Pub Date : 2022-01-01DOI: 10.1177/23978473211068834
C. Kruger, J. Symonds, D. Conze
TrueBroc® Glucoraphanin-Rich Broccoli Seed Extract (TrueBroc®), is a hot water extract of Brassica oleracea var. Italica Plenck (Brassicaceae) seeds. The broccoli seeds are non-genetically modified and are tested and selected for their specific glucosinolate content. TrueBroc® contains greater than 99% of the aliphatic glucosinolate glucoraphanin and its precursor glucoerucin in the glucosinolate fraction. A battery of toxicology assays was conducted on TrueBroc® which includes in vitro and in vivo genotoxicity studies, an acute oral toxicity study in rats, a subchronic toxicology study in rats. The result from the subchronic rat study establishes a NOAEL of 1500 mg/kg/day.
{"title":"Toxicological assessment of truebroc® glucoraphanin-rich broccoli seed extract","authors":"C. Kruger, J. Symonds, D. Conze","doi":"10.1177/23978473211068834","DOIUrl":"https://doi.org/10.1177/23978473211068834","url":null,"abstract":"TrueBroc® Glucoraphanin-Rich Broccoli Seed Extract (TrueBroc®), is a hot water extract of Brassica oleracea var. Italica Plenck (Brassicaceae) seeds. The broccoli seeds are non-genetically modified and are tested and selected for their specific glucosinolate content. TrueBroc® contains greater than 99% of the aliphatic glucosinolate glucoraphanin and its precursor glucoerucin in the glucosinolate fraction. A battery of toxicology assays was conducted on TrueBroc® which includes in vitro and in vivo genotoxicity studies, an acute oral toxicity study in rats, a subchronic toxicology study in rats. The result from the subchronic rat study establishes a NOAEL of 1500 mg/kg/day.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"455 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81792714","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 : 2022-01-01DOI: 10.1177/23978473221146222
E. Agoro, C. G. Ikimi
The translocation capacity of metals (Cd, Cr, As, Pb, and Hg) was determined in water and fish, and in the serum and vitreous humor harvested from New Zealand White (albino) rabbits fed with the processed fish. The sample size comprised 12 male rabbits divided equally into control and experimental groups. Both groups were fed with normal rabbit meal void of detectable metals for 3 months. Only animals grouped under the experimental group were fed fish meal harvested from River Imiringi, Bayelsa State, Nigeria. The metals of interest were estimated using Atomic Absorption Spectroscopy. Similarly, the choice statistical tool was the student t-test analyzed on SPSS version 18–22. The findings revealed that the studied heavy metal concentrations were higher in water and fish sourced from River Imiringi when compared with the World Health Organization’s minimum permissible limits. In the same vein, concentrations of cadmium, chromium, and total arsenic were significantly higher, whereas mercury was lower in fish when compared to that in the water. In addition, vitreous cadmium and lead concentrations were higher in the experimental group when compared with the control group, whereas vitreous chromium was lower. Furthermore, serum cadmium and chromium concentration comparisons were similar to that in the vitreous. The findings are indicative of the translocation capacity of metals from water to fish and then to serum and vitreous humor of rabbits. The increase in metal concentrations and their translocation capacity are potential risks to inhabitants of Imiringi that depends heavily on the river water resources.
