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VUSE electronic cigarette aerosol chemistry and cytotoxicity
Abstracts / Toxicology Letters 229S (2014) S40–S252
vacuolation (mid and lower layers) and erosion (at least moderate) were found to be the most relevant histopathological effects induced by products classified Category 1 in vivo. Histopathology criteria specifically developed for non-extreme pH detergent and cleaning products correctly identified materials classified as Category 1 based on in vivo persistent effects, and significantly increased the overall sensitivity of the standard ICE prediction model for Category 1 identification (to 75%) whilst maintaining good concordance (73%). In contrast, the EU CLP additivity approach for classification was considerable less predictive with 27% concordance and 100% overprediction of non-category 1 products. Use of histopathology as an additional endpoint in the ICE test method was therefore found suitable to identify EU CLP/UN GHS Category 1 non-extreme pH detergent and cleaning products and to allow better discrimination from Category 2 products. http://dx.doi.org/10.1016/j.toxlet.2014.06.708 P-4.25 Preclinical safety assessment of aqueous plant extracts containing pyrrolizidine alkaloids Claudia Turek ∗ , Nora Mörbt, Peter Vögele, Florian C. Stintzing WALA Heilmittel GmbH, Bad Boll, Germany Pyrrolizidine alkaloids (PAs) are secondary metabolites found worldwide in various plants. Ingestion of sufficient amounts is known to cause intoxication in livestock and occasionally humans. In particular, 1,2-unsaturated PAs may act as toxins and genotoxic carcinogens. Due to hepatic metabolism, the liver is the primary site for toxicity. Still, PAs are taken up through (unintended) consumption of the herb or via various foods (EFSA CONTAM. EFSA Journal 2011;9:2406). Possessing diverse pharmacological properties, plant species containing PAs are applied in traditional medicine. In Germany, PA content in medicinal products is regulated in the German Graduated Plan (Bundesanzeiger 1992;111:4805). Within Europe, risk assessment and regulation of PAs in the food and pharmaceutical sector is currently under discussion. The Committee on Herbal Medicinal Products of the European Medicines Agency recently published a second draft of its public statement on the use of herbal medicinal products containing toxic, unsaturated PAs (EMA/HMPC/893108/201, 06 Nov. 2013). In this study, different aqueous plant extracts from Asteraceae and Boraginaceae were analysed for their PA content and examined for their mutagenic as well as hepatotoxic potential in vitro. Primary human hepatocytes were exposed to different concentration levels of the test items and cytotoxicity was assessed via the MTT test. Concomitantly, extracts were subjected to bacterial reverse mutation assays conducted with and without exogenous metabolic activation following OECD guidelines. Extracts analysed exhibited no cytotoxic effect on primary human hepatocytes up to 50 L/mL. Moreover, none of the test items revealed any evidence for a genotoxic potential. http://dx.doi.org/10.1016/j.toxlet.2014.06.709
S211
P-4.26 VUSE electronic cigarette aerosol chemistry and cytotoxicity Eugenia Theophilus ∗ , Ryan Potts, Kathy Fowler, Wanda Fields, Betsy Bombick R. J. Reynolds Tobacco Company, Winston-Salem, NC, USA Electronic cigarettes (e-cigs) are of high interest worldwide as potential alternatives to combustible cigarettes. R. J. Reynolds Vapor Company has introduced VUSE, an e-cig, in the US market. A main criticism of e-cigs from various groups is insufficient data on exposure to potential toxicants and toxicological effects. This poster presents mainstream aerosol chemistry and cytotoxicity data for different commercial e-cigs and combustible cigarettes. Aerosol was collected using a machine puffing regimen (55 ml puff volume/30 s inter-puff interval/3 s puff duration) and either bell shaped or square wave puffing profiles. The chemistry test program included aerosol characterization of a subset of compounds currently listed on FDA’s Harmful and Potentially Harmful Constituents list for combustible cigarettes. The in vitro toxicology test program included toxicological effects characterization. The Neutral Red Uptake cytotoxicity study was conducted in CHO cells. VUSE aerosol was generated using the VitroCell® VC10® aerosol exposure system and cells were exposed at the air–liquid interface. Individual constituent yields, chromatographic profiling, and in vitro data for commercial VUSE products tested under the conditions of these studies indicated that: (1) VUSE aerosol was chemically significantly less complex than mainstream smoke from combustible cigarettes and (2) consistent with the simpler aerosol chemistry, VUSE aerosol was not cytotoxic (i.e., IC50 could not be derived) whereas combustible cigarette smoke was cytotoxic (IC50 was derived). http://dx.doi.org/10.1016/j.toxlet.2014.06.710 P-4.27 A survey data on ecotoxicological synergistic effects from binary pesticide mixtures Jongwoon Kim ∗ , Renuka Pasupuleti, Sanghun Kim KIST Europe, Saarbruecken, Saarland, Germany The interest in mixture toxicity is continuously growing in the field of ecotoxicology since many scientific papers have shown that the mixture toxicity can be caused by combined effects from two or more compounds even at no-effect concentrations. Especially, synergistic effects which mean greater effects than the summation of individual effects (e.g. additive toxicity) have been long challenged scientists and policy makers in the chemical risk assessment. The synergistic effect can be occurred by biochemical interactions among components with different modes of toxic action in living organisms. Although plenty of empirical data might be basically needed to develop predictive models covering the synergistic effect that can play a key role in mixture risk assessment, publically collective databases on ecotoxicological synergistic effects remain highly insufficient. Therefore, the objectives of this study were to investigate how much data is available at the present time, and to develop a survey data on ecotoxicological synergistic effects from literature reviews with a focus on binary pesticide mixtures. http://dx.doi.org/10.1016/j.toxlet.2014.06.711
