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At least 415 records · Page 23Linked to original sources
PubMed1989

Toxicologic studies on USAF aircraft accident casualties, 1973-1984.

The Armed Forces Institute of Pathology analyzed toxicology specimens on 294 cases submitted by the U.S. Air Force from 1973 through 1984. The fatal population consisted of 196 cases of which 43 (22%) had positive toxicology results. Of the fatalities, 14 (7%) had positive drug analyses. The nonfatal group consisted of 98 cases; 14 were positive for toxicology, with 6 positive for drugs. These toxicologic findings are analyzed according to aircrew position, aircraft, and accident scenario parameters.

Accidents, Aviation↗
PubMed1983

[Toxicologic characteristics of several pesticides and standards for them in water].

The progressive increase of production and application of chemicals for plant protection transmuted the problem of protection of water cleanliness into an international and national problem. The cases with incidental pesticide pollution of water-reservoirs became more numerous. A necessity arose of the supplement of our sanitary legislation with hygienic standards (MAC) for the water for the newly implemented chemicals for plant protection in the country. During the last several years, some of the most frequently used and formulated in our country pesticides were experimentally studied: Afalon and Patoran (from chemical group of carbamates and dithiocarbamates) and amide herbicide: Dimid, Ramrod, Lasso, Treflan. Complex hygienic-toxicological studies were carried out in order to study the toxicological effect of the pesticides mentioned and to elaborate hygienic norms (MAC) of the same in the water. The effect on the organoleptic qualities of water was determined as well as on the sanitary regime of waterreservoirs (according to BON5, sanitary-indictory microflora and toxicity for fishes). Toxicological studies were performed under the conditions of acute, subacute and chronic experiment. The results obtained allowed the hygienic-toxicological characteristics and the proposal of hygienic standards (MAC) for the pesticides studied in water.

Acetamides↗
PubMed1998

Principles and practices of integrating genotoxicity evaluation into routine toxicology studies: a pharmaceutical industry perspective.

In this article, an integrated in vivo genotoxicity testing philosophy and a practical approach, as applied to pharmaceuticals, are described. Recently, there has been an effort to integrate the rodent (primarily rat) micronucleus assay with routine 2-4-week toxicokinetic studies. This approach has several advantages: 1) it utilizes the general principles of toxicology that govern the overall toxicity profile of a test substance; 2) factors such as the dose and/or route of drug administration, drug metabolism, principles of toxicokinetics, and saturation of defense mechanisms are considered in evaluating genotoxicity; 3) it uses the concept of administering multiple tolerable doses aiding in achieving steady state plasma drug levels, which is more relevant for risk assessment compared to high acute doses; and 4) it helps minimize the amount of drug, number of animals used, and other resources. This integration approach can be extended to other toxicology studies and other relevant genotoxicity endpoints may be assessed. Based on the experience in our laboratory, integrating micronucleus assessment in routine toxicology testing is promising and should be utilized when practical.

Animal Rights↗
PubMed2005

Use of genetic toxicology information for risk assessment.

Genetic toxicology data are used worldwide in regulatory decision-making. On the 25th anniversary of Environmental and Molecular Mutagenesis, we think it is important to provide a brief overview of the currently available genetic toxicity tests and to outline a framework for conducting weight-of-the-evidence (WOE) evaluations that optimize the utility of genetic toxicology information for risk assessment. There are two major types of regulatory decisions made by agencies such as the Environmental Protection Agency (EPA) and the Food and Drug Administration (FDA): (1) the approval and registration of pesticides, pharmaceuticals, medical devices, and medical-use products, and (2) the setting of standards for acceptable exposure levels in air, water, and food. Genetic toxicology data are utilized for both of these regulatory decisions. The current default assumption for regulatory decisions is that chemicals that are shown to be genotoxic in standard tests are, in fact, capable of causing mutations in humans (in somatic and/or germ cells) and that they contribute to adverse health outcomes via a "genotoxic/mutagenic" mode of action (MOA). The new EPA Guidelines for Carcinogen Risk Assessment [Guidelines for Carcinogen Risk Assessment, USEPA, 2005, EPA Publication No. EPA/630/P-03/001F] emphasize the use of MOA information in risk assessment and provide a framework to help identify a possible mutagenic and/or nonmutagenic MOA for potential adverse effects. An analysis of the available genetic toxicity data is now, more than ever, a key component to consider in the derivation of an MOA for characterizing observed adverse health outcomes such as cancer. We provide our perspective and a two-step strategy for evaluating genotoxicity data for optimal use in regulatory decision-making. The strategy includes integration of all available information and provides, first, for a WOE analysis as to whether a chemical is a mutagen, and second, whether an adverse health outcome is mediated via a mutagenic MOA.

Animals↗
PubMed2006

Hyphenated mass spectrometric techniques-indispensable tools in clinical and forensic toxicology and in doping control.

