The Experts below are selected from a list of 225 Experts worldwide ranked by ideXlab platform
Antonietta Martelli - One of the best experts on this subject based on the ideXlab platform.
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Genotoxicity and Carcinogenicity Studies of Bronchodilators and AntiAsthma Drugs
Basic & Clinical Pharmacology & Toxicology, 2013Co-Authors: Giovanni Brambilla, Francesca Mattioli, Luigi Robbiano, Antonietta MartelliAbstract:This survey is a compendium of genotoxicity and Carcinogenicity information of bronchodilators and antiasthma drugs. Data from 46 marketed drugs were collected. Of these 46 drugs, 25 (54.3%) did not have retrievable genotoxicity or Carcinogenicity data. The remaining 21 (45.7%) had at least one genotoxicity or Carcinogenicity test result. Of these 21 drugs, 10 had at least one positive finding: three tested positive in at least one genotoxicity assay, eight in at least one Carcinogenicity assay, and one of them gave positive results in both genotoxicity assay and Carcinogenicity assay. Concerning the predictivity of genetic toxicology findings for the result(s) of long-term carcinogenesis assays, 15 drugs had both genotoxicity and Carcinogenicity data: seven of them (46.6%) were neither genotoxic nor carcinogenic, 6 (40.0%) were carcinogenic in at least one sex of mice or rats but tested negative in genotoxicity assays, 1 (6.7%) tested positive in genotoxicity assay but was non-carcinogenic, and 1 (6.7%) gave positive responses in both genotoxicity and Carcinogenicity assay. Only 11 (23.9%) of the 46 drugs considered had all data required by current guidelines for testing of pharmaceuticals, but a large fraction of them were developed and marketed prior to the present regulatory climate.
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Studies on genotoxicity and Carcinogenicity of antibacterial, antiviral, antimalarial and antifungal drugs
Mutagenesis, 2012Co-Authors: Giovanni Brambilla, Francesca Mattioli, Luigi Robbiano, Antonietta MartelliAbstract:: This review provides a compendium of retrievable results of genotoxicity and animal Carcinogenicity studies performed of antibacterial, antiviral, antimalarial and antifungal drugs of long-term or intermittent frequent use. Of the 48 drugs considered, 9 (18.75%) do not have retrievable data, whereas the other 39 (81.25%) have at least one genotoxicity or Carcinogenicity tests result. Of these 39 drugs, 24 tested positive in at least one genotoxicity assay and 19 in at least one Carcinogenicity assay; 14 of them gave a positive response in both at least one genotoxicity assay and at least one Carcinogenicity assay. Concerning the predictivity of genetic toxicology findings for the results of long-term carcinogenesis assays, of 23 drugs with both genotoxicity and Carcinogenicity data: 2 (8.7%) were neither genotoxic nor carcinogenic, 2 (8.7%) tested positive in at least one genotoxicity assay but were non-carcinogenic, 4 (17.4%) tested negative in genotoxicity assays but were carcinogenic, and 15 (65.2%) gave a positive response in at least one genotoxicity assay and in at least one Carcinogenicity assay. Only 18 (37.5%) of the 48 drugs examined had all data required by present guidelines for testing of pharmaceuticals, but a fraction of them (49%) were developed and marketed prior to the present regulatory climate. In the absence of compelling indications, the prescription of the 19 drugs that are animal carcinogens should be avoided.
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Genotoxicity and Carcinogenicity studies of antihistamines
Archives of Toxicology, 2011Co-Authors: Giovanni Brambilla, Francesca Mattioli, Luigi Robbiano, Antonietta MartelliAbstract:This review provides a compendium of the results of genotoxicity and Carcinogenicity assays performed on marketed antihistamines. Of the 70 drugs examined, 29 (41.4%) have at least one genotoxicity and/or Carcinogenicity test result: 12 tested positive in at least one genotoxicity assay, six in at least one Carcinogenicity assay, and four gave a positive response in both at least one genotoxicity assay and at least one Carcinogenicity assay. Of 19 drugs with both genotoxicity and Carcinogenicity data, eight were neither genotoxic nor carcinogenic, two were carcinogenic in at least one sex of mice or rats but tested negative in genotoxicity assays, five tested positive in at least one genotoxicity assay but were non-carcinogenic, and four gave a positive response in at least one genotoxicity assay and in at least one Carcinogenicity assay. Only 12 (17.1%) of the 70 drugs examined have all data required by present guidelines for testing of pharmaceuticals, but it should be considered that a large fraction of them were developed and marketed prior the present regulatory climate.
