Exposición intrauterina a disruptores endocrinos (ftalatos): fuentes de exposición y cuantificación de metabolitos urinarios / Intrauterine exposure to endocrine disruptors (phthalates): sources of exposure and quantification of urinary metabolites

Introducción: Los ftalatos son disruptores endocrinos usados en la fabricación de múltiples productos de la industria, principalmente plásticos. El periodo fetal representa la principal ventana de vulnerabilidad, y la exposición a ftalatos en esta etapa de vida genera efectos adversos fetales y postnatales. El biomarcador más fiable para medición de ftalatos es la orina. Objetivo: Caracterizar las diferentes fuentes de exposición a disruptores endocrinos y cuantificar la concentración urinaria de ftalatos en gestantes. Materiales y métodos: Estudio transversal, observacional y descriptivo que incluye 400 gestantes que asistieron a control prenatal en las instituciones de salud Génesis y Metrosalud (Medellín-Colombia). Se caracterizaron fuentes de exposición, se recolectó muestras de orina de todas las gestantes, y cuantificó la concentración de ftalatos de 38 mujeres. Resultados: Las medias geométricas de ftalato Di(2-ethylhexyl)phthalate(DEHP), Mono-n-butyl phthalate(MnBP), Mono-2-ethyl-5-hydroxyhexyl phthalate(MEHHP) y Mono-2-ethyl-5-oxohexyl phthalate(MEOHP) fueron 162,72µg/L, 58,5 µg/L, 33,93µg/L y 31,63µg/L respectivamente. Conclusiones: La mayoría de las gestantes evaluadas han estado expuestas a lo largo de su vida a fuentes potenciales de disruptores endocrinos, presentes en químicos domésticos, tabaco y uso frecuente de cosméticos faciales y corporales. Las concentraciones de MnBP, MEHHP y MEOHP en orina de las participantes, fueron superiores a los hallazgos a nivel mundial.

Introduction: Phthalates are endocrine disruptors used in the manufacture of various industrial products, mainly plastics. The fetal period represents the principal window of vulnerability, and the exposure to Phthalates in this stage of life generates adverse fetal and post-natal effects. The most reliable biomarker for the assessment of Phthalates is urine. Objective: To characterize the different exposure sources of endocrine disruptors and quantify the urinary concentration of Phthalates in pregnant women. Materials and methods: A cross-sectional, observational, and descriptive study which included 400 pregnant women who received prenatal care in the Genesis and Metrosalud health institutions (Medellín-Colombia). Exposure sources were characterized and urine samples were collected from all pregnant women and the Phthalate concentration was quantified in 38 women. Results: The geometric measures of Phthalate Di(2-ethylhexyl)phthalate(DEHP), Mono-n-butyl phthalate(MnBP), Mono-2-ethyl-5-hydroxyhexyl phthalate(MEHHP) and Mono-2-ethyl-5-oxohexyl phthalate(MEOHP) were 162.72µg/L, 58.5 µg/L, 33.93µg/L and 31.63µg/L respectively. Conclusions: The majority of pregnant women that were evaluated were exposed to potential sources of endocrine disruptors throughout their life, which are present in household chemicals, tobacco, and frequent use of facial and body cosmetics. The concentrations of MnBP, MEHHP y MEOHP in urine of participants were higher than those found worldwide.

Exposure to endocrine disruptors and alterations in mineralized tissues: a narrative review / Exposición a disruptores endocrinos y alteraciones en tejidos mineralizados: revisión narrativa

Background: Endocrine Disrupting Chemicals (EDCs) would cause alterations in organs/systems of exposed individuals or their progeny. Objetive: To identify and analyze the main published findings on the effects of exposure to EDCs on teeth, cartilage, and bone. Material and Methods: Two databases were analyzed: Medline and Web of Science. Only observational studies analyzing the effect of EDCs on mineralized tissues published since 2006 were included in the study. Results: 25 articles were selected, most of them involving EDCs pesticides, plasticizers, or personal care products, highlighting organochlorine compounds, bisphenols, phthalates, dioxins, parabens, and perfluoroalkyls. Thirty-six per cent of the studies reported an accumulation of EDCs in teeth or bones, while 64% reported alterations in their development or morphology, mainly at the bone level, primarily affecting their mineral density and size, as well as that of the bones of exposed individuals or their progeny. The type of effect observed was related to the EDCs analyzed, and it seemed to depend on variables such as age, sex, ethnicity/race, and even the metabolic status of the individuals in the different species analyzed. No evidence associated with effects on cartilage was found. Conclusion: EDCs in the environment, at work, or at home, under different exposure routes, are capable of accumulating in teeth and bone, particularly affecting the latter. It is necessary to study the effect of EDCs on mineralized tissues in agro-industrial areas, especially on teeth.

