A Systematic Assessment of the Epidemiologic Literature Regarding an Association between Acetaminophen Exposure and Cancer
The objective of this publication is to analyze the results of these epidemiologic studies using a framework that accounts for the inherent challenge of evaluating acetaminophen, including, broad population-wide use in multiple disease states, challenges with exposure measurement, protopathic bias, channeling bias, and recall bias. When evaluated using this framework, the data do not support a causal association between acetaminophen use and cancer.PMID:34517075 | DOI:10.1016/j.yrtph.2021.105043 (Source: Regulatory Toxicology and Pharmacology : RTP)
Source: Regulatory Toxicology and Pharmacology : RTP - September 13, 2021 Category: Toxicology Authors: Rachel Weinstein Amisha M Parikh-Das Raymark Salonga Martijn Schuemie Patrick B Ryan Evren Atillasoy Anne Vosatka Gary Eichenbaum Jesse A Berlin Source Type: research

A Systematic Assessment of the Epidemiologic Literature Regarding an Association between Acetaminophen Exposure and Cancer
The objective of this publication is to analyze the results of these epidemiologic studies using a framework that accounts for the inherent challenge of evaluating acetaminophen, including, broad population-wide use in multiple disease states, challenges with exposure measurement, protopathic bias, channeling bias, and recall bias. When evaluated using this framework, the data do not support a causal association between acetaminophen use and cancer.PMID:34517075 | DOI:10.1016/j.yrtph.2021.105043 (Source: Regulatory Toxicology and Pharmacology : RTP)
Source: Regulatory Toxicology and Pharmacology : RTP - September 13, 2021 Category: Toxicology Authors: Rachel Weinstein Amisha M Parikh-Das Raymark Salonga Martijn Schuemie Patrick B Ryan Evren Atillasoy Anne Vosatka Gary Eichenbaum Jesse A Berlin Source Type: research

A Systematic Assessment of the Epidemiologic Literature Regarding an Association between Acetaminophen Exposure and Cancer
The objective of this publication is to analyze the results of these epidemiologic studies using a framework that accounts for the inherent challenge of evaluating acetaminophen, including, broad population-wide use in multiple disease states, challenges with exposure measurement, protopathic bias, channeling bias, and recall bias. When evaluated using this framework, the data do not support a causal association between acetaminophen use and cancer.PMID:34517075 | DOI:10.1016/j.yrtph.2021.105043 (Source: Regulatory Toxicology and Pharmacology : RTP)
Source: Regulatory Toxicology and Pharmacology : RTP - September 13, 2021 Category: Toxicology Authors: Rachel Weinstein Amisha M Parikh-Das Raymark Salonga Martijn Schuemie Patrick B Ryan Evren Atillasoy Anne Vosatka Gary Eichenbaum Jesse A Berlin Source Type: research

A Systematic Assessment of the Epidemiologic Literature Regarding an Association between Acetaminophen Exposure and Cancer
The objective of this publication is to analyze the results of these epidemiologic studies using a framework that accounts for the inherent challenge of evaluating acetaminophen, including, broad population-wide use in multiple disease states, challenges with exposure measurement, protopathic bias, channeling bias, and recall bias. When evaluated using this framework, the data do not support a causal association between acetaminophen use and cancer.PMID:34517075 | DOI:10.1016/j.yrtph.2021.105043 (Source: Regulatory Toxicology and Pharmacology : RTP)
Source: Regulatory Toxicology and Pharmacology : RTP - September 13, 2021 Category: Toxicology Authors: Rachel Weinstein Amisha M Parikh-Das Raymark Salonga Martijn Schuemie Patrick B Ryan Evren Atillasoy Anne Vosatka Gary Eichenbaum Jesse A Berlin Source Type: research

A Systematic Assessment of the Epidemiologic Literature Regarding an Association between Acetaminophen Exposure and Cancer
The objective of this publication is to analyze the results of these epidemiologic studies using a framework that accounts for the inherent challenge of evaluating acetaminophen, including, broad population-wide use in multiple disease states, challenges with exposure measurement, protopathic bias, channeling bias, and recall bias. When evaluated using this framework, the data do not support a causal association between acetaminophen use and cancer.PMID:34517075 | DOI:10.1016/j.yrtph.2021.105043 (Source: Regulatory Toxicology and Pharmacology : RTP)
Source: Regulatory Toxicology and Pharmacology : RTP - September 13, 2021 Category: Toxicology Authors: Rachel Weinstein Amisha M Parikh-Das Raymark Salonga Martijn Schuemie Patrick B Ryan Evren Atillasoy Anne Vosatka Gary Eichenbaum Jesse A Berlin Source Type: research

A Systematic Assessment of the Epidemiologic Literature Regarding an Association between Acetaminophen Exposure and Cancer
The objective of this publication is to analyze the results of these epidemiologic studies using a framework that accounts for the inherent challenge of evaluating acetaminophen, including, broad population-wide use in multiple disease states, challenges with exposure measurement, protopathic bias, channeling bias, and recall bias. When evaluated using this framework, the data do not support a causal association between acetaminophen use and cancer.PMID:34517075 | DOI:10.1016/j.yrtph.2021.105043 (Source: Regulatory Toxicology and Pharmacology : RTP)
Source: Regulatory Toxicology and Pharmacology : RTP - September 13, 2021 Category: Toxicology Authors: Rachel Weinstein Amisha M Parikh-Das Raymark Salonga Martijn Schuemie Patrick B Ryan Evren Atillasoy Anne Vosatka Gary Eichenbaum Jesse A Berlin Source Type: research