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Genotoxic and carcinogenic effects of gastrointestinal drugs
Mutagenesis, 2010Co-Authors: Giovanni Brambilla, Francesca Mattioli, Antonietta MartelliAbstract:: This review provides a compendium of retrievable results of genotoxicity and Carcinogenicity assays performed on marketed gastrointestinal drugs. Of the 71 drugs considered, 38 (53.5%) do not have retrievable data, whereas the other 33 (46.5%) have at least one genotoxicity or Carcinogenicity test result. Of these 33 drugs, 15 tested positive in at least one genotoxicity assay and 13 in at least one Carcinogenicity assay; 8 of them gave a positive response in both at least one genotoxicity assay and at least one Carcinogenicity assay. Concerning the predictivity of genetic toxicology findings for the result(s) of long-term carcinogenesis assays, of 21 drugs with both genotoxicity and Carcinogenicity data: 6 (28.6%) are neither genotoxic nor carcinogenic, 2 (9.5%) tested positive in at least one genotoxicity assay but were non-carcinogenic, 5 (23.8%) tested negative in genotoxicity assays but were carcinogenic and 8 (38.1%) gave a positive response in at least one genotoxicity assay and in at least one Carcinogenicity assay. Only 12 (16.9%) of the 71 drugs examined have all data required by present guidelines for testing of pharmaceuticals, but a large fraction of them were developed and marketed prior the present regulatory climate.
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Genotoxic and Carcinogenic Effects of Antipsychotics and Antidepressants
Toxicology, 2009Co-Authors: Giovanni Brambilla, Francesca Mattioli, Antonietta MartelliAbstract:This review provides a compendium of the results of genotoxicity and Carcinogenicity assays performed on marketed antipsychotics and antidepressants. Of the 104 drugs examined, 47 (45.2%) do not have retrievable data. The remaining 57 (54.8%) have at least one and often more than one genotoxicity and/or Carcinogenicity test result. Of these 57 drugs, 33 (57.9%) have at least one positive finding: 24 tested positive in at least one genotoxicity assay, 14 in at least one Carcinogenicity assay, and 5 gave a positive response in both. Concerning the predictivity of genetic toxicology findings for the result(s) of long-term carcinogenesis assays, 25 drugs have both genotoxicity and Carcinogenicity data: 8 of them (32.0%) were neither genotoxic nor carcinogenic, 8 (32.0%) were carcinogenic in at least one sex of mice or rats but tested negative in genotoxicity assays, 4 (16.0%) tested positive in at least one genotoxicity assay but were non-carcinogenic, and 5 (20.0%) gave a positive response in at least one genotoxicity assay and in at least one Carcinogenicity assay. Only 16 (15.4%) of the 104 drugs examined have all data required by present guidelines for testing of pharmaceuticals, but it should be considered that a large fraction of them were developed and marketed prior to the present regulatory climate.
Joseph F Contrera - One of the best experts on this subject based on the ideXlab platform.
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an analysis of genetic toxicity reproductive and developmental toxicity and Carcinogenicity data ii identification of genotoxicants reprotoxicants and carcinogens using in silico methods
Regulatory Toxicology and Pharmacology, 2006Co-Authors: Edwin J Matthews, Naomi L Kruhlak, Michael C Cimino, Daniel R Benz, Joseph F ContreraAbstract:This study examined a novel method to identify carcinogens that employed expanded data sets composed of in silico data pooled with actual experimental genetic toxicity (genetox) and reproductive and developmental toxicity (reprotox) data. We constructed 21 modules using the MC4PC program including 13 of 14 (11 genetox and 3 reprotox) tests that we found correlated with results of rodent Carcinogenicity bioassays (rcbioassays) [Matthews, E.J., Kruhlak, N.L., Cimino, M.C., Benz, R.D., Contrera, J.F., 2005b. An analysis of genetic toxicity, reproductive and developmental toxicity, and Carcinogenicity data: I. Identification of carcinogens using surrogate endpoints. Regul. Toxicol. Pharmacol.]. Each of the 21 modules was evaluated by cross-validation experiments and those with high specificity (SP) and positive predictivity (PPV) were used to predict activities of the 1442 chemicals tested for Carcinogenicity for which actual genetox or reprotox data were missing. The expanded data sets had ∼70% in silico data pooled with ∼30% experimental data. Based upon SP and PPV, the expanded data sets showed good correlation with Carcinogenicity testing results and had correlation indicator (CI, the average of SP and PPV) values of 75.5–88.7%. Conversely, expanded data sets for 9 non-correlated test endpoints were shown not to correlate with Carcinogenicity results (CI values <75%). Results also showed that when Salmonella mutagenic carcinogens were removed from the 12 correlated, expanded data sets, only 7 endpoints showed added value by detecting significantly more additional carcinogens than non-carcinogens.