{"title":"Translocation capacity of some heavy metals in aquatic food chain of crude oil impacted community of Imiringi in Bayelsa state, Nigeria","authors":"E. Agoro, C. G. Ikimi","doi":"10.1177/23978473221146222","DOIUrl":"https://doi.org/10.1177/23978473221146222","url":null,"abstract":"The translocation capacity of metals (Cd, Cr, As, Pb, and Hg) was determined in water and fish, and in the serum and vitreous humor harvested from New Zealand White (albino) rabbits fed with the processed fish. The sample size comprised 12 male rabbits divided equally into control and experimental groups. Both groups were fed with normal rabbit meal void of detectable metals for 3 months. Only animals grouped under the experimental group were fed fish meal harvested from River Imiringi, Bayelsa State, Nigeria. The metals of interest were estimated using Atomic Absorption Spectroscopy. Similarly, the choice statistical tool was the student t-test analyzed on SPSS version 18–22. The findings revealed that the studied heavy metal concentrations were higher in water and fish sourced from River Imiringi when compared with the World Health Organization’s minimum permissible limits. In the same vein, concentrations of cadmium, chromium, and total arsenic were significantly higher, whereas mercury was lower in fish when compared to that in the water. In addition, vitreous cadmium and lead concentrations were higher in the experimental group when compared with the control group, whereas vitreous chromium was lower. Furthermore, serum cadmium and chromium concentration comparisons were similar to that in the vitreous. The findings are indicative of the translocation capacity of metals from water to fish and then to serum and vitreous humor of rabbits. The increase in metal concentrations and their translocation capacity are potential risks to inhabitants of Imiringi that depends heavily on the river water resources.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"340 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80756190","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 : 2022-01-01Epub Date: 2022-04-23DOI: 10.1177/23978473221091852
Airton C Martins, Miriam B Virgolini, Alexey A Tinkov, Anatoly V Skalny, Rohan P Tirumala, Marcelo Farina, Abel Santamaria, Rongzhu Lu, Michael Aschner
Iron (Fe) is an essential trace element required for several physiological processes. It plays important roles in mitochondrial function, synthesis, and metabolism of the neurotransmitter, as well as oxygen transport. However, excess Fe can cause toxicity. Particularly, Fe overload may result in neurotoxicity, contributing to the development and progression of neurodegenerative diseases, although the molecular mechanisms underlying Fe-induced neurodegeneration have yet to be entirely understood. Alternative (non-rodent) experimental models have been pointed as important approaches to elucidate molecular and physiological events mediating Fe-induced pathology. Among such alternative strategies, an advantageous experimental worm-model system, Caenorhabditis elegans (C. elegans), has been used to investigate Fe-induced neurotoxicity and neurodegenerative disorders. Its genome has been fully sequenced, corroborating that it shares significant homology with mammalians, and has approximately 40% of human disease-related genes. As part of this review, we discuss studies using the C. elegans model to study molecular mechanisms such as oxidative stress, mitochondrial dysfunction, disturbed homeostasis, and its potential contribution to the study of metal-induced neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD).
{"title":"Iron overload and neurodegenerative diseases: What can we learn from <i>Caenorhabditis elegans</i>?","authors":"Airton C Martins, Miriam B Virgolini, Alexey A Tinkov, Anatoly V Skalny, Rohan P Tirumala, Marcelo Farina, Abel Santamaria, Rongzhu Lu, Michael Aschner","doi":"10.1177/23978473221091852","DOIUrl":"https://doi.org/10.1177/23978473221091852","url":null,"abstract":"<p><p>Iron (Fe) is an essential trace element required for several physiological processes. It plays important roles in mitochondrial function, synthesis, and metabolism of the neurotransmitter, as well as oxygen transport. However, excess Fe can cause toxicity. Particularly, Fe overload may result in neurotoxicity, contributing to the development and progression of neurodegenerative diseases, although the molecular mechanisms underlying Fe-induced neurodegeneration have yet to be entirely understood. Alternative (non-rodent) experimental models have been pointed as important approaches to elucidate molecular and physiological events mediating Fe-induced pathology. Among such alternative strategies, an advantageous experimental worm-model system, <i>Caenorhabditis elegans</i> (<i>C. elegans</i>), has been used to investigate Fe-induced neurotoxicity and neurodegenerative disorders. Its genome has been fully sequenced, corroborating that it shares significant homology with mammalians, and has approximately 40% of human disease-related genes. As part of this review, we discuss studies using the <i>C. elegans</i> model to study molecular mechanisms such as oxidative stress, mitochondrial dysfunction, disturbed homeostasis, and its potential contribution to the study of metal-induced neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD).</p>","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"6 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/07/30/nihms-1827729.PMC9390093.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40714592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1177/23978473221144682
Folake M. Ogaji, A. Numbere, A. Obafemi, D. Ogaji
The proliferation of harmful gases is a major global problem caused by anthropogenic activities. This study hypothesized that the emission of noxious gases varies seasonally in indoor and outdoor environments. Air samples were collected from 40 georeferenced residential areas (N = 40) in Port Harcourt using Aeroqual 500 monitor to measure six gases: CH4, CO, NH4, NO2, O3, and SO2. Samples were collected at different times, locations, and seasons. The analysis of variance (ANOVA) indicates a significant difference in concentration between gases, times, and locations at p < 0.001. But the interaction effect shows that times and seasons significantly affect noxious gas concentration compared to location. In general, the concentration of CO was the highest, while that of O3 was the lowest. The order of concentration is CO > SO2 > NO2 > CH4 > NH4 > O3. The concentrations of NO2 and SO2 were higher than the WHO limit, while CO, CH4, NH, and O3 were below the WHO limit. Furthermore, CO concentration was highest in the morning, while NO2 and SO2 concentrations were highest in the evening. For seasons, the CH4, NH4, NO2, and SO2 were higher during the dry season, while CO concentration was higher during the wet season. Pollutant levels should be regularly monitored to help provide exposure advisory to city dwellers on the impact of atmospheric pollution on their health.
