Document OK8E7M52RxL7N5RqevzYB6bM

% AR226-2817 TRADE SECRET Study Title H-24921, H-26313, and H-26225: Evaluation of the Interference of the Test Substance in the Analysis of Rat Serum Lipids AUTHOR: Denise Hoban, B.A, MLT (ASCP) STUDY COMPLETED ON: October 13, 2004 TESTING FACILITY: E.I. du Pont de Nemours and Company Haskell81^ Laboratory for Health and Environmental Sciences Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 U.S.A. LABORATORY PROJECT ID: DuPont-15372 SPONSOR: E.I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. ^ ' "9 ^Comp.any sa*^,,.^"^03' CERTIFICATION I, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. Issued by Study Director: tV^lccA-^. Cj^h-^C^-->_______ Denise Hoban, B.A, MLT (ASCP) Staff Medical Technologist and Supervisor ISUCT^OO^ Date ~------wa ----^^^^ Compaq TABLE OF CONTENTS Page CERTIFICATION ........................................................................................................................2 STUDY INFORMATION............................................................................................................^ SUMMARY....................................................................................................................................6 OBJECTIVE..................................................................................................................................? EXPERIMENTAL DESIGN........................................................................................................ 7 MATERIALS AND METHODS ................................................................................................. 8 A. Test Substances................................................................................................................... 8 B. Phosphate Buffered Saline (PBS)........................................................................................ 8 C. Experimental Procedures..................................................................................................... 9 RESULTS AND DISCUSSION ................................................................................................. 12 A. Clinical Chemistry Analyses............................................................................................. 12 CONCLUSIONS......................................................................................................................... 12 RECORDS AND SAMPLE STORAGE ................................................................................... 12 13 TABLES....................................................................................................................................... TABLE 1 SUMMARY OF CLINICAL CHEMISTRY PARAMETERS FOR SERIAL DIUTIONS OF H-24921 IN PBS..........................................................................................................................................................15 TABLE 2 SUMMARY OF CLINICAL CHEMISTRY PARAMETERS FOR SERIAL DIUTIONS OF H-24921 IN SERUM...................................................................................................................................................16 TABLE 3 SUMMARY OF CLINICAL CHEMISTRY PARAMETERS FOR SERIAL DIUTIONS OF H-26313 IN PBS..........................................................................................................................................................17 TABLE 4 SUMMARY OF CLINICAL CHEMISTRY PARAMETERS FOR SERIAL DIUTIONS OF H-26313 IN SERUM................................................................................................................................................... 18 TABLE 5 SUMMARY OF CLINICAL CHEMISTRY PARAMETERS FOR SERIAL DIUTIONS OF H-26225 IN PBS.......................................................................................................................................................... 19 TABLE 6 SUMMARY OF CLINICAL CHEMISTRY PARAMETERS FOR SERIAL DIUTIONS OF H-26225 IN SERUM...................................................................................................................................................20 21 APPENDICES............................................................................................................................. APPENDIX A CLINICAL CHEMISTRY DATA ......................................................................................................22 3 - - , rsoe5 " ear^"- con^5 STUDY INFORMATION 9th Collective Nomenclature: Octanoic acid, pentadecafluoro-, ammonium salt Synonyms/Codes: Ammonium perfluorooctanoate . . 0 C-8 Perfluorooctanoate, ammonium salt PFOA H-24921 Haskell Number: 24921 CAS Registry Number: i Composition Physical Characteristics: White solid Stability: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed. -4- Company Sanies. ^ -c STUDY INFORMATION (Continued) Substance Tested: APFO Synonyms/Codes: Ammonium perfluorooctanoate Haskell Number: 26313 CAS Registry Number:[|H Known Impurities :n|^B Physical Characteristics: Water white to slightly opaque liquid Stability: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed. Substance Tested: APFO Haskell Number: 26225 Known Impurities: Physical Characteristics: White solid Stability: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed. Study Initiated/Completed: July 29, 2004 / (see report cover page) Experimental Start/Termination: July 29, 2004 / July 30, 2004 -5- c.^^1^00"' SUMMARY The objective of this study was to evaluate whether or not the in vitro addition ofH-24921, H-26313, and H-26225 to pooled normal fasted rat serum interfered with the determination of any of the following clinical pathology parameters: triglycerides, total cholesterol, high-density lipoprotein cholesterol, or non-high-density lipoprotein cholesterol. The test substance was added to fresh phosphate buffered saline (PBS) or pooled normal rat serum. Subsequently, serial dilutions were performed. Dilutions in PBS and serum, and negative controls of PBS and serum, were analyzed for triglyceride, total cholesterol, HDL cholesterol, and non-HDL cholesterol. Neither H-24921, H-26313, nor H-26225, at concentrations up to 720 ^g/mL, interfered with the determination of concentration of triglycerides, total cholesterol, HDL cholesterol, or non-HDL cholesterol in phosphate-buffered saline or in pooled normal rat serum. ^ ^ . -rSC^01 --------^^a^ OBJECTIVE The objective of this study was to evaluate whether or not the in vitro addition ofH-24921, H-26313, orH-26225 to pooled normal fasted rat serum interfered with the determination of any of the following clinical pathology parameters: triglycerides, total cholesterol, high-density lipoprotein cholesterol, or non-high-density lipoprotein cholesterol. EXPERIMENTAL DESIGN The following experimental design was conducted for each of the 3 test substances. Negative control samples were analyzed for each part of the study. Concentration of Test Substance 1 0 . 