Hyphenated mass spectrometric techniques, particularly gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS), are indispensable tools in clinical and forensic toxicology and in doping control owing to their high sensitivity and specificity. They are used for screening, library-assisted identification and quantification of drugs, poisons and their metabolites, prerequisites for competent expertise in these fields. In addition, they allow the study of metabolism of new drugs or poisons as a basis for developing screening procedures in biological matrices, most notably in urine, or toxicological risk assessment. Concepts and procedures using GC/MS and LC/MS techniques in the areas of analytical toxicology and the role of mass spectral libraries are presented and discussed in this feature article. Finally, perspectives of their future position are discussed.

Chromatography, Liquid↗
PubMed1994

Transgenic animals in toxicology.

Recent advances have been made in the characterization of a number of transgenic animal models. These animal models have provided a powerful toxicological tool for studying in vivo chemical effects and have increased our understanding of the role of specific genetic alterations as predisposing factors for chemical carcinogenesis. The goal of this symposium was to introduce the development of transgenic animals and the utilization of transgenics in toxicology research focusing on understanding tissue-specific mutation, chemical effects, and cancer. The production of transgenic animals, including gene insertions and gene knockouts, and the utilization of transgenic technology for studying multistage carcinogenesis and tumor suppressor genes are described. Data on the application and implications of transgenics as a genetic endpoint are also discussed. The use of transgenic animals in toxicology should improve our understanding of the role of specific genetic alterations in the carcinogenic process and lead to improved estimations of human health risks.

Animals↗
PubMed1997

Perturbation of the mitosis/apoptosis balance: a fundamental mechanism in toxicology.

Perturbations of the balance between cell gain via mitosis and cell loss by apoptosis play a pivotal role in mediating and modifying the action of carcinogens and other toxicants in tissues such as liver, brain, the immune system, the gastrointestinal tract, and the reproductive organs. Apoptosis describes a highly conserved morphology associated with the death of many different cell types from diverse tissues. This symposium focused on induced changes in this critical balance as a key mechanism of action of a variety of diverse toxicants. In the colon, the "toxicology" of 5 fluorouracil (5FU) is entirely dependent on p53, since p53 knockouts lose the pathology of 5FU damage. Presumably, this is because DNA damage is not detected and there is no cell cycle arrest. In the testes, testicular germ cell survival is mediated by adjacent Sertoli cells via the Fas ligand (FasL)-Fas receptor (Fas) system. This system appears to mediate germ cell apoptosis after exposure to testicular toxicants such as the phthalate, mono(2-ethylhexyl) phthalate (MEHP). Interestingly, MEHP is a member of the peroxisome proliferator (PP) class of nongenotoxic carcinogens. PPs perturb both hepatocyte apoptosis and mitosis. This suppression of apoptosis occurs via activation of the peroxisome proliferator-activated receptor alpha (PPARalpha), providing a paradigm for the regulation of liver growth via activation of nuclear receptors. Similarly, the toxicological effects of dioxins are mediated via the Ah receptor (AHR), another ligand-activated nuclear receptor. This receptor upregulates a variety of genes (the Ah gene battery) associated with the toxicology of dioxins. Taken together, the data presented in this symposium illustrate to the toxicologist the need to quantitate and interpret modulations in apoptosis alongside more conventional assessments of S-phase. Although the toxicant may initiate cell damage, genes like Bcl-2, p53, Fas, PPARalpha, and AHR are final arbiters of the choice between death, survival, and proliferation.

Animals↗
PubMed1993

The concept of multispecies testing in industrial toxicology.

The multispecies approach in toxicity testing was originally motivated by the frequent findings of species differences in responsiveness to the pharmacological and acute toxic effects of chemicals. When the guidelines for repeated-dose toxicity experiments were developed in the early 1940s, the concept of using several species of animals was automatically included without careful scientific validation. In response to demands from the U.S. Food and Drug Administration and other national and international regulatory bodies, the protocols for acute and repeated-dose toxicity testing became highly formalized, and the requirement to conduct all studies in a rodent and a nonrodent species was established. With time, most guidelines also specified the species that had to be used, and the most common recommendation was to use the rat as the rodent and the dog as the nonrodent. In recent years, many reasons for differences in responsiveness of various animal species and man to the toxic effects of chemicals have been identified. This knowledge is now used extensively to assess contradictory findings in routine safety studies in the rodent and the nonrodent species. It is often possible to identify the species that appears to be more predictive for man than the other, and risk assessment for man is then based mainly on the findings in the more representative species. Since contrary toxicological findings in rodents and nonrodents occur frequently, one could propose to perform detailed scientific investigations prior to the selection of the species for toxicological investigations, as it has already been suggested by the working group of the European Society for the Study of Drug Toxicology in 1965 and is still an option mentioned in the currently valid EEC drug safety guidelines of 1983. For practical reasons such early investigations of biological properties and pharmacokinetic and metabolic characteristics of test chemicals in various laboratory animal species are hardly ever done prior to the initiation of safety studies. However, techniques are now developed with which species selection for toxicity testing can be made on the basis of rational scientific investigations.

