Pub Date : 2023-01-01DOI: 10.1177/23978473231151258
B. Lynch, Tina Wang, T. Vo, S. Tafazoli, Jason Ryder
Naturally sweet proteins have no glycemic effect and offer a fundamentally new approach to sweetness and health for individuals seeking to reduce their added sugar intake. However, unlike many commercial sweeteners, little research has been performed on the potential safety implications of adding these uniquely sweet proteins to food and beverages. In this study, a naturally sweet protein found in the West African Oubli plant ( Pentadiplandra brazzeana), referred to as Oubli fruit sweet protein or brazzein, was expressed in Komagataella phaffii (formerly Pichia pastoris) and produced via precision fermentation, and a safety and risk assessment was undertaken for its use as a sweetener in food and beverages. Potential consumption levels of brazzein were estimated to be 3 mg/kg body weight/day based on the National Health and Nutrition Examination Survey. The safety of brazzein derived from K. phaffii was evaluated through in silico allergenicity, in vitro genotoxicity (reverse mutation and mammalian micronucleus assays), and a 90-day dietary oral toxicity study in rats. There was no indication of allergenicity in the in silico analyses. Brazzein was non-genotoxic in the in vitro assays and showed no adverse effects in the 90-day oral toxicity study up to the highest dose tested, where the no-observed-adverse-effect level (NOAEL) was 978 and 985 mg/kg body weight/day in males and females, respectively. The totality of evidence in the in silico allergenicity, in vitro genotoxicity, and 90-day dietary toxicity studies demonstrates that brazzein derived from K. phaffii is considered safe for use as a sweetener in food and beverages.
{"title":"Safety evaluation of oubli fruit sweet protein (brazzein) derived from Komagataella phaffii, intended for use as a sweetener in food and beverages","authors":"B. Lynch, Tina Wang, T. Vo, S. Tafazoli, Jason Ryder","doi":"10.1177/23978473231151258","DOIUrl":"https://doi.org/10.1177/23978473231151258","url":null,"abstract":"Naturally sweet proteins have no glycemic effect and offer a fundamentally new approach to sweetness and health for individuals seeking to reduce their added sugar intake. However, unlike many commercial sweeteners, little research has been performed on the potential safety implications of adding these uniquely sweet proteins to food and beverages. In this study, a naturally sweet protein found in the West African Oubli plant ( Pentadiplandra brazzeana), referred to as Oubli fruit sweet protein or brazzein, was expressed in Komagataella phaffii (formerly Pichia pastoris) and produced via precision fermentation, and a safety and risk assessment was undertaken for its use as a sweetener in food and beverages. Potential consumption levels of brazzein were estimated to be 3 mg/kg body weight/day based on the National Health and Nutrition Examination Survey. The safety of brazzein derived from K. phaffii was evaluated through in silico allergenicity, in vitro genotoxicity (reverse mutation and mammalian micronucleus assays), and a 90-day dietary oral toxicity study in rats. There was no indication of allergenicity in the in silico analyses. Brazzein was non-genotoxic in the in vitro assays and showed no adverse effects in the 90-day oral toxicity study up to the highest dose tested, where the no-observed-adverse-effect level (NOAEL) was 978 and 985 mg/kg body weight/day in males and females, respectively. The totality of evidence in the in silico allergenicity, in vitro genotoxicity, and 90-day dietary toxicity studies demonstrates that brazzein derived from K. phaffii is considered safe for use as a sweetener in food and beverages.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"88 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76846063","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 : 2023-01-01DOI: 10.1177/23978473231162859
Jayesh Muchhara, Kapil Vachhani, Sandip Dave, Rikesh Patel, Neha Lavle, Dhaval Kukadia, Avnish Patel, Chintan D Patel, R. Gokani, B. Mahadevan
Bacopa monnieri is an important medicinal plant widely used in various food systems and gaining interest these days for its health benefits such as boosting brain function and improving quality of life. The objective of the present study was to examine the safety of Bacognize®, a standardized botanical extract obtained from the whole herb Bacopa monnieri (L.) Wettst., in subchronic toxicity and genotoxicity studies conducted in compliance with Good Laboratory Practice (GLP) and test guidelines established by the Organization for Economic Cooperation and Development (OECD). In the subchronic toxicity study, treatment with Bacognize® did not result in any toxicologically significant treatment-related changes in clinical observations, and in the clinical pathology as studied by hematology, serum chemistry, urinalysis, and terminal necropsy. Treatment-related adverse effects were not observed in ophthalmic examinations, body weights, body weight gains, feed consumption, and organ weights. The results of genotoxicity studies as assessed by gene mutations in Salmonella typhimurium, in vitro chromosome aberrations and in vivo micronucleus test did not reveal any genotoxicity of Bacognize ®. The no-observed-adverse-effect level (NOAEL) for Bacognize® was established based on the subchronic study and was determined as at least 1000 mg/kg bw/day. These results indicate that Bacognize® does not cause significant adverse effects and suggest its tolerability up to 1000 mg/kg (highest dose tested) for the daily administration of 90 days in rats.