A Systematic Assessment of the Epidemiologic Literature Regarding an Association between Acetaminophen Exposure and Cancer
The objective of this publication is to analyze the results of these epidemiologic studies using a framework that accounts for the inherent challenge of evaluating acetaminophen, including, broad population-wide use in multiple disease states, challenges with exposure measurement, protopathic bias, channeling bias, and recall bias. When evaluated using this framework, the data do not support a causal association between acetaminophen use and cancer.PMID:34517075 | DOI:10.1016/j.yrtph.2021.105043 (Source: Regulatory Toxicology and Pharmacology : RTP)
Source: Regulatory Toxicology and Pharmacology : RTP - September 13, 2021 Category: Toxicology Authors: Rachel Weinstein Amisha M Parikh-Das Raymark Salonga Martijn Schuemie Patrick B Ryan Evren Atillasoy Anne Vosatka Gary Eichenbaum Jesse A Berlin Source Type: research

An evolution of risk assessment for potential carcinogens in food: Scientific session proceedings
Discussion. This Workshop Report provides an overview of key themes and information presented during the session. Summary statements were prepared by the authors and reviewed by the presenters but do not necessarily represent the position or policy of the FDA, the EPA, or other affiliations.PMID:34506878 | DOI:10.1016/j.yrtph.2021.105047 (Source: Regulatory Toxicology and Pharmacology : RTP)
Source: Regulatory Toxicology and Pharmacology : RTP - September 10, 2021 Category: Toxicology Authors: G Craig Llewellyn Marisa O Rihner Paul Hanlon Source Type: research

Inter-laboratory performance of ICE histopathology scoring to identify UN GHS Category 1 surfactants and non-extreme pH detergents
Regul Toxicol Pharmacol. 2021 Sep 7:105044. doi: 10.1016/j.yrtph.2021.105044. Online ahead of print.ABSTRACTThe inter-laboratory performance of Isolated Chicken Eye (ICE) histopathology scoring was assessed for predicting EU CLP/UN GHS Cat. 1 surfactants. Furthermore, the predictive capacity of ICE histopathology was evaluated for the combined dataset of surfactants and existing data for non-extreme pH (2
Source: Regulatory Toxicology and Pharmacology : RTP - September 10, 2021 Category: Toxicology Authors: Chantra Eskes Marcel V W Wijnands Martina Hermann Menk Prinsen Caroline Bertein Dominic Byrne Robert Kreutzer Vasanthi Mowat Ian Taylor Erwin van Vliet Klaus Weber Source Type: research

Occupational exposure to hexavalent chromium. Part II. Hazard assessment of carcinogenic effects
Regul Toxicol Pharmacol. 2021 Sep 7:105045. doi: 10.1016/j.yrtph.2021.105045. Online ahead of print.ABSTRACTHexavalent chromium (Cr(VI)) compounds have been studied extensively and several agencies have described their toxicological profile. In the past, personnel of the Dutch Ministry of Defence may have been exposed to Cr(VI) during maintenance activities on NATO equipment. To investigate if this exposure may have caused irreversible adverse health effects, the Dutch National Institute for Public Health and the Environment (RIVM) summarized all available knowledge from previous evaluations. This information was complemen...
Source: Regulatory Toxicology and Pharmacology : RTP - September 10, 2021 Category: Toxicology Authors: Shalenie P den Braver-Sewradj Jan van Benthem Yvonne C M Staal Janine Ezendam Aldert H Piersma Ellen V S Hessel Source Type: research

In silico assessment of genotoxicity. Combinations of sensitive structural alerts minimize false negative predictions for all genotoxicity endpoints and can single out chemicals for which experimentation can be avoided
Regul Toxicol Pharmacol. 2021 Sep 7:105042. doi: 10.1016/j.yrtph.2021.105042. Online ahead of print.ABSTRACTGenotoxicity assessment of chemicals has a crucial role in most regulations. Due to labor, time, cost, and animal welfare issues, attention is being given to (Q)SAR methods. A strategic application of alternative methods is to first use a sequence of conservative (very sensitive) (Q)SARs and/or in vitro models to arrive at the conclusion that no further testing is necessary for negatives, and to use mechanistically based, Weight-Of-Evidence approach to evaluate the chemicals showing positive results. The ICH M7 guide...
Source: Regulatory Toxicology and Pharmacology : RTP - September 10, 2021 Category: Toxicology Authors: Romualdo Benigni Source Type: research

An evolution of risk assessment for potential carcinogens in food: Scientific session proceedings
Discussion. This Workshop Report provides an overview of key themes and information presented during the session. Summary statements were prepared by the authors and reviewed by the presenters but do not necessarily represent the position or policy of the FDA, the EPA, or other affiliations.PMID:34506878 | DOI:10.1016/j.yrtph.2021.105047 (Source: Regulatory Toxicology and Pharmacology : RTP)
Source: Regulatory Toxicology and Pharmacology : RTP - September 10, 2021 Category: Toxicology Authors: G Craig Llewellyn Marisa O Rihner Paul Hanlon Source Type: research

Inter-laboratory performance of ICE histopathology scoring to identify UN GHS Category 1 surfactants and non-extreme pH detergents
Regul Toxicol Pharmacol. 2021 Sep 7:105044. doi: 10.1016/j.yrtph.2021.105044. Online ahead of print.ABSTRACTThe inter-laboratory performance of Isolated Chicken Eye (ICE) histopathology scoring was assessed for predicting EU CLP/UN GHS Cat. 1 surfactants. Furthermore, the predictive capacity of ICE histopathology was evaluated for the combined dataset of surfactants and existing data for non-extreme pH (2
Source: Regulatory Toxicology and Pharmacology : RTP - September 10, 2021 Category: Toxicology Authors: Chantra Eskes Marcel V W Wijnands Martina Hermann Menk Prinsen Caroline Bertein Dominic Byrne Robert Kreutzer Vasanthi Mowat Ian Taylor Erwin van Vliet Klaus Weber Source Type: research