vacuolation (mid and lower layers) and erosion (at least moderate) were found to be the most relevant histopathological effects induced by products classified Category 1 in vivo. Histopathology criteria specifically developed for non-extreme pH detergent and cleaning products correctly identified materials classified as Category 1 based on in vivo persistent effects, and significantly increased the overall sensitivity of the standard ICE prediction model for Category 1 identification (to 75%) whilst maintaining good concordance (73%). In contrast, the EU CLP additivity approach for classification was considerable less predictive with 27% concordance and 100% overprediction of non-category 1 products. Use of histopathology as an additional endpoint in the ICE test method was therefore found suitable to identify EU CLP/UN GHS Category 1 non-extreme pH detergent and cleaning products and to allow better discrimination from Category 2 products. http://dx.doi.org/10.1016/j.toxlet.2014.06.708 P-4.25 Preclinical safety assessment of aqueous plant extracts containing pyrrolizidine alkaloids Claudia Turek ∗ , Nora Mörbt, Peter Vögele, Florian C. Stintzing WALA Heilmittel GmbH, Bad Boll, Germany Pyrrolizidine alkaloids (PAs) are secondary metabolites found worldwide in various plants. Ingestion of sufficient amounts is known to cause intoxication in livestock and occasionally humans. In particular, 1,2-unsaturated PAs may act as toxins and genotoxic carcinogens. Due to hepatic metabolism, the liver is the primary site for toxicity. Still, PAs are taken up through (unintended) consumption of the herb or via various foods (EFSA CONTAM. EFSA Journal 2011;9:2406). Possessing diverse pharmacological properties, plant species containing PAs are applied in traditional medicine. In Germany, PA content in medicinal products is regulated in the German Graduated Plan (Bundesanzeiger 1992;111:4805). Within Europe, risk assessment and regulation of PAs in the food and pharmaceutical sector is currently under discussion. The Committee on Herbal Medicinal Products of the European Medicines Agency recently published a second draft of its public statement on the use of herbal medicinal products containing toxic, unsaturated PAs (EMA/HMPC/893108/201, 06 Nov. 2013). In this study, different aqueous plant extracts from Asteraceae and Boraginaceae were analysed for their PA content and examined for their mutagenic as well as hepatotoxic potential in vitro. Primary human hepatocytes were exposed to different concentration levels of the test items and cytotoxicity was assessed via the MTT test. Concomitantly, extracts were subjected to bacterial reverse mutation assays conducted with and without exogenous metabolic activation following OECD guidelines. Extracts analysed exhibited no cytotoxic effect on primary human hepatocytes up to 50 L/mL. Moreover, none of the test items revealed any evidence for a genotoxic potential. http://dx.doi.org/10.1016/j.toxlet.2014.06.709
S211
P-4.26 VUSE electronic cigarette aerosol chemistry and cytotoxicity Eugenia Theophilus ∗ , Ryan Potts, Kathy Fowler, Wanda Fields, Betsy Bombick R. J. Reynolds Tobacco Company, Winston-Salem, NC, USA Electronic cigarettes (e-cigs) are of high interest worldwide as potential alternatives to combustible cigarettes. R. J. Reynolds Vapor Company has introduced VUSE, an e-cig, in the US market. A main criticism of e-cigs from various groups is insufficient data on exposure to potential toxicants and toxicological effects. This poster presents mainstream aerosol chemistry and cytotoxicity data for different commercial e-cigs and combustible cigarettes. Aerosol was collected using a machine puffing regimen (55 ml puff volume/30 s inter-puff interval/3 s puff duration) and either bell shaped or square wave puffing profiles. The chemistry test program included aerosol characterization of a subset of compounds currently listed on FDA’s Harmful and Potentially Harmful Constituents list for combustible cigarettes. The in vitro toxicology test program included toxicological effects characterization. The Neutral Red Uptake cytotoxicity study was conducted in CHO cells. VUSE aerosol was generated using the VitroCell® VC10® aerosol exposure system and cells were exposed at the air–liquid interface. Individual constituent yields, chromatographic profiling, and in vitro data for commercial VUSE products tested under the conditions of these studies indicated that: (1) VUSE aerosol was chemically significantly less complex than mainstream smoke from combustible cigarettes and (2) consistent with the simpler aerosol chemistry, VUSE aerosol was not cytotoxic (i.e., IC50 could not be derived) whereas combustible cigarette smoke was cytotoxic (IC50 was derived). http://dx.doi.org/10.1016/j.toxlet.2014.06.710 P-4.27 A survey data on ecotoxicological synergistic effects from binary pesticide mixtures Jongwoon Kim ∗ , Renuka Pasupuleti, Sanghun Kim KIST Europe, Saarbruecken, Saarland, Germany The interest in mixture toxicity is continuously growing in the field of ecotoxicology since many scientific papers have shown that the mixture toxicity can be caused by combined effects from two or more compounds even at no-effect concentrations. Especially, synergistic effects which mean greater effects than the summation of individual effects (e.g. additive toxicity) have been long challenged scientists and policy makers in the chemical risk assessment. The synergistic effect can be occurred by biochemical interactions among components with different modes of toxic action in living organisms. Although plenty of empirical data might be basically needed to develop predictive models covering the synergistic effect that can play a key role in mixture risk assessment, publically collective databases on ecotoxicological synergistic effects remain highly insufficient. Therefore, the objectives of this study were to investigate how much data is available at the present time, and to develop a survey data on ecotoxicological synergistic effects from literature reviews with a focus on binary pesticide mixtures. http://dx.doi.org/10.1016/j.toxlet.2014.06.711