Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.392
Filtrar
1.
J Environ Pathol Toxicol Oncol ; 40(2): 65-79, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33822518

RESUMO

Environmental pollution (EP) is a well-known threat to wild animals, but its toxicological impact is poorly understood. In vitro toxicity evaluation using cells of lower predators could be a promising way to assess and monitor the effects of EPs on whole wildlife populations that are related in the food web. Here, we describe EPs' toxic effect and mechanism in the primary fibroblast derived from the embryo of the striped field mouse, Apodemus agrarius. Characterization of the primary fibroblast was via morphology, genetics, immunocytochemistry, and stable culture conditions for optimal toxicity screening. Cell viability assays-MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and lactate dehydrogenase (LDH)-were performed to observe cytotoxicity, and quantitative PCR was conducted to confirm gene alteration by EP exposure. MTT and LDH assays confirmed the cytotoxicity of transfluthrin (TF), benzyl butyl phthalate (BBP), and 17ß-estradiol (E2) with IC50 values of 10.56 µM, 10.82 µM, and 24.08 µM, respectively, following 48-h exposures. mRNA expression of androgen-binding protein, growth hormone receptor, cytochrome C oxidase, and cytochrome P450-1A1 was induced after exposure to TF, BBP, and E2. We unveiled new EP mechanisms at the mammalian cellular level and discovered potential biomarker genes for monitoring of EPs. Based on our findings, we propose the primary fibroblast of A. agrarius as a valuable model to assess the toxicological effects of EP on wildlife.


Assuntos
Ciclopropanos/toxicidade , Disruptores Endócrinos/toxicidade , Estradiol/toxicidade , Estrogênios/toxicidade , Fibroblastos/efeitos dos fármacos , Fluorbenzenos/toxicidade , Inseticidas/toxicidade , Ácidos Ftálicos/toxicidade , Proteína de Ligação a Androgênios/genética , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ciclo-Oxigenase 1/genética , Citocromo P-450 CYP1A1/genética , Embrião de Mamíferos/citologia , Fibroblastos/metabolismo , Murinae , Receptores da Somatotropina/genética
2.
Artigo em Inglês | MEDLINE | ID: mdl-33804363

RESUMO

BACKGROUND: Breast cancer is the most common cancer and the second leading cause of cancer-related death amongst American women. Endocrine-disrupting chemicals (EDCs), especially bisphenol A (BPA) and phthalates, have adverse effects on human health. However, the association of BPA and phthalates with breast cancer remains conflicting. This study aims to investigate the association of BPA and phthalates with breast cancer. METHODS: Correlative studies were identified by systematically searching three electronic databases, namely, PubMed, Web of Sciences, and Embase, up to November 2020. All data were analyzed using Stata 15.0. RESULTS: A total of nine studies, consisting of 7820 breast cancer cases and controls, were included. The urinary phthalate metabolite mono-benzyl phthalate (MBzP) and mono-2-isobutyl phthalate (MiBP) were negatively associated with breast cancer (OR = 0.73, 95% CI: 0.60-0.90; OR = 0.75, 95% CI: 0.58-0.98, respectively). However, the overall ORs for BPA, mono-ethyl phthalate (MEP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(3-carboxypropyl) phthalate (MCPP), and mono-butyl phthalate (MBP) were 0.85 (95% CI: 0.69-1.05), 0.96 (95% CI: 0.62-1.48), 1.12 (95% CI: 0.88-1.42), 1.13 (95% CI: 0.74-1.73), 1.01 (95% CI: 0.74-1.40), 0.74 (95% CI: 0.48-1.14), and 0.80 (95% CI: 0.55-1.15), respectively, suggesting no significant association. The sensitivity analysis indicated that the results were relatively stable. CONCLUSION: Phthalate metabolites MBzP and MiBP were passively associated with breast cancer, whereas no associations were found between BPA, MEP, MEHHP, MEHP, MEOHP, MCPP, and MBP and breast cancer. More high-quality case-control studies or persuasive cohort studies are urgently needed to draw the best conclusions.


Assuntos
Neoplasias da Mama , Poluentes Ambientais , Ácidos Ftálicos , Compostos Benzidrílicos/toxicidade , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/epidemiologia , Exposição Ambiental/análise , Feminino , Humanos , Fenóis , Ácidos Ftálicos/toxicidade
3.
Artigo em Inglês | MEDLINE | ID: mdl-33808331