Occupational exposure to hexavalent chromium. Part II. Hazard assessment of carcinogenic effects
Regul Toxicol Pharmacol. 2021 Sep 7:105045. doi: 10.1016/j.yrtph.2021.105045. Online ahead of print.ABSTRACTHexavalent chromium (Cr(VI)) compounds have been studied extensively and several agencies have described their toxicological profile. In the past, personnel of the Dutch Ministry of Defence may have been exposed to Cr(VI) during maintenance activities on NATO equipment. To investigate if this exposure may have caused irreversible adverse health effects, the Dutch National Institute for Public Health and the Environment (RIVM) summarized all available knowledge from previous evaluations. This information was complemen...
Source: Regulatory Toxicology and Pharmacology : RTP - September 10, 2021 Category: Toxicology Authors: Shalenie P den Braver-Sewradj Jan van Benthem Yvonne C M Staal Janine Ezendam Aldert H Piersma Ellen V S Hessel Source Type: research

In silico assessment of genotoxicity. Combinations of sensitive structural alerts minimize false negative predictions for all genotoxicity endpoints and can single out chemicals for which experimentation can be avoided
Regul Toxicol Pharmacol. 2021 Sep 7:105042. doi: 10.1016/j.yrtph.2021.105042. Online ahead of print.ABSTRACTGenotoxicity assessment of chemicals has a crucial role in most regulations. Due to labor, time, cost, and animal welfare issues, attention is being given to (Q)SAR methods. A strategic application of alternative methods is to first use a sequence of conservative (very sensitive) (Q)SARs and/or in vitro models to arrive at the conclusion that no further testing is necessary for negatives, and to use mechanistically based, Weight-Of-Evidence approach to evaluate the chemicals showing positive results. The ICH M7 guide...
Source: Regulatory Toxicology and Pharmacology : RTP - September 10, 2021 Category: Toxicology Authors: Romualdo Benigni Source Type: research

An evolution of risk assessment for potential carcinogens in food: Scientific session proceedings
Discussion. This Workshop Report provides an overview of key themes and information presented during the session. Summary statements were prepared by the authors and reviewed by the presenters but do not necessarily represent the position or policy of the FDA, the EPA, or other affiliations.PMID:34506878 | DOI:10.1016/j.yrtph.2021.105047 (Source: Regulatory Toxicology and Pharmacology : RTP)
Source: Regulatory Toxicology and Pharmacology : RTP - September 10, 2021 Category: Toxicology Authors: G Craig Llewellyn Marisa O Rihner Paul Hanlon Source Type: research

Inter-laboratory performance of ICE histopathology scoring to identify UN GHS Category 1 surfactants and non-extreme pH detergents
Regul Toxicol Pharmacol. 2021 Sep 7:105044. doi: 10.1016/j.yrtph.2021.105044. Online ahead of print.ABSTRACTThe inter-laboratory performance of Isolated Chicken Eye (ICE) histopathology scoring was assessed for predicting EU CLP/UN GHS Cat. 1 surfactants. Furthermore, the predictive capacity of ICE histopathology was evaluated for the combined dataset of surfactants and existing data for non-extreme pH (2
Source: Regulatory Toxicology and Pharmacology : RTP - September 10, 2021 Category: Toxicology Authors: Chantra Eskes Marcel V W Wijnands Martina Hermann Menk Prinsen Caroline Bertein Dominic Byrne Robert Kreutzer Vasanthi Mowat Ian Taylor Erwin van Vliet Klaus Weber Source Type: research

Occupational exposure to hexavalent chromium. Part II. Hazard assessment of carcinogenic effects
Regul Toxicol Pharmacol. 2021 Sep 7:105045. doi: 10.1016/j.yrtph.2021.105045. Online ahead of print.ABSTRACTHexavalent chromium (Cr(VI)) compounds have been studied extensively and several agencies have described their toxicological profile. In the past, personnel of the Dutch Ministry of Defence may have been exposed to Cr(VI) during maintenance activities on NATO equipment. To investigate if this exposure may have caused irreversible adverse health effects, the Dutch National Institute for Public Health and the Environment (RIVM) summarized all available knowledge from previous evaluations. This information was complemen...
Source: Regulatory Toxicology and Pharmacology : RTP - September 10, 2021 Category: Toxicology Authors: Shalenie P den Braver-Sewradj Jan van Benthem Yvonne C M Staal Janine Ezendam Aldert H Piersma Ellen V S Hessel Source Type: research

In silico assessment of genotoxicity. Combinations of sensitive structural alerts minimize false negative predictions for all genotoxicity endpoints and can single out chemicals for which experimentation can be avoided
Regul Toxicol Pharmacol. 2021 Sep 7:105042. doi: 10.1016/j.yrtph.2021.105042. Online ahead of print.ABSTRACTGenotoxicity assessment of chemicals has a crucial role in most regulations. Due to labor, time, cost, and animal welfare issues, attention is being given to (Q)SAR methods. A strategic application of alternative methods is to first use a sequence of conservative (very sensitive) (Q)SARs and/or in vitro models to arrive at the conclusion that no further testing is necessary for negatives, and to use mechanistically based, Weight-Of-Evidence approach to evaluate the chemicals showing positive results. The ICH M7 guide...
Source: Regulatory Toxicology and Pharmacology : RTP - September 10, 2021 Category: Toxicology Authors: Romualdo Benigni Source Type: research

