Pub Date : 2023-01-01DOI: 10.1177/23978473231154925
T. R. Paulsen, K. Jensen, J. van Harn, T. Veldkamp
Introduction: Intestinal colonisation of Salmonella is a major concern in the poultry industry, and a low dose of the high-purity synthetic capsaicin analogue phenylcapsaicin (PheCap) has the potential to be a phytobiotic alternative to antibiotics in reducing floor Salmonella in commercial broiler chicken houses. In this study we present the first safety assessment of PheCap at doses relevant for the poultry industry. Methods: In a completely randomized block design, Ross 308 male broilers were offered feed containing 0, 10, 15, or 150 mg PheCap/kg. Growth rates, mortality, haematology, clinical chemistry, foot pad lesions, litter quality and gross pathological examination of organs and tissues were evaluated for signs of toxicity over a two-phase, 35-day growth period. Results: No differences in feed intake and broiler growth were found, with broilers in the control group having the highest mortality. There was a statistically significant increase in the European Production Efficiency Factor (EPEF) for the 10 (p = 0.02) and 15 mg PheCap/kg feed (p = 0.003) treatment doses. No dose dependent adverse effects were found for any of the treatment doses. The No Observed Adverse Effect Level (NOAEL) of PheCap is probably higher than that of the highest weekly averaged daily intake of 36.3 mg/kg BW/day observed in the present study. Conclusions: The inclusion of PheCap in broiler feed at doses relevant for the commercial poultry industry is assumed not have any negative effects on broiler health.
{"title":"Safety assessment of the functional feed additive phenylcapsaicin in a commercial broiler diet","authors":"T. R. Paulsen, K. Jensen, J. van Harn, T. Veldkamp","doi":"10.1177/23978473231154925","DOIUrl":"https://doi.org/10.1177/23978473231154925","url":null,"abstract":"Introduction: Intestinal colonisation of Salmonella is a major concern in the poultry industry, and a low dose of the high-purity synthetic capsaicin analogue phenylcapsaicin (PheCap) has the potential to be a phytobiotic alternative to antibiotics in reducing floor Salmonella in commercial broiler chicken houses. In this study we present the first safety assessment of PheCap at doses relevant for the poultry industry. Methods: In a completely randomized block design, Ross 308 male broilers were offered feed containing 0, 10, 15, or 150 mg PheCap/kg. Growth rates, mortality, haematology, clinical chemistry, foot pad lesions, litter quality and gross pathological examination of organs and tissues were evaluated for signs of toxicity over a two-phase, 35-day growth period. Results: No differences in feed intake and broiler growth were found, with broilers in the control group having the highest mortality. There was a statistically significant increase in the European Production Efficiency Factor (EPEF) for the 10 (p = 0.02) and 15 mg PheCap/kg feed (p = 0.003) treatment doses. No dose dependent adverse effects were found for any of the treatment doses. The No Observed Adverse Effect Level (NOAEL) of PheCap is probably higher than that of the highest weekly averaged daily intake of 36.3 mg/kg BW/day observed in the present study. Conclusions: The inclusion of PheCap in broiler feed at doses relevant for the commercial poultry industry is assumed not have any negative effects on broiler health.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"2 2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88012487","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: 10.1177/23978473231215122
Ankit Rathi, Harshada Chandan, Chaitali Vira, Mukul P Pore
Background Alternansucrase is a glucansucrase enzyme that mainly functions in synthesis of glucan-like polysaccharides and can be used for production of novel oligosaccharides and polysaccharides having low glycemic index and prebiotics properties which makes them ideal candidates as dietary fibers and food. From a regulatory perspective, it is necessary to prove the safety of alternansucrase before it can be used in any application as it is a novel enzyme and has not been historically used in food processing. Objectives Alternansucrase obtained from Escherichia coli was subjected to toxicological tests to determine its safety for use in various industrial applications. Design Toxicity studies were conducted at acute oral and repeated sub-chronic (14 days and 90 days) levels in rats following the OECD guidelines. The genotoxicity studies were conducted using the bacterial reverse mutation test as well as in vitro mammalian cell micronucleus test as per the OECD guidelines. Results Alternansucrase did not induce any clinical abnormalities or mortality in rats at the dose level of 2000 mg/kg of body weight in the acute oral toxicity test. A 90-day sub chronic repeated dose oral toxicity study with alternansucrase at and up to dose of 1000 mg TOS/kg of body weight did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology parameters. Alternansucrase was found to be non-mutagenic up to 5000 µg TOS/plate concentration in the bacterial reverse mutation test. Alternansucrase was determined to be non-clastogenic and non-aneugenic up to the test concentration of 1250 µg TOS/mL during the in vitro mammalian cell micronucleus test. Conclusion The lethal dose (LD 50 ) based on this study is greater than 2000 mg/kg body weight, which falls into the category 5 criteria of Globally Harmonized System (GHS). No-Observed-Adverse-Effect-Level (NOAEL) was concluded to be greater than 1000 mg TOS/kg per day. The studies taken together substantiate the safety of alternansucrase enzyme in various food and associated industries. The present study paves a future for safe use of alternansucrase in varied industrial applications.
