Pub Date : 2020-12-29DOI: 10.1177/2397847320979751
S. Boué, Didier Goedertier, J. Hoeng, A. Iskandar, A. Kuczaj, D. Marescotti, C. Mathis, Anne May, B. Phillips, M. Peitsch, W. Schlage, Davide Sciuscio, W. Tan, P. Vanscheeuwijck
E-vapor products (EVP) have become popular alternatives for cigarette smokers who would otherwise continue to smoke. EVP research is challenging and complex, mostly because of the numerous and rapidly evolving technologies and designs as well as the multiplicity of e-liquid flavors and solvents available on the market. There is an urgent need to standardize all stages of EVP assessment, from the production of a reference product to e-vapor generation methods and from physicochemical characterization methods to nonclinical and clinical exposure studies. The objective of this review is to provide a detailed description of selected experimental setups and methods for EVP aerosol generation and collection and exposure systems for their in vitro and in vivo assessment. The focus is on the specificities of the product that constitute challenges and require development of ad hoc assessment frameworks, equipment, and methods. In so doing, this review aims to support further studies, objective evaluation, comparison, and verification of existing evidence, and, ultimately, formulation of standardized methods for testing EVPs.
{"title":"State-of-the-art methods and devices for generation, exposure, and collection of aerosols from e-vapor products","authors":"S. Boué, Didier Goedertier, J. Hoeng, A. Iskandar, A. Kuczaj, D. Marescotti, C. Mathis, Anne May, B. Phillips, M. Peitsch, W. Schlage, Davide Sciuscio, W. Tan, P. Vanscheeuwijck","doi":"10.1177/2397847320979751","DOIUrl":"https://doi.org/10.1177/2397847320979751","url":null,"abstract":"E-vapor products (EVP) have become popular alternatives for cigarette smokers who would otherwise continue to smoke. EVP research is challenging and complex, mostly because of the numerous and rapidly evolving technologies and designs as well as the multiplicity of e-liquid flavors and solvents available on the market. There is an urgent need to standardize all stages of EVP assessment, from the production of a reference product to e-vapor generation methods and from physicochemical characterization methods to nonclinical and clinical exposure studies. The objective of this review is to provide a detailed description of selected experimental setups and methods for EVP aerosol generation and collection and exposure systems for their in vitro and in vivo assessment. The focus is on the specificities of the product that constitute challenges and require development of ad hoc assessment frameworks, equipment, and methods. In so doing, this review aims to support further studies, objective evaluation, comparison, and verification of existing evidence, and, ultimately, formulation of standardized methods for testing EVPs.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79758607","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 : 2020-12-09DOI: 10.1177/2397847320972040
S. Owumi, Abigail O Ijadele, U. Arunsi, O. Odunola
The anti-neoplastic use of Doxorubicin (DOX) is hampered by several limitations, including reproductive toxicity. Luteolin (LUT)–a phytochemical-biological benefits include antioxidative and anti-inflammatory actions. Here we examined the protective effect of LUT against DOX-induced reproductive toxicity in an in vivo model—male albino Wistar rats—randomly assigned to five groups and treated as follows: Control (corn oil 2 mL/kg; per os), LUT (100 mg/kg; per os), DOX (2 mg/kg) by intraperitoneal injections, co-treated groups received LUT (50 and 100 mg/kg) with DOX. Treatment with DOX alone, significantly (p > 0.05), reduced biomarkers of testicular function, reproductive hormone levels, testicular and epididymal antioxidant, and anti-inflammatory cytokine. DOX increased (p > 0.05) sperm morphological abnormalities, as well as reactive oxygen and nitrogen species, lipid peroxidation, xanthine oxidase, a pro-inflammatory cytokine, and apoptotic biomarkers. Furthermore, testicular and epididymal histological lesion complemented the observed biochemical changes in treated rats. LUT co-treatment resulted in a dosage-dependent improvement in rats’ survivability, antioxidants capacity, reduction in biomarkers of oxidative stress, pro-inflammatory cytokines, and apoptosis in rat’s testis and epididymis. Also, LUT treatment resulted in improved histological features in the testis and epididymis, relative to DOX alone treated rats. LUT co-treatment abated DOX-mediated reproductive organ injuries associated with pro-oxidative, inflammatory, and apoptotic mechanisms. LUT supplementation may serve as a phyto-protective agent in alleviating male reproductive organ toxic injuries associated with Doxorubicin therapy.
