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.

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)

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).

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.

Plaguicidas e hipotiroidismo en agricultores en zonas de cultivo de plátano y café, en Quindío, Colombia / Pesticides and hypothyroidism in farmers of plantain and coffee growing areas in Quindio, Colombia

RESUMEN Objetivos Determinar relación entre hipotiroidismo y plaguicidas en sangre. Metodología Estudio de corte transversal, en agricultores y sus compañeros(as) permanentes en municipios productores de plátano y café. Se calculó muestra representativa. Se realizaron pruebas de función tiroidea, se utilizó un lector de ELISA Stat Fax 303/Plus, en una longitud de onda 450 nm. Se determinó la residualidad de plaguicidas organoclorados, se implementó un método de microextracción dispersiva en fase líquida (DLLME) asistida por sonicación, y se empleó cromatografía de gases con detector de micro captura de electrones (GC-µECD) para el análisis. Resultados Se incluyeron 819 participantes, 58,7% hombres y 41,3% mujeres; promedio de edad 48,1 años. Prevalencia de hipotiroidismo manifiesto 1,2% y de hipotiroidismo subclínico 6,7%, mayor prevalencia en personas mayores de 60 años (2,6% y 8,9% respectivamente). Se encontró asociación no causal de hipotiroidismo subclínico con plaguicidas organoclorados 4,4'-DDE (sig.0,006), Heptacloro (sig.0,04), y Endosulfán I (sig.0,02). Los anticuerpos antiperoxidasa (Anti TPO) ≥ 60 lU/ml se asociaron con h. subclínico, OR 2,6. Conclusiones La prevalencia de hipotiroidismo hallada es similar a lo referido en la literatura, es menor que en áreas urbanas; la prevalencia de hipotiroidismo subclínico es mayor y con riesgo de progresión a hipotiroidismo franco cuando se relaciona con Anti-TPO positivos, razón por la cual se requiere seguimiento en estos pacientes. Se asociaron a h. subclínico 3 plaguicidas organoclorados. Se recomienda tamizaje de TSH en personas de 40 y más años sobre todo si están expuestas a los agroquímicos mencionados.(AU)

ABSTRACT Objectives To establish the correlation between hypothyroidism and blood pesticide levels. Materials and Methods Cross-sectional study in agricultural workers and their permanent partners in plantain and coffee producing municipalities as reference population. A representative sample was estimated and thyroid function tests were performed using ELISA Stat Fax 303/Plus reader, at a wavelength of 450 nm. Organochlorine pesticide residuality was determined, a dispersive liquid-liquid microextraction (DLLME) assisted by sonication was implemented, and a gas chromatography-micro-electron capture detector (GC-pECD) was used for the analysis. Results 819 participants, 58.7% men and 41.3% women were included; their average age was 48.1 years. Prevalence of symptomatic hypothyroidism (1.2%) and subclinical hypothyroidism (6.7%) was observed, with a higher prevalence in people older than 60 years (2.6% and 8.9%, respectively). Non-causal association was found between subclinical hypothyroidism and the organochlorine pesticides 4,4'-DDE (sig.0,006), Heptachlor (sig.0,04), and Endosulfan I (sig.0,02). Antiperoxidase (Anti TPO) antibodies ≥60 lU/ml were associated with subclinical hypothyroidism (OR 2.6). Conclusions The prevalence of hypothyroidism in the studied population is similar to that reported in the literature, and lower than in urban areas. In turn, the prevalence of subclinical hypothyroidism is higher and positive anti-TPO values are related to risk of progression to frank hypothyroidism, which is why follow-up is required in these patients. Three organochlorine pesticides were associated with subclinical hypothyroidism. TSH screening is recommended in people aged 40 and over, especially if they are exposed to the aforementioned agrochemicals.(AU)

Cuantificación de Bisfenol-A libre en sangre de cordón umbilical humano a nivel de trazas / Quantification of free Bisphenol-A in human umbilical cord blood at trace level / Quantificação de Bisfenol-A livre em sangue de cordão umbilical humano a nível de traços

