This study investigated the influence of cadmium (Cd) on the pathogenesis of salt-induced hyperte... more This study investigated the influence of cadmium (Cd) on the pathogenesis of salt-induced hypertension in Dahl hypertension-sensitive (S) rats bred for susceptibility to the hypertensive effect of excess dietary salt (NaCl). Weanling female S rats were divided into two groups. The rats in the Cd group received 2 mg Cd/kg ip on week 3 (3 weeks of age) followed by 2nd and 3rd injections of 1 mg Cd/kg on weeks 6 and 23. The controls received the same volume of 0.9% aqueous NaCl ip. A high salt (4% NaCl) diet and tap water were available ad libitum. Cd enhanced the rate and the degree at which salt-induced hypertension developed (week 7), leading to an accelerated phase (week 24) associated with a mean systolic blood pressure of 245 mm Hg and drastically increased morbidity and mortality. Conversely, the hypertensive process in the controls averaging a blood pressure of 207 mm Hg was not heralded by other discernible toxic manifestations. Pathological lesions of periarteritis nodosa in ...
The US Environmental Protection Agency prepares Health Advisories (HA) for drinking water contami... more The US Environmental Protection Agency prepares Health Advisories (HA) for drinking water contaminants. The HA provide technical guidance to public health officials or other interested groups on many aspects concerning drinking water contamination. The HA contain information on the chemistry, health effects, analytical methods and treatment technologies for specific contaminants. In addition, the HA include a risk assessment section which provides concentrations of the contaminant in drinking water that are not anticipated to cause adverse, noncancer health effects for 1 or 10 days or for longer exposures. Because the HA include risk assessments for less than lifetime exposures, they are useful when accidental spills occur or when regulatory limits are temporarily exceeded. The guidance documents are updated when new information becomes available that would change the previous conclusions.
Abstract The Toxicology Forum convened an international state-of-the-science workshop Assessing C... more Abstract The Toxicology Forum convened an international state-of-the-science workshop Assessing Chemical Carcinogenicity: Hazard Identification, Classification, and Risk Assessment in December 2020. Challenges related to assessing chemical carcinogenicity were organized under the topics of (1) problem formulation; (2) modes-of-action; (3) dose-response assessment; and (4) the use of new approach methodologies (NAMs). Key topics included the mechanisms of genotoxic and non-genotoxic carcinogenicity and how these in conjunction with consideration of exposure conditions might inform dose-response assessments and an overall risk assessment; approaches to evaluate the human relevance of modes-of-action observed in rodent studies; and the characterization of uncertainties. While the scientific limitations of the traditional rodent chronic bioassay were widely acknowledged, knowledge gaps that need to be overcome to facilitate the further development and uptake of NAMs were also identified. Since one single NAM is unlikely to replace the bioassay, activities to combine NAMs into integrated approaches for testing and assessment, or preferably into defined approaches for testing and assessment that include data interpretation procedures, were identified as urgent research needs. In addition, adverse outcome pathway networks can provide a framework for organizing the available evidence/data for assessing chemical carcinogenicity. Since a formally accepted decision tree to guide use of the best and most current science to advance carcinogenicity risk assessment is currently unavailable, a Decision Matrix for carcinogenicity assessment could be useful. The workshop organizers developed and presented a decision matrix to be considered within a carcinogenicity hazard and risk assessment that is offered in tabular form.
Short-Term Bioassays in the Analysis of Complex Environmental Mixtures IV, 1985
Risk assessment of suspected carcinogens involves both a qualitative and quantitative evaluation.... more Risk assessment of suspected carcinogens involves both a qualitative and quantitative evaluation. The qualitative evaluation evaluates the relevant animal, epidemiologic, mutagenesis, and cell transformation studies as to the likelihood that the agent is a human carcinogen.
Human and Ecological Risk Assessment: An International Journal, 2010
... View full textDownload full text Full access. DOI: 10.1080/10807039.2010.526474 Octavia Coner... more ... View full textDownload full text Full access. DOI: 10.1080/10807039.2010.526474 Octavia Conerly a & Edward V. Ohanian a ... To face some new challenges, EPA's Office of Water (OW) has developed a specific strategy to address contaminants of emerging concern in support of ...