{"title":"Luteolin abates reproductive toxicity mediated by the oxido-inflammatory response in Doxorubicin-treated rats","authors":"S. Owumi, Abigail O Ijadele, U. Arunsi, O. Odunola","doi":"10.1177/2397847320972040","DOIUrl":"https://doi.org/10.1177/2397847320972040","url":null,"abstract":"The anti-neoplastic use of Doxorubicin (DOX) is hampered by several limitations, including reproductive toxicity. Luteolin (LUT)–a phytochemical-biological benefits include antioxidative and anti-inflammatory actions. Here we examined the protective effect of LUT against DOX-induced reproductive toxicity in an in vivo model—male albino Wistar rats—randomly assigned to five groups and treated as follows: Control (corn oil 2 mL/kg; per os), LUT (100 mg/kg; per os), DOX (2 mg/kg) by intraperitoneal injections, co-treated groups received LUT (50 and 100 mg/kg) with DOX. Treatment with DOX alone, significantly (p > 0.05), reduced biomarkers of testicular function, reproductive hormone levels, testicular and epididymal antioxidant, and anti-inflammatory cytokine. DOX increased (p > 0.05) sperm morphological abnormalities, as well as reactive oxygen and nitrogen species, lipid peroxidation, xanthine oxidase, a pro-inflammatory cytokine, and apoptotic biomarkers. Furthermore, testicular and epididymal histological lesion complemented the observed biochemical changes in treated rats. LUT co-treatment resulted in a dosage-dependent improvement in rats’ survivability, antioxidants capacity, reduction in biomarkers of oxidative stress, pro-inflammatory cytokines, and apoptosis in rat’s testis and epididymis. Also, LUT treatment resulted in improved histological features in the testis and epididymis, relative to DOX alone treated rats. LUT co-treatment abated DOX-mediated reproductive organ injuries associated with pro-oxidative, inflammatory, and apoptotic mechanisms. LUT supplementation may serve as a phyto-protective agent in alleviating male reproductive organ toxic injuries associated with Doxorubicin therapy.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88328004","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 : 2020-12-09DOI: 10.1177/2397847320972042
G. Ihegboro, C. Ononamadu, T. Owolarafe, Iko Shekwolo
Health forecasters predict that cases of diabetes will double in 2030; hence proactive action is required to salvage this problem. Thus, this study was undertaken to evaluate the toxicological and anti-diabetic potential of n-hexane extract of T. bangwensis leaves on α-amylase and α-glucosidase activity. The phytochemical screening, antioxidant activity as well as the inhibitory effect of the plant extract was determined by UV-spectrophotometry method while brine shrimp and Allium cepa methods were used for the toxicity study. Preliminary phytochemical screening detected the presence of flavonoid, phenol, tannin, alkaloid and cardiac glycoside whereas phlobatanin, steroid, terpenoid and saponin were absent. The result also showed that flavonoid concentration was the highest compared to others. The 2,2-diphenyl-1-picrylhydrazine (DPPH) and nitric oxide (NO) results showed that the plant extract exhibited significant antioxidant activity particularly at the highest concentration (100 µg/ml). Brine shrimp lethality result showed that the highest mortality rate of nauplii and median inhibition concentration (IC50) are 97% and 7.46 ± 0.33 µg/ml respectively. Furthermore, the results also revealed that mitotic index, root growth length and mitotic division (cytotoxicity indicators) decreased as concentration increases. Finally, the results showed that the plant extract exhibited significant inhibitory effect on α-amylase and α-glucosidase activities at 100 µg/ml; nevertheless, the effect was higher on α-amylase than α-glucosidase activity. In summary, the significant antioxidant and inhibitory effects may be attributed to the presence of the phytochemicals mentioned above. It can therefore be concluded that T. bangwensis leaves may demonstrate potent anti-diabetic effect.