{"title":"Safety evaluation of the genotoxicity and subchronic toxicity of standardized Bacopa extract (Bacognize®) from Bacopa monnieri","authors":"Jayesh Muchhara, Kapil Vachhani, Sandip Dave, Rikesh Patel, Neha Lavle, Dhaval Kukadia, Avnish Patel, Chintan D Patel, R. Gokani, B. Mahadevan","doi":"10.1177/23978473231162859","DOIUrl":"https://doi.org/10.1177/23978473231162859","url":null,"abstract":"Bacopa monnieri is an important medicinal plant widely used in various food systems and gaining interest these days for its health benefits such as boosting brain function and improving quality of life. The objective of the present study was to examine the safety of Bacognize®, a standardized botanical extract obtained from the whole herb Bacopa monnieri (L.) Wettst., in subchronic toxicity and genotoxicity studies conducted in compliance with Good Laboratory Practice (GLP) and test guidelines established by the Organization for Economic Cooperation and Development (OECD). In the subchronic toxicity study, treatment with Bacognize® did not result in any toxicologically significant treatment-related changes in clinical observations, and in the clinical pathology as studied by hematology, serum chemistry, urinalysis, and terminal necropsy. Treatment-related adverse effects were not observed in ophthalmic examinations, body weights, body weight gains, feed consumption, and organ weights. The results of genotoxicity studies as assessed by gene mutations in Salmonella typhimurium, in vitro chromosome aberrations and in vivo micronucleus test did not reveal any genotoxicity of Bacognize ®. The no-observed-adverse-effect level (NOAEL) for Bacognize® was established based on the subchronic study and was determined as at least 1000 mg/kg bw/day. These results indicate that Bacognize® does not cause significant adverse effects and suggest its tolerability up to 1000 mg/kg (highest dose tested) for the daily administration of 90 days in rats.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82962211","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 : 2023-01-01DOI: 10.1177/23978473231169090
W. Breslin, Jaime L Mesnard, R. Maronpot, Mihoko Koyanagi, Shuichi Chiba, Masayuki Nishino, S. Hayashi
Gardenia blue is a colorant widely used in Asia in food and beverages. The objectives of the present studies were to evaluate the maternal and prenatal embryo-fetal developmental toxicity of gardenia blue in rats and rabbits. Sprague Dawley rats and New Zealand White rabbits were administered gardenia blue daily by oral gavage at doses of 0 (deionized water vehicle), 500, 1000 or 2000 mg/kg/day on Gestation Days 6 through 20 (rats) and 7 through 28 (rabbits). Endpoints evaluated included clinical observations, body weight, food consumption, thyroid hormones (rats), thyroid weights and histopathology (rats), gross pathologic changes, ovarian and uterine observations, fetal weight and anogenital distance (rats) and fetal morphology (external, visceral and skeletal). Treatment related maternal findings attributed to the blue/dark color of the test substance included body surface staining, and dark/blue discoloration of the kidneys, gastrointestinal track and mesenteric lymph nodes at all or most doses in the rat and/or rabbit. Slight reductions in food consumption without effects on body weight were also observed in rats at all doses and in rabbits at 2000 mg/kg/day. There were no treatment related effects on maintenance of pregnancy, postimplantation loss, litter size, fetal weight and anogenital distance, or fetal external, visceral, or skeletal malformations and variations. Based on these results, the maternal and developmental no-observed-adverse-effect level for gardenia blue in rats and rabbits was ≥2000 mg/kg/day.
