Pub Date : 2009-12-15DOI: 10.1002/9780470744307.GAT096
T. Flaten, E. Steinnes
In nature, soil and water systems are intimately inter-related through a complex web of interactions. In this chapter, the nature and properties of soils are reviewed with emphasis on chemical composition and the binding, cycling and transformation of chemical substances in soil. The main focus is on metals, but organic compounds are also discussed. Water is discussed mainly as an exposure route from soil to humans. Various aspects of pollution of soil and water systems are discussed, including industry and mining, long-range atmospheric transport, pesticides and fertilizers and waste disposal sites. The possible health effects of soil and water acidification are treated, with emphasis on cadmium, lead, mercury and aluminium. Finally, some health aspects of drinking water are discussed, with emphasis on instances where toxic substances at least partly have their origin in soils, and where drinking water constitutes an important exposure pathway from soils to humans. This includes arsenic, with a focus on West Bengal, fluoride, water hardness, nitrate and chlorination by-products. Keywords: soil; drinking water; acidification; cadmium; lead; mercury; aluminium; arsenic; chlorination by-products
{"title":"Soil and Fresh Water","authors":"T. Flaten, E. Steinnes","doi":"10.1002/9780470744307.GAT096","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT096","url":null,"abstract":"In nature, soil and water systems are intimately inter-related through a complex web of interactions. In this chapter, the nature and properties of soils are reviewed with emphasis on chemical composition and the binding, cycling and transformation of chemical substances in soil. The main focus is on metals, but organic compounds are also discussed. Water is discussed mainly as an exposure route from soil to humans. Various aspects of pollution of soil and water systems are discussed, including industry and mining, long-range atmospheric transport, pesticides and fertilizers and waste disposal sites. The possible health effects of soil and water acidification are treated, with emphasis on cadmium, lead, mercury and aluminium. Finally, some health aspects of drinking water are discussed, with emphasis on instances where toxic substances at least partly have their origin in soils, and where drinking water constitutes an important exposure pathway from soils to humans. This includes arsenic, with a focus on West Bengal, fluoride, water hardness, nitrate and chlorination by-products. \u0000 \u0000 \u0000Keywords: \u0000 \u0000soil; \u0000drinking water; \u0000acidification; \u0000cadmium; \u0000lead; \u0000mercury; \u0000aluminium; \u0000arsenic; \u0000chlorination by-products","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124169936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-12-15DOI: 10.1002/9780470744307.GAT059
B. Weiss
Behaviour is now established as a fundamental dimension of toxicity and risk assessment. It emerged as a criterion of adverse effects because many questions about health risks centred on measures such as IQ and other neuropsychological indices. Methylmercury and lead risks are quantified in such terms and clinical entities such as autism and attention deficit hyperactivity disorder are basically behavioural disorders. Behavioural methods, as a consequence, are essential research tools for determining the risks of exposure to environmental chemicals, for studying the mechanisms by which drugs act on nervous system diseases and for determining the potential of new pharmaceuticals to alter behaviour, either therapeutically or adversely. To fulfil these roles effectively, behavioural research must examine a variety of end points. These range from naturalistic behaviours, such as those involved in reproduction, to activity patterns, to motor and sensory function and to complex cognitive processes. At the same time, behavioural methods must encompass techniques applicable to both laboratory animals and humans. Keywords: psychological tests; schedule-controlled operant behaviour; cognitive function; locomotor activity; functional observation battery; naturalistic behaviours; motor function; sensory function
{"title":"The Role of Behavioural Toxicity in Risk Assessment","authors":"B. Weiss","doi":"10.1002/9780470744307.GAT059","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT059","url":null,"abstract":"Behaviour is now established as a fundamental dimension of toxicity and risk assessment. It emerged as a criterion of adverse effects because many questions about health risks centred on measures such as IQ and other neuropsychological indices. Methylmercury and lead risks are quantified in such terms and clinical entities such as autism and attention deficit hyperactivity disorder are basically behavioural disorders. Behavioural methods, as a consequence, are essential research tools for determining the risks of exposure to environmental chemicals, for studying the mechanisms by which drugs act on nervous system diseases and for determining the potential of new pharmaceuticals to alter behaviour, either therapeutically or adversely. To fulfil these roles effectively, behavioural research must examine a variety of end points. These range from naturalistic behaviours, such as those involved in reproduction, to activity patterns, to motor and sensory function and to complex cognitive processes. At the same time, behavioural methods must encompass techniques applicable to both laboratory animals and humans. \u0000 \u0000 \u0000Keywords: \u0000 \u0000psychological tests; \u0000schedule-controlled operant behaviour; \u0000cognitive function; \u0000locomotor activity; \u0000functional observation battery; \u0000naturalistic behaviours; \u0000motor function; \u0000sensory function","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116766113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-12-15DOI: 10.1002/9780470744307.GAT040