Aluminum is a ubiquitous substance with over 4,000 uses. Aluminum, as aluminum sulfate, is common... more Aluminum is a ubiquitous substance with over 4,000 uses. Aluminum, as aluminum sulfate, is commonly used in the United States as a coagulant in the treatment of drinking water. For many years aluminum was not considered to be toxic to humans. However, reports associating aluminum with several skeletal and neurological disorders in humans suggest that exposure to aluminum may pose a health hazard. In 1983 the US Environmental Protection Agency (EPA) announced plans to regulate a number of substances, including aluminum, in drinking water. Aluminum was considered because of its occurrence and apparent toxicity. Upon further evaluation of the health effects data the EPA proposed not to regulate aluminum as a result of the uncertainty of the toxicity of ingested aluminum. Putative causal associations between aluminum exposure and neurological disorders such as Alzheimer's disease have yet to be substantiated. Although several issues regarding the toxicity of ingested aluminum are unresolved, aluminum has been specified in the 1986 Amendments to the Safe Drinking Water Act, as one of 83 substances in drinking water to be regulated by 1989. Additional data are needed before the potential risk of aluminum can be assessed; therefore the EPA has deferred possible regulation until 1991.
This study was undertaken to explore the effects of chronic low-level cadmium ingestion in Dahl h... more This study was undertaken to explore the effects of chronic low-level cadmium ingestion in Dahl hypertension-resistant (R) and hypertension-sensitive (S) lines of rats. Groups of weanling female R and S rats were given 0 or 1 mg cadmium/I. in drinking water and fed either a low salt (0.4 % NaCI) or a high salt (4%'o NaCi) diet for 28 weeks.
The Safe Drinking Water Act Amendments of 1986 required that the U.S. Environmental Protection Ag... more The Safe Drinking Water Act Amendments of 1986 required that the U.S. Environmental Protection Agency (EPA) establish standards for 83 contaminants by June 1989, and at least 25 added standards by January 1991, then 25 more every three years hence. Conceptually, the regulatory process employed by EPA consists of two steps. First, a detailed health risk assessment of a contaminant is performed in order to determine the Maximum Contaminant Level Goal (nonenforceable health goal) in water that should result in no known or anticipated health effects and allows adequate margin of safety. Second, the results of risk assessment and management (taking best available technology, treatment techniques, cost, and other means into consideration) are combined to derive the Maximum Contaminant Level (enforceable standard) which is set as close to the MCLG as feasible. With this overall regulatory process in mind, a detailed risk assessment process (hazard identification, dose-response assessment, ...
Boron, which is ubiquitous in the environment, causes developmental and reproductive effects in e... more Boron, which is ubiquitous in the environment, causes developmental and reproductive effects in experimental animals. This observation has led to efforts to establish a Tolerable Intake value for boron. Although risk assessors agree on the use of fetal weight decreases observed in rats as an appropriate critical effect, consensus on the adequacy of toxicokinetic data as a basis for replacement of default uncertainty factors remains to be reached. A critical analysis of the existing data on boron toxicokinetics was conducted to clarify the appropriateness of replacing default uncertainty factors (lO-fold for interspecies differences and 10-fold for intraspecies differences) with data-derived values. The default uncertainty factor for variability in response from animals to humans of lo-fold (default values of 4-fold for kinetics and 2.5-fold for dynamics) was recommended, since clearance of boron is 3- to 4-fold higher in rats than in humans and data on dynamic differences-in order t...
In conducting risk assessments on drinking water contaminants, the U.S. Environmental Protection ... more In conducting risk assessments on drinking water contaminants, the U.S. Environmental Protection Agency (EPA) attempts to evaluate all available toxicity data to develop Health Advisory (HA) and Maximum Contaminant Level Goal (MCLG) values. The EPA often has grappled with the issues surrounding the toxicity of chemical mixtures, including radioactive contaminants, nitrate/nitrite, and trihalomethanes (THMs). In evaluating the toxicity of chemical mixtures, the EPA's immediate concern is whether the individual HA values and MCLGs are protecting public health when multiple contaminants are present in drinking water. Potential toxic interactions between drinking water contaminants are difficult to predict because experimental studies are generally performed only at high doses relative to environmental levels. Although the contamination of drinking water involves mixtures of contaminants, drinking water regulations are generally based on an assessment of the risks of individual cont...
