Marieta Fernández

Nonylphenol and octylphenol in adipose tissue of women in Southern Spain

Alkylphenols (APs) and AP ethoxylates are environmental contaminants with endocrine disrupting activities in wildlife and humans. They have been largely used in industrial, agricultural, and domestic applications. Despite strong concerns about the consequences of human exposure to endocrine disrupters, little information is available on the presence in humans of compounds such as APs. The aim of the present study was to determine 4-nonylphenol (NP) and 4-octylphenol (OP) residues in adipose tissue of non-occupationally exposed women living in Southern Spain. NP was detected in 100% (n=20/20) and OP in 23.5% (n=4/20) of samples, with median levels of 57 and 4.5 ng g(-1) adipose tissue, respectively. Body mass index emerged as a determinant of exposure since it was associated with NP levels (p=0.041). Adipose tissue NP and OP levels are similar to the few data previously published in other countries. This is the first report on NP and OP levels in a population in Southern Spain. Further research is needed to determine trends in human exposure to these compounds and to investigate their consequences.

Urinary 1-hydroxypyrene and PAH exposure in 4-year-old Spanish children

AIMS Exposure to polycyclic aromatic hydrocarbons (PAH), among the main compounds present in polluted urban air, is of concern for childrens health. Childhood exposure to PAH was assessed by urinary monitoring of 1-hydroxypyrene (1-OHP), a pyrene metabolite, investigating its association with exposure to air pollution and other factors related to PAH in air. METHODS A group of 174 4-year-old children were recruited and a questionnaire on their indoor and outdoor residential environment was completed by parents. At the same time, environmental measurements of traffic-related air pollution (NO2) were carried out. A urine sample was collected from each child in order to analyze 1-OHP using HPLC with fluorescence detection, correcting for creatinine concentrations. Non-parametric tests and regression analyses were used to identify environmental factors that influence 1-OHP excretion. RESULTS Mean urinary 1-OHP concentration was 0.061 micromol/mol creatinine, ranging from 0.004 to 0.314 micromol/mol. Non-parametric tests and regression analysis showed positive and significant associations (P<or=0.05) between 1-OHP and predicted residential exposure to NO2 (which was based on outdoor environmental measurements and geo-statistical analysis), self-reported residential vehicle traffic, passive smoking and cooking appliance. 1-OHP levels tended to be higher among children living in urban areas (0.062 micromol/mol vs. 0.058 micromol/mol for children living in rural areas) but differences were not significant (P=0.20). CONCLUSION In Southern Spain, concentrations of urinary 1-OHP were in the lower range of those generally reported for children living in non-polluted areas in Western Europe and the USA. Traffic-related air pollution, passive smoking and cooking appliance influenced urinary 1-OHP level in the children, which should be prevented due to the health consequences of the inadvertent exposure to PAH during development.

Oestrogenicity of paper and cardboard extracts used as food containers

Bisphenol-A (BPA), dibutyl phthalate (DBP), and di-2-ethylhexyl phthalate (DEHP), which are common chemical residues in food-packaging materials, were investigated in paper and cardboard containers used for take-away food. The oestrogenicity of aqueous extracts was tested in E-Screen bioassay and analysis carried out by high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC/MS). Oestrogenicity was demonstrated in 90% of extracts (geometric mean [GM] = 11.97 pM oestradiol equivalents g−1). DEHP, DBP, and BPA (GM = 341.74, 37.59, and 2.38 ng g−1 of material) were present in 77.50, 67.50, and 47.50% of samples, respectively. In bivariate analyses, no significant association was found between the levels of these chemicals and oestrogenicity in cardboard/paper extracts. A close-to-significant association was found between oestrogenicity and DBP (β = 1.25; p = 0.06) in paper extracts, which reached statistical significance in multivariate analysis (β = 1.61; p = 0.03). Paper and cardboard used in food packaging may contribute to the inadvertent exposure of consumers to endocrine-disrupting chemicals.

La red de investigación "infancia y medio ambiente"(Red INMA): Protocolo de estudio

