Pub Date : 2009-03-19DOI: 10.2174/1874340400903010024
M. Chaudhary, Anupama Tamta, R. Sehgal
The present study investigated safety/toxicity profile of fixed dose combination of Ofloxacin-Ornidazole injec- tion in Mus musculus mice at three dose levels, ranging from asymptomatic to high dose. To enhance the antimicrobial spectrum of the quinolones against anaerobic organisms and gram positive bacteria, fixed dose combination of Ofloxacin and Ornidazole injection was introduced. It has been found highly effective as well as synergistic and has the potential of usage for empirical therapy because of extended spectrum. A 30 days repeat dose subchronic toxicity study was con- ducted on mice (male and female). Various physiological, hematological and biochemical parameters were studied. There were no signs of toxicity observed at any dose level used in this study. No mortality was seen in any of the treatment groups. Hematological as well as physiological parameters were unaltered at three dose levels in Ofloxacin-Ornidazole treatment groups. Results suggest that the fixed dose combination of Ofloxacin-Ornidazole injection is non toxic even at maximum dose level.
{"title":"Sub-Chronic Toxicity Study of Fixed Dose Combination of Ofloxacin- Ornidazole in Mus Musculus Mice","authors":"M. Chaudhary, Anupama Tamta, R. Sehgal","doi":"10.2174/1874340400903010024","DOIUrl":"https://doi.org/10.2174/1874340400903010024","url":null,"abstract":"The present study investigated safety/toxicity profile of fixed dose combination of Ofloxacin-Ornidazole injec- tion in Mus musculus mice at three dose levels, ranging from asymptomatic to high dose. To enhance the antimicrobial spectrum of the quinolones against anaerobic organisms and gram positive bacteria, fixed dose combination of Ofloxacin and Ornidazole injection was introduced. It has been found highly effective as well as synergistic and has the potential of usage for empirical therapy because of extended spectrum. A 30 days repeat dose subchronic toxicity study was con- ducted on mice (male and female). Various physiological, hematological and biochemical parameters were studied. There were no signs of toxicity observed at any dose level used in this study. No mortality was seen in any of the treatment groups. Hematological as well as physiological parameters were unaltered at three dose levels in Ofloxacin-Ornidazole treatment groups. Results suggest that the fixed dose combination of Ofloxacin-Ornidazole injection is non toxic even at maximum dose level.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"17 1","pages":"24-29"},"PeriodicalIF":0.0,"publicationDate":"2009-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88153802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-03-13DOI: 10.2174/1874340400903010016
R. Hokanson, R. Chowdhary, D. Busbee
Many natural and synthetic compounds, including a variety of the chemicals used as plasticizers or in the pro- duction of cosmetics and therapeutics, have steroid agonist or antagonist activities, altering hormone-regulated gene ex- pression. The phthalate (diethylphthalate, extensively used as a plasticizer and in consumer products, are evaluated using the human renal epithelial cell line 293T/17. Emphasis of the study was on genes essential for central nervous system de- velopment or function. Cells were treated with 1, 10 or 100 μM phthalate and gene expression was measured in treated cells, showing significant up- or down-regulation of a large number of genes in treated compared to untreated cells. Of the 19,000 human genes on the DNA array chip utilized, two specific genes, FGD1 and NGPF2, were selected to corroborate mRNA levels using quantitative real time PCR (qrtPCR) data to confirm results obtained from the microarray determina- tions. FGD1 (faciogenital dysplasia) and NGPF2 (neurite growth-promoting factor 2, also called Midkine, MDK), showed a significant, possibly estrogen-synergistic, down-regulation of genes essential for fetal brain development. These studies were designed to provide data on the gene expression-altering capacity of a widely distributed chemical, diethylphthalate (DEP), and to show possible associations between the previously reported widespread presence of DEP and the DEP me- tabolite, MEP, in urine samples from a reference population, the potential for altered gene expression in human cells in vi- tro, and possible neurodevelopmental effects that could be correlated with in utero exposure to DEP.
