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1.
Artigo em Inglês | MEDLINE | ID: mdl-34267309

RESUMO

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is diagnosed in ~7% of school-aged children. The role of endocrine-disrupting chemicals (EDC) and oxidative stress in ADHD etiology are not clear. OBJECTIVE: Assessment of the associations between simultaneous exposure to multiple compounds and ADHD in children. METHODS: The case-control study included 76 clinically diagnosed ADHD cases and 98 controls, aged 4-15 years old. Concentrations quartiles of urinary metabolites of acrylamide, acrolein, nonylphenol, phthalates, and organophosphate pesticides and biomarkers of oxidative stress were used to fit logistic regressions for each compound and weighted quantiles sum (WQS) regression for the mixture. RESULTS: Positive dose-response relationships with ADHD were observed for 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) (odds ratio(OR)Q4 = 3.73, 95%CI [1.32, 11.04], ptrend = 0.003), dimethyl phosphate (DMP) (ORQ4 = 4.04, 95%CI [1.34, 12.94], ptrend = 0.014) and diethyl phosphate (ORQ4 = 2.61, 95%CI = [0.93, 7.66], ptrend = 0.030), and for the mixture of compounds (ORWQS = 3.82, 95%CI = [1.78, 8.19]) with the main contributions from HNE-MA (28.9%) and DMP (18.4%). CONCLUSIONS: The dose-response relationship suggests enhanced susceptibility to EDC burden in children even at lower levels, whereas the main risk is likely from organophosphate pesticides. HNE-MA is recommended as a sensitive biomarker of lipid peroxidation in the further elucidation of the oxidative stress role in ADHD etiology.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34200176

RESUMO

Prenatal exposure to bisphenol A (BPA) may increase the risk of abnormal birth outcomes, and DNA methylation might mediate these adverse effects. This study aimed to investigate the effects of maternal BPA exposure on maternal and fetal DNA methylation levels and explore whether epigenetic changes are related to the associations between BPA and low birth weight. We collected urine and blood samples originating from 162 mother-infant pairs in a Taiwanese cohort study. We measured DNA methylation using the Illumina Infinium HumanMethylation 450 BeadChip in 34 maternal blood samples with high and low BPA levels based on the 75th percentile level (9.5 µg/g creatinine). Eighty-seven CpGs with the most differentially methylated probes possibly interacting with BPA exposure or birth weight were selected using two multiple regression models. Ingenuity pathway analysis (IPA) was utilized to narrow down 18 candidate CpGs related to disease categories, including developmental disorders, skeletal and muscular disorders, skeletal and muscular system development, metabolic diseases, and lipid metabolism. We then validated these genes by pyrosequencing, and 8 CpGs met the primer design score requirements in 82 cord blood samples. The associations among low birth weight, BPA exposure, and DNA methylation were analyzed. Exposure to BPA was associated with low birth weight. Analysis of the epigenome-wide findings did not show significant associations between BPA and DNA methylation in cord blood of the 8 CpGs. However, the adjusted odds ratio for the dehydrogenase/reductase member 9 (DHRS9) gene, at the 2nd CG site, in the hypermethylated group was significantly associated with low birth weight. These results support a role of BPA, and possibly DHRS9 methylation, in fetal growth. However, additional studies with larger sample sizes are warranted.


Assuntos
Metilação de DNA , Efeitos Tardios da Exposição Pré-Natal , Compostos Benzidrílicos/toxicidade , Peso ao Nascer , Estudos de Coortes , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Exposição Materna/efeitos adversos , Fenóis , Projetos Piloto , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Taiwan/epidemiologia
3.
Sci Total Environ ; 773: 145604, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33592467

RESUMO

This study will help to clarify the relationship between organophosphate pesticides (OPs) and attention deficit/hyperactivity disorder (ADHD) related to oxidative stress and paraoxonases (PON) polymorphisms to further characterize the gene-environment interaction. This case-control study enrolled 85 children with ADHD and 96 control subjects. Urinary OP levels were analyzed by using gas chromatography-mass spectrometry (GC-MS). Oxidative stress biomarkers, such as 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2-Gua), 8-iso-prostaglandin F2α (8-iso-PGF2α), and 4-hydroxy-2-nonenoic acid-mercapturic acid (HNE-MA), were analyzed by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S) were calculated to evaluate the additive interactions between OP exposure and PON genetic polymorphism on ADHD. A causal mediation analysis was conducted to clarify the mediation effects of oxidative stress due to OP exposure on ADHD. Children with ADHD had significantly higher DMP (238.95 nmol/g cre. vs. 164.83 nmol/g cre., p value = 0.01) and HNE-MA (30.75 µg/g cre. vs. 18.41 µg/g cre., p value<0.01) concentrations than control children. Children who carried the PON1 GG genotype (rs705379) had low urinary DMP levels, and the level increased with increasing numbers of allele variants. The risk for developing ADHD reached 2.06-fold (OR = 2.06, 95% CI:1.23-3.44) and 1.43-fold (OR = 1.45, 95% CI:1.04-2.03) when the DMP and HNE-MA levels increased by 1 natural log of the concentration, respectively. The estimated AP value was 0.66 (95% CI: 0.17-1.15), indicating that 66% of ADHD cases in DMP-exposed children with the PON1 CT/TT (rs705381) genotype were due to gene-environment interactions. No significant mediation of HNE-MA was observed between DMP exposure and the risk of ADHD. The estimated proportion mediated was only 7.0% (95% CI: -0.08-0.46). This research suggests the role of OP exposure in the occurrence of ADHD after adjusting for covariates.


