Perfluorinated compound levels in cord blood and neurodevelopment at 2 years of age.

BACKGROUND: Epidemiologic data regarding the potential neurotoxicity of perfluorinated compounds (PFCs) are inconclusive. We investigated the associations between in utero exposure to perfluorooctanoic acid (PFOA) and perfluorooctyl sulfonate (PFOS) and early childhood neurodevelopment. METHODS: We recruited 239 mother-infant pairs in northern Taiwan from the Taiwan Birth Panel Study, which was established in 2004. We examined the association between PFCs in cord blood and children's neurodevelopment at 2 years of age, using the Comprehensive Developmental Inventory for Infants and Toddlers. This tool contains cognitive, language, motor, social, and self-help domains; test scores were further transformed into developmental quotients according to standardized norms. All multivariate regression models were adjusted for infant sex and gestational age, maternal education, family income, cord blood cotinine levels, postnatal environmental tobacco smoke exposure, and breastfeeding. RESULTS: Prenatal PFOS concentrations in both untransformed and natural log (Ln)-transformed values were associated with adverse performance on the whole test and the domains related to development. A dose-response relationship was observed when PFOS levels were categorized into four groups. This association was most obvious in relation to the gross-motor subdomain. Across the PFOS interquartile range, the quotients of the gross-motor subdomain decreased by 3.7 points (95% confidence interval [CI] = -6.0 to -1.5), with an increasing odds ratio of poor performance (2.4; 95% CI = 1.3 to 4.2). In contrast, measures of association between PFOA concentrations and test scores were close to null. CONCLUSIONS: Prenatal exposure to PFOS, but not PFOA, may affect children's development, especially gross-motor development at 2 years of age.

Associations between levels of serum perfluorinated chemicals and adiponectin in a young hypertension cohort in Taiwan.

In animals, perfluorinated chemicals (PFCs), specifically perfluorooctanoic acid (PFOA) and perfluorooctane sulfate (PFOS), function as peroxisome proliferator-activated receptor (PPAR) alpha agonists. However, the relevance of animal (primarily rodent) data to humans is unresolved. While plasma adiponectin level is very responsive to PPAR gamma agonist drugs, it has not been determined whether adiponectin level is related to serum PFCs concentrations. In the present study, 287 subjects (12-30 years of age) were recruited to determine the relationship between serum level of PFCs and serum level of adiponectin. The results showed males had higher serum PFOS concentrations than females and that those with metabolic syndrome had lower serum PFOA than controls. Besides, it showed regional elevations of the perfluoroundecanoic acid (PFUA) (median concentration: 7.11 ng/mL) in the study subjects. No relationship of PFOA, PFOS, PFUA, and the sum of all four PFCs was found to glucose homeostasis, adiponectin level, lipid profile, and inflammatory markers. The median and the range of perfluorononanoic acid (PFNA) concentration (in ng/mL; for four categories corresponding to the <50, 50-74, 75-89, and ≥90th percentiles) were 0.38 (0.38-1.68), 3.22 (1.73-4.65), 5.85 (4.75-8.29), 10.56 (8.40-25.40), respectively. After controlling for confounding factors, multiple linear regression analysis revealed that the mean natural log-transformed level of adiponectin increased significantly across categories of PFNA (in ng/mL; 8.78, 8.73, 9.06, 9.36; P for trend = 0.010 in the full model). In conclusion, higher serum PFNA concentration is associated with elevated serum adiponectin concentration.

The effect of prenatal perfluorinated chemicals exposures on pediatric atopy.

