Pub Date : 2010-09-03DOI: 10.2174/1874340401004010051
R. Larson, Scott G. Story, K. Hegmann
Occupational exposure to respirable crystalline silica has the ability to cause silicosis. Silica is also suspected of being associated with an increased risk of lung cancer, kidney disease, rheumatoid arthritis, and other diseases. The specific mechanism(s) of pathogenesis for silicosis and these other potential health concerns remains unclear. This investigation measured dissolution rates of silicon dioxide (SiO 2 ) particles in simulated lung fluid to determine the residence times of such particles within the intracellular or extracellular spaces. Silicon dioxide dissolution rates were determined as a function of fluid pH, particle size, and SiO 2 concentration and mass. Gamble's solution was used to simulate intracellular and extracellular lung fluids at pH 6.0, pH 6.5, and pH 7.5. Test samples were paired by pH, particle size, and SiO 2 concentration/mass. Sample aliquots of filtered solution were collected over a 28-day test period. Results revealed SiO 2 became soluble and the dissolution rate increased with increasing pH and decreasing particle size. SiO 2 concentration and mass also appeared to have some effect on the rate of dissolution. These solubility characteristics appear likely to impact the residence times of particles within biological systems, suggesting a model for exposure and subsequent pathogenesis for systemic silica-related diseases.
{"title":"Assessing the Solubility of Silicon Dioxide Particles Using Simulated Lung Fluid","authors":"R. Larson, Scott G. Story, K. Hegmann","doi":"10.2174/1874340401004010051","DOIUrl":"https://doi.org/10.2174/1874340401004010051","url":null,"abstract":"Occupational exposure to respirable crystalline silica has the ability to cause silicosis. Silica is also suspected of being associated with an increased risk of lung cancer, kidney disease, rheumatoid arthritis, and other diseases. The specific mechanism(s) of pathogenesis for silicosis and these other potential health concerns remains unclear. This investigation measured dissolution rates of silicon dioxide (SiO 2 ) particles in simulated lung fluid to determine the residence times of such particles within the intracellular or extracellular spaces. Silicon dioxide dissolution rates were determined as a function of fluid pH, particle size, and SiO 2 concentration and mass. Gamble's solution was used to simulate intracellular and extracellular lung fluids at pH 6.0, pH 6.5, and pH 7.5. Test samples were paired by pH, particle size, and SiO 2 concentration/mass. Sample aliquots of filtered solution were collected over a 28-day test period. Results revealed SiO 2 became soluble and the dissolution rate increased with increasing pH and decreasing particle size. SiO 2 concentration and mass also appeared to have some effect on the rate of dissolution. These solubility characteristics appear likely to impact the residence times of particles within biological systems, suggesting a model for exposure and subsequent pathogenesis for systemic silica-related diseases.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"96 1","pages":"51-55"},"PeriodicalIF":0.0,"publicationDate":"2010-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83366265","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 : 2010-08-19DOI: 10.2174/1874340401004010043
S. Tharakan, G. Kuttan,, R. Kuttan, M. Kesavan, S. Austin, K. Rajagopalan
{"title":"Toxicity Studies of Sidha Medicine - Rasagandhi Mezhugu~!2010-04-05~!2010-05-03~!2010-08-09~!","authors":"S. Tharakan, G. Kuttan,, R. Kuttan, M. Kesavan, S. Austin, K. Rajagopalan","doi":"10.2174/1874340401004010043","DOIUrl":"https://doi.org/10.2174/1874340401004010043","url":null,"abstract":"","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"67 1","pages":"43-50"},"PeriodicalIF":0.0,"publicationDate":"2010-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76302658","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 : 2010-06-23DOI: 10.2174/1874340401004010039
D. Lachenmeier, Natalie Steinbrenner, S. Löbell-Behrends, H. Reusch, T. Kuballa
Food products containing carrots were analyzed for benzene contamination using headspace gas chromatography with mass spectrometric detection. Of 82 commercial samples, 88% contained benzene above the detection limit of 0.04 µg/kg. Canned and jarred carrots contained 0.2 µg/kg of benzene on average. Higher levels were found in jarred baby foods containing carrots (0.9 µg/kg on average). The highest concentrations were found in carrot juices specifically intended for infants (2.0 µg/l on average). In contrast, freshly home-prepared carrot juices (n=8) and baby foods (n=30) were all benzene-free. The detection of the human carcinogen benzene at µg/kg levels in canned foods, jarred baby food and juices containing carrots proves that the level of exposure to benzene through food products is currently underestimated. The potential of this substance to pose a cancer hazard for consumers should be evaluated. Further research into the occurrence of benzene in food products, including formation mechanisms and mitigation measures, is necessary.