Ability of mathematical models to predict human in vivo percutaneous penetration of steroids
In this study, accuracy of predicted flux (penetration/absorption) by the main mathematical model used by the EPA, the Potts and Guy model based on in vitro data is compared to actual human in vivo data from our laboratory of percutaneous absorption of topical steroid. We focused on steroids due to the availability of steroid in vivo human data in our laboratory. For most steroids the flux was underestimated by a factor 10-60. However, within the group itself, there was an association between the Potts and Guy model and experimental human in vivo data (Pearson Correlation = 0.8925, p = 0.0001). Additionally, some physioche...
Source: Regulatory Toxicology and Pharmacology : RTP - September 9, 2021 Category: Toxicology Authors: Anuk Burli Rebecca M Law Howard I Maibach Source Type: research

Post-Market Surveillance of Consumer Products: Framework for Adverse Event Management
Regul Toxicol Pharmacol. 2021 Sep 2:105028. doi: 10.1016/j.yrtph.2021.105028. Online ahead of print.ABSTRACTAnalysis of spontaneous reports of adverse events is an important source of information that can be used to improve consumer products. Various agencies have adverse event reporting requirements and many companies collect such data directly from consumers. Nonetheless, a universal framework is absent that identifies and evaluates spontaneously reported adverse events, and, most important, assesses the potential association between exposure and adverse events. We are presenting a three-part framework: Phase I - Intake ...
Source: Regulatory Toxicology and Pharmacology : RTP - September 5, 2021 Category: Toxicology Authors: R Kingston K Sioris J Gualtieri A Brutlag W Droege T G Osimitz Source Type: research

Post-Market Surveillance of Consumer Products: Framework for Adverse Event Management
Regul Toxicol Pharmacol. 2021 Sep 2:105028. doi: 10.1016/j.yrtph.2021.105028. Online ahead of print.ABSTRACTAnalysis of spontaneous reports of adverse events is an important source of information that can be used to improve consumer products. Various agencies have adverse event reporting requirements and many companies collect such data directly from consumers. Nonetheless, a universal framework is absent that identifies and evaluates spontaneously reported adverse events, and, most important, assesses the potential association between exposure and adverse events. We are presenting a three-part framework: Phase I - Intake ...
Source: Regulatory Toxicology and Pharmacology : RTP - September 5, 2021 Category: Toxicology Authors: R Kingston K Sioris J Gualtieri A Brutlag W Droege T G Osimitz Source Type: research

Appraisal of the human health related toxicological information available on dicyclopentadiene (DCPD) in view of assessing the substance's potential to cause endocrine disruption
Regul Toxicol Pharmacol. 2021 Aug 31:105040. doi: 10.1016/j.yrtph.2021.105040. Online ahead of print.ABSTRACTDicyclopentadiene (DCPD) is an olefinic hydrocarbon which is manufactured and imported into the European Union (EU) at greater than 1,000 tons per year. Concerns related to fetotoxic effects observed in reproductive toxicity studies at high doses led the REACH registrants to self-classify DCPD as a Category 2 reproductive toxicant under the EU CLP Regulation. DCPD was also reviewed in the European Union in the frame of an ongoing European Chemical Agency (ECHA) Community Rolling Action Plan (CoRAP) procedure and und...
Source: Regulatory Toxicology and Pharmacology : RTP - September 3, 2021 Category: Toxicology Authors: Francesca Tencalla Neslihan Aygun Kocabas Martijn Rooseboom Erik Rushton Nicholas Synhaeve Thomas Petry Source Type: research

Safety evaluation of food enzymes produced by a safe strain lineage of Bacillussubtilis
Regul Toxicol Pharmacol. 2021 Aug 27;126:105030. doi: 10.1016/j.yrtph.2021.105030. Online ahead of print.ABSTRACTThe safety of microbially-derived food enzymes must be carefully assessed before market introduction. The production strain's safety is central to the assessment. In this paper, we have determined that DSM's Bacillus subtilis strain lineage can be considered safe for food enzyme production. The mutations introduced into this non-pathogenic and non-toxigenic microorganism do not lead to any safety concerns, as ensured by a thorough characterization of the strain lineage. The safety of both targeted and randomly i...
Source: Regulatory Toxicology and Pharmacology : RTP - August 29, 2021 Category: Toxicology Authors: Melina Galano Myrthe W van den Dungen Tjeerd van Rij Hanna E Abbas Source Type: research

Species selection for nonclinical safety assessment of drug candidates: Examples of current industry practice
Regul Toxicol Pharmacol. 2021 Aug 27;126:105029. doi: 10.1016/j.yrtph.2021.105029. Online ahead of print.ABSTRACTIn drug development, nonclinical safety assessment is pivotal for human risk assessment and support of clinical development. Selecting the relevant/appropriate animal species for toxicity testing increases the likelihood of detecting potential effects in humans, and although recent regulatory guidelines state the need to justify or dis-qualify animal species for toxicity testing, individual companies have developed decision-processes most appropriate for their molecules, experience and 3Rs policies. These genera...
Source: Regulatory Toxicology and Pharmacology : RTP - August 29, 2021 Category: Toxicology Authors: Rostam Namdari Keith Jones Samuel S Chuang Steven Van Cruchten Zuhal Dincer Noel Downes Lars Friis Mikkelsen Joanna Harding Sven J äckel Bj örn Jacobsen Jacqueline Kinyamu-Akunda Andr éanne Lortie Sofiene Mhedhbi Susanne Mohr Michael W Schmitt Helen Pr Source Type: research