S. Gosselin, L. Ramaiah, L. Earl
Noncellular blood compartment (plasma or serum) and urine biochemical components are important indicators of overall animal health and can be used in conjunction with other parameters to investigate the toxicity of drugs and chemicals. This chapter describes the measurement and interpretation of clinical chemistry tests employed in toxicology studies in commonly used laboratory species. The introductory sections delineate methods for sample collection and data generation, and provide a general approach for data interpretation and reporting, with emphasis on distinguishing pre-analytical/analytical variations from test material-related changes. The following sections are organized by organ system, describing core clinical chemistry tests used in routine toxicology studies. These include protein, lipid and carbohydrate metabolisms, liver and kidney functions and electrolyte balance. Nonroutine tests evaluating cardiac and skeletal muscle, bone, blood vessels, the endocrine system, the nervous system are also presented. Because few clinical chemistry parameters are specific indicators of single organ toxicity, each section emphasizes the integrated interpretation of biochemistry changes with other study endpoints such as clinical signs, food consumption and bodyweight, haematology, electrocardiography, blood pressure and histopathology. Patterns of change are presented in the context of identifying organ toxicity. Keywords: clinical chemistry; serum; plasma; urine; kidney; liver; cardiac muscle; skeletal muscle; bone; blood vessel; adrenal; gonads; ovary; thyroid; GI tract; pancreas; nervous system
{"title":"Clinical Chemistry in Toxicity Testing: Scope and Methods","authors":"S. Gosselin, L. Ramaiah, L. Earl","doi":"10.1002/9780470744307.GAT040","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT040","url":null,"abstract":"Noncellular blood compartment (plasma or serum) and urine biochemical components are important indicators of overall animal health and can be used in conjunction with other parameters to investigate the toxicity of drugs and chemicals. This chapter describes the measurement and interpretation of clinical chemistry tests employed in toxicology studies in commonly used laboratory species. The introductory sections delineate methods for sample collection and data generation, and provide a general approach for data interpretation and reporting, with emphasis on distinguishing pre-analytical/analytical variations from test material-related changes. The following sections are organized by organ system, describing core clinical chemistry tests used in routine toxicology studies. These include protein, lipid and carbohydrate metabolisms, liver and kidney functions and electrolyte balance. Nonroutine tests evaluating cardiac and skeletal muscle, bone, blood vessels, the endocrine system, the nervous system are also presented. Because few clinical chemistry parameters are specific indicators of single organ toxicity, each section emphasizes the integrated interpretation of biochemistry changes with other study endpoints such as clinical signs, food consumption and bodyweight, haematology, electrocardiography, blood pressure and histopathology. Patterns of change are presented in the context of identifying organ toxicity. \u0000 \u0000 \u0000Keywords: \u0000 \u0000clinical chemistry; \u0000serum; \u0000plasma; \u0000urine; \u0000kidney; \u0000liver; \u0000cardiac muscle; \u0000skeletal muscle; \u0000bone; \u0000blood vessel; \u0000adrenal; \u0000gonads; \u0000ovary; \u0000thyroid; \u0000GI tract; \u0000pancreas; \u0000nervous system","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116001524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-12-15DOI: 10.1002/9780470744307.GAT123
E. Calabrese, Jd Paolo F. Ricci
The hormetic dose-response model has experienced a strong resurgence of interest in toxicology, risk assessment and pharmacology. This is based on its capacity for validation, reproducibility, generalizability, and its demonstrated ability to predict low-dose responses far more accurately than threshold and linear-at-low-dose models. This paper assesses capacity of hormesis models to impact the current risk assessment process, as well as the implications for risk assessment if regulatory agencies were to accept the hormetic dose-response as the default model. Keywords: hormesis; biphasic; dose-response; adaptive response; risk assessment; U-shaped; J-shaped
{"title":"Hormesis and Risk Assessment","authors":"E. Calabrese, Jd Paolo F. Ricci","doi":"10.1002/9780470744307.GAT123","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT123","url":null,"abstract":"The hormetic dose-response model has experienced a strong resurgence of interest in toxicology, risk assessment and pharmacology. This is based on its capacity for validation, reproducibility, generalizability, and its demonstrated ability to predict low-dose responses far more accurately than threshold and linear-at-low-dose models. This paper assesses capacity of hormesis models to impact the current risk assessment process, as well as the implications for risk assessment if regulatory agencies were to accept the hormetic dose-response as the default model. \u0000 \u0000 \u0000Keywords: \u0000 \u0000hormesis; \u0000biphasic; \u0000dose-response; \u0000adaptive response; \u0000risk assessment; \u0000U-shaped; \u0000J-shaped","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116722549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-12-15DOI: 10.1002/9780470744307.GAT140
