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INTRODUCTION 4 1. OECD Guidelines for the Testing of Chemicals are periodically reviewed in light of 5 scientific progress, changing regulatory needs, and animal welfare considerations. The first 6 Test Guideline (TG) for the determination of skin sensitisation in the mouse, the Local 7 Lymph Node Assay (LLNA; TG 429) was adopted in 2002 (1). The details of(More)
A major challenge in the emerging field of toxicogenomics is to define the relationships between chemically induced changes in gene expression and alterations in conventional toxicologic parameters such as clinical chemistry and histopathology. We have explored these relationships in detail using the rodent uterotrophic assay as a model system. Gene(More)
Toxicogenomics has the potential to reveal the molecular pathways and cellular processes that mediate the adverse responses to a toxicant. However, the initial output of a toxicogenomic experiment often consists of large lists of genes whose expression is altered after toxicant exposure. To interpret gene expression changes in the context of underlying(More)
We studied nine presumed nongenotoxic rodent carcinogens, as defined by the U.S. National Toxicology Program (NTP), to determine their ability to induce acute or subacute biochemical and tissue changes that may act as useful predictors of nongenotoxic rodent carcinogenesis. The chemicals selected included six liver carcinogens (two of which are peroxisome(More)
Langerhans cell (LC) migration from epidermis to draining lymph node is a critical first step in cutaneous immune responses. Both TNF-alpha and IL-1 beta are important signals governing this process, but the potential regulatory role of IL-1 alpha processing by caspase-1 is unknown. In wild-type (WT) mice, application of the contact allergens(More)
In January 2001 a Joint Food and Agriculture Organization of the United Nations/World Health Organization Expert Consultation Committee on Allergenicity of Foods Derived from Biotechnology published a report outlining in detail an approach for assessing the allergenic potential of novel proteins. One component of this decision tree is a determination of(More)
The advent of the local lymph node assay (LLNA), and efforts to develop in vitro alternatives for the identification of skin sensitizing chemicals has focused attention on the issue of false positive and false negative results. In essence, the question becomes 'what is the gold standard?' In this context, attention has focused primarily on the LLNA as this(More)
Hundreds of chemicals are contact allergens but there remains a need to identify and characterise accurately skin sensitising hazards. The purpose of this review was fourfold. First, when using the local lymph node assay (LLNA), consider whether an exposure concentration (EC3 value) lower than 100% can be defined and used as a threshold criterion for(More)
Several studies have demonstrated that antagonists of the corticotrophin releasing factor (CRF) receptor markedly inhibit experimentally induced excitotoxic, ischaemic and traumatic brain injury in the rat, and that CRF expression is elevated in response to experimentally induced stroke or traumatic brain injury. CRF is also induced by the pro-inflammatory(More)