Workshop on risk assessment in reproductive and developmental toxicology: addressing the assumptions and identifying the research needs

The risk assessment process is an imprecise procedure aimed at determining a toxicant exposure level with an acceptable risk to the human population. The lack of precision is due to the uncertainties in the assumptions that must be made due to the lack of specific scientific information or knowledge of how to use certain types of data. Unfortunately, every necessary piece of information cannot be obtained for every chemical requiring a risk assessment. In order to better identify and understand some of the assumptions that are made in the risk assessment of reproductive and developmental toxicants, a workshop was organized to specifically define the assumptions underlying the risk assessments for seven specific toxicants (dibromochloropropane, dioxin, glycol ethers, heptachlor, lead, tetrahydrocannabinol, and vitamin A) and to determine the potential research which would reduce the uncertainty associated with making those assumptions. The major assumptions discussed centered around the topics of heterogeneous populations, thresholds, safety factors, exposure assessment, quantitative structure-activity relationships, and mechanisms. This report is the summary of the workshop discussions.     

Nucleotides and their receptors in the nervous system. 1-2 August 1998, Leipzig, Germany

This meeting was the second in four months to cover the role of P2 purinoreceptors in tissue function and pathophysiology, the previous being the Sixth International Symposium on Adenosine and Adenine Nucleotides held in Ferrara, Italy in May. There was, therefore, a paucity of new data. A major theme of the meeting was the complexity of purinergic signaling due to ATP degradation to adenosine by ectonucleotidase activity. The characterization of receptor function was limited by the purported selectivity and potency of available antagonists, but some new P2Y1 receptor antagonists were presented. An interesting rumor emanating from the main IUPHAR meeting was that Pfizer had developed a P2X7 receptor knockout mouse that cannot produce IL-1beta, supporting the hypothesis, described below, that ATP acting via this receptor is critical in activating ICE (interleukin-1beta-converting enzyme). Approximately 120 people attended the meeting and 48 posters were presented.     

International Association for the Study of Pain--Ninth World congress. 22-27 August 1999, Vienna, Austria

At this meeting, novel analgesic effects were described for a number of compounds. Gabapentin was significantly effective in the treatment of pain associated with phantom limb pain after amputation and traumatic avulsion of the brachial plexus. Capsaicin analog, EC-665, prevented referred viscero-somatic hyperalgesia associated with bladder inflammation. Indomethacine was compared with UP-454-21, a selective COX-2 inhibitor showing comparable effectiveness between both drugs in their anti-inflammatory/analgesic properties. Contralateral treatment with local anesthetics resulted in a long-lasting anti-inflammatory effect in unilateral carra-geenan-induced inflammation. Spinal neostigmine reduced spinal bupivacaine-induced hypotension while lamo-trigine showed a definite benefit in varied patients with neuropathic pain. Intra-articular administration of a ketorolac and morphine combination following arthroscopic knee surgery showed a significant decrease in postoperative pain and the need for postoperative analgesic. Oral CR oxycodone was shown to be an effective analgesic for the oral management of postoperative pain.     

Harmonisation of rat fetal skeletal terminology and classification. report of the third workshop on the terminology in developmental toxicology: Berlin, 14–16 September 2000

The initial efforts of the Federal Institute for Health Protection of Consumers and Veterinary Medicine (BgVV) and the Free University of Berlin to standardise terminology in the field of developmental toxicology began in 1995. Procedures were undertaken to harmonise the terminology used by the International Federation of Teratology Societies (IFTS) and the International Programme on Chemical Safety (IPCS). This article reflects these activities and is a report on the Third Workshop on the Terminology in Developmental Toxicology held in September 2000. This Workshop served as a forum to discuss the results of a survey on the classification of skeletal anomalies that had been previously sent to scientists active in the field. Although high agreement was reached among the evaluators for several terms, the use of a number of terms was rather variable. Therefore, the discussions at the workshop among the experts from research institutions, regulatory agencies, and industry were mainly focussed on those terms for which there was disagreement and/or uncertainties and the possible reasons. Pictures provided by the participants for the illustration of “grey zone” anomalies constituted the basis for detailed discussions. In many of the cases with lower agreement, decisions were facilitated by the provision of the corresponding picture. The main reasons for lower agreement were imprecise terms, insufficient knowledge on postnatal consequences, theoretical terms that are unlikely to occur in isolation, and the possibility of observing a range of severity that might be decisive for the classification of either a malformation or variation. The attendees concluded that “grey-zone” anomalies will never disappear completely and that for the assessment, the grade of severity and/or the frequency of the observation can be decisive for the terminology chosen. A Joint IPCS/IFTS Project was proposed to further consensus of terminology and classification and to link these anomalies to pictures at different skeletal sites. In order to support the harmonisation of regulatory decisions, it was proposed to establish a “Clearinghouse” System under the umbrella of the IPCS. The Clearinghouse could be contacted either by the regulatory authorities or by any company to clarify their queries, particularly with regard to registration or authorisation processes. Finally, it was recommended to also carry out a similar survey on “soft tissue anomalies” and “external findings.” The results of this survey will be discussed at a Joint IPCS/IFTS Workshop in Berlin in 2002.     