Cada vez existe mayor evidencia de la influencia de la dieta y de la exposicion a dosis bajas de toxicos durante la etapa prenatal y primera infancia sobre la salud y el bienestar en etapas posteriores de la vida. Siguiendo las recomendaciones de la OMS y de la Union Europea en el ano 2003 se constituyo la Red de Investigacion Cooperativa Infancia y Medio Ambiente para estudiar los efectos del medio ambiente y la dieta en el desarrollo fetal e infantil en diversas zonas geograficas en Espana. La Red integra diversos grupos multidisciplinares de investigacion y esta constituida por seis cohortes, tres preexistentes y tres de novo, que seguiran de forma prospectiva a 3.600 mujeres embarazadas, desde el inicio del embarazo hasta los 4-6 anos del nino. Los objetivos generales de la red son: (1) Describir la exposicion individual a toxicos ambientales durante la gestacion y la primera infancia. (2) Evaluar los efectos de la exposicion a toxicos y de la dieta en el desarrollo fetal e infantil. (3) Evaluar la interaccion entre factores toxicos, nutricionales y geneticos en el desarrollo fetal e infantil. El seguimiento se realiza en cada trimestre de la gestacion, al nacimiento, al ano y hasta los cuatro o seis anos del nino. La informacion se recoge mediante cuestionarios, datos clinicos, exploracion fisica, ecografias, biomarcadores y mediciones ambientales. En este trabajo se presentan las caracteristicas generales de la red y se describe la situacion actual de cada una de las cohortes.

Exposición a contaminantes atmosféricos durante el embarazo y desarrollo prenatal y neonatal: protocolo de investigación en el proyecto INMA (Infancia y Medio Ambiente)

Introduccion: El proyecto INMA (Infancia y Medio Ambiente) es una red de investigacion cooperativa que tiene como objetivos estudiar los efectos del medio ambiente y la dieta en el desarrollo fetal e infantil. El objetivo de este articulo es presentar el protocolo de exposicion a contaminantes atmosfericos durante el embarazo y desarrollo prenatal y neonatal en el proyecto INMA. Metodos: La informacion para la evaluacion de la exposicion a contaminacion atmosferica durante el embarazo se basa en mediciones de contaminantes atmosfericos en el exterior (dioxido de nitrogeno [NO2], compuestos organicos volatiles [COV], ozono, particulas [PM10, PM2,5] y su composicion [hidrocarburos aromaticos policiclicos]), medicion de contaminantes de exposicion individual (en el interior de la vivienda y captadores personales [COV y NO2]), determinacion de un marcador biologico de exposicion a hidrocarburos (1-hidroxipireno), en informacion recogida mediante cuestionarios y en la utilizacion de sistemas de informacion geografica. Esta informacion permite elaborar indices de exposicion individual a contaminacion atmosferica con los que analizar su posible relacion con el desarrollo fetal y la salud del recien nacido. Discusion: El protocolo que se presenta y el tipo de estudio permiten obtener una aproximacion a la exposicion individual a contaminantes atmosfericos. Por ultimo, el elevado numero de participantes (n = 4.000), asi como la heterogeneidad de las caracteristicas ambientales y sociodemograficas, acrecienta el potencial del estudio.

Dioxins in adipose tissue of women in Southern Spain.

Seventeen polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were quantified in adipose tissue samples of non-occupationally exposed women living in Southern Spain. Geometric mean levels of sum of congeners and WHO(PCDD/F)-TEQ(2005) were 410 and 17.9pgg(-1) fat, respectively. Among PCDDs, octachlorodibenzo-p-dioxin (OCDD) showed the highest concentration with a mean value of 265pgg(-1) fat, followed by 1,2,3,6,7,8-HxCDD (49.3pgg(-1) fat) and 1,2,3,4,6,7,8-HpCDD (45.2pgg(-1) fat). These three congeners were responsible for around 90% of the sum of all PCDD/F congeners in adipose tissue. The geometric mean 2,3,7,8-TCDD value was 1.87pgg(-1) fat. 2,3,4,7,8-PeCDF (8.43pgg(-1) fat) showed the highest concentration among the PCDFs, followed by 1,2,3,4,7,8-HxCDF (4.17pgg(-1) fat) and 1,2,3,6,7,8-HxCDF (3.28pgg(-1) fat), and these three congeners were responsible for 4% of the sum of all studied PCDD/F congeners in adipose tissue and 76% of the sum of ten PCDFs. 1,2,3,7,8,9-HxCDF was the only congener not quantified in any sample, while 1,2,3,4,7,8,9-HpCDF, 1,2,3,7,8-PeCDF, OCDF and 2,3,7,8-TCDF were found in 5, 16, 16 and 19 samples, respectively. All other congeners were quantifiable in all 20 samples. Congeners contributing most to the WHO(PCDD/F)-TEQ(2005) were 1,2,3,7,8-PeCDD (31.6%), 1,2,3,6,7,8-HxCDD (28.3%) and 2,3,4,7,8-PeCDF (14.6%). The body burden of log-transformed WHO(PCDD/F)-TEQ(2005) levels increased with age (B=0.02; 95% CI=0.01, 0.03; p=0.02). Although these adipose tissue PCDD/F levels are similar to previously published findings in Spain and other European countries, further research is needed to determine trends in the exposure of women to these chemical residues.