Assuntos
Arildialquilfosfatase , Transtorno do Deficit de Atenção com Hiperatividade , Arildialquilfosfatase/genética , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Estudos de Casos e Controles , Criança , Cromatografia Líquida , Humanos , Organofosfatos/efeitos adversos , Estresse Oxidativo , Polimorfismo Genético , Espectrometria de Massas em Tandem
4.
PLoS One ; 15(12): e0243761, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33315949

RESUMO

BACKGROUND: Because there are no published biochemical reference intervals (RI) for pregnant Taiwanese women, we used an established islandwide birth cohort, the Taiwan Maternal and Infant Cohort Study, to establish RIs for important biochemical parameters in women during their 3rd trimester in Taiwan. Additionally, we compared the differences in these biochemical parameters between early third trimester (weeks 28 to 31) and late third trimester (weeks 37 to 40) of pregnant women as well as the differences in them between the third trimester and after delivery. METHODS: Between 2012 and 2015, we recruited a total of 2,136 pregnant women from nine hospitals located in northern (n = 3), central (n = 3), southern (n = 2), and eastern Taiwan (n = 1) to receive regular prenatal health examinations during their third trimester (weeks 28 to 40). After exclusion, samples obtained from 993 eligible pregnant women were analyzed. RESULTS: There were increases in both lower and upper normal limits for blood neutrophil, thyroid profile (triiodothyronine (T3) and thyroxine (T4)), testosterone, estradiol, and progesterone and decreases for RBC, hemoglobin (Hb), alanine aminotransferase (ALT) and creatinine (Cr) during their third trimesters. Women in their late third trimester (n = 378) had higher median RBC, Hb, aspartate aminotransferase (AST), Cr, thyroid-stimulating hormone (TSH), testosterone, estradiol, and progesterone and lower median platelet and insulin, compared with those in their early third trimester (n = 490). Twenty-three of the women had both third trimester and post-pregnancy data. After delivery, the women had lower median AST, ALT, insulin, T3, T4, testosterone, estradiol, and progesterone and higher median Cr, free T4, FSH, and luteinizing hormone (LH), compared to their third trimesters. CONCLUSIONS: Gestation-related changes in important biochemical parameters should be considered when evaluating clinical laboratory values in pregnant women.


Assuntos
Testes de Química Clínica/normas , Testes Hematológicos/normas , Primeiro Trimestre da Gravidez/sangue , Terceiro Trimestre da Gravidez/sangue , Adulto , Alanina Transaminase/sangue , Alanina Transaminase/normas , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/normas , Índice de Massa Corporal , Estudos de Coortes , Estradiol/sangue , Estradiol/normas , Feminino , Humanos , Contagem de Leucócitos , Neutrófilos/citologia , Período Pós-Parto , Gravidez , Gestantes , Valores de Referência , Hormônios Tireóideos/sangue , Hormônios Tireóideos/normas
5.
Sci Total Environ ; 737: 139833, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32526583