{"title":"Prenatal developmental toxicity of gardenia blue, a natural food colorant, in rats and rabbits","authors":"W. Breslin, Jaime L Mesnard, R. Maronpot, Mihoko Koyanagi, Shuichi Chiba, Masayuki Nishino, S. Hayashi","doi":"10.1177/23978473231169090","DOIUrl":"https://doi.org/10.1177/23978473231169090","url":null,"abstract":"Gardenia blue is a colorant widely used in Asia in food and beverages. The objectives of the present studies were to evaluate the maternal and prenatal embryo-fetal developmental toxicity of gardenia blue in rats and rabbits. Sprague Dawley rats and New Zealand White rabbits were administered gardenia blue daily by oral gavage at doses of 0 (deionized water vehicle), 500, 1000 or 2000 mg/kg/day on Gestation Days 6 through 20 (rats) and 7 through 28 (rabbits). Endpoints evaluated included clinical observations, body weight, food consumption, thyroid hormones (rats), thyroid weights and histopathology (rats), gross pathologic changes, ovarian and uterine observations, fetal weight and anogenital distance (rats) and fetal morphology (external, visceral and skeletal). Treatment related maternal findings attributed to the blue/dark color of the test substance included body surface staining, and dark/blue discoloration of the kidneys, gastrointestinal track and mesenteric lymph nodes at all or most doses in the rat and/or rabbit. Slight reductions in food consumption without effects on body weight were also observed in rats at all doses and in rabbits at 2000 mg/kg/day. There were no treatment related effects on maintenance of pregnancy, postimplantation loss, litter size, fetal weight and anogenital distance, or fetal external, visceral, or skeletal malformations and variations. Based on these results, the maternal and developmental no-observed-adverse-effect level for gardenia blue in rats and rabbits was ≥2000 mg/kg/day.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91052588","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 : 2023-01-01DOI: 10.1177/23978473231167422
Boma F. Eddie-Amadi, A. Ezejiofor, C. Orish, A. Ćirović, Aleksandar Cirovic, O. Orisakwe
This is an evaluation of the effects of banana peel BP extract on the heavy metals’ mixture HMM mediated oxido-inflammatory effects in the thyroid of female albino rats. Five groups (5 female rats/group) were treated as follows for 60 days: Group 1: Deionized water only; Group 2: (Pb, Hg, Mn and Al); Group 3: 200 mg/kg BP extract + HMM; Group 4: 400 mg/kg BP extract + HMM; Group 5: 800 mg/kg BP extract + HMM. On day 60 animals were euthanized, thyroid was harvested and used for, malondialdehyde MDA, nitric oxide NO, antioxidants, tumor necrosis factor alpha (TNF – α), interleukin 6 (IL – 6), Caspase-3, Nuclear factor erythroid 2- related factor 2 (Nrf2), Nuclear factor kappa B (NfkB) and Heme Oxygynase – 1 (Hmox-1) and histopathology. There was significant bioaccumulation of Pb, Al, Hg and MN; elevated IL-6 and Tnf-α, MDA and NO, caspase-3 and Nrf2, NF-κB and Hmox-1 in the HMM only group in comparison to the control. There was significant ( p < 0.05) decrease in SOD, CAT GSH activities in HMM only exposed group in comparison to the control deionized water group, whereas BP co-treatment with HMM significantly ( p < 0.05) increased SOD, CAT GSH activities. Co-treatment with BP extract also reversed most of these effects. BP extract may ameliorate HMM -induced thyrotoxicity in female albino rats by blunting oxido-inflammatory activities.
{"title":"Banana peel extract alleviate inflammation and oxidative stress via modulation of the Nrf2/Hmox-1 and NF-κB pathways in thyroid of heavy metal mixture exposed female rats","authors":"Boma F. Eddie-Amadi, A. Ezejiofor, C. Orish, A. Ćirović, Aleksandar Cirovic, O. Orisakwe","doi":"10.1177/23978473231167422","DOIUrl":"https://doi.org/10.1177/23978473231167422","url":null,"abstract":"This is an evaluation of the effects of banana peel BP extract on the heavy metals’ mixture HMM mediated oxido-inflammatory effects in the thyroid of female albino rats. Five groups (5 female rats/group) were treated as follows for 60 days: Group 1: Deionized water only; Group 2: (Pb, Hg, Mn and Al); Group 3: 200 mg/kg BP extract + HMM; Group 4: 400 mg/kg BP extract + HMM; Group 5: 800 mg/kg BP extract + HMM. On day 60 animals were euthanized, thyroid was harvested and used for, malondialdehyde MDA, nitric oxide NO, antioxidants, tumor necrosis factor alpha (TNF – α), interleukin 6 (IL – 6), Caspase-3, Nuclear factor erythroid 2- related factor 2 (Nrf2), Nuclear factor kappa B (NfkB) and Heme Oxygynase – 1 (Hmox-1) and histopathology. There was significant bioaccumulation of Pb, Al, Hg and MN; elevated IL-6 and Tnf-α, MDA and NO, caspase-3 and Nrf2, NF-κB and Hmox-1 in the HMM only group in comparison to the control. There was significant ( p < 0.05) decrease in SOD, CAT GSH activities in HMM only exposed group in comparison to the control deionized water group, whereas BP co-treatment with HMM significantly ( p < 0.05) increased SOD, CAT GSH activities. Co-treatment with BP extract also reversed most of these effects. BP extract may ameliorate HMM -induced thyrotoxicity in female albino rats by blunting oxido-inflammatory activities.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76366657","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 : 2023-01-01DOI: 10.1177/23978473231197835