{"title":"Concentration of noxious gases inside and outside residential apartments across different settlements in Port Harcourt metropolis, Nigeria","authors":"Folake M. Ogaji, A. Numbere, A. Obafemi, D. Ogaji","doi":"10.1177/23978473221144682","DOIUrl":"https://doi.org/10.1177/23978473221144682","url":null,"abstract":"The proliferation of harmful gases is a major global problem caused by anthropogenic activities. This study hypothesized that the emission of noxious gases varies seasonally in indoor and outdoor environments. Air samples were collected from 40 georeferenced residential areas (N = 40) in Port Harcourt using Aeroqual 500 monitor to measure six gases: CH4, CO, NH4, NO2, O3, and SO2. Samples were collected at different times, locations, and seasons. The analysis of variance (ANOVA) indicates a significant difference in concentration between gases, times, and locations at p < 0.001. But the interaction effect shows that times and seasons significantly affect noxious gas concentration compared to location. In general, the concentration of CO was the highest, while that of O3 was the lowest. The order of concentration is CO > SO2 > NO2 > CH4 > NH4 > O3. The concentrations of NO2 and SO2 were higher than the WHO limit, while CO, CH4, NH, and O3 were below the WHO limit. Furthermore, CO concentration was highest in the morning, while NO2 and SO2 concentrations were highest in the evening. For seasons, the CH4, NH4, NO2, and SO2 were higher during the dry season, while CO concentration was higher during the wet season. Pollutant levels should be regularly monitored to help provide exposure advisory to city dwellers on the impact of atmospheric pollution on their health.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86401455","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 : 2022-01-01DOI: 10.1177/23978473221108881
M. Dziwenka, A. Mozingo
Nicotinamide riboside (NR) is an analog of vitamin B3, which is naturally present in trace amounts in selected foods. Several B3 analogs are known precursors in the synthesis of nicotinamide adenine dinucleotide, including nicotinic acid (niacin) and nicotinamide (niacinamide). The safety of nicotinamide riboside hydrogen malate (NRHM), a salt of NR, was assessed in a bacterial reverse mutagenesis assay (Ames), in vitro micronucleus assay in human peripheral lymphocytes, a 14-day acute toxicology test (Sprague-Dawley rats), and a 90-day sub-chronic toxicology study in Sprague-Dawley rats. Based on the results of the 14-day study, the 90-day sub-chronic study was conducted comparing oral NRHM at 1000, 1500, and 3000 mg/kg/day with a vehicle control. No genotoxicity was observed. There were no mortalities or clinical observations attributed to the NRHM test substance administration over the course of the study. The no-observed-adverse effect level for NRHM was determined to be 3000 mg/kg bw/day in the female rats but 2000 mg/kg bw/day in the male rats due to a significantly lower body weight in males at the high dose. The results of this study imply that NRHM can be manufactured at a high level of purity, is not genotoxic, and is well-tolerated in in Sprague-Dawley rats.