I. Dewhurst, T. Marrs
Pesticides are a group of substances with heterogeneous toxicity, whose desired activity is the killing of unwanted living organisms. The main groups are insecticides, fungicides, herbicides and rodenticides. Many, but not all, pesticides have mammalian toxicity that is related to their toxicity to the target organism. To be weighed against their mammalian toxicity are the facts that insects and fungi are important sources of agricultural loss and give rise to much damage to buildings, where construction is often of wood. Furthermore, many insects carry diseases such as malaria and sleeping sickness, which in the absence of control measures may render land uninhabitable or agriculturally unusable. The key to a successful pesticide is selective toxicity and some of the more modern pesticides have actions that are target-organism specific. In recent years, there has been some concern as to the possibility of deleterious effects from multiple pesticides exposure, either as residues in food or at the workplace. Another recent development is the use of microbial pest control agents: these are plant-protection products that have a micro-organism, that is, a bacterium, fungus, virus, protozoan, microscopic nematode or microsporidium, as the active material. Keywords: pesticides; insecticides; fungicides; biological pesticides; herbicides; rodenticides; acetylcholinesterase; human data
{"title":"Toxicology of Pesticides","authors":"I. Dewhurst, T. Marrs","doi":"10.1002/9780470744307.GAT140","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT140","url":null,"abstract":"Pesticides are a group of substances with heterogeneous toxicity, whose desired activity is the killing of unwanted living organisms. The main groups are insecticides, fungicides, herbicides and rodenticides. Many, but not all, pesticides have mammalian toxicity that is related to their toxicity to the target organism. To be weighed against their mammalian toxicity are the facts that insects and fungi are important sources of agricultural loss and give rise to much damage to buildings, where construction is often of wood. Furthermore, many insects carry diseases such as malaria and sleeping sickness, which in the absence of control measures may render land uninhabitable or agriculturally unusable. The key to a successful pesticide is selective toxicity and some of the more modern pesticides have actions that are target-organism specific. In recent years, there has been some concern as to the possibility of deleterious effects from multiple pesticides exposure, either as residues in food or at the workplace. Another recent development is the use of microbial pest control agents: these are plant-protection products that have a micro-organism, that is, a bacterium, fungus, virus, protozoan, microscopic nematode or microsporidium, as the active material. \u0000 \u0000 \u0000Keywords: \u0000 \u0000pesticides; \u0000insecticides; \u0000fungicides; \u0000biological pesticides; \u0000herbicides; \u0000rodenticides; \u0000acetylcholinesterase; \u0000human data","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115831340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-12-15DOI: 10.1002/9780470744307.GAT174
R. Kammula
Medical devices and their component materials are potential sources of toxins that may produce undesirable local and/or systemic toxic responses when used clinically. The evaluation of toxic responses of medical devices using various toxicological test methods is also called biocompatibility evaluation of medical devices. The evaluation of toxicity (biocompatibility) of medical devices has been a complex task, because the devices are made of a diverse range of materials and have various intended uses, with body contact ranging from transient skin contact to permanent implantation. The safety and effectiveness of medical devices marketed in the United States (USA) is regulated by the Center for Devices and Radiological Health (CDRH) of the US Food and Drug Administration (FDA). The medical devices marketed in the European Union (EU) are required to comply with EU Medical Devices Directive 93/42/EEC, which specifies requirements for safety assessment. There are several national and international standards that address the toxicological evaluation of medical devices. In recent years the FDA—in particular the CDRH—uses and accepts toxicological data generated using the national and international biocompatibility standards to evaluate the safety of medical devices. The EU and Japan (MHLW) also use and accept toxicological data generated using international standards. This chapter is an introduction to a relatively new and rather complicated field in toxicology—the toxicological testing of medical devices. It discusses the toxicological considerations for establishing the safety of medical devices to meet the requirements of regulatory agencies. The guidelines for testing of medical devices are discussed and a general description of the various test procedures given. Developments in the field of biocompatibility regarding international harmonization are also addressed. Keywords: medical devices; biocompatibility of medical devices; toxicity testing of medical devices; regulatory requirements; classification of medical devices; International Standards and Guidelines