{"title":"Screening for toxicological and anti-diabetic potential of n-hexane extract of Tapinanthus bangwensis leaves","authors":"G. Ihegboro, C. Ononamadu, T. Owolarafe, Iko Shekwolo","doi":"10.1177/2397847320972042","DOIUrl":"https://doi.org/10.1177/2397847320972042","url":null,"abstract":"Health forecasters predict that cases of diabetes will double in 2030; hence proactive action is required to salvage this problem. Thus, this study was undertaken to evaluate the toxicological and anti-diabetic potential of n-hexane extract of T. bangwensis leaves on α-amylase and α-glucosidase activity. The phytochemical screening, antioxidant activity as well as the inhibitory effect of the plant extract was determined by UV-spectrophotometry method while brine shrimp and Allium cepa methods were used for the toxicity study. Preliminary phytochemical screening detected the presence of flavonoid, phenol, tannin, alkaloid and cardiac glycoside whereas phlobatanin, steroid, terpenoid and saponin were absent. The result also showed that flavonoid concentration was the highest compared to others. The 2,2-diphenyl-1-picrylhydrazine (DPPH) and nitric oxide (NO) results showed that the plant extract exhibited significant antioxidant activity particularly at the highest concentration (100 µg/ml). Brine shrimp lethality result showed that the highest mortality rate of nauplii and median inhibition concentration (IC50) are 97% and 7.46 ± 0.33 µg/ml respectively. Furthermore, the results also revealed that mitotic index, root growth length and mitotic division (cytotoxicity indicators) decreased as concentration increases. Finally, the results showed that the plant extract exhibited significant inhibitory effect on α-amylase and α-glucosidase activities at 100 µg/ml; nevertheless, the effect was higher on α-amylase than α-glucosidase activity. In summary, the significant antioxidant and inhibitory effects may be attributed to the presence of the phytochemicals mentioned above. It can therefore be concluded that T. bangwensis leaves may demonstrate potent anti-diabetic effect.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"76 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87047794","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 : 2020-12-07DOI: 10.1177/2397847320977540
R. Adamson
The major factors (macro) which cause human cancer have been elucidated and include tobacco use, diet, infection, reproductive and sexual behavior and, to a lesser extent, alcohol consumption and occupational factors. Several reports have been published about endogenous chemicals made in humans which produce DNA adducts; however, few have linked them to possible carcinogenic activity. This paper discussed four chemicals made in humans (formaldehyde, acetaldehyde, isoprene and ethylene oxide), pathways of their formation, their animal carcinogenicity and questions about these and other endogenous chemicals’ possible role in human cancer. In addition, the author posits a simplified formula for development of cancer and a formula for causing mutations by various agents.
{"title":"A speculative discussion of four animal carcinogens endogenously produced in humans and a formula for cancer development","authors":"R. Adamson","doi":"10.1177/2397847320977540","DOIUrl":"https://doi.org/10.1177/2397847320977540","url":null,"abstract":"The major factors (macro) which cause human cancer have been elucidated and include tobacco use, diet, infection, reproductive and sexual behavior and, to a lesser extent, alcohol consumption and occupational factors. Several reports have been published about endogenous chemicals made in humans which produce DNA adducts; however, few have linked them to possible carcinogenic activity. This paper discussed four chemicals made in humans (formaldehyde, acetaldehyde, isoprene and ethylene oxide), pathways of their formation, their animal carcinogenicity and questions about these and other endogenous chemicals’ possible role in human cancer. In addition, the author posits a simplified formula for development of cancer and a formula for causing mutations by various agents.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88360104","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 : 2020-11-27DOI: 10.1177/2397847320977782
F. Philippe, M. Xiang, M. Morgeneyer, Yan-ming Chen, P. Charles, F. Guingand, C. Bressot
Particles from brake, road and tire wear contribute to about half of the emissions (PM10) of particulate traffic pollution. It is estimated that 50 to 70% of the brake debris material is transformed into an emission of polydisperse aerosols. In order to improve the understanding of the brake debris generation and its dependency on the brake material, the wear of a disc and a brake pad from a standard production car were studied. The disc was made of perlitic cast iron with lamellar graphite and subjected to standard braking cycles. Microscopic evaluation was performed on the disc track, as well as analyses by Energy Dispersive Spectroscopy (EDS). Finally, a metallographic section has been made in the longitudinal direction of friction to better understand the morphology. The study focuses on disc surface oxidation and morphology of a thin layer on both disc and pin surface. Particle concentrations increase with the friction power and the area of contact surface. The observations show that the generation of particles can be the result of the oxidation of the disc surface during friction by two- and three-body abrasion when braking.
