- Email: [email protected]
A study on the heavy metal contents of cosmetic products in Korea
Abstracts / Toxicology Letters 280S (2017) S92–S106
entific Committee on Occupational Exposure Limits (SCOEL) of the European Commission, judged the sufficiency of the available data. The OEL documentation from 2006 to 2016 published by the two groups was examined for relevant statements. For each substance identified as lacking sufficient data by one group, the corresponding documentation was also collected from the other group, regardless of publication date. We identified 19 substances/substance groups in total, 9 via the SCG (whereof SCOEL had assessed 4) and 10 via the SCOEL (whereof SCG had assessed 7). For 8 substances (ethanolamine, hydrogen chloride, methyl isocyanate, naphthalene, N-methylpyrrolidone, phosphoric acid, phtalic anhydride, soluble platinum compounds), one group identified a critical effect level and/or proposed and OEL, whereas the other group judged the data to be insufficient. Strikingly, for all these substances the documents from the group concluding data insufficiency were published later than the ones that identified a critical effect level. We conclude that there are discrepancies between the two expert groups. These differences might be due to differences in what kind of data are accepted by the group (e.g. unpublished reports) and how the sufficiency of the evidence is judged, even for similar or identical data sets. Nevertheless, both groups seem to have increased their requirements for acceptance over time. http://dx.doi.org/10.1016/j.toxlet.2017.07.260 P-01-02-09 Ambient air pollution in beirut: Attributable cancer risk and mortality burden Hassan Dhaini 1 , Thérèse Salameh 2 , Antoine Waked 3 , Stéphane Sauvage 4 , Agnès Borbon 5 , Paola Formenti 5 , Jean-Franc¸ois Doussin 5 , Nadine Locoge 2 , Charbel Afif 3 1
Department of Environmental Health, American University of Beirut, Beirut, Lebanon 2 Mines Douai, Sciences de l’Atmosphère et Génie de l’Environnement (SAGE), Douai Cedex, France 3 EMMA Laboratory, EGFEM, Centre D’Analyses et de Recherche, Faculty of Science, University Saint-Joseph, Beirut, Lebanon 4 Université de Lille, Lille, France 5 LISA, UMR-CNRS, Université Paris Est Créteil (UPEC), Université Paris Diderot (UPD), Institut Pierre Simon Laplace (IPSL), Créteil, France Lebanon is a rapidly urbanizing country on the Eastern Mediterranean coast. So far, health risks associated with ambient air pollution have not been well characterized. This study aims to assess health risks of non-methane hydrocarbons (NMHCs) and particulate matter (PM) based on two field-sampling campaigns conducted in Beirut in 2011-2012 as part of the Emission and Chemistry of Organic Carbon in East Mediterranean (ECOCEM) project. Collected samples were analyzed as following: 70 NMHCs by TDGC-FID, PM2.5 elemental carbon components using a Lab OC-EC aerosol analyzer, and PAHs by GC–MS. The US EPA fraction-based approach was used to assess non-cancer hazard and cancer risk for aliphatic and aromatic hydrocarbons mixture. The burden of local mortality attributable to PM2.5 was estimated following the UK COMEAP guidelines. The average cumulative cancer risk was found to exceed the EPA acceptable level (10−6 ) by 40-fold in summer and 30-fold in winter. Benzene was found to be the highest contributor to cancer risk (39–43%) followed by 1,3-butadiene (25–29%), and was traced back to traffic gasoline evaporation and combustion. On a typical day, cumulative cancer risk peaks around 12:00 am during summer, and at 10:00 am during winter. The average attributable number of deaths (AD) and years of life lost (YLL) were found to range between 257–327 and 3086–3923, respectively.
