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Probabilistic exposure assessment to nail cosmetics by French consumers
Abstracts / Toxicology Letters 221S (2013) S59–S256
with GG and DG were conducted using S9 fractions of normal and cancer human breast tissue to answer the question to what degree normal and diseased tissue can deconjugate, and thus bio-activate, glucuronide metabolites. The results obtained provide evidence that the most abundant glucuronide metabolites in blood (i.e. GG and DG), are not estrogenic as such and need deconjugation to the corresponding aglycone to become estrogenic. http://dx.doi.org/10.1016/j.toxlet.2013.05.545
P20-27 Post hoc ergo propter hoc?—The CIOMS scale to differentiate time and causal association in hepatotoxicity Johannes Schulze 1,∗ , Rolf Teschke 2 1
Institute of Industrial, Social and Environmental Medicine, Medical Faculty, Goethe-University Frankfurt/Main, Germany, 2 Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Academic Teaching Hospital of the Medical Faculty of the Goethe University Frankfurt/Main, Germany After observing newly developed signs of clinical hepatotoxicity by drugs and herbs, causality assessment is the next step necessary. Not every cause in timely connection with this observation necessarily contributes to the result as illustrated by the philosophical statement “post hoc ergo propter hoc” – “because it happened later it must be because of it”. In order to affirm causality, other conditions must be met, especially the exclusion of other causes relevant to hepatotoxicity and confirmation of an appropriate response to dechallenge. Prior publication of hepatotoxicity will add to the certainty of the judgement also a positive reexposure observation albeit these two may not be present. In order to allow a well founded and rapid evaluation of newly observed cases of hepatotoxicity by nonexperts, we have updated and amended the CIOMS scale (Danan and Bénichou, Journal of Clinical Epidemiology 1993; 46:1323). This list – after confirmation of hepatocellular or cholestatic/mixed type liver injury – provides a framework to collect and evaluate data for seven essential aspects, namely time to onset of symptoms, course of laboratory parameters after withdrawal of the suspected agent, presence of general risk factors for hepatotoxicity, concomitant use of other potentially hepatotoxic agents, exclusion of other causes for liver injury, namely infectious causes, availability of previous information and reexposure results. All topics are graded with points, major factors are allocated + 3 points, whereas evidence for other causes will subtract 3 points. For every case the points are summarized (+14 to −10), causality is given according to the resulting number: ≤0, excluded; 1–2, unlikely; 3–5, possible; 6–8, probable; ≥9, highly probable. All items are unambiguous allowing to establish a well based likelihood even for scientists inexperienced in hepatic diseases. The CIOMS scale has been regularly updated, its results have been validated by application to published hepatotoxicity cases with good positive and negative predictive values and excellent sensitivity and specificity. In addition, it gives a framework for prospective data collection to allow reassessments based on an excellent data base, as well as a reminder to exclude all relevant alternative causes present in a clinical context. Thus, the CIOMS scale allows to quickly and reliably assess hepatotoxic causality. http://dx.doi.org/10.1016/j.toxlet.2013.05.546
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P20-28 Probabilistic exposure assessment to nail cosmetics by French consumers Typhaine Morisset ∗ , Anne-Sophie Ficheux, Cindy Postic, Grégoire Chevillotte, Alain-Claude Roudot Laboratoire d’Evaluation du Risque Chimique pour le Consommateur, Brest, France Nail cosmetics are very often used by women of all ages. Main ingredients are organic solvents (as toluene), plasticizer (phthalates) and synthetic resin (sulphonamide). The aim of this study was to generate data for evaluating exposure assessment to nail products in French population. First, a survey was done on 1512 adults and 302 children (0–17 years) to know the percentage of consumers, frequency of use, and main nail cosmetics consumed. This survey, made on a web panel, was defined by a quota method. Secondly, quantities used by consumers were estimated through experimental tests at laboratory. Then, frequency and quantity data were combined through a probabilistic method (Monte Carlo) to assess chronic exposure. Exposure assessment was done for cutaneous, inhalation and oral routes. 60% of adults and 41% of children use regularly nail cosmetics on hands. The median frequency of use is 1 week−1 for adults and 0.8 week−1 for children. High consumers use nail products 3.3 and 4.7 week−1 for adults and children, respectively. Durations of application and drying during which alarge part of thesolvents evaporate are 13 (median) and 38 min (P95), showing the importance of an exposure assessment by inhalation route. Amounts of nail polish applied per coat are 196 (median) and 360 mg (P95). Half of the women keep nail cosmetics during 1 week. As 15% of nail product users bite their nails (up to 31% for 18–24 years), oral exposure is of great interest. Exposure assessment is currently explored. http://dx.doi.org/10.1016/j.toxlet.2013.05.547
P20-29 Quantitative risk assessment for infant and children’s products based on child specific exposure considerations Taryn Kirsch ∗ , Susan Felter Procter & Gamble, Cincinnati, USA Methods for quantitative risk assessment (QRA) generally consider the variability of the human population, including the potential for sensitive subpopulations. In the absence of data, a default uncertainty factor (UF) of 10× has been used to account for this variability. Although infants and children have historically been considered to be covered by the 10× UF, there has been some ongoing debate as to whether this provides adequate protection, particularly for infants. The potential for higher exposure is one reason that infants/children can have a higher potential risk than adults, since they are growing rapidly and have a greater food/water/air intake per kg body weight. They also have a greater skin surface area per kg body weight. This can raise concerns when a QRA is based on adult exposure parameters, and is why, for example, an Acceptable Daily Intake established for a food chemical is not intended to be used for infants < 4 months old. Therefore, any assessment of a product intended for use by infants/children should include an exposure assessment done specifically for this population, rather than extrapolating from adult values. The focus of
