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Bruce K. Bernard - One of the best experts on this subject based on the ideXlab platform.
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Studies of the Toxicological Potential of Capsinoids, XII: Pharmacokinetic Study of Capsinoid-Containing CH-19 Sweet Extract in Rats
2016Co-Authors: Ryuichi Mihara, Bruce K. BernardAbstract:Pharmacokinetics of the main capsinoid components of CH-19 Sweet extract (capsiate, dihydrocapsiate, and nordihydrocapsiate) were investigated in rats receiving a single gavage dose of extract containing 10 or 100 mg of Capsinoids per kilogram in medium-chain triglyceride. Resultant blood levels of these Capsinoids and a capsinoid metabolite, vanillyl alcohol, were measured in portal vein and systemic blood. Capsinoids were never detected. Portal compartment vanillyl alcohol concentrations and area under the plasma concentration versus time curve increased approximately with dose, whereas the time to maximum concentration of vanillyl alcohol was independent of dose (30 minutes post dosing), suggesting that precipitation in the stomach or intestines was unlikely. Vanillyl alcohol levels were just barely detectable in systemic plasma (5 minutes post dosing). Significant levels of vanillyl alcohol conjugates, sulfate, and glucuronide were detected in the systemic blood. Given that the orally administered Capsinoids were never detected in the portal vein or systemic circulation, these compounds must be broken down (chemically or enzyma-tically) to vanillyl alcohol
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2008c. Studies of the toxicological potential of Capsinoids VIII: A 13-week toxicity study of commercial grade dihydrocapsiate in
2016Co-Authors: Eri Watanabe, Shoji Tsubuku, Terutaka Kodama, Takeshi Masuyama, Akira Otabe, Masahiro Mochizuki, Madoka Nakajima, Shoji Masumori, Bruce K. BernardAbstract:A single-dose oral toxicity lethal-dose study was conducted to examine the toxicity of Capsinoids contained in CH-19 Sweet ex-tract. CH-19 Sweet extract was administered once by gavage to SPF (Crl:CD(SD)) Sprague-Dawley male and female rats at dose levels of 0 (vehicle), 5, 10, or 20 ml/kg of body weight (BW). The concen-tration of Capsinoids in the CH-19 Sweet extract was 71.25 mg/ml; this resulted in administered dose levels of Capsinoids of 356.25, 712.5, and 1425 mg/kg BW, respectively. The toxicity of CH-19 Sweet extract by single oral administration was low; only transient salivation or decreased spontaneous movement was observed on the day of administration at ≥10 ml/kg BW. It was concluded that the lethal dose of CH-19 Sweet extract was estimated to be higher than 20 ml/kg (1425 mg/kg as Capsinoids) for both males and females since no deaths were observed at any dose in this study. A bacte-rial reverse mutation test of CH-19 Sweet extract was performe
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Shoji Tsubuku
2015Co-Authors: Terutaka Kodama, Eri Watanabe, Takeshi Masuyama, Akira Otabe, Masahiro Mochizuki, Bruce K. BernardAbstract:A 26-week oral toxicity study of Capsinoids-containing CH-19 Sweet extract was conducted in Sprague- Dawley rats (20 males and 20 females per group) at 6 weeks of age. The test substance was administered by gavage for 26 weeks at dose levels of 0 (vehicle), 1.25, 2.5 and 5.0 mL/kg/day. The concentration of Capsinoids in the CH-19 Sweet extract employed was 71.25-73.15 mg/mL, resulting in dose levels of Capsinoids of 89.06 to 91.44, 178.13 to 182.88 and 356.25 to 365.75 mg/kg, respectively. Adverse test article-related changes were only observed in males, not in females, and within the males, only at the high dose (5.0 mL/kg). Within that group (high-dose males), increases were observed in the numbers of segmented neutrophils, AST, ALT and LDH activities, liver weights and in the incidence and severity of hepatocellular focal necrosis. No test substance-related changes were detected in clinical signs, body weight, food consumption, water intake, ophthalmology or urinalysis. No adverse test article changes were observed in low or mid-dose males or in females at any dose. Based on the results of this chronic gavage study, the target organ was the liver and the no-observed-adverse-effect-level (NOAEL) for CH-19 Sweet extract in the rat was 2.5 mL/kg/day in males an
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RUNNING TITLE:
