Jack H Dean | Search PubMed

PubMed2003

Consensus workshop on methods to evaluate developmental immunotoxicity.

A workshop cosponsored by the National Institute of Environmental Health Sciences and the National Institute for Occupational Safety and Health was convened in Washington, DC, on 17-18 October 2001 with the goal of developing a consensus document on the most appropriate experimental approaches and assays available to assess developmental immunotoxicity. The work group was composed of scientists from academia, the chemical and pharmaceutical industries, and federal agencies with expertise in developmental immunology, developmental toxicology, immunotoxicology, and risk evaluation. This consensus document presents an overview of the major summations made by the work group. A summary of early work in the field is provided, which includes potential immunotoxic agents, followed by brief discussions of our current understanding of developmental immunology. This report concludes with the work group's consensus of the most appropriate experimental design and tests to screen for potential developmental immunotoxic agents in experimental models, including potential limitations and data gaps.

Environmental Pollutants↗

PubMedDate not supplied

A brief history of immunotoxicology and a review of the pharmaceutical guidelines.

This article provides a brief history of the development of the field of immunotoxicology from one individual perspective and separates the discussion into five phases: the methods development and validation phase; the compound testing phase; the many meetings and organization of the specialty section phase; the mechanistic studies phase; and the guidelines phase. During the discussion of each phase, major highlights, accomplishments, contributors and key references are provided. The immunotoxicology guidelines for the testing of pharmaceutical chemical entities across the three major geographic axes are also presented and compared, along with some of the concerns raised by industry with these guidelines. The mandatory requirement of functional tests represents the major concern and difference between the Committee of Proprietary Medicinal Products (CPMP) and the new Food and Drug Administration (FDA) guidance. The scientific basis for the recommendation of the functional tests proposed in the guidance documents based on National Institute of Environmental Health and Safety/National Toxicology Program (NIEHS/NTP)-sponsored studies is described. Experience at Sanofi-Synthelabo, with the testing of 29 new chemical drug entities developed across a broad range of therapeutic classes using this testing paradigm and functional tests to define their immunotoxic potential, yielded a low number of compounds (6.8%) that produced any abnormal reaction. The two positive compounds might have been anticipated based on their pharmacology.

Drug-Related Side Effects and Adverse Reactions↗