{"title":"Benzene Contamination in Heat-Treated Carrot Products Including Baby Foods~!2010-01-15~!2010-05-11~!2010-06-23~!","authors":"D. Lachenmeier, Natalie Steinbrenner, S. Löbell-Behrends, H. Reusch, T. Kuballa","doi":"10.2174/1874340401004010039","DOIUrl":"https://doi.org/10.2174/1874340401004010039","url":null,"abstract":"Food products containing carrots were analyzed for benzene contamination using headspace gas chromatography with mass spectrometric detection. Of 82 commercial samples, 88% contained benzene above the detection limit of 0.04 µg/kg. Canned and jarred carrots contained 0.2 µg/kg of benzene on average. Higher levels were found in jarred baby foods containing carrots (0.9 µg/kg on average). The highest concentrations were found in carrot juices specifically intended for infants (2.0 µg/l on average). In contrast, freshly home-prepared carrot juices (n=8) and baby foods (n=30) were all benzene-free. The detection of the human carcinogen benzene at µg/kg levels in canned foods, jarred baby food and juices containing carrots proves that the level of exposure to benzene through food products is currently underestimated. The potential of this substance to pose a cancer hazard for consumers should be evaluated. Further research into the occurrence of benzene in food products, including formation mechanisms and mitigation measures, is necessary.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"9 1","pages":"39-42"},"PeriodicalIF":0.0,"publicationDate":"2010-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86278320","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 : 2010-06-11DOI: 10.2174/1874340401004010032
H. P. Magalhães, Matheus Philippe Teixeira de Sena, D. Nelson
In the present study, the kinetic characterization of leucurobin, a thrombin-like enzyme isolated from the venom of Bothrops leucurus was evaluated. This serpent is very common in the northeast of Brazil, but little is known about its venom. Leucurobin showed amidase activity against chromogenic substrates of the peptidyl-pNA type containing an Arg residue at P1. D-Phe-Pro-Arg-pNA was observed to be the best substrate of those tested. The amidase activity of leucurobin with this substrate was strongly inhibited by sodium and potassium ions and was weakly inhibited by calcium and magnesium ions. Leucurobin presented a high coagulating activity in vitro with citrated human plasma and with purified bovine fibrinogen. The coagulating activity with fibrinogen was inhibited by the presence of sodium and potassium ions, but not by calcium or magnesium ions. No interference in the amidase and coagulating activities by the glycoside fraction of native leucurobin was observed. The S1 site was found to be anionic, and the S2 and S3 sites are hydrophobic.