{"title":"Diethylphthalate, Possible Interactions in Fetal Brain Development","authors":"R. Hokanson, R. Chowdhary, D. Busbee","doi":"10.2174/1874340400903010016","DOIUrl":"https://doi.org/10.2174/1874340400903010016","url":null,"abstract":"Many natural and synthetic compounds, including a variety of the chemicals used as plasticizers or in the pro- duction of cosmetics and therapeutics, have steroid agonist or antagonist activities, altering hormone-regulated gene ex- pression. The phthalate (diethylphthalate, extensively used as a plasticizer and in consumer products, are evaluated using the human renal epithelial cell line 293T/17. Emphasis of the study was on genes essential for central nervous system de- velopment or function. Cells were treated with 1, 10 or 100 μM phthalate and gene expression was measured in treated cells, showing significant up- or down-regulation of a large number of genes in treated compared to untreated cells. Of the 19,000 human genes on the DNA array chip utilized, two specific genes, FGD1 and NGPF2, were selected to corroborate mRNA levels using quantitative real time PCR (qrtPCR) data to confirm results obtained from the microarray determina- tions. FGD1 (faciogenital dysplasia) and NGPF2 (neurite growth-promoting factor 2, also called Midkine, MDK), showed a significant, possibly estrogen-synergistic, down-regulation of genes essential for fetal brain development. These studies were designed to provide data on the gene expression-altering capacity of a widely distributed chemical, diethylphthalate (DEP), and to show possible associations between the previously reported widespread presence of DEP and the DEP me- tabolite, MEP, in urine samples from a reference population, the potential for altered gene expression in human cells in vi- tro, and possible neurodevelopmental effects that could be correlated with in utero exposure to DEP.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"50 1","pages":"16-23"},"PeriodicalIF":0.0,"publicationDate":"2009-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74240604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-03-08DOI: 10.2174/1874340400903010008
Kimberly J. Swanson, N. Kado, William E. Funk, J. Pleil, M. Madden, A. Ghio
Biodiesel, an alkyl ester of plant oils that can be used in an unmodified diesel engine, is the first renewable die- sel fuel alternative to become a commercially accepted part of our nation's energy infrastructure. For traditional diesel fuel exhaust, it has been demonstrated that the particulate matter (PM) organic components play a role in acute inflamma- tory reactions. However, there have been only a few cytotoxicity and mutagenicity studies on biodiesel emissions. In this study, BEAS-2B cells, a transformed human airway epithelial cell line, were exposed in vitro to the PM organic extracts from Standard Reference Material (SRM) 1975, soy ethyl ester (SEE), soy methyl ester (SME), and petroleum diesel for 24 hours. This study demonstrated that the organic extracts of biodiesel PM in an aqueous solution can increase the re- lease of pro-inflammatory cytokines IL-8 and IL-6 by respiratory epithelial cells. On a microgram PM equivalent per ml (μg PM eq/ml) basis, exposure to biodiesel extracts was associated with a greater release of IL-8 and IL-6 relative to or- ganic extracts of two diesel PM samples. The dose range tested was not cytotoxic. It was also noted that the solvent ex- change method, which was used to prepare the aqueous exposure doses, may not be appropriate for the investigation of biodiesel extracts, though it has been used extensively in petroleum diesel research. A valuable new finding from these experiments is that the soluble organic fraction (SOF) of biodiesel PM begins to elicit a cytokine response in BEAS-2B cells at an exposure lower than petroleum diesel PM extract (approximately 40 μg PM eq/ml). However, more research is required to better characterize the potency of the organic fraction of biodiesel compared to petroleum diesel.