RESUMO

PURPOSE OF REVIEW: Bisphenol A and phthalate have been found in the environment, as well as in humans. In this narrative review pre- and postnatal bisphenol A and phthalate exposures, their relationship to neurodevelopment, and the behavioral outcomes of children are elucidated, focusing in particular on the recent case-control, cross-sectional, and longitudinal studies. This review also introduces some of the possible mechanisms behind the observed associations between exposures and outcomes. RECENT FINDINGS: Although bisphenol A and phthalate exposure have been reported to influence neurobehavioral development in children, there are various kinds of test batteries for child neurodevelopmental assessment at different ages whose findings have been inconsistent among studies. In addition, the timing and number of exposure assessments have varied. SUMMARY: Overall, this review suggests that prenatal exposure to bisphenol A and phthalates may contribute to neurobehavioral outcomes in children. The evidence is still limited; however, Attention Deficit Hyperactivity Disorder (ADHD) symptoms, especially among boys, constantly suggested association with both prenatal and concurrent exposure to bisphenol A. Although there is limited evidence on the adverse effects of prenatal and postnatal bisphenol A and phthalate exposures provided, pregnant women and young children should be protected from exposure based on a precautionary approach.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Efeitos Tardios da Exposição Pré-Natal , Compostos Benzidrílicos/análise , Compostos Benzidrílicos/toxicidade , Criança , Pré-Escolar , Estudos Transversais , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Feminino , Humanos , Masculino , Fenóis , Ácidos Ftálicos/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-33668677

RESUMO

The association of prenatal phthalate exposure with physical reasoning was assessed in 159 (78 female; 81 male) 4.5-month-old infants from a prospective cohort. Phthalate metabolites were quantified in urine from 16-18 gestational weeks and a pool of five urines from across pregnancy. Infants' looking times to physically impossible and possible events were recorded via infrared eye-tracking. Infants that recognize that one of the events is impossible will look at that event longer. Associations of phthalate biomarkers with looking time differences (impossible-possible) were adjusted for maternal age, infant sex, and order of event presentation, and effect modification by infant sex was assessed. Each interquartile range (IQR) increase of monoethyl phthalate in the pooled sample was associated with females' increased looking time (ß = 1.0; 95%CI = 0.3, 1.7 s) to the impossible event. However, for males, an IQR increase in monoethyl phthalate at 16-18 weeks (ß = -2.5; 95%CI = -4.4,-0.6 s), the sum of di(isononyl) phthalate metabolites in the pooled sample (ß = -1.0; 95%CI = -1.8, -0.1 s), and the sum of all phthalate metabolites in both samples (ß = -2.3; 95%CI = -4.4, -0.2 s) were associated with increased looking to the possible event, suggesting that higher prenatal phthalate exposure is associated with poorer physical reasoning in male infants.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Efeitos Tardios da Exposição Pré-Natal , Criança , Cognição , Poluentes Ambientais/toxicidade , Feminino , Humanos , Lactente , Masculino , Exposição Materna/efeitos adversos , Ácidos Ftálicos/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Estudos Prospectivos
5.
Environ Int ; 152: 106458, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33677245

RESUMO

This study investigated concentrations of phthalates (diesters of phthalic acids) in blubber/adipose tissue of blue whales (Balaenoptera musculus), fin whales (Balaenoptera physalus), bowhead whales (Balaena mysticetus) and polar bears (Ursus maritimus) sampled in the Svalbard Archipelago (extending westward in the case of bowhead whales). Additionally, total concentrations (free and conjugated forms) of eight phthalate monoester metabolites were analysed in plasma of polar bears. Bis(2-ethylhexyl) phthalate (DEHP) was the only phthalate quantified among the 12 phthalates investigated. This compound was present in 6/7 fin whale samples, 4/7 blue whale samples, 2/5 bowhead whale samples and 1/12 polar bear samples. DEHP concentrations ranged from <20-398 ng/g wet weight. Phthalate metabolites, mono-n-butyl phthalate and monoisobutyl phthalate, were found in low concentrations (<1.2 ng/mL) in some of the polar bear samples. In vitro reporter gene assays were used to assess transcriptional activity of fin whale peroxisome proliferator-activated receptor gamma (PPARG), glucocorticoid receptor (GR) and the thyroid hormone receptor beta (THRB) by DEHP and diisononyl phthalate (DiNP). Due to the high degree of similarity of the ligand binding domain in the THRB and PPARG among whales, polar bears and humans, the transactivation results also apply for these species. DEHP showed both agonistic and antagonistic effects towards whale THRB at considerably higher concentrations than measured in the study animals; DiNP was a weak agonist of whale THRB. No significant agonistic or antagonistic effects were detected for DEHP or DiNP for whale PPARG, whereas DEHP and DiNP decreased basal luciferase activity mediated by whale GR at several test concentrations. In conclusion, DEHP was detected in the blubber of marine mammals from the Norwegian Arctic and it appears to have potential to modulate the transcriptional activity of whale THRB, but current DEHP concentrations do not modulate the function of the studied nuclear receptors in adipose tissue of blue whales, fin whales, bowhead whales or polar bears sampled from the Norwegian Arctic.