{"title":"Preclinical safety assessments of nicotinamide riboside hydrogen malate","authors":"M. Dziwenka, A. Mozingo","doi":"10.1177/23978473221108881","DOIUrl":"https://doi.org/10.1177/23978473221108881","url":null,"abstract":"Nicotinamide riboside (NR) is an analog of vitamin B3, which is naturally present in trace amounts in selected foods. Several B3 analogs are known precursors in the synthesis of nicotinamide adenine dinucleotide, including nicotinic acid (niacin) and nicotinamide (niacinamide). The safety of nicotinamide riboside hydrogen malate (NRHM), a salt of NR, was assessed in a bacterial reverse mutagenesis assay (Ames), in vitro micronucleus assay in human peripheral lymphocytes, a 14-day acute toxicology test (Sprague-Dawley rats), and a 90-day sub-chronic toxicology study in Sprague-Dawley rats. Based on the results of the 14-day study, the 90-day sub-chronic study was conducted comparing oral NRHM at 1000, 1500, and 3000 mg/kg/day with a vehicle control. No genotoxicity was observed. There were no mortalities or clinical observations attributed to the NRHM test substance administration over the course of the study. The no-observed-adverse effect level for NRHM was determined to be 3000 mg/kg bw/day in the female rats but 2000 mg/kg bw/day in the male rats due to a significantly lower body weight in males at the high dose. The results of this study imply that NRHM can be manufactured at a high level of purity, is not genotoxic, and is well-tolerated in in Sprague-Dawley rats.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78754748","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 : 2022-01-01DOI: 10.1177/23978473221123955
J. Doherty
Chemical Epidemiology Studies (CES) can be both protective for humans of adverse health effects of chemicals as well as cause alarm leading to unwarranted remedial action and litigation. Inherent problems in conducting CES especially related to the study design goals and assessment of exposure are recognized. Many CES report adverse health outcomes at very low exposure levels implying that humans are uniquely or especially sensitive to the toxicity of these chemicals. Such unique sensitivity to humans would be especially important to scientists in human physiology, medical and toxicology communities. CES are currently appearing in the open literature more frequently and it is expected that they will be appearing even more frequently in the future especially if animal toxicity testing is reduced or eliminated. Experts on the nature of the reported adverse health outcomes should be playing a more critical role in the interpretation of CES because they are best suited to understand the many factors affecting natural and induced variability. Should animal toxicity testing be reduced, the role of toxicologists in the interpretation of CES will need to evolve. This manuscript addresses the need for more uniform standards in conducting, reporting, and review by independent, fully focused experts if CES studies reported in the open literature will be included in the health risk characterization and litigation of chemicals.
{"title":"The interpretation of chemical epidemiology studies requires integration with experts on the nature of the reported adverse outcome and toxicologists","authors":"J. Doherty","doi":"10.1177/23978473221123955","DOIUrl":"https://doi.org/10.1177/23978473221123955","url":null,"abstract":"Chemical Epidemiology Studies (CES) can be both protective for humans of adverse health effects of chemicals as well as cause alarm leading to unwarranted remedial action and litigation. Inherent problems in conducting CES especially related to the study design goals and assessment of exposure are recognized. Many CES report adverse health outcomes at very low exposure levels implying that humans are uniquely or especially sensitive to the toxicity of these chemicals. Such unique sensitivity to humans would be especially important to scientists in human physiology, medical and toxicology communities. CES are currently appearing in the open literature more frequently and it is expected that they will be appearing even more frequently in the future especially if animal toxicity testing is reduced or eliminated. Experts on the nature of the reported adverse health outcomes should be playing a more critical role in the interpretation of CES because they are best suited to understand the many factors affecting natural and induced variability. Should animal toxicity testing be reduced, the role of toxicologists in the interpretation of CES will need to evolve. This manuscript addresses the need for more uniform standards in conducting, reporting, and review by independent, fully focused experts if CES studies reported in the open literature will be included in the health risk characterization and litigation of chemicals.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85364455","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 : 2021-12-12DOI: 10.1177/23978473211062804
Vernieda B. Vergara, Jessica F. Hoffman, J. Kalinich
Background: Injuries with fragments of embedded metal are a common occurrence in armed conflicts. Unfortunately, the list of metals encountered on the modern battlefield are practically endless while the short- and long-term health effects, especially when embedded as in a shrapnel wound, are not well understood. One of the major concerns with these types of injuries is the solubilization of the embedded metal and the translocation and deposition to various organs of the body. Methods: Using a rodent model system developed in our laboratory to assess the health effects of embedded metal fragments, we surgically implanted metal pellets into the gastrocnemius muscles of male Sprague-Dawley rats. Test metals were chosen from a list promulgated by the U.S. Department of Defense as “metals of concern” with respect to embedded fragment wounds and included tungsten, nickel, cobalt, iron, copper, aluminum, lead, and depleted uranium. Tantalum was used as a control metal. Cohorts of the metal-implanted