Laboratory of Environmental Toxicology
Laboratory of Environmental Toxicology
Gascon M.,Center for Research in Environmental Epidemiology |
Gascon M.,CIBER ISCIII |
Gascon M.,IMIM Hospital Del Mar Medical Research Institute |
Gascon M.,University Pompeu Fabra |
And 43 more authors.
Epidemiology | Year: 2014
BACKGROUND: Persistent organic pollutants may affect the immune and respiratory systems, but available evidence is based on small study populations. We studied the association between prenatal exposure to dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyl 153 (PCB 153) and children's respiratory health in European birth cohorts. METHODS: We included 4608 mothers and children enrolled in 10 birth cohort studies from 7 European countries. Outcomes were parent-reported bronchitis and wheeze in the first 4 years of life. For each cohort, we performed Poisson regression analyses, modeling occurrences of the outcomes on the estimates of cord-serum concentrations of PCB 153 and DDE as continuous variables (per doubling exposure) and as cohort-specific tertiles. Summary estimates were obtained through random-effects meta-analyses. RESULTS: The risk of bronchitis or wheeze (combined variable) assessed before 18 months of age increased with increasing DDE exposure (relative risk [RR] per doubling exposure = 1.03 [95% confidence interval = 1.00-1.07]). When these outcomes were analyzed separately, associations appeared stronger for bronchitis. We also found an association between increasing PCB 153 exposure and bronchitis in this period (RR per doubling exposure = 1.06 [1.01-1.12]) but not between PCB 153 and wheeze. No associations were found between either DDE or PCB 153 and ever-wheeze assessed after 18 months. Inclusion of both compounds in the models attenuated risk estimates for PCB 153 tertiles of exposure, whereas DDE associations were more robust. CONCLUSION: This large meta-analysis suggests that prenatal DDE exposure may be associated with respiratory health symptoms in young children (below 18 months), whereas prenatal PCB 153 levels were not associated with such symptoms. Copyright © 2014 by Lippincott Williams & Wilkins.
Mello M.S.C.,Laboratory of Environmental Toxicology |
Mello M.S.C.,Federal University of Rio de Janeiro |
Delgado I.F.,National Institute of Health Quality Control |
Favareto A.P.A.,São Paulo State University |
And 4 more authors.
Toxicology Reports | Year: 2014
This study investigated the effects of pre- and peripubertal exposure (PND 15-45) to triphenyltin hydroxide (TPT: 0, 1.875, 3.75, 7.5 and 15. mg/kg bw/d po) on mouse sexual maturation and fertility. Half of the mice were euthanized on PND 46 and the remaining mice were submitted to fertility tests on PND 65-75. TPT caused a transient decrease of weight gain at 3.75. mg/kg bw/d, and deaths and body weight deficits at higher doses. Delays of testes descent (TD), vaginal opening (VO) and first estrus (FE) occurred at doses ≥3.75 (TD) and ≥7.5. mg/kg bw/d (VO, FE), respectively. Body weight on the days of TD, VO and FE did not differ among groups. TPT at doses ≥3.75. mg/kg decreased sperm and spermatid counts at the end of treatment (PND 46) but no alteration was noted later on PND 75. Testicular histopathology (PND 46) showed a dose-dependent reduction of seminiferous tubules diameter, a greater degree of vacuolation in Sertoli cells and germ cell degeneration and necrosis in TPT-treated mice. TPT did not affect the outcome of fertility tests. Study-derived NOAEL was 1.875. mg TPT/kg bw/d for males and 3.75. mg TPT/kg bw/d for females. The detrimental effects of TPT on spermatogenesis were reversed after treatment discontinuation. © 2014 The Authors.
Friedrich K.,Laboratory of Environmental Toxicology |
Vieira F.A.,Laboratory of Environmental Toxicology |
Vieira F.A.,Pontifical Catholic University of Rio de Janeiro |
Porrozzi R.,Oswaldo Cruz Institute |
And 4 more authors.