Assuntos
Baleia Comum , Ácidos Ftálicos , Animais , Regiões Árticas , Ácidos Ftálicos/toxicidade , Svalbard
6.
Environ Int ; 151: 106459, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33684682

RESUMO

BACKGROUND: Several in vitro and in vivo studies have demonstrated the effects of phthalates on androgen synthesis, and the adverse outcomes of phthalate exposure on male reproductive function have been reported. However, the direct relationship among these three factors remains unknown. OBJECTIVE: To explore the potential roles of steroids involved in androgen synthesis in the association between phthalate exposure and semen quality. METHODS: Eighteen phthalate metabolites (mPAEs) and nine steroids were analyzed in semen samples of 403 male participants aged 18-54 years from a hospital in Shenzhen, China. The associations across phthalate metabolites, steroids, and eleven semen quality parameters were evaluated by multivariate linear regression and logistical regression models. The potential contributions of steroids to the associations between phthalate metabolites and semen quality outcomes were explored by mediation effect analysis. RESULTS: In this cross-sectional study, mono-n-butyl phthalate (MnBP) was inversely associated with nine continuous semen quality parameters in a dose-dependent manner (all p for trend < 0.05). Positive associations were observed between MnBP tertiles and androstenedione (ADD) and pregnenolone (PGL), of which only ADD was significantly associated with sperm quality (i.e., motility, p < 0.05). The estimated average mediated effects of seminal ADD on the associations between MnBP and lower sperm motility parameters (i.e., total motility, TR; progressive motility, PR; curvi-linear velocity, VCL) were 6.4-11.9% (all p < 0.05). The potential mediated effects of ADD on the increasing risks of TR (9.8%) and PR (8.5%) abnormalities induced by MnBP exposure were also observed in logistical regression analysis. CONCLUSION: Our results indicated that androgen synthesis in reproductive system may be potentially affected by phthalate exposure, thereby resulting in reduced sperm motility in adult men. Further studies are needed to understand the actual roles and underlying mechanism of action of androstenedione on these associations.


Assuntos
Androgênios , Ácidos Ftálicos , Adolescente , Adulto , China , Estudos Transversais , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Humanos , Masculino , Pessoa de Meia-Idade , Ácidos Ftálicos/toxicidade , Sêmen , Análise do Sêmen , Motilidade Espermática , Espermatozoides , Adulto Jovem
8.
Mar Pollut Bull ; 166: 112222, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33711610

RESUMO

A marine diatom (Phaeodactylum tricornutum) was exposed to different concentrations of dimethyl phthalate (DMP) and diethyl phthalate (DEP) for 96 h within a batch-culture system to investigate their toxicities. Results showed that P. tricornutum could remove DMP and DEP effectively with removal rates of 0.20-0.30 and 0.14-0.21 mg L-1 h-1, respectively. In addition, DMP and DEP significantly inhibited the photosynthesis and chlorophyll a biosynthesis of P. tricornutum with 96-h EC50 values of 390.5 mg L-1 and 74.0 mg L-1, respectively. Results of reactive oxygen species (ROS) level suggested that the two PAEs could induce excessive ROS production in the diatom. Moreover, activities of antioxidant enzymes (i.e., SOD and POD) in the diatom increased with the increase of DMP and DEP concentrations. The results will help to understand the toxic mechanisms of PAEs, and provide strong evidences for evaluating their ecological risks in the marine environment.


Assuntos
Diatomáceas , Ácidos Ftálicos , Clorofila A , Ésteres , Estresse Oxidativo , Ácidos Ftálicos/toxicidade
9.
Artigo em Inglês | MEDLINE | ID: mdl-33671626

RESUMO

In this study, we measured the occurrence of organophosphate esters (OPEs) and phthalates in the settled dust (floor and air conditioner filter dust) and in suspended particulate matter (PM10) from different microenvironments (households (n = 20), offices (n = 10) and hotels (n = 10)) of Jeddah, Saudi Arabia. Bis (2-Ethylhexyl) phthalate (DEHP) was the major pollutant (contributing >85% of total chemicals burden) in all types of indoor dust with a concentration up to 3,901,500 ng g-1. While dibutyl phthalate (DBP) and DEHP together contributed >70% in PM10 (1900 ng m-3), which indicate PM10 as a significant source of exposure for DBP and DEHP in different Saudi indoor settings. Tris (1-chloro-2-propyl) phosphate (TCPP) was the major OPE in PM10 with a concentration of up to 185 ng m-3 and the occurrence of OPEs in indoor dust varied in studied indoor settings. The estimated daily intake (EDI) of studied chemicals via dust ingestion and inhalation of PM10 was below the reference dose (RfD) of individual chemicals. However, estimated incremental lifetime cancer risk (ILCR) with moderate risk (1.5 × 10-5) for Saudi adults and calculated hazardous index (HI) of >1 for Saudi children from DEHP showed a cause of concern to the local public health.