El Bisfenol-A (BPA) es ampliamente utilizado en la producción de plásticos de policarbonato, por lo que está presente en productos de uso masivo. Es un disruptor endócrino e incide en el desarrollo gonadal y del sistema nervioso central. La exposición de mujeres embarazadas al BPA es particularmente preocupante para el feto en desarrollo, debido a que atraviesa la placenta pasando a la sangre de cordón y al líquido amniótico. Esto se suma a la escasa o nula actividad enzimática fetal para biotransformarlo en BPA-glucurónido inactivo, causando posibles efectos nocivos a la descendencia a dosis muy bajas y sostenidas. Con el propósito de estudiar la exposición al BPA y sus efectos en la población de Argentina se desarrolló y validó un método analítico por cromatografía líquida acoplada a espectrometría de masa, que permite la cuantificación de trazas de BPA libre (forma estrogénica, activa) en plasma de cordón umbilical. La técnica consiste en la precipitación de proteínas de la sangre de cordón por agregado de acetonitrilo y posterior centrifugado e inyección del sobrenadante. Se utilizó una elución isocrática en la cromatografía líquida, y la espectrometría de masa se realizó empleando Electrospray negativo en modo de monitoreo de reacciones múltiples. Los valores de BPA libre cuantificados están en el rango de 1,0 a 12,1 ng/mL, límite de detección: 0,6 ng/mL.

Bisphenol-A (BPA) is widely used in the production of polycarbonate plastics and therefore, it is present in products of massive use. It is known as an endocrine disruptor and has an impact on gonadal and central nervous system development. Exposure of pregnant women to BPA is particularly worrying for the developing fetus because it crosses the placenta into the cord blood and amniotic fluid, coupled with little or no fetal enzymatic activity to biotransform it into inactive BPA-glucuronide, causing possible harmful effects to the offspring at very low and sustained doses. With the aim to study the exposure to BPA and its effects on the population of Argentina, an analytical method was developed and validated by liquid chromatography coupled to mass spectrometry, which allows the quantification of trace amounts of free BPA (estrogenic, active form) in plasma of umbilical cord. The method involves protein precipitation by the addition of acetonitrile and subsequent centrifugation and injection of supernatant. An isocratic elution was used in liquid chromatography, and mass spectrometry was performed using negative Electrospray mode in multiple reaction monitoring. Quantified free BPA values are in the range of 1.0 to 12.1 ng/mL, Detection Limit: 0,6 ng/mL.

O Bisfenol-A (BPA) é amplamente utilizado na produção de plásticos de policarbonato, portanto está presente em produtos de uso massiço. Ele é um disruptor endócrino e tem um impacto no desenvolvimento gonadal e do sistema nervoso central. A exposição de mulheres grávidas ao BPA é particularmente preocupante para o feto em desenvolvimento, visto que atravessa a placenta passando ao sangue do cordão e ao líquido amniótico Isso é adicionado à pouca ou nula atividade enzimática fetal para biotransformá-lo em BPA-glicuronídeo inativo, o que causa possíveis efeitos nocivos aos descendentes em doses muito baixas e sustentadas. Visando a estudar a exposição ao BPA e seus efeitos na população da Argentina, foi desenvolvido e validado um método analítico por cromatografia líquida acoplada à espectrometria de massa, que permitem a quantificação de vestígios de BPA livre (forma estrogênica, livre) em plasma do cordão umbilical. A técnica consiste na precipitação de proteínas do sangue de cordão por adição de acetonitrila e posterior centrifugação e injeção no sobrenadante. Na cromatografia líquida, foi utilizada uma eluição isocrática, e a espectrometria de massa foi realizada utilizando Electrospray negativo em modo de monitoramento de reações múltiplas. Os valores de BPA livre quantificados estão na faixa de 1,0 a 12,1 ng/mL, limite de detecção: 0,6 ng/mL.