Brianna J. Stubbs, Chad Cook, Traci M. Blonquist, Kristen Taggart, Dawn Beckman, C. Kruger, Dietrich Conze, A. Boileau
Bis-octanoyl (R)-1,3-butanediol (BO-BD) is a novel, palatable ketone ester that, when consumed, is hydrolyzed in the gastrointestinal tract into octanoic acid (OCT) and (R)-1,3-butanediol (BDO) which are subsequently metabolized into beta-hydroxybutyrate (BHB). Metabolism of BO-BD is hypothesized to be similar to bis-hexanoyl (R)-1,3-butanediol (BH-BD), apart from release of octanoic acid instead of hexanoic acid (HEX). As part of the safety assessment for BO-BD a randomized, cross-over, open-label study in middle-aged, healthy adults ( n = 12) was undertaken to provide a qualitative comparison of plasma BHB, OCT, HEX and BDO concentrations for 8 h following consumption of 12.5 or 25 g of BO-BD and 12.5 g of BH-BD. All study products increased plasma BHB and BDO up to 4 h post-consumption. BH-BD increased HEX, whereas BO-BD increased OCT. All kinetic parameters for BHB and BDO were similar between 12.5 g servings of BH-BD and BO-BD while Cmax and AUC for OCT were higher following 12. 5 g servings of BO-BD as compared to HEX with 12.5 g of BH-BD. All metabolites returned to baseline by 8 h post-consumption. BHB, BDO and OCT Cmax and AUC were increased with serving size of BO-BD from 12.5 to 25 g. Sensory acceptability scores of BO-BD were significantly higher than for BH-BD. An in vitro hydrolysis experiment using human blood plasma further confirmed that plasma esterases possess the ability to break down the novel ketone esters into BDO, and OCT or HEX. The two novel ketone ester molecules exhibit similar metabolic breakdown to BHB and BDO and result in transiently higher concentrations of the plasma fatty acids, OCT and HEX, in vivo. Given the similar ketone delivery with greater acceptability, BO-BD may offer a more broadly translatable tool to induce physiologic ketosis than BH-BD.
双辛烷酸(R)-1,3-丁二醇(BO-BD)是一种新型的、美味的酮类酯，当食用时，在胃肠道中水解成辛烷酸(OCT)和(R)-1,3-丁二醇(BDO)，随后代谢成β -羟基丁酸(BHB)。假设BO-BD的代谢类似于双己醇(R)-1,3-丁二醇(BH-BD)，只是释放的是辛酸而不是己酸(HEX)。作为BO-BD安全性评估的一部分，在中年健康成人(n = 12)中进行了一项随机、交叉、开放标签的研究，以提供在摄入12.5或25 g BO-BD和12.5 g BH-BD后8小时血浆BHB、OCT、HEX和BDO浓度的定性比较。所有研究产品在服用后4小时内均可增加血浆BHB和BDO。BHB - bd增加了HEX，而BO-BD增加了OCT。所有BHB和BDO的动力学参数在12.5 g BHB - bd和BO-BD之间相似，而OCT的Cmax和AUC在12 g后更高。5 g的BO-BD与12.5 g的hb - bd相比。所有代谢产物在摄入后8小时恢复到基线水平。BHB、BDO和OCT Cmax和AUC随BO-BD食用量从12.5 g增加到25 g。BO-BD患者的感觉可接受性评分明显高于BH-BD患者。利用人血浆进行的体外水解实验进一步证实，血浆酯酶具有将新型酮酯分解成BDO、OCT或HEX的能力。这两种新型酮酯分子表现出与BHB和BDO相似的代谢分解，并导致体内血浆脂肪酸、OCT和HEX浓度短暂升高。鉴于类似的酮传递和更大的可接受性，BO-BD可能比BH-BD提供更广泛的可翻译工具来诱导生理性酮症。
{"title":"A randomized, open-label, cross-over pilot study investigating metabolic product kinetics of the palatable novel ketone ester, bis-octanoyl (R)-1,3-butanediol, and bis-hexanoyl (R)-1,3-butanediol ingestion in healthy adults","authors":"Brianna J. Stubbs, Chad Cook, Traci M. Blonquist, Kristen Taggart, Dawn Beckman, C. Kruger, Dietrich Conze, A. Boileau","doi":"10.1177/23978473231197835","DOIUrl":"https://doi.org/10.1177/23978473231197835","url":null,"abstract":"Bis-octanoyl (R)-1,3-butanediol (BO-BD) is a novel, palatable ketone ester that, when consumed, is hydrolyzed in the gastrointestinal tract into octanoic acid (OCT) and (R)-1,3-butanediol (BDO) which are subsequently metabolized into beta-hydroxybutyrate (BHB). Metabolism of BO-BD is hypothesized to be similar to bis-hexanoyl (R)-1,3-butanediol (BH-BD), apart from release of octanoic acid instead of hexanoic acid (HEX). As part of the safety assessment for BO-BD a randomized, cross-over, open-label study in middle-aged, healthy adults ( n = 12) was undertaken to provide a qualitative comparison of plasma BHB, OCT, HEX and BDO concentrations for 8 h following consumption of 12.5 or 25 g of BO-BD and 12.5 g of BH-BD. All study products increased plasma BHB and BDO up to 4 h post-consumption. BH-BD increased HEX, whereas BO-BD increased OCT. All kinetic parameters for BHB and BDO were similar between 12.5 g servings of BH-BD and BO-BD while Cmax and AUC for OCT were higher following 12. 5 g servings of BO-BD as compared to HEX with 12.5 g of BH-BD. All metabolites returned to baseline by 8 h post-consumption. BHB, BDO and OCT Cmax and AUC were increased with serving size of BO-BD from 12.5 to 25 g. Sensory acceptability scores of BO-BD were significantly higher than for BH-BD. An in vitro hydrolysis experiment using human blood plasma further confirmed that plasma esterases possess the ability to break down the novel ketone esters into BDO, and OCT or HEX. The two novel ketone ester molecules exhibit similar metabolic breakdown to BHB and BDO and result in transiently higher concentrations of the plasma fatty acids, OCT and HEX, in vivo. Given the similar ketone delivery with greater acceptability, BO-BD may offer a more broadly translatable tool to induce physiologic ketosis than BH-BD.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"101 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76856862","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 : 2023-01-01DOI: 10.1177/23978473231156620