{"title":"Safety evaluations of alternansucrase enzyme expressed in <i>Escherichia coli</i> shows no adverse effects <i>in</i><i>vivo</i> and <i>in</i><i>vitro</i>","authors":"Ankit Rathi, Harshada Chandan, Chaitali Vira, Mukul P Pore","doi":"10.1177/23978473231215122","DOIUrl":"https://doi.org/10.1177/23978473231215122","url":null,"abstract":"Background Alternansucrase is a glucansucrase enzyme that mainly functions in synthesis of glucan-like polysaccharides and can be used for production of novel oligosaccharides and polysaccharides having low glycemic index and prebiotics properties which makes them ideal candidates as dietary fibers and food. From a regulatory perspective, it is necessary to prove the safety of alternansucrase before it can be used in any application as it is a novel enzyme and has not been historically used in food processing. Objectives Alternansucrase obtained from Escherichia coli was subjected to toxicological tests to determine its safety for use in various industrial applications. Design Toxicity studies were conducted at acute oral and repeated sub-chronic (14 days and 90 days) levels in rats following the OECD guidelines. The genotoxicity studies were conducted using the bacterial reverse mutation test as well as in vitro mammalian cell micronucleus test as per the OECD guidelines. Results Alternansucrase did not induce any clinical abnormalities or mortality in rats at the dose level of 2000 mg/kg of body weight in the acute oral toxicity test. A 90-day sub chronic repeated dose oral toxicity study with alternansucrase at and up to dose of 1000 mg TOS/kg of body weight did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology parameters. Alternansucrase was found to be non-mutagenic up to 5000 µg TOS/plate concentration in the bacterial reverse mutation test. Alternansucrase was determined to be non-clastogenic and non-aneugenic up to the test concentration of 1250 µg TOS/mL during the in vitro mammalian cell micronucleus test. Conclusion The lethal dose (LD 50 ) based on this study is greater than 2000 mg/kg body weight, which falls into the category 5 criteria of Globally Harmonized System (GHS). No-Observed-Adverse-Effect-Level (NOAEL) was concluded to be greater than 1000 mg TOS/kg per day. The studies taken together substantiate the safety of alternansucrase enzyme in various food and associated industries. The present study paves a future for safe use of alternansucrase in varied industrial applications.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"74 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":"135710887","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: 10.1177/23978473211052700
T. Osimitz, K. Sioris, John F. Gualtieri, D. Filandrinos, Ryan Seaverson, Angeline Carlson, W. Droege, Rick Kingston
The Pyrethrins Stewardship Program (PSP) was established to better understand adverse effects following exposure to pyrethrins-containing insecticide products. Running from April 2010 through December 2016, symptomatic dermal and inhalation exposures were entered into Phase I of the PSP and analyzed for exposure details and nature of the effects reported. Phase II consisted of an in-depth telephone interview using an enhanced questionnaire to investigate additional exposure details. Phase III scored the association between exposure and reported effects. Based on the data collected and analyzed, we conclude that: (1) Both in absolute number and relative to the wide distribution and use by consumers, adverse respiratory or dermal events after product exposure were rare; (2) Most outcomes for the reported events involving either dermal or respiratory effects were of minor severity and self-limiting; (3) None of the data collected and analyzed indicate that pyrethrins-containing products, including those formulated with synthetic pyrethroids and/or synergists, pose a significant risk of serious dermal or respiratory reactions even in cases where the exposed individual reported having allergies or asthma; (4) No additional label warnings or other mitigation techniques are warranted with pyrethrins-containing products formulated with or without synthetic pyrethroids and/or synergists.