Safety evaluation of food enzymes produced by a safe strain lineage of Bacillus subtilis
Regul Toxicol Pharmacol. 2021 Aug 26:105030. doi: 10.1016/j.yrtph.2021.105030. Online ahead of print.ABSTRACTThe safety of microbially-derived food enzymes must be carefully assessed before market introduction. The production strain's safety is central to the assessment. In this paper, we have determined that DSM's Bacillus subtilis strain lineage can be considered safe for food enzyme production. The mutations introduced into this non-pathogenic and non-toxigenic microorganism do not lead to any safety concerns, as ensured by a thorough characterization of the strain lineage. The safety of both targeted and randomly intro...
Source: Regulatory Toxicology and Pharmacology : RTP - August 29, 2021 Category: Toxicology Authors: Melina Galano Myrthe W van den Dungen Tjeerd van Rij Hanna E Abbas Source Type: research

Species selection for nonclinical safety assessment of drug candidates: Examples of current industry practice
Regul Toxicol Pharmacol. 2021 Aug 26:105029. doi: 10.1016/j.yrtph.2021.105029. Online ahead of print.ABSTRACTIn drug development, nonclinical safety assessment is pivotal for human risk assessment and support of clinical development. Selecting the relevant/appropriate animal species for toxicity testing increases the likelihood of detecting potential effects in humans, and although recent regulatory guidelines state the need to justify or dis-qualify animal species for toxicity testing, individual companies have developed decision-processes most appropriate for their molecules, experience and 3Rs policies. These generally ...
Source: Regulatory Toxicology and Pharmacology : RTP - August 29, 2021 Category: Toxicology Authors: Rostam Namdari Keith Jones Samuel S Chuang Steven Van Cruchten Zuhal Dincer Noel Downes Lars Friis Mikkelsen Joanna Harding Sven J äckel Bjoern Jacobsen Jacqueline Kinyamu-Akunda Andr éanne Lortie Sofiene Mhedhbi Susanne Mohr Michael W Schmitt Helen Pri Source Type: research

Perspectives on the elimination of animal assays in the assessment of carcinogenicity
Regul Toxicol Pharmacol. 2021 Aug 24;126:105031. doi: 10.1016/j.yrtph.2021.105031. Online ahead of print.NO ABSTRACTPMID:34437954 | DOI:10.1016/j.yrtph.2021.105031 (Source: Regulatory Toxicology and Pharmacology : RTP)
Source: Regulatory Toxicology and Pharmacology : RTP - August 26, 2021 Category: Toxicology Authors: Akiyoshi Nishikawa Source Type: research

Perspectives on the elimination of animal assays in the assessment of carcinogenicity
Regul Toxicol Pharmacol. 2021 Aug 23:105031. doi: 10.1016/j.yrtph.2021.105031. Online ahead of print.NO ABSTRACTPMID:34437954 | DOI:10.1016/j.yrtph.2021.105031 (Source: Regulatory Toxicology and Pharmacology : RTP)
Source: Regulatory Toxicology and Pharmacology : RTP - August 26, 2021 Category: Toxicology Authors: Akiyoshi Nishikawa Source Type: research

The safety of a Kluyveromyces lactis strain lineage for enzyme production
Regul Toxicol Pharmacol. 2021 Aug 21:105027. doi: 10.1016/j.yrtph.2021.105027. Online ahead of print.ABSTRACTKluyveromyces lactis is broadly considered as a safe yeast in food and a suitable organism for the production of food enzymes. The K. lactis enzyme production strains of DSM are used to produce a variety of enzymes, for example beta-galactosidase (lactase), chymosin and esterase. All of these production strains are derived from the same lineage, meaning they all originate from the same ancestor strain after classical mutagenesis and/or genetic engineering. Four different enzyme preparations produced with strains wit...
Source: Regulatory Toxicology and Pharmacology : RTP - August 24, 2021 Category: Toxicology Authors: Myrthe W van den Dungen R émon Boer Lonneke C Wilms Yulia Efimova Hanna E Abbas Source Type: research

The safety of a Kluyveromyces lactis strain lineage for enzyme production
Regul Toxicol Pharmacol. 2021 Aug 21:105027. doi: 10.1016/j.yrtph.2021.105027. Online ahead of print.ABSTRACTKluyveromyces lactis is broadly considered as a safe yeast in food and a suitable organism for the production of food enzymes. The K. lactis enzyme production strains of DSM are used to produce a variety of enzymes, for example beta-galactosidase (lactase), chymosin and esterase. All of these production strains are derived from the same lineage, meaning they all originate from the same ancestor strain after classical mutagenesis and/or genetic engineering. Four different enzyme preparations produced with strains wit...
Source: Regulatory Toxicology and Pharmacology : RTP - August 24, 2021 Category: Toxicology Authors: Myrthe W van den Dungen R émon Boer Lonneke C Wilms Yulia Efimova Hanna E Abbas Source Type: research

The Dilemma of Perfluorooctanoate (PFOA) Human Half-life
Regul Toxicol Pharmacol. 2021 Aug 13:105025. doi: 10.1016/j.yrtph.2021.105025. Online ahead of print.ABSTRACTDisparity in the results from human observational and clinical studies is not uncommon, but risk assessment efforts often judge one set of data more relevant with the loss of valuable information. The assessment for perfluorooctanoate (PFOA) is a good example of this problem. The estimation of its safe dose is disparate among government groups due in part to differences in understanding of its half-life in humans. These differences are due in part to incomplete information on sources of exposure in the human observa...
Source: Regulatory Toxicology and Pharmacology : RTP - August 17, 2021 Category: Toxicology Authors: Michael Dourson Bernard Gadagbui Source Type: research

