The Systemic Injury by Environmental Exposure (SIEE) Special Emphasis Panel reviews applications related to the pharmacological and toxicological mechanisms whereby xenobiotics (including toxicants, alcohol, drugs, biopharmaceuticals, phytochemicals and other non-drug chemicals) affect distinct organ systems, other than the digestive and nervous systems. Specifically, SIEE reviews applications related to the cardiovascular, musculoskeletal, hematopoietic, renal, respiratory/pulmonary, immune, endocrine and reproductive systems. Other areas included are skin, oral, dental and craniofacial tissues, pregnancy and development. Applications addressing the effects of xenobiotics at the multi-organ level may also be considered.
Specific areas covered by SIEE:
- Mechanisms of action of xenobiotics, including toxicological and/or pharmacological effects.
- Development of animal models that study the effects of xenobiotics.
- Molecular basis for susceptibility to xenobiotics-induced toxicity and disease (e.g., pharmacogenetics, pharmacogenomics, toxicogenetics, toxicogenomics).
- Identification of biomarkers of xenobiotics-induced toxicity.
SIEE has the following shared interests within the DIG IRG:
- With Xenobiotic and Nutrient Disposition and Action [XNDA]: There is a shared interest with XNDA in the area of mechanisms of disposition and action of xenobiotics. Applications that focus mainly on disposition (absorption, metabolism, distribution and excretion) of xenobiotics, regardless of the organ system, could be assigned to XNDA. Studies dealing largely with the mechanisms whereby xenobiotics exert their deleterious effects at the organ level could be reviewed in SIEE, except if they are focused on the gastrointestinal system, including liver. In this case, XNDA would be appropriate. Applications studying the effects of xenobiotics and other environmental factors in in vitro cell systems or transcending organ systems could be reviewed in XNDA, whereas those studying organ-specific effects could be reviewed in SIEE. Studies dealing with multi-organ toxicity, where the gastrointestinal activity is not dominant, are appropriate for SIEE.
- With Hepatobiliary Pathophysiology [HBPP]: There is shared interest in the area of xenobiotic effects between HBPP and SIEE. Where the focus is on the mechanisms whereby xenobiotics induce liver injury the application could be assigned to HBPP. Where the focus is on multi-organ systems and the hepatic activity is not dominant, the application could be assigned to SIEE.
- With Clinical and Integrative Gastrointestinal Pathobiology [CIGP]: There is shared interest in the area of xenobiotic effects between CIGP and SIEE. Where the focus is on the pathophysiology of xenobiotic-related pancreatic or intestinal disorders, the application could be assigned to CIGP. Where the focus is on multi-organ systems and the pancreatic or intestinal activities are not dominant, the application could be assigned to SIEE.
SIEE has the following shared interests outside the DIG IRG:
- With the Biology of Development and Aging [BDA] IRG: Shared interests exist in the area of development and stem cell biology. Applications that focus on general mechanisms of development and basic biology of stem cells could be assigned to BDA. Studies focused on the effects of xenobiotics are relevant to SIEE.
- With the Genes, Genomes and Genetics [GGG] IRG: There is shared interest with GGG in genomic studies, specifically on the discovery and interpretation of genetic and genomic variation in xenobiotic-induced disease. Applications with a primary focus on molecular basis for susceptibility to xenobiotics-induced toxicity and disease would be appropriate for SIEE. Studies of quantitative genetics, genetic epidemiology and genetic analysis of complex traits, and genetically engineered animals with an emphasis on genetics rather than mechanisms of toxicity may be assigned to the GGG IRG.
- With the Integrative, Functional and Cognitive Neuroscience [IFCN] IRG: Shared interests exist in areas where the pharmacological and/or toxicological effects of xenobiotics on the nervous system are studied. Where studies of xenobiotics relate primarily to effects on the nervous system, they could be assigned to the IFCN IRG. Where the focus is on multi-organ systems and the nervous system component is not dominant, the application could be assigned to SIEE.
- With the Infectious Diseases and Microbiology [IDM] IRG: When the emphasis is on the evaluation of the therapeutic mechanisms of action of novel agents that are potentially useful against infectious diseases, assignment to the IDM IRG may be appropriate. Applications where the primary focus is on toxicological effects on the hosts’ organ systems, other than the digestive and nervous systems, may be appropriate for SIEE.
- With the Immunology [IMM] IRG: There is shared interest with IMM in studies involving the effect of xenobiotics on the immune system. Applications that focus on basic immunological aspects could be assigned to IMM. Studies focused on the effects of xenobiotics could be reviewed by SIEE.
- With the Oncological Sciences [ONC] IRG: Shared interests exist in the area of effects of xenobiotics on cancer initiation, promotion and progression, as well as side effects of biopharmaceuticals for cancer treatment. When the emphasis is on carcinogenic mechanisms, or development and testing of cancer therapeutics, ONC IRG would be appropriate. However, SIEE would be appropriate for applications dealing with toxic side effects of cancer therapeutics in organs other than the intended therapeutic targets.
- With the Surgical Sciences, Biomedical Imaging and Bioengineering [SBIB] IRG: Studies of toxicology of general or local anesthetic agents may be assigned to SBIB. Studies of bioengineering approaches to facilitate drug delivery and studies of the use of biomaterials to modify drug delivery should be considered for assignment to SBIB. General studies of the mechanisms of action of xenobiotics when they relate to normal and pathological conditions of distinct organ systems, except the digestive and nervous systems, may be appropriate for SIEE.
- With the Organ-system/Disease IRGs-Cardiovascular Sciences [CVS]; Endocrinology, Metabolism, Nutrition, and Reproductive Sciences [EMNR]; Hematology [HEME]; Musculoskeletal, Oral, and Skin Sciences [MOSS]; Respiratory Sciences [RES]; and Renal and Urological Sciences [RUS]: There is shared interest with these IRGs in studies involving the effect of xenobiotics. Studies focused on specific effects of xenobiotics on these systems could be reviewed by SIEE. Studies that use xenobiotics as model compounds to address fundamental questions regarding the physiology and pathophysiology of individual organs and systems could be assigned to the appropriate IRG.
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