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1.
Ecotoxicol Environ Saf ; 225: 112756, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34507040

RESUMO

Exposure to melamine, which is ubiquitous in daily life, is linked to adverse kidney outcomes. The melamine tolerable daily intake in humans is based on the no-observed-effect-level (NOEL) established in a single-toxicant murine model. However, humans are often simultaneously exposed to multiple environmental nephrotoxicants. The NOEL of melamine during coexposure with other toxicants needs to be evaluated. Oxalate is a potentially nephrotoxic terminal metabolite, and hyperoxaluria is reportedly associated with chronic kidney disease. We explored whether these two potential nephrotoxicants can interact and enhance kidney injury. We established a Sprague-Dawley rat model of coexposure to the melamine NOEL (63 mg/kg/day) and 2% hydroxy-L-proline (HLP, an oxalate precursor) in drinking water to simulate human environmental melamine exposure. Melamine/oxalate coexposure increased proximal tubular cell mitochondrial reactive oxygen species levels, lipid peroxidation and oxidative DNA damage. The degrees of mitochondrial damage, tubular cell apoptosis, tubular atrophy, and interstitial fibrosis were elevated in coexposed rat kidneys. The evidence indicated that exposure to the melamine NOEL can cause renal tubular injury via oxidative stress and that this effect may be enhanced via interaction of melamine with other environmental factors, such as oxalate. Thus, melamine risk assessment and toxicity prevention should be conducted carefully in different susceptible populations.


Assuntos
Oxalatos , Estresse Oxidativo , Animais , Rim , Camundongos , Ratos , Ratos Sprague-Dawley , Triazinas
2.
Environ Int ; 156: 106652, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34034116

RESUMO

Environmental melamine exposure has been associated with deteriorating kidney function in early-stage chronic kidney disease patients. In this study, a benchmark dose (BMD) approach was used to establish melamine exposure threshold in 293 patients with eGFR≥30 ml/min per 1.73 m2. The patients were enrolled 2006-2010 and followed-up for a median of 7.0 years to monitor kidney outcomes. Average daily intakes (AvDI) of melamine were estimated using one-spot urine samples collected at enrollment. BMDs and corresponding one-sided 95% lower bound (BMDLs) were derived using established dose-response models relating estimated AvDIs and dichotomous kidney outcomes: doubling of serum creatine levels, eGFR decreased > 3 ml/min per 1.73 m2 per year, and >30% decline in eGFR during the first 2 years. In addition, survival time to doubling of serum creatinine and eGFR decline over time were assessed as continuous endpoints. Given a benchmark response of 0.10, BMDLs ranged from 0.74 to 2.03 µg/kg_bw/day after Bayesian model averaging, a range one to two orders lower than the current WHO recommended tolerable daily intake of 200 µg/kg_bw/day and the US FDA's 63 µg/kg_bw/day. Our results suggest that early-stage CKD patients should strictly refrain from using melamine tableware and related melamine-made products.


Assuntos
Benchmarking , Insuficiência Renal Crônica , Teorema de Bayes , Humanos , Rim , Triazinas/toxicidade
3.
Ecotoxicol Environ Saf ; 200: 110741, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32497990

RESUMO

Environmental exposure to melamine has been associated with early renal injury in urolithiasis patients even when urinary concentrations of melamine are low. The aim of this study was to derive a benchmark dose (BMD) for melamine for urolithiasis patients. To do this, one-spot urine sample from 309 participants was obtained to measure urinary melamine and N-acetyl ß-D-glucosaminidase (NAG), an early renal damage biomarker. The participants were then classified into four exposure groups based on the outcomes of melamine tableware usage questionnaire. A beta distribution of urinary excretion fraction for each group was assumed to estimate their average daily intakes (AvDIs) of melamine. The BMD and the corresponding one-sided 95% lower bound (BMDL) was then derived based on Bayesian model averaging of alternative regression models between the participants' NAG levels and their estimated AvDIs, adjusting for age, gender, and other covariates. Bayesian Markov chain Monte Carlo simulations were used for all the estimates. With a benchmark response of 0.10, the simulated BMDL of 4.89 µg/kg-bw/day for melamine exposure threshold was much lower than the WHO's current recommended tolerable daily intake of 200 µg/kg_bw/day and the US FDA's 63 µg/kg_bw/day. The current regulation level of melamine might not safeguard urolithiasis patients from further deterioration of renal function.