Journal of the American College of Toxicology, 1992
The Safe Drinking Water Act Amendments of 1986 required that the U.S. Environmental Protection Ag... more The Safe Drinking Water Act Amendments of 1986 required that the U.S. Environmental Protection Agency (EPA) establish standards for 83 contaminants by June 1989, and at least 25 added standards by January 1991, then 25 more every three years hence. Conceptually, the regulatory process employed by EPA consists of two steps. First, a detailed health risk assessment of a contaminant is performed in order to determine the Maximum Contaminant Level Goal (nonenforceable health goal) in water that should result in no known or anticipated health effects and allows adequate margin of safety. Second, the results of risk assessment and management (taking best available technology, treatment techniques, cost, and other means into consideration) are combined to derive the Maximum Contaminant Level (enforceable standard) which is set as close to the MCLG as feasible. With this overall regulatory process in mind, a detailed risk assessment process (hazard identification, dose-response assessment, ...
Human and Ecological Risk Assessment: An International Journal, 1997
Abstract The Safe Drinking Water Act Amendments of 1996 will bring substantial changes to the nat... more Abstract The Safe Drinking Water Act Amendments of 1996 will bring substantial changes to the national drinking water utilities, States, and the U.S. Environmental Protection Agency (USEPA), as well as greater protection and information to the 240 million Americans served by public water systems. These changes comprise a balanced, integrated framework of reform, and represent a major national commitment to new and stronger approaches to prevent contamination; better information for consumers; and regulatory improvements, including better science, prioritization of effort, risk assessment, management and communication. Specifically, the Amendments require the use of the best available, peer‐reviewed science and supporting studies conducted in accordance with sound and objective scientific practices. The 1995 USEPA Risk Characterization Policy satisfies some of these requirements since it must feature values such as transparency in decision making process; clarity in communicating with each other and the pu...
... Prix indicatif 141,18 Ajouter au panier le livre de LIPSCOMB John C., OHANIAN Guy W. Date d... more ... Prix indicatif 141,18 Ajouter au panier le livre de LIPSCOMB John C., OHANIAN Guy W. Date de parution : 10-2006 Langue : ANGLAIS 362p. 15x23 Hardback Disponible chez l'éditeur (délai d'approvisionnement : 14 jours). Résumé de Toxicokinetics & risk assessment : ...
This study investigated the influence of cadmium (Cd) on the pathogenesis of salt-induced hyperte... more This study investigated the influence of cadmium (Cd) on the pathogenesis of salt-induced hypertension in Dahl hypertension-sensitive (S) rats bred for susceptibility to the hypertensive effect of excess dietary salt (NaCl). Weanling female S rats were divided into two groups. The rats in the Cd group received 2 mg Cd/kg ip on week 3 (3 weeks of age) followed by 2nd and 3rd injections of 1 mg Cd/kg on weeks 6 and 23. The controls received the same volume of 0.9% aqueous NaCl ip. A high salt (4% NaCl) diet and tap water were available ad libitum. Cd enhanced the rate and the degree at which salt-induced hypertension developed (week 7), leading to an accelerated phase (week 24) associated with a mean systolic blood pressure of 245 mm Hg and drastically increased morbidity and mortality. Conversely, the hypertensive process in the controls averaging a blood pressure of 207 mm Hg was not heralded by other discernible toxic manifestations. Pathological lesions of periarteritis nodosa in ...
The US Environmental Protection Agency prepares Health Advisories (HA) for drinking water contami... more The US Environmental Protection Agency prepares Health Advisories (HA) for drinking water contaminants. The HA provide technical guidance to public health officials or other interested groups on many aspects concerning drinking water contamination. The HA contain information on the chemistry, health effects, analytical methods and treatment technologies for specific contaminants. In addition, the HA include a risk assessment section which provides concentrations of the contaminant in drinking water that are not anticipated to cause adverse, noncancer health effects for 1 or 10 days or for longer exposures. Because the HA include risk assessments for less than lifetime exposures, they are useful when accidental spills occur or when regulatory limits are temporarily exceeded. The guidance documents are updated when new information becomes available that would change the previous conclusions.