2015Co-Authors: Terutaka Kodama, Eri Watanabe, Takeshi Masuyama, Akira Otabe, Yoshihiro Katsumata, Bruce K. BernardAbstract:2 CH-19 Sweet extract, containing 66.5-75.05 mg/mL Capsinoids, was administered once daily by gavage, to two generations of male and female Sprague-Dawley rats, at dose levels of 0 (vehicle), 1.25, 2.5 and 5.0 mL/kg/day (83.13 to 93.81, 166.25 to 187.63 and 332.50 to 375.25 mg/kg as Capsinoids, respectively) in order to determine its potential reproductive effects. In first generation (F0) males and females, there were no test substance-related deaths, toxic changes, gross pathological findings or adverse findings in clinical signs, body weight, or food consumption. There were no test substance-related effects on estrous cycles, copulation index, days required for copulation, fertility index, number of implantations, gestation period, number of liveborn pups, delivery index, stillbirth index, livebirth index, or lactation or nursing. In the second generation (F1), there were no test substance-related changes observed in clinical signs, body weights, sex ratios at birth, external abnormalities, differences in survival at any point from birth to weaning and no deaths after weaning. here were no changes suggestive of adverse test substance-induce
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Shoji Tsubuku
2015Co-Authors: Terutaka Kodama, Takeshi Masuyama, Akira Otabe, Masahiro Mochizuki, Madoka Nakajima, Bruce K. BernardAbstract:2 A single dose oral toxicity lethal dose study was conducted to examine the toxicity of Capsinoids contained in CH-19 Sweet extract. CH-19 Sweet extract was administered once by gavage to SPF (Crl:CD(SD)) Sprague-Dawley male and female rats at dose levels of 0 (vehicle), 5, 10 or 20 mL/kg of body weight (BW). The concentration of Capsinoids in the CH-19 Sweet extract was 71.25 mg/mL; this resulted in administered dose levels of Capsinoids of 356.25, 712.5 and 1425 mg/kg BW, respectively. The toxicity of CH-19 Sweet extract by single oral administration was low; only transient salivation or decreased spontaneous movement was observed on the day of administration at>10 mL/kg BW. It was concluded that the lethal dose of CH-19 Sweet extract was estimated to be higher than 20 mL/kg (1425 mg/kg as Capsinoids) for both males and females since no deaths were observed at any dose in this study. A bacterial reverse mutation test of CH-19 Sweet extract was performed employing S. typhimurium and E. coli and using the pre-incubation method. Treatment with CH-19 Sweet extract did not increase the number of revertant colonies compared with negative controls eithe
Gerardo F. Barbero - One of the best experts on this subject based on the ideXlab platform.
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Changes in Capsiate Content in Four Chili Pepper Genotypes (Capsicum spp.) at Different Ripening Stages
Agronomy, 2020Co-Authors: Mercedes Vázquez-espinosa, Miguel Palma, Oreto Fayos, Ana V. González-de-peredo, Estrella Espada-bellido, Marta Ferreiro-gonzález, Ana Garcés-claver, Gerardo F. BarberoAbstract:Interest in the consumption of the fruits of pepper (Capsicum spp.) is not only due to its organoleptic characteristics, but also due to its bioactive compounds content, which are reported to provide essential benefits to human health. However, the amount and diversity of these compounds in each fruit specimen depend on its genotype and on a number of environmental factors. This work describes the quantitative ultra-high-performance liquid chromatography coupled to photodiode-array (UHPLC-PDA) analysis of the Capsinoids content in four varieties of pepper (‘Habanero’, ‘Habanero Roxo’, ‘Bode’, and ‘Malagueta’) grown until different development stages in a greenhouse under controlled conditions. In all the varieties analyzed, capsiate was the only capsinoid found. The accumulation of capsiate, in all the pepper varieties, started from the 10th to the 20th day post-anthesis (dpa), and increased during the first days (between the 20th and the 27th dpa). From that moment a drastic reduction took place until the end of the ripening stage, except for ‘Bode’ peppers, where the capsiate content increased from the first harvest point on the 20th dpa up to the 76th dpa. The capsiate accumulation patterns over the development of the fruit has been related to the capsaicionoids accumulation patterns in the same samples of the four varieties of pepper. According to our results, the content evolution of both families of compounds will vary depending on each fruit’s genotype, as well as on environmental conditions. No clear trends have been established and, therefore, an in-depth analysis under controlled conditions should be carried out.