Antecedentes: Los Químicos Disruptores Endocrinos (EDCs) causarían alteraciones en órganos/sistemas de individuos expuestos, o su progenie. Objetivo: Identificar y analizar los principales hallazgos publicados sobre el efecto de la exposición a EDCs en dientes, cartílago y hueso. Material y Métodos: Se analizaron dos bases de datos: Medline y Web of Science, incluyendo solo estudios observacionales publicados desde el 2006, analizando el efecto de los EDCs sobre tejidos mineralizados. Resultados:25 artículos fueron seleccionados, siendo la mayoría de los EDCs pesticidas, plastificantes o productos de cuidado personal, destacando los compuestos Organo-clorados, Bisfenoles, Ftalatos, Dioxinas, Parabenos y los Perfluoroalquilos. Un 36% de los estudios reportaron un acúmulo de EDCs en dientes o huesos, mientras que un 64% informaron de alteraciones en su desarrollo o morfología, particularmente a nivel de huesos, afectando principalmente su densidad mineral y su tamaño, así como el de los individuos expuestos o su progenie. El tipo de efecto observado tuvo relación con el EDCs analizado, pareciendo depender de variables tales como edad, sexo, etnia/raza e incluso el estado metabólico de los individuos, en las diferentes especies analizadas. No se encontraron evidencias asociadas a efectos en el cartílago. Conclusión: Los EDCs en el medio ambiente, ámbito laboral o doméstico, bajo distintas rutas de exposición, son capaces de acumularse en diente y hueso, afectando particularmente a este último. Es necesario estudiar el efecto de los EDCs en los tejidos mineralizados en zonas agroindustriales, particularmente a nivel de dientes.

The effect of Endocrine disrupting chemicals on myocardial fibrosis and related mechanism / 中华劳动卫生职业病杂志

Endocrine-disrupting chemicals (EDCs) an exogenous agent that interferes with the synthesis, secretion, transport, binding, action, or can mimic the occurrence of natural hormones that damage for the balance of homeostasis. Exposure to EDCs results in damage to human health that may persist in the long term. In recent years, accumulative evidence has demonstrated that EDCs also play a pivotal role in the onset and development of myocardial fibrosis, including heart failure, hypertension and vascular stiffening. Studies indicate that EDCs plays the negative effects of the cardiovascular system, however, EDCs-induced toxicity on heart remains unclear. This review summarized EDCs-induced myocardial fibrosis, and discuss the possible mechanisms of myocardial fibrosis induced by EDCs. This paper could provide further understandings for prevention, diagnosis and treatment of myocardial fibrosis.

Hormônios estrogênicos em matrizes aquáticas: revisão sistemática de literatura / Estrogen hormones in aquatic matrices: a systematic review of the literature

Os disruptores endócrinos apresentam riscos à saúde humana e ambiental mesmo em concentrações a níveis de traços. Os hormônios femininos naturais, estradiol, estriol e estrona, e o sintético etinilestradiol, fazem parte desse grupo de agentes. Nesse contexto, o presente trabalho teve como objetivo realizar uma revisão sistemática da literatura sobre estudos produzidos com o intuito de detectar e quantificar a presença dessas substâncias em matrizes aquáticas. Para tanto, foi realizada uma busca sistemática de evidências científicas em três bases de dados: Scopus, Web of Science e Biblioteca Virtual em Saúde (BVS). A busca foi realizada no período de janeiro de 2015 a janeiro de 2021, utilizando a string "(estrone OR estriol OR estradiol OR ethinylestradiol) AND (wastewater OR sewage OR river OR surface water OR drinking water OR potable water) AND (LC-MS/MS OR GC-MS/MS OR UPLC OR HPLC)". A busca resultou em 380 estudos, sendo: 61 da Scopus, 124 da Web of Science e 195 da BVS. Após a aplicação dos testes de relevância, 91 estudos foram definitivamente selecionados para extração de dados. A maioria dos artigos se dedicou à busca de estrogênios em águas superficiais, provavelmente pela importância dessa matriz. Os países asiáticos, como China e Índia, foram os que apresentaram as maiores concentrações de estrogênios naturais (E1, E2 e E3), em água potável. Altas concentrações de E1, E2 e EE2 foram verificadas em águas residuais do Brasil, Espanha e Irã; além de E1, E2 e E3 em águas superficiais da China e da África do Sul, mais precisamente da Cidade do Cabo. Nos últimos anos, os países desenvolvidos e em desenvolvimento foram os que mais investiram em pesquisas voltadas ao monitoramento dos efeitos desses contaminantes, principalmente no corpo humano. Porém, apenas a União Europeia e os Estados Unidos possuem regulamentação e estudos aprofundados com o propósito de se determinar os limites máximos aceitáveis para esses contaminantes na água. Disso, nota-se a necessidade de adoção de tecnologias de tratamento de efluentes capazes de eliminar os disruptores endócrinos e que sejam economicamente acessíveis para países em desenvolvimento e subdesenvolvidos. O que se propõe é o aprimoramento de uma medida preventiva, cuja implementação, além de promover melhoria na qualidade de vida da população - que é o que mais importa - e do meio ambiente, permita a economia de recursos públicos por minimizar a incidência de diversas doenças como cânceres, obesidade, entre outras