本文研究了一种从白刺鼠毒液中分离得到的凝血酶样酶-亮氨酸血红素的动力学特性。这种蛇在巴西东北部非常常见，但人们对它的毒液知之甚少。亮色素对P1处含有精氨酸残基的肽基pna型显色底物显示出酶活性。结果表明，d - ph - pro - arg - pna是最佳底物。含该底物的亮色素的酶活性受到钠、钾离子的强烈抑制，而受到钙、镁离子的微弱抑制。亮氨酸血红素在体外与柠檬酸人血浆和纯化牛纤维蛋白原具有较高的凝血活性。钠、钾离子对纤维蛋白原的凝血活性有抑制作用，钙、镁离子对纤维蛋白原的凝血活性无抑制作用。结果表明，天然亚绿素的糖苷部分对酶和凝血活性无干扰。S1位点为阴离子，S2和S3位点为疏水性。
{"title":"Kinetic Characterization of Leucurobin, a Coagulant Thrombin-Like Enzyme from the Venom of Bothrops leucurus","authors":"H. P. Magalhães, Matheus Philippe Teixeira de Sena, D. Nelson","doi":"10.2174/1874340401004010032","DOIUrl":"https://doi.org/10.2174/1874340401004010032","url":null,"abstract":"In the present study, the kinetic characterization of leucurobin, a thrombin-like enzyme isolated from the venom of Bothrops leucurus was evaluated. This serpent is very common in the northeast of Brazil, but little is known about its venom. Leucurobin showed amidase activity against chromogenic substrates of the peptidyl-pNA type containing an Arg residue at P1. D-Phe-Pro-Arg-pNA was observed to be the best substrate of those tested. The amidase activity of leucurobin with this substrate was strongly inhibited by sodium and potassium ions and was weakly inhibited by calcium and magnesium ions. Leucurobin presented a high coagulating activity in vitro with citrated human plasma and with purified bovine fibrinogen. The coagulating activity with fibrinogen was inhibited by the presence of sodium and potassium ions, but not by calcium or magnesium ions. No interference in the amidase and coagulating activities by the glycoside fraction of native leucurobin was observed. The S1 site was found to be anionic, and the S2 and S3 sites are hydrophobic.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2010-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84510103","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 : 2010-03-26DOI: 10.2174/1874340401004010013
Hyun-Yi Youn, A. P. Cullen, Chou B.R., J. Sivak
This work involves the evaluation of UV blocking efficiency of commercially available intraocular lens (IOL) materials using a retinal cell culture and a biological in vitro model that was developed in a previous study, as an effort to examine the sensitivity of this in vitro approach for evaluating toxicity of UV radiation on the retinal pigment epithelial cells. The human retinal pigment epithelial (RPE) cell line, ARPE-19, was cultured, and cells were irradiated with broadband UVB radiations at energy levels of 0.2 and 0.4 J/cm� . Some treated cells were not shielded from the radiation while others were shielded using two thicknesses (0.9 and 1.5 mm) of IOL material. After irradiation, cellular viability, mitochondrial distribution, nuclei morphology, and phagocytotic activity were analyzed using the Alamar blue assay, Rhodamine 123 staining, the Hoechst assay, and a phagocytotic activity assay. The results demonstrate that UVB radiation can cause significant decreases in RPE cell viability as well as in phagocytotic activity. Also, the results show that UVB radiation can induce the degradation of DNA and mitochondria in cultured RPE cells. However, the two different thickness IOL material sheets (0.9 and 1.5 mm) showed very effective UV blocking ability, allowing no cellular damage at all. Thus, the finding suggest that these four assays together can be used as a sensitive, and meaningful in vitro biomarker method for evaluating toxicity of UV radiation on RPE cells, and also for examining IOL effectiveness.
{"title":"Phototoxicity of Ultraviolet (UV) Radiation: Evaluation of UV-Blocking Efficiency of Intraocular Lens (IOL) Materials Using Retinal Cell Culture and in vitro Bioassays","authors":"Hyun-Yi Youn, A. P. Cullen, Chou B.R., J. Sivak","doi":"10.2174/1874340401004010013","DOIUrl":"https://doi.org/10.2174/1874340401004010013","url":null,"abstract":"This work involves the evaluation of UV blocking efficiency of commercially available intraocular lens (IOL) materials using a retinal cell culture and a biological in vitro model that was developed in a previous study, as an effort to examine the sensitivity of this in vitro approach for evaluating toxicity of UV radiation on the retinal pigment epithelial cells. The human retinal pigment epithelial (RPE) cell line, ARPE-19, was cultured, and cells were irradiated with broadband UVB radiations at energy levels of 0.2 and 0.4 J/cm� . Some treated cells were not shielded from the radiation while others were shielded using two thicknesses (0.9 and 1.5 mm) of IOL material. After irradiation, cellular viability, mitochondrial distribution, nuclei morphology, and phagocytotic activity were analyzed using the Alamar blue assay, Rhodamine 123 staining, the Hoechst assay, and a phagocytotic activity assay. The results demonstrate that UVB radiation can cause significant decreases in RPE cell viability as well as in phagocytotic activity. Also, the results show that UVB radiation can induce the degradation of DNA and mitochondria in cultured RPE cells. However, the two different thickness IOL material sheets (0.9 and 1.5 mm) showed very effective UV blocking ability, allowing no cellular damage at all. Thus, the finding suggest that these four assays together can be used as a sensitive, and meaningful in vitro biomarker method for evaluating toxicity of UV radiation on RPE cells, and also for examining IOL effectiveness.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2010-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82142207","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 : 2009-11-24DOI: 10.2174/1874340400903010058