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Assessment of Capsaicinoid and Capsinoid Accumulation Patterns during Fruit Development in Three Chili Pepper Genotypes ( Capsicum spp.) Carrying Pun1 and pAMT Alleles Related to Pungency.
Journal of Agricultural and Food Chemistry, 2019Co-Authors: Oreto Fayos, Gerardo F. Barbero, María Savirón, Jesús Orduna, Cristina Mallor, Neftalí Ochoa-alejo, Octavio Martínez De La Vega, Ana Garcés-claverAbstract:Quantification, using an accurate analytical approach, of Capsinoids and capsaicinoids was performed on three chili pepper (Capsicum spp.) genotypes: “Chiltepin”, “Tampiqueno 74”, and “Bhut Joloki...
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Optimizing and Comparing Ultrasound- and Microwave-Assisted Extraction Methods Applied to the Extraction of Antioxidant Capsinoids in Peppers
Agronomy, 2019Co-Authors: Mercedes Vázquez-espinosa, Gerardo F. Barbero, Miguel Palma, Carmelo García Barroso, Marta Ferreiro-gonzález, Ana V. González De Peredo, Estrella Espada-bellidoAbstract:Capsinoids are very similar antioxidant compounds to capsaicinoids, but less irritating, non-pungent and more palatable, and can thus be used in greater concentrations for food applications. To date, three Capsinoids (capsiate, dihydrocapsiate, and nordihydrocapsiate) have been isolated from the pepper fruits. Due to its substantial commercial importance, it would be convenient to determine which pepper varieties have a richer content. Ultrasound- (UAE) and microwave- (MAE) assisted extraction have been implemented and analyzed using multivariate statistical methods. Firstly, different solvents were tested individually. The three best solvents were used in a set mixture design, where 42% methanol and 58% ethyl acetate were determined as the optimum combination for UAE, and 100% methanol for MAE. Subsequently, a Box–Behnken experimental design with four variables for both UAE and MAE (time, temperature, pH and sample mass:solvent volume “ratio”) was performed. The sample mass:solvent volume was the most influential variable in UAE; while for MAE no variable was any more influential than the others. Finally, both optimized extraction methods were successfully applied to different varieties of peppers. Besides, to demonstrate the efficiency of both extraction methods, a recovery study was performed. The results prove the potential of both techniques as highly adequate methods for the extraction of Capsinoids from peppers.
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Quantitation of capsiate and dihydrocapsiate and tentative identification of minor Capsinoids in pepper fruits (Capsicum spp.) by HPLC-ESI-MS/MS(QTOF).
Food Chemistry, 2019Co-Authors: Oreto Fayos, Gerardo F. Barbero, María Savirón, Jesús Orduna, Cristina Mallor, Ana Garcés-claverAbstract:Abstract A highly sensitive, selective method has been developed and validated for determination of capsiate and dihydrocapsiate for the first time using HPLC-ESI/MS(QTOF). For both Capsinoids, LODs and LOQs were 0.02 and 0.05 µmol/l, respectively. The intra- and interday repeatability values (RSD %) were 0.26–0.41% for retention time, and 2.25–2.11% for peak area. Recoveries were up to 98% and 97% for capsiate and dihydrocapsiate, respectively. This method was successfully applied to quantify capsiate and dihydrocapsiate in eight pepper fruit accessions. Capsinoids were found in the range of 1.21–544.59 μg/g DW for capsiate and of 0.61–81.95 μg/g DW for dihydrocapsiate. In the ‘Tabasco’ accession, capsiate and dihydrocapsiate were quantified for the first time, ranging from 3.09 to 58.76 and 1.80 to 6.94 μg/g DW, respectively. Additionally, the ESI-MS/MS(QTOF) analysis has allowed the tentative identification of two other minor Capsinoids by exact mass and fragmentation pattern, in the ‘Bhut Jolokia’ accession.