Endocrine disruptors pose risks to human and environmental health even at low concentrations. The natural female hormones, estradiol, estriol and estrone, and the synthetic ethinylestradiol, are part of this group of agents. In this context, the present work aimed to carry out a systematic review of the literature on studies produced with the aim of detecting and quantifying the presence of these substances in aquatic matrices. Therefore, a systematic search for scientific evidence was carried out in three databases: Scopus, Web of Science and Biblioteca Virtual em Saúde (BVS). The search was carried out from January 2015 to January 2021, using the string "(estrone OR estriol OR estradiol OR ethinylestradiol) AND (wastewater OR sewage OR river OR surface water OR drinking water OR potable water) AND (LC-MS/MS OR GC-MS/MS OR UPLC OR HPLC)". The search resulted in 380 studies, being: 61 from Scopus, 124 from Web of Science and 195 from BVS. After applying the relevance tests, 91 studies were definitively selected for data extraction. Most articles were dedicated to the search for estrogens in surface water, probably due to the importance of this matrix. Asian countries, such as China and India, were the ones with the highest concentrations of natural estrogens (E1, E2 and E3) in drinking water. High concentrations of E1, E2 and EE2 were found in wastewater from Brazil, Spain and Iran; in addition to E1, E2 and E3 in surface waters in China and South Africa, more precisely in Cape Town. In recent years, developed and developing countries have invested the most in research aimed at monitoring the effects of these contaminants, mainly on the human body. However, only the European Union and the United States have regulations and in-depth studies aimed at determining the maximum acceptable limits for these contaminants in water. From this, there is a need to adopt effluent treatment technologies capable of eliminating endocrine disruptors and that are affordable for developing and underdeveloped countries. What is proposed is the improvement of a preventive measure, whose implementation, in addition to promoting an improvement in the quality of life of the population - which is what matters most - and of the environment, allows the economy of public resources by minimizing the incidence of various diseases such as cancer, obesity, among others

Disruptores endócrinos: interações com o meio ambiente e puberdade / Endocrine disruptors: interactions with the environment and puberty

Este estudo tem como objetivo apresentar substâncias conhecidas como disruptores endócrinos e suas possíveis interferências no desenvolvimento puberal das meninas. Trata-se de uma revisão da literatura feita a partir do levantamento e análise de 37 referências bibliográficas nas quais os autores chamam a atenção para as diversas formas de absorção de produtos ricos em componentes desequilibradores hormonais que, por ação conjunta e prolongada, interferem no sistema endócrino, promovendo antecipação no desenvolvimento dos caracteres sexuais secundários. Concluiu-se que a exposição a inúmeros agentes disruptores presentes no dia a dia das meninas, por ação prolongada e acumulativa, pode promover uma antecipação na maturação dos caracteres sexuais secundários.(AU)

This study aims to present substances known as endocrine disruptors and theirpossible interference in girls puberal development. This is a systematic review of the literaturebased on the survey and analysis of 37 bibliographical references in which the authors drawattention to the multiple ways of absorption of products rich in hormonal imbalancecomponents that by combined and prolonged action, interfere in the endocrine system, promoting anticipation in the development of secondary sexual characteristics. In conclusion, the exposure to numerous disrupting agents present in the daily lives of girls, by prolonged andcumulative action, can promote an anticipation in the maturation of secondary sexual characteristics.(AU)

Chronic exposure of bisphenol S (BPS) affect hypothalamic-pituitary-testicular activities in adult male rats: possible in estrogenic mode of action

BACKGROUND@#The industrial revolution has resulted in increased synthesis and the introduction of a variety of compounds into the environment and their potentially hazardous effects have been observed in the biota. The present study was aimed to evaluate the potential endocrine-disrupting effects of chronic exposure to the low concentrations of bisphenol S (BPS) in male rats.@*METHODS@#Weaning male Sprague-Dawley rats (22 days old) were either exposed to water containing 0.1% ethanol for control or different concentrations of BPS (0.5, 5, and 50 μg/L) in drinking water for 48 weeks in the chronic exposure study. After completion of the experimental period, animals were dissected and different parameters (hormone concentrations, histology of testis and epididymis, oxidative stress and level of antioxidant enzymes in the testis, daily sperm production (DSP), and sperm parameters) were determined.@*RESULTS@#Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organ weights. Oxidative stress in the testis was significantly elevated while sperm motility, daily sperm production, and the number of sperm in epididymis were reduced. Plasma testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) concentrations were reduced and estradiol levels were high in the 50 μg/L-exposed group. Histological observations involved a significant reduction in the epithelial height of the testis along with disrupted spermatogenesis, an empty lumen of the seminiferous tubules, and the caput region of the epididymis.@*CONCLUSION@#These results suggest that exposure to 5 and 50 μg/L of BPS for the chronic duration started from an early age can induce structural changes in testicular tissue architecture and endocrine alterations in the male reproductive system which may lead to infertility in males.