{"title":"Release of the Pro-Inflammatory Markers by BEAS-2B Cells Following In Vitro Exposure to Biodiesel Extracts","authors":"Kimberly J. Swanson, N. Kado, William E. Funk, J. Pleil, M. Madden, A. Ghio","doi":"10.2174/1874340400903010008","DOIUrl":"https://doi.org/10.2174/1874340400903010008","url":null,"abstract":"Biodiesel, an alkyl ester of plant oils that can be used in an unmodified diesel engine, is the first renewable die- sel fuel alternative to become a commercially accepted part of our nation's energy infrastructure. For traditional diesel fuel exhaust, it has been demonstrated that the particulate matter (PM) organic components play a role in acute inflamma- tory reactions. However, there have been only a few cytotoxicity and mutagenicity studies on biodiesel emissions. In this study, BEAS-2B cells, a transformed human airway epithelial cell line, were exposed in vitro to the PM organic extracts from Standard Reference Material (SRM) 1975, soy ethyl ester (SEE), soy methyl ester (SME), and petroleum diesel for 24 hours. This study demonstrated that the organic extracts of biodiesel PM in an aqueous solution can increase the re- lease of pro-inflammatory cytokines IL-8 and IL-6 by respiratory epithelial cells. On a microgram PM equivalent per ml (μg PM eq/ml) basis, exposure to biodiesel extracts was associated with a greater release of IL-8 and IL-6 relative to or- ganic extracts of two diesel PM samples. The dose range tested was not cytotoxic. It was also noted that the solvent ex- change method, which was used to prepare the aqueous exposure doses, may not be appropriate for the investigation of biodiesel extracts, though it has been used extensively in petroleum diesel research. A valuable new finding from these experiments is that the soluble organic fraction (SOF) of biodiesel PM begins to elicit a cytokine response in BEAS-2B cells at an exposure lower than petroleum diesel PM extract (approximately 40 μg PM eq/ml). However, more research is required to better characterize the potency of the organic fraction of biodiesel compared to petroleum diesel.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"10 1","pages":"8-15"},"PeriodicalIF":0.0,"publicationDate":"2009-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86470848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-02-12DOI: 10.2174/1874340400903010001
T. Pinto, T. I. Ikeda, L. Miyamaru, M. C. Santa, Bárbara R.P. Santos, Á. S. Cruz
The procedures described by Draize have been criticized for ethical reasons. Thus, a comparative study was performed between ocular and cutaneous irritation tests, using rabbits and in vitro test through agar diffusion with the use of NCTC clone 929, FPC-IAL and SIRC cell lines. The results obtained revealed that the agar diffusion test positive sam- ples, which presented up to degree 3 reactivity rate, according to USP 31, did not provoke ocular or cutaneous irritation. The samples which presented reactivity grade 4 also showed different degrees of ocular and cutaneous irritation, with the exception of two units of liquid soap for children use. According to the data, the diffusion agar method, using the Ameri- can Pharmacopeia graduation, can be adopted as a sorting procedure in the evaluation of cosmetics. This is a result of its capacity of predicting irritation, what largely contributes for a decrease in the use of animals in tests.
