CHEMISTRY SUPPORT SERVICES TO THE ENVIRONMENTAL TOXICOLOGY PROGRAM

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In support of National Toxicology Program (NTP), in their efforts of toxicological evaluations of toxicants, we have completed nearly 100 chemistry tasks were performed during FY2009. Dental composites are complex mixtures containing an organic resin matrix, reinforcing inorganic filler and a silane-coupling agent. It has been shown that the compound like bisphenol A (BPA) and bis-GMA were present in saliva after placement of a specific dental sealant that are shown to posses estrogenic activity. In this regard biological (human urine and saliva) samples were received from three different places for the assay of analytes: BPA and its possible derivatives and metabolites bisphenol A glycerolate dimethacrylate (bis-GMA), bisphenol A dimethacrylate (BPADM), bisphenol A diglycidyl ether (BADGE), bisphenol A bis (2,3-dihydroxypropyl) ether (BPAHPE), and tri (ethylene glycol) dimethacrylate (TEGDMA)]. The development method included the determination of the lowest quantifiable matrix concentration using liquid chromatography with mass spectrometric detection (LC/MS) and evaluation of matrix interferences. In an ongoing support of NTP¿s new initiative called ¿High Throughput Screening (HTS) program¿ for the toxicity testing different tasks are in progress. During the Fiscal Year hundreds of chemicals were tested for solubility, prepared 10/20mM solutions and shipped to different labs for high through-put screening experiments. The compound tris(2-Chloroisopropyl)phosphate (TCPP: mixture of four isomers), a flame retardant added to flexible polyurethane foam used in home furnishings includes. Following studies were performed for this compound: a bulk chemical limited analysis, dose formulation development study in NTP-2000 & NIH-07 feeds and in 0.5%,a 14-Day palatability study on at 50,000; 40,000; 30,000 ppm (¿g/g of feed) concentration of TCPP in NTP-2000 and NIH-07 feeds; nih07 for both Wistar Han rats and B6C3F1 mice. In continues studies on Ionic Liquids (IL) in the current year conducted Dose Formulation Development study in water and Bulk Chemical Reanalysis for the following IL¿s: 1-butyl-1-methyl-pyrrolidinium chloride, 1-butyl-3-methyl-imidazonium chloride, 1-ethyl-3-methyl-imidazonium chloride, and N-butyl-pyridinium chloride. To support the carcinogenic evaluation of n n-Butyl glycidyl ether (BGE), a comprehensive chemical analysis and dose formulation development study were performed. In support of studies on natural produces, gum guggul extract (GGE), a mixture of several steroid-lipids isolated from the plant Commiphora mukul (gum guggul) of Indian origin, containing Z- and E- isomers of guggulsterone as major constituents. In support of NTP studies a method was developed and validated for the assay of GGE in corn oil formulations. In support of the internal staff support program for LUMI-CELL¿ ER assay international validation study chemicals were purchased, coded, and shipped to labs in Japan, Italy and USA. Under above staff support program different compounds were shipped to the lab for MCF-7 estrogen receptor cell proliferation assay as requested by the internal staff. Also under GenTox Testing program chemicals were shipped for salmonella testing. Additionally 25 compounds are procured, prepared solutions as per the requirement and shipped to the lab for hemotoxicity assay. Additionally in support of the of the internal staff support program the study was conducted to determine the peptidyl-α-amidating monooxygenase (PAM) activity in soluble and membrane fractions of 4-phenyl-3-butenoic acid (PBA) treated prostate cancer cell (PC-3) lysates. With the TNP-tripeptide as substrate, the two reaction products, glycine-extended intermediate (TNP-D-Tyr-Val-α-hydroxy-Gly) and the amidated TNP-dipeptide (TNP-D-Tyr-Val-NH2) were determined using HPLC-UV. From the product concentration results and the cell lysate protein concentrations, the specific activity, was determined. Animal room water testing was conducted annually. Peroxide test on n-Butylglycidylether was performed every three months. Every year disposal of chemical and of biological samples was conducted. Following posters were presented in the 48th Society of Toxicology meeting, held in Baltimore, MD, during 15-19, 2009: ¿ Analytical Method Validation of Tris(chloropropyl) phosphate, Mixture in NTP-2000 and NIH-07 Rodent Diets ¿ Analytical Method Validation of 2-Methoxy-4-nitroaniline in NTP-2000 and NIH-07 Rodent Diets ¿ Preliminary Palatability Testing of Tris (chloropropyl) phosphate (TCPP) in Wistar Han Rats and B6C3F1 Mice ¿ Analytical Method Development for the Extraction and Analysis of Tris(chloropropyl)phosphate, mixture, 1-Chloroacetone and N-Acetyl-L-Cysteine