RESUMO

The present study assessed the association between phthalate exposure and mitochondrial DNA (mtDNA) polymerase γ (POLG) methylation along with the potential effect on the characteristics of body fat in children. A total of 152 children were enrolled. The urinary concentrations of phthalate metabolites were measured using ultraperformance liquid chromatography-tandem mass spectrometry. Genomic DNA was extracted from the buffy coat, and bisulfite-treated DNA was subjected to a pyrosequencing assay. In total, 17 CpG sites in the exon 2 region of POLG were included in the analysis. A multivariable regression model was applied to determine whether characteristics of body fat were associated with phthalate exposure and methylation of POLG. After adjustment for covariates, male children with a ten-fold increase in mono-methyl phthalate (MMP) or mono-benzyl phthalate (MBzP) concentrations had significantly higher measurements for total body fat (MMP: ß = 6.47%; MBzP: ß = 3.54%), and trunk fat (MMP: ß = 6.67%; MBzP: ß = 3.90%). Male children who had hypermethylation at the 2nd CpG site in exon 2 of POLG also had high measurements for BMI (ß = 1.66 kg/m2), waist (ß = 4.49 cm) and hip (ß = 4.81 cm) circumference, total body fat (ß = 5.48%), and trunk fat (ß = 6.21%). A dose-response relationship existed between methylation at the 2nd CpG site in exon 2 of POLG and characteristics of body fat (p for trend<0.01). This study suggested that male children who are exposed to phthalic acid esters have high body weight, BMI, and body and trunk fat percentages. Methylation of the exon 2 region of POLG is a possible mechanism behind the causal effect of endocrine-disrupting substances.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Tecido Adiposo , Criança , Cromatografia Líquida , Metilação de DNA , Exposição Ambiental/análise , Feminino , Humanos , Masculino
6.
Environ Pollut ; 264: 114648, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32380394

RESUMO

BACKGROUND: No information is available on the long-term effects on thyroid and growth hormones of children exposed to phthalate-tainted products, despite the infamous 2011 Taiwan phthalate episode. We investigated estimated daily intake levels and their long-term effects on serum thyroid and growth hormone levels in children. METHODS: We recruited 166 children (2-18 years old) in three visits who provided specimens and filled out a questionnaire from the Risk Assessment of Phthalate Incident in Taiwan (RAPIT) project study from 2012 to 2016. Morning spot urine samples were analyzed for nine phthalate metabolites. Serum thyroid (triiodothyronine [T3], thyroxine [T4], and free T4) and growth hormone (insulin-like growth factor-1 [IGF-1] and its binding protein 3 [IGF-BP3]) levels were measured. A generalized estimating equation model was used to evaluate associations between phthalate metabolite levels and children's thyroid and growth hormone levels. RESULTS: The median metabolite levels of monomethyl phthalate (MMP), Σdibutyl phthalate (DBP), and Σdi-(2-ethylhexyl) phthalate (DEHP) at visits 1, 2, and 3 were 6.59, 10.5, and 21.0 ng/mL, 0.15, 0.24, and 0.20 nmol/mL, and 0.15, 0.17, and 0.12 nmol/mL, respectively. After adjusting for potential confounding factors, we found that levels of urinary MMP were negatively associated with T3 (ß = -0.013, p = 0.047), T4 (ß = -0.016, p = 0.006), free T4 (ß = -0.012, p = 0.002), and IGF-BP3 (ß = -0.025, p = 0.003). Urinary mono-ethyl phthalate (MEP) was negatively associated with IGF-1 (ß = -0.027, p = 0.029) and IGF-BP3 (ß = -0.016, p = 0.018). In addition, serum free T4 was positively associated with urinary mono-2-ethyl-5-hydroxy hexyl phthalate (MEHHP) (ß = 0.016, p = 0.043), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (ß = 0.015, p = 0.024), and ΣDEHPm (ß = 0.019, p = 0.020). CONCLUSIONS: Our findings support the hypothesis that specific phthalates disturb the hemostasis of thyroid and growth hormone levels in children exposed to phthalate-tainted products.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Adolescente , Criança , Pré-Escolar , Exposição Ambiental/análise , Hormônio do Crescimento , Humanos , Estudos Longitudinais , Taiwan , Glândula Tireoide
7.
Artigo em Inglês | MEDLINE | ID: mdl-31906378

RESUMO

Epidemiological studies have reported the relationship between bisphenol A (BPA) exposure and increased prevalence of asthma, but the mechanisms remain unclear. Here, we investigated whether BPA exposure and DNA methylation related to asthma in children. We collected urinary and blood samples from 228 children (Childhood Environment and Allergic Diseases Study cohort) aged 3 years. Thirty-three candidate genes potentially interacting with BPA exposure were selected from a toxicogenomics database. DNA methylation was measured in 22 blood samples with top-high and bottom-low exposures of BPA. Candidate genes with differential methylation levels were validated by qPCR and promoter associated CpG islands have been investigated. Correlations between the methylation percentage and BPA exposure and asthma were analyzed. According to our findings, MAPK1 showed differential methylation and was further investigated in 228 children. Adjusting for confounders, urinary BPA glucuronide (BPAG) level inversely correlated with MAPK1 promoter methylation (ß = -0.539, p = 0.010). For the logistic regression analysis, MAPK1 methylation status was dichotomized into higher methylated and lower methylated groups with cut off continuous variable of median of promoter methylation percentage (50%) while performing the analysis. MAPK1 methylation was lower in children with asthma than in children without asthma (mean ± SD; 69.82 ± 5.88% vs. 79.82 ± 5.56%) (p = 0.001). Mediation analysis suggested that MAPK1 methylation acts as a mediation variable between BPA exposure and asthma. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of MAPK1 methylation. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of MAPK1 methylation.