{"title":"Cosmetic Safety: Proposal for the Replacement of In Vivo (Draize) by In Vitro Test","authors":"T. Pinto, T. I. Ikeda, L. Miyamaru, M. C. Santa, Bárbara R.P. Santos, Á. S. Cruz","doi":"10.2174/1874340400903010001","DOIUrl":"https://doi.org/10.2174/1874340400903010001","url":null,"abstract":"The procedures described by Draize have been criticized for ethical reasons. Thus, a comparative study was performed between ocular and cutaneous irritation tests, using rabbits and in vitro test through agar diffusion with the use of NCTC clone 929, FPC-IAL and SIRC cell lines. The results obtained revealed that the agar diffusion test positive sam- ples, which presented up to degree 3 reactivity rate, according to USP 31, did not provoke ocular or cutaneous irritation. The samples which presented reactivity grade 4 also showed different degrees of ocular and cutaneous irritation, with the exception of two units of liquid soap for children use. According to the data, the diffusion agar method, using the Ameri- can Pharmacopeia graduation, can be adopted as a sorting procedure in the evaluation of cosmetics. This is a result of its capacity of predicting irritation, what largely contributes for a decrease in the use of animals in tests.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"13 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2009-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81858722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-01-02DOI: 10.2174/1874340400802010071
D. D. Pomerai, P. Madhamshettiwar, C. Anbalagan, M. Loose, Mainul Haque, J. King, D. K. Chowdhuri, P. Sinha, B. Johnsen, D. Baillie
Increasing evidence indicates that numerous genetic pathways responding to environmental stress in animals are regulated co-ordinately as well as independently. These stress-response systems should therefore be viewed in holistic terms as a network. As such, their behaviour is susceptible to mathematical modelling using a systems biology approach. This review outlines relevant evidence and describes a newly launched project to develop just such a model using stress- response data from multiple transgenic strains of C. elegans and D. melanogaster. We hope that our eventual model will be capable of predicting the effects of simple stressor mixtures with reasonable accuracy. To maximise the effectiveness and scope of this model, we appeal for help from colleagues to share reagents and data relevant to this project. We also present preliminary data where RNA interference has implicated the key transcription factor DAF-16 in an unexpected up- regulation of cyp-34A9 reporter expression by high cadmium. 1. STRESS RESPONSES AND MIXTURE TOXICITY In multicellular organisms, the defensive cellular re- sponses evoked by environmental stresses do not result from simple linear pathways, but rather from a network of inter- linked pathways with multiple outputs. This makes it diffi- cult to predict the biological effects of multiple stressors acting together, even though this is the normal situation for industrial pollution of soil or water, where several different contaminants are usually present together. There are few studies and no useful predictive models describing the mo- lecular responses of multicellular organisms to several toxi- cants acting in concert. This is essentially a systems biology problem, requiring integration of complex molecular and toxicological information. Under the auspices of a Major Award from the UK-India Education and Research Initiative (UK-IERI), we intend to develop an in silico model describ- ing the principal elements of a consensus stress response network (SRN) and its in vivo responses to single stressors, using data from two invertebrate model systems, the nema- tode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. This model will be used to predict the likely SRN responses to stressor mixtures, and such predictions will then be tested experimentally in both species so that the model can be refined accordingly. Since the SRN core path- ways are highly conserved among animal taxa, general fea- tures of this model should find wider application in ecotoxi-
{"title":"The Stress-Response Network in Animals: Proposals to Develop a Predictive Mathematical Model","authors":"D. D. Pomerai, P. Madhamshettiwar, C. Anbalagan, M. Loose, Mainul Haque, J. King, D. K. Chowdhuri, P. Sinha, B. Johnsen, D. Baillie","doi":"10.2174/1874340400802010071","DOIUrl":"https://doi.org/10.2174/1874340400802010071","url":null,"abstract":"Increasing evidence indicates that numerous genetic pathways responding to environmental stress in animals are regulated co-ordinately as well as independently. These stress-response systems should therefore be viewed in holistic terms as a network. As such, their behaviour is susceptible to mathematical modelling using a systems biology approach. This review outlines relevant evidence and describes a newly launched project to develop just such a model using stress- response data from multiple transgenic strains of C. elegans and D. melanogaster. We hope that our eventual model will be capable of predicting the effects of simple stressor mixtures with reasonable accuracy. To maximise the effectiveness and scope of this model, we appeal for help from colleagues to share reagents and data relevant to this project. We also present preliminary data where RNA interference has implicated the key transcription factor DAF-16 in an unexpected up- regulation of cyp-34A9 reporter expression by high cadmium. 