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use of multivariate statistical techniques to optimize the separation of 17 Capsinoids by ultra performance liquid chromatography using different columns
Talanta, 2015Co-Authors: Janclei Pereira Coutinho, Gerardo F. Barbero, Helena Teixeira Godoy, Miguel Palma, Oreto Fayos Avellán, Ana Garcesclaver, Carmelo García BarrosoAbstract:In this work a multivariate statistical tool (Derringer and Suich optimization) was proposed for the separation of seventeen Capsinoids (natural and synthetic) using the UHPLC-DAD chromatography. Capsinoids were analyzed at 280 nm. The variables optimized were the mobile phase (water (0.1% acetic acid as solvent A) and acetonitrile (0.1% as solvent B)), gradient time and flow rate. Two columns with different length (50 and 100 mm) were used for the chromatographic separation. The two columns used properly separated the seventeen Capsinoids, however the 100 mm column length showed a better chromatographic separation with a shorter run time and smaller peak widths. These results provided better values of limit of detection and quantification for the 100 mm column length. The better conditions of separation with the 100 mm column length were established with: initial mobile phase with 41.8% of solvent B; 3.96 min of linear gradient time to reach 100% of solvent B; flow rate of 0.679 mL min−1. A validation of the method has been done with excellent values of repeatability (RSD<1.92) and intermediate precision (RSD<3.92). The developed method has been applied to real samples. Capsiate has been identified and quantified in some varieties of peppers.
M. Assunta Dessì - One of the best experts on this subject based on the ideXlab platform.
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Antioxidant activity of Capsinoids
Journal of Agricultural and Food Chemistry, 2002Co-Authors: Antonella Rosa, Stefania Paccagnini, Mauro Ballero, Giovanni Appendino, Monica Deiana, Viviana Casu, M. Assunta DessìAbstract:Hot peppers are a good source of dietary antioxidants, encompassing, apart from widespread compounds (flavonoids, phenolic acids, carotenoids, vitamin A, ascorbic acid, tocopherols), also specific constituents such as the pungent capsaicinoids (capsaicin, dihydrocapsaicin, and related analogues). We have shown that Capsinoids also show remarkable antioxidant activity. These benign analogues of capsaicin could protect linoleic acid against free radical attack in simple in vitro systems, inhibiting both its autoxidation and its iron- or EDTA-mediated oxidation. These properties were retained in some simple synthetic analogues (vanillyl nonanoate and its dimerization products). Capsiate, dihydrocapsiate, and their analogues were devoid of pro-oxidant activity and showed a highly significant antioxidant activity in all systems investigated. Vanillyl nonanoate, a simple capsinoid mimic, was also tested on cell cultures for cytotoxic activity and the capacity to inhibit FeCl(3)-induced oxidation.
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Antioxidant activity of Capsinoids.
Journal of Agricultural and Food Chemistry, 2002Co-Authors: Antonella Rosa, Stefania Paccagnini, Mauro Ballero, Giovanni Appendino, Monica Deiana, Viviana Casu, M. Assunta DessìAbstract:Hot peppers are a good source of dietary antioxidants, encompassing, apart from widespread compounds (flavonoids, phenolic acids, carotenoids, vitamin A, ascorbic acid, tocopherols), also specific constituents such as the pungent capsaicinoids (capsaicin, dihydrocapsaicin, and related analogues). We have shown that Capsinoids also show remarkable antioxidant activity. These benign analogues of capsaicin could protect linoleic acid against free radical attack in simple in vitro systems, inhibiting both its autoxidation and its iron- or EDTA-mediated oxidation. These properties were retained in some simple synthetic analogues (vanillyl nonanoate and its dimerization products). Capsiate, dihydrocapsiate, and their analogues were devoid of pro-oxidant activity and showed a highly significant antioxidant activity in all systems investigated. Vanillyl nonanoate, a simple capsinoid mimic, was also tested on cell cultures for cytotoxic activity and the capacity to inhibit FeCl3-induced oxidation. Keywords: Antiox...
Byoung-cheorl Kang - One of the best experts on this subject based on the ideXlab platform.