The Dilemma of Perfluorooctanoate (PFOA) Human Half-life
Regul Toxicol Pharmacol. 2021 Aug 13:105025. doi: 10.1016/j.yrtph.2021.105025. Online ahead of print.ABSTRACTDisparity in the results from human observational and clinical studies is not uncommon, but risk assessment efforts often judge one set of data more relevant with the loss of valuable information. The assessment for perfluorooctanoate (PFOA) is a good example of this problem. The estimation of its safe dose is disparate among government groups due in part to differences in understanding of its half-life in humans. These differences are due in part to incomplete information on sources of exposure in the human observa...
Source: Regulatory Toxicology and Pharmacology : RTP - August 17, 2021 Category: Toxicology Authors: Michael Dourson Bernard Gadagbui Source Type: research

The Dilemma of Perfluorooctanoate (PFOA) Human Half-life
Regul Toxicol Pharmacol. 2021 Aug 13:105025. doi: 10.1016/j.yrtph.2021.105025. Online ahead of print.ABSTRACTDisparity in the results from human observational and clinical studies is not uncommon, but risk assessment efforts often judge one set of data more relevant with the loss of valuable information. The assessment for perfluorooctanoate (PFOA) is a good example of this problem. The estimation of its safe dose is disparate among government groups due in part to differences in understanding of its half-life in humans. These differences are due in part to incomplete information on sources of exposure in the human observa...
Source: Regulatory Toxicology and Pharmacology : RTP - August 17, 2021 Category: Toxicology Authors: Michael Dourson Bernard Gadagbui Source Type: research

The Dilemma of Perfluorooctanoate (PFOA) Human Half-life
Regul Toxicol Pharmacol. 2021 Aug 13:105025. doi: 10.1016/j.yrtph.2021.105025. Online ahead of print.ABSTRACTDisparity in the results from human observational and clinical studies is not uncommon, but risk assessment efforts often judge one set of data more relevant with the loss of valuable information. The assessment for perfluorooctanoate (PFOA) is a good example of this problem. The estimation of its safe dose is disparate among government groups due in part to differences in understanding of its half-life in humans. These differences are due in part to incomplete information on sources of exposure in the human observa...
Source: Regulatory Toxicology and Pharmacology : RTP - August 17, 2021 Category: Toxicology Authors: Michael Dourson Bernard Gadagbui Source Type: research

The Dilemma of Perfluorooctanoate (PFOA) Human Half-life
Regul Toxicol Pharmacol. 2021 Aug 13:105025. doi: 10.1016/j.yrtph.2021.105025. Online ahead of print.ABSTRACTDisparity in the results from human observational and clinical studies is not uncommon, but risk assessment efforts often judge one set of data more relevant with the loss of valuable information. The assessment for perfluorooctanoate (PFOA) is a good example of this problem. The estimation of its safe dose is disparate among government groups due in part to differences in understanding of its half-life in humans. These differences are due in part to incomplete information on sources of exposure in the human observa...
Source: Regulatory Toxicology and Pharmacology : RTP - August 17, 2021 Category: Toxicology Authors: Michael Dourson Bernard Gadagbui Source Type: research

The Dilemma of Perfluorooctanoate (PFOA) Human Half-life
Regul Toxicol Pharmacol. 2021 Aug 13:105025. doi: 10.1016/j.yrtph.2021.105025. Online ahead of print.ABSTRACTDisparity in the results from human observational and clinical studies is not uncommon, but risk assessment efforts often judge one set of data more relevant with the loss of valuable information. The assessment for perfluorooctanoate (PFOA) is a good example of this problem. The estimation of its safe dose is disparate among government groups due in part to differences in understanding of its half-life in humans. These differences are due in part to incomplete information on sources of exposure in the human observa...
Source: Regulatory Toxicology and Pharmacology : RTP - August 17, 2021 Category: Toxicology Authors: Michael Dourson Bernard Gadagbui Source Type: research

Paving the way for application of next generation risk assessment to safety decision-making for cosmetic ingredients
Regul Toxicol Pharmacol. 2021 Aug 10;125:105026. doi: 10.1016/j.yrtph.2021.105026. Online ahead of print.ABSTRACTNext generation risk assessment (NGRA) is an exposure-led, hypothesis-driven approach that has the potential to support animal-free safety decision-making. However, significant effort is needed to develop and test the in vitro and in silico (computational) approaches that underpin NGRA to enable confident application in a regulatory context. A workshop was held in Montreal in 2019 to discuss where effort needs to be focussed and to agree on the steps needed to ensure safety decisions made on cosmetic ingredients...
Source: Regulatory Toxicology and Pharmacology : RTP - August 14, 2021 Category: Toxicology Authors: M P Dent E Vaillancourt R S Thomas P L Carmichael G Ouedraogo H Kojima J Barroso J Ansell T S Barton-Maclaren S H Bennekou K Boekelheide J Ezendam J Field S Fitzpatrick M Hatao R Kreiling M Lorencini C Mahony B Montemayor R Mazaro-Costa J Oliveira V Rogie Source Type: research

