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Carcinogenicity testing for pharmaceuticals - an update
S34
Abstracts / Toxicology Letters 221S (2013) S31–S56
individual exposure to pesticides, to be used in studies on health effects. We will present here a synthesis of data obtained in vinegrowing (Bordeaux area, France) from 2001 to 2007. Sixty-seven operators, 46 re-entry workers and 48 harvesters were observed in relation with dithiocarbamate or folpet treatments. Detailed information on the tasks (general conditions, operator, farm and equipment characteristics) were considered and dermal contamination was measured (patches and hand-washing). During treatment tasks, the exposure was mainly determined by the number of phases, characteristics of the equipment, educational level of the operator, his status (farm -worker or -owner), and general characteristics of the vines. For re-entry and harvesting, the type of task was the parameter the most strongly associated with contamination. During re-entry, the highest contaminations were observed during raising of wires and cutting of branches. During the harvest, the contamination was maximal for grape-picking. The delay since the last treatment and the rate of pesticide per hectare played a role, together with meteorological factors, crop and farm characteristics, gloves and clothes. Algorithms were built to estimate daily external contamination according to these relevant parameters. With additional information of frequency and duration of use, they will enable to calculate exposure indices usable in studies on farmers’ health. http://dx.doi.org/10.1016/j.toxlet.2013.06.224 Workshop 3: Carcinogenicity testing for pharmaceuticals
W03-1 Carcinogenicity testing for pharmaceuticals - an update Paul Baldrick Nonclinical Regulatory Strategy, Covance Inc., Harrogate, UK Carcinogenicity testing is a requirement for pharmaceuticals to be used for >6 months clinical administration or for intermittent clinical use exceeding this duration. For many years, standard design rodent bioassays have been performed to assess tumourigenic potential but in recent times drug companies and regulatory agencies have been looking at the robustness and suitability of these designs as appropriate for tumour risk assessment. Furthermore, there is a greater understanding on how to interpret and extrapolate findings in carcinogenicity studies. An introduction into current testing practices will be given along with comment on areas such as survival, tumour findings and risk assessment as well as indication of potential/ongoing areas of change. http://dx.doi.org/10.1016/j.toxlet.2013.06.118
W03-2 Practical considerations when setting up and conducting a carcinogenicity study Guy Healing
they should be measured will be covered, with particular reference to palpation, clinical pathology and toxicokinetics.Finally the pathology considerations will be detailed and specific considerations for interpreting, peer reviewing and reporting the studies discussed. http://dx.doi.org/10.1016/j.toxlet.2013.06.119
W03-3 Transgenic versus conventional carcinogenicity testing David R Jones MHRA, London, UK Carcinogenicity testing is a requirement for most pharmaceuticals intended to be used for long term clinical administration. Standard design life-span rodent bioassays have been conducted to assess carcinogenic potential for many years. However, in recent times drug companies and regulatory agencies have been looking at alternative assays using transgenic animals in an attempt to increase the predictability for human cancer. The talk will discuss regulatory experiences with assays using transgenic animals and their usefulness. http://dx.doi.org/10.1016/j.toxlet.2013.06.120
W03-4 Case studies or how to deal with ‘difficult’ results Martin Bopst Non-Clinical Safety, F. Hoffmann –La Roche AG, Basel, Switzerland The discussion on the usefulness of carcinogenicity testing has been going on for a long time. Questions raised are on dose level selection, study designs, relevant models, inclusion of newer endpoints/measurements, and of course also on the interpretation of data. In particular, when it comes to the translation of rodent data to the human situation, the topic becomes very interesting and challenging. This talk will provide some recent examples and also include aspects and case studies of how to interpret “difficult” results. http://dx.doi.org/10.1016/j.toxlet.2013.06.121 Workshop 4: Advances in the application of the Threshold of Toxicological Concern (TTC) as a pragmatic risk assessment tool for cosmetics
W04-1 Chemical risk assessment in absence of adequate toxicological data Benoît Schilter
AstraZeneca, Macclesfield, UK Nestlé Research Center, Lausanne, Switzerland The key components of a rodent in vivo carcinogenicity study will be discussed, including the preparation, conduct and reporting. The required facilities, equipment, skills, training and background data required if setting up a study will be detailed, as well as the animal strains that are commonly used, their age, housing, numbers and why they are selected. Dose routes and the relative risks of cross-contamination, in-life parameters and how regularly
There is an increasing demand for methodologies to establish levels of safety concern for chemicals without toxicological testing. This has concernedfor examplesemergency situations requiring fast decision making, but also the setting of priorities for further investigations, as well as the design of safe chemicals.In this context, the Threshold of Toxicological Concern (TTC) has been the