{"title":"Retrospective analysis of adverse effects associated with pyrethrins-containing products","authors":"T. Osimitz, K. Sioris, John F. Gualtieri, D. Filandrinos, Ryan Seaverson, Angeline Carlson, W. Droege, Rick Kingston","doi":"10.1177/23978473211052700","DOIUrl":"https://doi.org/10.1177/23978473211052700","url":null,"abstract":"The Pyrethrins Stewardship Program (PSP) was established to better understand adverse effects following exposure to pyrethrins-containing insecticide products. Running from April 2010 through December 2016, symptomatic dermal and inhalation exposures were entered into Phase I of the PSP and analyzed for exposure details and nature of the effects reported. Phase II consisted of an in-depth telephone interview using an enhanced questionnaire to investigate additional exposure details. Phase III scored the association between exposure and reported effects. Based on the data collected and analyzed, we conclude that: (1) Both in absolute number and relative to the wide distribution and use by consumers, adverse respiratory or dermal events after product exposure were rare; (2) Most outcomes for the reported events involving either dermal or respiratory effects were of minor severity and self-limiting; (3) None of the data collected and analyzed indicate that pyrethrins-containing products, including those formulated with synthetic pyrethroids and/or synergists, pose a significant risk of serious dermal or respiratory reactions even in cases where the exposed individual reported having allergies or asthma; (4) No additional label warnings or other mitigation techniques are warranted with pyrethrins-containing products formulated with or without synthetic pyrethroids and/or synergists.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75004540","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: 10.1177/23978473221109475
S. Adelakun, A. Ojewale, S. Jeje, O. A. Adedotun
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder, causes irregular menstrual cycles, dyslipidemia, excessive body weight, oxidative stress, hyperandrogenism, and infertility. This study focused on the impact of Cyperus esculentus (CES) on letrozole-induced PCOS in female Sprague-Dawley rats. Twenty (20) normal rats and twenty (20) PCOS rats (150–200 g, 8 weeks old) were randomly divided into four groups of ten (n = 10) rats each. Group A served as normal control group received 2 mL of normal saline, group B treated with 500 mg/kg body weight of CES, group C PCOS control group received 2 mL of normal saline, and group D PCOS rats post-treated with 500 mg/kg body weight of CES daily through gastric gavage for 30 days. Estrus cyclicity, body and ovaries weights, biochemical and histological parameters were measured. Observed irregular estrus cyclicity and multiple cysts in PCOS rats, increase glycemia, ovarian weight, triglycerides, total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, malondialdehyde, luteinizing hormone (LH), testosterone, and decrease high-density lipoprotein cholesterol, estradiol, progesterone, catalase, reduced glutathione (GSH), and superoxide dismutase levels, compared with control. The intervention of CES ameliorated and restored the estrus cyclicity reproductive hormone, biochemical, and structural alterations. Moreover, CES significantly decreased cystic follicles, LH, and testosterone levels, but increased estradiol concentration. This plant may be beneficial in the management and treatment of PCOS-related reproductive and metabolic disorders.
{"title":"Histomorphometric and biochemical activities of bioactive component of Cyperus esculentus tubers extract on letrozole-induced polycystic ovarian syndrome and cholesterol homeostasis in female Sprague-Dawley rats","authors":"S. Adelakun, A. Ojewale, S. Jeje, O. A. Adedotun","doi":"10.1177/23978473221109475","DOIUrl":"https://doi.org/10.1177/23978473221109475","url":null,"abstract":"Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder, causes irregular menstrual cycles, dyslipidemia, excessive body weight, oxidative stress, hyperandrogenism, and infertility. This study focused on the impact of Cyperus esculentus (CES) on letrozole-induced PCOS in female Sprague-Dawley rats. Twenty (20) normal rats and twenty (20) PCOS rats (150–200 g, 8 weeks old) were randomly divided into four groups of ten (n = 10) rats each. Group A served as normal control group received 2 mL of normal saline, group B treated with 500 mg/kg body weight of CES, group C PCOS control group received 2 mL of normal saline, and group D PCOS rats post-treated with 500 mg/kg body weight of CES daily through gastric gavage for 30 days. Estrus cyclicity, body and ovaries weights, biochemical and histological parameters were measured. Observed irregular estrus cyclicity and multiple cysts in PCOS rats, increase glycemia, ovarian weight, triglycerides, total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, malondialdehyde, luteinizing hormone (LH), testosterone, and decrease high-density lipoprotein cholesterol, estradiol, progesterone, catalase, reduced glutathione (GSH), and superoxide dismutase levels, compared with control. The intervention of CES ameliorated and restored the estrus cyclicity reproductive hormone, biochemical, and structural alterations. Moreover, CES significantly decreased cystic follicles, LH, and testosterone levels, but increased estradiol concentration. This plant may be beneficial in the management and treatment of PCOS-related reproductive and metabolic disorders.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"153 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79649944","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: 10.1177/23978473211055363