A. M. Alves, Leonardo da Silva Vidal, R. Kuster, Claudia de Alencar Santos Lage, Á. Leitão
Erva cidreira (Melissa officinalis) is a plant with sedative properties and in Brazil it has been used for insomnia and anxiety. It is also employed to stimulate liver functions and normalize menstruation and for intestinal constipation. The aim of this work was to evaluate the genotoxic and mutagenic effects of erva cidreira. Results indicate the presence of genotoxic activity in the lyophilized extract, with lysogenic induction increasing about 80-fold over the spontaneous background after treatment with lyophilized total aqueous extract. Beta-galactosidase levels raised 9-fold in indicator strains after treatment under the same conditions. A deeper look into the mechanism underlying the genotoxic action implicated reactive oxygen species generated by compounds retained in the ethyl-acetate, polar partition of the total aqueous extract. The spectrum of mutations revealed a great trend for base substitutions, mainly in guanines and adenines. The presence of phenolic compounds, especially caffeic acid derivatives, may be correlated to its genotoxic activity. We thus conclude that compounds present in current concentrations of erva cidreira extracts are genotoxic and mutagenic, and might have carcinogenic potential.
{"title":"Genotoxic and Mutagenic Effects of Melissa officinalis (Erva Cidreira) Extracts","authors":"A. M. Alves, Leonardo da Silva Vidal, R. Kuster, Claudia de Alencar Santos Lage, Á. Leitão","doi":"10.2174/1874340400903010058","DOIUrl":"https://doi.org/10.2174/1874340400903010058","url":null,"abstract":"Erva cidreira (Melissa officinalis) is a plant with sedative properties and in Brazil it has been used for insomnia and anxiety. It is also employed to stimulate liver functions and normalize menstruation and for intestinal constipation. The aim of this work was to evaluate the genotoxic and mutagenic effects of erva cidreira. Results indicate the presence of genotoxic activity in the lyophilized extract, with lysogenic induction increasing about 80-fold over the spontaneous background after treatment with lyophilized total aqueous extract. Beta-galactosidase levels raised 9-fold in indicator strains after treatment under the same conditions. A deeper look into the mechanism underlying the genotoxic action implicated reactive oxygen species generated by compounds retained in the ethyl-acetate, polar partition of the total aqueous extract. The spectrum of mutations revealed a great trend for base substitutions, mainly in guanines and adenines. The presence of phenolic compounds, especially caffeic acid derivatives, may be correlated to its genotoxic activity. We thus conclude that compounds present in current concentrations of erva cidreira extracts are genotoxic and mutagenic, and might have carcinogenic potential.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"8 1","pages":"58-69"},"PeriodicalIF":0.0,"publicationDate":"2009-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87441082","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 : 2009-10-02DOI: 10.2174/1874340400903010047
C. Pascale, C. Domenicotti, M. Nitti, B. Marengo, Mariafrancesca Catalano, C. Scanarotti, R. Sanguineti, M. Siri, S. Ledda, S. Penco, A. Bassi
Cytochrome P4501A1 (CYP1A1), an enzyme known to metabolize polycyclic aromatic hydrocarbons, is regulated by the aryl hydrocarbon receptor (AhR). The involvement of protein kinase C (PKC) in the regulation of AhR signal transduction pathway, has been widely studied but the role of specific PKC isoform(s) involved in this process it is not well clarified. To study which PKC isoform(s) is implicated in the regulation of CYP1A1, in the poorly tumorigenic MH1C1 rat hepatoma cells, we examined the effects of some PKC pharmacological inhibitors, Calphostin C (CAL), Staurosporine (STA) and H7, and of 12-0-tetradecanoyl phorbol 13-acetate (TPA), a PKC activator, on basal and 3- methylcholanthrene (MC)-induced CYP1A1 protein expression and mediated ethoxyresorufin O-deethylation (EROD) activity. In parallel, the activities of PKC-α, -βI, -δ and -e isoforms, the most expressed in MH1C1 cells, were monitored. After pre-treatment with CAL, STA and H7, the MC-induced CYP1A1 protein and EROD activity were rapidly reduced with temporal profile similar to the profile of the activity of α and β1 PKC isoforms. Moreover, TPA pre-treatment induced a biphasic effect on EROD activity, and a decline of PKC -βI and -α, in first instance, and -δ and -e activities later on. These findings clearly show that, in MH1C1 cells, PKC is involved in CYP1A1 regulation and that α and βI classic PKC isoforms play an active role in modulating this process.
