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PubMed1996

Specificity and dosimetry of toxicologic responses.

Toxicology has two goals. The first is to identify and characterize the adverse effects that can be produced in biological systems by exposure to chemicals and the second is to use this information to predict the type and severity of responses in other species and exposure situations. The tools that the toxicologist uses to detect and describe the adverse effects of chemical exposure include the traditional acute, subchronic, and chronic studies in animals plus a variety of special studies designed to demonstrate specific organ damage, reproductive and teratogenic effects, neurotoxicity, immunotoxicity, genotoxicity, and other responses. These are often supplemented with studies of the kinetics and the mechanism of action and more recently with studies designed to elucidate the molecular basis for cancer and other effects. Theses studies together with the information on exposure provide the basis for subsequent toxicologic predictions. Although general effects such as weight loss and mortality are included in toxicity protocols, most of the toxicology tests are related to specific end-organ toxicity or to mechanism or behavioral studies. We do not have animal protocols to study individually the subjective symptoms described for multiple chemical sensitivity, such as depression, fatigue, headache, and memory loss, and our tests lack sufficient specificity to evaluate a syndrome which is composed primarily of such symptoms. Since all chemicals can produce adverse effects under some conditions of exposure, toxicologic predictions are most useful when they specify both the type of adverse effect anticipated and the dose required to produce the effect. Multiple chemical sensitivity does not appear to consistently involve specific chemicals or specific adverse effects and the effects observed are reported to lack evidence of a threshold and to occur at extremely low levels. It is difficult to include these parameters in any reasonable toxicologic prediction relating cause and response in multiple chemical sensitivity or similar conditions.

Environmental Illness↗

PubMed1989

The advisory subgroup in toxicology of the european medical research councils.

The European Medical Research Councils set up an Advisory Group in Toxicology which met from 1975 to 1988. Since encouragement of cross discipline research is still difficult, a resumé is presented of the procedures developed to encourage interdisciplinary research in toxicology in Europe. A programme of grants in toxicology for collaborative research between European countries was begun in 1981 under the auspices of the European Science Foundation. Resulting from the final meeting of AST in Milan, the need for the development of links between epidemiology and molecular aspects of toxicology and for new approaches in eco-toxicology are briefly discussed.

Environmental Monitoring↗

PubMedDate not supplied

Role of the toxicology laboratory in the treatment of acute poisoning.

The modern toxicology laboratory can play an important role in the evaluation of poisoning. In order to appreciate the nature and extent of this role, several essential elements necessary to an acute care toxicology service should be considered. When an ongoing and effective dialogue between clinicians and the toxicology laboratory staff is established, and a broadly based analytical approach is applied to the analysis of the appropriate biological fluids, a dynamic and viable toxicology service will result. How these elements work together to facilitate this service will be discussed, based primarily on experience in a large teaching hospital. This experience indicates that if the elements necessary to provide laboratory support in the investigation of an alleged poisoning are in place, the toxicology laboratory plays an important role in ensuring optimum and effective patient care.

Clinical Laboratory Techniques↗

PubMed1983

Characteristics and capabilities of U.S. commercial toxicological testing laboratories.

About 800 commercial chemical testing laboratories were surveyed by telephone to determine how many provide toxicological testing services and what characteristics the toxicological testing laboratories portrayed. The survey identified 274 laboratories that performed toxicological testing in 1981. These are estimated to account for 94 to 98% of the toxicology laboratory population. The survey data provided a general profile of these laboratories, showed the number of laboratories capable of performing different types of tests, indicated the amount of excess capacity, and identified the most critical constraints to future expansion of testing. There were an estimated 180 laboratories providing mammalian toxicological tests, 150 providing in vitro tests, 150 providing environmental effects tests, and 140 providing chemical fate tests. At the time of the survey, the industry appeared able to do about 20% additional testing before reaching capacity.

Animals↗

PubMed1981

Toxicology investigations with cell culture systems.

This review concerns some of the cell culture systems that are most frequently used in toxicology investigations. In particular, it sets out to evaluate the effectiveness of these cell culture systems in assessing the toxic potential of chemicals. Metabolic studies and general and specific toxicology investigations are highlighted. Specific toxicology investigations relate to the effects of the tests substances on the highly specialized functions typical of the cell systems chosen. The general toxicology investigations include most of the other studies where differentiated or undifferentiated cells have been used to evaluate the effects of the tested substances on common basic biochemical processes essential for life. Lastly, we have attempted to focus attention on the most promising applications of cell cultures in toxicology studies for the near future and to identify those areas where further research is needed. Because of the several excellent reviews that already exist, we have decided not to consider cell cultures utilized in screening potential mutagens and carcinogens. We have also excluded investigations of drug therapeutic effects and action mechanisms of drugs.

Animals↗

PubMed1995

Toxicology databases in the metadatabank of online databases.