BACKGROUND: The role of perfluorinated compounds (PFCs) in the immune system and allergic diseases is not well-known. This study examined the effects of pre-natal exposure to PFCs on immunoglobulin E (IgE) levels and atopic dermatitis (AD). METHODS: In Taiwan Birth Panel cohort study, newborns with cord blood and peri-natal factors (i.e. birth body weight, weeks of gestation, and type of delivery) gathered at birth were evaluated. At the age of 2 years, information on the development of AD, environmental exposures, and serum total IgE were collected. The AD and non-AD children were compared for the concentration of cord blood serum PFCs measured by Ultra-performance liquid chromatography/triple-quadrupole mass (UPLC-MS/MS). Correlations among cord blood IgE, serum total IgE at 2 years of age, and cord blood PFC levels were made. RESULTS: Of 244 children who completed the follow-up and specimen collections, 43 (17.6%) developed AD. Concentrations of cord blood serum perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) were median (range) 1.71 (0.75-17.40), 5.50 (0.11-48.36), 2.30 (0.38-63.87), and 0.035 (0.035-0.420)ng/mL, respectively. PFOA and PFOS levels positively correlated with cord blood IgE levels (per ln-unit: ß=0.134 KU/l, p=0.047 for PFOA; ß=0.161 KU/l, p=0.017 for PFOS). Analyses stratified by gender revealed that PFOA and PFOS levels positively correlated with cord blood IgE levels only in boys (per ln-unit: ß=0.206 KU/l, p=0.025 for PFOA; ß=0.175 KU/l, p=0.053 for PFOS). When dividing cord blood serum PFCs into quartiles in the fully adjusted models, AD had no significant association with PFOS. CONCLUSIONS: Pre-natal PFOA and PFOS exposures positively correlated with cord blood IgE levels.

Lipid responses to environmental perfluoroalkyl substance exposure in a Taiwanese Child cohort.

Although recent epidemiologic studies have focused on some of the health effects of perfluoroalkyl substance (PFASs) exposure in humans, the associations between PFASs exposure and the lipidome in children are still unclear. The purpose of this study was to assess lipid changes in children to understand possible molecular events of environmental PFASs exposure and suggest potential health effects. A total of 290 Taiwanese children (8-10 years old) were included in this study. Thirteen PFASs were analyzed in their serum by high-performance liquid chromatography-tandem mass spectrometry (LC-MS). MS-based lipidomic approaches were applied to examine lipid patterns in the serum of children exposed to different levels of PFASs. LC coupling with triple quadrupole MS technology was conducted to analyze phosphorylcholine-containing lipids. Multivariate analyses, such as partial least squares analysis along with univariate analyses, including multiple linear regression, were used to analyze associations between s exposure and unique lipid patterns. Our results showed that different lipid patterns were discovered in children exposed to different levels of specific PFASs, such as PFTrDA, PFOS, and PFDA. These changes in lipid levels may be involved in hepatic lipid metabolism, metabolic disorders, and PFASs-membrane interactions. This study showed that lipidomics is a powerful approach to identify critical PFASs that cause metabolite perturbation in the serum of children and suggest possible adverse health effects of these chemicals in children.

Comparison of electrospray ionization, atmospheric pressure chemical ionization and atmospheric pressure photoionization for determining estrogenic chemicals in water by liquid chromatography tandem mass spectrometry with chemical derivatizations.

This study compared the sensitivities and matrix effects of four ionization modes and four reversed-phase liquid chromatographic (LC) systems on analyzing estrone (E1), 17beta-estradiol (E2), estriol (E3), 17alpha-ethinylestradiol (EE2), 4-nonylphenol (NP), 4-tert-octylphenol (OP), bisphenol A (BPA) and their derivatives of dansyl chloride or pentafluorobenzyl bromide (PFBBr) in water matrixes using a triple-quadrupole mass spectrometer with selected reaction monitoring (SRM). The four probes were electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), atmospheric pressure photoionization (APPI) and APCI/APPI; the four LC systems were ultra-performance liquid chromatography (UPLC) with or without post-column split, a mixed-mode column and two-dimensional LC (2D-LC). Dansylated compounds with ESI at UPLC condition had the most intense signals and less matrix effects of the various combinations of ionization and LC systems. The on-column limits of detection (LODs) of dansylated estrogens by SRM were 0.05-0.20 pg, and the LODs in sewage treatment plant effluent and in river water were 0.23-0.52 and 0.56-0.91 ng/L, respectively. The LODs using selected ion monitoring (SIM) reached low ng/L levels in real samples and measured concentrations were comparable with those of SRM.