Levels of BPA in makdous, a traditional Syrian food, using solid-phase extraction followed by HPLC

Bisphenol A (BPA), an endocrine disrupter, can migrate from packaging material into food stuff. This research was designed to measure BPA levels in makdous, a traditional Syrian food. Forty three samples of makdous stored in different plastic containers (polyethylene (PE), polypropylene (PP), and unspecified plastic containers) were analyzed every 3 months for one year beginning July 2017. Quantification of BPA was carried out by an RP-HPLC system equipped with fluorescence detector after solid phase extraction. Migration was found in PE and PP plastic containers with slight differences. Statistically significant differences in BPA levels were observed between samples assayed after two weeks of preparation and samples assayed after 12 months (mean 16.32 vs. 38.26 µg/kg, p value=0.003). According to these amounts, BPA levels were all under the specific migration limit of 0.05 mg/kg as newly referred in Regulation (EU) No 2018/213. These levels of exposure would only contribute to 2.15% and 2.75% of the EFSA t-TDI in both men and women respectively based on mean dietary exposure estimates derived from a 24-h dietary information study from 875 participants. Hence there are no concerns about potential health risks from makdous consumption

Bisfenol-A: cuantificacion en orina de mujeres embarazadas por cromatografia gaseosa-espectrometria de masa / Bisfenol-A: quantification in urine of pregnant women by gas chromatography-mass spectrometry / Bisfenol-A: quantificacao em urina de gestantes por cromatografia gasosa-espectrometria de massa

El uso de bisfenol-A (BPA) a nivel de la industria global se ha venido incrementando en los ultimos anos, y fueron los mercados emergentes los impulsores de esta demanda creciente. Las aplicaciones de BPA en la industria de los alimentos y bebidas representan solo del 3 al 4% del consumo global de policarbonato, pero su uso esta siendo reexaminado debido a que se conocieron varios trabajos cientificos que indican la existencia de una relacion directa entre el BPA y los efectos adversos para la salud. La contaminacion de los alimentos y bebidas se produce por migracion del BPA desde los envases que los contienen (alimentos enlatados, vinos, etc.), y es la principal fuente de exposicion en el humano. Para evaluar dicha exposicion se desarrollo y valido un metodo analitico por cromatografia gaseosa acoplada a espectrometria de masa para la cuantificacion de BPA total en orina de mujeres embarazadas atendidas en el Hospital Italiano de Buenos Aires en el ano 2013, con un limite de cuantificacion de 2,0 ng/mL y un limite de deteccion de 0,8 ng/mL. De las 149 muestras de orina analizadas, el 66,4% fueron cuantificables, con la mediana de BPA total de 4,8 ng/mL (4,3 ng/mg de creatinina) y la media geometrica de 4,8 ng/mL (4,7 ng/mg de creatinina).

The use of bisphenol-A (BPA) at the level of the global industry has been increasing in recent years, with emerging markets being the drivers of this growing demand. BPA applications in the food and beverage industry represent only 3 to 4% of the global consumption of polycarbonate, but its use is being reexamined because several scientific works were reported indicating the existence of a direct relationship between BPA and adverse effects on health. The contamination of food and beverages is produced by the migration of BPA from the containers that hold them (canned foods, wines, etc.) and it is the main source of exposure in humans. To evaluate this exposure, an analytical method was developed by gas chromatography coupled to mass spectrometry for the quantification of total BPA in urine of pregnant women treated at the Hospital Italiano de Buenos Aires in 2013, with a limit of quantification of 2.0 ng/mL and of detection of 0.8 ng/mL. Of the 149 urine samples analyzed, 66.4% were quantifiable, with a median total BPA of 4.8 ng/mL (4.3 ng/mg creatinine) and a geometric mean of 4.8 ng/mL (4.7 ng/mg creatinine).

O uso de bisfenol-A (BPA) ao nivel da industria global foi aumentando nos ultimos anos, e foram os mercados emergentes que deram impulso a essa demanda crescente. As aplicacoes de BPA na industria de alimentos e bebidas representam apenas 3 a 4% do consumo global de policarbonato, mas seu uso esta sendo reexaminado visto que varios trabalhos cientificos indicando a existencia de uma relacao direta entre o BPA e os efeitos adversos na saude foram conhecidos. A contaminacao dos alimentos e bebidas e produzida pela migracao de BPA das embalagens que os contem (alimentos enlatados, vinhos, etc.) e e a principal fonte de exposicao em humanos. Para avaliar esta exposicao, foi desenvolvido e avaliado um metodo analitico por cromatografia gasosa acoplada a espectrometria de massas para a quantificacao do BPA total na urina de gestantes atendidas no Hospital Italiano de Buenos Aires em 2013, com um limite de quantificacao de 2,0 ng/mL e um limite de deteccao de 0,8 ng/mL. Das 149 amostras de urina analisadas, 66,4% foram quantificaveis, com uma mediana de BPA total de 4,8 ng/mL (4,3 ng/mg de creatinina) e a media geometrica de 4,8 ng/mL (4,7 ng/mg de creatinina).