Databases in science and technology dealing with toxicology subjects are of great and increasing interest to the scientific community. International hosts pay their tribute in creating toxicology clusters as a user-aid. Toxicology clusters of DataStar, DIALOG, DIMDI and STN are listed and compared. At the German National Research Centre for Environment and Health an 'Information System for Environmental Chemicals' has been developed. Within this research project approximately 400 online databases have been evaluated and the results are stored in the Metadatabank of Online Databases called DADB. A further step in this project is to assist the users of these metadatabases to choose the most appropriate database(s) for a special query. The retrieval of information out of a multitude of differently structured databases can be optimized using different evaluation criteria. We distinguished three groups of evaluation criteria: (1) general evaluation criteria, e.g. size of database, update frequency, cost of online search, etc., (2) evaluation criteria based on the characterization of environmental chemicals, and (3) evaluation criteria based on environmental-relevant data-types. We studied the influence of a number of different criteria in order to rank a set of objects, in this particular case toxicology databases. We used a six-number scoring system. The scoring is carried out using the scientific background of lattice theory and its graphical evaluation. The application of this scoring system for toxicologically-relevant databases, which is still in an early development stage, is useful in selecting the most appropriate database(s) in accordance with special items of interest. Applying our five chosen criteria, the databank CA (Chemical Abstracts) turns out to be the best, followed by four other databanks, which cannot be compared with each other.

Databases, Factual↗

PubMed2005

Paradigm lost, paradigm found: the re-emergence of hormesis as a fundamental dose response model in the toxicological sciences.

This paper provides an assessment of the toxicological basis of the hormetic dose-response relationship including issues relating to its reproducibility, frequency, and generalizability across biological models, endpoints measured and chemical class/physical stressors and implications for risk assessment. The quantitative features of the hormetic dose response are described and placed within toxicological context that considers study design, temporal assessment, mechanism, and experimental model/population heterogeneity. Particular emphasis is placed on an historical evaluation of why the field of toxicology rejected hormesis in favor of dose response models such as the threshold model for assessing non-carcinogens and linear no threshold (LNT) models for assessing carcinogens. The paper argues that such decisions were principally based on complex historical factors that emerged from the intense and protracted conflict between what is now called traditional medicine and homeopathy and the overly dominating influence of regulatory agencies on the toxicological intellectual agenda. Such regulatory agency influence emphasized hazard/risk assessment goals such as the derivation of no observed adverse effect levels (NOAELs) and the lowest observed adverse effect levels (LOAELs) which were derived principally from high dose studies using few doses, a feature which restricted perceptions and distorted judgments of several generations of toxicologists concerning the nature of the dose-response continuum. Such historical and technical blind spots lead the field of toxicology to not only reject an established dose-response model (hormesis), but also the model that was more common and fundamental than those that the field accepted.

Animals↗

PubMed2005

Distance learning and toxicology: new horizons for Paracelsus.

Distance learning offers many advantages to students and teachers of almost any scientific discipline. Toxicology is no exception. For example, should Paracelsus be interested in learning more about toxicology at Drexel University, he would have the opportunity to take two courses in this subject utilizing the content management software, WebCT. The two courses would offer a website from which he could view and/or download his notes for each class. He could correspond with the instructor as well as fellow students, participate in discussions about timely topics, and make presentations to the class, all via electronic communication. Moreover, his examinations would also be computerized. Although he might have the option of attending traditional "face-to-face" lectures with other students in the class, he could also access these lectures at any time from a remote location by using the archive of taped lectures on the class website. Overall, Paracelsus would have access to many tools to enhance his understanding of toxicology, and he probably would never have to worry about parking before class (!). The two WebCT modules in toxicology that we have developed at Drexel represent the successful migration of two courses from a traditional "face-to-face" model of classroom instruction to hybrid models that combine "face-to-face" interaction with online instruction. Student and faculty evaluations of these courses have been very positive. Future plans include linking the two modules together so that students in the advanced class can do "review" or "remedial" work in the basic module. Furthermore, a library of video clips is also planned in which researchers will be discussing their work on various toxicologic topics. Students will be able to access these clips as resources from which to write research papers.

Education, Distance↗

PubMed2005

Distance learning in toxicology: Australia's RMIT program.