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an analysis of genetic toxicity reproductive and developmental toxicity and Carcinogenicity data i identification of carcinogens using surrogate endpoints
Regulatory Toxicology and Pharmacology, 2006Co-Authors: Edwin J Matthews, Naomi L Kruhlak, Michael C Cimino, Daniel R Benz, Joseph F ContreraAbstract:A retrospective analysis of standard genetic toxicity (genetox) tests, reproductive and developmental toxicity (reprotox) studies, and rodent Carcinogenicity bioassays (rcbioassay) was performed to identify the genetox and reprotox endpoints whose results best correlate with rcbioassay observations. A database of 7205 chemicals with genetox (n = 4961), reprotox (n = 2173), and rcbioassay (n = 1442) toxicity data was constructed; 1112 of the chemicals have both genetox and rcbioassay data and 721 chemicals have both reprotox and rcbioassay data. This study differed from previous studies by using conservative weight of evidence criteria to classify chemical carcinogens, data from 63 genetox and reprotox toxicological endpoints, and a new statistical parameter of correlation indicator (CI, the average of specificity and positive predictivity) to identify good surrogate endpoints for predicting Carcinogenicity. Among 63 endpoints, results revealed that Carcinogenicity was well correlated with certain tests for gene mutation (n = 8), in vivo clastogenicity (n = 2), unscheduled DNA synthesis assay (n = 1), and reprotox (n = 3). The current FDA regulatory battery of four genetox tests used to predict Carcinogenicity includes two tests with good correlation (gene mutation in Salmonella and in vivo micronucleus) and two tests with poor correlation (mouse lymphoma gene mutation and in vitro chromosome aberrations) by our criteria.
Giovanni Brambilla - One of the best experts on this subject based on the ideXlab platform.
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Genotoxicity and Carcinogenicity Studies of Bronchodilators and AntiAsthma Drugs
Basic & Clinical Pharmacology & Toxicology, 2013Co-Authors: Giovanni Brambilla, Francesca Mattioli, Luigi Robbiano, Antonietta MartelliAbstract:This survey is a compendium of genotoxicity and Carcinogenicity information of bronchodilators and antiasthma drugs. Data from 46 marketed drugs were collected. Of these 46 drugs, 25 (54.3%) did not have retrievable genotoxicity or Carcinogenicity data. The remaining 21 (45.7%) had at least one genotoxicity or Carcinogenicity test result. Of these 21 drugs, 10 had at least one positive finding: three tested positive in at least one genotoxicity assay, eight in at least one Carcinogenicity assay, and one of them gave positive results in both genotoxicity assay and Carcinogenicity assay. Concerning the predictivity of genetic toxicology findings for the result(s) of long-term carcinogenesis assays, 15 drugs had both genotoxicity and Carcinogenicity data: seven of them (46.6%) were neither genotoxic nor carcinogenic, 6 (40.0%) were carcinogenic in at least one sex of mice or rats but tested negative in genotoxicity assays, 1 (6.7%) tested positive in genotoxicity assay but was non-carcinogenic, and 1 (6.7%) gave positive responses in both genotoxicity and Carcinogenicity assay. Only 11 (23.9%) of the 46 drugs considered had all data required by current guidelines for testing of pharmaceuticals, but a large fraction of them were developed and marketed prior to the present regulatory climate.