T. Kobets, M. Iatropoulos, G. Williams
Acrylonitrile, an industrial chemical, is a multisite carcinogen in rats and mice, producing tumors in four tissues with barrier function, that is, brain, forestomach, Zymbal’s gland, and Harderian gland. To assess mechanism(s) of action (MoA) for induction of neoplasia and to evaluate whether the findings in rodents are indicative of human hazard, data on the potential key effects produced by acrylonitrile in the four rodent target tissues of carcinogenicity were evaluated. A notable finding was depletion of glutathione in various organs, including two target tissues, the brain, and forestomach, suggesting that this effect could be a critical initiating event. An additional combination of oxidative DNA damage and cytotoxic effects of acrylonitrile and its metabolites, cyanide, and 2-cyanoethylene oxide, could initiate pro-inflammatory signaling and sustained cell and tissue injury, leading to compensatory cell proliferation and neoplastic development. The in vivo DNA-binding and genotoxicity of acrylonitrile has been studied in several target tissues with no compelling positive results. Thus, while some mutagenic effects were reported in acrylonitrile-exposed rodents, data to determine whether this mutagenicity stems from direct DNA reactivity of acrylonitrile are insufficient. Accordingly, the induction of tumors in rodents is consistent primarily with a non-genotoxic MoA, although a contribution from weak mutagenicity cannot be ruled out. Mechanistic data to support conclusions regarding human hazard from acrylonitrile exposure is weak. Comparison of metabolism of acrylonitrile between rodents and humans provide little support for human hazard. Three of the tissues affected in bioassays (forestomach, Zymbal’s gland, and Harderian gland) are present only in rodents, while the brain is anatomically different between rodents and humans, diminishing relevance of tumor induction in these tissues to human hazard. Extensive epidemiological data has not revealed causation of human cancer by acrylonitrile.
{"title":"Acrylonitrile induction of rodent neoplasia: Potential mechanism of action and relevance to humans","authors":"T. Kobets, M. Iatropoulos, G. Williams","doi":"10.1177/23978473211055363","DOIUrl":"https://doi.org/10.1177/23978473211055363","url":null,"abstract":"Acrylonitrile, an industrial chemical, is a multisite carcinogen in rats and mice, producing tumors in four tissues with barrier function, that is, brain, forestomach, Zymbal’s gland, and Harderian gland. To assess mechanism(s) of action (MoA) for induction of neoplasia and to evaluate whether the findings in rodents are indicative of human hazard, data on the potential key effects produced by acrylonitrile in the four rodent target tissues of carcinogenicity were evaluated. A notable finding was depletion of glutathione in various organs, including two target tissues, the brain, and forestomach, suggesting that this effect could be a critical initiating event. An additional combination of oxidative DNA damage and cytotoxic effects of acrylonitrile and its metabolites, cyanide, and 2-cyanoethylene oxide, could initiate pro-inflammatory signaling and sustained cell and tissue injury, leading to compensatory cell proliferation and neoplastic development. The in vivo DNA-binding and genotoxicity of acrylonitrile has been studied in several target tissues with no compelling positive results. Thus, while some mutagenic effects were reported in acrylonitrile-exposed rodents, data to determine whether this mutagenicity stems from direct DNA reactivity of acrylonitrile are insufficient. Accordingly, the induction of tumors in rodents is consistent primarily with a non-genotoxic MoA, although a contribution from weak mutagenicity cannot be ruled out. Mechanistic data to support conclusions regarding human hazard from acrylonitrile exposure is weak. Comparison of metabolism of acrylonitrile between rodents and humans provide little support for human hazard. Three of the tissues affected in bioassays (forestomach, Zymbal’s gland, and Harderian gland) are present only in rodents, while the brain is anatomically different between rodents and humans, diminishing relevance of tumor induction in these tissues to human hazard. Extensive epidemiological data has not revealed causation of human cancer by acrylonitrile.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74179706","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: 10.1177/23978473221115817