1. STRESS RESPONSES AND MIXTURE TOXICITY In multicellular organisms, the defensive cellular re- sponses evoked by environmental stresses do not result from simple linear pathways, but rather from a network of inter- linked pathways with multiple outputs. This makes it diffi- cult to predict the biological effects of multiple stressors acting together, even though this is the normal situation for industrial pollution of soil or water, where several different contaminants are usually present together. There are few studies and no useful predictive models describing the mo- lecular responses of multicellular organisms to several toxi- cants acting in concert. This is essentially a systems biology problem, requiring integration of complex molecular and toxicological information. Under the auspices of a Major Award from the UK-India Education and Research Initiative (UK-IERI), we intend to develop an in silico model describ- ing the principal elements of a consensus stress response network (SRN) and its in vivo responses to single stressors, using data from two invertebrate model systems, the nema- tode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. This model will be used to predict the likely SRN responses to stressor mixtures, and such predictions will then be tested experimentally in both species so that the model can be refined accordingly. Since the SRN core path- ways are highly conserved among animal taxa, general fea- tures of this model should find wider application in ecotoxi-","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"57 1","pages":"71-76"},"PeriodicalIF":0.0,"publicationDate":"2009-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90959122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-07-23DOI: 10.2174/1874340400802010061
M. Mannerström, H. Mäenpää, S. Räty, J. Sand, T. Ylikomi, H. Tähti
Carbamazepine and selegiline, although neuroprotective themselves, are presumed to have toxic metabolites. The aim of this study was to investigate the possible metabolism-induced toxicity of selegiline and carbamazepine with a novel in vitro method: The drugs were incubated with target cells (neuroblastoma SH-SY5Y) with or without a pre- incubation with mouse or human hepatocytes. The viability of SH-SY5Y cells was then measured by using total cellular ATP as an indicator of the cell viability. For the pre-incubation with hepatocytes two different methods were used: Hepa- tocytes were grown either in multiwell plates (Model 1) or in filter inserts (Model 2). Selegiline itself increased SH-SY5Y viability, but the pre-incubation with both mouse and human hepatocytes made se- legiline slightly toxic to SH-SY5Y cells. The biotransformation of carbamazepine seemed to be more complex and showed variation in different hepatocyte models. In general, human hepatocytes increased carbamazepine toxicity to SH- SY5Y cells, whereas mouse hepatocytes had no such effect. The methodology used (especially Model 1) could form a ba- sis in developing a test system for a qualitative detection of metabolism-induced (neuro)toxicity in the early phase of drug discovery. In this respect, the present study might be promising for further evaluation by means of a larger number of in- dependent experiments and different types of compounds.
{"title":"Metabolism-Induced Toxicity of Selegiline and Carbamazepine Studied with an In Vitro Method","authors":"M. Mannerström, H. Mäenpää, S. Räty, J. Sand, T. Ylikomi, H. Tähti","doi":"10.2174/1874340400802010061","DOIUrl":"https://doi.org/10.2174/1874340400802010061","url":null,"abstract":"Carbamazepine and selegiline, although neuroprotective themselves, are presumed to have toxic metabolites. The aim of this study was to investigate the possible metabolism-induced toxicity of selegiline and carbamazepine with a novel in vitro method: The drugs were incubated with target cells (neuroblastoma SH-SY5Y) with or without a pre- incubation with mouse or human hepatocytes. The viability of SH-SY5Y cells was then measured by using total cellular ATP as an indicator of the cell viability. For the pre-incubation with hepatocytes two different methods were used: Hepa- tocytes were grown either in multiwell plates (Model 1) or in filter inserts (Model 2). Selegiline itself increased SH-SY5Y viability, but the pre-incubation with both mouse and human hepatocytes made se- legiline slightly toxic to SH-SY5Y cells. The biotransformation of carbamazepine seemed to be more complex and showed variation in different hepatocyte models. In general, human hepatocytes increased carbamazepine toxicity to SH- SY5Y cells, whereas mouse hepatocytes had no such effect. The methodology used (especially Model 1) could form a ba- sis in developing a test system for a qualitative detection of metabolism-induced (neuro)toxicity in the early phase of drug discovery. In this respect, the present study might be promising for further evaluation by means of a larger number of in- dependent experiments and different types of compounds.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"56 1","pages":"61-70"},"PeriodicalIF":0.0,"publicationDate":"2008-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83413276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-07-09DOI: 10.2174/1874340400802010042
L. Plunkett, R. Becker
Questions have been raised concerning whether standard toxicological testing paradigms for characterizing hazards are applicable for children. In this paper, the standard toxicological testing paradigm for industrial chemicals 1 is examined. The analysis includes examination of the basic principles and elements of hazard characterization methodology based on animal toxicity data, examination of the characteristics of the standard toxicity tests that apply to assessing haz- ards of industrial chemicals to children's health, and an appraisal of specific industrial chemical hazard characterizations developed by USEPA covering more than 200 substances (High Production Volume (HPV) Challenge datasets 2 ) with re- gard to their relevancy for use in screening for potential risks to children's health. We conclude that the standard toxicity tests used for industrial chemicals that comprise the USEPA's HPV Challenge provide adequate information for develop- ing screening-level hazard characterizations for children's health, and when coupled with child-specific exposure informa- tion should provide adequate screening-level risk evaluations for children. Key Word: Children's health, HPV chemical, hazard characterization, toxicity testing, industrial chemicals.