rats were humanely euthanized at 1, 3, 6, and 12-months post-implantation and a variety of tissues collected and analyzed for metal content using inductively coupled plasma-mass spectrometry. Results: With few exceptions, the embedded metal fragments eventually released solubilized metal ions, with the metals deposited in numerous tissues in the rats. Not all of the embedded metals localized to all tissues at significant levels. Copper, iron, and aluminum were not found in statistically significant levels, versus control, in any of the tissues analyzed. The other metals tested all appeared in elevated levels in the kidney which is not surprising since previous research has shown that they are also excreted in the urine at appreciable amounts. Tungsten and nickel were found in only a small number of tissues, tungsten in spleen, and nickel in liver and testes. Cobalt, lead, and depleted uranium showed the widest distribution with significant levels in liver, spleen, testes, lung, tibia, fibula, and femur. Conclusion: In this study, we showed that embedded metal fragments, such as those suffered in a shrapnel wound, could solubilize and metals become deposited in tissues far from the original site of implantation. Tissue deposition was metal-specific and many of the metals were found to cross the blood-testes barrier and were also found in bone. Since standard surgical guidance recommends leaving embedded fragments in place except for certain circumstances, this report will expand the understanding of tissue deposition of the solubilized metals and will hopefully aid healthcare professionals in developing long-term treatment strategies for dealing with these types of wounds.
{"title":"Metal distribution patterns in tissues from implanted Sprague-Dawley rats","authors":"Vernieda B. Vergara, Jessica F. Hoffman, J. Kalinich","doi":"10.1177/23978473211062804","DOIUrl":"https://doi.org/10.1177/23978473211062804","url":null,"abstract":"Background: Injuries with fragments of embedded metal are a common occurrence in armed conflicts. Unfortunately, the list of metals encountered on the modern battlefield are practically endless while the short- and long-term health effects, especially when embedded as in a shrapnel wound, are not well understood. One of the major concerns with these types of injuries is the solubilization of the embedded metal and the translocation and deposition to various organs of the body. Methods: Using a rodent model system developed in our laboratory to assess the health effects of embedded metal fragments, we surgically implanted metal pellets into the gastrocnemius muscles of male Sprague-Dawley rats. Test metals were chosen from a list promulgated by the U.S. Department of Defense as “metals of concern” with respect to embedded fragment wounds and included tungsten, nickel, cobalt, iron, copper, aluminum, lead, and depleted uranium. Tantalum was used as a control metal. Cohorts of the metal-implanted rats were humanely euthanized at 1, 3, 6, and 12-months post-implantation and a variety of tissues collected and analyzed for metal content using inductively coupled plasma-mass spectrometry. Results: With few exceptions, the embedded metal fragments eventually released solubilized metal ions, with the metals deposited in numerous tissues in the rats. Not all of the embedded metals localized to all tissues at significant levels. Copper, iron, and aluminum were not found in statistically significant levels, versus control, in any of the tissues analyzed. The other metals tested all appeared in elevated levels in the kidney which is not surprising since previous research has shown that they are also excreted in the urine at appreciable amounts. Tungsten and nickel were found in only a small number of tissues, tungsten in spleen, and nickel in liver and testes. Cobalt, lead, and depleted uranium showed the widest distribution with significant levels in liver, spleen, testes, lung, tibia, fibula, and femur. Conclusion: In this study, we showed that embedded metal fragments, such as those suffered in a shrapnel wound, could solubilize and metals become deposited in tissues far from the original site of implantation. Tissue deposition was metal-specific and many of the metals were found to cross the blood-testes barrier and were also found in bone. Since standard surgical guidance recommends leaving embedded fragments in place except for certain circumstances, this report will expand the understanding of tissue deposition of the solubilized metals and will hopefully aid healthcare professionals in developing long-term treatment strategies for dealing with these types of wounds.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89966314","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 : 2021-05-10DOI: 10.1177/23978473211016816
Y. Ahn, Jin Sil Choi, Dae hyun Kim, Temuulen Batsaikhan, Y. Seo
Sensorineural hearing loss due to ototoxic drugs remains as a conflict as the treatment option with aminoglycosides. Ototoxic mouse model was produced with the administration of ototoxic drugs aminoglycoside kanamycin and loop-diuretic furosemide, thus validation of auditory function of the mouse model is needed to determine the efficacy of the drugs. Kanamycin sulfate 550 mg/kg (VWR life sciences, PA, USA) and furosemide 130 mg/kg (Lasix, Handok, Korea) were administered through subcutaneous and intraperitoneal injection respectively. Auditory brainstem response and distortion otoacoustic emission tests were performed on days 3,5,7,10,14 post administration of the ototoxic drug. Thresholds in response to the stimulus given in the auditory brainstem recordings and distortion otoacoustic emission tests were obtained. The hearing threshold shift to high stimulus intensity was observed post administration of the ototoxic drug. Latency of the ABR peak waves were recorded and analyzed, latency delay was observed as hearing threshold increases. These findings will further support in the application of this animal model in various studies regarding ototoxic hearing loss.
