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Research Project

Impact of transplacental exposure to tobacco smoke in the DNA of newborn. Evaluation of genetic damage and epigenetic changes. Evolution throughout childhood.

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Publications

Cytotoxicity and DNA damage of a panel of manufactured nanomaterials in rat alveolar epithelial RLE-6TN cells
Publication . Brandão, Fátima; Fraga, Sónia; Costa, Carla; Bessa, Maria João; Haase, Andrea; Teixeira, João Paulo
Main goal: The aim of this study was to evaluate the cyto- and genotoxicity of a panel of MNMs, including SiO2 NPs, graphene oxide, and nano-sized pigments in rat alveolar epithelial cells (RLE-6TN), a primary target following inhalation exposure.
The impact of comet assay data normalization in human biomonitoring studies outcomes
Publication . Esteves, Filipa; Amaro, Raquel; Silva, Susana; Sánchez-Flores, María; Teixeira, João Paulo; Costa, Carla
The comet assay has been extensively used in biomonitoring studies. To avoid intra-experimental variability, the incorporation of assay controls in each work session for data normalization has been suggested by some authors but has never been thoroughly analyzed. The aim of this study was to address the impact of data normalization in the results of a biomonitoring study using different normalization models. Human peripheral blood mononuclear cells (PBMC) from 140 healthy individuals were analyzed using the alkaline and FPG-modified version of the comet assay across seven different work sessions. In addition to negative standards, methyl methanesulfonate (MMS) and Ro 19−8022 plus light treated PBMC, were also included in the assay as positive standards. To verify the impact of data normalization, some demographic, lifestyle and environmental exposure-related variables were selected. Significant associations with independent study variables were observed using normalized comet endpoints, as opposed to raw data. After normalization, levels of DNA strand breaks were significantly higher among males and older individuals (>71 years), while net FPG-sensitive sites were positively related to smoking habits and environmental exposures (i.e. air pollution and bottled water consumption). This study highlights how the normalization strategies can influence the statistical results of a human biomonitoring study and lead to different data interpretations.
Assessment of indoor air exposure at residential homes: Inhalation dose and lung deposition of PM10, PM2.5 and ultrafine particles among newborn children and their mothers
Publication . Madureira, Joana; Slezakova, Klara; Silva, Ana Inês; Lage, Bruna; Mendes, Ana; Aguiar, Lívia; Pereira, Maria Carmo; Teixeira, João Paulo; Costa, Carla
Accurate assessment of particulate matter (PM) dose and respiratory deposition is essential to better understand the risks of exposure to PM and, consequently, to develop the respective risk-control strategies. In homes, this is especially relevant in regards to ultrafine particles (UFP; <0.1 μm) which origin in these environments is mostly due to indoor sources. Thus, this study aimed to estimate inhalation doses for different PM mass/number size fractions (i.e., PM10, PM2.5 and UFP) in indoor air of residential homes and to quantify the deposition (total, regional and lobar) in human respiratory tract for both newborn children and mothers. Indoor real-time measurements of PM10, PM2.5 and UFP were conducted in 65 residential homes situated in Oporto metropolitan area (Portugal). Inhalation doses were estimated based on the physical characteristics of individual subjects and their activity patterns. The multi-path particle dosimetry model was used to quantify age-specific depositions in human respiratory tract. The results showed that 3-month old infants exhibited 4-fold higher inhalation doses than their mothers. PM10 were primarily deposited in the head region (87%), while PM2.5 and UFP depositions mainly occurred in the pulmonary area (39% and 43%, respectively). Subject age affected the pulmonary region and the total lung deposition; higher deposition being observed among the newborns. Similarly, lower lobes (left lobe: 37% and right lobe: 30%) received higher PM deposition than upper and middle lobes; right lobes lung are prone to be more susceptible to respiratory problems, since asymmetric deposition was observed. Considering that PM-related diseases occur at specific sites of respiratory system, quantification of site-specific particle deposition should be predicted in order to better evidence the respective health outcomes resulting from inhaled PM.