Abstract The Toxicology Forum convened an international state-of-the-science workshop Assessing C... more Abstract The Toxicology Forum convened an international state-of-the-science workshop Assessing Chemical Carcinogenicity: Hazard Identification, Classification, and Risk Assessment in December 2020. Challenges related to assessing chemical carcinogenicity were organized under the topics of (1) problem formulation; (2) modes-of-action; (3) dose-response assessment; and (4) the use of new approach methodologies (NAMs). Key topics included the mechanisms of genotoxic and non-genotoxic carcinogenicity and how these in conjunction with consideration of exposure conditions might inform dose-response assessments and an overall risk assessment; approaches to evaluate the human relevance of modes-of-action observed in rodent studies; and the characterization of uncertainties. While the scientific limitations of the traditional rodent chronic bioassay were widely acknowledged, knowledge gaps that need to be overcome to facilitate the further development and uptake of NAMs were also identified. Since one single NAM is unlikely to replace the bioassay, activities to combine NAMs into integrated approaches for testing and assessment, or preferably into defined approaches for testing and assessment that include data interpretation procedures, were identified as urgent research needs. In addition, adverse outcome pathway networks can provide a framework for organizing the available evidence/data for assessing chemical carcinogenicity. Since a formally accepted decision tree to guide use of the best and most current science to advance carcinogenicity risk assessment is currently unavailable, a Decision Matrix for carcinogenicity assessment could be useful. The workshop organizers developed and presented a decision matrix to be considered within a carcinogenicity hazard and risk assessment that is offered in tabular form.
Short-Term Bioassays in the Analysis of Complex Environmental Mixtures IV, 1985
Risk assessment of suspected carcinogens involves both a qualitative and quantitative evaluation.... more Risk assessment of suspected carcinogens involves both a qualitative and quantitative evaluation. The qualitative evaluation evaluates the relevant animal, epidemiologic, mutagenesis, and cell transformation studies as to the likelihood that the agent is a human carcinogen.
Human and Ecological Risk Assessment: An International Journal, 2010
... View full textDownload full text Full access. DOI: 10.1080/10807039.2010.526474 Octavia Coner... more ... View full textDownload full text Full access. DOI: 10.1080/10807039.2010.526474 Octavia Conerly a & Edward V. Ohanian a ... To face some new challenges, EPA's Office of Water (OW) has developed a specific strategy to address contaminants of emerging concern in support of ...
Aluminum is a ubiquitous substance with over 4,000 uses. Aluminum, as aluminum sulfate, is common... more Aluminum is a ubiquitous substance with over 4,000 uses. Aluminum, as aluminum sulfate, is commonly used in the United States as a coagulant in the treatment of drinking water. For many years aluminum was not considered to be toxic to humans. However, reports associating aluminum with several skeletal and neurological disorders in humans suggest that exposure to aluminum may pose a health hazard. In 1983 the US Environmental Protection Agency (EPA) announced plans to regulate a number of substances, including aluminum, in drinking water. Aluminum was considered because of its occurrence and apparent toxicity. Upon further evaluation of the health effects data the EPA proposed not to regulate aluminum as a result of the uncertainty of the toxicity of ingested aluminum. Putative causal associations between aluminum exposure and neurological disorders such as Alzheimer's disease have yet to be substantiated. Although several issues regarding the toxicity of ingested aluminum are unresolved, aluminum has been specified in the 1986 Amendments to the Safe Drinking Water Act, as one of 83 substances in drinking water to be regulated by 1989. Additional data are needed before the potential risk of aluminum can be assessed; therefore the EPA has deferred possible regulation until 1991.
This study was undertaken to explore the effects of chronic low-level cadmium ingestion in Dahl h... more This study was undertaken to explore the effects of chronic low-level cadmium ingestion in Dahl hypertension-resistant (R) and hypertension-sensitive (S) lines of rats. Groups of weanling female R and S rats were given 0 or 1 mg cadmium/I. in drinking water and fed either a low salt (0.4 % NaCI) or a high salt (4%'o NaCi) diet for 28 weeks.
The Safe Drinking Water Act Amendments of 1986 required that the U.S. Environmental Protection Ag... more The Safe Drinking Water Act Amendments of 1986 required that the U.S. Environmental Protection Agency (EPA) establish standards for 83 contaminants by June 1989, and at least 25 added standards by January 1991, then 25 more every three years hence. Conceptually, the regulatory process employed by EPA consists of two steps. First, a detailed health risk assessment of a contaminant is performed in order to determine the Maximum Contaminant Level Goal (nonenforceable health goal) in water that should result in no known or anticipated health effects and allows adequate margin of safety. Second, the results of risk assessment and management (taking best available technology, treatment techniques, cost, and other means into consideration) are combined to derive the Maximum Contaminant Level (enforceable standard) which is set as close to the MCLG as feasible. With this overall regulatory process in mind, a detailed risk assessment process (hazard identification, dose-response assessment, ...