{"title":"Toxicological Considerations in Relation to the Regulatory Safety Evaluation of Medical Devices","authors":"R. Kammula","doi":"10.1002/9780470744307.GAT174","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT174","url":null,"abstract":"Medical devices and their component materials are potential sources of toxins that may produce undesirable local and/or systemic toxic responses when used clinically. The evaluation of toxic responses of medical devices using various toxicological test methods is also called biocompatibility evaluation of medical devices. The evaluation of toxicity (biocompatibility) of medical devices has been a complex task, because the devices are made of a diverse range of materials and have various intended uses, with body contact ranging from transient skin contact to permanent implantation. The safety and effectiveness of medical devices marketed in the United States (USA) is regulated by the Center for Devices and Radiological Health (CDRH) of the US Food and Drug Administration (FDA). The medical devices marketed in the European Union (EU) are required to comply with EU Medical Devices Directive 93/42/EEC, which specifies requirements for safety assessment. There are several national and international standards that address the toxicological evaluation of medical devices. In recent years the FDA—in particular the CDRH—uses and accepts toxicological data generated using the national and international biocompatibility standards to evaluate the safety of medical devices. The EU and Japan (MHLW) also use and accept toxicological data generated using international standards. This chapter is an introduction to a relatively new and rather complicated field in toxicology—the toxicological testing of medical devices. It discusses the toxicological considerations for establishing the safety of medical devices to meet the requirements of regulatory agencies. The guidelines for testing of medical devices are discussed and a general description of the various test procedures given. Developments in the field of biocompatibility regarding international harmonization are also addressed. \u0000 \u0000 \u0000Keywords: \u0000 \u0000medical devices; \u0000biocompatibility of medical devices; \u0000toxicity testing of medical devices; \u0000regulatory requirements; \u0000classification of medical devices; \u0000International Standards and Guidelines","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114908580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-12-15DOI: 10.1002/9780470744307.GAT108
S. Fairhurst, E. Ball
The purpose of this chapter is to discuss the interplay between the disciplines of toxicology and occupational (or industrial) hygiene in understanding and controlling the hazards and risks to health posed by chemicals, in an occupational setting. Ten years ago, the chapter ‘Industrial Toxicology and Hygiene’, produced for the second edition of General and Applied Toxicology, offered a perspective on the main approaches, roles and responsibilities that, in a regulatory context, had held for a considerable period of time within chemical legislation. This updated chapter is written from within the European Union (EU) at a time when it is embarking on a new era of chemicals legislation that promises to change things profoundly. On 1 June 2007 the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation came into force in the EU. This legislation changes the nature and balance of roles between industry and regulatory authorities—and modifies the conventional approaches to, and interplay between, toxicology and occupational hygiene—in regulating industrial and commercial chemicals within the EU. In its information requirements for registration purposes, REACH creates a tension between desires to improve the extent and quality of data available on chemicals, but also to minimize experimental animal testing. In relation to toxicology, this poses challenges to all concerned. REACH removes the distinction and associated data-expectation requirements between ‘new’ and ‘existing’ substances within the EU. REACH also expands and reinforces the ‘customer care’ principle that suppliers of chemicals take responsibility for understanding the uses to which their chemicals are to be put and specifying the risk management measures that should be followed in such uses. This will be a big challenge to the occupational hygiene profession. And all of this also comes at a time when the EU is in the process of adopting the globally harmonized system (GHS) of classification and labelling (C&L) of chemicals, which will modify the EU C&L system that has operated for the previous several decades. So it is a time of change—and no one is quite sure how things will work out in the next 10 years. This chapter attempts to portray how these recent developments build on, or change, what has gone before, and discusses some of the key issues that are ahead for the toxicology and occupational-hygiene fields, operating in this new regulatory context. Keywords: occupational toxicology; occupational hygiene; REACH; regulatory toxicology; risk assessment; classification and labelling; occupational exposure limits; OELs; epigenetics