{"title":"Emission rate assessment of airborne brake particles by characterization of the pad and disc surfaces from a pin-on-disc tribometer","authors":"F. Philippe, M. Xiang, M. Morgeneyer, Yan-ming Chen, P. Charles, F. Guingand, C. Bressot","doi":"10.1177/2397847320977782","DOIUrl":"https://doi.org/10.1177/2397847320977782","url":null,"abstract":"Particles from brake, road and tire wear contribute to about half of the emissions (PM10) of particulate traffic pollution. It is estimated that 50 to 70% of the brake debris material is transformed into an emission of polydisperse aerosols. In order to improve the understanding of the brake debris generation and its dependency on the brake material, the wear of a disc and a brake pad from a standard production car were studied. The disc was made of perlitic cast iron with lamellar graphite and subjected to standard braking cycles. Microscopic evaluation was performed on the disc track, as well as analyses by Energy Dispersive Spectroscopy (EDS). Finally, a metallographic section has been made in the longitudinal direction of friction to better understand the morphology. The study focuses on disc surface oxidation and morphology of a thin layer on both disc and pin surface. Particle concentrations increase with the friction power and the area of contact surface. The observations show that the generation of particles can be the result of the oxidation of the disc surface during friction by two- and three-body abrasion when braking.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90322619","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 : 2020-11-24DOI: 10.1177/2397847320971255
P. Hanlon
Human Milk Oligosaccharides (HMOs) are the third most abundant, solid component of human milk after lactose and fat. As novel processes are developed to cost-effectively produce commercial volumes of these oligosaccharides, they are becoming more common components of infant formulas worldwide. The study evaluated the safety of a novel mixture of HMOs in a neonatal piglet model with the objective of identifying potential effects during the sensitive, preweaning developmental stage of life. The mixture of HMOs (HMO MIX 1) was composed of 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3′-sialyllactose (3′-SL), and 6′-sialyllactose (6′-SL), and was administered to 2-day old piglets at either 5.75 or 8.0 g/L for a period of 21 days. Piglets in the 5.75 and 8.0 g/L HMO MIX 1 dosing groups did not exhibit differences in body weight, food consumption, or feed efficiency. Analysis of clinical chemistry parameters on Study Day 7 and Study Day 21 did not demonstrate any effects that could be attributed to HMO MIX 1, nor were there any findings in organ weight, macroscopic, or microscopic inspection of tissues that could be attributed to this oligosaccharide blend. Therefore, since administration of HMO MIX 1 in a liquid diet up to 8.0 g/L resulted in no toxicologically-relevant effects in comparison with animals fed a control diet, this study supports the safety of this ingredient for addition to infant formula products.
{"title":"A safety evaluation of mixed human milk oligosaccharides in neonatal farm piglets","authors":"P. Hanlon","doi":"10.1177/2397847320971255","DOIUrl":"https://doi.org/10.1177/2397847320971255","url":null,"abstract":"Human Milk Oligosaccharides (HMOs) are the third most abundant, solid component of human milk after lactose and fat. As novel processes are developed to cost-effectively produce commercial volumes of these oligosaccharides, they are becoming more common components of infant formulas worldwide. The study evaluated the safety of a novel mixture of HMOs in a neonatal piglet model with the objective of identifying potential effects during the sensitive, preweaning developmental stage of life. The mixture of HMOs (HMO MIX 1) was composed of 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3′-sialyllactose (3′-SL), and 6′-sialyllactose (6′-SL), and was administered to 2-day old piglets at either 5.75 or 8.0 g/L for a period of 21 days. Piglets in the 5.75 and 8.0 g/L HMO MIX 1 dosing groups did not exhibit differences in body weight, food consumption, or feed efficiency. Analysis of clinical chemistry parameters on Study Day 7 and Study Day 21 did not demonstrate any effects that could be attributed to HMO MIX 1, nor were there any findings in organ weight, macroscopic, or microscopic inspection of tissues that could be attributed to this oligosaccharide blend. Therefore, since administration of HMO MIX 1 in a liquid diet up to 8.0 g/L resulted in no toxicologically-relevant effects in comparison with animals fed a control diet, this study supports the safety of this ingredient for addition to infant formula products.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78915500","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 : 2020-11-04DOI: 10.1177/2397847320971259
C. Patel, Sivakumar Prasanth Kumar, R. Rawal, M. Thaker, H. Pandya