细胞色素P4501A1 (CYP1A1)是一种已知的代谢多环芳烃的酶，受芳烃受体(AhR)调节。蛋白激酶C (PKC)参与AhR信号转导通路的调控已被广泛研究，但PKC特异性异构体参与这一过程的作用尚不清楚。为了研究PKC亚型与低致瘤性MH1C1大鼠肝癌细胞中CYP1A1的调控有关，我们检测了PKC药物抑制剂Calphostin C (CAL)、Staurosporine (STA)和H7，以及PKC激活剂12-0-十四烷醇- 13-乙酸酯(TPA)对基础和3-甲基胆蒽(MC)诱导的CYP1A1蛋白表达和介导的乙氧基间苯二酚o -去乙基化(EROD)活性的影响。同时，对MH1C1细胞中表达最多的PKC-α、-βI、-δ和-e亚型的活性进行了监测。经CAL、STA和H7预处理后，mc诱导的CYP1A1蛋白和EROD活性迅速降低，其时间谱与α和β1 PKC亚型的活性谱相似。此外，TPA预处理诱导了EROD活性的双相影响，PKC -βI和-α首先下降，随后-δ和-e活性下降。这些发现清楚地表明，在MH1C1细胞中，PKC参与CYP1A1的调节，而α和βI经典PKC亚型在调节这一过程中发挥积极作用。
{"title":"Modulation of CYP1A1 by PKC Inhibitors and TPA Pre-Treatments in MH1C1 Rat Hepatoma Cells Exposed to 3 -Methylcholanthrene","authors":"C. Pascale, C. Domenicotti, M. Nitti, B. Marengo, Mariafrancesca Catalano, C. Scanarotti, R. Sanguineti, M. Siri, S. Ledda, S. Penco, A. Bassi","doi":"10.2174/1874340400903010047","DOIUrl":"https://doi.org/10.2174/1874340400903010047","url":null,"abstract":"Cytochrome P4501A1 (CYP1A1), an enzyme known to metabolize polycyclic aromatic hydrocarbons, is regulated by the aryl hydrocarbon receptor (AhR). The involvement of protein kinase C (PKC) in the regulation of AhR signal transduction pathway, has been widely studied but the role of specific PKC isoform(s) involved in this process it is not well clarified. To study which PKC isoform(s) is implicated in the regulation of CYP1A1, in the poorly tumorigenic MH1C1 rat hepatoma cells, we examined the effects of some PKC pharmacological inhibitors, Calphostin C (CAL), Staurosporine (STA) and H7, and of 12-0-tetradecanoyl phorbol 13-acetate (TPA), a PKC activator, on basal and 3- methylcholanthrene (MC)-induced CYP1A1 protein expression and mediated ethoxyresorufin O-deethylation (EROD) activity. In parallel, the activities of PKC-α, -βI, -δ and -e isoforms, the most expressed in MH1C1 cells, were monitored. After pre-treatment with CAL, STA and H7, the MC-induced CYP1A1 protein and EROD activity were rapidly reduced with temporal profile similar to the profile of the activity of α and β1 PKC isoforms. Moreover, TPA pre-treatment induced a biphasic effect on EROD activity, and a decline of PKC -βI and -α, in first instance, and -δ and -e activities later on. These findings clearly show that, in MH1C1 cells, PKC is involved in CYP1A1 regulation and that α and βI classic PKC isoforms play an active role in modulating this process.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"89 1","pages":"47-57"},"PeriodicalIF":0.0,"publicationDate":"2009-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80355718","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 : 2009-04-17DOI: 10.2174/1874340400903010039
Harold J. Daigle,Jr., Derek N. Cole, J. Carlson, W. Lee, V. L. Wilson