Nonpersistent endocrine disrupting chemicals and reproductive health of women

Disruptores endocrinos en reproducción / Endocrine disruptors in reproduction

Este es un artículo de revisión en el que se describe cómo los disruptores endocrinos pueden interferir en la actividad hormonal y reproductiva normal e incluyen productos naturales como los fitoestrógenos y artificiales como dioxinas y compuestos similares. Se pueden encontrar en muchos productos cotidianos, incluidos botellas de plástico, metal, latas de alimentos, detergentes, retardantes de llama, alimentos, juguetes, cosméticos y pesticidas. Se pueden ingerir a través de alimentos, inhalar por gases o exposición a través de la piel y pueden llegar al feto por paso por la placenta. A largo plazo pueden tener efecto sobre el crecimiento de las mamas, el desarrollo de la pubertad, el tamaño de los testículos y el pene. Su forma de actuar puede ser suplantando las hormonas naturales, bloqueando su acción o variando sus niveles. Pueden actuar a través de factores de transcripción y reflejarse en cambios epigenéticos. Se describen diversos compuestos como pesticidas, alquifenoles, bisfenol A, ftalatos, parabenos y su impacto sobre el sistema endocrino y reproductivo.

This is a review article that describes the way endocrine disruptors can interfere with hormonal and reproductive normal activity, and includes natural products such as phytoestrogens and artificial products like dioxins and similar compounds. They can be found in many daily products including plastic bottles metal, food cans, detergents, flame retardants toys, cosmetics and pesticides. They can be eaten through foods, inhaled with gases or exposed by the skin and can arrive to the fetus crossing the placenta. On long term they can have effects on breast growth, puberty development, and the size of the testicles and penis. They can act supplanting natural hormones, blocking its action or varying its levels. They can also act through transcription factors and impact epigenetic changes. Various compounds are described such as pesticides, alquiphenoles, bisphenol A, faltes, parabenes and their impacto in endocrine and reproductive systems.

Ecotoxicological risk assessment due to the presence of bisphenol A and caffeine in surface waters in the Sinos River Basin - Rio Grande do Sul - Brazil / Risco ecotoxicológico devido à presença de bisfenol A e cafeína nas águas superficiais na Bacia do Rio Sinos - Rio Grande do Sul - Brasil

Abstract Bisphenol A (BPA) is an emerging contaminant, regularly detected in aquatic ecosystems, considered as an endocrine disrupting compound (EDC). Caffeine is another chemical related to human activity, often found in surface waters. The objective of this study was to evaluate the ecotoxicological risk due to BPA and caffeine in water samples from the Sinos River basin, Rio Grande do Sul, Brazil. Water samples were collected at three sites monthly from May 9 th, 2016 to April 11th, 2017 (n = 36). BPA concentrations in water samples collected were in the range of not detected to 517 ng L-1 and caffeine concentrations in the range of 41.7 to 28,439.6 ng L-1. The concentration of BPA in the analyzed samples had a moderate correlation with caffeine (rs = 0.402). High ecotoxicological risk for BPA was characterized in 77.77% of samples, with 11.11% presenting medium and 11.1% presenting low risk. For caffeine 13.9%, 50% and 36.11% of the samples presented high, medium and low risk, respectively. Caffeine concentrations in water can be used as predictors of BPA concentrations above 10 ng L-1, the lower concentration of ecotoxicological risk, with specificity of 66.7% and sensitivity of 70.4%. The assessment of aquatic risks has shown that both investigated compounds pose risks to organisms in the studied surface waters, mouth of the Pampa stream, mouth of the Luiz Rau stream and catchment point for public supply in Lomba Grande.

Resumo Bisfenol A (BPA) é um contaminante emergente regularmente detectado em ecossistemas aquáticos, é considerado um agente modificador endócrino (EDC). Além disso, outro produto químico relacionado com atividade humana, encontrado com frequência nas águas superficiais, é a cafeína. O objetivo deste estudo foi avaliar a ocorrência de risco ecotoxicológico devido a BPA e cafeína em amostras de água da Bacia Hidrográfica do Rio Sinos, Rio Grande do Sul, Brasil. Foram coletadas amostras de água em três locais mensalmente no período de 9 de maio de 2016 a 11 de abril de 2017 (n = 36). As concentrações de BPA em amostras de água coletadas estavam na faixa de não detectada a 517 ng L-1 e concentrações de cafeína na faixa de 41,7 a 28,439,6 ng L-1. A concentração de BPA nas amostras analisadas apresentou correlação moderada com a cafeína (rs = 0,402). Alto risco ecotoxicológico para BPA foi caracterizado em 77,77% das amostras, com 11,11% apresentando médio e 11,1% apresentando baixo risco. Para cafeína 13,9%, 50% e 36,11% das amostras apresentaram risco alto, médio e baixo, respectivamente. Concentrações de cafeína em água podem ser utilizadas como preditoras de concentrações de BPA acima de 10 ng L-1, menor concentração de risco ecotoxicológico, com especificidade de 66,7% e sensibilidade de 70,4%. A avaliação dos riscos aquáticos revelou que ambos os compostos investigados representam risco para os organismos nas águas superficiais estudadas, foz do arroio Pampa, foz do arroio Luiz Rau e ponto de captação para abastecimento público em Lomba Grande.