with GG and DG were conducted using S9 fractions of normal and cancer human breast tissue to answer the question to what degree normal and diseased tissue can deconjugate, and thus bio-activate, glucuronide metabolites. The results obtained provide evidence that the most abundant glucuronide metabolites in blood (i.e. GG and DG), are not estrogenic as such and need deconjugation to the corresponding aglycone to become estrogenic. http://dx.doi.org/10.1016/j.toxlet.2013.05.545
P20-27 Post hoc ergo propter hoc?—The CIOMS scale to differentiate time and causal association in hepatotoxicity Johannes Schulze 1,∗ , Rolf Teschke 2 1
Institute of Industrial, Social and Environmental Medicine, Medical Faculty, Goethe-University Frankfurt/Main, Germany, 2 Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Academic Teaching Hospital of the Medical Faculty of the Goethe University Frankfurt/Main, Germany After observing newly developed signs of clinical hepatotoxicity by drugs and herbs, causality assessment is the next step necessary. Not every cause in timely connection with this observation necessarily contributes to the result as illustrated by the philosophical statement “post hoc ergo propter hoc” – “because it happened later it must be because of it”. In order to affirm causality, other conditions must be met, especially the exclusion of other causes relevant to hepatotoxicity and confirmation of an appropriate response to dechallenge. Prior publication of hepatotoxicity will add to the certainty of the judgement also a positive reexposure observation albeit these two may not be present. In order to allow a well founded and rapid evaluation of newly observed cases of hepatotoxicity by nonexperts, we have updated and amended the CIOMS scale (Danan and Bénichou, Journal of Clinical Epidemiology 1993; 46:1323). This list – after confirmation of hepatocellular or cholestatic/mixed type liver injury – provides a framework to collect and evaluate data for seven essential aspects, namely time to onset of symptoms, course of laboratory parameters after withdrawal of the suspected agent, presence of general risk factors for hepatotoxicity, concomitant use of other potentially hepatotoxic agents, exclusion of other causes for liver injury, namely infectious causes, availability of previous information and reexposure results. All topics are graded with points, major factors are allocated + 3 points, whereas evidence for other causes will subtract 3 points. For every case the points are summarized (+14 to −10), causality is given according to the resulting number: ≤0, excluded; 1–2, unlikely; 3–5, possible; 6–8, probable; ≥9, highly probable. All items are unambiguous allowing to establish a well based likelihood even for scientists inexperienced in hepatic diseases. The CIOMS scale has been regularly updated, its results have been validated by application to published hepatotoxicity cases with good positive and negative predictive values and excellent sensitivity and specificity. In addition, it gives a framework for prospective data collection to allow reassessments based on an excellent data base, as well as a reminder to exclude all relevant alternative causes present in a clinical context. Thus, the CIOMS scale allows to quickly and reliably assess hepatotoxic causality. http://dx.doi.org/10.1016/j.toxlet.2013.05.546
S227
P20-28 Probabilistic exposure assessment to nail cosmetics by French consumers Typhaine Morisset ∗ , Anne-Sophie Ficheux, Cindy Postic, Grégoire Chevillotte, Alain-Claude Roudot Laboratoire d’Evaluation du Risque Chimique pour le Consommateur, Brest, France Nail cosmetics are very often used by women of all ages. Main ingredients are organic solvents (as toluene), plasticizer (phthalates) and synthetic resin (sulphonamide). The aim of this study was to generate data for evaluating exposure assessment to nail products in French population. First, a survey was done on 1512 adults and 302 children (0–17 years) to know the percentage of consumers, frequency of use, and main nail cosmetics consumed. This survey, made on a web panel, was defined by a quota method. Secondly, quantities used by consumers were estimated through experimental tests at laboratory. Then, frequency and quantity data were combined through a probabilistic method (Monte Carlo) to assess chronic exposure. Exposure assessment was done for cutaneous, inhalation and oral routes. 60% of adults and 41% of children use regularly nail cosmetics on hands. The median frequency of use is 1 week−1 for adults and 0.8 week−1 for children. High consumers use nail products 3.3 and 4.7 week−1 for adults and children, respectively. Durations of application and drying during which alarge part of thesolvents evaporate are 13 (median) and 38 min (P95), showing the importance of an exposure assessment by inhalation route. Amounts of nail polish applied per coat are 196 (median) and 360 mg (P95). Half of the women keep nail cosmetics during 1 week. As 15% of nail product users bite their nails (up to 31% for 18–24 years), oral exposure is of great interest. Exposure assessment is currently explored. http://dx.doi.org/10.1016/j.toxlet.2013.05.547
P20-29 Quantitative risk assessment for infant and children’s products based on child specific exposure considerations Taryn Kirsch ∗ , Susan Felter Procter & Gamble, Cincinnati, USA Methods for quantitative risk assessment (QRA) generally consider the variability of the human population, including the potential for sensitive subpopulations. In the absence of data, a default uncertainty factor (UF) of 10× has been used to account for this variability. Although infants and children have historically been considered to be covered by the 10× UF, there has been some ongoing debate as to whether this provides adequate protection, particularly for infants. The potential for higher exposure is one reason that infants/children can have a higher potential risk than adults, since they are growing rapidly and have a greater food/water/air intake per kg body weight. They also have a greater skin surface area per kg body weight. This can raise concerns when a QRA is based on adult exposure parameters, and is why, for example, an Acceptable Daily Intake established for a food chemical is not intended to be used for infants < 4 months old. Therefore, any assessment of a product intended for use by infants/children should include an exposure assessment done specifically for this population, rather than extrapolating from adult values. The focus of