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110 100 90 Blank 1.95 3.91 7.81 g ml Hydrochlorothiazide 0.5 1.5 1 Blank 3.9 7.8 15.6 g ml Caeisoprodol 1.5 1 0.5 0 3.5 3 2.5 D. Kirkland, M. Aardema, L. Henderson and L. Muller, Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens: I. Sensitivity, specificity and relative predictivity, Mutation Research, 584 2005 ; 1-256. 2. Matthews, E. J., Kruhlak, N. L., Cimino, M. C., Benz, R. D. & Contrera, J. F. An analysis of genetic toxicity, reproductive and developmental toxicity, and carcinogenicity data: I. Identification of carcinogens using surrogate endpoints. Regulatory Toxicology and Pharmacology 44, 83-96 2006 ; . 3. P.Hastwell, L. Chai, K. Roberts, T. Webster, J. Harvey, R. Rees, and R. Walmsley. High specificity and high sensitivity genotoxicity assessment in a human cell line: validation of the GADD45a-GFP genotoxicity assay. Mutation Research, 607 2006 ; 160-175. 4. Q. Zhan. Gadd45a, a p53- and BRCA1-regulated stress protein, in cellular response to DNA damage, Mutation Research, 569 2005 ; 133-143. 5. Szuts, D., and T. Krude. Cell cycle arrest at the initiation step of human chromosomal DNA replication causes DNA damage. Journal of Cell Science 2004 ; 117: 4897-4908. TOXICOLOGY The toxicity data on serotonin that are available in the literature are mostly related to increased endogenous serotonin or its metabolites level by metabolic or medication effect. Acute toxicity Human Acute toxicity of serotonin is displayed when the endogenous serotonin level or its metabolites is raised by exogenous factors drugs serotonin reuptake inhibitor, monoamine oxidase inhibitor ; , food banana or walnuts ; in combination with alcohol, tryptophan ; or by serotonin hyperproduction in the body carcinoid tumor ; . The most common clinical symptoms observed are: nausea, vomiting, headache, diarrhea and uremic anorexia 11, 35, 36 ; . The serotonin syndrome SS ; is a toxic reaction to a relative ; hyperserotonergic condition in the brainstem and the spinal cord. Motoric restlessness and anxiety, fever, diaphoresis, and myoclonus characterize the syndrome. The syndrome is probably an extreme form of well-known adverse effects. A particular high risk is seen at combination treatments with monoamine oxidase inhibitors and serotonergic agents 37 ; . Animal sc-rat LD50: 285 mg kg 38 ; iv-rat LD50: 30 mg kg 38 ; oral-mouse LD50: 60 mg kg 38 ; ipr-mouse LD50: 160 mg kg 38 ; sc-mouse LD50: 601 mg kg 38 ; iv-mouse LD50: 81 mg kg 38 ; ims-mouse LD50: 750 mg kg 38 ; iv-guinea-pig LD50: 12, 8 mg kg 38 ; Local tolerance Human No data available Animal No data available Repeated dose toxicity Subacute No data available Semichronic No data available Chronic Serotonin is a vasoactive amine, which has been suggested to be a mediator in a wide number of vascular pathologies in human. Alterations in peripheral serotonin have been related to a major risk in suffering vascular diseases in the diabetic population. Also, the valvular thickening seen in carcinoid heart syndrome could be associated with serotonin. The mechanism of the plaque formation is poorly understood, and may involve either kinins or serotonin and its metabolite, 5-hydroxyindoleacetic acid. Its role in hemostasis and thrombosis is not clear. It does amplify aggregation induced by other aggregating agents and in certain individuals can induce aggregation alone and ceftin.

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