S95
Our findings provide a solid baseline for air monitoring and cancer prevention programs particularly by reducing traffic-related carcinogenic emissions. http://dx.doi.org/10.1016/j.toxlet.2017.07.261 P-01-02-10 Comparison of routine clinical pathology parameters in Wistar Han rats at different ages Zhimei Wang, Sue McPherson Toxicology, WuXi AppTec, Suzhou, China Clinical Pathology parameters are routinely assessed during the conduct of toxicology studies. This study was conducted to see if there were any differences in hematology and serum chemistry parameters in Wistar Han rats at three different ages: 11-21, 20-21 and 33-34 weeks. Rats were sourced from a Charles River site in Taiwan. The results from the three data sets were analyzed using the rats aging 11-21 weeks as reference control point. Analysis showed overall whilst most of the parameters were comparable among the three age groups, some parameters did change over time. Analysis of the hematology data showed that slightly lower white blood cell count, lymphocytes (absolute and percentage), increased neutrophils (percentage) in both sexes aging 33-34 weeks as well as males aging 20-21 weeks, increased neutrophils count in males only and decreased reticulocytes amount in both sexes at both ages. Differences in serum chemistry included decreased alkaline phosphatase and inorganic phosphorus, increased glucose in both sexes at both ages, increased total cholesterol and triglyceride in both sexes aging 33-34 weeks as well as males rats aging 20-21 weeks and increased alanine aminotransferase in both sexes aging 33-34 weeks. The tendency of change was consistent with the published reference for this species. These background data collected from this study can serve as a tool to help the toxicologist evaluate study data and put potential findings in context when compared to both the concurrent controls and these data sets. http://dx.doi.org/10.1016/j.toxlet.2017.07.262 P-01-02-11 A study on the heavy metal contents of cosmetic products in Korea Yongkyu Choi Cosmetics Research Team, Ministry of Food and Drug Safety, Cheongju-si, Chungcheongbuk-do, Republic of Korea Most cosmetics in the markets contain technically unavoidable traces of metals from impurities of natural source, manufacturing process or synthesis of ingredients. Among them, metals such as arsenic, lead, antimony, cadmium, mercury are called as heavy metals, which are present naturally in the earth. Chronic exposure of these compounds, however, may cause skin irritation, allergic reaction or adverse effects on the nervous systems. The cosmetic regulation of heavy metal provides that each heavy metal use in cosmetic products should be prohibited in Korea and the authority regulates that each heavy metal regarded as impurities detection limits in cosmetics for lead (20 ppm), arsenic (10 ppm), mercury (1 ppm), antimony (10 ppm) and cadmium (5 ppm). For this reason, this study analysed the content of heavy metals in various types of commercialised cosmetics, including face-cream, rinse-off (cleanser, shampoo), face-makeup
S96
Abstracts / Toxicology Letters 280S (2017) S92–S106
(lipstick, blushes), eye products (eye shadow, eyeliner, mascara) and nail polishes. According to the results, the range of average concentrations in cosmetics formulation for each heavy metal is; Pb 0.333∼4.794 g/mL, As 0.102∼1.676 g/mL, Sb 0∼4.168 g/mL, Cd 0∼0.689 g/mL, Ag 0.00002∼0.00105 g/mL, respectively. The mean concentrations of heavy metal were highly dependent on their formulation. The powder formulation such as eye shadows and blushers mostly contains lead. Eye shadows also contain high level of antimony, which is thought to be due to glitters in the products. The results of this study will be used for risk assessment of heavy metals in cosmetic ingredients. http://dx.doi.org/10.1016/j.toxlet.2017.07.263 P-01-02-12 Role of in silico tools and text mining in the safety assessment of selected plant coumarins Giuseppa Raitano 1 , Emilio Benfenati 1 , Sophia Ananiadou 2 , Xiao Fu 2 , Quoc Tuan Do 3 , Patrice Rat 4 , Laurent Sousselier 5 1
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy National Centre for Text Mining, University of Manchester, Manchester, United Kingdom 3 Greenpharma, Orléans, France 4 Laboratoire de Chimie-Toxicologie Analytique et Cellulaire, Université Paris Descartes, Paris, France 5 Unitis, Paris, France 2