Malformações congênitas em regiões de monocultivo no estado de Minas Gerais, Brasil / Congenital malformations in monoculture regions in the state of Minas Gerais, Brazil

Objetivo: analisar a associação entre o uso de agrotóxicos e as malformações congênitas em municípios com maior exposição, assim como avaliar a natureza da correlação existente entre a tendência observada e o volume de agrotóxicos considerados como disruptores endócrinos no estado de Minas Gerais, Brasil, entre 1994 e 2014. Modelo do Estudo: estudo transversal, de caráter exploratório, descritivo e quantitativo. Metodologia: foram analisadas as informações dos nascidos vivos (SINASC/ Ministério da Saúde), elaborando-se taxas de malformações ocorridas de 1994-2003 e 2004-2014. A associação entre os tipos de malformações e as variáveis foi testada pelo Odds Ratio para cada variável separadamente. A significância utilizada foi de p<0,05. Resultados: houve uma tendência crescente nas taxas de malformação congênita no estado de Minas Gerais, com destaque às regiões do Triângulo Mineiro/ Alto Paraíba e Vale do Mucuri/Jequitinhonha. Constatou-se que as taxas referentes às malformações congênitas foram maiores para os anos de maior exposição (2004-2014) e tiveram associação estatisticamente significativa para todas as malformações congênitas no estado de Minas Gerais. Conclusão: A exposição materna aos agrotóxicos foi relacionada à maior ocorrência de malformações congênitas. (AU)

Objective: to analyze the association between the use of agrochemicals and congenital malformations in municipalities with greater exposure, as well as to evaluate the nature of the correlation between the trend observed and the volume of agrochemicals considered as endocrine disruptors in the state of Minas Gerais, Brazil, between 1994 and 2014. Model Study: Cross-sectional study, exploratory, descriptive and quantitative character. Method: Rates of malformations for the periods 1994-2003 and 2004-2014 were calculated from the information on live births available at SINASC/Ministry of Health. Odds Ratio tested the association between types of malformations and variables for each variable separately. The significance was set at p<0.05. Results: there was an increasing trend in the rates of congenital malformation in the state of Minas Gerais, especially at Triângulo Mineiro/Alto Paraíba and Vale do Mucuri/Jequitinhonha regions. It was found that the rates for congenital malformations were higher for the years of greatest exposure (2004-2014) and had a statistically significant association for all congenital malformations in the state of Minas Gerais. Conclusion: Maternal exposure to pesticides was related with higher incidence of congenital malformations. (AU)

Determinación preliminar de triclosán por espectroscopia UV-Vis en aguas residuales de la ciudad de Guatemala / Preliminary determination of triclosan by UV-Vis spectroscopy in wastewater from Guatemala city

Estimar el grado de remoción de contaminantes emergentes en el proceso de tratamiento de aguas residuales es de importancia para evaluar la efectividad de las técnicas empleadas en la actualidad. El triclosán (TCS) es un agente antimicrobiano sintético de amplio espectro, estudios recientes sugieren que presenta elevado potencial como interruptor endocrino. Se determinó la concentración de TCS en cuatro muestras de aguas residuales obtenidas en diferentes etapas del proceso de tratamiento de aguas en la Planta Piloto para el Tratamiento de Aguas Residuales Ingeniero Arturo Pazos Sosa (IAPS). Las muestras de agua fueron filtradas en membrana, tratadas por adición de TCS estándar y formación de un compuesto complejo coloreado amarillo-café cuya absorbancia a 475 nm fue registrada en un espectrofotómetro Cary® 50 UV-Vis. Se identificó la presencia de TCS en concentraciones por arriba de 200 µg/L en tres diferentes etapas del tratamiento de aguas residuales en la planta piloto IAPS lo que permitió concluir que el grado de remoción de TCS en esta planta de tratamiento de aguas osciló entre 31 y 95% dependiendo de la etapa de tratamiento, sin embargo el agua del efluente de la planta no puede considerarse como potable ya que la concentración de TCS determinada en este estudio sobrepasa por al menos un orden de magnitud de diez los niveles a los cuales no se han reportado efectos adversos hacia organismos vivos.