Assuntos
Asma , Compostos Benzidrílicos , Metilação de DNA , Fenóis , Asma/sangue , Asma/epidemiologia , Asma/urina , Compostos Benzidrílicos/toxicidade , Compostos Benzidrílicos/urina , Pré-Escolar , Estudos de Coortes , Ilhas de CpG/genética , Feminino , Glucuronídeos/urina , Humanos , Masculino , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Fenóis/toxicidade , Fenóis/urina , Regiões Promotoras Genéticas/genética
8.
Sci Rep ; 9(1): 12369, 2019 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-31451752

RESUMO

Exposure to bisphenol A (BPA) in utero is associated with adverse health outcome of the offspring. Differential DNA methylation at specific CpG sites may link BPA exposure to health impacts. We examined the association of prenatal BPA exposure with genome-wide DNA methylation changes in cord blood in 277 mother-child pairs in the Hokkaido Study on Environment and Children's Health, using the Illumina HumanMethylation 450 BeadChip. We observed that a large portion of BPA-associated differentially methylated CpGs with p-value < 0.0001 was hypomethylated among all newborns (91%) and female infants (98%), as opposed to being hypermethylated (88%) among males. We found 27 and 16 CpGs with a false discovery rate (FDR) < 0.05 in the analyses for males and females, respectively. Genes annotated to FDR-corrected CpGs clustered into an interconnected genetic network among males, while they rarely exhibited any interactions in females. In contrast, none of the enrichment for gene ontology (GO) terms with FDR < 0.05 was observed for genes annotated to the male-specific CpGs with p < 0.0001, whereas the female-specific genes were significantly enriched for GO terms related to cell adhesion. Our epigenome-wide analysis of cord blood DNA methylation implies potential sex-specific epigenome responses to BPA exposure.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Metilação de DNA/genética , Epigenoma , Sangue Fetal/metabolismo , Fenóis/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/genética , Caracteres Sexuais , Adulto , Ilhas de CpG/genética , Feminino , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez
9.
Int J Hyg Environ Health ; 222(6): 955-964, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31248753

RESUMO

Parabens are a group of esters of parahydroxybenzoic acid and are utilized as antimicrobial preservatives in the majority of personal care products (PCPs). Epidemiological studies regarding the adverse effects of parabens on fetuses are still limited. The aim of this study was to determine the association between maternal paraben exposure and birth outcomes. One hundred and ninety-nine pregnant women were enrolled, and maternal urine was collected in the third trimester. The urine concentrations of four parabens (methyl (MP), ethyl (EP), propyl (PP), and butyl (BP)) were determined by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Generalized additive model-penalized regression splines and a multivariable regression model were employed to determine the association between paraben exposure levels and birth outcomes. A causal mediation analysis was conducted to determine the mediation effect of oxidative stress on birth outcomes. The geometric means of urinary MP, EP, PP, and BP were 51.79, 1.26, 4.21, and 1.25 µg/g cre., respectively. In the penalized regression splines, sex-specific associations between maternal MP levels and birth outcomes were observed; a downward curvature was observed between the MP level and birth weight, length, head circumference, and thoracic circumference among female newborns. Pregnant women in the group with MP levels above the third quartile had neonates with significantly lower body weight (ß = -215.98 g, p value = 0.02) compared to those in the group with MP levels lower than the third quartile. No significant mediation of oxidative stress was observed between maternal MP exposure and female birth weight. The estimated proportion mediated ranged from -6% to 15%. The negative association between maternal paraben exposure and female birth outcomes in relation to child development should be carefully considered.


Assuntos
Anti-Infecciosos/urina , Tamanho Corporal , Poluentes Ambientais/urina , Exposição Materna , Parabenos/análise , Adulto , Monitoramento Biológico , Feminino , Humanos , Masculino , Troca Materno-Fetal , Estresse Oxidativo , Gravidez , Caracteres Sexuais , Taiwan
10.
Chemosphere ; 226: 290-297, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30933738

