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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.,Sao 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. Source

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. Source

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. Source

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. Source

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. Source

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