{"title":"Occupational Toxicology and Occupational Hygiene within the European Union (EU) Chemicals Regulation","authors":"S. Fairhurst, E. Ball","doi":"10.1002/9780470744307.GAT108","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT108","url":null,"abstract":"The purpose of this chapter is to discuss the interplay between the disciplines of toxicology and occupational (or industrial) hygiene in understanding and controlling the hazards and risks to health posed by chemicals, in an occupational setting. Ten years ago, the chapter ‘Industrial Toxicology and Hygiene’, produced for the second edition of General and Applied Toxicology, offered a perspective on the main approaches, roles and responsibilities that, in a regulatory context, had held for a considerable period of time within chemical legislation. This updated chapter is written from within the European Union (EU) at a time when it is embarking on a new era of chemicals legislation that promises to change things profoundly. On 1 June 2007 the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation came into force in the EU. This legislation changes the nature and balance of roles between industry and regulatory authorities—and modifies the conventional approaches to, and interplay between, toxicology and occupational hygiene—in regulating industrial and commercial chemicals within the EU. In its information requirements for registration purposes, REACH creates a tension between desires to improve the extent and quality of data available on chemicals, but also to minimize experimental animal testing. In relation to toxicology, this poses challenges to all concerned. REACH removes the distinction and associated data-expectation requirements between ‘new’ and ‘existing’ substances within the EU. REACH also expands and reinforces the ‘customer care’ principle that suppliers of chemicals take responsibility for understanding the uses to which their chemicals are to be put and specifying the risk management measures that should be followed in such uses. This will be a big challenge to the occupational hygiene profession. And all of this also comes at a time when the EU is in the process of adopting the globally harmonized system (GHS) of classification and labelling (C&L) of chemicals, which will modify the EU C&L system that has operated for the previous several decades. So it is a time of change—and no one is quite sure how things will work out in the next 10 years. This chapter attempts to portray how these recent developments build on, or change, what has gone before, and discusses some of the key issues that are ahead for the toxicology and occupational-hygiene fields, operating in this new regulatory context. \u0000 \u0000 \u0000Keywords: \u0000 \u0000occupational toxicology; \u0000occupational hygiene; \u0000REACH; \u0000regulatory toxicology; \u0000risk assessment; \u0000classification and labelling; \u0000occupational exposure limits; \u0000OELs; \u0000epigenetics","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127448003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-12-15DOI: 10.1002/9780470744307.GAT152
J. Lord, G. Griffiths
The chapter covers the origins of ricin toxin, which is present in the seeds of the many cultivars of the castor oil plant. The structure and biogenesis of the dimeric (A and B chain toxin) ricin (RCA60) is described, compared with the related, but less toxic, Ricinus agglutinin (RCA120) and the toxic activity of ricin, the N-glycosidase activity of the A chain, is explained. The intoxication process is further described and developed through in vitro and in vivo studies, which then focus on several possible routes of exposure. These include inhalation, that route which has been the primary focus of military-oriented research through oral and parenteral routes of intoxication; histopathology and symptomatology are described, using evidence from human cases of ricin poisoning, wherever possible. Information is then presented on the development of medical countermeasures against ricin poisoning, including pretreatment approaches (vaccines) and postexposure approaches, which include antitoxins. More novel and currently research-based studies are considered, including inhibitors of N-glycosidase, substrate competitors or approaches to interfere with the binding of the ricin B chain to galactose moieties. Keywords: ricinus cultivars; structure; biogenesis; inhalation toxicology; oral toxicology; parenteral toxicology; medical countermeasures; vaccines; antitoxin; inhibitor studies
{"title":"Ricin: Chemistry, Sources, Exposures, Toxicology and Medical Aspects","authors":"J. Lord, G. Griffiths","doi":"10.1002/9780470744307.GAT152","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT152","url":null,"abstract":"The chapter covers the origins of ricin toxin, which is present in the seeds of the many cultivars of the castor oil plant. The structure and biogenesis of the dimeric (A and B chain toxin) ricin (RCA60) is described, compared with the related, but less toxic, Ricinus agglutinin (RCA120) and the toxic activity of ricin, the N-glycosidase activity of the A chain, is explained. The intoxication process is further described and developed through in vitro and in vivo studies, which then focus on several possible routes of exposure. These include inhalation, that route which has been the primary focus of military-oriented research through oral and parenteral routes of intoxication; histopathology and symptomatology are described, using evidence from human cases of ricin poisoning, wherever possible. Information is then presented on the development of medical countermeasures against ricin poisoning, including pretreatment approaches (vaccines) and postexposure approaches, which include antitoxins. More novel and currently research-based studies are considered, including inhibitors of N-glycosidase, substrate competitors or approaches to interfere with the binding of the ricin B chain to galactose moieties. \u0000 \u0000 \u0000Keywords: \u0000 \u0000ricinus cultivars; \u0000structure; \u0000biogenesis; \u0000inhalation toxicology; \u0000oral toxicology; \u0000parenteral toxicology; \u0000medical countermeasures; \u0000vaccines; \u0000antitoxin; \u0000inhibitor studies","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121636992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-12-15DOI: 10.1002/9780470744307.GAT050