RESUMO

This study determined whether maternal bisphenol A (BPA) exposure influences birth outcomes through oxidative stress and estimated the daily intake of BPA through breast milk for infants. One hundred and eighty-six pregnant women without pregnancy complications were enrolled and maternal urine was collected in the third trimester. Postnatal breast milk was collected in the first and third months after delivery. Concentrations of BPA were determined through ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Generalized additive model-penalized regression splines and a multivariable regression model were employed to determine the effects of BPA exposure and oxidative stress levels on birth outcomes. A causal mediation analysis was conducted to clarify the mediation effects of oxidative stress due to maternal BPA exposure on birth outcomes. The daily intake of BPA in breast milk was calculated using probabilistic risk assessment methods. The geometric means (geometric standard deviation) of BPA levels for maternal urine and first- and third-month breast milk were 2.19 (2.88) µg/g creatinine., 1.35 (3.53) ng/g, and 3.17 (2.97) ng/g, respectively. No significant mediation existed among maternal BPA exposure, oxidative stress level, and neonatal head circumference. Three percent of 1-monthold babies and 1% of 3-month-old babies exceeded the BPA tolerable daily intake of 4 µg/kg-bw/day proposed by the European Food Safety Authority. This study revealed the BPA exposure profile for pregnant women and infants in northern Taiwan. The marginally significant correlation between maternal BPA exposure and neonatal head circumference should be considered.


Assuntos
Compostos Benzidrílicos/análise , Exposição Materna/efeitos adversos , Leite Humano/química , Estresse Oxidativo/efeitos dos fármacos , Fenóis/análise , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Adulto , Pesos e Medidas Corporais , Cromatografia Líquida de Alta Pressão , Estudos de Coortes , Feminino , Humanos , Lactente , Saúde do Lactente , Recém-Nascido , Espectrometria de Massas , Gravidez , Análise de Regressão , Medição de Risco , Taiwan
11.
Sci Total Environ ; 648: 135-143, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30114584

RESUMO

BACKGROUND: Fetuses are susceptible to phthalates, known endocrine disrupting chemicals, within sensitive windows of development. It is crucial to determine the major sources of phthalates to reduce exposure. This study aims to examine the associations between usage patterns of personal care products (PCPs) and urinary levels of phthalate metabolites across pregnancy in a multi-hospital based birth cohort. METHODS: During 2012-2015, we conducted a birth cohort study named the Taiwan Mother Infant Cohort Study (TMICS). Usage patterns of PCPs were obtained using structured questionnaires during the third trimester of pregnancy. Spot urine samples were collected at each trimester, and levels of eleven phthalate metabolites were measured by liquid chromatography tandem mass spectrometry. The association of PCPs use with urinary phthalate metabolite concentrations was assessed using GEE models. RESULTS: Among the 1676 pregnant women participated in TMICS, 281 who provided two or three urine samples across pregnancy were included. The levels of several phthalate metabolites were significantly associated with the use of PCPs, particularly leave-on PCPs. With the increasing use of skin toners (11.7%; 95% CI: 1.5%, 22.9%), lipsticks (13.2%; 95% CI: 4.6%, 22.5%), and essential oils (21.8%; 95% CI: 9.1%, 36.0%), individuals are exposed to higher concentrations of mono-ethyl phthalate (MEP). Additionally, a positive trend was found regarding the number of leave-on PCPs used and the measured change in MEP concentrations (P for trend = 0.01). Other positive associations included MBzP and body lotions (7.9%; 95% CI: 0.1%, 16.2%). With regard to rinse-off PCPs, we found a positive association between urinary MBzP and shampoo use, and a negative association between urinary MMP and face wash. CONCLUSION: Leave-on PCPs were found to be a more probable source of phthalate exposure than the use of rinse-off PCPs. We suggest pregnant women reduce the frequency of leave-on PCPs use during pregnancy to avoid such phthalate exposure.


Assuntos
Cosméticos/metabolismo , Monitoramento Ambiental , Poluentes Ambientais/metabolismo , Exposição Materna , Ácidos Ftálicos/metabolismo , Adulto , Cromatografia Líquida , Estudos de Coortes , Feminino , Humanos , Gravidez , Terceiro Trimestre da Gravidez , Taiwan , Espectrometria de Massas em Tandem , Adulto Jovem
12.
Environ Res ; 167: 567-574, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30165327

RESUMO

Nonylphenol (NP) and/or bisphenol A (BPA) may have reproductive effects. Although the mechanisms of action remain unclear, steroid hormones biosynthesis, hypothalamus pituitary adrenal axis activity, oxidative stress, and crosstalk interaction of NP and BPA mixture and its pathways may play a contributory role. This cross-sectional study examined whether the interactive effects of NP/BPA and oxidative stress biomarkers played a role in reproductive indices (penis length and anogenital distance (AGD)) in 244 mother-fetus pairs. Four biomarkers of oxidative stress, (8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua), 8-iso-prostaglandin F2α (8-isoPF2α), and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)) were simultaneously analyzed using the high-performance liquid chromatography-electrospray ionization tandem mass spectrometry method. No significant associations were found between reproductive indices and NP/BPA or oxidative stress biomarkers. Maternal exposure to a mixture of NP and BPA may enhance 8-OHdG. Interactive effects were found in the high 8-isoPF2α group, and prenatal NP exposure was inversely associated with penis length (ß = -3.68 mm; p = 0.01). Similar results were noted among boys who were born to mothers in the high 8-isoPF2α group, in which BPA was inversely associated with penis length (ß = -4.43 mm; p = 0.005). Our findings suggest important implications for prenatal exposure to oxidative stress, as evidenced by the 8-isoPF2α level. Thus, NP and BPA may interact to shape fetal reproductive tract development, particularly in boys. The interactive effects of NP/BPA, oxidative stress, and reproductive indices should be considered.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Genitália Masculina/anatomia & histologia , Estresse Oxidativo , Fenóis/efeitos adversos , Estudos Transversais , Feminino , Feto/anatomia & histologia , Humanos , Masculino , Gravidez
14.
Allergy Asthma Immunol Res ; 10(2): 172-179, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29411558