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Studies on genotoxicity and Carcinogenicity of antibacterial, antiviral, antimalarial and antifungal drugs
Mutagenesis, 2012Co-Authors: Giovanni Brambilla, Francesca Mattioli, Luigi Robbiano, Antonietta MartelliAbstract:: This review provides a compendium of retrievable results of genotoxicity and animal Carcinogenicity studies performed of antibacterial, antiviral, antimalarial and antifungal drugs of long-term or intermittent frequent use. Of the 48 drugs considered, 9 (18.75%) do not have retrievable data, whereas the other 39 (81.25%) have at least one genotoxicity or Carcinogenicity tests result. Of these 39 drugs, 24 tested positive in at least one genotoxicity assay and 19 in at least one Carcinogenicity assay; 14 of them gave a positive response in both at least one genotoxicity assay and at least one Carcinogenicity assay. Concerning the predictivity of genetic toxicology findings for the results of long-term carcinogenesis assays, of 23 drugs with both genotoxicity and Carcinogenicity data: 2 (8.7%) were neither genotoxic nor carcinogenic, 2 (8.7%) tested positive in at least one genotoxicity assay but were non-carcinogenic, 4 (17.4%) tested negative in genotoxicity assays but were carcinogenic, and 15 (65.2%) gave a positive response in at least one genotoxicity assay and in at least one Carcinogenicity assay. Only 18 (37.5%) of the 48 drugs examined had all data required by present guidelines for testing of pharmaceuticals, but a fraction of them (49%) were developed and marketed prior to the present regulatory climate. In the absence of compelling indications, the prescription of the 19 drugs that are animal carcinogens should be avoided.
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Genotoxicity and Carcinogenicity studies of antihistamines
Archives of Toxicology, 2011Co-Authors: Giovanni Brambilla, Francesca Mattioli, Luigi Robbiano, Antonietta MartelliAbstract:This review provides a compendium of the results of genotoxicity and Carcinogenicity assays performed on marketed antihistamines. Of the 70 drugs examined, 29 (41.4%) have at least one genotoxicity and/or Carcinogenicity test result: 12 tested positive in at least one genotoxicity assay, six in at least one Carcinogenicity assay, and four gave a positive response in both at least one genotoxicity assay and at least one Carcinogenicity assay. Of 19 drugs with both genotoxicity and Carcinogenicity data, eight were neither genotoxic nor carcinogenic, two were carcinogenic in at least one sex of mice or rats but tested negative in genotoxicity assays, five tested positive in at least one genotoxicity assay but were non-carcinogenic, and four gave a positive response in at least one genotoxicity assay and in at least one Carcinogenicity assay. Only 12 (17.1%) of the 70 drugs examined have all data required by present guidelines for testing of pharmaceuticals, but it should be considered that a large fraction of them were developed and marketed prior the present regulatory climate.
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Genotoxic and carcinogenic effects of gastrointestinal drugs
Mutagenesis, 2010Co-Authors: Giovanni Brambilla, Francesca Mattioli, Antonietta MartelliAbstract:: This review provides a compendium of retrievable results of genotoxicity and Carcinogenicity assays performed on marketed gastrointestinal drugs. Of the 71 drugs considered, 38 (53.5%) do not have retrievable data, whereas the other 33 (46.5%) have at least one genotoxicity or Carcinogenicity test result. Of these 33 drugs, 15 tested positive in at least one genotoxicity assay and 13 in at least one Carcinogenicity assay; 8 of them gave a positive response in both at least one genotoxicity assay and at least one Carcinogenicity assay. Concerning the predictivity of genetic toxicology findings for the result(s) of long-term carcinogenesis assays, of 21 drugs with both genotoxicity and Carcinogenicity data: 6 (28.6%) are neither genotoxic nor carcinogenic, 2 (9.5%) tested positive in at least one genotoxicity assay but were non-carcinogenic, 5 (23.8%) tested negative in genotoxicity assays but were carcinogenic and 8 (38.1%) gave a positive response in at least one genotoxicity assay and in at least one Carcinogenicity assay. Only 12 (16.9%) of the 71 drugs examined have all data required by present guidelines for testing of pharmaceuticals, but a large fraction of them were developed and marketed prior the present regulatory climate.