Dilute-and-shoot enhances sensitivity of phthalate urinary concentrations for assessing the exposure in children.

Phthalates are not covalently bound to plastics. They can leach from experimental plastic devices. Due to the development of sensitive techniques, exogenous sources that interfere with the accuracy of phthalate monoester analysis can be easily detected. Here, we propose the simple and rapid dilute-and-shoot method to minimize sample handling and limit contact with laboratory apparatus, which efficiently reduced phthalate interferences mainly from experimental plasticware and improved the accuracy of analysis. Chemical additives in the mobile phase and modifiers in reconstituted solution were evaluated to improve peak shape and liquid chromatography separation. Under optimal conditions, the limit of detection ranged from 0.01 to 0.5 ng/mL. No phthalate monoesters were detected above the limit of detection in blank water while the leached concentrations of MMP, MEP, MiBP, MnBP and MEHP from the conventional solid phase extraction procedure were 1.9, 2.7, 0.9, 2.0 and 1.1 ng/mL, respectively. In 304 samples collected from primary school- children aged 9-10 years, we observed a positive association between body mass index (BMI) and urinary MMP and MiBP concentrations in boys, while MEOHP and MEHHP were inversely related to BMI in girls. Furthermore, detectable phthalate monoesters may be considered potential chemical obesogens related to BMI in children.

Determining estrogenic steroids in Taipei waters and removal in drinking water treatment using high-flow solid-phase extraction and liquid chromatography/tandem mass spectrometry.

River water and wastewater treatment plant (WWTP) effluents from metropolitan Taipei, Taiwan were tested for the presence of the pollutants estrone (E1), estriol (E3), 17beta-estradiol (E2), and 17alpha-ethinylestradiol (EE2) using a new methodology that involves high-flow solid-phase extraction and liquid chromatography/tandem mass spectrometry. The method was also used to investigate the removal of the analytes by conventional drinking water treatment processes. Without adjusting the pH, we extracted 1-L samples with PolarPlus C18 Speedisks under a flow rate exceeding 100 mL/min, in which six samples could be done simultaneously using an extraction station. The adsorbent was washed with 40% methanol/60% water and then eluted by 50% methanol/50% dichloromethane. The eluate was concentrated until almost dry and was reconstituted by 20 microL of methanol. Quantitation was done by LC-MS/MS-negative electrospray ionization in the selected reaction monitoring mode with isotope-dilution techniques. The mobile phase was 10 mM N-methylmorpholine aqueous solution/acetonitrile with gradient elution. Mean recoveries of spiked Milli-Q water were 65-79% and precisions were within 2-20% of the tested concentrations (5.0-200 ng/L). The method was validated with spiked upstream river water; precisions were most within 10% of the tested concentrations (10-100 ng/L) with most RSDs<10%. LODs of the environmental matrixes were 0.78-7.65 ng/L. A pre-filtration step before solid-phase extraction may significantly influence the measurement of E1 and EE2 concentrations; disk overloading by water matrix may also impact analyte recoveries along with ion suppression. In the Taipei water study, the four steroid estrogens were detected in river samples (ca. 15 ng/L for E2 and EE2 and 35-45 ng/L for E1 and E3). Average levels of 19-26 ng/L for E1, E2, and EE2 were detected in most wastewater effluents, while only a single effluent sample contained E3. The higher level in the river was likely caused by the discharge of untreated human and farming waste into the water. In the drinking water treatment simulations, coagulation removed 20-50% of the estrogens. An increased dose of aluminum sulfate did not improve the performance. Despite the reactive phenolic moiety in the analytes, the steroids were decreased only 20-44% of the initial concentrations in pre- or post-chlorination. Rapid filtration, with crushed anthracite playing a major role, took out more than 84% of the estrogens. Except for E3, the whole procedure successfully removed most of the estrogens even if the initial concentration reached levels as high as 500 ng/L.

Effects of Gender on the Association of Urinary Phthalate Metabolites with Thyroid Hormones in Children: A Prospective Cohort Study in Taiwan.