Pogisego Dinake, Obakeng Motswetla, T. T. Kereeditse, Rosemary Kelebemang
Background: Toxic metals in cosmetic products can lead to serious health problems among consumers. Skin lightening cosmetics are popular among women who may be unaware of prevalence of toxic metals in such products. Purpose: This study assessed the content of toxic metals in cosmetic products imported into Botswana. There are currently no regulations in Botswana governing maximum contaminants limits for contaminants such as metal ions in cosmetic products. Research Design: Sample analysis was carried out using inductively coupled plasma optical emission spectrometry after microwave-assisted acid sample digestion. Results: Total concentrations of metals were in the order Pb > Ni > Cr > As. The concentrations of metals analysed were in the range of 45.75–193.60; 2.99–9.50; 3.32–7.41 and 1.95–4.52 mg/kg for Pb, Ni, Cr and As respectively. The concentrations of Pb in all 14 samples exceeded the maximum impurity level of 10 mg/kg in cosmetics as per the United States Food and Drug Administration (US FDA). Concentrations of Ni, As and Cr were also higher than the set US FDA limits in some cosmetic samples under study. A human health risk assessment was conducted using hazard quotient, average daily intake and health risk index. A hazard quotient of greater than one was determined for Pb (HQ ∼ 177.0–749.2) in all 14 cosmetic samples investigated indicating potential adverse effects to human health. Conclusion: Overall results of total concentration and health risk assessment indicate that cosmetic products imported into Botswana are harmful to consumers. Therefore, quality control measures should be enforced to ensure metal concentrations in facial cosmetic products do not exceed regulatory limits.
{"title":"Assessment of level of heavy metals in cosmetics","authors":"Pogisego Dinake, Obakeng Motswetla, T. T. Kereeditse, Rosemary Kelebemang","doi":"10.1177/23978473231156620","DOIUrl":"https://doi.org/10.1177/23978473231156620","url":null,"abstract":"Background: Toxic metals in cosmetic products can lead to serious health problems among consumers. Skin lightening cosmetics are popular among women who may be unaware of prevalence of toxic metals in such products. Purpose: This study assessed the content of toxic metals in cosmetic products imported into Botswana. There are currently no regulations in Botswana governing maximum contaminants limits for contaminants such as metal ions in cosmetic products. Research Design: Sample analysis was carried out using inductively coupled plasma optical emission spectrometry after microwave-assisted acid sample digestion. Results: Total concentrations of metals were in the order Pb > Ni > Cr > As. The concentrations of metals analysed were in the range of 45.75–193.60; 2.99–9.50; 3.32–7.41 and 1.95–4.52 mg/kg for Pb, Ni, Cr and As respectively. The concentrations of Pb in all 14 samples exceeded the maximum impurity level of 10 mg/kg in cosmetics as per the United States Food and Drug Administration (US FDA). Concentrations of Ni, As and Cr were also higher than the set US FDA limits in some cosmetic samples under study. A human health risk assessment was conducted using hazard quotient, average daily intake and health risk index. A hazard quotient of greater than one was determined for Pb (HQ ∼ 177.0–749.2) in all 14 cosmetic samples investigated indicating potential adverse effects to human health. Conclusion: Overall results of total concentration and health risk assessment indicate that cosmetic products imported into Botswana are harmful to consumers. Therefore, quality control measures should be enforced to ensure metal concentrations in facial cosmetic products do not exceed regulatory limits.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79155340","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 : 2023-01-01DOI: 10.1177/23978473231208760
James Maina Githinji, Michael Mungoma, Kinara Fossa, Jesse Ngugi, Samwel Ondiek, Prabhjot Juttla, Alfred Owino Odongo, Moses Ndiritu, Magoma Mwancha-Kwasa