A. Buha, L. Manić, D. Maric, A. Tinkov, Anatoly Skolny, B. Antonijević, A. Hayes
To understand the effects of endocrine-disrupting chemicals (EDCs), the mechanism(s) by which EDCs exert their harmful effects on humans and their offspring needs careful examination and clarification. Epigenetic modification, including DNA methylation, expression of aberrant microRNA (miRNA), and histone modification, is one mechanism assumed to be a primary pathway leading to the untoward effects of endocrine disruptors. However, it remains unclear whether such epigenetic changes caused by EDCs are truly predicting adverse outcomes. Therefore, it is important to understand the relationship between epigenetic changes and various endocrine endpoints or markers. This paper highlights the possibility that certain chemicals (Cd, As, Pb, bisphenol A, phthalate, polychlorinated biphenyls) reported having ED properties may adversely affect the epigenome. Electronic database sources PubMed, SCOPUS, JSTOR, and the Google Scholar web browser were used to search the literature. The search was based on keywords from existing theories and basic knowledge of endocrine disorders and epigenetic effects, well-known EDCs, and previous search results. Unclear and often conflicting results regarding the effects of EDCs indicate the need for further research to support better risk assessments and management of these chemicals. Graphical Abstract
{"title":"The effects of endocrine-disrupting chemicals (EDCs) on the epigenome-A short overview","authors":"A. Buha, L. Manić, D. Maric, A. Tinkov, Anatoly Skolny, B. Antonijević, A. Hayes","doi":"10.1177/23978473221115817","DOIUrl":"https://doi.org/10.1177/23978473221115817","url":null,"abstract":"To understand the effects of endocrine-disrupting chemicals (EDCs), the mechanism(s) by which EDCs exert their harmful effects on humans and their offspring needs careful examination and clarification. Epigenetic modification, including DNA methylation, expression of aberrant microRNA (miRNA), and histone modification, is one mechanism assumed to be a primary pathway leading to the untoward effects of endocrine disruptors. However, it remains unclear whether such epigenetic changes caused by EDCs are truly predicting adverse outcomes. Therefore, it is important to understand the relationship between epigenetic changes and various endocrine endpoints or markers. This paper highlights the possibility that certain chemicals (Cd, As, Pb, bisphenol A, phthalate, polychlorinated biphenyls) reported having ED properties may adversely affect the epigenome. Electronic database sources PubMed, SCOPUS, JSTOR, and the Google Scholar web browser were used to search the literature. The search was based on keywords from existing theories and basic knowledge of endocrine disorders and epigenetic effects, well-known EDCs, and previous search results. Unclear and often conflicting results regarding the effects of EDCs indicate the need for further research to support better risk assessments and management of these chemicals. Graphical Abstract","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"169 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86628511","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: 10.1177/23978473221085746
Caitlin Thompson, M. Williams
Kambô is an Amazonian ritual which includes the application of the defensive secretion of the Phyllomedusa bicolor frog to superficial burns made on the skin of human participants. The secretion, which contains a range of biologically active linear peptides, induces a short purgative experience that is extensively reported by participants to leave them with positive physical, emotional and spiritual after-effects. Various peptides identified in the secretion exert analgesic, vascular, and gastric effects in vivo, and antimicrobial and anti-cancer effects, among others, in vitro. While there has been some investigation into the physiological effects of various individual peptides isolated from the P. bicolor secretion, very little is known about the putative synergistic effects of concurrent administration of the complete substance through the transdermal methods used traditionally in the Kambô ritual. In this review and commentary, the authors summarize the existing biological information from animal research on peptides from the P. bicolor secretion, then consider the evidence in the context of Kambô administration to humans. The presented information suggests that specific peptides are likely to contribute to analogous physiological effects of Kambô in humans. The possibility that beyond their physiological action, the experiential or phenomenological component of these effects may have therapeutic applications is discussed, concluding with a consideration of the feasibility of human clinical research.