Challenges to regulate products containing bisphenol A: Implications for policy / Desafíos para regular los productos que contienen bisfenol A: implicaciones para la política

Abstract: Bisphenol A (BPA), found in plastics and epoxy resins, is one of the most studied chemicals. BPA is regarded as an endocrine disruptor and has been related to adverse health effects in humans. However, some regulatory agencies around the world have concluded that BPA is safe at current human exposure levels. As the scientific community attempts to settle the debate on BPA's health effects, regulatory agencies have been put into a challenging public health policy situation. The United States has implemented no regulatory actions due to safety concerns, while Europe has used the precautionary principle to guide its regulation in the face of scientific uncertainty. In this paper, we explore the debate surrounding BPA regulation and the possibility for countries to introduce guidelines, using Mexico as an example. Policy change determinants analysis suggest that countries can and should impose regulations on BPA.

Resumen: El bisfenol A (BPA), presente en plásticos y resinas epoxi, es uno de los químicos más estudiados. Se considera un disruptor endocrino y se ha relacionado con efectos adversos para la salud humana. Algunas agencias regulatorias en el mundo han concluido que el BPA es seguro a los niveles de exposición humana actuales. Mientas la comunidad científica intenta resolver el debate sobre dichos efectos, las agencias regulatorias enfrentan una difícil situación de política pública. Los Estados Unidos de América no han implementado acciones reglamentarias por razones precautorias, mientras que Europa ha utilizado el principio precautorio para guiar su regulación ante la incertidumbre científica. En este documento exploramos el debate que rodea la regulación del BPA y la posibilidad de que los países introduzcan directrices, usando a México como ejemplo. El análisis de los determinantes del cambio de políticas sugiere que los países pueden y deben regular el BPA.

Mecanismo carcinogénico asociado a la exposición al Bisfenol A / Carcinogenic mechanism associated of Bisphenol A exposure

Resumen Introducción: El Bisfenol A (BPA) es un producto químico al que los seres humanos están expuestos ampliamente por la vía oral, inhalación y transdérmica. Justificación: Dada la importancia de la patología oncológica que puede estar asociada a exposición a este químico, resulta imprescindible comprender mejor sus posibles mecanismos de acción asociados a carcinogénesis. Objetivo General: Investigar el mecanismo carcinogénico asociado a la exposición a BPA. Resultados: Aunque la mayoría de las investigaciones se han orientado hacia el efecto disruptor endocrino, con la limitante que los estudios in vivo son realizados en animales, existen estudios recientes que muestran su posible efecto carcinogénico en tejidos humanos. Sin embargo, se requiere más investigación sobre el papel del BPA de dosis baja (como ocurre en condiciones ambientales normales) y su efecto en la regulación de los cambios globales de expresión génica y las alteraciones epigenéticas en las células, que permitan establecer vínculos con carcinogénesis; esta revisión demuestra que los estudios realizados hasta la fecha señalan varios factores que pueden estar involucrados, como efectos mutagénicos que incluyen cambios en la transcripción génica y enzimáticos que promueven la proliferación celular limitando la apoptosis y favorecen la angiogénesis y migración de células tumorales. Conclusión: Si bien en la actualidad se reconoce que la célula cancerígena adquiere características patológicas que le ayudan a sobrevivir en el organismo, estas características obedecen a mecanismos moleculares genéticos y epigéneticos, muchos de los cuales han sido descritos para el caso de la exposición humana al BPA.

Abstract Introduction: Bisphenol A (BPA) is a chemical to which humans are extensively exposed orally, inhaled and transdermally. Justification: Given the importance of the oncological pathology that may be associated with exposure to this chemical, it is essential to better understand its possible mechanisms of action associated with carcinogenesis. Objective: To investigate the carcinogenic mechanism associated with BPA exposure. Results: Although the majority of investigations have been oriented towards the endocrine disrupting effect, with the limitation that in vivo studies are carried out in animals, recent studies have shown that they can be carcinogenic in human tissues. However, more research is required on the role of low-dose BPA (as occurs under normal environmental conditions) and its effect on the regulation of global changes in gene expression and epigenetic alterations in cells, which allow establishing links with carcinogenesis; this review shows that the studies carried out to date point to several factors that may be involved, such as mutagenic effects that include changes in gene transcription and enzymes that promote cell proliferation, limiting apoptosis and promoting angiogenesis and migration of tumor cells. Conclusion: Although it is currently recognized that the cancer cell acquires pathological characteristics that help it to survive in the organism, these characteristics are due to genetic and epigenetic molecular mechanisms, many of which have been described for the case of human exposure to BPA.