Phthalates are considered endocrine disruptors. Our study assessed the gender-specific effects of phthalate exposure on thyroid function in children. In total, 189 Taiwanese children were enrolled in the study. One-spot urine and blood samples were collected for analyzing 12 phthalate metabolites in urine and thyroid hormones. The association between urinary phthalate metabolites and serum thyroid hormones was determined using a generalized linear model with a log link function; the children were categorized into groups for analysis according to the 33rd and 66th percentiles. The data were stratified according to gender and adjusted for a priori defined covariates. In girls, a positive association existed between urinary di-2-ethylhexyl phthalate (DEHP) metabolites (mono-(2-ethylhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-(2-ethyl-5-hydroxyhexyl) phthalate) and free thyroxine (T4). In boys, urinary dibutyl phthalate (DBP) metabolites (mono-i-butyl phthalate and mono-n-butyl phthalate) were positively associated with free triiodothyronine (T3). After categorizing each exposure into three groups, urinary DEHP metabolites were positively associated with free T3 levels in boys. Our results suggested that DEHP is associated with free T4 in girls and that DBP is associated with free T3 in boys. Higher DEHP metabolite concentrations exerted larger effects on free T3 in boys. These results reveal the gender-specific relationships between phthalate metabolites and thyroid hormones.

Perfluoroalkyl substances in cord blood and attention deficit/hyperactivity disorder symptoms in seven-year-old children.

OBJECTIVE: The effect of perfluoroalkyl substances (PFASs) on the development of neurotoxicity in children is still controversial. This study aimed to evaluate the association between in utero exposure to four PFASs and the development of neurobehavioral symptoms related to attention deficit hyperactivity disorder (ADHD) in early childhood. METHODS: Eligible study subjects were selected from the Taiwan Birth Panel Study and the Taiwan Early-Life Cohort, which enrolled a total of 1526 mother-infant pairs during 2004 and 2005. We collected umbilical cord blood and analyzed perfluorooctanoic acid (PFOA), perfluorooctanyl sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA) levels. When a child was 7 years old, to evaluate ADHD related neurobehavioral symptoms, their parents completed the Swanson, Nolan, and Pelham IV scale (SNAP-IV), the Child Behavior Checklist (CBCL), and the Strengths and Difficulties Questionnaire (SDQ) questionnaires. We used linear regression models with inverse probability weighting to explore the association between prenatal exposure to four PFASs and ADHD rating scores. RESULTS: A total of 282 subjects have completed the PFASs analysis and questionnaire survey. After adjusted for potential confounders, we observed that PFNA is inversely associated with inattention and oppositional defiant disorder of SNAP-IV, and hyperactivity/inattention of SDQ. No association between PFOA, PFOS, or PFUA and ADHD symptoms was found. CONCLUSIONS: Prenatal exposure to PFNA was found to associate with neurobehavioral symptoms related to ADHD among Asian seven-year-old children. Further studies are needed to elucidate the causal relationship.

Serum perfluorinated chemicals, glucose homeostasis and the risk of diabetes in working-aged Taiwanese adults.

BACKGROUND: The link among perfluoroalkyl and polyfluoroalkyl substances (PFASs), abnormal glucose homeostasis and the risk of diabetes has been intensively debated with conflicting evidence. OBJECTIVES: We evaluated the associations among PFASs, oral glucose tolerance testing (OGTT) curves and diabetes prevalence in 571 working-aged Taiwanese participants. METHODS: Exposure measures included serum perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA). Outcomes were OGTT curves and prevalent diabetes defined by fasting blood glucose (FBG) ≥126mg/dL, 2-h glucose ≥200mg/dL, or glycated hemoglobin ≥6.5%. Analyses were performed with multiple logistic regression and functional data analysis. RESULTS: A total of 39 participants (6.8%) had diabetes in this study. After full adjustment, the increase in the geometric means of FBG, 2-h glucose concentrations, and area under the OGTT curve (AUC120) with a doubling increase in PFOS was 3% (95% CI 1-4), 8% (5-12), and 6% (4-9), respectively. Compared to the lowest-quartile of PFOS concentrations (<2.4ng/ml), the OGTT trajectories were significantly steeper in participants of the highest-quartile PFOS exposure (>4.8ng/ml) and the vertical shifting of the mean curve for each PFOS quartile showed a dose-response pattern. The adjusted odds ratio for diabetes comparing the highest to lowest quartile was 3.37 (95% CI 1.18-9.65). For PFOA, PFNA, and PFUA, the opposite pattern of OGTT trajectory and the opposite risk profile for diabetes were observed. CONCLUSIONS: Chronic PFOS exposure was associated with impaired glucose homeostasis and the increased prevalence of diabetes. However, PFOA, PFNA, and PFUA showed a potential protective effect against glucose intolerance and the risk of diabetes. Future research focusing on clarifying possible differential effects of different species of PFASs on glucose homeostasis and establishing the prospective associations between PFASs and diabetes is needed.