{"title":"A validation study of auditory function in an aminoglycoside-furosemide ototoxicity mouse model: Auditory brainstem response and distortion product otoacoustic emissions","authors":"Y. Ahn, Jin Sil Choi, Dae hyun Kim, Temuulen Batsaikhan, Y. Seo","doi":"10.1177/23978473211016816","DOIUrl":"https://doi.org/10.1177/23978473211016816","url":null,"abstract":"Sensorineural hearing loss due to ototoxic drugs remains as a conflict as the treatment option with aminoglycosides. Ototoxic mouse model was produced with the administration of ototoxic drugs aminoglycoside kanamycin and loop-diuretic furosemide, thus validation of auditory function of the mouse model is needed to determine the efficacy of the drugs. Kanamycin sulfate 550 mg/kg (VWR life sciences, PA, USA) and furosemide 130 mg/kg (Lasix, Handok, Korea) were administered through subcutaneous and intraperitoneal injection respectively. Auditory brainstem response and distortion otoacoustic emission tests were performed on days 3,5,7,10,14 post administration of the ototoxic drug. Thresholds in response to the stimulus given in the auditory brainstem recordings and distortion otoacoustic emission tests were obtained. The hearing threshold shift to high stimulus intensity was observed post administration of the ototoxic drug. Latency of the ABR peak waves were recorded and analyzed, latency delay was observed as hearing threshold increases. These findings will further support in the application of this animal model in various studies regarding ototoxic hearing loss.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86721025","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 : 2021-01-01DOI: 10.1177/2397847321992752
D. Thorne, J. Adamson, E. T. Sticken, R. Wieczorek, H. Behrsing, S. Steiner, Shoaib Majeed, S. Frentzel, S. Ishikawa, S. Ito, L. Simms, K. Yoshino, J. Hoeng, M. Gaca
Given the complexity of inhaled substances, the aerosol exposure environment has seen diversification and development of setups in conjunction with the evolving in vitro toxicology space. Each laboratory uses its in vitro exposure system differently (different protocols, adaptations, and biological analysis). Unfortunately, as systems diversify, so does the complexity of comparing multiple systems in a “standardized” manner. As yet, no one has compared simply whether these diverse systems can all generate a consistent aerosol stream, which is paramount prior to transit and exposure. This study has compared, at source, aerosol generation (using nicotine as an exposure marker) in nine in vitro whole-aerosol exposure setups (seven different systems) across five distinct geographically independent locations, including the UK, the USA, Switzerland, Germany, and Japan. The results demonstrate that, despite system-wide differences (adaptations, nuances, and application), these systems—when appropriately maintained and used under a prescribed set of established conditions can all generate a consistent and statistically comparable aerosol stream. These data will be invaluable for new researchers and established laboratories, so they may benchmark against this study. Finally, this interlaboratory comparison combined with the wealth of transit and exposure interface data, may help the environment move towards a truly validated and consistent approach to aerosol exposure. Such an approach could be replicated for other aerosolized products, such as e-cigarettes and heated tobacco products.