Background: Bioinformatics and statistical analysis have been employed to develop a classification model to distinguish toxic and non-toxic molecules. Aims: The primary objective of this study is to enumerate the cut-off values of various physico-chemical (ligand-centric) and target interaction (receptor-centric) descriptors which forms the basis for classifying cardiotoxic and non-toxic molecules. We also sought correlation of molecular docking, absorption, distribution, metabolism, excretion, and toxicology (ADMET) parameters, Lipinski rules, physico-chemical parameters, etc. of human cardiotoxicity drugs. Methods: A training and test set of 91 compounds were applied to linear discriminant analysis (LDA) using 2D and 3D descriptors as discriminating variables representing various molecular modeling parameters to identify which function of descriptor type is responsible for cardiotoxicity. Internal validation was performed using the leave-one-out cross-validation methodology ensuing in good results, assuring the stability of the discriminant function (DF). Results: The values of the statistical parameters Fisher Discriminant Analysis (FDA) and Wilk’s λ for the DF showed reliable statistical significance, as long as the success rate in the prediction for both the training and the test set attained more than 93% accuracy, 87.50% sensitivity and 94.74% specificity. Conclusion: The predictive model was built using a hybrid approach using organ-specific targets for docking and ADMET properties for the FDA (Food and Drug Administration) approved and withdrawn drugs. Classifiers were developed by linear discriminant analysis and the cut-off was enumerated by receiver operating characteristic curve (ROC) analysis to achieve reliable specificity and sensitivity.
背景:利用生物信息学和统计分析方法建立了一种区分有毒和无毒分子的分类模型。目的:本研究的主要目的是列举各种物理化学(以配体为中心)和靶标相互作用(以受体为中心)描述符的截止值，这些描述符构成了心脏毒性和无毒分子分类的基础。我们还寻求人类心脏毒性药物的分子对接、吸收、分布、代谢、排泄和毒理学(ADMET)参数、Lipinski规则、理化参数等的相关性。方法:将91个化合物的训练和测试集应用于线性判别分析(LDA)，使用2D和3D描述符作为代表各种分子建模参数的判别变量，以确定描述符类型的功能负责心脏毒性。使用留一交叉验证方法进行内部验证，结果良好，保证了判别函数(DF)的稳定性。结果:只要训练集和测试集的预测成功率均达到93%以上的准确率、87.50%的灵敏度和94.74%的特异性，DF的统计参数Fisher Discriminant Analysis (FDA)和Wilk’s λ的值具有可靠的统计学意义。结论:该预测模型采用混合方法建立，结合器官特异性靶点对接和ADMET特性，适用于FDA (Food and Drug Administration, FDA)批准和撤销的药物。采用线性判别分析建立分类器，采用受试者工作特征曲线(ROC)分析列举截止值，达到可靠的特异性和敏感性。
{"title":"Development of cardiotoxicity model using ligand-centric and receptor-centric descriptors","authors":"C. Patel, Sivakumar Prasanth Kumar, R. Rawal, M. Thaker, H. Pandya","doi":"10.1177/2397847320971259","DOIUrl":"https://doi.org/10.1177/2397847320971259","url":null,"abstract":"Background: Bioinformatics and statistical analysis have been employed to develop a classification model to distinguish toxic and non-toxic molecules. Aims: The primary objective of this study is to enumerate the cut-off values of various physico-chemical (ligand-centric) and target interaction (receptor-centric) descriptors which forms the basis for classifying cardiotoxic and non-toxic molecules. We also sought correlation of molecular docking, absorption, distribution, metabolism, excretion, and toxicology (ADMET) parameters, Lipinski rules, physico-chemical parameters, etc. of human cardiotoxicity drugs. Methods: A training and test set of 91 compounds were applied to linear discriminant analysis (LDA) using 2D and 3D descriptors as discriminating variables representing various molecular modeling parameters to identify which function of descriptor type is responsible for cardiotoxicity. Internal validation was performed using the leave-one-out cross-validation methodology ensuing in good results, assuring the stability of the discriminant function (DF). Results: The values of the statistical parameters Fisher Discriminant Analysis (FDA) and Wilk’s λ for the DF showed reliable statistical significance, as long as the success rate in the prediction for both the training and the test set attained more than 93% accuracy, 87.50% sensitivity and 94.74% specificity. Conclusion: The predictive model was built using a hybrid approach using organ-specific targets for docking and ADMET properties for the FDA (Food and Drug Administration) approved and withdrawn drugs. Classifiers were developed by linear discriminant analysis and the cut-off was enumerated by receiver operating characteristic curve (ROC) analysis to achieve reliable specificity and sensitivity.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87524612","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 : 2020-10-23DOI: 10.1177/2397847320951377
C. Berry
Following a number of published expressions of concern about the reliability of experimental science and the implications of non-reproducibility for regulatory toxicology, the European Risk Forum undertook to consider what practises might improve the basis on which regulatory decisions might be made. Guidelines which may be useful in assessments are presented. The document acknowledges the value of the experimental standards used in most regulatory studies but indicates how these may fail to provide the ‘best outcome’ and how imperfect studies based on outdated views of pathophysiology of disease in H. Sapiens may offer little of predictive value.