Patterns of lung cancer mortality in 23 countries: application of the age-period-cohort model.

BACKGROUND: Smoking habits do not seem to be the main explanation of the epidemiological characteristics of female lung cancer mortality in Asian countries. However, Asian countries are often excluded from studies of geographical differences in trends for lung cancer mortality. We thus examined lung cancer trends from 1971 to 1995 among men and women for 23 countries, including four in Asia. METHODS: International and national data were used to analyze lung cancer mortality from 1971 to 1995 in both sexes. Age-standardized mortality rates (ASMR) were analyzed in five consecutive five-year periods and for each five-year age group in the age range 30 to 79. The age-period-cohort (APC) model was used to estimate the period effect (adjusted for age and cohort effects) for mortality from lung cancer. RESULTS: The sex ratio of the ASMR for lung cancer was lower in Asian countries, while the sex ratio of smoking prevalence was higher in Asian countries. The mean values of the sex ratio of the ASMR from lung cancer in Taiwan, Hong Kong, Singapore, and Japan for the five 5-year period were 2.10, 2.39, 3.07, and 3.55, respectively. These values not only remained quite constant over each five-year period, but were also lower than seen in the western countries. The period effect, for lung cancer mortality as derived for the 23 countries from the APC model, could be classified into seven patterns. CONCLUSION: Period effects for both men and women in 23 countries, as derived using the APC model, could be classified into seven patterns. Four Asian countries have a relatively low sex ratio in lung cancer mortality and a relatively high sex ratio in smoking prevalence. Factors other than smoking might be important, especially for women in Asian countries.

Association between maternal serum perfluoroalkyl substances during pregnancy and maternal and cord thyroid hormones: Taiwan maternal and infant cohort study.

BACKGROUND: Perfluoroalkyl substances (PFASs) are synthetic compounds that are widely used in industry and are often detectable in humans. In pregnant rats and their pups, PFASs can interfere with thyroid hormone homeostasis. In humans, maternal thyroid hormones supply the fetus throughout pregnancy, and thyroid hormones play a critical role in fetal growth and neurodevelopment. OBJECTIVES: We investigated the association between maternal PFAS exposure and thyroid hormone status in pregnant women and neonates. METHODS: In a study of environmental exposure and health in Taiwan, we measured serum concentrations of nine PFASs and four thyroid hormones for 285 pregnant women in their third trimester, and also measured cord serum thyroid hormones for 116 neonates. Associations between maternal PFASs and maternal and cord thyroid hormones were examined in multiple linear regression models. RESULTS: Perfluorohexanesulfonic acid concentrations were positively associated with maternal thyroid-stimulating hormone (TSH) levels. Pregnant women with higher levels of perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) had lower free thyroxine (T4) and total T4 levels. For example, we estimated that maternal free T4 levels decreased 0.019 ng/dL (95% CI: -0.028, -0.009) with each nanogram per milliliter increase in maternal PFNA. Finally, maternal PFNA, PFUnDA, and PFDoDA levels were associated with lower cord total triiodothyronine (T3) and total T4 levels, and maternal perfluorodecanoic acid (PFDeA) was associated with lower cord total T3. CONCLUSIONS: Our results suggest that exposure to some PFASs during pregnancy may interfere with thyroid hormone homeostasis in pregnant women and fetuses.