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Marker-assisted backcross breeding for development of pepper varieties (Capsicum annuum) containing Capsinoids
Molecular Breeding, 2015Co-Authors: Hyeon-seok Jeong, Koeun Han, Jin-kyung Kwon, Siyoung Jang, Byoung-cheorl KangAbstract:Capsinoids have similar biological effects as capsaicinoids, including anticancer and anti-obesity properties. The Capsicum chinense ‘SNU11-001’ variety of pepper was previously reported to contain high levels of Capsinoids due to a mutation in the putative aminotransferase ( pAMT ) gene, which leads to production of the capsinoid precursor vanillyl alcohol. Here, to develop Capsicum annuum pepper varieties with high capsinoid contents, marker-assisted backcrossing was performed during backcross breeding. For foreground selection, plants carrying the pAMT/pamt genotype were selected from BC_1F_1 and BC_2F_1 populations using SCAR markers derived from the unique pamt mutation of ‘SNU11-001.’ To obtain background selection markers, 412 single nucleotide polymorphism (SNP) markers were screened to identify SNP markers polymorphic between the ‘Shinhong’ paternal lines and ‘SNU11-001.’ Of the 412 SNP markers, 204 polymorphic SNP markers evenly distributed in pepper genome were selected. BC_1F_1 and BC_2F_1 plants carrying the pAMT/pamt genotype were subjected to background selection using these SNP markers. Multiple genotypes were analyzed using a high-throughput genotyping system. As a result, one BC_1F_1 plant 84 % similar to the recurrent parent and seven BC_2F_1 plants showing more than 96 % recovery of the recurrent parent genotype were selected. Genetic backgrounds of the selected BC_2F_1 plants were evaluated using the genotype-by-sequencing (GBS) method to confirm the background selection results from the SNP marker set. GBS results showed that the recovery rate and positions of introgressed segments were well matched between two methods, demonstrating MABC can be successfully performed with only ~200 SNP markers.
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molecular breeding of pepper varieties capsicum annuum containing high levels of Capsinoids
2015 한국육종학회 차세대BG21사업단 GSP사업단 공동심포지엄, 2015Co-Authors: Hyeon-seok Jeong, Siyoung Jang, Heebum Yang, Byoung-cheorl KangAbstract:Capsinoids, low-pungent compounds, have the same biological effects as capsaicinoids such as anticancer and anti-obesity. A precursor of Capsinoids, vanillyl alcohol, is known to be produced by mutations in the putative-aminotransferase (pAMT) gene. In the previous study, ‘SNU11-001’ (Capsicum chinense) containing high levels of Capsinoids was identified in germplasm collections of Capsicum. This collection has a unique mutation in the pAMT gene that can cause dysfunction of this gene. In order to develop pepper varieties containing high Capsinoids contents, marker-assisted foreground and background selections were performed during backcross breeding. Compared to the conventional backcrossing, marker-assisted backcrossing (MABC) is extremely useful for recovery of a recurrent parent’s genetic background. For foreground selection, plants carrying the pAMT/pamt genotype were selected from a BC1F1 and BC2F1 populations using SCAR markers derived from the unique pAMT mutation of ‘SNU11-001’. To obtain background selection markers, a total of 412 single nucleotide polymorphism (SNP) markers was screened on ‘Shinghong’ parental lines and ‘SNU11-001’ to obtain polymorphic SNP markers. Of the 412 SNP markers, 144 and 204 polymorphic SNP markers evenly distributed in pepper genome were finally selected. BC1F1 and BC2F1 plants carrying the pAMT/pamt genotype were subjected to background selection using the selected marker sets. Multiple genotype analysis was done using a high-throughput genotyping system (EP1TM, Fluidigm®, USA). As a result, one BC1F1 plant 84% similar to the recurrent parent and several BC2F1 plants more than 96% recovery rate of the recurrent parent were selected. Genetic backgrounds of the selected BC2F1 plants were evaluated by the genotype-by-sequencing (GBS) method in order to confirm the background selection results using the SNP marker set. GBS results showed that recovery rate and positions of introgressed segments were well matched between two methods demonstrating MABC can be successfully done with a couple hundred SNP markers.