Animals↗
PubMed1999

Toxicology of hydrogen fluoride in relation to major accident hazards.

A major industrial accident involving the release of hydrogen fluoride has the potential to cause serious injury and possibly death in the surrounding human population. Given the potential for such serious and large-scale effects, there is a need for scientifically based risk assessments for determining appropriate on-site risk control measures, as well as for informing off-site emergency plans and land-use development decisions. Within Great Britain, the Health and Safety Executive (HSE) has the statutory responsibility for providing land-use planning advice in the vicinity of major accident hazard sites. The advice is based on quantified assessment of the individual risk of exposure to a specified amount of the toxic substance. Among other things this requires a consistent, reliable, and transparent understanding of the major hazard toxicology of the substance concerned. An assessment of the toxicology of hydrogen fluoride in relation to major accident hazards, based on conventional inhalation toxicity studies, was published by HSE in 1993. Recently, studies have been reported in which rats inhaled hydrogen fluoride via a mouthpiece attached to an endotracheal cannula. HSE has explored the use of this "mouth-breathing" rat model as a possible basis for human health risk assessment for hydrogen fluoride in the context of major accident hazards. A number of uncertainties in the use of this animal model have been identified that warrant caution in the use of this model for regulatory purposes. Overall, the results from the "mouth-breathing" rat model did not lead to a change in the HSE assessment of hydrogen fluoride, which remains based on experimental data obtained following "mainstream" toxicological practices.

Accidents, Occupational↗
PubMed1995

Applying simulation modeling to problems in toxicology and risk assessment--a short perspective.

The goals of this perspective have been to examine areas where quantitative simulation models may be useful in toxicology and related risk assessment fields and to offer suggestions for preparing manuscripts that describe these models. If developments in other disciplines serve as a bell-wether, the use of mathematical models in toxicology will continue to increase, partly, at least, because the new generations of scientists are being trained in an electronic environment where computation of all kinds is learned at an early age. Undoubtedly, however, the utility of these models will be directly tied to the skills of investigators in accurately describing models in their research papers. These publications should convey descriptions of both the insights obtained and the opportunities provided by these models to integrate existing data bases and suggest new and useful experiments. We hope these comments serve to facilitate the expansion of good modeling practices as applied to toxicological problems.

Computer Simulation↗
PubMed1982

Statistical analysis of behavioral toxicology data and studies.

One of the areas of toxicology in which a wide variation occurs in the statistical procedures used to analyze experimental data is behavioral toxicology. Due to either limitations in statistical training in the toxicologists or to a lack of understanding of the underlying biological mechanisms on the part of the statisticians, data is frequently analyzed by methodologies which either do not have optimal characteristics of sensitivity and power or for which the underlying assumptions as to the nature of the data are not valid. To establish a firm basis for an identification of the optimal and most appropriate forms of statistical analysis of behavioral toxicology data (and to design efficient and sensitive studies), the four general types of data (observational scores, response rates, error rates, and times-to-endpoints) and one special class of data (teratology and reproduction) are examined in detail. The present practices as to statistical analysis are then reviewed and suggestions as to optimal methods (based on experience, with data sets presented as examples) are developed and presented. The underlying key to this entire process is to establish the biological and statistical nature of the data being generated and to design and analyze experiments accordingly.

Amphetamine↗
PubMed1987

Toxicology, disappointments and promise.

The development of toxicology during the past 50 years is traced, with particular reference to chronic testing and carcinogenesis. The increasing dichotomy between the study of human disease and the accumulation of routine experimental data is examined. It is suggested that a drastic change is needed in toxicological approaches that replaces rote testing with more thoughtful scientific research. The relationship between toxicology and human disease needs to be re-emphasized and the medical profession encouraged to take a more active role in this field.

Animals↗
PubMed1979

Governmental toxicology regulations: an encumbrance to drug research?

The science of toxicology has become infinitely more complex and sophisticated over the past 20 years, a trend which has been particularly marked within the research-based pharmaceutical industry. Governmental rules and regulations have had a strong impact on the types of toxicity test now performed on drugs both in the course of their development and after their introduction on the market, and have thus contributed to the increased cost--in terms of time and money--of drug development. However, it will never be possible to measure or predict the safety of drugs in man by the application of toxicological techniques alone. Close collaboration between toxicologists and the authorities responsible for drawing up toxicological regulations is called for in order to ensure that the rules applied during the important and fascinating process of discovering and developing new drugs do not become unnecessarily burdensome.

Costs and Cost Analysis↗
PubMed1989

A report on methods to reduce, refine and replace animal testing in industrial toxicology laboratories.