Assuntos
Cálcio , Rim/efeitos dos fármacos , Triazinas/toxicidade , Triazinas/urina , Urolitíase/urina , Acetilglucosaminidase/urina , Adulto , Idoso , Teorema de Bayes , Biomarcadores/urina , Exposição Ambiental , Feminino , Humanos , Rim/fisiopatologia , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Método de Monte Carlo , Probabilidade , Urolitíase/fisiopatologia
4.
Environ Res ; 181: 108902, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31785779

RESUMO

BACKGROUND: Phthalic acid esters are established as endocrine disruptors. The study aimed to evaluate the association between urinary phthalate metabolites and prostate cancer occurrence. METHODS: The study was based on the Taiwan Community-Based Cancer Screening Program, which was set up in 1991-1992 and followed periodically. By 2010, 80 incident prostate cancer cases were identified in the 12,020 men. For each case, 2 controls were randomly selected, matched by age (±3 years), urine collection date (±3 months), and residential township. Frequently used phthalate metabolites from the urine samples were quantified by liquid chromatography/electrospray ionization tandem mass spectrometry. Logistic regression was conducted to assess the association between the exposure levels and prostate cancer occurrence. RESULTS: Exposure to di (2-ethylhexyl), butyl-benzyl and di-isobutyl phthalates (DEHP, BBzP, DiBP) was positively associated with prostate cancer in men with waist circumference (WC) ≥90 cm but not in the leans. Odds ratio for the DEHP metabolite summary score (upper tertile compared to the rest) and prostate cancer were 7.76 (95% CI = 1.95-30.9) for WC ≥ 90 cm. CONCLUSIONS: DEHP, BBzP, and DiBP exposure were associated with prostate cancer occurrence in abdominally obese men. The main limitation remains the lack of mechanistic experiments and comparable toxicological data.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Ácidos Ftálicos , Neoplasias da Próstata/epidemiologia , Estudos de Casos e Controles , Exposição Ambiental , Humanos , Masculino , Taiwan/epidemiologia
5.
Int J Hyg Environ Health ; 222(6): 971-980, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31221485

RESUMO

INTRODUCTION: Prenatal exposure to di(2-ethylhexyl) phthalate (DEHP) has been reported to be associated with adverse effects on neurodevelopment that yield behavior syndromes in young children with an estimated median exposure lower than the currently recommended tolerable daily intake (TDI) and reference dose (RfD). OBJECTIVES: Our aim was to derive the benchmark dose for prenatal exposure to DEHP for the neurodevelopmental health in children. METHODS: A total of 122 mother-child pairs from the Taiwan Maternal and Infant Cohort Study were analyzed for the dose-response relationship between maternal exposure to DEHP and children's behavioral syndromes evaluated at 8 years (n = 122, 2009), 11 years (n = 96, 2012), and 14 years (n = 78, 2015) of age. We employed a multivariate regression model to assess the statistical associations between the estimated maternal average daily intake of DEHP and child's individual CBCL scores for boys and girls at each separate age, followed by a mixed model for all the children across three ages accounting for individual variations. We then employed structural equation models by combining the children's specific behavioral problem scores at different ages and obtained a simulated overall latent score in relation to maternal exposure. Based on the established dose-response relationship, we derived the benchmark dose (BMD) and the lower limit (BMDL). RESULTS: Associations of maternal DEHP exposure (median 4.54µg/kg_bw/day) with the Child Behavior Checklist (CBCL) scores were all significant, except for somatic complaints, adjusting for child's age, gender, IQ, and family income. The BMDL, given a benchmark response of 0.10 (0.05) and a background response of 0.05, was 6.01 (2.16) µg/kg_bw/dayfor an integrated CBCL score. CONCLUSIONS: The current TDI (RfD) of 50 (20) µg/kg_bw/day for DEHP might not protect pregnant women for their children from behavioral problems. There remains the lack of comparable toxicological data. Further investigations are needed.