Ethylene dichloride (EDC) is a high use compound in chemical industry today. Although a potent alkylating agent and carcinogen, EDC has not been associated previously with adverse fertility consequences. Intraperitoneal 5 to 40 mg/kg once a day for five days in C57BL/6 mice rendered males infertile for 6 months and longer. Two of three mice treated with EDC at 5 mg/kg recovered to fertility after a 3 and 5-week sterile period, respectively. Significant testicular pathology was evident within 8 days post treatment with EDC, which progressed to resemble Sertoli Cell-Only syndrome. Although the observed effects on Leydig cell populations were equivocal, a precipitous loss of spermatogonia was evident with increasing time post EDC treatment for mice dosed with either 5 or 10 mg/kg of EDC. These results suggest that intraperitoneal EDC adversely impacts the testes and spermatogenesis in mice.
{"title":"Ethylene Dichloride Disruption of Fertility in Male Mice","authors":"Harold J. Daigle,Jr., Derek N. Cole, J. Carlson, W. Lee, V. L. Wilson","doi":"10.2174/1874340400903010039","DOIUrl":"https://doi.org/10.2174/1874340400903010039","url":null,"abstract":"Ethylene dichloride (EDC) is a high use compound in chemical industry today. Although a potent alkylating agent and carcinogen, EDC has not been associated previously with adverse fertility consequences. Intraperitoneal 5 to 40 mg/kg once a day for five days in C57BL/6 mice rendered males infertile for 6 months and longer. Two of three mice treated with EDC at 5 mg/kg recovered to fertility after a 3 and 5-week sterile period, respectively. Significant testicular pathology was evident within 8 days post treatment with EDC, which progressed to resemble Sertoli Cell-Only syndrome. Although the observed effects on Leydig cell populations were equivocal, a precipitous loss of spermatogonia was evident with increasing time post EDC treatment for mice dosed with either 5 or 10 mg/kg of EDC. These results suggest that intraperitoneal EDC adversely impacts the testes and spermatogenesis in mice.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"24 1","pages":"39-46"},"PeriodicalIF":0.0,"publicationDate":"2009-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72638211","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 : 2009-04-07DOI: 10.2174/1874340400903010035
V. Steenkamp, T. Mokoele, C. E. J. Rensburg
A. venosum and B. micrantha are widely used ethnomedically and B. micrantha has furthermore indicated the potential to be developed into a drug due to the various biological activities previously reported. However, the safety of a plant must be determined before drug development. Cytotoxicity was determined using human adenocarcinoma cells of the cervix (HeLa), human breast cells (MCF-12A), lymphocytes (both resting and stimulated) as well as primary porcine hepatocytes. Acute systemic toxicity was determined using the luminescent bacteria, Vibrio fischerii and the vertebrate, Poecilia reticulata (guppy). Toxicity was found to be concentration dependent when HeLa and MCF-12A cells were ex- posed to the plant extracts. The IC50 was not reached at the concentrations tested (0.1 μg/ml - 1 mg/ml) for the hepato- cytes as well as the resting and stimulated lymphocytes, indicative that both plant extracts showed little or no direct cyto- toxicity against primary cultures. Both extracts resulted in 100% mortality of the guppies. This study illustrated that ex- tracts of both B. micrantha and A. venosum are cytotoxic and possess acute systemic toxicity.