Estimating the degree of contaminants' removal during wastewater treatment is important to evaluate the effectiveness of the current treatment techniques. Triclosan (TCS) is a synthetic broad spectrum antimicrobial agent and recent investigations suggest that this compound has high potential as endocrine disruptor. The concentration of TCS was measured in four wastewater samples obtained at different processing steps at the Ingeniero Arturo Pazos Sosa (IAPS) pilot plant. The wastewater samples were treated by membrane filtration, standard addition of TCS and the subsequent formation of a brown-yellow colored complex, whose absorbance at 475nm was measured in a Cary 50® UV-Vis spectrophotometer. TCS was found at concentrations over 200 µg/L in three different phases of the wastewater treatment at the IAPS plant. In conclusion, the degree of TCS removal in this plant was between 31 and 95% depending on the treatment stage. However plant effluent cannot be considered potable since the TCS concentration found in this study is at least ten times higher than those at which adverse effects to living organisms have not been detected.

Bisphenol (A) uremic toxin to take into account in the Renal disease in Hemodialysis / Bisfenol (A) una toxina a tener en cuenta en el enfermo renal en hemodiálisis

Abstract Introduction: Most uremic toxins are by-products of protein metabolism by action of intestinal flora. The metabolism of aromatic amino acids originates phenolic type residues. The most studied is p-cresol that is associated with renal function and vascular damage. Bisphenol A (BPA) is an exogenous molecule with characteristics similar to these aromatic uremic toxins. BPA is an estrogenic endocrine disruptor, found in tin cans, plastic bottles, epoxy resins and in some dialyzers. This molecule accumulates in patients who have impaired renal function. Observational studies have shown that exposure of BPA is linked to renal and cardiovascular injury, among many others in humans, and in animal studies a causal link has been described. Kidneys with normal renal function rapidly excrete BPA, but insufficient excretion in patients with CKD results in accumulation of BPA in the body.

Resumen Muchas toxinas urémicas son originadas como consecuencia del catabolismo proteico por la flora intestinal. El metabolismo de aminoácidos aromáticos origina residuos de tipo fenólico. De estas toxinas, la más estudiada es el p-cresol, que se asocia a la función renal y daño vascular. El Bisfenol A (BPA) es una molécula exógena de características semejantes a estas toxinas urémicas aromáticas. El BPA es un disruptor endocrino estrogénico que se encuentra en latas de conserva, botellas de plástico, resinas epoxi y en algunos dializadores. Esta molécula se acumula en pacientes que tienen deteriorada la función renal. Estudios observacionales han demostrado que una exposición a BPA está vinculada, entre otras muchas, a lesión renal y cardiovascular en los seres humanos; en estudios en animales se ha descrito un vínculo causal. Los riñones con función renal normal excretan rápidamente BPA, pero una excreción insuficiente en pacientes con ERC da lugar a la acumulación del BPA en el organismo.

Impacto na saúde humana de disruptores endócrinos presentes em corpos hídricos: existe associação com a obesidade? / Impact on human health of endocrine disruptors present in environmental water bodies: is there an association with obesity?

Resumo Há evidências crescentes de que os desreguladores endócrinos (DE) podem afetar negativamente os seres humanos. Águas superficiais e subterrâneas são as principais fontes de obter a sua potabilidade, no entanto, podem ser contaminadas por DE, que não são totalmente removidos pelos processos convencionais de tratamento de água e esgoto. Alguns problemas de saúde estão relacionados à exposição dos seres humanos aos DE, sendo a obesidade um deles. Atualmente vive-se um aumento da prevalência da obesidade em todo o mundo, fato considerado preocupante, tendo em vista seu potencial impacto no sistema de saúde, pois, as principais doenças crônicas como diabetes e doenças cardiovasculares, têm a obesidade como grande fator de risco. Por meio de revisão de literatura, este artigo buscou reunir publicações científicas relacionando a exposição aos DE com a obesidade, com o objetivo de verificar a importância de sua remoção dos corpos hídricos, preservando a saúde da população e da biota aquática. A maioria dos estudos selecionados sugere associação entre DE e obesidade em humanos.

