International Federation Of Societies Of Toxicologic Pathologists Research Articles

Modern Pathology Methods for Neural Investigations

This session at the 2010 joint symposium of the Society of Toxicologic Pathology (STP) and the International Federation of Societies of Toxicologic Pathologists (IFSTP) explored modern neuropathology methods for assessing the neurotoxicologic potential of xenobiotics. Conventional techniques to optimally prepare and evaluate the central and peripheral neural tissues while minimizing artifact were reviewed, and optimal schemes were set forth for evaluation of the nervous system during both routine (i.e., general toxicity) studies and enhanced (i.e., specialized neurotoxicity) studies. Stereology was introduced as the most appropriate means of examining the possible impact of toxicants on neural cell numbers. A focused discussion on brain sampling took place among a panel of expert neuroscientists (anatomists and pathologists) and the audience regarding the proper balance between sufficient sampling and cost- and time-effectiveness of the analysis. No consensus was reached on section orientation (coronal sections of both sides vs. a parasagittal longitudinal section with several unilateral hemisections from the contralateral side), but most panelists favored sampling at least 8 sections (or approximately double to triple the current complement) in routine toxicity studies.

Proceedings of the 2010 National Toxicology Program Satellite Symposium.

The 2010 annual National Toxicology Program (NTP) Satellite Symposium, entitled "Pathology Potpourri," was held in Chicago, Illinois, in advance of the scientific symposium sponsored jointly by the Society of Toxicologic Pathology (STP) and the International Federation of Societies of Toxicologic Pathologists (IFSTP). The goal of the annual NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for voting or discussion. Some topics covered during the symposium included a comparison of rat and mouse hepatocholangiocarcinoma, a comparison of cholangiofibrosis and cholangiocarcinoma in rats, a mixed pancreatic neoplasm with acinar and islet cell components, an unusual preputial gland tumor, renal hyaline glomerulopathy in rats and mice, eosinophilic substance in the nasal septum of mice, INHAND nomenclature for proliferative and nonproliferative lesions of the CNS/PNS, retinal gliosis in a rat, fibroadnexal hamartoma in rats, intramural plaque in a mouse, a treatment-related chloracne-like lesion in mice, and an overview of mouse ovarian tumors.

Gene Expression, Biomarkers, and Glial Cells in Nervous System Diseases

Session 3 of the "Toxicologic Neuropathology" Symposium sponsored jointly by the Society of Toxicologic Pathology (STP) and the International Federation of Societies of Toxicologic Pathologists (IFSTP) focused on advances in the understanding of cellular and molecular mechanisms of the nervous system and neurodegenerative diseases, and on new information on the function and roles of microglia cells and astrocytes. This overview highlights the major themes of the presentations in General Session 3; these themes are covered in greater detail in four papers in this issue of Toxicologic Pathology.

Animal Models for Neural Diseases

"Animal Models of Neural Disease" was the focus of General Session 5 at a 2010 scientific symposium that was sponsored jointly by the Society of Toxicologic Pathology (STP) and the International Federation of Societies of Toxicologic Pathologists (IFSTP). The objective was to consider issues that dictate the choice of animal models for neuropathology-based studies used to investigate neurological diseases and novel therapeutic agents to treat them. In some cases, no animal model exists that recapitulates the attributes of the human disease (e.g., fibromyalgia syndrome). Alternatively, numerous animal models are available for other conditions, so an essential consideration is selecting the most appropriate experimental system (e.g., Alzheimer's disease). New technologies (e.g., genetically engineered rodent models) promise the opportunity to generate suitable animal models for syndromes that currently lack any in vivo animal model, while in vitro models offer the opportunity to evaluate xenobiotic effects in specific neural cell populations. The complex nature of neurological disease requires regular reassessment of available and potential options to ensure that animal-derived data sets support translational medicine efforts to improve public health.

Introduction and Commentary: “Toxicologic Neuropathology”—and a Whole Lot More!