Workshop Report: AAPS Workshop on Method Development,Validation, and Troubleshooting of Ligand-Binding Assays in the Regulated Environment

A novel format was introduced at the recent AAPS NBC Workshop on Method Development, Validation and Troubleshooting in San Diego on 18th May 2014. The workshop format was initiated by Binodh De Silva; Marie Rock and Sherri Dudal joined the initiative to develop and chair the workshop. Questions were solicited by a variety of avenues, including a Linked-In Discussion Group. Once collated and clarified, the topics covered assay development, validation, and analysis of PK, Immunogenicity, and Biomarkers with an additional topic on alternative bioanalytical technologies. A panel of experts (workshop report co-authors) was assigned to each topic to bring forward thought-provoking aspects of each topic. The format of the workshop was developed to target the needs of bioanalytical scientists with intermediate to advanced experience in the field ranging to enable robust discussion and to delve deeper into the current bioanalytical hot topics. While the new format allowed for an interactive session with the topical discussion driven by the audience members, it did not foster equal discussion time for all of the proposed topics, especially Biomarkers and alternative LBA technologies.KEY WORDS: antibody, bioanalytical, biomarker, ligand-binding assays, immunogenicity     

American Society of Gene Therapy--First Annual Meeting. Education session: the ABCs of non-viral vectors for gene therapy. 28-31 May 1998, Seattle, Washington, USA

In July 1996, the American Society of Gene Therapy (ASGT) was established in San Francisco by George Stamatoyannopoulos (President of ASGT, Professor of Genetics and Medical Genetics at the University of Washington, USA), James M Wilson (President Elect of ASGT, Director of the Institute for Human Gene Therapy, University of Pennsylvania, USA) and other gene therapy experts. In May 1998, this society held its first annual meeting, in Seattle, WA. The aim of the annual meeting is to provide a forum for all investigators, including students, young scientists, academic researchers and those working in industry. To avoid the risk of bias through election of one program committee, symposia, workshops and poster sessions are organized by different committees. There are nine committees in total, so each discipline within the diverse field of gene therapy is properly represented. An education program was organized by Savio LC Woo (Mount Sinai of Medicine, New York, USA) and there was a high school student symposium to encourage interest from the younger generation. Professor Stamatoyannopoulos said that he would like to see the NIH establishing centers of excellence of gene therapy, as they did for cancer 25 years ago. James Wilson then thanked George for all his work founding the society, as he took over as president. There are already 14,000 members of the ASGT and more than 1500 scientists attended this conference. There were 18 sessions of oral presentations and 750 abstracts.     

Workshop on the qualitative and quantitative comparability of human and animal developmental neurotoxicity, Work Group IV report: triggers for developmental neurotoxicity testing

A Work Group was formed to evaluate the criteria considered important in determining when to require developmental neurotoxicity testing in animal studies (i.e., triggers for testing). The primary objective of the Work Group was to determine whether there is sufficient scientific evidence to support the triggers identified by the Environmental Protection Agency and determine whether there is sufficient evidence to use structure activity relationships (SAR) to trigger automatic testing of certain classes of chemicals. A weight of evidence (WOE) approach was recommended by the Work Group in order to assist in determining which agents should undergo developmental neurotoxicity testing and to what level of testing. Evaluation of biological effects, length and duration of exposure, and quality and quantity of data available on an agent should be used in the WOE approach. Agents that are teratogenic to the central nervous system (CNS) were considered of highest priority for developmental neurotoxicity testing, especially if there is the potential for a high degree of exposure. Neuropathic and neuroactive compounds, chemicals with hormone-like activity, and developmental toxicants (with effects other than structural abnormalities of the CNS) were also considered likely candidates for such testing. Although reluctant to recommend testing based solely on SAR or chemical class, the Work Group recognized the importance of considering SAR along with other toxicity data, pharmacokinetic data and potential human exposure in making final requirements or recommendations for further testing.(ABSTRACT TRUNCATED AT 250 WORDS)     

In silico methods for evaluating human allergenicity to novel proteins: International Bioinformatics Workshop Meeting Report, 23-24 February 2005.

The ILSI Health and Environmental Sciences Institute (HESI) hosted an expert workshop 22-24 February 2005 in Mallorca, Spain, to review the state-of-the-science for conducting a sequence homology/bioinformatics evaluation in the context of a comprehensive allergenicity assessment for novel proteins, to obtain consensus on the value and role of bioinformatics in evaluating novel proteins, and to discuss the utility and methods of allergen-specific IgE testing in the diagnosis of food allergy. The workshop participants included over forty international experts from academia, industry, and government. The workshop was hosted by the HESI Protein Allergenicity Technical committee, which has established a long-term program whose mission is to advance the scientific understanding of the relevant parameters for characterizing the allergenic potential of novel proteins.     

Highlights from the First International Conference in Vascular Medicine, held August 26-28, 2005, in Melbourne, Australia. Vascular medicine in Australia and Germany

Recent developments highlighted from the First International Conference in Vascular Medicine, held in Melbourne, Australia, August 26-28, 2005, are in nitric oxide signaling, oxidative stress, homeostasis, the angiotensin-aldosterone system, diabetes, new vessel formation and P-selectin.