{"title":"Toxicity Testing of Two Medicinal Plants, Bridelia micrantha and Antidesma venosum","authors":"V. Steenkamp, T. Mokoele, C. E. J. Rensburg","doi":"10.2174/1874340400903010035","DOIUrl":"https://doi.org/10.2174/1874340400903010035","url":null,"abstract":"A. venosum and B. micrantha are widely used ethnomedically and B. micrantha has furthermore indicated the potential to be developed into a drug due to the various biological activities previously reported. However, the safety of a plant must be determined before drug development. Cytotoxicity was determined using human adenocarcinoma cells of the cervix (HeLa), human breast cells (MCF-12A), lymphocytes (both resting and stimulated) as well as primary porcine hepatocytes. Acute systemic toxicity was determined using the luminescent bacteria, Vibrio fischerii and the vertebrate, Poecilia reticulata (guppy). Toxicity was found to be concentration dependent when HeLa and MCF-12A cells were ex- posed to the plant extracts. The IC50 was not reached at the concentrations tested (0.1 μg/ml - 1 mg/ml) for the hepato- cytes as well as the resting and stimulated lymphocytes, indicative that both plant extracts showed little or no direct cyto- toxicity against primary cultures. Both extracts resulted in 100% mortality of the guppies. This study illustrated that ex- tracts of both B. micrantha and A. venosum are cytotoxic and possess acute systemic toxicity.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"37 1","pages":"35-38"},"PeriodicalIF":0.0,"publicationDate":"2009-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87188669","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 : 2009-03-27DOI: 10.2174/1874340400903010030
D. Lachenmeier
The risk of developing cancer from carcinogens occurring in food is of widespread interest to scientific researchers, food policymakers and food surveillance institutions, as well as to the general public. When evaluating the risk of carcinogenic food contaminants or carcinogenic foodstuff per se (e.g., alcoholic beverages), the level of scientific evidence should be reflected more clearly. In the past, interest often focused on ‘fashionable’ agents with only moderate levels of evidence of their carcinogenicity (e.g., acrylamide or furan); whereas agents with the highest level of evidence (e.g., substances classified by the International Agency for Research on Cancer (IARC) as group 1, being ‘carcinogenic to humans’) were sometimes disregarded. For example, important carcinogens such as arsenic (a contaminant in drinking water), cadmium and other heavy metals, but also benzene, were not even mentioned in a recent review article about carcinogenic food contaminants. Research, control and prevention strategies for carcinogenic agents in food should comprise a risk-oriented approach and should not lose sight of agents that pose an immediate and scientifically quantifiable threat. Suitable strategies include the use of quantitative risk assessments, for example the use of the Margin of Exposure (MOE)
{"title":"Carcinogens in Food: Opportunities and Challenges for Regulatory Toxicology","authors":"D. Lachenmeier","doi":"10.2174/1874340400903010030","DOIUrl":"https://doi.org/10.2174/1874340400903010030","url":null,"abstract":"The risk of developing cancer from carcinogens occurring in food is of widespread interest to scientific researchers, food policymakers and food surveillance institutions, as well as to the general public. When evaluating the risk of carcinogenic food contaminants or carcinogenic foodstuff per se (e.g., alcoholic beverages), the level of scientific evidence should be reflected more clearly. In the past, interest often focused on ‘fashionable’ agents with only moderate levels of evidence of their carcinogenicity (e.g., acrylamide or furan); whereas agents with the highest level of evidence (e.g., substances classified by the International Agency for Research on Cancer (IARC) as group 1, being ‘carcinogenic to humans’) were sometimes disregarded. For example, important carcinogens such as arsenic (a contaminant in drinking water), cadmium and other heavy metals, but also benzene, were not even mentioned in a recent review article about carcinogenic food contaminants. Research, control and prevention strategies for carcinogenic agents in food should comprise a risk-oriented approach and should not lose sight of agents that pose an immediate and scientifically quantifiable threat. Suitable strategies include the use of quantitative risk assessments, for example the use of the Margin of Exposure (MOE)","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"5 1","pages":"30-34"},"PeriodicalIF":0.0,"publicationDate":"2009-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78138485","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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