC = 0.09). Concentrations changed with age, suggesting age-related changes in phthalate exposure and perhaps metabolism. Our findings suggest that fast food consumption may be a source of butylbenzyl phthalate and di-isononyl phthalate (DiNP) exposure, and some personal care products may be sources of diethyl phthalate exposure. Concentrations of ΣDEHP metabolites decreased over the study period; however, concentrations of DiNP metabolites increased. This finding suggests that manufacturer practices and regulations, like the Consumer Product Safety Improvement Act of 2008, may decrease DEHP exposure, but additional work characterizing the nature and toxicity of replacements is critically needed.
The Journal of Physical Chemistry B, 2008
Computational methods based on DFT procedures have been used to investigate proton-transfer proce... more Computational methods based on DFT procedures have been used to investigate proton-transfer processes in irradiated 9-ethylguanine crystals. Previous experimental results from X-irradiation and study of this system at 10 K found significant concentrations of two main products, R1, formed by N7-hydrogenation of the purine ring, and R2, the primary one-electron oxidation product (Jayatilaka, N.; Nelson, W. H. J. Phys. Chem. B 2007, 111, 7887). The objective of this work is to describe the processes leading to these products using computational methods that take into account molecular packing and bulk dielectric properties. The basic concept is that a proton will transfer following ionization if the net electronic energy of the system, consisting of the donor plus the acceptor plus any intervening molecules, becomes lower. Three approaches were used to investigate this concept, two based on energies computed for single molecules and one based on energies computed for two-molecule clusters arranged as in the crystals. The results are that the methods successfully predict the observed behavior, that it is energetically favorable on one-electron reduction for proton H1 to transfer from a neutral molecule to N7 of the neighbor, forming the N7-hydrogenated product, and that there is virtually no energy advantage for a proton to transfer upon one-electron oxidation. The results also support the proposal that the C8 H-addition radical, found only upon irradiation at 300 K, was the product of intramolecular transfer of the H7 proton to C8 in a process apparently requiring sufficient thermal energy for activation. Finally, the computations predict hyperfine couplings and tensors in very good agreement with those from experiment, thereby providing additional evidence for the success of the computations in describing the experimental observations.
Journal of Pharmaceutical and Biomedical Analysis, 2010
Ethyl methanesulfonate (EMS) is a mesylate ester, which is known to be a potent mutagen, teratoge... more Ethyl methanesulfonate (EMS) is a mesylate ester, which is known to be a potent mutagen, teratogen, and possibly carcinogen. Mesylate esters have been found in pharmaceuticals as contaminants formed during the manufacturing process and may potentially pose an exposure hazard to humans. We have developed and validated a method for detection of trace amounts (ng/ml levels) of EMS in human plasma and breast milk. The samples were extracted by matrix solid-phase dispersion with ethyl acetate using Hydromatrix and the ASE 200 Accelerated Solvent Extractor. The extracts were separated by high-performance liquid chromatography (HPLC) using a HILIC column. The detection was performed with a triple quadrupole mass spectrometer (TSQ Quantum Ultra, Thermo Electron Corporation) using atmospheric pressure chemical ionization in negative-ion mode and multiple reaction monitoring. The use of a surrogate internal standard in combination with HPLC-MS/MS provided a high degree of accuracy and precision. The extraction efficiency was greater than 70%. Repeated analyses of plasma and breast milk samples spiked with high (100 ng/ml), medium (50 ng/ml) and low (5 ng/ml) concentrations of the analytes gave relative standard deviations of less than 12%. The limits of detection were in the range of 0.5-0.9 ng/ml for both matrices.
Journal of Chromatography B, 2010
We have developed a highly selective and sensitive analytical method to quantify paraquat and diq... more We have developed a highly selective and sensitive analytical method to quantify paraquat and diquat by use of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The sample preparation includes solid phase extraction that uses weak cation exchange cartridges. These highly charged dual quaternary amines were not retained by standard reversed phase columns, but they could be adequately separated through HPLC with a HILIC column. The detection was carried out with a triple quadrupole mass spectrometer with an electrospray ionization probe in positive ion mode in multiple reaction monitoring. Repeated analysis in human urine samples spiked with low (5 ng/ml), medium (15 ng/ml), and high (30 ng/ml) concentrations of the analytes yielded relative standard deviations of less than 9%. The extraction efficiencies ranged from 77.7% to 94.2%. The limits of detection were in the range of 1 ng/ml.
Physics & Astronomy Dissertations, 2006
In this work, the energetics and the proton transfer reactions in 9 ethyl guanine (9EtG) base pai... more In this work, the energetics and the proton transfer reactions in 9 ethyl guanine (9EtG) base pair anion and cation radicals in the crystallographic geometry were studied using ab initio density functional theory. Here we employed DFT theory with UB3LYP functional and the 6-31+G(D) basis set. Even though there are two possible protontransfers associated with this 9EtG crystallographic arrangement, only the N1H proton transfer was succeeded at the level of theory considered. For both anion and cation radicals, N1H of molecule (b) transferred to N7 of molecule (a). The stabilized structures for initial, proton transferred and transition structures were found for both anion and cation radical pairs. However the located transition structure for base-pair anion radical did not connect the initial and proton transferred structures either energetically or structurally. The forward and reverse activation energies as well as reaction enthalpies and free energy changes were also calculated. On the basis of these thermodynamic data, the proton transfer process is unfavorable even for the cationic base-pair. Electron affinities (EA) and ionization energies (IE) of 9EtG base-pair as well as single 9EtG molecule are also calculated and reported.
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Papers by Nayana Jayatilaka