Paumgartten F.J.R.,Laboratorio Of Toxicologia Ambiental
Journal of Toxicology and Environmental Health - Part A: Current Issues | Year: 2010
The relevance of fetal abnormalities noted at maternally toxic doses is a long-standing issue regarding the interpretation of findings of segment II studies. A number of diseases and conditions during pregnancy are known to adversely affect embryo/fetal development, and along this line many scientists believe that any marked disturbance of maternal homeostasis produced by chemical exposure may eventually produce a teratogenic effect. Although there is little doubt that developmental toxicity may be maternally mediated, the notion that, in principle, any maternal toxicity leads to birth defects is disputed. When embryotoxicity is noted only within the maternally toxic dose range, it is not possible to ascertain whether it is in fact maternally mediated or not (i.e., embryo development may have been impaired by a direct action of the chemical at doses that also adversely affect the mother; in these circumstances it would still be a selective developmental toxicant). However, currently, a chemical is not regarded as a "developmental toxicant" (or "teratogenic agent") if embryotoxicity is apparent only at doses that are also toxic to the mother. In the European Union, developmental hazard identification exerts a strong influence on the classification and labeling of chemicals. In Brazil, registration of any pesticide that proved to be teratogenic in animal studies is strictly forbidden by law (Pesticide Law, Federal Law 7.802, 1989). Therefore, interpretation of findings from developmental toxicity studies in light of maternal toxicity is particularly relevant to regulatory agencies, and becomes even more important when labeling or cutoff decision-making criteria are adopted regarding teratogenicity. © 2010 Taylor & Francis Group, LLC.
Clinical use and control of the dispensing of thalidomide in Brasilia-Federal District, Brazil, from 2001 to 2012 [Uso clínico e controle sobre a dispensação de talidomida em Brasília-DF, Brasil, de 2001 a 2012]
Paumgartten F.J.R.,Laboratorio Of Toxicologia Ambiental |
de Souza N.R.,Laboratorio Of Toxicologia Ambiental
Ciencia e Saude Coletiva | Year: 2013
The use of thalidomide was never discontinued in Brazil where it is prescribed for leprosy type 2 reaction. Babies with birth defects compatible with the thalidomide embryopathy phenotype were born after 1965, an indication that control on drug dispensing and use failed in the country. The article reports data on thalidomide dispensing and clinical uses in the Federal District in 2011/12, when new rules were put into effect, and data on drug dispensing and use obtained ten years earlier. It was found that the number of patients making use of thalidomide declined from 819 in 2001 to 369 in 2011/12. Leprosy accounted for over 70% of prescriptions in both time periods analyzed in this study. In the same time interval, however, use for lupus erythematosus decreased from 13.7 to 4.9%, while that for multiple myeloma increased from 2.9 to 20.3% of all prescriptions. Thalidomide prescription for the remaining approved indications was far less frequent, and so was the use for off label indications that accounted for <1% of prescriptions in 2001 and 2011/12. Registration of prescribing doctors, patients and dispensing units at the state department of health, apparently rendered this control more effective and reliable.
Moreira D.A.,Laboratorio Of Toxicologia Ambiental |
Furtado C.,Instituto Nacional do Cancer INCA |
Parente T.E.,Laboratorio Of Toxicologia Ambiental
Gene | Year: 2015
Mitochondrial genes and genomes have long been applied in phylogenetics. Current protocols to sequence mitochondrial genomes rely almost exclusively on long range PCR or on the direct sequencing. While long range PCR includes unnecessary biases, the purification of mtDNA for direct sequencing is not straightforward. We used total RNA extracted from liver and Illumina HiSeq technology to sequence mitochondrial transcripts from three fish (Ancistrus spp.) and assemble their mitogenomes. Based on the mtDNA sequence of a close related species, we estimate to have sequenced 92%, 95% and 99% of the mitogenomes. Taken the sequences together, we sequenced all the 13 protein-coding genes, two ribosomal RNAs, 22 tRNAs and the D-loop known in vertebrate mitogenomes. The use of transcriptomic data allowed the observation of the punctuation pattern of mtRNA maturation, to analyze the transcriptional profile, and to detect heteroplasmic sites. The assembly of mtDNA from transcriptomic data is complementary to other approaches and overcomes some limitations of traditional strategies for sequencing mitogenomes. Moreover, this approach is faster than traditional methods and allows a clear identification of genes, in particular for tRNAs and rRNAs. © 2015 Elsevier B.V.
Najera-Martinez M.,Laboratorio Of Toxicologia Ambiental |
Garcia-Latorre E.A.,Laboratorio Of Inmunoquimica I |
Reyes-Maldonado E.,National Polytechnic Institute of Mexico |
Dominguez-Lopez M.L.,Laboratorio Of Inmunoquimica I |
Vega-Lopez A.,Laboratorio Of Toxicologia Ambiental
Inhalation Toxicology | Year: 2012
Halomethanes (HMs) can be formed during the chlorination process to obtain drinking water. In liver cells, HMs had been shown to be mutagenic and carcinogenic; however, their bioactivation by CYP 2E1 and GSTT1 is required. Although inhalation is the most common pathway of exposure, reports on the toxic effects induced by HMs in human lung are contradictory. The aim of this study was therefore to evaluate in vitro cytotoxicity and cell proliferation induced by CH2Cl2, CHCl3 and BrCHCl2 in human lung NL20-TA epithelial cells and MRC-5 fibroblasts, and their relationship with CYP 2E1 and GSTT1 activity. High concentrations of these HMs induced cytotoxicity, particularly in cells treated with BrCHCl2. Low concentrations of BrCHCl2 stimulated hyperproliferation of fibroblasts, the most probable consequence of which is regenerative proliferation related to collagen induction. Fibroblasts exposed to BrCHCl2 exhibited low levels of CYP 2E1 activity suggesting that released bromine is able to alter this activity by affecting the active site or auto regulating the activity itself. GSTT1 was up to ten times more active than CYP 2E1 in both cell lines, indicating that potential lung damage is due to formation of pro-carcinogens such as formaldehyde. © 2012 Informa Healthcare USA, Inc.
Gomez-Olivan L.M.,Laboratorio Of Toxicologia Ambiental |
Gomez-Olivan L.M.,National Autonomous University of Mexico |
Neri-Cruz N.,Laboratorio Of Toxicologia Ambiental |
Galar-Martinez M.,Laboratorio Of Toxicologia Acuatica |
And 5 more authors.
Water, Air, and Soil Pollution | Year: 2012
Paracetamol is an antipyretic analgesic widely used globally. It has been recurrently found in water bodies and is known to elicit toxic effects in aquatic species; however, its potential ability to induce oxidative stress in sentinel species remains unknown The objective was to establish a methodology to evaluate the toxicity elicited on the sentinel species Hyalella azteca by paracetamol-enriched sediment using oxidative stress tests. Concentrations used in assays were determined using the previously obtained median lethal concentration (72 h LC 50). The following oxidative stress biomarkers were evaluated: lipid peroxidation (LPO), protein carbonyl content (PCC) in order to determine oxidized protein content, and the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). LPO and PCC increased significantly while SOD, CAT, and GPX decreased significantly (p<0.05) with respect to controls. Paracetamol induces oxidative stress on H. azteca, and the set of tests employed is helpful in evaluating the toxicity of this group of pharmaceuticals on aquatic species. © Springer Science+Business Media B.V. 2012.