Urinary cotinine assessment of maternal smoking and environmental tobacco smoke exposure status and its associations with perinatal outcomes: a cross-sectional birth study
Publication . Silva, Ana Inês; Camelo, Alexandra; Madureira, Joana; Reis, Ana Teresa; Machado, Ana Paula; Teixeira, João Paulo; Costa, Carla
Abstract: Tobacco consumption and environmental tobacco smoke (ETS) exposure remains an important public health concern. Pregnant women require particular attention as active and passive smoking during pregnancy are associated with multiple adverse perinatal outcomes. This study aimed to biochemically validate self-reported smoking and ETS exposure status among pregnant women, to more precisely ascertain its association with adverse perinatal outcomes. Data refers to 595 pregnant women who sought prenatal care in a public hospital in Porto, Portugal. A standard questionnaire on smoking and ETS-related variables was completed. Urinary cotinine (UC) concentrations were assessed by solid-phase competitive ELISA, in maternal urine samples collected on the day of delivery. The results showed that the optimal UC cut-off value to distinguish smokers from non-smokers and within non-smokers those who were exposed to ETS from those non-exposed in the third trimester of pregnancy was 74.1 ng/mL (sensitivity and specificity of 96.7% and 98.0%, respectively) and 1.6 ng/mL (sensitivity of 66.2% and specificity of 75.7%, respectively). The agreement between maternal self-reported and UC-based smoking status was very good (κ=0.919, p<0.001), but much lower for ETS exposure (κ=0.386, p<0.001). Maternal active smoking in the third trimester of pregnancy was associated with a significant decrease in birth weight, length and head circumference of 157.66 g (95% CI: −245.81, −69.52; p<0.001), 0.78 cm (95% CI: −1.22, −0.34; p=0.001) and 0.39 cm (95% CI: −0.70, −0.07; p=0.016), respectively. Maternal ETS exposure in the third trimester of pregnancy was associated with a non-significant increase in birth weight of 38.37 g (95% CI: −28.91, 105.64; p=0.263). Furthermore, maternal smoking cessation was associated with the increase of approximately 172 g in birth weight (95% CI: 50.00, 293.19). As such, there is an urgent need for increased public health awareness campaigns to encourage smoking cessation during pregnancy, in order to improve perinatal outcomes.
From trihalomethanes chronic daily intake through multiple exposure routes to cancer and non-cancer health risk assessment: Evidence from public Portuguese indoor swimming pools facilities using a probabilistic approach
Publication . Costa, Carla; Assunção, Ricardo; Sequeira, Diana; Esteves, Filipa; Valdiglesias, Vanessa; Laffon, Blanca; Teixeira, João Paulo; Madureira, Joana
This study aimed to estimate chronic daily intake (CDI) and to predict the attributable lifetime cancer risk (LCR) and hazard index (HI) from concurrent exposure to four trihalomethanes (THMs; chloroform, bromodichloromethane, dibromochloromethane and bromoform), via multiple exposure routes (oral ingestion, dermal contact and inhalation), among 238 non-competitive attendees of 10 Portuguese public indoor swimming pools (SPs), using a probabilistic approach based on Monte Carlo simulations. Exposure parameters of study participants were collected via questionnaires and THMs levels in SPs water were determined according the respective normative standards. The CDI for total THMs calculated for male and female participants considering all routes was 7.52 and 8.97 mg/kg/day, respectively. SP attendees presented higher CDI through inhalation than via the other two exposure routes, and chloroform was the compound contributing the most to total THMs CDI. The risk analysis indicated that the total LCR and HI from the targeted THMs were higher than the negligible risk levels (1 × 10-6 and 1, respectively) in the scenarios examined (central tendency exposure and reasonable maximum exposure), and the health risk for females was slightly higher than for males. This study suggests that there are possible adverse health risks, thus, to protect pool attendees, adequate mitigation measures, and comprehensive regulatory guidelines on individual THMs concentrations are needed.

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Funding agency

Fundação para a Ciência e a Tecnologia

Funding programme

Funding Award Number

SFRH/BPD/96196/2013

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