Boron, which is ubiquitous in the environment, causes developmental and reproductive effects in e... more Boron, which is ubiquitous in the environment, causes developmental and reproductive effects in experimental animals. This observation has led to efforts to establish a Tolerable Intake value for boron. Although risk assessors agree on the use of fetal weight decreases observed in rats as an appropriate critical effect, consensus on the adequacy of toxicokinetic data as a basis for replacement of default uncertainty factors remains to be reached. A critical analysis of the existing data on boron toxicokinetics was conducted to clarify the appropriateness of replacing default uncertainty factors (lO-fold for interspecies differences and 10-fold for intraspecies differences) with data-derived values. The default uncertainty factor for variability in response from animals to humans of lo-fold (default values of 4-fold for kinetics and 2.5-fold for dynamics) was recommended, since clearance of boron is 3- to 4-fold higher in rats than in humans and data on dynamic differences-in order t...
In conducting risk assessments on drinking water contaminants, the U.S. Environmental Protection ... more In conducting risk assessments on drinking water contaminants, the U.S. Environmental Protection Agency (EPA) attempts to evaluate all available toxicity data to develop Health Advisory (HA) and Maximum Contaminant Level Goal (MCLG) values. The EPA often has grappled with the issues surrounding the toxicity of chemical mixtures, including radioactive contaminants, nitrate/nitrite, and trihalomethanes (THMs). In evaluating the toxicity of chemical mixtures, the EPA's immediate concern is whether the individual HA values and MCLGs are protecting public health when multiple contaminants are present in drinking water. Potential toxic interactions between drinking water contaminants are difficult to predict because experimental studies are generally performed only at high doses relative to environmental levels. Although the contamination of drinking water involves mixtures of contaminants, drinking water regulations are generally based on an assessment of the risks of individual cont...
Journal of the American College of Toxicology, 1992
The Safe Drinking Water Act Amendments of 1986 required that the U.S. Environmental Protection Ag... more The Safe Drinking Water Act Amendments of 1986 required that the U.S. Environmental Protection Agency (EPA) establish standards for 83 contaminants by June 1989, and at least 25 added standards by January 1991, then 25 more every three years hence. Conceptually, the regulatory process employed by EPA consists of two steps. First, a detailed health risk assessment of a contaminant is performed in order to determine the Maximum Contaminant Level Goal (nonenforceable health goal) in water that should result in no known or anticipated health effects and allows adequate margin of safety. Second, the results of risk assessment and management (taking best available technology, treatment techniques, cost, and other means into consideration) are combined to derive the Maximum Contaminant Level (enforceable standard) which is set as close to the MCLG as feasible. With this overall regulatory process in mind, a detailed risk assessment process (hazard identification, dose-response assessment, ...
Human and Ecological Risk Assessment: An International Journal, 1997
Abstract The Safe Drinking Water Act Amendments of 1996 will bring substantial changes to the nat... more Abstract The Safe Drinking Water Act Amendments of 1996 will bring substantial changes to the national drinking water utilities, States, and the U.S. Environmental Protection Agency (USEPA), as well as greater protection and information to the 240 million Americans served by public water systems. These changes comprise a balanced, integrated framework of reform, and represent a major national commitment to new and stronger approaches to prevent contamination; better information for consumers; and regulatory improvements, including better science, prioritization of effort, risk assessment, management and communication. Specifically, the Amendments require the use of the best available, peer‐reviewed science and supporting studies conducted in accordance with sound and objective scientific practices. The 1995 USEPA Risk Characterization Policy satisfies some of these requirements since it must feature values such as transparency in decision making process; clarity in communicating with each other and the pu...
... Prix indicatif 141,18 Ajouter au panier le livre de LIPSCOMB John C., OHANIAN Guy W. Date d... more ... Prix indicatif 141,18 Ajouter au panier le livre de LIPSCOMB John C., OHANIAN Guy W. Date de parution : 10-2006 Langue : ANGLAIS 362p. 15x23 Hardback Disponible chez l'éditeur (délai d'approvisionnement : 14 jours). Résumé de Toxicokinetics & risk assessment : ...
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