A regrettable tendency throughout recorded human history is that neurotoxicants have initially been discovered during human epidemics of neurotoxicity. Well-known agents illustrating this trend include ethanol, n-hexane, lead, mercury, polychlorinated biphenyls (PCBs), and tri-ortho cresyl phosphate (TOCP) (Costa et al. 2004; Inoue et al. 1988). During the late 20th and early 21st centuries, neural dysfunction has remained a key occupational hazard for adults (Connelly and Malkin 2007; Gobba 2003) and a devastating congenital event in children (Bearer 2001). Both of these age groups may be exposed to neurotoxicants via endogenous production of toxic metabolites during the course of certain diseases (ammonia, unconjugated bilirubin) or, more commonly, by contact with exogenous materials in the external habitat (e.g., agrochemicals, metals, pesticides, solvents) or deliberately introduced into the body (i.e., biopharmaceuticals, drugs, natural toxins [animals, microbes, plants]). The potential scale of toxicant-induced neuropathology is enormous. Each year, about 85,000 chemicals are manufactured and another 2,000 to 3,000 new compounds are registered in the United States alone (Goldman 1998). At least 2,500 (3%) of these entities are thought to be neurotoxic to some extent (Claudio 1992), though many—including up to two-thirds of chemicals made annually in amounts exceeding one million pounds—have not received a detailed analysis to assess their neurotoxic potential (Environmental Defense Fund 1997). Thus, a main aim of neurotoxicologic research today is to prospectively identify the neurotoxic capacity of novel compounds rather than to discover it retrospectively after neurotoxicity epidemics appear in humans. Many toxicologic pathologists are outstanding contributors to this public health effort. The collective interest by the toxicologic pathology community has resulted in the selection of ‘‘Toxicologic Neuropathology’’ as the focus of the Society of Toxicologic Pathology’s annual scientific symposium about every decade during the past 30 years, with the subsequent production of dedicated issues of Toxicologic Pathology that collate the then current, state-of-the-art concepts and practices in this field. (Prior STP symposium issues devoted to toxicologic neuropathology may be accessed in Toxicologic Pathology [1990] 18, 81–224 and Toxicologic Pathology [2000] 28, 1–214.) The rapid growth of the discipline in the past decade again led to the choice of toxicologic neuropathology for the STP’s 29th annual scientific symposium, which was jointly sponsored by the International Federation of Societies of Toxicologic Pathologists (IFSTP) and held in Chicago, Illinois, USA, June 20–24, 2010. As noted during the previous STP symposium on toxicologic neuropathology, the three factors driving growth in this field are (1) our greatly increased understanding of neural structure and function; (2) an intense effort to find new therapies for treating neurodegenerative, neurooncologic, and neurovascular diseases; and (3) a greater demand by global regulatory agencies for specific neurotoxicity testing in the registration packages for new products (Fix 2000). These same factors retain their importance at the present time.

Perspectives on Past Practices and Future Trends in Toxicologic Neuropathology

Dr. Peter S. Spencer, a pioneering neurotoxicologist of international renown, delivered the keynote address at the 2010 Joint Scientific Symposium of the Society of Toxicologic Pathology (STP) and the International Federation of Societies of Toxicologic Pathologists (IFSTP). He has made many landmark discoveries during his four-decade career. Dr. Spencer's address communicated several fundamental principles of past and present toxicologic neuropathology research, and he also predicted future trends in the field. First, classic approaches to toxicologic neuropathology emphasized morphologic techniques such as light microscopic and ultrastructural assessment. However, neuropathology methods alone rarely reveal the mechanism(s) and etiology of neurotoxic conditions, so neurotoxicity problems are now being investigated using a multidisciplinary approach in which neuropathologic assessment is but one component of the analysis. The two primary trends for future toxicologic neuropathology investigations, in both animals and humans, will be an increased use of noninvasive neural imaging and greater preference for in situ molecular ("omic") methods, which provide functional information in a structural context. These trends will significantly enhance the ability of scientists to translate animal data to human situations, thereby improving our understanding of disease mechanisms and facilitating efforts to design new therapies for neural diseases.

International Recommendations for Training Future Toxicologic Pathologists Participating in Regulatory-type, Nonclinical Toxicity Studies

The International Federation of Societies of Toxicologic Pathologists (IFSTP) proposes a common global framework for training future toxicologic pathologists who will support regulatory-type, nonclinical toxicology studies. Optimally, trainees should undertake a scientific curriculum of at least five years at an accredited institution leading to a clinical degree (veterinary medicine or medicine). Trainees should then obtain four or more years of intensive pathology practice during a residency and/or on-the-job "apprenticeship," at least two years of which must be focused on regulatory-type toxicologic pathology topics. Possession of a recognized pathology qualification (i.e., certification) is highly recommended. A nonclinical pathway (e.g., a graduate degree in medical biology or pathology) may be possible if medically trained pathologists are scarce, but this option is not optimal. Regular, lifelong continuing education (peer review of nonclinical studies, professional meetings, reading, short courses) will be necessary to maintain and enhance one's understanding of current toxicologic pathology knowledge, skills, and tools. This framework should provide a rigorous yet flexible way to reliably train future toxicologic pathologists to generate, interpret, integrate, and communicate data in regulatory-type, nonclinical toxicology studies.

International Recommendations for Training Future Toxicologic Pathologists Participating in Regulatory-Type, Nonclinical Toxicity Studies

The International Federation of Societies of Toxicologic Pathologists (IFSTP) proposes a common global framework for training future toxicologic pathologists who will support regulatory-type nonclinical toxicology studies. Trainees optimally should undertake a scientific curriculum of at least 5 years at an accredited institution leading to a clinical degree (veterinary medicine or medicine). Trainees should then obtain 4 or more years of intensive pathology practice during a residency and/or on-the-job “apprenticeship,” at least 2 years of which must be focused on regulatory-type toxicologic pathology topics. Possession of a recognized pathology qualification (i.e., certification) is highly recommended. A non-clinical pathway (e.g., a graduate degree in medical biology or pathology) may be possible if medically trained pathologists are scarce, but this option is not optimal. Regular, lifelong continuing education (peer review of nonclinical studies, professional meetings, reading, short courses) will be necessary to maintain and enhance one’s understanding of current toxicologic pathology knowledge, skills, and tools. This framework should provide a rigorous yet flexible way to reliably train future toxicologic pathologists to generate, interpret, integrate, and communicate data in regulatory-type, nonclinical toxicology studies.