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Biosynthesis of capsinoid is controlled by the Pun1 locus in pepper
Molecular Breeding, 2013Co-Authors: Koeun Han, Hee-jin Jeong, Joohee Sung, Young Soo Keum, Myeong-cheoul Cho, Jeong-han Kim, Jin-kyung Kwon, Byung-dong Kim, Byoung-cheorl KangAbstract:Pungency in pepper ( Capsicum annuum L.) has unique characteristics due to the alkaloid compound group, capsaicinoids, which includes capsaicin. Although capsaicinoids have been proved to have pharmacological and physiological effects on human health, the application of capsaicinoids has been limited because of their pungency. Capsinoids found in non-pungent peppers share closely related structures with capsaicinoids and show similar biological effects. Previous studies demonstrated that mutations in the p - AMT gene were related to the production of Capsinoids; however, the pathway of capsinoid synthesis has not yet been fully elucidated. In this study, we performed genetic analysis to determine the mechanism of capsinoid synthesis using a F6 recombinant inbred line population. In this population, the presence/absence of Capsinoids co-segregated with the genotype of the Pun1 locus, without exception. In addition, we screened the patterns of capsinoid synthesis and the correlation between the Pun1 locus and capsinoid synthesis in p - AMT mutant accessions. In Capsicum germplasms, we selected amino-acid-substituted mutants in the PLP binding domain of the p - AMT gene. Capsinoids were not synthesized with the recessive pun1 gene, regardless of the p - AMT genotype, and no relationship was found between p - AMT mutant type and capsinoid content. We concluded that the Pun1 gene, which is responsible for capsaicinoid synthesis, also controls capsinoid synthesis.
Terutaka Kodama - One of the best experts on this subject based on the ideXlab platform.
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2008c. Studies of the toxicological potential of Capsinoids VIII: A 13-week toxicity study of commercial grade dihydrocapsiate in
2016Co-Authors: Eri Watanabe, Shoji Tsubuku, Terutaka Kodama, Takeshi Masuyama, Akira Otabe, Masahiro Mochizuki, Madoka Nakajima, Shoji Masumori, Bruce K. BernardAbstract:A single-dose oral toxicity lethal-dose study was conducted to examine the toxicity of Capsinoids contained in CH-19 Sweet ex-tract. CH-19 Sweet extract was administered once by gavage to SPF (Crl:CD(SD)) Sprague-Dawley male and female rats at dose levels of 0 (vehicle), 5, 10, or 20 ml/kg of body weight (BW). The concen-tration of Capsinoids in the CH-19 Sweet extract was 71.25 mg/ml; this resulted in administered dose levels of Capsinoids of 356.25, 712.5, and 1425 mg/kg BW, respectively. The toxicity of CH-19 Sweet extract by single oral administration was low; only transient salivation or decreased spontaneous movement was observed on the day of administration at ≥10 ml/kg BW. It was concluded that the lethal dose of CH-19 Sweet extract was estimated to be higher than 20 ml/kg (1425 mg/kg as Capsinoids) for both males and females since no deaths were observed at any dose in this study. A bacte-rial reverse mutation test of CH-19 Sweet extract was performe
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Shoji Tsubuku
2015Co-Authors: Terutaka Kodama, Eri Watanabe, Takeshi Masuyama, Akira Otabe, Masahiro Mochizuki, Bruce K. BernardAbstract:A 26-week oral toxicity study of Capsinoids-containing CH-19 Sweet extract was conducted in Sprague- Dawley rats (20 males and 20 females per group) at 6 weeks of age. The test substance was administered by gavage for 26 weeks at dose levels of 0 (vehicle), 1.25, 2.5 and 5.0 mL/kg/day. The concentration of Capsinoids in the CH-19 Sweet extract employed was 71.25-73.15 mg/mL, resulting in dose levels of Capsinoids of 89.06 to 91.44, 178.13 to 182.88 and 356.25 to 365.75 mg/kg, respectively. Adverse test article-related changes were only observed in males, not in females, and within the males, only at the high dose (5.0 mL/kg). Within that group (high-dose males), increases were observed in the numbers of segmented neutrophils, AST, ALT and LDH activities, liver weights and in the incidence and severity of hepatocellular focal necrosis. No test substance-related changes were detected in clinical signs, body weight, food consumption, water intake, ophthalmology or urinalysis. No adverse test article changes were observed in low or mid-dose males or in females at any dose. Based on the results of this chronic gavage study, the target organ was the liver and the no-observed-adverse-effect-level (NOAEL) for CH-19 Sweet extract in the rat was 2.5 mL/kg/day in males an