Abstract There is growing evidence that endocrine disruptors (ED) may adversely affect humans. Surface and underground water are the main sources for obtaining potable water, however they can be contaminated with ED, which are not completely removed by conventional water and sewage treatment processes. Some health problems are related to the exposure of humans to ED, obesity being one of them. There is currently an increase in the prevalence of obesity worldwide, a fact that is considered a concern in view of its potential impact on the health care system, since obesity is the major risk factor of the leading chronic diseases including diabetes and cardiovascular disease. By means of a review of the literature, this paper sought to gather scientific publications linking exposure to ED with obesity, in order to verify the importance of removal of ED from water bodies, thereby preserving the population’s health and aquatic biota. Most of the selected studies suggest an association between ED and obesity in humans.

Contaminación, disruptores endocrinos y cáncer / Contamination, endocrine disruptors and cancer

Desde mediados del siglo XX numerosas especies, muy diferentes entre sí y ubicadas en todas las áreas y rincones del planeta, comenzaron a presentar diversas alteraciones, muchas de las cuales sugerían estar relacionadas con trastornos del sistema endocrino. Las investigaciones demostraron que tales alteraciones eran producidas por la exposición a diferentes sustancias químicas contaminantes, las cuales podían alterar la salud y producir graves enfermedades. Dentro de ellas destacó un grupo heterogéneo de compuestos con estructuras químicas muy diferentes, capaces de actuar a dosis muy bajas, mostrar distintos mecanismos de acción y ser capaces de alterar el equilibrio hormonal, por lo que se les denominó “disruptores endocrinos químicos”. Estas sustancias, al ser liberadas al medioambiente o formar parte de objetos, alimentos o medicinas, constituyen un gran riesgo para los seres humanos y toda la vida del planeta, produciendo no solo disfunciones endocrinas sino también diferentes tipos de cáncer, destacando los más frecuentes. A pesar de la trascendencia y significado del impacto de estos compuestos, ellos no son suficientemente conocidos ni entendidos, por lo que el objetivo de esta revisión es mostrar su origen e impacto en la salud humana, resaltando su papel como inductores de cáncer, lo cual ha motivado múltiples investigaciones clínicas y biológicas.

Since the mid-twentieth century, many species, very different from each other and located in all areas and corners of the planet, began presenting various alterations, many of which suggested to be related to endocrine disorders. Research has shown that such alterations were caused by exposure to various chemical contaminants that could affect the health and cause serious illnesses. Among them stands a diverse and large group of compounds, with very different chemical structures, capable of altering the hormonal balance, act at very low doses and with different mechanisms of action, that are called “endocrine disrupting chemicals”. When released into the environment or as part of objects, food or medicines, constitute a major risk to animals and humans, which produces not only endocrine dysfunctions but also different cancers, which include the most common types. Despite the importance and significance of the impact of these compounds, they are not sufficiently known or understood, so the aim of this review is to show their origin and impact in the field of human health, highlighting their role as inducers of cancer, which has led to multiple clinical and biological investigations.

Regulamentação do estrogênio sintético 17-etinilestradiol em matrizes aquáticas na Europa, Estados Unidos e Brasil / Regulación del estrógeno sintético 17-etinilestradiol en matrices acuáticas en Europa, Estados Unidos y Brasil / Regulation of the synthetic estrogen 17-ethinylestradiol in water bodies in Europe, the United States, and Brazil

O estrogênio sintético 17α-etinilestradiol, principal componente utilizado em formulações de contraceptivos orais, tem sido apontado como um dos principais compostos responsáveis por provocar efeitos adversos no sistema endócrino de várias espécies. O objetivo deste estudo foi analisar o estado da arte dos dispositivos legais e normativos referentes ao controle desse estrogênio sintético nas águas da Europa e dos Estados Unidos, e traçar um paralelo com a realidade brasileira. No geral, os países têm buscado ampliar a regulamentação e monitoramento de alguns micropoluentes emergentes que antes não eram objeto de atenção por parte dos dispositivos legais. A Europa está mais avançada no que tange à qualidade dos corpos hídricos, enquanto que nos Estados Unidos esta substância é alvo de regulamentação apenas para a água destinada ao consumo humano. No Brasil, ainda não há nenhum dispositivo legal ou normativo que aborde esse estrogênio, o que pode ser associado a uma baixa maturidade do sistema brasileiro quanto ao controle de poluentes hídricos.