Abstracts / Toxicology Letters 221S (2013) S31–S56
individual exposure to pesticides, to be used in studies on health effects. We will present here a synthesis of data obtained in vinegrowing (Bordeaux area, France) from 2001 to 2007. Sixty-seven operators, 46 re-entry workers and 48 harvesters were observed in relation with dithiocarbamate or folpet treatments. Detailed information on the tasks (general conditions, operator, farm and equipment characteristics) were considered and dermal contamination was measured (patches and hand-washing). During treatment tasks, the exposure was mainly determined by the number of phases, characteristics of the equipment, educational level of the operator, his status (farm -worker or -owner), and general characteristics of the vines. For re-entry and harvesting, the type of task was the parameter the most strongly associated with contamination. During re-entry, the highest contaminations were observed during raising of wires and cutting of branches. During the harvest, the contamination was maximal for grape-picking. The delay since the last treatment and the rate of pesticide per hectare played a role, together with meteorological factors, crop and farm characteristics, gloves and clothes. Algorithms were built to estimate daily external contamination according to these relevant parameters. With additional information of frequency and duration of use, they will enable to calculate exposure indices usable in studies on farmers’ health. http://dx.doi.org/10.1016/j.toxlet.2013.06.224 Workshop 3: Carcinogenicity testing for pharmaceuticals
W03-1 Carcinogenicity testing for pharmaceuticals - an update Paul Baldrick Nonclinical Regulatory Strategy, Covance Inc., Harrogate, UK Carcinogenicity testing is a requirement for pharmaceuticals to be used for >6 months clinical administration or for intermittent clinical use exceeding this duration. For many years, standard design rodent bioassays have been performed to assess tumourigenic potential but in recent times drug companies and regulatory agencies have been looking at the robustness and suitability of these designs as appropriate for tumour risk assessment. Furthermore, there is a greater understanding on how to interpret and extrapolate findings in carcinogenicity studies. An introduction into current testing practices will be given along with comment on areas such as survival, tumour findings and risk assessment as well as indication of potential/ongoing areas of change. http://dx.doi.org/10.1016/j.toxlet.2013.06.118
W03-2 Practical considerations when setting up and conducting a carcinogenicity study Guy Healing
they should be measured will be covered, with particular reference to palpation, clinical pathology and toxicokinetics.Finally the pathology considerations will be detailed and specific considerations for interpreting, peer reviewing and reporting the studies discussed. http://dx.doi.org/10.1016/j.toxlet.2013.06.119
W03-3 Transgenic versus conventional carcinogenicity testing David R Jones MHRA, London, UK Carcinogenicity testing is a requirement for most pharmaceuticals intended to be used for long term clinical administration. Standard design life-span rodent bioassays have been conducted to assess carcinogenic potential for many years. However, in recent times drug companies and regulatory agencies have been looking at alternative assays using transgenic animals in an attempt to increase the predictability for human cancer. The talk will discuss regulatory experiences with assays using transgenic animals and their usefulness. http://dx.doi.org/10.1016/j.toxlet.2013.06.120
W03-4 Case studies or how to deal with ‘difficult’ results Martin Bopst Non-Clinical Safety, F. Hoffmann –La Roche AG, Basel, Switzerland The discussion on the usefulness of carcinogenicity testing has been going on for a long time. Questions raised are on dose level selection, study designs, relevant models, inclusion of newer endpoints/measurements, and of course also on the interpretation of data. In particular, when it comes to the translation of rodent data to the human situation, the topic becomes very interesting and challenging. This talk will provide some recent examples and also include aspects and case studies of how to interpret “difficult” results. http://dx.doi.org/10.1016/j.toxlet.2013.06.121 Workshop 4: Advances in the application of the Threshold of Toxicological Concern (TTC) as a pragmatic risk assessment tool for cosmetics
W04-1 Chemical risk assessment in absence of adequate toxicological data Benoît Schilter
AstraZeneca, Macclesfield, UK Nestlé Research Center, Lausanne, Switzerland The key components of a rodent in vivo carcinogenicity study will be discussed, including the preparation, conduct and reporting. The required facilities, equipment, skills, training and background data required if setting up a study will be detailed, as well as the animal strains that are commonly used, their age, housing, numbers and why they are selected. Dose routes and the relative risks of cross-contamination, in-life parameters and how regularly
There is an increasing demand for methodologies to establish levels of safety concern for chemicals without toxicological testing. This has concernedfor examplesemergency situations requiring fast decision making, but also the setting of priorities for further investigations, as well as the design of safe chemicals.In this context, the Threshold of Toxicological Concern (TTC) has been the