STP Debate on the Desirability of an International Mechanism for Recognizing Qualified Toxicologic Pathologists

The June 2009 Town Hall meeting of the Society of Toxicologic Pathology (STP) and a subsequent survey considered whether or not STP should endorse a published proposal (Toxicol Pathol 37: 553-561, 2009) by the International Federation of Societies of Toxicologic Pathologists (IFSTP) to provide global recognition by credential review for toxicologic pathologists engaged in regulatory-type, nonclinical toxicology studies. One-third (374 of 1082) of STP members answered the survey. The majority of respondents rejected the IFSTP proposal (55% against) but favored the concept of global recognition (57% for), if available to both anatomic pathologists and clinical pathologists (67% for). Members preferred recognition by credential review (49% for) or via an internationally authored "best practices" document detailing the ideal educational and work experiences required for entry-level proficiency in toxicologic pathology (43% for). Therefore, the STP Executive Committee does not endorse the current IFSTP proposal but will continue discussions on global recognition of qualified toxicologic pathologists with other societies of toxicologic pathology.

Global recognition of qualified toxicologic pathologists: Credential review as a potential route for recognizing the proficiency of pathologists involved in regulatory-type nonclinical studies

Recent international summits of the International Federation of Societies of Toxicologic Pathologists (IFSTP) have debated the desirability and potential means by which the proficiency of an individual toxicologic pathologist might be recognized and communicated throughout the world. The present document describes the advantages and disadvantages of implementing such a global recognition system by any means, and provides a proposal whereby recognition might be accorded via rigorous credential review of a practitioner's education and experience.

Global Recognition of Qualified Toxicologic Pathologists: Credential Review as a Potential Route for Recognizing the Proficiency of Pathologists Involved in Regulatory-type Nonclinical Studies.

Recent international summits of the International Federation of Societies of Toxicologic Pathologists (IFSTP) have debated the desirability and potential means by which the proficiency of an individual toxicologic pathologist might be recognized and communicated throughout the world. The present document describes the advantages and disadvantages of implementing such a global recognition system by any means, and provides a proposal whereby recognition might be accorded via rigorous credential review of a practitioner’s education and experience.

Genetically modified foods: Hazard identification and risk assessment – Session summary: Session Report from the Joint STP/IFSTP International Symposium “Toxicologic Pathology in the New Millenium” June 24–28, 2001, in Orlando, Florida

During a Joint Society of Toxicologic Pathology (STP)/International Federation of Societies of Toxicologic Pathologists (IFSTP) International Symposium, held between June 24 and 28, 2001, in Orlando, FL, USA, there was a session entitled as "Genetically Modified Foods: Hazard Identification and Risk Assessment". The purpose of this session was to present and discuss the current situations in the US, European Union and Japan for the public concerns, safety assessments and regulations on genetically modified (GM) products used as foods or food ingredients. Assuming the wide and fast growing of the usage of GM products, it is the duty for us as toxicologic pathologists, to supply reliable data on their safety and possible risks or hazards as a world-wide basis to not only governments or regulatory agencies but also general public of our countries.

Genetically Modified Foods-Hazard Identification and Risk Assessment

During a Joint Society of Toxicologic Pathologists (STP)/International Federation of Societies of Toxicologic Pathologists (IFSTP) International Symposium, held between June 24 and 28, 2001, in Orlando, FL, USA, there was a session entitled as “Genetically Modified Foods-Hazard Identification and Risk Assessment”. The purpose of this session was to present and discuss the current situations in the US, European Union and Japan for the public concerns, safety assessments and regulations on genetically modified (GM) products used as food or food ingredients. Assuming the wide and fast growing of the usage of GM products, it is the duty for us, toxicologic pathologists, to supply reliable data on their safety and possible risks or hazards as a world-wide basis to not only governments or regulatory agencies but also general public of our countries.

Third Conference of the International Federation of Societies of Toxicologic Pathologists (IFSTP)

Third Conference of the International Federation of Societies of Toxicologic Pathologists (IFSTP)

First Conference of the International Federation of Societies of Toxicologic Pathologists (IFSTP)

First Conference of the International Federation of Societies of Toxicologic Pathologists (IFSTP)

International Federation of Societies of Toxicologic Pathologists (IFSTP)

International Federation of Societies of Toxicologic Pathologists (IFSTP)