{"title":"Does The Standard Toxicological Testing Paradigm for Industrial Chemicals Apply to Screening for Children’s Health Risks?","authors":"L. Plunkett, R. Becker","doi":"10.2174/1874340400802010042","DOIUrl":"https://doi.org/10.2174/1874340400802010042","url":null,"abstract":"Questions have been raised concerning whether standard toxicological testing paradigms for characterizing hazards are applicable for children. In this paper, the standard toxicological testing paradigm for industrial chemicals 1 is examined. The analysis includes examination of the basic principles and elements of hazard characterization methodology based on animal toxicity data, examination of the characteristics of the standard toxicity tests that apply to assessing haz- ards of industrial chemicals to children's health, and an appraisal of specific industrial chemical hazard characterizations developed by USEPA covering more than 200 substances (High Production Volume (HPV) Challenge datasets 2 ) with re- gard to their relevancy for use in screening for potential risks to children's health. We conclude that the standard toxicity tests used for industrial chemicals that comprise the USEPA's HPV Challenge provide adequate information for develop- ing screening-level hazard characterizations for children's health, and when coupled with child-specific exposure informa- tion should provide adequate screening-level risk evaluations for children. Key Word: Children's health, HPV chemical, hazard characterization, toxicity testing, industrial chemicals.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"35 1","pages":"42-60"},"PeriodicalIF":0.0,"publicationDate":"2008-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81109878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-07-04DOI: 10.2174/1874340400802010022
Suresh Panthee, S. Lohani
Introduction: Adsorption capacity of activated charcoal to paracetamol was determined at simulated gastric en- vironment, pH 3.4 and simulated intestinal environment pH 7.2. Three formulations of activated charcoal; powder, cap- sule and suspension were tested. Paracetamol was derived from tablet to simulate in vivo intoxication conditions. Methods: Activated charcoal and paracetamol were mixed at both the pHs. The amount of activated charcoal was varied to obtain activated charcoal-paracetamol ratio from 10:1 to 1:1. Then the mixtures were shaken, filtered and the content of remaining paracetamol was determined by UV spectrophotometer. Results: The maximal adsorption capacity, milligram of paracetamol adsorbed per gram of activated charcoal, was deter- mined by using Langmuir adsorption isotherm. The maximal adsorption capacity (95% confidence intervals in square brackets) was 284.47 (221.50; 347.44) at pH 3.4 and 303.03 (303.03; 303.03) at pH 7.2 for powder; 175.49 (133.79; 217.18) at pH 3.4 and 213.23 (182.56; 243.90) at pH 7.2 for capsule; and 254.27 (245.08; 263.47) at pH 3.4 and 263.64 (229.13; 298.15) at pH 7.2 for suspension. The effect of pH on adsorption capacity was not significant. Discussion: Under simulated conditions, the three formulations of activated charcoal adsorbed sufficient amount of paracetamol. The data show that activated charcoal 1g/kg body weight is sufficient a poisoned patient from if given shortly after intoxication.