Assuntos
Poluição do Ar em Ambientes Fechados , Ácidos Ftálicos , Adulto , Poluição do Ar em Ambientes Fechados/análise , Criança , Poeira/análise , Exposição Ambiental/análise , Ésteres/análise , Humanos , Organofosfatos/análise , Organofosfatos/toxicidade , Ácidos Ftálicos/análise , Ácidos Ftálicos/toxicidade , Arábia Saudita
10.
Artigo em Inglês | MEDLINE | ID: mdl-33673219

RESUMO

Exposures to phthalates, parabens, and other phenols are often correlated due to their ubiquitous use in personal care products and plastics. Examining these compounds as a complex mixture may clarify inconsistent relationships between individual chemicals and childhood adiposity. Using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal cohort of children in Salinas Valley, California (n = 309), we examined biomarkers of 11 phthalate metabolites and 9 phenols, including several parabens and bisphenol A, measured in maternal urine at two time points during pregnancy. We measured child height and weight at age five to calculate the body mass index (BMI) z-scores and overweight/obesity status. The association between prenatal urinary concentrations of biomarkers with the childhood BMI z-score and overweight/obesity status was analyzed using single-pollutant models and two mixture methods: Bayesian hierarchical modeling (BMH) and Bayesian kernel machine regression (BKMR). Urinary concentrations of monoethyl phthalate, monocarboxy-isononly phthalate (metabolites of diethyl phthalate and di-isodecyl phthalate, respectively), and propylparaben were consistently associated with an increased BMI z-score and overweight/obesity status across all modeling approaches. Higher prenatal exposures to the cumulative biomarker mixture also trended with greater childhood adiposity. These results, robust across two methods that control for co-pollutant confounding, suggest that prenatal exposure to certain phthalates and parabens may increase the risk for obesity in early childhood.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Efeitos Tardios da Exposição Pré-Natal , Teorema de Bayes , Criança , Pré-Escolar , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Poluentes Ambientais/toxicidade , Feminino , Humanos , Obesidade/induzido quimicamente , Obesidade/epidemiologia , Parabenos/efeitos adversos , Fenóis/toxicidade , Ácidos Ftálicos/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia
11.
Environ Pollut ; 278: 116799, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33743268

RESUMO

The mediating influence of thyroid function on the association of phthalate exposure with glucose metabolism, including insulin resistance, remains unclear. We explored the mediating influence of thyroid hormone levels on the phthalate exposure-insulin resistance association. This cross-sectional study of 217 Taiwanese adults assessed insulin resistance (Homeostatic Model Assessment for Insulin Resistance, HOMA-IR scores) and the levels of 11 urinary phthalate metabolites and 5 thyroid hormones. Multiple regression models were used to analyze the associations among serum thyroid hormone levels, urinary phthalate metabolite levels, and HOMA-IR scores. The mediation analysis assessed the influence of thyroid function on the phthalate exposure-HOMA-IR association. Our data indicated urinary mono-ethylhexyl phthalate (MEHP) levels was negatively associated with free thyroxine (T4) (ß = -0.018; 95% confidence interval [CI]: -0.031, -0.005) and positively associated with HOMA-IR scores (ß = 0.051, 95% CI: 0.012, 0.090). The study also revealed urinary mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) levels was negatively associated with free T4 (ß = -0.036, 95% CI: -0.056, -0.017) and HOMA-IR (ß = 0.070, 95% CI: 0.013, 0.126). Free T4 and HOMA-IR had a negative association (ß = -0.757, 95% CI: -1.122, -0.392). In the mediation analysis, free T4 mediated 24% and 35% of the associations of urinary MEHP and MEOHP with HOMA-IR, respectively. Our findings revealed the mediating role of thyroid function in the phthalate exposure-glucose metabolism association in adults.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Estudos Transversais , Dietilexilftalato/toxicidade , Exposição Ambiental , Glucose , Ácidos Ftálicos/toxicidade , Glândula Tireoide
12.
Chemosphere ; 271: 129740, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33736212

RESUMO

Di(2-ethylhexyl) phthalate (DEHP) has been well acknowledged for its endocrine disruption and associated metabolic diseases, leading to the search for safer industrial alternatives including di-isononyl phthalate (DINP). However, safety data for the latter chemical has been relatively scarce particularly regarding potential damage to the kidney at low doses. Five-week-old ICR male mice were exposed to vehicle, DEHP or DINP (0.05 and 4.8 mg/kg bw) daily via gavage for 5 weeks. We observed increased levels of reactive oxygen species and malondialdehyde, decreased levels of reduced glutathione, in the kidney at higher dose for both chemicals suggestive of oxidative damage. Elevated levels of inflammatory cytokines tumor necrosis factor-α and interleukin-6 of the kidney further suggested inflammatory status as a result of phthalate exposure in both high dose groups. Targeted lipidomics demonstrated greatest changes in the kidney induced by high dose of DEHP, although DINP also induced significant changes in phospholipids diacylglycerides that are associated with lipid accumulation in glomerular podocytes and inflammatory responses. Our data suggest that oxidative stress may be involved in both DEHP- and DINP-induced renal lipidomic disruption and continue to question the suitability of DINP as proper DEHP substitute.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Animais , Dietilexilftalato/toxicidade , Rim , Lipidômica , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo , Ácidos Ftálicos/toxicidade
13.
Environ Res ; 195: 110882, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33621597