R. Myers, Bennett J. Varsho
Because of ethical, scientific, social and legal considerations, toxicological research with animals must be conducted humanely and with careful attention to proper animal care. Animal welfare legislation specifies facility construction, primary enclosure space, feed, water, temperature, lighting, humidity, sanitation and staff requirements for maintaining animal health. For technical personnel, experience and training should be confirmed by the American Association for Laboratory Animal Science (or equivalent) certification. The animal research facility itself should be certified in the appropriate care and use of animals by an agency such as the Association for Assessment and Accreditation of Laboratory Animal Care International. Humane research in animals should be guided by the ‘three Rs’: reduction of numbers of test animals, refinement towards less pain or distress and replacement with alternatives to whole-animal models. Increasingly, alternative models are being validated and incorporated into protocols and regulatory guidelines. Everyone involved in animal research must be cognizant of, and committed to, standards for humane animal research. To this end, the Institutional Animal Care and Use Committee oversees test justification, adequacy of facility and staff, prevention of pain or suffering and concerns about animal treatment. Conflicts must be resolved through a balance between study goals and animal welfare. Keywords: animal alternatives; animal research; animal care; animal testing; animal care and use committee; animal toxicology; animal laboratory; animal use; animal legislation; animal welfare
{"title":"Animal Welfare in the Toxicology Laboratory","authors":"R. Myers, Bennett J. Varsho","doi":"10.1002/9780470744307.GAT050","DOIUrl":"https://doi.org/10.1002/9780470744307.GAT050","url":null,"abstract":"Because of ethical, scientific, social and legal considerations, toxicological research with animals must be conducted humanely and with careful attention to proper animal care. Animal welfare legislation specifies facility construction, primary enclosure space, feed, water, temperature, lighting, humidity, sanitation and staff requirements for maintaining animal health. For technical personnel, experience and training should be confirmed by the American Association for Laboratory Animal Science (or equivalent) certification. The animal research facility itself should be certified in the appropriate care and use of animals by an agency such as the Association for Assessment and Accreditation of Laboratory Animal Care International. Humane research in animals should be guided by the ‘three Rs’: reduction of numbers of test animals, refinement towards less pain or distress and replacement with alternatives to whole-animal models. Increasingly, alternative models are being validated and incorporated into protocols and regulatory guidelines. Everyone involved in animal research must be cognizant of, and committed to, standards for humane animal research. To this end, the Institutional Animal Care and Use Committee oversees test justification, adequacy of facility and staff, prevention of pain or suffering and concerns about animal treatment. Conflicts must be resolved through a balance between study goals and animal welfare. \u0000 \u0000 \u0000Keywords: \u0000 \u0000animal alternatives; \u0000animal research; \u0000animal care; \u0000animal testing; \u0000animal care and use committee; \u0000animal toxicology; \u0000animal laboratory; \u0000animal use; \u0000animal legislation; \u0000animal welfare","PeriodicalId":325382,"journal":{"name":"General, Applied and Systems Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128364654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-12-15DOI: 10.1002/9780470744307.GAT087
I. Choonara
Neonates, infants and young children may experience the same drug toxicity as adults. They may also experience specific drug toxicity that adults do not experience. This may be associated with toxicity related to growth and development, for example the adverse effect of corticosteroids on growth or development of the brain following exposure in the early period of neonatal life. Alternatively they may develop a specific toxicity in relation to a condition that does not occur in adults, for example Reye's syndrome following exposure to salicylates during the presence of a viral infection. The altered drug metabolism within paediatric patients is an additional risk factor for drug toxicity. This is most marked in the neonatal period and is illustrated by the impaired metabolism of chloramphenicol which results in cardiovascular collapse. Similarly, the altered metabolism of antiepileptic drugs such as sodium valproate in children less than two years of age predisposes this particular age group to hepatotoxicity. Other specific examples of drug toxicity in paediatric patients are given in this chapter and these include examples of percutaneous and excipient toxicity. Keywords: drug toxicity; children; percutaneous; chloramphenicol; sulfonamides; dexamethasone; sodium valproate; salicylates; vigabatrin; propofol; diethylene glycol
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