Journal of Toxicology and Environmental Health - Part A: Current Issues | Year: 2012
Antimony (Sb) disposition and toxicity was evaluated in Leishmania braziliensis-infected monkeys (Macaca mulatta) treated with a 21-d course of low (LOW) or standard (STD) meglumine antimoniate (MA) dosage regimens (5 or 20 mg Sb V/kg body weight/d im). Antimony levels in biological matrices were determined by inductively coupled plasma mass spectrometry (ICPMS), while on-line ion chromatography coupled to ICPMS was used to separate and quantify Sb species in plasma. Nadir Sb levels rose steadily from 19.6 ± 4 and 65.1 ± 17.4 ng/g, 24 h after the first injection, up to 27.4 ± 5.8 and 95.7 ± 6.6 ng/g, 24 h after the 21st dose in LOW and SDT groups, respectively. Subsequently, Sb plasma levels gradually declined with a terminal elimination phase half-life of 35.8 d. Antimony speciation in plasma on posttreatment days 1-9 indicated that as total Sb levels declined, proportion of Sb V remained nearly constant (11-20%), while proportion of Sb III rose from 5% (d 1) to 50% (d 9). Plasma [Sb]/erythrocyte [Sb] ratio was >1 until 12 h after dosing and reversed thereafter. Tissue Sb concentrations (posttreatment days 55 and 95) were as follows: >1000 ng/g in thyroid, nails, liver, gall bladder and spleen; >200 and <1000 ng/g in lymph nodes, kidneys, adrenals, bones, skeletal muscles, heart and skin; and <200 ng/g in various brain structures, thymus, stomach, colon, pancreas. and teeth. Results from this study are therefore consistent with view that Sb V is reduced to Sb III, the active form, within cells from where it is slowly eliminated. Localization of Sb active forms in the thyroid gland and liver and the pathophysiological consequences of marked Sb accumulation in these tissues warrant further studies. © 2012 Copyright Taylor and Francis Group, LLC.
Oliveira-Filho E.C.,Laboratory of Environmental Toxicology |
Oliveira-Filho E.C.,Laboratory of Ecotoxicology |
Geraldino B.R.,Laboratory of Environmental Toxicology |
Coelho D.R.,Laboratory of Environmental Toxicology |
And 2 more authors.
Chemosphere | Year: 2010
Plant molluscicides have been regarded as possible alternatives to the costly and environmentally hazardous molluscicides currently available. This study was undertaken to compare the developmental toxicity of a plant molluscicide (Euphorbia milii latex, LAT) with that of three synthetic molluscicidal compounds. Biomphalaria glabrata egg masses (0-15h after spawning) were exposed to molluscicides for 96h and thereafter examined up to the 14th day after spawning. Embryo deaths, abnormal embryo development (malformations) and the day of hatching were recorded. Although exhibiting a weak ovicidal effect, LAT markedly impaired the development of snail embryos at concentrations ≥1000μgL-1 and produced anomalies (EC50=2040μgL-1) such as abnormal shells, hydropic embryos, cephalic and non-specific malformations. Embryolethal potencies of molluscicides were as follows: triphenyltin hydroxide (TPTH; LC50=0.30μgL-1)>niclosamide (NCL; LC50=70μgL-1)>copper sulphate (CuSO4; LC50=2190μgL-1) ⋙ LAT (LC50=34030μgL-1). A few malformations were recorded in embryos exposed to concentrations of TPTH within the range of lethal concentrations, while almost no anomalies were noted among those treated with NCL or CuSO4. A hatching delay (hatching on day 10 after spawning or later) was observed among LAT-exposed embryos. The effects of NCL, TPTH and CuSO4 on hatching were to some extent masked by their marked embryolethality. The no-observed effect concentrations (NOEC) for embryotoxicity were as follows: TPTH, 0.1μgL-1; NCL, 25.0μgL-1; CuSO4, 500.0μgL-1 and LAT, 500.0μgL-1. Results from this study suggest that, although LAT was not acutely embryolethal after a short-term exposure, it markedly disrupted snail development. The marked embryotoxicity of E. milii possibly contributes to its effectiveness as a molluscicide. © 2010 Elsevier Ltd.