RESUMO

Phthalates are the most ubiquitous contaminants that we are exposed to daily due to their wide use as plasticizers in various consumer products. A few studies have suggested that in utero exposure to phthalates can disturb fetal growth and development in humans, because phthalates can interfere with endocrine function. We collected spot urine samples from 291 pregnant women in their first trimester (9.8 ± 2.3 gestational weeks) recruited in an ongoing prospective cohort study in Saudi Arabia. A second urine sample was collected within 1-7 d after enrollment. The aims of this study were to: (1) assess the extent of exposure to phthalates during the first trimester and (2) estimate the risk from single and cumulative exposures to phthalates. Most phthalate metabolites' urinary levels were high, several-fold higher than those reported in relevant studies from other countries. The highest median levels of monoethyl phthalate, mono-n-butyl phthalate (MnBP), mono-iso-butyl phthalate (MiBP), and mono-(2-ethylhexyl) phthalate (MEHP) in µg/l (µg/g creatinine) were 245.62 (197.23), 114.26 (99.45), 39.59 (34.02), and 23.51 (19.92), respectively. The MEHP levels were highest among three di (2-ethylhexyl) phthalate (DEHP) metabolites. %MEHP4, the ratio of MEHP to four di (2-ethylhexyl) phthalate metabolites (∑4DEHP), was 44%, indicating interindividual differences in metabolism and excretion. The hazard quotient (HQ) of individual phthalates estimated based on the reference dose (RfD) of the U.S. Environmental Protection Agency indicated that 58% (volume-based) and 37% (creatinine-based) of the women were at risk of exposure to ∑4DEHP (HQ > 1). Based on the tolerable daily intake (TDI) from the European Food Safety Authority, 35/12% (volume-/creatinine-based data) of the women were at risk of exposure to two dibutyl phthalate (∑DBP) metabolites (MiBP and MnBP). The cumulative risk was assessed using the hazard index (HI), the sum of HQs of all phthalates. The percentages of women (volume-/creatinine-based data) at health risks with an HI > 1 were 64/40% and 42/22% based on RfD and TDI, respectively. In view of these indices for assessing risk, our results for the anti-androgenic effects of exposing pregnant women to ∑4DEHP and ∑DBP early during pregnancy are alarming.


Assuntos
Transtorno Autístico , Poluentes Ambientais , Ácidos Ftálicos , Exposição Ambiental/análise , Poluentes Ambientais/toxicidade , Feminino , Humanos , Ácidos Ftálicos/toxicidade , Gravidez , Primeiro Trimestre da Gravidez , Estudos Prospectivos , Arábia Saudita/epidemiologia
14.
Environ Int ; 149: 106403, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33524667

RESUMO

BACKGROUND: Prenatal phthalate exposure has been linked with altered neurodevelopment, including externalizing behaviors and attention-deficit hyperactivity disorder (ADHD). However, the implicated metabolite, neurobehavioral endpoint, and child sex have not always been consistent across studies, possibly due to heterogeneity in neurodevelopmental instruments. The complex set of findings may be synthesized using executive function (EF), a construct of complex cognitive processes that facilitate ongoing goal-directed behaviors. Impaired EF can be presented with various phenotypes of poor neurodevelopment, differently across structured conditions, home/community, or preschool/school. We evaluated the relationship between prenatal phthalate exposure and comprehensive assessment of preschool EF. METHODS: Our study comprised 262 children with clinically significant/subthreshold ADHD symptoms and 78 typically developing children who were born between 2003 and 2008 and participated in the Preschool ADHD Substudy, which is nested within a population-based prospective cohort study, the Norwegian Mother, Father, and Child Cohort (MoBa). Twelve phthalate metabolites were measured from urine samples that their mothers had provided during pregnancy, at 17 weeks' gestation. All children, at approximately 3.5-years, took part in a detailed clinical assessment that included parent-and teacher-rated inventories and administered tests. We used instruments that measured constructs related to EF, which include a parent-and teacher-reported Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) and three performance-based tests: A Developmental NEuroPSYchological Assessment (NEPSY), Stanford-Binet intelligence test V (SB5), and the cookie delay task (CDT). The standard deviation change in test score per interquartile range (IQR) increase in phthalate metabolite was estimated with multivariable linear regression. We applied weighting in all models to account for the oversampling of children with clinically significant or subthreshold symptoms of ADHD. Additionally, we assessed modification by child sex and potential co-pollutant confounding. RESULTS: Elevated exposure to mono-benzyl phthalate (MBzP) during pregnancy was associated with poorer EF, across all domains and instruments, in both sex. For example, an IQR increase in MBzP was associated with poorer working memory rated by parent (1.23 [95% CI: 0.20, 2.26]) and teacher (1.13 [0.14, 2.13]) using BRIEF-P, and administered tests such as SB5 (no-verbal: 0.19 [0.09, 0.28]; verbal: 0.13 [0.01, 0.25]). Adverse associations were also observed for mono-n-butyl phthalate (MnBP) and mono-iso-butyl phthalate (MiBP), although results varied by instruments. EF domains reported by parents using BRIEF-P were most apparently implicated, with stronger associations among boys (e.g., MnBP and inhibition: 2.74 [1.77, 3.72]; MiBP and inhibition: 1.88 [0.84, 2.92]) than among girls (e.g., MnBP and inhibition: -0.63 [-2.08, 0.83], interaction p-value: 0.04; MiBP and inhibition: -0.15 [-1.04, 0.74], interaction p-value: 0.3). Differences by sex, however, were not found for the teacher-rated BRIEF-P or administered tests including NEPSY, SB5, and CDT. CONCLUSION AND RELEVANCE: Elevated mid-pregnancy MBzP, MiBP, and MnBP were associated with more adverse profiles of EF among preschool-aged children across a range of instruments and raters, with some associations found only among boys. Given our findings and accumulating evidence of the prenatal period as a critical window for phthalate exposure, there is a timely need to expand the current phthalate regulations focused on baby products to include pregnancy exposures.