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Genotoxic and Carcinogenic Effects of Antipsychotics and Antidepressants
Toxicology, 2009Co-Authors: Giovanni Brambilla, Francesca Mattioli, Antonietta MartelliAbstract:This review provides a compendium of the results of genotoxicity and Carcinogenicity assays performed on marketed antipsychotics and antidepressants. Of the 104 drugs examined, 47 (45.2%) do not have retrievable data. The remaining 57 (54.8%) have at least one and often more than one genotoxicity and/or Carcinogenicity test result. Of these 57 drugs, 33 (57.9%) have at least one positive finding: 24 tested positive in at least one genotoxicity assay, 14 in at least one Carcinogenicity assay, and 5 gave a positive response in both. Concerning the predictivity of genetic toxicology findings for the result(s) of long-term carcinogenesis assays, 25 drugs have both genotoxicity and Carcinogenicity data: 8 of them (32.0%) were neither genotoxic nor carcinogenic, 8 (32.0%) were carcinogenic in at least one sex of mice or rats but tested negative in genotoxicity assays, 4 (16.0%) tested positive in at least one genotoxicity assay but were non-carcinogenic, and 5 (20.0%) gave a positive response in at least one genotoxicity assay and in at least one Carcinogenicity assay. Only 16 (15.4%) of the 104 drugs examined have all data required by present guidelines for testing of pharmaceuticals, but it should be considered that a large fraction of them were developed and marketed prior to the present regulatory climate.
Edwin J Matthews - One of the best experts on this subject based on the ideXlab platform.
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an analysis of genetic toxicity reproductive and developmental toxicity and Carcinogenicity data ii identification of genotoxicants reprotoxicants and carcinogens using in silico methods
Regulatory Toxicology and Pharmacology, 2006Co-Authors: Edwin J Matthews, Naomi L Kruhlak, Michael C Cimino, Daniel R Benz, Joseph F ContreraAbstract:This study examined a novel method to identify carcinogens that employed expanded data sets composed of in silico data pooled with actual experimental genetic toxicity (genetox) and reproductive and developmental toxicity (reprotox) data. We constructed 21 modules using the MC4PC program including 13 of 14 (11 genetox and 3 reprotox) tests that we found correlated with results of rodent Carcinogenicity bioassays (rcbioassays) [Matthews, E.J., Kruhlak, N.L., Cimino, M.C., Benz, R.D., Contrera, J.F., 2005b. An analysis of genetic toxicity, reproductive and developmental toxicity, and Carcinogenicity data: I. Identification of carcinogens using surrogate endpoints. Regul. Toxicol. Pharmacol.]. Each of the 21 modules was evaluated by cross-validation experiments and those with high specificity (SP) and positive predictivity (PPV) were used to predict activities of the 1442 chemicals tested for Carcinogenicity for which actual genetox or reprotox data were missing. The expanded data sets had ∼70% in silico data pooled with ∼30% experimental data. Based upon SP and PPV, the expanded data sets showed good correlation with Carcinogenicity testing results and had correlation indicator (CI, the average of SP and PPV) values of 75.5–88.7%. Conversely, expanded data sets for 9 non-correlated test endpoints were shown not to correlate with Carcinogenicity results (CI values <75%). Results also showed that when Salmonella mutagenic carcinogens were removed from the 12 correlated, expanded data sets, only 7 endpoints showed added value by detecting significantly more additional carcinogens than non-carcinogens.
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an analysis of genetic toxicity reproductive and developmental toxicity and Carcinogenicity data i identification of carcinogens using surrogate endpoints
Regulatory Toxicology and Pharmacology, 2006Co-Authors: Edwin J Matthews, Naomi L Kruhlak, Michael C Cimino, Daniel R Benz, Joseph F ContreraAbstract:A retrospective analysis of standard genetic toxicity (genetox) tests, reproductive and developmental toxicity (reprotox) studies, and rodent Carcinogenicity bioassays (rcbioassay) was performed to identify the genetox and reprotox endpoints whose results best correlate with rcbioassay observations. A database of 7205 chemicals with genetox (n = 4961), reprotox (n = 2173), and rcbioassay (n = 1442) toxicity data was constructed; 1112 of the chemicals have both genetox and rcbioassay data and 721 chemicals have both reprotox and rcbioassay data. This study differed from previous studies by using conservative weight of evidence criteria to classify chemical carcinogens, data from 63 genetox and reprotox toxicological endpoints, and a new statistical parameter of correlation indicator (CI, the average of specificity and positive predictivity) to identify good surrogate endpoints for predicting Carcinogenicity. Among 63 endpoints, results revealed that Carcinogenicity was well correlated with certain tests for gene mutation (n = 8), in vivo clastogenicity (n = 2), unscheduled DNA synthesis assay (n = 1), and reprotox (n = 3). The current FDA regulatory battery of four genetox tests used to predict Carcinogenicity includes two tests with good correlation (gene mutation in Salmonella and in vivo micronucleus) and two tests with poor correlation (mouse lymphoma gene mutation and in vitro chromosome aberrations) by our criteria.