RMIT University was the first to offer a comprehensive Masters of Toxicology in Australasia 19 years ago. In 2001 the program was transformed into two stages, leading to a Graduate Diploma and Master of Applied Science in Toxicology. Now, these programs are fully online and suitable for graduates living and working anywhere in the world. The modular distance-learning courses are specifically designed to equip students with essential skills for entering fields such as chemical and drug evaluation; risk assessment of chemicals in the workplace; environmental and food toxicology. RMIT's online course delivery system has made it possible to deliver the toxicology programs, both nationally and internationally. The learning material and interactive activities (tests and quizzes, discussion boards, chat sessions) use Blackboard and WebBoard, each with a different educational function. Students log in to a Learning Hub to access their courses. The Learning Hub enables students to extend their learning beyond the classroom to the home, workplace, library and any other location with Internet access. The teaching staff log in to the Learning Hub to maintain and administer the online programs and courses which they have developed and/or which they teach. The Learning Hub is also a communication tool for students and staff, providing access to email, a diary and announcements. The early experience of delivering a full toxicology program online is very positive. However this mode of teaching continues to present many interesting technical, educational and cultural challenges, including: the design and presentation of the material; copyright issues; internationalization of content; interactive participation; and the assessment procedures.

Australia↗

PubMed2002

Integrating toxicology and ecology: putting the "eco" into ecotoxicology.

Environmental toxicology has been and continues to be an important discipline (e.g., single-species testing for screening purposes). However, ecological toxicology (ecotoxicology--more realism in tests, test species and exposures) is required for predicting real world effects and for site-specific assessments. Ecotoxicology and ecology have shown similar developmental patterns over time; closer cooperation between ecologists and toxicologists would benefit both disciplines. Ecology can be incorporated into toxicology either extrinsically (separately, e.g., providing information on pre-selected test species) or intrinsically (e.g., as part of test species selection)--the latter is preferable. General guidelines for acute and chronic testing and criteria for species selection differ for ecotoxicology and environmental toxicology, and are outlined. An overall framework is proposed based on ecological risk assessment (ERA), for combining ecology and toxicology (environmental and ecological) for decision-making. Increased emphasis on ecotoxicology represents a shift from reductionist to holistic approaches.

Animals↗

PubMed1998

A Japanese view on a global toxicology testing program before ICH1 and after ICH4.

Many unharmonized points on the toxicological evaluation on pharmaceuticals have been solved by the discussion for 8 years in the ICH. The following issues are representative ones in which the Japanese view on a toxicology testing program after ICH4 is different from that before ICH1: (1) a new guideline and pre-mating treatment period in reproductive toxicity; (2) 9-month chronic studies for non-rodent species; (3) a new guideline of toxicokinetics; and (4) selection of high dose levels and a new guideline using short-term alternative tests in carcinogenicity. Hazard evaluation of pharmaceuticals to man in toxicological studies in Japan before ICH1 has been conducted on the basis of the traditional toxicological evaluation. After ICH4, in line with the ICH strategy, Japan will adopt the analytical/integrative toxicological evaluation taking into account the 'weight of evidence' approach, exposures of the test drug and species differences between experimental animals and humans. However, since there still remain many things that need to be clarified for the better understanding of the guidelines, Japan should take more flexible regulatory approaches for the evaluation.

Animals↗

PubMedDate not supplied

The common marmoset (Callithrix jacchus) as a model in toxicology.

The common marmoset, Callithrix jacchus, is the smallest nonhuman primate commonly used in biomedical research. Marmoset characteristics and propensities have enabled them to be used in a wide range of research as a model of human disease, physiology, drug metabolism, general toxicology, and reproductive biology. This paper provides a general overview of the marmoset with special emphasis on the benefits and disadvantages of this species as a model for inclusion in preclinical drug development programmes. In view of its small size in comparison with other nonrodent species marmosets have become of value for toxicology studies with biotechnology products where compound supply is limited. In general toxicology studies, marmosets have been successfully used to meet regulatory endpoints also for specific investigatory purposes. The widespread use of this species has allowed extensive background information to become available and a summary of the most frequently measured parameters are presented. Marmosets apparently represent an interesting animal model for comparative research on primate reproductive physiology. However, several basic aspects of reproductive processes exhibit cardinal discrepancies to those described for macaques and human. Thus, from the viewpoint of reproductive toxicology, the relevance of the marmoset primate model for human reproduction remains unclear to date and further research is obviously needed. Given our current knowledge of marmoset reproductive features, the use of this animal model cannot be recommended for reproductive toxicology assessment.

Animals↗

PubMedDate not supplied

History of toxicology and allied sciences: a bibliographic review and guide to suggested readings.

With roots extending to antiquity, toxicology is a profession that recognizes that the past is often prologue to the present. In that spirit, this article provides a comprehensive bibliographic overview of writings on the history of toxicology and allied sciences. These writings pertain to the evolution of toxicology, its various methods, concepts, and theories; as well as pioneers of the profession and the growth of professional toxicological organizations. It is not an exhaustive survey, but provides a thorough accounting of literature pertaining to the history of toxicology.

Animals↗

PubMed1992

Importance of information in forensic toxicology.