Assuntos
Poluentes Ambientais , Função Executiva , Ácidos Ftálicos , Efeitos Tardios da Exposição Pré-Natal , Pré-Escolar , Exposição Ambiental , Poluentes Ambientais/toxicidade , Feminino , Humanos , Masculino , Noruega/epidemiologia , Ácidos Ftálicos/toxicidade , Gravidez , Estudos Prospectivos
15.
Environ Int ; 149: 106393, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33529853

RESUMO

A total diet study (TDS) was conducted in France to assess the health risks related to the chemicals in food of non-breastfed children under three years of age (Infant TDS). For the first time, substances coming from food contact materials, such as bisphenol A (BPA), bisphenol A diglycidyl ether (BADGE) and its derivatives, some phthalates, and some ink photoinitiators, were targeted because of growing interest in these substances. Food samples were collected to be representative of the whole diet of non-breastfed children aged 1-36 months, and prepared as consumed prior to analysis. Dietary exposure was assessed for 705 representative children under three years of age. Generally, the substances from food contact materials were detected in few samples: 38% for BPA, 0% for BADGE and its derivatives, 0-35% for phthalates, 1.9% for benzophenone, and 0% for the other ink photoinitiators. Regarding exposure levels, the situation was deemed tolerable for BADGE and its hydrolysis products, di-isodecyl phthalate, dibutyl phthalate, butyl benzyl phthalate, bis(2-ethylhexyl) phthalate, and di-isononyl phthalate, benzophenone, and 4-methylbenzophenone. Only for BPA, the exposure levels of some children exceeded the lowest toxicological value established by the French Agency for Food, Environmental and Occupational Health & Safety at 0.083 µg.kg bw-1.d-1. The temporary tolerable daily intake of the European Food Safety Authority (EFSA), set at 4 µg.kg bw-1.d-1, was never exceeded. However, actual exposure to BPA was probably overestimated, as well as the associated risk, because the foods were sampled prior to the recent regulations banning BPA in food packaging. This study is the first worldwide to provide an estimate of infant food contamination levels and exposures of children under 3 years of age, based on a TDS approach. It therefore provides key data on the exposure of this particularly sensitive population to substances released from food contact materials, and presents useful data for studies evaluating exposure to mixtures or aggregated exposure.


Assuntos
Exposição Dietética , Exposição Ambiental , Ácidos Ftálicos , Compostos Benzidrílicos/toxicidade , Pré-Escolar , Dieta , Exposição Ambiental/análise , Contaminação de Alimentos/análise , Embalagem de Alimentos , França , Humanos , Lactente , Ácidos Ftálicos/toxicidade
16.
Environ Int ; 151: 106440, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33640694