Background Rising poisoning incidences worldwide, primarily in developing countries, remain ambiguous due to paucity of data and poison centres. This study evaluates patterns and factors causing poor outcomes in Kiambu County, Kenya. Methods A records-based retrospective cross-sectional study of poisoning cases who presented to nine facilities between June 2015 and July 2020 was conducted. The data collected was analysed through descriptive, bivariate, and multivariate logistic regression using STATA version 13. Results Kiambu county has a minimum prevalence of poisoning of 3.2%. A total of 434 cases were studied. Most cases (85.5%) resulted from acute exposures, with 75% being intentional. Pesticides (61.1%), paraffin (18.7%), alcohol (6.5%), and pharmaceutical drugs (4.4%) were the primary poisons used. 3.9% didn't fit these categories, while 5.5% remained unknown. Common presentations at admission were vomiting (35.3%) and unconsciousness (21.6%). Pesticides were responsible for 72.0% of deaths. Sequelae occurred in 7.8%, full but delayed recovery in 17.6%, and 6.0% died. The largest cluster of total cases was found in Thika town sub-county. It also contained the primary clusters of alcohol and pesticide poisoning. Being male (AOR 4.577, 95% CI [1.244–16.842]) was significantly associated with adverse outcomes. Regardless of the poison, the majority 78.8% made a full recovery. Conclusion Due to the lack of standardized poisoning data tools, patient records lack vital information reflecting the quality of care that the patient received, reflecting a lack of structures to collect, analyse and utilise poisoning data for decision making. This study underpins the need for the establishment of a PC in Kiambu county, Kenya.
{"title":"Poisoning patterns and factors associated with treatment outcomes among patients: A case study of Kiambu county hospitals, Kenya","authors":"James Maina Githinji, Michael Mungoma, Kinara Fossa, Jesse Ngugi, Samwel Ondiek, Prabhjot Juttla, Alfred Owino Odongo, Moses Ndiritu, Magoma Mwancha-Kwasa","doi":"10.1177/23978473231208760","DOIUrl":"https://doi.org/10.1177/23978473231208760","url":null,"abstract":"Background Rising poisoning incidences worldwide, primarily in developing countries, remain ambiguous due to paucity of data and poison centres. This study evaluates patterns and factors causing poor outcomes in Kiambu County, Kenya. Methods A records-based retrospective cross-sectional study of poisoning cases who presented to nine facilities between June 2015 and July 2020 was conducted. The data collected was analysed through descriptive, bivariate, and multivariate logistic regression using STATA version 13. Results Kiambu county has a minimum prevalence of poisoning of 3.2%. A total of 434 cases were studied. Most cases (85.5%) resulted from acute exposures, with 75% being intentional. Pesticides (61.1%), paraffin (18.7%), alcohol (6.5%), and pharmaceutical drugs (4.4%) were the primary poisons used. 3.9% didn't fit these categories, while 5.5% remained unknown. Common presentations at admission were vomiting (35.3%) and unconsciousness (21.6%). Pesticides were responsible for 72.0% of deaths. Sequelae occurred in 7.8%, full but delayed recovery in 17.6%, and 6.0% died. The largest cluster of total cases was found in Thika town sub-county. It also contained the primary clusters of alcohol and pesticide poisoning. Being male (AOR 4.577, 95% CI [1.244–16.842]) was significantly associated with adverse outcomes. Regardless of the poison, the majority 78.8% made a full recovery. Conclusion Due to the lack of standardized poisoning data tools, patient records lack vital information reflecting the quality of care that the patient received, reflecting a lack of structures to collect, analyse and utilise poisoning data for decision making. This study underpins the need for the establishment of a PC in Kiambu county, Kenya.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135447006","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 : 2023-01-01DOI: 10.1177/23978473231173093
R. Maronpot, Mihoko Koyanagi, S. Hayashi, Debabrata Mahapatra, Masayuki Nishino, Minoru Iniwa
Gardenia blue is currently being considered as a naturally derived food colorant for use in the global marketplace. To assess its carcinogenic potential, 100 female and 100 male CByB6F1-Tg (HRAS)2Jic (rasH2) mice were allocated to four dose groups and exposed to gardenia blue in the diet for 26 weeks at dose levels of 0.0% (control), 0.5%, 2.5%, or 5.0% (corresponding to 0.0, 664.8, 3341.0, and 6623.2 mg/kg/day in male mice and 0.0, 1182.7, 5561.1, and 10,440.3 mg/kg/day in female mice, respectively). An additional group of 10 males and 10 females was administered intraperitoneal N-methyl-N-nitrosourea (MNU) as a positive control. Clinical observations, body and organ weights, clinical chemistry, hematology, and hormone analyses were performed in addition to urinalysis and histopathology. The positive control elicited expected responses specific to rasH2 mice. There were sporadic background non-dose-related findings in clinical pathology parameters and anatomic pathology common to rasH2 mice in the absence of any gardenia blue induced dose-related changes. Under these study conditions, the no-observed-adverse-effect level was 5% gardenia blue (6623.2 mg/kg/day in male mice and 10,440.3 mg/kg/day in female mice). Based on this study a high dietary level of gardenia blue was negative for carcinogenicity in the rasH2 mouse test system.