Air pollutant exposure during pregnancy and fetal and early childhood development: Research protocol of the INMA (Childhood and Environment Project)

INTRODUCTION The INMA (INfancia y Medio Ambiente [Spanish for Environment and Childhood]) project is a cooperative research network. This project aims to study the effects of environment and diet on fetal and early childhood development. This article aims to present the air pollutant exposure protocol during pregnancy and fetal and early childhood development of the INMA project. METHODS The information to assess air pollutant exposure during pregnancy is based on outdoor measurement of air pollutants (nitrogen dioxide [NO2], volatile organic compounds [VOC], ozone, particulate matter [PM10, PM2,5 ] and of their composition [polycyclic aromatic hydrocarbons]); measurement of indoor and personal exposure (VOC and NO2); urinary measurement of a biological marker of hydrocarbon exposure (1-hydroxypyrene); and data gathered by questionnaires and geographic information systems. These data allow individual air pollutant exposure indexes to be developed, which can then be used to analyze the possible effects of exposure on fetal development and child health. CONCLUSION This protocol and the type of study allow an approximation to individual air pollutant exposure to be obtained. Finally, the large number of participants (N = 4,000), as well as their geographic and social diversity, increases the studys potential.

Human Exposure to Endocrine Disrupting Chemicals: The Case of Bisphenols

Knowledge about human exposure to endocrine disrupters is expanding at a time when we are discovering new chemical compounds that can alter the hormonal balance. As the list of new endocrine disrupters lengthens, we are also identifying exposure pathways and how these substances enter the human organism. The present work is a review of the biological activity of bisphenols and of human exposure to them. Bisphenols are a group of chemical compounds that were initially designed as synthetic oestrogenic hormones and now form a part of innumerable manufactured products, such as epoxy resins and polycarbonates. The oestrogenicity of bisphenols was first documented in 1936, when they were already being used in the formation of synthetic polymers, and bisphenol-F was a base monomer in bakelite. Although bisphenols have been used for all of 90 years, account has only recently been taken of human exposure or potential consequential health risks. It can be affirmed that: i) ‘bisphenols’ is a broad term that includes various compounds that are structurally similar to bisphenol-A and are widely used in the chemical industry; ii) human exposure to bisphenols is a significant, demonstrated and increasing phenomenon; iii) the biological effects of bisphenols are well documented, fundamentally with respect to their oestrogenic activity. However, the causal relationship between endocrine disruption by bisphenols and human disease remains elusive and these uncertainties allow differing conclusions to be drawn. Nevertheless, it is clear that these chemicals are hormonally active, interfere in the homeostasis of the hormonal system, and may thus disrupt the endocrine system.

Association of light-to-moderate alcohol drinking in pregnancy with preterm birth and birth weight: elucidating bias by pooling data from nine European cohorts

Women who drink light-to-moderately during pregnancy have been observed to have lower risk of unfavourable pregnancy outcomes than abstainers. This has been suggested to be a result of bias. In a pooled sample, including 193 747 live-born singletons from nine European cohorts, we examined the associations between light-to-moderate drinking and preterm birth, birth weight, and small-for-gestational age in term born children (term SGA). To address potential sources of bias, we compared the associations from the total sample with a sub-sample restricted to first-time pregnant women who conceived within six months of trying, and examined whether the associations varied across calendar time. In the total sample, drinking up to around six drinks per week as compared to abstaining was associated with lower risk of preterm birth, whereas no significant associations were found for birth weight or term SGA. Drinking six or more drinks per week was associated with lower birth weight and higher risk of term SGA, but no increased risk of preterm birth. The analyses restricted to women without reproductive experience revealed similar results. Before 2000 approximately half of pregnant women drank alcohol. This decreased to 39% in 2000–2004, and 14% in 2005–2011. Before 2000, every additional drink was associated with reduced mean birth weight, whereas in 2005–2011, the mean birth weight increased with increasing intake. The period-specific associations between low-to-moderate drinking and birth weight, which also were observed for term SGA, are indicative of bias. It is impossible to distinguish if the bias is attributable to unmeasured confounding, which change over time or cohort heterogeneity.