{"title":"An interlaboratory in vitro aerosol exposure system reference study","authors":"D. Thorne, J. Adamson, E. T. Sticken, R. Wieczorek, H. Behrsing, S. Steiner, Shoaib Majeed, S. Frentzel, S. Ishikawa, S. Ito, L. Simms, K. Yoshino, J. Hoeng, M. Gaca","doi":"10.1177/2397847321992752","DOIUrl":"https://doi.org/10.1177/2397847321992752","url":null,"abstract":"Given the complexity of inhaled substances, the aerosol exposure environment has seen diversification and development of setups in conjunction with the evolving in vitro toxicology space. Each laboratory uses its in vitro exposure system differently (different protocols, adaptations, and biological analysis). Unfortunately, as systems diversify, so does the complexity of comparing multiple systems in a “standardized” manner. As yet, no one has compared simply whether these diverse systems can all generate a consistent aerosol stream, which is paramount prior to transit and exposure. This study has compared, at source, aerosol generation (using nicotine as an exposure marker) in nine in vitro whole-aerosol exposure setups (seven different systems) across five distinct geographically independent locations, including the UK, the USA, Switzerland, Germany, and Japan. The results demonstrate that, despite system-wide differences (adaptations, nuances, and application), these systems—when appropriately maintained and used under a prescribed set of established conditions can all generate a consistent and statistically comparable aerosol stream. These data will be invaluable for new researchers and established laboratories, so they may benchmark against this study. Finally, this interlaboratory comparison combined with the wealth of transit and exposure interface data, may help the environment move towards a truly validated and consistent approach to aerosol exposure. Such an approach could be replicated for other aerosolized products, such as e-cigarettes and heated tobacco products.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"220 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77443282","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 : 2021-01-01DOI: 10.1177/23978473211061428
T. Vo, Jwar Meetro, S. Floyd, B. Lynch, S. Tafazoli, Akio Ichihara, G. Chikamatsu
Purine nucleosidase (EC 3.2.2.1) catalyzes the N-riboside hydrolysis of purine nucleosides to D-ribose and a purine base. This enzyme may be used in the production of beer and other alcoholic beverages to reduce the purine content of these products. Purine nucleosidase was obtained from Aspergillus luchuensis naturally occurring in grain sources. The safety profile of purine nucleosidase is not well documented in the scientific literature, and a series of toxicological studies were undertaken to investigate the safety of its use in food production. Purine nucleosidase from A. luchuensis was non-mutagenic and non-clastogenic in a standard Ames test and in vitro mammalian chromosome aberration assay. Administration of purine nucleosidase in a 90-day subchronic toxicity study in Sprague-Dawley rats did not elicit adverse findings on any hematology, clinical chemistry, urinalysis, organ weight, or histopathological parameter at doses up to 1700 mg total organic solids (TOS)/kg body weight/day, the highest dose tested. The results suggest purine nucleosidase to lack systemic toxic effect. The no-observed-adverse-effect level was concluded to be 1700 mg TOS/kg body weight/day. The results of the toxicology studies support the safety of purine nucleosidase from a non-genetically modified strain of A. luchuensis when used in food production.
{"title":"Safety assessment of purine nucleosidase from Aspergillus luchuensis","authors":"T. Vo, Jwar Meetro, S. Floyd, B. Lynch, S. Tafazoli, Akio Ichihara, G. Chikamatsu","doi":"10.1177/23978473211061428","DOIUrl":"https://doi.org/10.1177/23978473211061428","url":null,"abstract":"Purine nucleosidase (EC 3.2.2.1) catalyzes the N-riboside hydrolysis of purine nucleosides to D-ribose and a purine base. This enzyme may be used in the production of beer and other alcoholic beverages to reduce the purine content of these products. Purine nucleosidase was obtained from Aspergillus luchuensis naturally occurring in grain sources. The safety profile of purine nucleosidase is not well documented in the scientific literature, and a series of toxicological studies were undertaken to investigate the safety of its use in food production. Purine nucleosidase from A. luchuensis was non-mutagenic and non-clastogenic in a standard Ames test and in vitro mammalian chromosome aberration assay. Administration of purine nucleosidase in a 90-day subchronic toxicity study in Sprague-Dawley rats did not elicit adverse findings on any hematology, clinical chemistry, urinalysis, organ weight, or histopathological parameter at doses up to 1700 mg total organic solids (TOS)/kg body weight/day, the highest dose tested. The results suggest purine nucleosidase to lack systemic toxic effect. The no-observed-adverse-effect level was concluded to be 1700 mg TOS/kg body weight/day. The results of the toxicology studies support the safety of purine nucleosidase from a non-genetically modified strain of A. luchuensis when used in food production.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"21 2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90690210","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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