{"title":"Gardenia blue is not carcinogenic in the rasH2 mouse","authors":"R. Maronpot, Mihoko Koyanagi, S. Hayashi, Debabrata Mahapatra, Masayuki Nishino, Minoru Iniwa","doi":"10.1177/23978473231173093","DOIUrl":"https://doi.org/10.1177/23978473231173093","url":null,"abstract":"Gardenia blue is currently being considered as a naturally derived food colorant for use in the global marketplace. To assess its carcinogenic potential, 100 female and 100 male CByB6F1-Tg (HRAS)2Jic (rasH2) mice were allocated to four dose groups and exposed to gardenia blue in the diet for 26 weeks at dose levels of 0.0% (control), 0.5%, 2.5%, or 5.0% (corresponding to 0.0, 664.8, 3341.0, and 6623.2 mg/kg/day in male mice and 0.0, 1182.7, 5561.1, and 10,440.3 mg/kg/day in female mice, respectively). An additional group of 10 males and 10 females was administered intraperitoneal N-methyl-N-nitrosourea (MNU) as a positive control. Clinical observations, body and organ weights, clinical chemistry, hematology, and hormone analyses were performed in addition to urinalysis and histopathology. The positive control elicited expected responses specific to rasH2 mice. There were sporadic background non-dose-related findings in clinical pathology parameters and anatomic pathology common to rasH2 mice in the absence of any gardenia blue induced dose-related changes. Under these study conditions, the no-observed-adverse-effect level was 5% gardenia blue (6623.2 mg/kg/day in male mice and 10,440.3 mg/kg/day in female mice). Based on this study a high dietary level of gardenia blue was negative for carcinogenicity in the rasH2 mouse test system.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"2016 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86302184","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 : 2023-01-01DOI: 10.1177/23978473231197837
M. Oldham, F. Lucci, A. Kuczaj
For in vivo inhalation studies, aerosol dosimetry links aerosol exposure and deposited dose within the respiratory tract. Aerosol dosimetry programs like the Multiple Path Particle Deposition model utilize respiratory tract geometry, respiratory physiology, and aerosol properties to predict particle deposition within the respiratory tract. A challenge to wider use of these dosimetry programs for in vivo inhalation studies is the lack of species-specific or strain specific respiratory tract anatomy, and in some cases, strain specific respiratory physiology data. The objective of this work was to develop aerosol dosimetry predictions for the in vivo human disease models of chronic obstructive pulmonary disease (COPD; C57BL/6 mice) cardiovascular disease (CVD; ApoE-/- mice), and lung cancer (AJ mice) using the Multiple Path Particle Deposition dosimetry model. Microcomputed tomography derived tracheobronchial geometry data were combined with available pulmonary geometry data for C57BL/6, ApoE-/-, and AJ mice and incorporated into the Multiple Path Particle Deposition dosimetry model. Mouse strain specific respiratory physiology literature values were used as input into the Multiple Path Particle Deposition dosimetry model. The resulting particle deposition predictions compared well with the very limited strain specific experimental particle deposition data. Since multiple tracheobronchial geometries and thus pulmonary anatomies were used for C57BL/6 and ApoE-/- mice, an estimate of intrastrain variability in predicted particle deposition was obtained. The intrastrain variability in predicted particle deposition for C57BL/6 and ApoE-/- mice was always smaller in the tracheobronchial compared to pulmonary airways. The differences in reported respiratory physiology values for C57BL/6 mice resulted in greater intrastrain variability in predicted particle deposition than observed with the different tracheobronchial geometries and pulmonary anatomies. These mouse strain specific aerosol dosimetry predictions can provide insight into the delivered dose to specific respiratory tract regions that can be correlated with in vivo endpoints.