The Committee to Promote Principles of Reduction, Refinement and Replacement of Animal Testing in Industrial Toxicology Laboratories was established in 1987 to work toward industrywide improvements in laboratory animal testing methods. The committee's goals are to gather information about effective nonanimal testing techniques and other methods of conserving and improving the care of laboratory animals, to work toward the systematic validation of nonanimal alternatives, and to disseminate useful information about progressive programs and policies throughout the industrial toxicology community. This is the first in a continuing series of reports the committee plans to produce as part of an ongoing program to promote communication among industrial toxicologists about successful methods of reducing, refining and replacing animal testing. Here are some of the report's major findings: (1) Animal care and use committees charged with the oversight of laboratory animal use are a universal practice at the companies surveyed. (2) Significant reductions in the number of animals used for acute toxicity testing have taken place at all the companies during the last 5- to 10-year period. (3) Structure-activity relationships (predicting a test compound's properties based on the known properties of familiar chemicals with similar structures) are widely used to minimize, but not replace, the use of animals. (4) Tissue and organ culture systems are being used with increasing frequency for screening and mechanistic studies, but are not completely replacing animal evaluations as a final step. (5) There is a pressing need for the systematic and scientifically sound validation of nonanimal alternative techniques to reduce the use of animals in toxicology testing while satisfying requirements for the protection of public safety.

Advisory Committees↗
PubMed2001

Careers in toxicology in Europe--options and requirements. Report of a workshop organized on behalf of the Individual Members of EUROTOX during the EUROTOX Congress 2000 in London (September 17-20, 2000).

In view of the lack of information regarding careers for toxicologists in Europe, the Individual Members of EUROTOX organised a workshop on careers in toxicology during the EUROTOX Congress 2000 in London. Toxicologists are mainly employed in academia, regulatory agencies, contract research organisations (CROs) and the chemical and pharmaceutical industries. There are also a few governmental institutes involved with toxicological work other than teaching or regulation. Toxicologists can also work as independent consultants, especially for commercial organisations. The requirements for starting a career in any of the above organisations, the need and the advantages and disadvantages of specialisation, and further career prospects are summarised and briefly discussed. The organisations, and also working as an independent toxicology consultant, offer interesting professional work of relevance to modern-day society. There is currently a shortage of toxicologists not only in the traditional field of risk assessment but also especially in new areas, e.g. toxicogenomics. This shortage may be at least in part due to insufficient training opportunities. Further consideration of career opportunities is planned and will be published in due course.

Career Mobility↗
PubMed1987

Toxicology then and now.

A review of the history of the evolution of the science of toxicology from the original concepts of Paracelsus through the early development of analytical chemistry and its contributions to the detection of toxic substances in foods and drugs as these have led to modern regulatory rules for public protection is presented. The legal actions taken to protect against adulteration of food prior to the early steps by the U.S. Department of Agriculture that concluded with the passage of the 1906 Food and Drug Act are systematically documented. The history is reviewed of the Food and Drug Administration's role in the use of animal toxicity studies to develop reasonable criteria for safety of foods and drugs for man. Modern concepts of molecular distribution, metabolism, and excretion of substances in the animal body are discussed as these impinge on the so-called "protection index." The legal and often litigious controversies over the claimed carcinogenicity of chemical substances is documented with comments on the Delaney dilemma and the role of in vitro tests in toxicology. The review concludes with a discussion of the hazards of use of stochastic mathematical models to assess carcinogenicity and suggests that the criteria employed in the report of the Scientific Committee of the Food Safety Council are properly structured to give a contemporary evaluation of all the currently available data. References give documentation of events over the past 200 years that explain the present state of toxicology as a discipline.

Europe↗
PubMed1980

Summing up the International Workshop on the Application of Tissue Culture in Toxicology.

A summary is given of the present state of the use of tissue cultures in toxicology, as it emerged from the workshop. The need for better education in in vitro toxicology and for extensive comparison of results with those from in vivo studies is pointed out. Some of the important difficulties in the application of tissue cultures to toxicological problems are highlighted, as are the needs for basic research on tissue cultures and those for better communication between scientists, legislators, money sources and laymen.

Animals↗
PubMedDate not supplied

The framework of toxicology information.

The scientific and societal underpinnings of toxicology are reviewed, as is the structure and flow of its information. Historical sources are presented, followed by a summary of patterns of publication in and access to the periodical, monographic, and special report literature. Computerized information is stressed and specialized systems such as TOXNET and CIS are described. Other innovative electronic projects, including micro-CSIN and the ANSWER workstation are touched upon. Important organizations active in the toxicology field are highlighted and information applications in the legislative, regulatory, and judicial areas are discussed. Finally, the work of international organizations is reviewed and new directions in toxicology information are explored.

Information Services↗