Analysis of individual and combined estrogenic effects of bisphenol, nonylphenol and diethylstilbestrol in immature rats with mathematical models

BACKGROUND@#Traditional toxicological studies focus on individual compounds. However, this single-compound approach neglects the fact that the mixture exposed to human may act additively or synergistically to induce greater toxicity than the single compounds exposure due to their similarities in the mode of action and targets. Mixture effects can occur even when all mixture components are present at levels that individually do not produce observable effects. So the individual chemical effect thresholds do not necessarily protect against combination effects, an understanding of the rules governing the interactive effects in mixtures is needed. The aim of the study was to test and analyze the individual and combined estrogenic effects of a mixture of three endocrine disrupting chemicals (EDCs), bisphenol A (BPA), nonylphenol (NP) and diethylstilbestrol (DES) in immature rats with mathematical models.@*METHOD@#In the present study, the data of individual estrogenic effects of BPA, NP and DES were obtained in uterotrophic bioassay respectively, the reference points for BPA, NP and DES were derived from the dose-response ralationship by using the traditional no observed adverse effect (NOAEL) or lowest observed adverse effect level (LOAEL) methods, and the benchmark dose (BMD) method. Then LOAEL values and the benchmark dose lower confidence limit (BMDL) of single EDCs as the dose design basis for the study of the combined action pattern. Mixed prediction models, the 3 × 2 factorial design model and the concentration addition (CA) model, were employed to analyze the combined estrogenic effect of the three EDCs.@*RESULTS@#From the dose-response relationship of estrogenic effects of BPA, NP and DES in the model of the prepuberty rats, the BMDL(NOAEL) of the estrogenic effects of BPA, NP and DES were 90(120) mg/kg body weight, 6 mg/kg body weight and 0.10(0.25) μg/kg body weight, and the LOAEL of the the estrogenic effects of three EDCs were 240 mg/kg body weight, 15 mg/kg body weight and 0.50 μg/kg body weight, respectively. At BMDL doses based on the CA concept and the factorial analysis, the mode of combined effects of the three EDCs were dose addition. Mixtures in LOAEL doses, NP and DES combined effects on rat uterine/body weight ratio indicates antagonistic based on the CA concept but additive based on the factorial analysis. Combined effects of other mixtures are all additive by using the two models.@*CONCLUSION@#Our results showed that CA model provide more accurate results than the factorial analysis, the mode of combined effects of the three EDCs were dose addition, except mixtures in LOAEL doses, NP and DES combined effects indicates antagonistic effects based on the CA model but additive based on the factorial analysis. In particular, BPA and NP produced combination effects that are larger than the effect of each mixture component applied separately at BMDL doses, which show that additivity is important in the assessment of chemicals with estrogenic effects. The use of BMDL as point of departure in risk assessment may lead to underestimation of risk, and a more balanced approach should be considered in risk assessment.

Effects of Di(2-ethylhexyl)phthalate on Bone Metabolism in Ovariectomized Mice

BACKGROUND: The molecular pathways of how endocrine disruptors affect bone mineral density (BMD) and bone remodeling are still unclear. The purpose of this experimental study is to determine the effects of di(2-ethylhexyl)phthalate (DEHP) on bone metabolism in ovariectomized mice. METHODS: Twenty-six-month-old female CD-1 mice were divided into 4 groups: control, low-dose DEHP, high-dose DEHP, and estrogen groups (n=5, each group). All mice were subjected to ovariectomy for the induction of artificial menopause and then exposed to corn oil, DEHP, and estrogen for 2 months. Micro-computed tomography (Micro-CT) of the bone and analysis of blood samples for bone markers were performed to observe the changes in bone metabolism. RESULTS: Osteocalcin level was decreased in the control, low-dose and high-dose DEHP group, the reduction width was greater in the high-dose DEHP group (−0.219 ng/mL) than control group (−0.077 ng/mL, P<0.05). C-terminal telopeptide of type I collagen level was increased in the control, low-dose and high-dose DEHP group, the increase range of low-dose DEHP group (0.329 ng/mL) showed greater than control group (0.093 ng/mL, P<0.05). Micro-CT analysis revealed that the BMD was significantly lower in the high-dose DEHP group (19.8×10⁻² g/cm³) than control group (27.2×10⁻² g/cm³, P<0.05). The structure model index was significantly higher in the high-dose DEHP group (2.737) than low-dose DEHP group (2.648) and estrogen group (2.63, P<0.05). It means the progression of osteoporosis in the high-dose DEHP group. CONCLUSIONS: These results confirm the negative effects of DEHP on bone health in ovariectomized mice. Further continuous studies on genetic pathways and other endocrine disruptors will be necessary to validate these findings.

Understanding the molecular mechanisms of bisphenol A action in spermatozoa / 대한생식의학회지

Bisphenol A (BPA) is an endocrine-disrupting chemical that is capable of interfering with the normal function of the endocrine system in the body. Exposure to this chemical from BPA-containing materials and the environment is associated with deleterious health effects, including male reproductive abnormalities. A search of the literature demonstrated that BPA, as a toxicant, directly affects the cellular oxidative stress response machinery. Because of its hormone-like properties, it can also bind with specific receptors in target cells. Therefore, the tissue-specific effects of BPA mostly depend on its endocrine-disrupting capabilities and the expression of those particular receptors in target cells. Although studies have shown the possible mechanisms of BPA action in various cell types, a clear consensus has yet to be established. In this review, we summarize the mechanisms of BPA action in spermatozoa by compiling existing information in the literature.