{"title":"Review of the physiological effects of Phyllomedusa bicolor skin secretion peptides on humans receiving Kambô","authors":"Caitlin Thompson, M. Williams","doi":"10.1177/23978473221085746","DOIUrl":"https://doi.org/10.1177/23978473221085746","url":null,"abstract":"Kambô is an Amazonian ritual which includes the application of the defensive secretion of the Phyllomedusa bicolor frog to superficial burns made on the skin of human participants. The secretion, which contains a range of biologically active linear peptides, induces a short purgative experience that is extensively reported by participants to leave them with positive physical, emotional and spiritual after-effects. Various peptides identified in the secretion exert analgesic, vascular, and gastric effects in vivo, and antimicrobial and anti-cancer effects, among others, in vitro. While there has been some investigation into the physiological effects of various individual peptides isolated from the P. bicolor secretion, very little is known about the putative synergistic effects of concurrent administration of the complete substance through the transdermal methods used traditionally in the Kambô ritual. In this review and commentary, the authors summarize the existing biological information from animal research on peptides from the P. bicolor secretion, then consider the evidence in the context of Kambô administration to humans. The presented information suggests that specific peptides are likely to contribute to analogous physiological effects of Kambô in humans. The possibility that beyond their physiological action, the experiential or phenomenological component of these effects may have therapeutic applications is discussed, concluding with a consideration of the feasibility of human clinical research.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74607196","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: 10.1177/23978473221117230
A. Nikiforov, T. Osimitz
Pharmacokinetic studies on the undiluted insect repellent active ingredient, DEET, were assessed for relevance to exposure assessment for humans. Five studies designed to define the DEET plasma concentration profiles of systemic exposure occurring at the respective NOAELs for two laboratory species using dermal and/or oral exposure scenarios and human volunteers at the 95th percentile of consumer use were undertaken to support EPA re-registration. The studies reported herein demonstrate that the DEET plasma concentration for Sprague-Dawley rats and Beagle dogs at the respective NOAELs following oral bolus dosing is much greater in terms of Cmax and AUC than that achieved following human dermal administration at the 95th percentile of consumer use. In addition, these plasma level data confirm that a high-dose rat subchronic dermal toxicity study with DEET is the most relevant model for human safety assessment of this topically applied insect repellent active ingredient. Therefore, utilization of pharmacokinetic plasma level data is important to exposure assessment of DEET and significantly reduces uncertainty in human health safety assessment.
{"title":"Analysis and interpretation of pharmacokinetic studies following DEET administration to rats, dogs, and humans","authors":"A. Nikiforov, T. Osimitz","doi":"10.1177/23978473221117230","DOIUrl":"https://doi.org/10.1177/23978473221117230","url":null,"abstract":"Pharmacokinetic studies on the undiluted insect repellent active ingredient, DEET, were assessed for relevance to exposure assessment for humans. Five studies designed to define the DEET plasma concentration profiles of systemic exposure occurring at the respective NOAELs for two laboratory species using dermal and/or oral exposure scenarios and human volunteers at the 95th percentile of consumer use were undertaken to support EPA re-registration. The studies reported herein demonstrate that the DEET plasma concentration for Sprague-Dawley rats and Beagle dogs at the respective NOAELs following oral bolus dosing is much greater in terms of Cmax and AUC than that achieved following human dermal administration at the 95th percentile of consumer use. In addition, these plasma level data confirm that a high-dose rat subchronic dermal toxicity study with DEET is the most relevant model for human safety assessment of this topically applied insect repellent active ingredient. Therefore, utilization of pharmacokinetic plasma level data is important to exposure assessment of DEET and significantly reduces uncertainty in human health safety assessment.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78361418","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: 10.1177/23978473221147176
B. Ephraim-Emmanuel, E. Okokon, B. Ordinioha