{"title":"In Vitro Adsorption Studies of Paracetamol to Activated Charcoal Capsule, Powder and Suspension","authors":"Suresh Panthee, S. Lohani","doi":"10.2174/1874340400802010022","DOIUrl":"https://doi.org/10.2174/1874340400802010022","url":null,"abstract":"Introduction: Adsorption capacity of activated charcoal to paracetamol was determined at simulated gastric en- vironment, pH 3.4 and simulated intestinal environment pH 7.2. Three formulations of activated charcoal; powder, cap- sule and suspension were tested. Paracetamol was derived from tablet to simulate in vivo intoxication conditions. Methods: Activated charcoal and paracetamol were mixed at both the pHs. The amount of activated charcoal was varied to obtain activated charcoal-paracetamol ratio from 10:1 to 1:1. Then the mixtures were shaken, filtered and the content of remaining paracetamol was determined by UV spectrophotometer. Results: The maximal adsorption capacity, milligram of paracetamol adsorbed per gram of activated charcoal, was deter- mined by using Langmuir adsorption isotherm. The maximal adsorption capacity (95% confidence intervals in square brackets) was 284.47 (221.50; 347.44) at pH 3.4 and 303.03 (303.03; 303.03) at pH 7.2 for powder; 175.49 (133.79; 217.18) at pH 3.4 and 213.23 (182.56; 243.90) at pH 7.2 for capsule; and 254.27 (245.08; 263.47) at pH 3.4 and 263.64 (229.13; 298.15) at pH 7.2 for suspension. The effect of pH on adsorption capacity was not significant. Discussion: Under simulated conditions, the three formulations of activated charcoal adsorbed sufficient amount of paracetamol. The data show that activated charcoal 1g/kg body weight is sufficient a poisoned patient from if given shortly after intoxication.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"107 1","pages":"22-25"},"PeriodicalIF":0.0,"publicationDate":"2008-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76239912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-07-04DOI: 10.2174/1874340400802010026
M. Somayajulu-Niţu, Danijela Domazet-Damjanov, Anca Matei, Edward Schwartzenberger, J. Cohen, S. Pandey
Neuronal cells are exclusively dependent on oxidative phosphorylation for energy and are under constant threat of oxidative damage due to mitochondrial production of reactive oxygen species by partial reduction of molecular oxygen. These cells also have a multitude of antioxidative defense mechanisms, but there is a slow decline of antioxidative de- fence capacity with aging. The result is the increased vulnerability of cells to oxidative stress, particularly neuronal cells. Any environmental, inflammatory or psychological stress that can topple the redox balance will eventually lead to oxida- tive stress and neuronal cell death. Indeed, cell death induced by oxidative stress has been implicated in age-related loss of neurons during normal aging and several neurodegenerative disorders. It is critical to understand the mechanisms by which different risk factors lead to neuronal cell death in order to identify pathways involved in neurodegenerative dis- eases. In this review we focus on the implications of various factors such as environmental toxins, drugs and psychologi- cal stress in neurodegenerative diseases with specific focus on Parkinson's disease and Alzheimer's disease. Here we highlight the recent progress that supports the role of molecular mechanisms of oxidative stress, neuroinflammation and mitochondrial dysfunction as contributors to neurotoxicity and research on developing therapeutics that could potentially slow down the progression of neurodegeneration.