Information in forensic toxicology plays a very important role. The forensic pathologist usually seeks toxicologic analyses on basis of the information available at the time of the medicolegal autopsy. Such information may be obtained from different sources: hospitals, authorities, relatives, friends, or neighbors of the deceased and, obviously, macroscopic findings at the time of the autopsy. In order to evaluate the relative importance of these different sources of information, the authors have studied, retrospectively, results of 580 postmortem examinations performed at the Institute of Legal Medicine of Lisbon, wherein toxicologic analyses had been requested. These cases pertain to the years 1987 and 1988, but do not include alcohol determination in the blood in cases of traffic accidents. In 274 (47.4%) of the 580 cases, there were positive findings while in the remaining 306 (52.6%) findings were negative. In cases with positive findings, circumstances and factors, which may have influenced the pathologist's decision to request toxicologic analysis, are discussed. In more than half the cases, hospital information was the decisive factor, while in approximately 25% of the cases, autopsy findings were the justification. In contrast, it is worth mentioning that in approximately 45% of the cases with analytical negative results, requests were made, in cases of blank autopsies, for toxicologic analyses in order to exclude the possibility of poisoning. It is interesting to note that in the same proportion requests were justified on grounds of hospital information. Some of the factors that may explain this apparent discrepancy are discussed. Finally, the relevance of background information is emphasized at the level of the interpretation of analytical results, whether positive or negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Monoxide Poisoning↗

PubMed2001

Rational use of toxicology testing in children.

The majority of all patients with poison exposures in the United States are children. The evaluation and management of poisoned patients may be aided by the use of laboratory assays, ranging from basic assessments not uniquely indicated for the poisoned patient to highly sophisticated laboratory tests with very specific indications. Literature concerning poisoning in pregnant patients is evaluated and recommendations regarding the utility of pregnancy testing in poisoned females are discussed. Recent studies evaluating the use of toxicology testing in pediatrics have concluded that the use of comprehensive toxicology screening in pediatric patients is costly and does not affect the medical management of most poisoned patients. The utility of focused quantitative serum assays to determine serum levels of particular poisons is reviewed. Toxicology tests used for detection of drugs of abuse, with a particular focus on the capabilities and limitations of such tests, are discussed. The potential pitfalls that occur when toxicology tests are obtained indiscriminately, are misapplied, or are misunderstood are analyzed. Hair sampling as nonemergent toxicology testing for drugs of abuse is discussed.

Child↗

PubMed2000

From quantal counts to mechanisms and systems: the past, present, and future of biometrics in environmental toxicology.

As appreciation for human impact on the environment has developed, so have the experimental systems and associated statistical tools that quantify this impact. Toxicological study in particular has grown in its complexity and its need for advanced statistical support. Within this perspective, we describe statistical practice in environmental toxicology and risk assessment. We present two case studies, one from mammalian toxicology and one from aquatic toxicology, that highlight the evolution of statistical practice in environmental toxicology.

Biometry↗

PubMed2005

Clinical toxicology: clinical science to public health.

1. The aims of the present paper are to: (i) review progress in clinical toxicology over the past 40 years and to place it in the context of modern health care by describing its development; and (ii) illustrate the use of clinical toxicology data from Scotland, in particular, as a tool for informing clinical care and public health policy with respect to drugs. 2. A historical literature review was conducted with amalgamation and comparison of a series of published and unpublished clinical toxicology datasets from NPIS Edinburgh and other sources. 3. Clinical databases within poisons treatment centres offer an important method of collecting data on the clinical effects of drugs in overdose. These data can be used to increase knowledge on drug toxicity mechanisms that inform licensing decisions, contribute to evidence-based care and clinical management. Combination of this material with national morbidity datasets provides another valuable approach that can inform public health prevention strategies. 4. In conclusion, clinical toxicology datasets offer clinical pharmacologists a new study area. Clinical toxicology treatment units and poisons information services offer an important health resource.

Analgesics, Opioid↗

PubMed1998

Guidelines for the interpretation of analytical toxicology results and unit of measurement conversion factors.

A data compilation has been published on the World Wide Web [http:// www.leeds.ac.uk/acb/annals] which aims to assist in the interpretation of analytical toxicology results in individual patients. 'Therapeutic' or 'normal' plasma/whole blood/urine concentrations, as well as the concentrations associated with serious toxicity (if known), for some 700 analytes of toxicological interest are given together with (when possible) relative atomic or formula masses, and mass/amount and amount/mass concentration conversion factors. This paper gives background and supplementary information which should be borne in mind when providing interpretation or using the Web table. Supplementary tables listing (i) common therapeutic drug monitoring assays and guidelines for interpretation of results, (ii) emergency toxicology analyses which may influence active treatment, (iii) blood carboxyhaemoglobin saturation and clinical features of toxicity, (iv) information important when interpreting the results of toxicology investigations, (v) factors which may affect interpretation of analytical toxicology results, and (vi) conversion factors for volatile compounds are included.

Computer Communication Networks↗