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RUNNING TITLE:
2015Co-Authors: Terutaka Kodama, Eri Watanabe, Takeshi Masuyama, Akira Otabe, Yoshihiro Katsumata, Bruce K. BernardAbstract:2 CH-19 Sweet extract, containing 66.5-75.05 mg/mL Capsinoids, was administered once daily by gavage, to two generations of male and female Sprague-Dawley rats, at dose levels of 0 (vehicle), 1.25, 2.5 and 5.0 mL/kg/day (83.13 to 93.81, 166.25 to 187.63 and 332.50 to 375.25 mg/kg as Capsinoids, respectively) in order to determine its potential reproductive effects. In first generation (F0) males and females, there were no test substance-related deaths, toxic changes, gross pathological findings or adverse findings in clinical signs, body weight, or food consumption. There were no test substance-related effects on estrous cycles, copulation index, days required for copulation, fertility index, number of implantations, gestation period, number of liveborn pups, delivery index, stillbirth index, livebirth index, or lactation or nursing. In the second generation (F1), there were no test substance-related changes observed in clinical signs, body weights, sex ratios at birth, external abnormalities, differences in survival at any point from birth to weaning and no deaths after weaning. here were no changes suggestive of adverse test substance-induce
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Shoji Tsubuku
2015Co-Authors: Terutaka Kodama, Takeshi Masuyama, Akira Otabe, Masahiro Mochizuki, Madoka Nakajima, Bruce K. BernardAbstract:2 A single dose oral toxicity lethal dose study was conducted to examine the toxicity of Capsinoids contained in CH-19 Sweet extract. CH-19 Sweet extract was administered once by gavage to SPF (Crl:CD(SD)) Sprague-Dawley male and female rats at dose levels of 0 (vehicle), 5, 10 or 20 mL/kg of body weight (BW). The concentration of Capsinoids in the CH-19 Sweet extract was 71.25 mg/mL; this resulted in administered dose levels of Capsinoids of 356.25, 712.5 and 1425 mg/kg BW, respectively. The toxicity of CH-19 Sweet extract by single oral administration was low; only transient salivation or decreased spontaneous movement was observed on the day of administration at>10 mL/kg BW. It was concluded that the lethal dose of CH-19 Sweet extract was estimated to be higher than 20 mL/kg (1425 mg/kg as Capsinoids) for both males and females since no deaths were observed at any dose in this study. A bacterial reverse mutation test of CH-19 Sweet extract was performed employing S. typhimurium and E. coli and using the pre-incubation method. Treatment with CH-19 Sweet extract did not increase the number of revertant colonies compared with negative controls eithe
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Eri Watanabe
2014Co-Authors: Bruce K. Bernard, Shoji Tsubuku, Terutaka Kodama, Akira Otabe, Yoshihiro Katsumata, Tetsuya Matsuoka, Takeshi MasuyamaAbstract:2 In order to evaluate the safety of CH-19 Sweet extract which contains Capsinoids, teratology studies were conducted in pregnant Sprague-Dawley rats (20 rats per group) and pregnant New Zealand White rabbits (17 to 22 animals per group). The test substance was administered to rats by gavage for 11 days on gestation days 7-17 at doses of 0 (vehicle), 1.25, 2.5 and 5.0 mL/kg and to rabbits for 13 days on gestation days 6-18 at doses of 0 (vehicle), 0.25, 0.5 and 1.0 mL/kg. As the concentration of Capsinoids in CH-19 Sweet extract was 72.2- 75.05 mg/mL, the resulting dose of Capsinoids administered to rats was 90.25, 180.5 and 361 mg/kg, and to rabbits was 18.76, 37.53 and 75.05 mg/kg in the vehicle, low- mid-, and high-dose groups, respectively In the rat study, no deaths occurred in any group and there were no test substance-related changes or abnormalities in clinical signs, body weight, food consumption or gross pathological findings. There were no test substance-related changes in the number of corpora lutea, number or index of implantations, index of embryo-fetal deaths, number of live fetuses, sex ratio, feta