Background and aim Artisanal refining of crude oil is an illegal refining process that contributes to environmental pollution through the release of Polycyclic Aromatic Hydrocarbons (PAHs). PAHs compounds are known for their destructive effects on the environment as well as their harmful effects on human health. This study thus assessed the concentrations of PAHs in water, soil, and fish in communities where artisanal refining of crude oil is practiced in Bayelsa State. Materials and methods This descriptive, comparative study was conducted in Sampou (mildly exposed community), Gbarain, and Nembe (severely exposed communities) in Bayelsa State. Water, fish, and soil samples were collected using pre-existing environmental media collection guidelines and sent to the laboratory for GC-FID determination of the PAH concentrations. The data obtained were analyzed using the Statistical Package for Social Sciences (SPSS) software. Results Mean and (total) PAHs concentration in water samples obtained from Sampou was 3.50 ± 4.51 (59.59) μg/L; Gbarain 1.76 ± 4.35 (29.87) μg/L and Nembe 1.90 ± 4.20 (32.25) μg/L. A significant difference in the concentrations was also identified p-value: of 0.021. The mean concentration of PAHs in soil samples obtained from Sampou was 10.73 ± 15.53 (183.38) μg/kg; Gbarain 12.00 ± 19.57 (204.32) μg/kg and Nembe was 8.49 ± 10.07 (144.48) μg/kg. Finally, the mean concentration in fish samples obtained from Sampou was 5.62 ± 5.92 (95.43) μg/kg; Gbarain 3.81 ± 5.57 (64.75) μg/kg and Nembe 4.61 ± 5.33 (78.35) μg/kg. The difference in these concentrations was however not significant. Source diagnostic ratios of the PAHs in the water included Flt/(Flt + Pyr) ratio of 0.23, 0.16, and 0.21; Ant/(Ant + Phe) ratio of 0.87, 0.76, and 0.87 as well as BaA/(BaA + Chr) ratio of 0.43, 0.51 and 0.66 in Sampou, Gbarain and Nembe respectively. Conclusion Concentrations of total PAHs in water and fish samples obtained from the three communities exceeded the acceptable limits for ƩPAHs of 2.0 μg/L and 2 μg/kg in water and fish respectively stipulated by the United States Environmental Protection Agency and the Nigerian Petroleum Regulatory Authority. ƩPAHs concentrations from the samples obtained from Sampou were also higher than the other two communities. There is a need for regular environmental monitoring of PAH concentrations, especially in oil-producing communities, and a shift of focus toward the elimination of pyrolytic sources of PAH pollution.
{"title":"Polycyclic Aromatic Hydrocarbons: Evaluation of concentrations in environmental media in Bayelsa State","authors":"B. Ephraim-Emmanuel, E. Okokon, B. Ordinioha","doi":"10.1177/23978473221147176","DOIUrl":"https://doi.org/10.1177/23978473221147176","url":null,"abstract":"Background and aim Artisanal refining of crude oil is an illegal refining process that contributes to environmental pollution through the release of Polycyclic Aromatic Hydrocarbons (PAHs). PAHs compounds are known for their destructive effects on the environment as well as their harmful effects on human health. This study thus assessed the concentrations of PAHs in water, soil, and fish in communities where artisanal refining of crude oil is practiced in Bayelsa State. Materials and methods This descriptive, comparative study was conducted in Sampou (mildly exposed community), Gbarain, and Nembe (severely exposed communities) in Bayelsa State. Water, fish, and soil samples were collected using pre-existing environmental media collection guidelines and sent to the laboratory for GC-FID determination of the PAH concentrations. The data obtained were analyzed using the Statistical Package for Social Sciences (SPSS) software. Results Mean and (total) PAHs concentration in water samples obtained from Sampou was 3.50 ± 4.51 (59.59) μg/L; Gbarain 1.76 ± 4.35 (29.87) μg/L and Nembe 1.90 ± 4.20 (32.25) μg/L. A significant difference in the concentrations was also identified p-value: of 0.021. The mean concentration of PAHs in soil samples obtained from Sampou was 10.73 ± 15.53 (183.38) μg/kg; Gbarain 12.00 ± 19.57 (204.32) μg/kg and Nembe was 8.49 ± 10.07 (144.48) μg/kg. Finally, the mean concentration in fish samples obtained from Sampou was 5.62 ± 5.92 (95.43) μg/kg; Gbarain 3.81 ± 5.57 (64.75) μg/kg and Nembe 4.61 ± 5.33 (78.35) μg/kg. The difference in these concentrations was however not significant. Source diagnostic ratios of the PAHs in the water included Flt/(Flt + Pyr) ratio of 0.23, 0.16, and 0.21; Ant/(Ant + Phe) ratio of 0.87, 0.76, and 0.87 as well as BaA/(BaA + Chr) ratio of 0.43, 0.51 and 0.66 in Sampou, Gbarain and Nembe respectively. Conclusion Concentrations of total PAHs in water and fish samples obtained from the three communities exceeded the acceptable limits for ƩPAHs of 2.0 μg/L and 2 μg/kg in water and fish respectively stipulated by the United States Environmental Protection Agency and the Nigerian Petroleum Regulatory Authority. ƩPAHs concentrations from the samples obtained from Sampou were also higher than the other two communities. There is a need for regular environmental monitoring of PAH concentrations, especially in oil-producing communities, and a shift of focus toward the elimination of pyrolytic sources of PAH pollution.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89931139","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: 10.1177/23978473221122880