RESUMO

PURPOSE: Bisphenol A (BPA) exposure may increase the risk of asthma. Genetic polymorphisms of oxidative stress-related genes, glutathione S-transferases (GSTM1, GSTP1), manganese superoxide dismutase, catalase, myeloperoxidase, and microsomal epoxide hydrolase may be related to BPA exposure. The aim is to evaluate whether oxidative stress genes modulates associations of BPA exposure with asthma. METHODS: We conducted a case-control study comprised of 126 asthmatic children and 327 controls. Urine Bisphenol A glucuronide (BPAG) levels were measured by ultra-performance liquid chromatography/tandem mass spectrometry, and genetic variants were analyzed by a TaqMan assay. Information on asthma and environmental exposure was collected. Analyses of variance and logistic regressions were performed to determine the association of genotypes and urine BPAG levels with asthma. RESULTS: BPAG levels were significantly associated with asthma (adjusted odds ratio [aOR], 1.29 per log unit increase in concentration; 95% confidence interval [CI], 1.081.55). Compared to the GG genotype, children with a GSTP1 AA genotype had higher urine BPAG concentrations (geometric mean [standard error], 12.72 [4.16] vs 11.42 [2.82]; P=0.036). In children with high BPAG, the GSTP1 AA genotype was related to a higher odds of asthma than the GG genotype (aOR, 4.84; 95% CI, 1.0223.06). CONCLUSIONS: GSTP1 variants are associated with urine BPA metabolite levels. Oxidative stress genes may modulate the effect of BPA exposure on asthma.

15.
J Expo Sci Environ Epidemiol ; 28(6): 589-598, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29463903

RESUMO

Acrylamide (AA), a probable human carcinogen, is a widely-used industrial chemical but is also present in tobacco smoke and carbohydrate-rich foods processed at high temperatures. AA is metabolized to glycidamide (GA) to cause the formation of DNA adducts. N7-(2-carbamoyl-2-hydroxyethyl) guanine (N7-GAG), the most abundant DNA adduct induced by GA, was recently detected in urine of smokers and non-smokers. In this study, we assessed the variability of AA exposure and biomarkers of AA exposure in urine samples repeatedly collected from AA-exposed workers and explored the half-life of N7-GAG. A total of 8 AA-exposed workers and 36 non-exposed workers were recruited. Pre-shift and post-shift urine samples were collected from the exposed group in parallel with personal sampling for eight consecutive days and from the control group on day 1 of the study. Urinary N7-GAG and the mercapturic acids of AA and GA, namely N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-(R,S)-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) were analyzed using on-line solid phase extraction-liquid chromatography-electrospray ionization/tandem mass spectrometry methods. We found that N7-GAG levels in urine were significantly higher in exposed workers than in controls and that N7-GAG level correlated positively with AAMA and GAMA levels. Results from this study showed that AAMA and GAMA possibly remain the more preferred biomarkers of AA exposure and that N7-GAG levels could be elevated by occupational exposures to AA and serve as a biomarker of AA-induced genotoxicity for epidemiological studies.


Assuntos
Acrilamida/urina , Biomarcadores/urina , Guanina/análogos & derivados , Guanina/urina , Exposição Ocupacional/análise , Adulto , Análise de Variância , Cromatografia Líquida/métodos , Cromatografia Líquida/normas , Monitoramento Ambiental/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Espectrometria de Massas em Tandem/métodos , Espectrometria de Massas em Tandem/normas
16.
Environ Res ; 160: 339-346, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29054088