Objective: Plant extracts are widely used in a number of industrial sectors. Their complexity and, for cosmetics, that animal tests are no longer possible, warrants a new approach based on natural molecules to allow for their safety assessment. Using coumarins as an example, this study outlines new methodologies developed in the frame of the NCSTOX project to undertake safety assessments of plant components based on in silico tools and text mining. Methods: Instead of assessing each extract, information was gathered on all plant constituents. Coumarins, which are present in numerous plants and known to exhibit safety concerns, were chosen to validate the methodology. An innovative multi-step text mining approach, using the integrative ARGO workbench, was combined with the use of various in silico models, including VEGA, to predict safe levels of use. Critical compounds were identified as those associated with genotoxicity or classified as high potency skin sensitizers. Other molecules were classified according to a Threshold of Toxicological Concern (TTC) approach. Results: Information on 200 coumarins was compiled. The results demonstrate the key modulating effect and role of the position of certain substituents (e.g. the hydroxyl group) on the coumarins’ scaffold with regard to their safe level of use. Conclusions: The safety assessment of selected coumarins validated a new methodology to establish the toxicological profile of plant constituents. Using text mining methods we curated a novel database to provide the scientific community with animal-free, safe levels of use for plant constituents. http://dx.doi.org/10.1016/j.toxlet.2017.07.264
P-01-02-13 Effect of adiantum capillus veneris against irradiation-induced oxidative stress in adult rats Nitin Verma School of Pharmacy & Emerging Sciences, Baddi University of Emerging Sciences & Technology, Baddi, India Many synthetic and natural agents have been investigated in the recent past for their efficacy to protect against radiation damage. Some isolated plant products capable of giving radioprotection through various mechanism such as free radical scavenging, inhibition of lipid peroxidation etc. The present study aims to evaluate the effect of Adiantum capillus veneris extract against Irradiation induced oxidative stress in adult rats. Forty-two healthy adult Wister rats were divided into four groups: normal control, irradiated control, pre-treated irradiated group and pre and post-treated irradiated group. Results showed significant increase in liver relative weight in irradiated control group after one and fourteen days postirradiation compared to normal control group. Feeding rats with extraxt showed significant decrease in the liver relative weight of the two groups (Pre-treated irradiated and pre- and post-treated irradiated) compared to irradiated control group. Exposing rats to irradiation showed significant (P < 0.05) increase in the level of liver enzymes (AST, ALT and ALP) in irradiated control group after fourteen days post irradiation. Regarding the changes occurred in antioxidants enzymes in liver tissues, a significant (P < 0.05) decrease (GSH & SOD) and increase in (LOP) in irradiated control group. There were significant (P < 0.05) increase in GSH & SOD levels of Pre and Post-Treated Irradiated group at both one and fourteen days post irradiation. In irradiated rats, exposure to radiation caused severe liver damage including hepatocyte edema, necrosis of the hepatocytes, karyolysis, proliferation of kupffer cells and dilated sinusoids. http://dx.doi.org/10.1016/j.toxlet.2017.07.265 P-01-02-14 Sharing and verifying systems toxicology methods and data via the INTERVALS and sbv IMPROVER platforms Stephanie Boue, Arkadiusz K. Kuczaj, David Page, Laure Cannesson, Marianne Seijo, Vincenzo Belcastro, Elena Scotti, Filipe Bonjour, Julia Hoeng, Manuel C. Peitsch Biomedical Research, Philip Morris International, Neuchatel, Switzerland International toxicology programs (e.g., Tox21, ToxCast, EUToxRisk, SEURAT, and TG-GATEs) generate large and complex datasets. Moreover, important streams of data, software and state-of-theart methods are created via industrial R&D programs which are often not publicly shared. Therefore, sharing these industry-owned datasets represents a great opportunity to push forward frontiers of knowledge for the scientific community as a whole. A proof-of-concept database and website (‘INTERVALS’) has been developed to share protocols, software, data and results from inhalation studies and in vitro studies conducted by Philip Morris International R&D that assess potential Modified Risk Tobacco Products (MRTP). The data modeling for INTERVALS took into account the latest standards in terms of data sharing and reproducible research.