RESUMO

BACKGROUND: Parental preconception exposure to select phenols and phthalates was previously associated with increased risk of preterm birth in single chemical analyses. However, the joint effect of phenol and phthalate mixtures on preterm birth is unknown. METHODS: We included 384 female and 211 male (203 couples) participants seeking infertility treatment in the Environment and Reproductive Health (EARTH) Study who gave birth to 384 singleton infants between 2005 and 2018. Mean preconception urinary concentrations of bisphenol A (BPA), parabens, and eleven phthalate biomarkers, including di(2-ethylhexyl) phthalate (DEHP) metabolites, were examined. We used principal component analysis (PCA) with log-Poisson regression and Probit Bayesian Kernel Machine Regression (BKMR) with hierarchical variable selection to examine maternal and paternal phenol and phthalate mixtures in relation to preterm birth. Couple-based BKMR model was fit to assess couples' joint mixtures in relation to preterm birth. RESULTS: PCA identified the same four factors for maternal and paternal preconception mixtures. Each unit increase in PCA scores of maternal (adjusted Risk Ratio (aRR): 1.36, 95%CI: 1.00, 1.84) and paternal (aRR: 1.47, 95%CI: 0.90, 2.42) preconception DEHP-BPA factor was positively associated with preterm birth. Maternal and paternal BKMR models consistently presented the DEHP-BPA factor with the highest group Posterior Inclusion Probability (PIP). BKMR models further showed that maternal preconception BPA and mono(2-ethyl-5-hydroxyhexyl) phthalate, and paternal preconception mono(2-ethylhexyl) phthalate were positively associated with preterm birth when the remaining mixture components were held at their median concentrations. Couple-based BKMR models showed a similar relative contribution of paternal (PIP: 61%) and maternal (PIP: 77%) preconception mixtures on preterm birth. We found a positive joint effect on preterm birth across increasing quantiles of couples' total mixture concentrations. CONCLUSION: In this prospective cohort of subfertile couples, maternal BPA and DEHP, and paternal DEHP exposure before conception were positively associated with preterm birth. Both parental windows jointly contributed to the outcome. These results suggest that preterm birth may be a couple-based pregnancy outcome.


Assuntos
Dietilexilftalato , Exposição Materna/efeitos adversos , Exposição Paterna/efeitos adversos , Ácidos Ftálicos , Nascimento Prematuro , Teorema de Bayes , Compostos Benzidrílicos/toxicidade , Dietilexilftalato/toxicidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fenol , Fenóis/toxicidade , Ácidos Ftálicos/toxicidade , Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/epidemiologia , Estudos Prospectivos
17.
Am J Public Health ; 111(4): 687-695, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33600256

RESUMO

Robust data from longitudinal birth cohort studies and experimental studies of perinatally exposed animals indicate that exposure to ortho-phthalates can impair brain development and increase risks for learning, attention, and behavioral disorders in childhood. This growing body of evidence, along with known adverse effects on male reproductive tract development, calls for immediate action.Exposures are ubiquitous; the majority of people are exposed to multiple ortho-phthalates simultaneously. We thus recommend that a class approach be used in assessing health impacts as has been done with other chemical classes. We propose critically needed policy reforms to eliminate ortho-phthalates from products that lead to exposure of pregnant women, women of reproductive age, infants, and children. Specific attention should be focused on reducing exposures among socially vulnerable populations such as communities of color, who frequently experience higher exposures.Ortho-phthalates are used in a vast array of products and elimination will thus necessitate a multipronged regulatory approach at federal and state levels. The fact that manufacturers and retailers have already voluntarily removed ortho-phthalates from a wide range of products indicates that this goal is feasible.


Assuntos
Encéfalo/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Ácidos Ftálicos , Formulação de Políticas , Efeitos Tardios da Exposição Pré-Natal , Reprodução/efeitos dos fármacos , Animais , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Feminino , Regulamentação Governamental , Humanos , Lactente , Estudos Longitudinais , Masculino , Ácidos Ftálicos/efeitos adversos , Ácidos Ftálicos/toxicidade , Gravidez
18.
Environ Int ; 150: 106409, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33556913

RESUMO

BACKGROUND: Findings from epidemiological studies of prenatal phthalate exposure and child cognitive development are inconsistent. Methods for evaluating mixtures of phthalates, such as weighted quantile sum (WQS) regression, have rarely been applied. We developed a new extension of the WQS method to improve specificity of full-sample analyses and applied it to estimate associations between prenatal phthalate mixtures and cognitive and language outcomes in a diverse pregnancy cohort. METHODS: We measured 22 phthalate metabolites in third trimester urine from mother-child dyads who completed early childhood visits in the Conditions Affecting Neurodevelopment and Learning in Early childhood (CANDLE) study. Language and cognitive ability were assessed using the Bayley Scales of Infant Development (age 3) and the Stanford Binet-5 (age 4-6), respectively. We used multivariable WQS regression to identify phthalate mixtures that were negatively and positively associated with language score and full-scale IQ, in separate models, adjusted for maternal IQ, race, marital status, smoking, BMI, socioeconomic status (SES), child age, sex, and breastfeeding. We evaluated effect modification by sex and SES. If full sample 95% WQS confidence intervals (which are known to be anti-conservative) excluded the null, we calculated a p-value using a permutation test (ppermutation). The performance of this new approach to WQS regression was evaluated in simulated data. We compared the power and type I error rate of WQS regression conducted within datasets split into training and validation samples (WQSSplit) and in the full sample (WQSNosplit) to WQS regression with a permutation test (WQSpermutation). Individual metabolite associations were explored in secondary analyses. RESULTS: The analytic sample (N = 1015) was 62.1% Black/31.5% White, and the majority of mothers had a high school education or less (56.7%) at enrollment. Associations between phthalate mixtures and primary outcomes (language score and full-scale IQ) in the full sample were null. Individual metabolites were not associated with IQ, and only one metabolite (mono-benzyl phthalate, MBzP) was associated with Bayley language score (ß = -0.68, 95% CI: -1.37, 0.00). In analyses stratified by sex or SES, mixtures were positively and negatively associated with outcomes, but the precision of full-sample WQS regression results were not supported by permutation tests, with one exception. In the lowest SES category, a phthalate mixture dominated by mono-methyl phthalate (MMP) and mono-carboxy-isooctyl phthalate (MCOP) was associated with higher language scores (ßlow SES = 2.41, full-sample 95%CI: 0.58, 4.24; ppermutation = 0.04). Performance testing in simulated data showed that WQSpermutation had improved power over WQSSplit (90% versus 56%) and a lower type I error rate than WQSNosplit (7% versus 47%). CONCLUSIONS: In the largest study of these relationships to date, we observed predominantly null associations between mixtures of prenatal phthalates and both language and IQ. Our novel extension of WQS regression improved sensitivity to detect true associations by obviating the need to split the data into training and test sets and should be considered for future analyses of exposure mixtures.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Efeitos Tardios da Exposição Pré-Natal , Criança , Pré-Escolar , Estudos de Coortes , Exposição Ambiental , Poluentes Ambientais/toxicidade , Feminino , Humanos , Lactente , Mães , Ácidos Ftálicos/toxicidade , Gravidez
19.
Artigo em Inglês | MEDLINE | ID: mdl-33563085