Paving the Way for Application of Next Generation Risk Assessment to Safety Decision-Making for Cosmetic Ingredients
Regul Toxicol Pharmacol. 2021 Aug 10:105026. doi: 10.1016/j.yrtph.2021.105026. Online ahead of print.ABSTRACTNext generation risk assessment (NGRA) is an exposure-led, hypothesis-driven approach that has the potential to support animal-free safety decision-making. However, significant effort is needed to develop and test the in vitro and in silico (computational) approaches that underpin NGRA to enable confident application in a regulatory context. A workshop was held in Montreal in 2019 to discuss where effort needs to be focussed and to agree on the steps needed to ensure safety decisions made on cosmetic ingredients are...
Source: Regulatory Toxicology and Pharmacology : RTP - August 14, 2021 Category: Toxicology Authors: M P Dent E Vaillancourt R S Thomas P L Carmichael G Ouedraogo H Kojima J Barroso J Ansell T S Barton-Maclaren S H Bennekou K Boekelheide J Ezendam J Field S Fitzpatrick M Hatao R Kreiling M Lorencini C Mahony B Montemayor R Mazaro-Costa J Oliveira V Rogie Source Type: research

Paving the Way for Application of Next Generation Risk Assessment to Safety Decision-Making for Cosmetic Ingredients
Regul Toxicol Pharmacol. 2021 Aug 10:105026. doi: 10.1016/j.yrtph.2021.105026. Online ahead of print.ABSTRACTNext generation risk assessment (NGRA) is an exposure-led, hypothesis-driven approach that has the potential to support animal-free safety decision-making. However, significant effort is needed to develop and test the in vitro and in silico (computational) approaches that underpin NGRA to enable confident application in a regulatory context. A workshop was held in Montreal in 2019 to discuss where effort needs to be focussed and to agree on the steps needed to ensure safety decisions made on cosmetic ingredients are...
Source: Regulatory Toxicology and Pharmacology : RTP - August 14, 2021 Category: Toxicology Authors: M P Dent E Vaillancourt R S Thomas P L Carmichael G Ouedraogo H Kojima J Barroso J Ansell T S Barton-Maclaren S H Bennekou K Boekelheide J Ezendam J Field S Fitzpatrick M Hatao R Kreiling M Lorencini C Mahony B Montemayor R Mazaro-Costa J Oliveira V Rogie Source Type: research

Using historical control data in bioassays for regulatory toxicology
Regul Toxicol Pharmacol. 2021 Aug 5;125:105024. doi: 10.1016/j.yrtph.2021.105024. Online ahead of print.ABSTRACTHistorical control data (HCD) consist of pooled control group responses from bioassays. These data must be collected and are often used or reported in regulatory toxicology studies for multiple purposes: as quality assurance for the test system, to help identify toxicological effects and their effect-size relevance and to address the statistical multiple comparison problem. The current manuscript reviews the various classical and potential new approaches for using HCD. Issues in current practice are identified an...
Source: Regulatory Toxicology and Pharmacology : RTP - August 8, 2021 Category: Toxicology Authors: Felix M Kluxen Klaus Weber Christian Strupp Signe M Jensen Ludwig A Hothorn Jean-Christophe Garcin Thomas Hofmann Source Type: research

Using historical control data in bioassays for regulatory toxicology
Regul Toxicol Pharmacol. 2021 Aug 5;125:105024. doi: 10.1016/j.yrtph.2021.105024. Online ahead of print.ABSTRACTHistorical control data (HCD) consist of pooled control group responses from bioassays. These data must be collected and are often used or reported in regulatory toxicology studies for multiple purposes: as quality assurance for the test system, to help identify toxicological effects and their effect-size relevance and to address the statistical multiple comparison problem. The current manuscript reviews the various classical and potential new approaches for using HCD. Issues in current practice are identified an...
Source: Regulatory Toxicology and Pharmacology : RTP - August 8, 2021 Category: Toxicology Authors: Felix M Kluxen Klaus Weber Christian Strupp Signe M Jensen Ludwig A Hothorn Jean-Christophe Garcin Thomas Hofmann Source Type: research

Using historical control data in bioassays for regulatory toxicology
Regul Toxicol Pharmacol. 2021 Aug 5:105024. doi: 10.1016/j.yrtph.2021.105024. Online ahead of print.ABSTRACTHistorical control data (HCD) consist of pooled control group responses from bioassays. These data must be collected and are often used or reported in regulatory toxicology studies for multiple purposes: as quality assurance for the test system, to help identify toxicological effects and their effect-size relevance and to address the statistical multiple comparison problem. The current manuscript reviews the various classical and potential new approaches for using HCD. Issues in current practice are identified and re...
Source: Regulatory Toxicology and Pharmacology : RTP - August 8, 2021 Category: Toxicology Authors: Felix M Kluxen Klaus Weber Christian Strupp Signe M Jensen Ludwig A Hothorn Jean-Christophe Garcin Thomas Hofmann Source Type: research

Using historical control data in bioassays for regulatory toxicology
Regul Toxicol Pharmacol. 2021 Aug 5:105024. doi: 10.1016/j.yrtph.2021.105024. Online ahead of print.ABSTRACTHistorical control data (HCD) consist of pooled control group responses from bioassays. These data must be collected and are often used or reported in regulatory toxicology studies for multiple purposes: as quality assurance for the test system, to help identify toxicological effects and their effect-size relevance and to address the statistical multiple comparison problem. The current manuscript reviews the various classical and potential new approaches for using HCD. Issues in current practice are identified and re...
Source: Regulatory Toxicology and Pharmacology : RTP - August 8, 2021 Category: Toxicology Authors: Felix M Kluxen Klaus Weber Christian Strupp Signe M Jensen Ludwig A Hothorn Jean-Christophe Garcin Thomas Hofmann Source Type: research