{"title":"Frameworks for evaluation and integration of data in regulatory evaluations: The need for excellence in regulatory toxicology","authors":"C. Berry","doi":"10.1177/2397847320951377","DOIUrl":"https://doi.org/10.1177/2397847320951377","url":null,"abstract":"Following a number of published expressions of concern about the reliability of experimental science and the implications of non-reproducibility for regulatory toxicology, the European Risk Forum undertook to consider what practises might improve the basis on which regulatory decisions might be made. Guidelines which may be useful in assessments are presented. The document acknowledges the value of the experimental standards used in most regulatory studies but indicates how these may fail to provide the ‘best outcome’ and how imperfect studies based on outdated views of pathophysiology of disease in H. Sapiens may offer little of predictive value.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"108 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87258942","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 : 2020-10-14DOI: 10.1177/2397847320966961
Carr J. Smith, T. Perfetti, Richard G Morford
Ten years ago, the Halogenated Solvents Industry Alliance (HSIA) and the New York State Department of Environmental Conservation petitioned the US Environmental Protection Agency (USEPA) to classify 1-bromopropane (1-BP) as a hazardous air pollutant (HAP), the first such classification of a chemical since 1990. The USEPA plans to classify 1-BP as a HAP. One of the putative exposures supporting HAP classification is 1-BP-based dry cleaning solvents. Only two 1-BP-based dry cleaning solvents have ever been marketed domestically, i.e. the dominant market share product DrySolv® (DrySolv) and less commonly used FabrisolvTM XL (Fabrisolv). The use of 1-BP-based dry cleaning solvents has been declining for several years. Fabrisolv is no longer marketed as a dry cleaning agent. In the first half of 2020, less than 1,600 pounds of DrySolv have been sold for the remaining six dedicated dry cleaning machines still in operation in the United States. It is expected that the number of dedicated DrySolv dry cleaning machines in operation will be reduced to three by the end of 2020. In addition, no 1-BP-based spot cleaner has ever been marketed in the United States. USEPA currently classifies 187 chemicals as HAPs, with a subset of 30 HAPS classified as urban air toxics. Dry cleaning is considered to be one of the 68 “area sources” that contribute to sub-classification of 1-BP as an urban air toxic. In the near future, 1-BP-based products will not be employed in the dry cleaning industry.