RESUMO

The objective of this study was to investigate 13 phthalic acid esters (PAEs) with medium or long straight-alkyl-chain, branching or unsaturated side chains, because their structural characteristics make them difficult to biodegrade or highly toxic. A biodegradability and biotoxicity multi-effect pharmacophore model was built using comprehensive evaluation method. The results suggested that introducing hydrophobic groups to the side chains of the PAEs could improve the molecules' biodegradability and biotoxicity effects simultaneously. Thus, 40 target PAE (HEHP, DNOP, DUP) derivatives were designed. Two environmentally friendly PAE derivatives (HEHP-Anthryl and HEHP-Naphthyl) were screened via the test of environmental friendliness and functionality. In addition, the biodegradation and biotoxicity of derivatives were found to have improved as a result of the change in van der Waals forces between molecules and their corresponding proteins. Moreover, the environmental safety of the screened PAE derivatives was confirmed by predicting the toxicity of their intermediates and calculating the energy barrier values for biodegradation and metabolic pathways. This study could provide theoretical guidance for the practical development of environmentally friendly plasticizer.


Assuntos
Ésteres , Modelos Teóricos , Ácidos Ftálicos , Plastificantes , Animais , Biodegradação Ambiental , Decápodes/efeitos dos fármacos , Ésteres/química , Ésteres/metabolismo , Ésteres/toxicidade , Interações Hidrofóbicas e Hidrofílicas , Ácidos Ftálicos/química , Ácidos Ftálicos/metabolismo , Ácidos Ftálicos/toxicidade , Plastificantes/química , Plastificantes/metabolismo , Plastificantes/toxicidade
20.
Ecotoxicol Environ Saf ; 213: 112041, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33601174

RESUMO

Awareness of risks posed by widespread presence of nanoplastics (NPs) and bioavailability and potential to interact with organic pollutants has been increasing. Inhalation is one of the more important pathways of exposure of humans to NPs. In this study, combined toxicity of concentrations of polystyrene NPs and various phthalate esters (PAEs), some of the most common plasticizers, including dibutyl phthalate (DBP) and di-(2-ethyl hexyl) phthalate (DEHP) on human lung epithelial A549 cells were investigated. When co-exposed, 20 µg NPs/mL increased viabilities of cells exposed to either DBP or DEHP and the modulation of toxic potency of DEHP was greater than that of DBP, while the 200 µg NPs/mL resulted in lesser viability of cells. PAEs sorbed to NPs decreased free phase concentrations (Cfree) of PAEs, which resulted in a corresponding lesser bioavailability and joint toxicity at the lesser concentration of NPs. The opposite effect was observed at the greater concentration of NPs, which may result from the dominated role of NPs in the combined toxicity. Furthermore, our data showed that oxidative stress and inflammatory reactions were mechanisms for combined cytotoxicities of PAEs and NPs on A549 cells. Results of this study emphasized the combined toxic effects and mechanisms on human lung cells, which are helpful for assessing the risk of the co-exposure of NPs and organic contaminants in humans.


Assuntos
Poluentes Ambientais/toxicidade , Microplásticos/toxicidade , Ácidos Ftálicos/toxicidade , Poliestirenos/toxicidade , Células A549 , China , Dibutilftalato/toxicidade , Dietilexilftalato , Ésteres , Humanos , Pulmão , Estresse Oxidativo , Plastificantes
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...