Jhl Bröcker, W. Stone, A. Carstens, GM Wolfaardt
Environmental water sources are constantly polluted by anthropogenic compounds, not always minimized by conventional water treatment methods to remove these compounds at the micro- and nano-range. The absolute concentrations of a suite of seven representative environmental micropollutants were compared pre- and post-treatment with both ozone and microbial biofilms, in terms of removal efficiencies and toxicity assays. Both synthetic micropollutant mixes and environmental water samples were evaluated. The study started with two representative micropollutants (carbamazepine, CBZ, and sulfamethoxazole, SMX), and broadened into a suite of pollutants, evaluating whole-sample eco-toxicological footprints. An ozone concentration of 4.24 ± 0.27 mg/L in tap water, resulted in an 87.9% and 96.5% removal of CBZ and SMX, respectively, within 1 min. Despite almost immediate removal of parent micropollutants by oxidation, endocrine disruption potential (anti-estrogenicity) of CBZ and SMX required up to 240 min of ozone treatment to show no assay effect. A broader suite of micropollutants in more complex environmental matrices showed scavenging of ozone (2.95 ± 0.17–0.25 ± 0.03 mg/L) and varying micropollutant recalcitrance to oxidation. Lower matrix pollution led to lower reduction in eco-toxicity. Microbial degradation of CBZ and SMX (56% and 70% versus 19% and 79%, respectively, in duplicate biofilms) by nutrient-limited biofilms showed less removal than ozonation, with marked variation due to the stochastic nature of biofilm sloughing. Microbial degradation of CBZ and SMX resulted in an increase of >90% in both estrogenicity and Aliivibrio inhibition. The results obtained from this study address a gap in understanding the removal efficiency of micropollutants, where the removal process often receives more attention than the comparative reduction of toxicological effects. This shift from a controlled laboratory environment to real-world scenarios also provided comparative insights into the removal of micropollutants and the eco-toxicity of the transformation by-products of each process.
{"title":"Micropollutant transformation and toxicity: Electrochemical ozonation versus biological metabolism","authors":"Jhl Bröcker, W. Stone, A. Carstens, GM Wolfaardt","doi":"10.1177/23978473221122880","DOIUrl":"https://doi.org/10.1177/23978473221122880","url":null,"abstract":"Environmental water sources are constantly polluted by anthropogenic compounds, not always minimized by conventional water treatment methods to remove these compounds at the micro- and nano-range. The absolute concentrations of a suite of seven representative environmental micropollutants were compared pre- and post-treatment with both ozone and microbial biofilms, in terms of removal efficiencies and toxicity assays. Both synthetic micropollutant mixes and environmental water samples were evaluated. The study started with two representative micropollutants (carbamazepine, CBZ, and sulfamethoxazole, SMX), and broadened into a suite of pollutants, evaluating whole-sample eco-toxicological footprints. An ozone concentration of 4.24 ± 0.27 mg/L in tap water, resulted in an 87.9% and 96.5% removal of CBZ and SMX, respectively, within 1 min. Despite almost immediate removal of parent micropollutants by oxidation, endocrine disruption potential (anti-estrogenicity) of CBZ and SMX required up to 240 min of ozone treatment to show no assay effect. A broader suite of micropollutants in more complex environmental matrices showed scavenging of ozone (2.95 ± 0.17–0.25 ± 0.03 mg/L) and varying micropollutant recalcitrance to oxidation. Lower matrix pollution led to lower reduction in eco-toxicity. Microbial degradation of CBZ and SMX (56% and 70% versus 19% and 79%, respectively, in duplicate biofilms) by nutrient-limited biofilms showed less removal than ozonation, with marked variation due to the stochastic nature of biofilm sloughing. Microbial degradation of CBZ and SMX resulted in an increase of >90% in both estrogenicity and Aliivibrio inhibition. The results obtained from this study address a gap in understanding the removal efficiency of micropollutants, where the removal process often receives more attention than the comparative reduction of toxicological effects. This shift from a controlled laboratory environment to real-world scenarios also provided comparative insights into the removal of micropollutants and the eco-toxicity of the transformation by-products of each process.","PeriodicalId":23155,"journal":{"name":"Toxicology Research and Application","volume":"116 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73406527","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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