Using historical control data in bioassays for regulatory toxicology
Regul Toxicol Pharmacol. 2021 Aug 5:105024. doi: 10.1016/j.yrtph.2021.105024. Online ahead of print.ABSTRACTHistorical control data (HCD) consist of pooled control group responses from bioassays. These data must be collected and are often used or reported in regulatory toxicology studies for multiple purposes: as quality assurance for the test system, to help identify toxicological effects and their effect-size relevance and to address the statistical multiple comparison problem. The current manuscript reviews the various classical and potential new approaches for using HCD. Issues in current practice are identified and re...
Source: Regulatory Toxicology and Pharmacology : RTP - August 8, 2021 Category: Toxicology Authors: Felix M Kluxen Klaus Weber Christian Strupp Signe M Jensen Ludwig A Hothorn Jean-Christophe Garcin Thomas Hofmann Source Type: research

Calculating Qualified Non-Mutagenic Impurity Levels: Harmonization of Approaches
Regul Toxicol Pharmacol. 2021 Aug 4:105023. doi: 10.1016/j.yrtph.2021.105023. Online ahead of print.ABSTRACTThe presence of impurities in drugs is unavoidable. As impurities offer no direct benefit to the patient, it is critical that impurities do not compromise patient safety. Current guidelines on the derivation of acceptable impurity levels leave aspects of calculations open for interpretation, resulting in inconsistencies across industry and regulators. To understand current impurity qualification practices from a safety standpoint, regulatory expectations and the safety risk that impurities pose, the IQ DruSafe Impuri...
Source: Regulatory Toxicology and Pharmacology : RTP - August 7, 2021 Category: Toxicology Authors: Jessica C Graham Mark W Powley Erika Udovic Susanne Glowienke John Nicolette Patricia Parris Michelle Kenyon Angela White Ailis Maisey James Harvey Elizabeth A Martin Eric Dowdy Melisa Masuda-Herrera Alejandra Trejo-Martin Joel Bercu Source Type: research

AOP and IATA applied to ocular surface toxicity
Regul Toxicol Pharmacol. 2021 Aug 1;125:105021. doi: 10.1016/j.yrtph.2021.105021. Online ahead of print.ABSTRACTUntil now, the Draize test on rabbits has been the only test performed to anticipate ocular toxicity of pharmaceutical compounds, mainly irritation. The OECD is urging the scientific community to develop and validate alternative methods to reduce the need for animal testing. Since the models and tests used cannot reflect the entire biologic response, it is necessary to combine them into integrated approaches to testing and assessment (IATA) to obtain robust data. IATAs, along with adverse outcome pathways (AOP) t...
Source: Regulatory Toxicology and Pharmacology : RTP - August 4, 2021 Category: Toxicology Authors: No émie Bonneau Christophe Baudouin Fran çoise Brignole-Baudouin Source Type: research

AOP and IATA applied to ocular surface toxicity
Regul Toxicol Pharmacol. 2021 Aug 1:105021. doi: 10.1016/j.yrtph.2021.105021. Online ahead of print.ABSTRACTUntil now, the Draize test on rabbits has been the only test performed to anticipate ocular toxicity of pharmaceutical compounds, mainly irritation. The OECD is urging the scientific community to develop and validate alternative methods to reduce the need for animal testing. Since the models and tests used cannot reflect the entire biologic response, it is necessary to combine them into integrated approaches to testing and assessment (IATA) to obtain robust data. IATAs, along with adverse outcome pathways (AOP) that ...
Source: Regulatory Toxicology and Pharmacology : RTP - August 4, 2021 Category: Toxicology Authors: No émie Bonneau Christophe Baudouin Fran çoise Brignole-Baudouin Source Type: research

AOP and IATA applied to ocular surface toxicity
Regul Toxicol Pharmacol. 2021 Aug 1:105021. doi: 10.1016/j.yrtph.2021.105021. Online ahead of print.ABSTRACTUntil now, the Draize test on rabbits has been the only test performed to anticipate ocular toxicity of pharmaceutical compounds, mainly irritation. The OECD is urging the scientific community to develop and validate alternative methods to reduce the need for animal testing. Since the models and tests used cannot reflect the entire biologic response, it is necessary to combine them into integrated approaches to testing and assessment (IATA) to obtain robust data. IATAs, along with adverse outcome pathways (AOP) that ...
Source: Regulatory Toxicology and Pharmacology : RTP - August 4, 2021 Category: Toxicology Authors: No émie Bonneau Christophe Baudouin Fran çoise Brignole-Baudouin Source Type: research

Progress Towards an OECD Reporting Framework for Transcriptomics and Metabolomics in Regulatory Toxicology
Regul Toxicol Pharmacol. 2021 Jul 29:105020. doi: 10.1016/j.yrtph.2021.105020. Online ahead of print.ABSTRACTOmics methodologies are widely used in toxicological research to understand modes and mechanisms of toxicity. Increasingly, these methodologies are being applied to questions of regulatory interest such as molecular point-of-departure derivation and chemical grouping/read-across. Despite its value, widespread regulatory acceptance of omics data has not yet occurred. Barriers to the routine application of omics data in regulatory decision making have been: 1) lack of transparency for data processing methods used to c...
Source: Regulatory Toxicology and Pharmacology : RTP - August 1, 2021 Category: Toxicology Authors: Joshua A Harrill Mark R Viant Carole L Yauk Magdalini Sachana Timothy W Gant Scott S Auerbach Richard D Beger Mounir Bouhifd Jason O'Brien Lyle Burgoon Florian Caiment Donatella Carpi Tao Chen Brian N Chorley John Colbourne Raffaella Corvi Laurent Debrauw Source Type: research