entific Committee on Occupational Exposure Limits (SCOEL) of the European Commission, judged the sufficiency of the available data. The OEL documentation from 2006 to 2016 published by the two groups was examined for relevant statements. For each substance identified as lacking sufficient data by one group, the corresponding documentation was also collected from the other group, regardless of publication date. We identified 19 substances/substance groups in total, 9 via the SCG (whereof SCOEL had assessed 4) and 10 via the SCOEL (whereof SCG had assessed 7). For 8 substances (ethanolamine, hydrogen chloride, methyl isocyanate, naphthalene, N-methylpyrrolidone, phosphoric acid, phtalic anhydride, soluble platinum compounds), one group identified a critical effect level and/or proposed and OEL, whereas the other group judged the data to be insufficient. Strikingly, for all these substances the documents from the group concluding data insufficiency were published later than the ones that identified a critical effect level. We conclude that there are discrepancies between the two expert groups. These differences might be due to differences in what kind of data are accepted by the group (e.g. unpublished reports) and how the sufficiency of the evidence is judged, even for similar or identical data sets. Nevertheless, both groups seem to have increased their requirements for acceptance over time. http://dx.doi.org/10.1016/j.toxlet.2017.07.260 P-01-02-09 Ambient air pollution in beirut: Attributable cancer risk and mortality burden Hassan Dhaini 1 , Thérèse Salameh 2 , Antoine Waked 3 , Stéphane Sauvage 4 , Agnès Borbon 5 , Paola Formenti 5 , Jean-Franc¸ois Doussin 5 , Nadine Locoge 2 , Charbel Afif 3 1
Department of Environmental Health, American University of Beirut, Beirut, Lebanon 2 Mines Douai, Sciences de l’Atmosphère et Génie de l’Environnement (SAGE), Douai Cedex, France 3 EMMA Laboratory, EGFEM, Centre D’Analyses et de Recherche, Faculty of Science, University Saint-Joseph, Beirut, Lebanon 4 Université de Lille, Lille, France 5 LISA, UMR-CNRS, Université Paris Est Créteil (UPEC), Université Paris Diderot (UPD), Institut Pierre Simon Laplace (IPSL), Créteil, France Lebanon is a rapidly urbanizing country on the Eastern Mediterranean coast. So far, health risks associated with ambient air pollution have not been well characterized. This study aims to assess health risks of non-methane hydrocarbons (NMHCs) and particulate matter (PM) based on two field-sampling campaigns conducted in Beirut in 2011-2012 as part of the Emission and Chemistry of Organic Carbon in East Mediterranean (ECOCEM) project. Collected samples were analyzed as following: 70 NMHCs by TDGC-FID, PM2.5 elemental carbon components using a Lab OC-EC aerosol analyzer, and PAHs by GC–MS. The US EPA fraction-based approach was used to assess non-cancer hazard and cancer risk for aliphatic and aromatic hydrocarbons mixture. The burden of local mortality attributable to PM2.5 was estimated following the UK COMEAP guidelines. The average cumulative cancer risk was found to exceed the EPA acceptable level (10−6 ) by 40-fold in summer and 30-fold in winter. Benzene was found to be the highest contributor to cancer risk (39–43%) followed by 1,3-butadiene (25–29%), and was traced back to traffic gasoline evaporation and combustion. On a typical day, cumulative cancer risk peaks around 12:00 am during summer, and at 10:00 am during winter. The average attributable number of deaths (AD) and years of life lost (YLL) were found to range between 257–327 and 3086–3923, respectively.