{"title":"Use of 1-bromopropane (N-propyl bromide) in dry cleaning is rare and rapidly declining toward obsolescence","authors":"Carr J. Smith, T. Perfetti, Richard G Morford","doi":"10.1177/2397847320966961","DOIUrl":"https://doi.org/10.1177/2397847320966961","url":null,"abstract":"Ten years ago, the Halogenated Solvents Industry Alliance (HSIA) and the New York State Department of Environmental Conservation petitioned the US Environmental Protection Agency (USEPA) to classify 1-bromopropane (1-BP) as a hazardous air pollutant (HAP), the first such classification of a chemical since 1990. The USEPA plans to classify 1-BP as a HAP. One of the putative exposures supporting HAP classification is 1-BP-based dry cleaning solvents. Only two 1-BP-based dry cleaning solvents have ever been marketed domestically, i.e. the dominant market share product DrySolv® (DrySolv) and less commonly used FabrisolvTM XL (Fabrisolv). The use of 1-BP-based dry cleaning solvents has been declining for several years. Fabrisolv is no longer marketed as a dry cleaning agent. In the first half of 2020, less than 1,600 pounds of DrySolv have been sold for the remaining six dedicated dry cleaning machines still in operation in the United States. It is expected that the number of dedicated DrySolv dry cleaning machines in operation will be reduced to three by the end of 2020. In addition, no 1-BP-based spot cleaner has ever been marketed in the United States. USEPA currently classifies 187 chemicals as HAPs, with a subset of 30 HAPS classified as urban air toxics. Dry cleaning is considered to be one of the 68 “area sources” that contribute to sub-classification of 1-BP as an urban air toxic. In the near future, 1-BP-based products will not be employed in the dry cleaning industry.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"83 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76298727","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 : 2020-10-12DOI: 10.1177/2397847320964908
R. Maronpot, A. M. Leggett, D. A. Donahue, S. Hayashi, W. Breslin
An embryo-fetal survival and development study was conducted to augment the toxicity database for alpha-glycosyl isoquercitrin (AGIQ), a generally recognized as safe (GRAS) additive and flavor in food and beverages. In Phase I, 24 naturally mated New Zealand white (NZW) female rabbits per group were administered AGIQ by oral gavage at 0, 250, 500, or 1000 mg/kg/day once daily during gestation days 6–28, followed by necropsy. There was no evidence of maternal or fetal toxicity except for equivocal findings of unilateral absent kidney and ureter in one and two unrelated fetuses at 500 and 1000 mg/kg/day, respectively. To more thoroughly assess fetal kidney/ureter development, in Phase II groups of time mated NZW rabbits were administered AGIQ at 0, 500, or 1000 mg/kg/day, under the same conditions as Phase I. No occurrences of absent kidney/ureter were noted in the AGIQ-treated Phase II dams or fetuses; although, one control fetus had unilateral missing kidney/ureter. Given the lack of reproducibility following treatment with AGIQ in Phase II using 48 animals per group, the missing kidney/ureter observations in Phase I were considered unrelated to treatment. Since oral gavage administration of AGIQ to pregnant female NZW rabbits at dose levels of 250, 500, or 1000 mg/kg/day was well-tolerated with no adverse treatment-related effects on the maternal animal, pregnancy, or the developing conceptus, the no-observed-adverse-effect-level (NOAEL) for maternal toxicity and embryo-fetal survival, growth, and development was 1000 mg/kg/day.
{"title":"Embryo-fetal developmental toxicity study of alpha-glycosyl isoquercitrin administered orally to New Zealand White rabbits","authors":"R. Maronpot, A. M. Leggett, D. A. Donahue, S. Hayashi, W. Breslin","doi":"10.1177/2397847320964908","DOIUrl":"https://doi.org/10.1177/2397847320964908","url":null,"abstract":"An embryo-fetal survival and development study was conducted to augment the toxicity database for alpha-glycosyl isoquercitrin (AGIQ), a generally recognized as safe (GRAS) additive and flavor in food and beverages. In Phase I, 24 naturally mated New Zealand white (NZW) female rabbits per group were administered AGIQ by oral gavage at 0, 250, 500, or 1000 mg/kg/day once daily during gestation days 6–28, followed by necropsy. There was no evidence of maternal or fetal toxicity except for equivocal findings of unilateral absent kidney and ureter in one and two unrelated fetuses at 500 and 1000 mg/kg/day, respectively. To more thoroughly assess fetal kidney/ureter development, in Phase II groups of time mated NZW rabbits were administered AGIQ at 0, 500, or 1000 mg/kg/day, under the same conditions as Phase I. No occurrences of absent kidney/ureter were noted in the AGIQ-treated Phase II dams or fetuses; although, one control fetus had unilateral missing kidney/ureter. Given the lack of reproducibility following treatment with AGIQ in Phase II using 48 animals per group, the missing kidney/ureter observations in Phase I were considered unrelated to treatment. Since oral gavage administration of AGIQ to pregnant female NZW rabbits at dose levels of 250, 500, or 1000 mg/kg/day was well-tolerated with no adverse treatment-related effects on the maternal animal, pregnancy, or the developing conceptus, the no-observed-adverse-effect-level (NOAEL) for maternal toxicity and embryo-fetal survival, growth, and development was 1000 mg/kg/day.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86880539","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：