Association between levels of serum perfluorooctane sulfate and carotid artery intima-media thickness in adolescents and young adults.

BACKGROUND: Perfluorinated chemicals (PFCs) have been widely used for years in a variety of products worldwide. Although epidemiological findings have shown that PFC levels are positively associated with cholesterol and uric acid levels, it is unknown whether PFCs are associated with atherosclerosis. METHODS: We recruited 664 subjects (12-30 years) from a population-based sample of adolescents and young adults based on a mass urine screening to determine the relationship between serum levels of PFCs and carotid intima-media thickness (CIMT). RESULTS: The median concentrations and ranges of perfluorooctanoic acid (PFOA), perfluorooctane sulfate (PFOS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFUA) were 3.49 (0.75-52.2) ng/mL, 8.65 (0.11-85.90) ng/mL, 0.38 (0.38-25.4) ng/mL, and 6.59 (1.50-105.7) ng/mL, respectively. After controlling for age, gender, smoking status, systolic blood pressure, body mass index, low-density lipoprotein cholesterol, triglyceride, high-sensitivity C-reactive protein, and homeostasis model assessment of insulin resistance, multiple linear regression analysis revealed that CIMT increased significantly across quartiles of PFOS (0.434 mm, 0.446 mm, 0.458 mm, 0.451 mm; P for trend <0.001). Subpopulation analysis showed the association between PFOS and CIMT was more evident and significant in females, non-smokers, subjects of age 12-19 years, BMI<24, and those with APOE genotype of E2 carrier and E3/E3. CONCLUSIONS: Higher serum concentrations of PFOS were associated with an increase of carotid IMT in this cohort of adolescents and young adults. Further studies are warranted to clarify the causal relationship between PFOS and atherosclerosis.

Neonatal-maternal factors and perfluoroalkyl substances in cord blood.

Perfluoroalkyl substances (PFASs) can cross the placenta, enter fetal circulation, and were found to correlate with adverse fetal growth. However, determinants of cord blood PFASs are not fully characterized. The study aimed to explore the association between PFASs and neonatal-maternal factors within a Taiwanese birth cohort. We selected subjects from Taiwan Birth Panel Study, which enrolled 486 infant-mother pairs in 2004-2005. We collected cord blood and analyzed perfluorooctanoic acid (PFOA), perfluorooctanyl sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUA) using a simple protein precipitation and an ultra-high performance liquid chromatography/tandem mass spectrometry. We retrieved information pertaining to maternal socio-demographics, lifestyle- and dietary-related factors through structured questionnaires during the postpartum hospital stay. A total of 439 subjects, with 90% response rate, have completed serum analysis and questionnaire survey. The median concentrations for PFOA, PFOS, PFNA, and PFUA in cord blood were 1.86, 5.67, 3.00, and 13.5ngmL(-1), respectively. After adjusting for potential confounders, multiple linear regression models revealed that log10-PFOA was positively associated with maternal age (ß=0.011) and negatively associated with multiparity (ß=-0.044). Log10-PFOS was negatively correlated with birth weight (ß=-0.011) and higher maternal education (senior high school: ß=-0.067; university: ß=-0.088). Log10-PFUA tended to negatively associate with gender, male infants (ß=-0.075), and using cosmetics during pregnancy (ß=-0.065). Interestingly, presence of cockroaches in the home was positively associated with log10-PFOA (ß=0.041) and 1og10-PFNA (ß=0.123). In conclusion, this study demonstrated several factors to correlate with cord blood PFASs and further investigation are still needed for confirmation of exposure routes.

The associations between serum perfluorinated chemicals and thyroid function in adolescents and young adults.