RESUMO

OBJECTIVE: The aim of this study was to clarify the association between organophosphate pesticides (OPs) and attention-deficit/hyperactivity disorder (ADHD) related to oxidative stress and genetic polymorphisms. METHODS: This case-control study enrolled 93 children with ADHD and 112 control children in north Taiwan. Six dialkyl phosphate (DAP) metabolites of OPs and oxidative stress biomarkers were analyzed. Polymorphisms of the dopamine receptor D4 gene (DRD4) were identified. RESULTS: Children with ADHD had significantly higher dimethylphosphate (DMP, 236.69nmol/g cre. vs. 186.84nmol/g cre., p value = 0.01) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA, 28.95µg/g cre. vs. 16.55µg/g cre., p value<0.01) concentrations than control children. Children who carried DRD4 GA/AA genotypes (rs752306) were less likely than those who carried the DRD4 GG genotype to have ADHD (odds ratio [OR]: 0.45, 95% CI: 0.24-0.84). The estimated value of the AP (attributable proportion due to interaction) was 0.59 (95% CI: 0.13-1.05), indicating that 59% of ADHD cases in DMP-exposed children with the DRD4 GG genotype were due to the gene-environment interaction. After adjustment for other covariates, children who carried the DRD4 GG genotype, had been exposed to high DMP levels (more than the median), and had high HNE-MA levels had a significantly increased risk for developing ADHD (OR = 11.74, 95% CI: 2.12-65.04). CONCLUSION: This study indicated a gene-environment interaction in the risk of ADHD in children. The association between DMP and ADHD in children might relate to the mechanism of lipid peroxidation. Dose-response relationships and the combined effects of OPs, oxidative stress, and genetic polymorphism on ADHD should not be neglected.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Organofosfatos/toxicidade , Estresse Oxidativo , Praguicidas/toxicidade , Receptores de Dopamina D4/genética , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Peroxidação de Lipídeos , Masculino , Polimorfismo de Nucleotídeo Único
17.
Sci Total Environ ; 618: 635-644, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29055577

RESUMO

The contamination of a clouding agent with di(2-ethylhexyl) phthalate (DEHP), a substitute emulsifier-containing compound used in a variety of foods was announced on May 23, 2011. The aims of this study were as follows (1) compare the urine phthalates (PAE) metabolites concentration and estimate the daily intake (DI) of PAEs in pregnant women before and after the tainted food scandal and (2) examine the effect of relatively high PAEs exposure on birth outcome. One-hundred twelve pregnant women in Northern Taiwan participated in this study from March to December 2010, i.e., before the tainted food scandal. After the tainted food scandal, we collected 69, 73, and 180 urine specimens (January 2013 to August 2014) from women whom were in their first, second, and third trimesters of pregnancy, respectively. We measure urinary DEHP metabolite concentrations to estimate the DI of DEHP and the hazard quotient (HQ) of subjects. This was the first study to assess the effects of DEHP-tainted food scandal exposure in pregnant women across the three trimesters of pregnancy. After the tainted food report, the concentrations of urine PAE metabolite were significantly decreased, especially those of DEHP metabolites. Based on different reference limit values, the percentages of pregnant women whose HQDEHP value exceeded the limit ranged from 0.53% to 8.93%. Despite this low frequency, the higher ΣPAE exposure during the second trimester may significantly increase the risk of relatively low birth height compared to the lower exposure group (ß=-0.63 (-1.20 to -0.06)). Our results support the hypothesis that exposure to relatively high concentrations of DEHP in pregnant Taiwanese women may have an adverse effect on birth outcomes. The percentage of subjects whose exposure level exceeded the exposure limit was low; however, high PAEs exposure appears to be significantly associated with birth outcomes. Therefore, we suggest that reference dose for PAEs should be revised.


Assuntos
Exposição Dietética , Dietilexilftalato/análise , Contaminação de Alimentos , Ácidos Ftálicos/urina , Adulto , Feminino , Humanos , Gravidez , Taiwan
18.
Sci Total Environ ; 612: 1373-1379, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-28898944

RESUMO

BACKGROUND: Arsenic exposure is a global health concern. Several studies have focused on chronic arsenic exposure in adults; however, limited data are available regarding the potential adverse effects of prenatal exposure on fetuses and neonates. OBJECTIVES: To assess which time point maternal arsenic exposure may influence the fetus during pregnancy and birth outcomes. METHODS: In this study, total arsenic concentrations were analyzed in urine samples collected from 130 women with singleton pregnancies (22-45years old) in Taiwan from March to December of 2010. All fetal biometric measurements in each trimester period and birth outcomes at delivery were obtained. We applied a generalized estimating equation model and multivariate regression models to evaluate the associations between maternal urinary total arsenic (UtAs) exposure during pregnancy, fetal biometric measurements, and neonatal birth outcomes. RESULTS: We observed statistically significant correlations between maternal UtAs levels and the fetal biparietal diameter over all three trimesters (ß=-1.046mm, p<0.05). Multiple regression analyses showed a negative association between maternal UtAs levels and chest circumference in the first trimester (ß=-0.721cm, p<0.05), and second-trimester UtAs exposure was associated with decreases in birth weight (ß=-173.26g, p<0.01), head circumference (ß=-0.611cm, p<0.05), and chest circumference (ß=-0.654cm, p<0.05). Dose-response relationships were also observed for maternal UtAs exposure and birth outcomes. CONCLUSIONS: We identified a negative relationship between maternal UtAs levels during pregnancy, fetal development, and neonatal birth outcomes. These findings should be confirmed in future studies with large sample sizes.