{"title":"Role of Environmental and Inflammatory Toxicity in Neuronal Cell Death","authors":"M. Somayajulu-Niţu, Danijela Domazet-Damjanov, Anca Matei, Edward Schwartzenberger, J. Cohen, S. Pandey","doi":"10.2174/1874340400802010026","DOIUrl":"https://doi.org/10.2174/1874340400802010026","url":null,"abstract":"Neuronal cells are exclusively dependent on oxidative phosphorylation for energy and are under constant threat of oxidative damage due to mitochondrial production of reactive oxygen species by partial reduction of molecular oxygen. These cells also have a multitude of antioxidative defense mechanisms, but there is a slow decline of antioxidative de- fence capacity with aging. The result is the increased vulnerability of cells to oxidative stress, particularly neuronal cells. Any environmental, inflammatory or psychological stress that can topple the redox balance will eventually lead to oxida- tive stress and neuronal cell death. Indeed, cell death induced by oxidative stress has been implicated in age-related loss of neurons during normal aging and several neurodegenerative disorders. It is critical to understand the mechanisms by which different risk factors lead to neuronal cell death in order to identify pathways involved in neurodegenerative dis- eases. In this review we focus on the implications of various factors such as environmental toxins, drugs and psychologi- cal stress in neurodegenerative diseases with specific focus on Parkinson's disease and Alzheimer's disease. Here we highlight the recent progress that supports the role of molecular mechanisms of oxidative stress, neuroinflammation and mitochondrial dysfunction as contributors to neurotoxicity and research on developing therapeutics that could potentially slow down the progression of neurodegeneration.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"29 1","pages":"26-41"},"PeriodicalIF":0.0,"publicationDate":"2008-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91538545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-06-23DOI: 10.2174/1874340400802010013
T. Whitsett, V. Kalia, I. Eltoum, C. Lamartiniere
Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine-disrupting chemical that alters cellular organiza- tion at both macroscopic and molecular levels. Our goal was to determine the effects that prenatal TCDD exposure has on uterine morphology, cell proliferation, apoptosis, and protein expression. Pregnant Sprague-Dawley rats were treated with 3 μg TCDD/kg body weight by gavage on gestational day 15. At 50 days postpartum, female offspring exposed in utero to TCDD displayed uteri that were atrophic in appearance, but with a 2-fold significant increase in luminal epithelial cell proliferation and a significant decrease in apoptosis (10- and 4-fold in glandular and luminal epithelium, respectively), compared to the controls. Epidermal growth factor receptor (EGFR) was significantly increased and superoxide dismutase 1 (SOD1) was significantly decreased in uteri of rats exposed prenatally to TCDD. We conclude that TCDD can inhibit maturation and modulate uterine proteins that are known to play a role in uterine growth as well as alter epithelial cell pro- liferation and apoptosis in a manner that may enhance disease, including carcinogenesis.
{"title":"Prenatal TCDD Exposure Delays Differentiation and Alters Cell Proliferation and Apoptosis in the Uterus of the Sprague-Dawley Rat","authors":"T. Whitsett, V. Kalia, I. Eltoum, C. Lamartiniere","doi":"10.2174/1874340400802010013","DOIUrl":"https://doi.org/10.2174/1874340400802010013","url":null,"abstract":"Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine-disrupting chemical that alters cellular organiza- tion at both macroscopic and molecular levels. Our goal was to determine the effects that prenatal TCDD exposure has on uterine morphology, cell proliferation, apoptosis, and protein expression. Pregnant Sprague-Dawley rats were treated with 3 μg TCDD/kg body weight by gavage on gestational day 15. At 50 days postpartum, female offspring exposed in utero to TCDD displayed uteri that were atrophic in appearance, but with a 2-fold significant increase in luminal epithelial cell proliferation and a significant decrease in apoptosis (10- and 4-fold in glandular and luminal epithelium, respectively), compared to the controls. Epidermal growth factor receptor (EGFR) was significantly increased and superoxide dismutase 1 (SOD1) was significantly decreased in uteri of rats exposed prenatally to TCDD. We conclude that TCDD can inhibit maturation and modulate uterine proteins that are known to play a role in uterine growth as well as alter epithelial cell pro- liferation and apoptosis in a manner that may enhance disease, including carcinogenesis.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"168 1","pages":"13-21"},"PeriodicalIF":0.0,"publicationDate":"2008-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75083987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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