Sarpa M.,Laboratory of Environmental Toxicology |
Lopes C.M.T.,Oswaldo Cruz Foundation |
Delgado I.F.,Oswaldo Cruz Foundation |
Paumgartten F.J.R.,Laboratory of Environmental Toxicology
Journal of Toxicology and Environmental Health - Part A: Current Issues | Year: 2010
Fentin or triphenylthin (TPT) is an organotin compound (OTC) widely used as an agricultural fungicide and miticide. It is well known that TPT exerts adverse effects on the reproductive and immune systems and may disrupt the endocrine system, raising concerns regarding the risks posed by exposure to this metal on environmental and human health. In this study the effects of maternal exposure to TPT at doses of control (0), 1.875, 3.75, or 7.5 mg/kg body weight/d, po, were examined during gestation and lactation on offspring growth, organ weights, and fertility. Except for a significant liver enlargement at the highest dose, TPT produced no maternal toxicity. Increased neonatal mortality (death of 3 entire litters from a total of 18 treated litters) was noted at 7.5 mg/kg. Pup body weight at birth was significantly reduced at all dose levels, but no marked weight loss was found on postnatal day (PND) 5 and thereafter. Offspring maturation (ear unfolding, incisor eruption, vagina opening, and testes descent) and fertility in adulthood were not significantly affected by maternal exposure to TPT. In conclusion, data provided by this study indicate that maternal treatment with TPT during pregnancy and lactation delayed prenatal growth but did not impair postnatal development and fertility in exposed offspring in adulthood. © 2010 Taylor & Francis Group, LLC.
Osornio-Vargas A.,University of Alberta |
Quintana-Belmares R.,Laboratory of Environmental Toxicology |
Meng Q.,Center for Global Public Health |
Kirn T.J.,New Brunswick Laboratory |
And 4 more authors.
Infection and Immunity | Year: 2015
Inhalation exposure to indoor air pollutants and cigarette smoke increases the risk of developing tuberculosis (TB). Whether exposure to ambient air pollution particulate matter (PM) alters protective human host immune responses against Mycobacterium tuberculosis has been little studied. Here, we examined the effect of PM from Iztapalapa, a municipality of Mexico City, with aerodynamic diameters below 2.5 μm(PM2.5) and 10 μm(PM10) on innate antimycobacterial immune responses in human alveolar type II epithelial cells of the A549 cell line. Exposure to PM2.5 or PM10 deregulated the ability of the A549 cells to express the antimicrobial peptides human β-defensin 2 (HBD-2) and HBD-3 upon infection with M. tuberculosis and increased intracellular M. tuberculosis growth (as measured by CFU count). The observed modulation of antibacterial responsiveness by PM exposure was associated with the induction of senescence in PM-exposed A549 cells and was unrelated to PM-mediated loss of cell viability. Thus, the induction of senescence and downregulation of HBD-2 and HBD-3 expression in respiratory PM-exposed epithelial cells leading to enhanced M. tuberculosis growth represent mechanisms by which exposure to air pollution PM may increase the risk of M. tuberculosis infection and the development of TB. © 2015, American Society for Microbiology.
De-Oliveira A.C.A.,Laboratory of Environmental Toxicology |
Carvalho R.S.,Laboratory of Environmental Toxicology |
Paixo F.H.,Laboratory of Environmental Toxicology |
Tavares H.S.,Laboratory of Environmental Toxicology |
And 3 more authors.
Malaria Journal | Year: 2010
Background. The mechanisms by which malaria up and down-regulates CYP activities are not understood yet. It is also unclear whether CYP activities are modulated during non-lethal malaria infections. This study was undertaken to evaluate the time course of CYP alterations in lethal (Plasmodium berghei ANKA) and non-lethal (Plasmodium chabaudi chabaudi) murine malaria. Additionally, hypotheses on the association of CYP depression with enhanced nitric oxide (NO) production, and of CYP2a5 induction with endoplasmic reticulum dysfunction, enhanced haem metabolism and oxidative stress were examined as well. Methods. Female DBA-2 and C57BL/6 mice were infected with P.berghei ANKA or P. chabaudi and killed at different post-infection days. Infection was monitored by parasitaemia rates and clinical signs. NO levels were measured in the serum. Activities of CYP1a (ethoxyresorufin-O-deethylase), 2b (benzyloxyresorufin-O- debenzylase), 2a5 (coumarin-7-hydroxylase) and uridine-diphosphoglucuronyl- transferase (UGT) were determined in liver microsomes. Glutathione-S-transferase (GST) activity and concentrations of gluthatione (GSH) and thiobarbituric acid-reactive substances (TBARS) were determined in the liver. Levels of glucose-regulated protein 78 (GRP78) were evaluated by immunoblotting, while mRNAs of haemoxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS) were determined by quantitative RT-PCR. Results. Plasmodium berghei depressed CYP1a and 2b and induced 2a5 in DBA-2 mice. In P.berghei-infected C57BL/6 mice CYP activities remained unaltered. In both strains, GST and UGT were not affected by P.berghei. Plasmodium c. chabaudi depressed CYP1a and 2b and induced 2a5 activities on the day of peak parasitaemia or near this day. CYP2a5 induction was associated with over-expression of HO-1 and enhanced oxidative stress, but it was not associated with GRP78 induction, a marker of endoplasmic reticulum stress. Plasmodium chabaudi increased serum NO on days near the parasitaemia peak in both strains. Although not elevating serum NO, P.berghei enhanced iNOS mRNA expression in the liver. Conclusion. Down-regulation of CYP1a and 2b and induction of 2a5 occurred in lethal and non-lethal infections when parasitaemia rates were high. A contribution of NO for depression of CYP2b cannot be ruled out. Results were consistent with the view that CYP2a5 and HO-1 are concurrently up-regulated and suggested that CYP2a5 induction may occur in the absence of enhanced endoplasmic reticulum stress. © 2010 De-Oliveira et al.