{"title":"Predicted aerosol dosimetry for mouse models of chronic obstructive pulmonary disease, cardiovascular disease and lung cancer","authors":"M. Oldham, F. Lucci, A. Kuczaj","doi":"10.1177/23978473231197837","DOIUrl":"https://doi.org/10.1177/23978473231197837","url":null,"abstract":"For in vivo inhalation studies, aerosol dosimetry links aerosol exposure and deposited dose within the respiratory tract. Aerosol dosimetry programs like the Multiple Path Particle Deposition model utilize respiratory tract geometry, respiratory physiology, and aerosol properties to predict particle deposition within the respiratory tract. A challenge to wider use of these dosimetry programs for in vivo inhalation studies is the lack of species-specific or strain specific respiratory tract anatomy, and in some cases, strain specific respiratory physiology data. The objective of this work was to develop aerosol dosimetry predictions for the in vivo human disease models of chronic obstructive pulmonary disease (COPD; C57BL/6 mice) cardiovascular disease (CVD; ApoE-/- mice), and lung cancer (AJ mice) using the Multiple Path Particle Deposition dosimetry model. Microcomputed tomography derived tracheobronchial geometry data were combined with available pulmonary geometry data for C57BL/6, ApoE-/-, and AJ mice and incorporated into the Multiple Path Particle Deposition dosimetry model. Mouse strain specific respiratory physiology literature values were used as input into the Multiple Path Particle Deposition dosimetry model. The resulting particle deposition predictions compared well with the very limited strain specific experimental particle deposition data. Since multiple tracheobronchial geometries and thus pulmonary anatomies were used for C57BL/6 and ApoE-/- mice, an estimate of intrastrain variability in predicted particle deposition was obtained. The intrastrain variability in predicted particle deposition for C57BL/6 and ApoE-/- mice was always smaller in the tracheobronchial compared to pulmonary airways. The differences in reported respiratory physiology values for C57BL/6 mice resulted in greater intrastrain variability in predicted particle deposition than observed with the different tracheobronchial geometries and pulmonary anatomies. These mouse strain specific aerosol dosimetry predictions can provide insight into the delivered dose to specific respiratory tract regions that can be correlated with in vivo endpoints.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"263 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73060860","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 : 2023-01-01DOI: 10.1177/23978473231169078
M. Oldham, R. W. Desai, J. Randazzo, Guy Lalonde, R. Weil
WS-5 is a flavor ingredient that provides a cooling sensation similar to that of menthol but without the characteristic menthol flavor. In the available toxicological evaluations of WS-5 there was no data specific to inhalation exposure. A 90-days nose-only inhalation study was conducted using Sprague Dawley rats exposed to Filtered air, propylene glycol/glycerin (40/60 by weight; vehicle control), or one of three WS-5 concentrations (0.2, 0.4, or 0.8% by weight) to assess the inhalation toxicity of WS-5. The study design was consistent with the Organization for Economic Development and Cooperation test guideline 413 and included a 28-day and 6-week recovery sacrifices, in addition to the 13-week assessment. Food consumption and body weights were unaffected by WS-5 exposure compared to vehicle control or Filtered air. No WS-5 exposure related alterations were observed in serum chemistry, hematology, coagulation, urinalysis or bronchoalveolar lavage fluid cytology and clinical chemistry. Macroscopic examinations and terminal organ weights revealed no observations associated with exposure to WS-5. Histopathology findings of alveolar hemorrhage and mixed cell infiltration at the 28-day necropsy were either not present in the WS-5 exposed groups or were present at similar frequencies in the vehicle control and/or Filtered air groups at the 13-weeks necropsy and thus, were not considered to be vehicle control or WS-5 related. Based on the absence of adverse effects, the no-observed-adverse effect concentration was considered to be 2.5 mg/L of aerosolized 0.8 w% WS-5 that achieved a mean measured exposure concentration of approximately 18 μg WS-5/L
{"title":"Evaluation of the toxicity of WS-5 in a 90-days nose-only exposure in sprague-dawley rats","authors":"M. Oldham, R. W. Desai, J. Randazzo, Guy Lalonde, R. Weil","doi":"10.1177/23978473231169078","DOIUrl":"https://doi.org/10.1177/23978473231169078","url":null,"abstract":"WS-5 is a flavor ingredient that provides a cooling sensation similar to that of menthol but without the characteristic menthol flavor. In the available toxicological evaluations of WS-5 there was no data specific to inhalation exposure. A 90-days nose-only inhalation study was conducted using Sprague Dawley rats exposed to Filtered air, propylene glycol/glycerin (40/60 by weight; vehicle control), or one of three WS-5 concentrations (0.2, 0.4, or 0.8% by weight) to assess the inhalation toxicity of WS-5. The study design was consistent with the Organization for Economic Development and Cooperation test guideline 413 and included a 28-day and 6-week recovery sacrifices, in addition to the 13-week assessment. Food consumption and body weights were unaffected by WS-5 exposure compared to vehicle control or Filtered air. No WS-5 exposure related alterations were observed in serum chemistry, hematology, coagulation, urinalysis or bronchoalveolar lavage fluid cytology and clinical chemistry. Macroscopic examinations and terminal organ weights revealed no observations associated with exposure to WS-5. Histopathology findings of alveolar hemorrhage and mixed cell infiltration at the 28-day necropsy were either not present in the WS-5 exposed groups or were present at similar frequencies in the vehicle control and/or Filtered air groups at the 13-weeks necropsy and thus, were not considered to be vehicle control or WS-5 related. Based on the absence of adverse effects, the no-observed-adverse effect concentration was considered to be 2.5 mg/L of aerosolized 0.8 w% WS-5 that achieved a mean measured exposure concentration of approximately 18 μg WS-5/L","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"18 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91403868","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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