Assuntos
Poluentes Ambientais/urina , Exposição Materna , Ácidos Ftálicos/urina , Efeitos Tardios da Exposição Pré-Natal , Comportamento Problema , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Troca Materno-Fetal , Gravidez
6.
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
7.
PLoS One ; 11(3): e0151070, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26960145

RESUMO

BACKGROUND: In May 2011, di(2-ethylhexyl) phthalates (DEHP) and, to a lesser extent, di-iso-nonyl phthalate (DiNP) were found to have been illegally used for many years in Taiwan as clouding agents in foods including sports drinks, juice beverages, tea drinks, fruit jam/nectar/jelly, and health or nutrient supplements. OBJECTIVE: To estimate the DEHP exposure for the study participants for the follow-up epidemiological study and health risk assessment. METHODS: A total of 347 individuals possibly highly exposed to phthalate-tainted foods participated in the study. Exposure assessment was performed based on the participants' responses to a structured questionnaire, self-report of exposure history, urinary metabolite concentrations, and DEHP concentration information in 2449 food records. A Bayesian statistical approach using Markov chain Monte Carlo simulation was employed to deal with the uncertainties in the DEHP concentrations of the contaminated foods and the participants' likelihood of being exposed. RESULTS: An estimated 37% and 15% of children younger than 12 years old were exposed to DEHP at medium (20-50 µg / kg_bw / day) and high AvDIs (50-100 µg / kg_bw / day), respectively, prior to the episode (9% and 3% in adults, respectively). Moreover, 11% of children and 1% of adults were highly exposed (> 100 µg / kg_bw / day), with a maximum of 414.1 µg / kg_bw / day and 126.4 µg / kg_bw / day, respectively. CONCLUSIONS: The phthalate exposure-associated adverse health effects for these participants warrant further investigation. The estimation procedure may be applied to other exposure assessment with various sources of uncertainties.


Assuntos
Bebidas/análise , Monitoramento Ambiental , Ácidos Ftálicos/análise , Adolescente , Adulto , Teorema de Bayes , Criança , Pré-Escolar , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/análise , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Medição de Risco , Inquéritos e Questionários , Taiwan/epidemiologia , Adulto Jovem
8.
Int J Hyg Environ Health ; 218(7): 603-15, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26163779

RESUMO

BACKGROUND: Some phthalic acid esters (PAEs) and nonylphenol (NP) are endocrine-disrupting chemicals (EDCs) that are widely used in consumer products. Consequently, the general population is exposed simultaneously to both groups of chemicals. OBJECTIVE: To investigate the single- and co-exposure effects of PAEs (DMP, DEP, DnBP, DiBP, BBzP, and DEHP) and NP on obesity and pubertal maturity to compare the body sizes of general adolescents with the complainants of the phthalate-tainted foods scandal that occurred in Taiwan. METHODS: This study included 270 general adolescents aged 6.5-15.0 years and 38 complainants aged 6.5-8.5 years. Nine metabolites of the five PAEs and of NP were measured in urine. We used a questionnaire to evaluate pubertal maturity, measured anthropometric indices (APs) to assess body size, and collected urine samples to measure the two groups of chemicals. RESULTS: We found that urinary PAE metabolite concentrations (specifically, metabolites of DEP, DnBP, DiBP, and DEHP) were positively associated with the APs for abdominal obesity (including skinfold thickness, waist circumference, waist-to-height ratio, and waist-to-hip) and indicated a dose-response relationship. Mono-methyl phthalate (MMP) exposure was inversely associated with pubarche among boys. The daily intake of DEHP in general adolescents exceeded the reference doses (RfD-20 µg/kgbw/day) and tolerable daily intake (TDI-50 µg/kgbw/day) by 3.4% and 0.4%, respectively. No associations were observed between NP exposure or co-exposure and the APs or pubertal maturity. No significant differences were observed between general adolescents and the complainants with regard to weight, height, or BMI. CONCLUSIONS: The study suggests that PAE (specifically, DEP, DnBP, DiBP, and DEHP) exposure is associated with abdominal obesity in adolescents and that the APs for abdominal obesity are more sensitive than BMI for measuring obesity among adolescents. We suggest that the RfD and TDI for PAEs should be revised to provide sufficient protection.