Perfluorinated chemicals (PFCs) have been widely used in a variety of products worldwide for years. However, the effect of PFCs on thyroid function has not yet been clearly defined. We recruited 567 subjects (aged 12-30 years) in a population-based cohort of adolescents and young adults with abnormal urinalysis in the childhood to determine the relationship between serum level of PFCs and the levels of serum free thyroxine (T4) and thyroid stimulating hormone (TSH). The geometric means and geometric standard deviation concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUA) were 2.67 (2.96) ng/ml, 7.78 (2.42) ng/ml, 1.01 (3.48) ng/ml and 5.81 (2.92) ng/ml, respectively. Differences in the levels of free T4 and TSH across different categories of PFOA, PFOS and PFUA were insignificant. After controlling for confounding factors, multiple linear regression analyses revealed mean serum level of free T4 increased significantly across categories (<60th, 60-89 and >90th percentiles) of PFNA (P for trend =0.012 in the full model). The association between PFNA and free T4 was more significant in male subjects in age group 20-30, active smokers and in those with higher body mass index in stratified analysis. Serum concentrations of PFNA were associated with serum free T4 levels in adolescents and young adults.

Positive association between urinary levels of 8-hydroxydeoxyguanosine and the acrylamide metabolite N-acetyl-S-(propionamide)-cysteine in adolescents and young adults.

Acrylamide is present in mainstream cigarette smoke and in some foods prepared at high temperatures. Animal studies have shown that acrylamide exposure increases oxidative stress; however, it is not known if this also occurs in humans. We recruited 800 subjects (mean age, 21.3 years, range, 12-30 years) from a population-based sample of Taiwanese adolescents and young adults to determine if urinary levels of the acrylamide metabolite N-acetyl-S-(propionamide)-cysteine (AAMA) and the oxidative stress product 8-hydroxydeoxyguanosine (8-OHdG) are associated. The mean (SD) AAMA and 8-OHdG were 76.54 (76.42)µg/L and 3.48 (2.37)µg/L, respectively. In linear regression analyses, a 1-unit increase in natural log AAMA was significantly associated with an increase in natural log 8-OHdG (µg/g creatinine) (ß=0.044, SE=0.019, P=0.020) after controlling for covariates. Subpopulation analyses showed AAMA and 8-OHdG were significantly associated with males, adolescents, non-current smokers, without alcohol consumption, subjects, body mass index ≥ 24, and homeostasis model assessment of insulin resistance score ≥ 0.9. In conclusion, higher urinary AAMA concentrations were associated with increased levels of urinary 8-OHdG in this cohort. Further studies are warranted to determine if there is a causal relationship between acrylamide exposure and oxidative stress.

Perfluorinated compounds in umbilical cord blood and adverse birth outcomes.

BACKGROUND: Previous animal studies have shown that perfluorinated compounds (PFCs) have adverse impacts on birth outcomes, but the results have been inconclusive in humans. We investigated associations between prenatal exposure to perfluorooctanoic acid (PFOA), perfluorooctyl sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA) and birth outcomes. METHODS: In total, 429 mother-infant pairs were recruited from the Taiwan Birth Panel Study (TBPS). Demographic data were obtained by interviewing mothers using a structured questionnaire and birth outcomes were extracted from medical records. Cord blood was collected for PFOA, PFOS, PFNA, and PFUA analysis by ultra-high-performance liquid chromatography/tandem mass spectrometry. RESULTS: The geometric mean (standard deviation) levels of PFOA, PFOS, PFNA, and PFUA in cord blood plasma were 1.84 (2.23), 5.94 (1.95), 2.36(4.74), and 10.26 (3.07) ng/mL, respectively. Only PFOS levels were found to be inversely associated with gestational age, birth weight, and head circumference [per ln unit: adjusted ß (95% confidence interval, CI) = -0.37 (-0.60, -0.13) wks, -110.2 (-176.0, -44.5) gm and -0.25 (-0.46, -0.05) cm]. Additionally, the odds ratio of preterm birth, low birth weight, and small for gestational age increased with PFOS exposure [per ln unit: adjusted odds ratio (OR) (95%CI) = 2.45 (1.47, 4.08), 2.61(0.85, 8.03) and 2.27 (1.25, 4.15)]. When PFOS levels were divided into quartiles, a dose-response relation was observed. However, PFOA, PFNA, and PFUA were not observed to have any convincing impact on birth outcomes. CONCLUSIONS: An adverse dose-dependent association was observed between prenatal PFOS exposure and birth outcomes. However, no associations were found for the other examined PFCs.