Early-life exposure to endocrine-disrupting chemicals and pubertal development in girls

Over the last decades, the onset of puberty in girls has occurred earlier, but the tempo of pubertal progression has been relatively slower, resulting in a younger age at puberty onset without a change in age at menarche. Sufficient energy availability and adiposity contribute to early pubertal development, and environmental factors, such as endocrine-disrupting chemicals (EDCs), may affect not only the control of energy balance, but also puberty and reproduction. EDCs are hormonally active substances that can perturb puberty by acting both peripherally on target organs, such as adipose tissue or adrenal glands, and/or centrally on the hypothalamic-pituitary-gonadal (HPG) axis. Depending on whether the exposure takes place earlier during fetal and neonatal life or later during early childhood, EDCs can lead to different outcomes through different mechanisms. Evidence of associations between exposures to EDCs and altered pubertal timing makes it reasonable to support their relationship. However, human epidemiologic data are limited or inconsistent and cannot provide sufficient evidence for a causal relationship between EDC exposure and changes in pubertal timing. Further investigation is warranted to determine the overall or different effects of EDCs exposure during prenatal or childhood windows on pubertal milestones and to reveal the underlying mechanisms, including epigenetic marks, whereby early-life exposure to EDCs affect the HPG-peripheral tissue axis.

Di (2-ethylhexyl) phthalate Disorders Lipid Metabolism via TYK2/STAT1 and Autophagy in Rats / 生物医学与环境科学（英文）

OBJECTIVE@#Previous studies have indicated that the plasticizer di (2-ethylhexyl) phthalate (DEHP) affects lipid accumulation; however, its underlying mechanism remains unclear. We aim to clarify the effect of DEHP on lipid metabolism and the role of TYK2/STAT1 and autophagy.@*METHODS@#In total, 160 Wistar rats were exposed to DEHP [0, 5, 50, 500 mg/(kg•d)] for 8 weeks. Lipid levels, as well as mRNA and protein levels of TYK2, STAT1, PPARγ, AOX, FAS, LPL, and LC3 were detected.@*RESULTS@#The results indicate that DEHP exposure may lead to increased weight gain and altered serum lipids. We observed that DEHP exposure affected liver parenchyma and increased the volume or number of fat cells. In adipose tissue, decreased TYK2 and STAT1 promoted the expression of PPARγ and FAS. The mRNA and protein expression of LC3 in 50 and 500 mg/(kg•d) groups was increased significantly. In the liver, TYK2 and STAT1 increased compensatorily; however, the expression of FAS and AOX increased, while LPL expression decreased. Joint exposure to both a high-fat diet and DEHP led to complete disorder of lipid metabolism.@*CONCLUSION@#It is suggested that DEHP induces lipid metabolism disorder by regulating TYK2/STAT1. Autophagy may play a potential role in this process as well. High-fat diet, in combination with DEHP exposure, may jointly have an effect on lipid metabolism disorder.

Bisphenols and Thyroid Hormone

In recent decades, attention has been directed toward the effects of bisphenol A (BPA) on human health. BPA has estrogenic activity and is regarded as a representative endocrine disruptor. In addition, mounting evidence indicates that BPA can disrupt thyroid hormone and its action. This review examined human epidemiological studies to investigate the association between BPA exposure and thyroid hormone levels, and analyzed in vivo and in vitro experiments to identify the causal relationship and its mechanism of action. BPA is involved in thyroid hormone action not only as a thyroid hormone receptor antagonist, but also through several other mechanisms. Since the use of bisphenols other than BPA has recently increased, we also reviewed the effects of other bisphenols on thyroid hormone action.

Effects of Sleep Pattern, Stress, Menstrual Attitude, and Behavior That Reduces Exposure to Endocrine Disrupting Chemicals on Premenstrual Syndrome in Adolescents / 여성건강간호학회지

PURPOSE: The study aimed to examine the effects of sleep pattern, stress, and attitude towards menstruation, and behavior that causes a reduction in exposure to endocrine disrupting chemicals (EDCs) in the course of premenstrual syndrome (PMS) in female adolescents.METHOD: In total, 200 girls attending middle school in K city were recruited via convenience sampling between December 11 and 31, 2018, and 192 subjects were selected for the analysis. Data were analyzed using descriptive statistics, an independent t-test, ANOVA, Pearson's correlation coefficient, and multiple regression.RESULTS: Overall, 9 (4.7%), 152 (79.2%), and 31 (16.1%) students had morning-, intermediate-, and evening-type sleep pattern, respectively. The mean scores for school-related stress were highest. Scores for stress regarding relationships with friends were the lowest. The mean score for attitudes toward menstruation was 72.33 out of 147. The mean score for behavior that led to a reduction in EDCs exposure was 56.57 out of 85. The mean scores for PMS severity were 25.30 and 38.39 out of 60. Analysis of factors affecting PMS revealed that severity of menstrual pain (β=.28), use of analgesics during menstruation (β=.17), family history of PMS (β=−.16), stress (β=.19), and behavior that reduces EDCs exposure (β=−.17) exerted significant effects on PMS. The explanatory power of these variables was 37%.CONCLUSION: The findings propose the necessity of a health intervention program including educational information, which can reduce PMS in adolescents, induce the behaviors which can decrease exposure to EDCs, and activities for managing the stress levels.