Assuntos
Arsênio/urina , Desenvolvimento Fetal , Exposição Materna/efeitos adversos , Adulto , Peso ao Nascer , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Pessoa de Meia-Idade , Análise Multivariada , Gravidez , Análise de Regressão , Taiwan , Adulto Jovem
19.
Sci Total Environ ; 607-608: 1126-1135, 2017 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-28724251

RESUMO

Prenatal exposure to phenols, phthalates (PAEs), and organophosphate (OP) pesticides may increase the risk of abnormal birth outcomes. However, many previous studies have examined exposure to a limited number of chemical classes or exposure profiles limited to a specific stage of pregnancy. This study aims to characterize the concurrent exposure scenario throughout pregnancy by simultaneously monitoring internal doses of several endocrine-disrupting compounds (EDCs), including 2 phenols (nonylphenol (NP) and bisphenol A (BPA)), 9 PAEs, and 6 OP pesticide metabolites and to assess the relationships between concurrent exposure to EDCs and infant birth weight, length, and head and chest circumference. One hundred and sixty two women provided three spot urine samples at approximately 11 and 26weeks gestation and at delivery. We applied multivariable linear regression and ridge regression models to estimate the effects of separate and correlated exposures. Multivariable linear regression models revealed that women with short birth-length infants had significantly higher urinary second-trimester NP levels (50th percentile, 5.03µg/g creatinine) (ß=-0.47cm; 95% CI=-0.93 to -0.01). Similarly significant relationships were observed between second-trimester mono-methyl phthalate (MMP) exposure and short birth length, second-trimester ΣPAEs and short birth length, second-trimester ΣPAEs exposure and reduced head and chest circumference, second-trimester diethylphosphate (DEP) exposure and reduced birth weight and length, and second-trimester ΣDEPs exposure and short birth length. Women with urinary BPA above the 75th percentile or ΣPAEs levels above the 50th percentile in the third trimester had infants with significantly reduced head circumference. These observations suggest that the second trimester may be the critical stage of susceptibility for fetal development. In ridge regression models, for which women with fewer measures for exposure to NP, BPA, MMP, ΣPAEs, DEP and ΣDEPs simultaneously were available, no relationships were found with infant size at birth. Additional studies with larger sample sizes are warranted.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Exposição Materna/efeitos adversos , Organofosfatos/efeitos adversos , Fenóis/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Peso ao Nascer , Estatura , Estudos de Coortes , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Humanos , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Taiwan
20.
Int J Hyg Environ Health ; 220(5): 869-879, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28457892

RESUMO

Phthalate exposure is omnipresent and known to have developmental and reproductive effects in children. The aim of this study was to determine the phthalate exposure sources and their relative contributions among children in Taiwan. During the first wave of the Risk Assessment of Phthalate Incident in Taiwan (RAPIT), in 2012, we measured 8 urinary phthalate metabolites in 226 children aged 1-11 years old and in 181 children from the same cohort for the wave 2 study in 2014. A two-stage statistical analysis approach was adopted. First, a stepwise regression model was used to screen 80 questions that explored the exposure frequency and lifestyle for potential associations. Second, the remaining questions with positive regression coefficients were grouped into the following 6 exposure categories: plastic container/packaging, food, indoor environment, personal care products, toys, and eating out. A mixed model was then applied to assess the relative contributions of these categories for each metabolite. The use of plastic container or food packaging were dominant exposure sources for mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and mono-n-butyl phthalate (MnBP). The indoor environment was a major exposure source of mono-methyl phthalate (MMP), mono-benzyl phthalate (MBzP), and mono-isobutyl phthalate (MiBP). The consumption of seafood showed a significant correlation with MEHP. The children's modified dietary behavior and improved living environment in the second study wave were associated with lower phthalate metabolite levels, showing that phthalate exposures can be effectively reduced.


Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/urina , Ácidos Ftálicos/urina , Plastificantes/análise , Animais , Criança , Pré-Escolar , Crustáceos , Dieta , Feminino , Peixes , Contaminação de Alimentos , Embalagem de Alimentos , Humanos , Lactente , Masculino , Alimentos Marinhos , Inquéritos e Questionários , Taiwan
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