S95
Our findings provide a solid baseline for air monitoring and cancer prevention programs particularly by reducing traffic-related carcinogenic emissions. http://dx.doi.org/10.1016/j.toxlet.2017.07.261 P-01-02-10 Comparison of routine clinical pathology parameters in Wistar Han rats at different ages Zhimei Wang, Sue McPherson Toxicology, WuXi AppTec, Suzhou, China Clinical Pathology parameters are routinely assessed during the conduct of toxicology studies. This study was conducted to see if there were any differences in hematology and serum chemistry parameters in Wistar Han rats at three different ages: 11-21, 20-21 and 33-34 weeks. Rats were sourced from a Charles River site in Taiwan. The results from the three data sets were analyzed using the rats aging 11-21 weeks as reference control point. Analysis showed overall whilst most of the parameters were comparable among the three age groups, some parameters did change over time. Analysis of the hematology data showed that slightly lower white blood cell count, lymphocytes (absolute and percentage), increased neutrophils (percentage) in both sexes aging 33-34 weeks as well as males aging 20-21 weeks, increased neutrophils count in males only and decreased reticulocytes amount in both sexes at both ages. Differences in serum chemistry included decreased alkaline phosphatase and inorganic phosphorus, increased glucose in both sexes at both ages, increased total cholesterol and triglyceride in both sexes aging 33-34 weeks as well as males rats aging 20-21 weeks and increased alanine aminotransferase in both sexes aging 33-34 weeks. The tendency of change was consistent with the published reference for this species. These background data collected from this study can serve as a tool to help the toxicologist evaluate study data and put potential findings in context when compared to both the concurrent controls and these data sets. http://dx.doi.org/10.1016/j.toxlet.2017.07.262 P-01-02-11 A study on the heavy metal contents of cosmetic products in Korea Yongkyu Choi Cosmetics Research Team, Ministry of Food and Drug Safety, Cheongju-si, Chungcheongbuk-do, Republic of Korea Most cosmetics in the markets contain technically unavoidable traces of metals from impurities of natural source, manufacturing process or synthesis of ingredients. Among them, metals such as arsenic, lead, antimony, cadmium, mercury are called as heavy metals, which are present naturally in the earth. Chronic exposure of these compounds, however, may cause skin irritation, allergic reaction or adverse effects on the nervous systems. The cosmetic regulation of heavy metal provides that each heavy metal use in cosmetic products should be prohibited in Korea and the authority regulates that each heavy metal regarded as impurities detection limits in cosmetics for lead (20 ppm), arsenic (10 ppm), mercury (1 ppm), antimony (10 ppm) and cadmium (5 ppm). For this reason, this study analysed the content of heavy metals in various types of commercialised cosmetics, including face-cream, rinse-off (cleanser, shampoo), face-makeup
S96
Abstracts / Toxicology Letters 280S (2017) S92–S106
(lipstick, blushes), eye products (eye shadow, eyeliner, mascara) and nail polishes. According to the results, the range of average concentrations in cosmetics formulation for each heavy metal is; Pb 0.333∼4.794 g/mL, As 0.102∼1.676 g/mL, Sb 0∼4.168 g/mL, Cd 0∼0.689 g/mL, Ag 0.00002∼0.00105 g/mL, respectively. The mean concentrations of heavy metal were highly dependent on their formulation. The powder formulation such as eye shadows and blushers mostly contains lead. Eye shadows also contain high level of antimony, which is thought to be due to glitters in the products. The results of this study will be used for risk assessment of heavy metals in cosmetic ingredients. http://dx.doi.org/10.1016/j.toxlet.2017.07.263 P-01-02-12 Role of in silico tools and text mining in the safety assessment of selected plant coumarins Giuseppa Raitano 1 , Emilio Benfenati 1 , Sophia Ananiadou 2 , Xiao Fu 2 , Quoc Tuan Do 3 , Patrice Rat 4 , Laurent Sousselier 5 1
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy National Centre for Text Mining, University of Manchester, Manchester, United Kingdom 3 Greenpharma, Orléans, France 4 Laboratoire de Chimie-Toxicologie Analytique et Cellulaire, Université Paris Descartes, Paris, France 5 Unitis, Paris, France 2