Naomi L Kruhlak - One of the best experts on this subject based on the ideXlab platform.
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an analysis of genetic toxicity reproductive and developmental toxicity and Carcinogenicity data ii identification of genotoxicants reprotoxicants and carcinogens using in silico methods
Regulatory Toxicology and Pharmacology, 2006Co-Authors: Edwin J Matthews, Naomi L Kruhlak, Michael C Cimino, Daniel R Benz, Joseph F ContreraAbstract:This study examined a novel method to identify carcinogens that employed expanded data sets composed of in silico data pooled with actual experimental genetic toxicity (genetox) and reproductive and developmental toxicity (reprotox) data. We constructed 21 modules using the MC4PC program including 13 of 14 (11 genetox and 3 reprotox) tests that we found correlated with results of rodent Carcinogenicity bioassays (rcbioassays) [Matthews, E.J., Kruhlak, N.L., Cimino, M.C., Benz, R.D., Contrera, J.F., 2005b. An analysis of genetic toxicity, reproductive and developmental toxicity, and Carcinogenicity data: I. Identification of carcinogens using surrogate endpoints. Regul. Toxicol. Pharmacol.]. Each of the 21 modules was evaluated by cross-validation experiments and those with high specificity (SP) and positive predictivity (PPV) were used to predict activities of the 1442 chemicals tested for Carcinogenicity for which actual genetox or reprotox data were missing. The expanded data sets had ∼70% in silico data pooled with ∼30% experimental data. Based upon SP and PPV, the expanded data sets showed good correlation with Carcinogenicity testing results and had correlation indicator (CI, the average of SP and PPV) values of 75.5–88.7%. Conversely, expanded data sets for 9 non-correlated test endpoints were shown not to correlate with Carcinogenicity results (CI values <75%). Results also showed that when Salmonella mutagenic carcinogens were removed from the 12 correlated, expanded data sets, only 7 endpoints showed added value by detecting significantly more additional carcinogens than non-carcinogens.
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an analysis of genetic toxicity reproductive and developmental toxicity and Carcinogenicity data i identification of carcinogens using surrogate endpoints
Regulatory Toxicology and Pharmacology, 2006Co-Authors: Edwin J Matthews, Naomi L Kruhlak, Michael C Cimino, Daniel R Benz, Joseph F ContreraAbstract:A retrospective analysis of standard genetic toxicity (genetox) tests, reproductive and developmental toxicity (reprotox) studies, and rodent Carcinogenicity bioassays (rcbioassay) was performed to identify the genetox and reprotox endpoints whose results best correlate with rcbioassay observations. A database of 7205 chemicals with genetox (n = 4961), reprotox (n = 2173), and rcbioassay (n = 1442) toxicity data was constructed; 1112 of the chemicals have both genetox and rcbioassay data and 721 chemicals have both reprotox and rcbioassay data. This study differed from previous studies by using conservative weight of evidence criteria to classify chemical carcinogens, data from 63 genetox and reprotox toxicological endpoints, and a new statistical parameter of correlation indicator (CI, the average of specificity and positive predictivity) to identify good surrogate endpoints for predicting Carcinogenicity. Among 63 endpoints, results revealed that Carcinogenicity was well correlated with certain tests for gene mutation (n = 8), in vivo clastogenicity (n = 2), unscheduled DNA synthesis assay (n = 1), and reprotox (n = 3). The current FDA regulatory battery of four genetox tests used to predict Carcinogenicity includes two tests with good correlation (gene mutation in Salmonella and in vivo micronucleus) and two tests with poor correlation (mouse lymphoma gene mutation and in vitro chromosome aberrations) by our criteria.