Analysis of perfluorinated chemicals in umbilical cord blood by ultra-high performance liquid chromatography/tandem mass spectrometry.

Perfluorinated compounds (PFCs) can cross the placental barrier and enter fetal circulation. This study aimed at developing a fast and sensitive ultra-high performance liquid chromatography/tandem mass spectrometry method for the determination of twelve perfluorinated compounds in cord blood. Samples were processed with protein precipitation using formic acid and methanol, mixed with stable isotope labeled standard, followed by sonication and centrifugation, and were analyzed using a Waters ACQUITY UPLC coupled with a Waters Quattro Premier XE triple-quadrupole mass spectrometer. The instrument was operated in selected reaction monitoring (SRM) with negative electrospray ionization. Using BEH C(18) column (2.1 mm×50 mm, 1.7 µm) with 10-mM N-methylmorpholine/methanol gradient elution provided a fast chromatographic separation (5.5 min) and sharp peaks. Intra- and inter-day calibration bias was less than 7% and intra- and inter-day calibration of relative standard deviations were within 0.02-8.22% for all the analytes and concentrations. The recoveries of PFCs spiked into bovine serum ranged from 85 to 104% with relative standard deviations from 0.02 to 6.37%. The limits of quantitation (LOQs), defined as a signal-to-noise ratio of ten, ranged from 0.15 to 3.1 ng/mL for the twelve PFCs. Perfluorooctanoic acid (PFOA), perfluorooctyl sulfonate (PFOS), perfluoroundecanoic acid (PFUA) and perfluorononanoic acid (PFNA) were detected in up to 68% of umbilical cord plasma (n=444) in Taiwan Birth Panel Study and the health effect of these chemicals on children developmental deserves further investigation.

Analysis of polycyclic aromatic hydrocarbons by liquid chromatography/tandem mass spectrometry using atmospheric pressure chemical ionization or electrospray ionization with tropylium post-column derivatization.

Polycyclic aromatic hydrocarbons (PAHs) with four to six rings are potent carcinogens. This study analyzed ten of the sixteen US EPA priority PAHs using reversed-phase liquid chromatography/tandem mass spectrometry (LC/MS/MS) in selected reaction monitoring mode with two ionization sources: positive atmospheric pressure chemical ionization (APCI+) or positive elecrtrospray ionization (ESI+) with tropylium post-column derivatization. Several factors were investigated, including mobile phases, stationary phases of columns and chromatographic temperature, to determine how optimal separation and sensitivity might be achieved. Methanol used as an organic mobile phase provided better sensitivities for most PAHs than acetonitrile, although some PAHs co-eluted. Acidic buffers did not increase analyte signals. Use of Restek Pinnacle II PAH columns (250 x 4.6 mm or 250 x 2.1 mm, 5 microm) with water/acetonitrile gradient at 27 degrees C made possible a good separation of the ten analytes. [M]+. were the best precursor ions in both APCI and ESI, although fluoranthene could not be detected in ESI mode when tropylium post-column derivatization was performed. [M-28]+ and [M-52]+ were the major product ions of PAHs after collision-induced dissociation, a result of neutral losses of C(2)H(4) and (C(2)H(2))(2), respectively. Chromatographic separation for PAH isomers was crucial because the mass spectra were so similar that even MS/MS could not distinguish them from each other. The recoveries of sample preparations of PAHs spiked onto air-sampling filters ranged between 77.5 and 106% with relative standard deviations between 1.1 and 15.9%. This method was validated by analyzing NIST SRM 1649a (urban dust), producing results comparable with the certified PAH concentrations. The detection limits using APCI and ESI interfaces, defined as three times the noise levels, ranged between 0.23 and 0.83 ng and between 0.16 and 0.84 ng of on-column injection, respectively.