Objective: Plant extracts are widely used in a number of industrial sectors. Their complexity and, for cosmetics, that animal tests are no longer possible, warrants a new approach based on natural molecules to allow for their safety assessment. Using coumarins as an example, this study outlines new methodologies developed in the frame of the NCSTOX project to undertake safety assessments of plant components based on in silico tools and text mining. Methods: Instead of assessing each extract, information was gathered on all plant constituents. Coumarins, which are present in numerous plants and known to exhibit safety concerns, were chosen to validate the methodology. An innovative multi-step text mining approach, using the integrative ARGO workbench, was combined with the use of various in silico models, including VEGA, to predict safe levels of use. Critical compounds were identified as those associated with genotoxicity or classified as high potency skin sensitizers. Other molecules were classified according to a Threshold of Toxicological Concern (TTC) approach. Results: Information on 200 coumarins was compiled. The results demonstrate the key modulating effect and role of the position of certain substituents (e.g. the hydroxyl group) on the coumarins’ scaffold with regard to their safe level of use. Conclusions: The safety assessment of selected coumarins validated a new methodology to establish the toxicological profile of plant constituents. Using text mining methods we curated a novel database to provide the scientific community with animal-free, safe levels of use for plant constituents. http://dx.doi.org/10.1016/j.toxlet.2017.07.264
P-01-02-13 Effect of adiantum capillus veneris against irradiation-induced oxidative stress in adult rats Nitin Verma School of Pharmacy & Emerging Sciences, Baddi University of Emerging Sciences & Technology, Baddi, India Many synthetic and natural agents have been investigated in the recent past for their efficacy to protect against radiation damage. Some isolated plant products capable of giving radioprotection through various mechanism such as free radical scavenging, inhibition of lipid peroxidation etc. The present study aims to evaluate the effect of Adiantum capillus veneris extract against Irradiation induced oxidative stress in adult rats. Forty-two healthy adult Wister rats were divided into four groups: normal control, irradiated control, pre-treated irradiated group and pre and post-treated irradiated group. Results showed significant increase in liver relative weight in irradiated control group after one and fourteen days postirradiation compared to normal control group. Feeding rats with extraxt showed significant decrease in the liver relative weight of the two groups (Pre-treated irradiated and pre- and post-treated irradiated) compared to irradiated control group. Exposing rats to irradiation showed significant (P < 0.05) increase in the level of liver enzymes (AST, ALT and ALP) in irradiated control group after fourteen days post irradiation. Regarding the changes occurred in antioxidants enzymes in liver tissues, a significant (P < 0.05) decrease (GSH & SOD) and increase in (LOP) in irradiated control group. There were significant (P < 0.05) increase in GSH & SOD levels of Pre and Post-Treated Irradiated group at both one and fourteen days post irradiation. In irradiated rats, exposure to radiation caused severe liver damage including hepatocyte edema, necrosis of the hepatocytes, karyolysis, proliferation of kupffer cells and dilated sinusoids. http://dx.doi.org/10.1016/j.toxlet.2017.07.265 P-01-02-14 Sharing and verifying systems toxicology methods and data via the INTERVALS and sbv IMPROVER platforms Stephanie Boue, Arkadiusz K. Kuczaj, David Page, Laure Cannesson, Marianne Seijo, Vincenzo Belcastro, Elena Scotti, Filipe Bonjour, Julia Hoeng, Manuel C. Peitsch Biomedical Research, Philip Morris International, Neuchatel, Switzerland International toxicology programs (e.g., Tox21, ToxCast, EUToxRisk, SEURAT, and TG-GATEs) generate large and complex datasets. Moreover, important streams of data, software and state-of-theart methods are created via industrial R&D programs which are often not publicly shared. Therefore, sharing these industry-owned datasets represents a great opportunity to push forward frontiers of knowledge for the scientific community as a whole. A proof-of-concept database and website (‘INTERVALS’) has been developed to share protocols, software, data and results from inhalation studies and in vitro studies conducted by Philip Morris International R&D that assess potential Modified Risk Tobacco Products (MRTP). The data modeling for INTERVALS took into account the latest standards in terms of data sharing and reproducible research.