Assuntos
Peso Corporal/efeitos dos fármacos , Disruptores Endócrinos/efeitos adversos , Exposição Ambiental/efeitos adversos , Obesidade Pediátrica/etiologia , Fenóis/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Puberdade/efeitos dos fármacos , Adolescente , Antropometria , Tamanho Corporal/efeitos dos fármacos , Criança , Dietilexilftalato/efeitos adversos , Dietilexilftalato/urina , Disruptores Endócrinos/urina , Exposição Ambiental/análise , Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/urina , Feminino , Contaminação de Alimentos , Humanos , Masculino , Obesidade Abdominal/etiologia , Obesidade Abdominal/urina , Obesidade Pediátrica/urina , Fenóis/urina , Ácidos Ftálicos/urina , Valores de Referência , Caracteres Sexuais , Taiwan
9.
PLoS One ; 9(4): e94020, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24736322

RESUMO

Although the incidence of variant Creutzfeldt-Jakob disease (vCJD) has declined to 1 since 2012 in the UK, uncertainty remains regarding possible future cases and the size of the subclinical population that may cause secondary transmission of the disease through blood transfusion. Estimating the number of individuals who were exposed to the bovine spongiform encephalopathy (BSE) infectious agent and may be susceptible to vCJD will help to clarify related public health concerns and plan strategies. In this paper, we explore this estimate by describing the probability of potential exposure due to dietary intake throughout the BSE epidemic period from 1980 to 1996 as a stochastic Poisson process. We estimate the age- and gender-specific exposure intensities in food categories of beef and beef-containing dishes, burgers and kebabs, pies, and sausages, separating the two periods of 1980-1989 and 1990-1996 due to the specified bovine offal legislation of 1989. The estimated total number of (living) exposed individuals during each period is 5,089,027 (95% confidence interval [CI] 4,514,963-6,410,317), which was obtained by multiplying the population size of different birth cohorts by the probability of exposure via dietary intake and the probability of survival until the end of 2013. The estimated number is approximately doubled, assuming a contamination rate of [Formula: see text]. Among those individuals estimated, 31,855 (95% CI 26,849-42,541) are susceptible to infection. We also examined the threshold hypothesis by fitting an extreme-value distribution to the estimated infectious dose of the exposed individuals and obtained a threshold estimate of 13.7 bID50 (95% CI 6.6-26.2 bID50) (Weibull). The results provide useful information on potential carriers of prion disease who may pose a threat of infection via blood transfusion and thus provide insight into the likelihood of new incidents of vCJD occurring in the future.


Assuntos
Síndrome de Creutzfeldt-Jakob/epidemiologia , Dieta/efeitos adversos , Encefalopatia Espongiforme Bovina/transmissão , Exposição Ambiental , Microbiologia de Alimentos , Adolescente , Adulto , Animais , Portador Sadio , Bovinos , Criança , Pré-Escolar , Estudos de Coortes , Síndrome de Creutzfeldt-Jakob/história , Feminino , História do Século XX , Humanos , Lactente , Masculino , Produtos da Carne , Vigilância em Saúde Pública , Reino Unido/epidemiologia , Adulto Jovem
10.
Risk Anal ; 33(11): 1958-68, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23755826

RESUMO

To date, the variant Creutzfeldt-Jakob disease (vCJD) risk assessments that have been performed have primarily focused on predicting future vCJD cases in the United Kingdom, which underwent a bovine spongiform encephalopathy (BSE) epidemic between 1980 and 1996. Surveillance of potential BSE cases was also used to assess vCJD risk, especially in other BSE-prevalent EU countries. However, little is known about the vCJD risk for uninfected individuals who accidentally consume BSE-contaminated meat products in or imported from a country with prevalent BSE. In this article, taking into account the biological mechanism of abnormal prion PrP(res) aggregation in the brain, the probability of exposure, and the expected amount of ingested infectivity, we establish a stochastic mean exponential growth model of lifetime exposure through dietary intake. Given the findings that BSE agents behave similarly in humans and macaques, we obtained parameter estimates from experimental macaque data. We then estimated the accumulation of abnormal prions to assess lifetime risk of developing clinical signs of vCJD. Based on the observed number of vCJD cases and the estimated number of exposed individuals during the BSE epidemic period from 1980 to 1996 in the United Kingdom, an exposure threshold hypothesis is proposed. Given the age-specific risk of infection, the hypothesis explains the observations very well from an extreme-value distribution fitting of the estimated BSE infectivity exposure. The current BSE statistics in the United Kingdom are provided as an example.


Assuntos
Síndrome de Creutzfeldt-Jakob/etiologia , Encefalopatia Espongiforme Bovina/transmissão , Produtos da Carne/efeitos adversos , Animais , Bovinos , Síndrome de Creutzfeldt-Jakob/epidemiologia , Encefalopatia Espongiforme Bovina/epidemiologia , Humanos , Incidência , Produtos da Carne/virologia , Modelos Teóricos , Fatores de Risco , Reino Unido/epidemiologia
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