La salud reproductiva del varón amenazada

Resumen Contexto Estamos asistiendo a un deteriora de la salud reproductiva de los jo-venes europeos. En muchos paises cerca del 20% de los jovenes pre-sentan parametras de calidad seminal por debajo de los estandares de referencia de la OMS, lo que probablemente afectara a su fertilidad. La ncidencia de cancer de testiculo sufre un incremento continuo y sign ifi-cativo desde hace 30 anos, igual que la prevalencia de malformaciones urogenitales como criptorquidia e hipospadias; ambas asociadas a una disminucion de la fertilidad y a un mayor riesgo de cancer testicular. El deteriora de la salud reproductiva tendra consecuencias graves sobre los indices de natalidad y una gran trascendencia social y economica. La demanda de tecnicas de reproduccion asistida, que ha crecido de forma alarmante y que es atribuida tanto a problemas de la mujer como del hombre, creara una desigualdad social importante por las dificultades de acceso a tecnicas medicas complejas y costosas. Desde el punto de vista sanitario, el deteriora de la salud reproductiva se presume asocia-do y puede contribuir al aumento de enfermedades cardiovasculares y metabolicas en el varon. De hecho, el reconocimiento de una asociacion entre los niveles de testosterona serica y obesidad abdominal, asi como la caida secular de los niveles de la hormona sexual masculina sugieren que el deterioro de salud reproductiva y el aumento de estos cuadros comparten patogenias comunes. Hipotesis Las tendencias temporales y la distribucion geografica en la distribu-cion de problemas de salud reproductiva sugieren que son los factores medioambientales y los habitos de vida, mas que las causas geneti-cas, responsables del cambio observado. La exposicion inadvertida de las embarazadas, en fases tempranas de su desarrollo embrionario, a sustancias quimicas contaminantes ambientales que alteran la homeostasis hormonal -disruptores endocrinos- se ha postulado como una hipotesis de trabajo digna de ser investigada en la genesis de las patologias observadas en la descendencia masculina. Aspectos tan controvertidos como el efecto combinado de diferentes residuos quimicos actuando a traves de un mecanismo comun y resultando en un efecto aditivo, sinergico o antagonico rara vez se han tenido en consideracion en toxicologia reguladora y, sin embargo, son de gran nteres para tipificar el efecto disruptor endocrino tras la exposicion materno-infantil. Conclusion Mientras se llevan a cabo mas investigaciones y se buscan nuevas fuen-tes de financiacion para hacerlas posible, seria recomendable optar por la prevencion informando a los responsables de la salud publica y a los sanitarios sobre las fuentes de exposicion y como disminuir la exposicion de la poblacion general y, muy especialmente, de las mujeres en edad de procrear, las gestantes y la infancia. Fuente de financiacion: No consta. Comentario El interes mostrado por la comunidad cientifica por esclarecer la realidad de la salud reproductiva en Europa y en otros paises occidentales, ha con-ducido a la redaccion de una serie de recomendaciones, propuestas por expertes en el campo, que sirvan de orientacion para politicas de financiacion de la investigacion. El debate sobre el deteriora de la salud reproductiva delvaron europeo ha llegado a su fin. Ya nadie duda de que tante los parametras de medida directa como los indicadores indirectes de la fertilidad masculina manifiestan ese dano. Lo que es realmente novedoso en la propuesta es, de una parte, la vinculacion entre el deteriora en salud reproductiva -incluida la caida secular en los niveles de testosterona circulante del varon-y el riesgode enfermedad cardiovascular y diabetes; de otra parte, la presentacion formal de una hipotesis etiologica que requiere la investigacion de la exposicion materno-infantil a contaminantes quimicos con actividad hormonal y sugiere una actitud precautoria. Los disruptores endocrinos son componentes de cosmeticos, detergentes, medicamentos y alimentes de consumo y uso diario. Mientras sesudos cientificos en toda Europa abordan este asunto tratando de fortalecer la hipotesis, ?que corresponde a los sanitarios y responsables de politicas de salud?, lo habituai, informarse e informar. Conocer y trasmitir de forma inteligible recomendaciones en habites de vida y exposiciones ambien-tales que sirvan para proteger a la poblacion general de un dano que se presume importante. Desafortunadamente las noticias sobre exposicion quimica ambiental llegan mas facilmente a las paginas de ciencia de los diarios nacionales que a las bibliotecas de los sanitarios. El mensaje no parece llegar a los foras adecuados ni en el momente oportuno. Los auto-res del articulo insisten en que el gasto en remedios terapeuticos costosos estaria mejor empleado en orientaciones preventivas. Somos de la opinion de que el coste de aplicar la cautela -el principio de prevencion- en la disminucion de exposiciones es socialmente y economicamente asumible; aun en el caso hipotetico de que no estuvieramos en lo cierto en lo referente a la restriccion en el uso de ciertos compuestos quimicos, adoptando una actitud precautoria tan solo habriamos renunciado a alguna como-didad o alguien habria dejado de ganar algun dinero. Pero si la hipotesis demuestra ser cierta y no actuamos, estaremos corriendo un riesgo con consecuencias que ahora empiezan a entreverse.