PubMed | University of California at San Diego, Salk Institute for Biological Studies, University of California at Davis and Laboratory of Environmental Toxicology
Type: Journal Article | Journal: Proceedings of the National Academy of Sciences of the United States of America | Year: 2014
Triclosan [5-chloro-2-(2,4-dichlorophenoxy)phenol; TCS] is a synthetic, broad-spectrum antibacterial chemical used in a wide range of consumer products including soaps, cosmetics, therapeutics, and plastics. The general population is exposed to TCS because of its prevalence in a variety of daily care products as well as through waterborne contamination. TCS is linked to a multitude of health and environmental effects, ranging from endocrine disruption and impaired muscle contraction to effects on aquatic ecosystems. We discovered that TCS was capable of stimulating liver cell proliferation and fibrotic responses, accompanied by signs of oxidative stress. Through a reporter screening assay with an array of nuclear xenobiotic receptors (XenoRs), we found that TCS activates the nuclear receptor constitutive androstane receptor (CAR) and, contrary to previous reports, has no significant effect on mouse peroxisome proliferation activating receptor (PPAR). Using the procarcinogen diethylnitrosamine (DEN) to initiate tumorigenesis in mice, we discovered that TCS substantially accelerates hepatocellular carcinoma (HCC) development, acting as a liver tumor promoter. TCS-treated mice exhibited a large increase in tumor multiplicity, size, and incidence compared with control mice. TCS-mediated liver regeneration and fibrosis preceded HCC development and may constitute the primary tumor-promoting mechanism through which TCS acts. These findings strongly suggest there are adverse health effects in mice with long-term TCS exposure, especially on enhancing liver fibrogenesis and tumorigenesis, and the relevance of TCS liver toxicity to humans should be evaluated.
PubMed | Center for Global Public Health, Laboratory of Environmental Toxicology, University of Alberta, Desert Research Institute and 2 more.
Type: Journal Article | Journal: Infection and immunity | Year: 2015
Inhalation exposure to indoor air pollutants and cigarette smoke increases the risk of developing tuberculosis (TB). Whether exposure to ambient air pollution particulate matter (PM) alters protective human host immune responses against Mycobacterium tuberculosis has been little studied. Here, we examined the effect of PM from Iztapalapa, a municipality of Mexico City, with aerodynamic diameters below 2.5 m (PM2.5) and 10 m (PM10) on innate antimycobacterial immune responses in human alveolar type II epithelial cells of the A549 cell line. Exposure to PM2.5 or PM10 deregulated the ability of the A549 cells to express the antimicrobial peptides human -defensin 2 (HBD-2) and HBD-3 upon infection with M. tuberculosis and increased intracellular M. tuberculosis growth (as measured by CFU count). The observed modulation of antibacterial responsiveness by PM exposure was associated with the induction of senescence in PM-exposed A549 cells and was unrelated to PM-mediated loss of cell viability. Thus, the induction of senescence and downregulation of HBD-2 and HBD-3 expression in respiratory PM-exposed epithelial cells leading to enhanced M. tuberculosis growth represent mechanisms by which exposure to air pollution PM may increase the risk of M. tuberculosis infection and the development of TB.