El estrógeno sintético 17α-etinilestradiol, principal componente utilizado en fórmulas de contraceptivos orales, ha sido apuntado como uno de los principales compuestos responsables por provocar efectos adversos en el sistema endócrino de varias especies. El objetivo de este estudio fue analizar el estado de la cuestión de los dispositivos legales y normativos referentes al control de este estrógeno sintético en las aguas de Europa y de los Estados Unidos, y trazar un paralelo con la realidad brasileña. En general, los países han buscado ampliar la regulación y el monitoreo de algunos microcontaminantes emergentes que antes no eran objeto de atención por parte de los dispositivos legales. Europa está más avanzada en lo que se refiere a la calidad de los cuerpos hídricos, mientras que en los Estados Unidos esta substancia es objeto de regulación solamente para el agua destinada al consumo humano. En Brasil todavía no existe ningún dispositivo legal o normativo que aborde este estrógeno, lo que puede ser asociado a una inmadurez del sistema brasileño respecto al control de contaminantes hídricos.

The synthetic estrogen 17α-ethinylestradiol, the principal component of oral contraceptives, has been identified as one of the main compounds accounting for adverse effects on the endocrine system in various species. This study aimed to analyze the state-of-the-art in legislation and guidelines for the control of this synthetic estrogen in water bodies in Europe and the United States and to draw a parallel with the Brazilian reality. Countries have generally attempted to expand the regulation and monitoring of certain emerging micropollutants not previously covered by legislation. Europe is more advanced in terms of water quality, while in the United States this estrogen is only regulated in water for human consumption. Brazil still lacks legal provisions or standards for this estrogen, which can be explained by the relatively limited maturity of the country's system for controlling water pollutants.

El organofosforado clorpirifos como disruptor estrogénico y factor de riesgo para el cáncer de mama / The organophosphorus chlorpyrifos as endocrine disruptor and breast cancer factor risk

El clorpirifos (CPF) es un insecticida de amplio espectro que se utiliza en Argentina y en otros países de Latinoamérica. Se emplea para el control de plagas en la producción de frutas, hortalizas, cereales y plantas ornamentales. El principal mecanismo de acción descripto para este insecticida es la inhibición de la acetilcolinesterasa. Sin embargo, reportes más recientes sugieren múltiples efectos del plaguicida independientes de la inhibición de esa enzima. El objetivo de este trabajo es transmitir a la comunidad los resultados de nuestras investigaciones obtenidos utilizando diferentes dosis de CPF en distintos modelos experimentales, tanto in vitro como in vivo. En relación a esto, hemos evidenciado una acción del CPF sobre el sistema redox celular que conduce al incremento de especies reactivas del oxígeno y consecuentemente a la activación de diferentes vías de señalización. Además, hemos determinado que el insecticida CPF puede comportarse como un disruptor endócrino modulando la acción de los estrógenos y alterando la normal estructura del tejido mamario. Nuestros resultados alertan sobre el impacto que este compuesto podría tener sobre la salud, sugiriendo la necesidad de revisar su uso dado que manifiesta acciones a dosis encontradas en el ambiente.

Chlorpyrifos (CPF) is a broad spectrum insecticide used in Argentina and other Latin American countries. It is commonly used for pest control in the production of fruits, vegetables, cereals and ornamental plants. The main mechanism of action described for this insecticide is the inhibition of acetylcholinesterase activity. However, more recent reports suggest multiple effects for this pesticide in an independent way from the inhibition of this enzyme. The objective of this work is to convey to the community the results of our investigations obtained using different doses of CPF in various experimental models, both in vitro and in vivo. In this connection, we have shown a CPF action on the cellular redox system which leads to increased reactive oxygen species and the consequent activation of different signaling pathways. In addition, we have determined that the insecticide CPF acts as an endocrine disruptor modulating the action of estrogen and altering the normal structure of breast tissue. Our findings warn about the impact that this compound might have on health, suggesting the need to review its use since adverse actions were found at environmentally relevant doses.