0 ^ / Dilution 2 4 (^g/mL)________PBS_______Pooled Normal Rat Serum (PBS Negative Control) ^ (Serum Negative Control) 720.0 ^ ^ 360.0 ^ ^ 5 180.0 ^ ^ 6 90.0 ^/ ^/ 7 45.0 ^ ^ 8 22.5 ^ ^ 9 11.3 ^ ^ 10 5.6 ^/ ^/ 11 2.8 ^ ^1 12 1.4 ^ ^1 13 0.7 ^ ^ -7- , ^.noio^"TM*^ ^,,,,nvS.r,,*."-- H-24921, H-26313, and H-26225: Evaluation of the Interference of the Test Substances in the Analysis of Rat Serum Lipids______DuPont-15372 MATERIALS AND METHODS A. Test Substances Test Substances: The test substances were assigned the following Haskell Laboratory numbers: Part A: H-24921 for APFOjk------------\ Part B: H-26313 for APFO^^^^^^^ APFOjBq Part C: H-26225 for combining H-26203 andH-26204. H-26225 is made by [APFoJiffI, A: H-24921 DMSO. a solid, was mixed with B: H-26313 [APF^O^B^|^B^J|f|t a liquid, was mixed with DMSO. C: H-26203 andH-26204^ solids, were combined to form [APFO[f|p H-26225 Stock solutions for the highest concentration were made with H-26203 and H-26204 using DMSO. The stock solutionsweremixed together at a ratio of Dilutions were not analyzed to verify concentration and stability Purity/Assay: Confirmation of identity and purity of the test substance were conducted on a recent study, and were not conducted on this study.0-2) Stock Concentration: 14,400 /xg/rnL (or 14.4 mg/mL) in volumes of approximately ImL Vehicle: dimethylsulfoxide (DMSO) Storage Conditions: The test substances were stored at normal room temperature and humidity prior to preparation of the solutions. B. Phosphate Buffered Saline (PBS) Manufacturer: Fluka BioChemika Expiration Date: April 2009 -8- eo^-^03-.^^F^' H-24921, H-26313, and H-26225: Evaluation of the Interference of the Test Substances in the Analysis of Rat Serum Lipids_______DuPont-15372 Lot Number: Physical State: clear, colorless liquid Storage Conditions: normal room temperature and humidity Known Contaminants: none C. Experimental Procedures Animal Care and Housing: Stock male Crl:CD(SD)IGSBR rats previously obtained from Charles River Laboratories, me were used in this study. The Crl:CD(SD)IGSBR male rat was selected because it was used in a previous study with these test substances. All rats were housed in stainless steel, wire-mesh cages suspended above cage boards. Animal rooms were maintained at a temperature of 22 3C and a relative humidity of 50 20%. Animal rooms were artificially illuminated (fluorescent light) on an approximate 12-hour light/dark cycle. All rats were provided tap water ad libitum. All rats were fed PMI Nutrition International, LLC Certified Rodent LabDiet 5002 except when fasted. Rats were fasted overnight prior to sample collection. As specified in the Haskell Laboratory animal health and environmental monitoring program, the following procedures are performed periodically to ensure that contaminant levels are below those that would be expected to impact the scientific integrity of the study: Water samples are analyzed for total bacterial counts, and the presence of conforms, lead, and other contaminants. Samples from freshly washed cages and cage racks are analyzed to ensure adequate sanitation by the cagewashers. Certified animal feed is used, guaranteed by the manufacturer to meet specified nutritional requirements and not to exceed stated maximum concentrations of key contaminants, including specified heavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates. The presence of these contaminants below the maximum concentration stated by the manufacturer would not be expected to impact the integrity of the study. ------------------------------------------------^------------^n---T^S.^C"^Aw^^ CoWpa"^, The animal health and environmental monitoring program is administered by the attending laboratory animal veterinarian. Evaluation of these data did not indicate any conditions that affected the validity of the study. Blood Source and Collection Site: Descending aorta or the abdominal vena cava from healthy fasted stock Crl:CD(SD)IGSBR rats approximately 8 weeks of age or older. Blood was collected while rats were under carbon dioxide anesthesia. After blood collection, rats were euthanized and discarded. Blood Handling: Approximately 6-8 mL of whole blood was collected from each rat and placed into commercially available serum separator collection tubes. Blood was processed to serum after centrifugation at 2500 rpm for 15 minutes and pooled. PBS Negative Control: PBS without test substance was tested as the PBS negative control. Serum Negative Control: Rat serum (pooled) without test substance was used as the serum negative control. Addition of Test Substances to PBS or Serum: For each part of the study, the test substance was added to fresh PBS or serum as follows: test substance at 14,400 ^ig/mL was diluted 1:2 in both PBS and serum (concentrations of 7200 /xg/mL). These working solutions were diluted using 1:10 dilutions to achieve concentrations of 720 jug/mL in PBS or serum. Subsequently, serial dilutions were performed according to the Experimental Design. The test samples in PBS and in serum were prepared at approximately the same time. The test samples in PBS and in serum were gently mixed prior to incubation at room temperature. Incubation, Processing, and Analysis: Test samples in PBS and serum, and negative controls were incubated at ambient temperature for approximately 10 minutes. Immediately after incubation, the samples were frozen at approximately -80C in plastic tubes until the analysis was run (at least overnight, but not more than 3 days). Prior to analysis, the samples were thawed, placed on the Olympus AU 640 clinical chemistry analyzer and analyzed in triplicate (one tube analyzed 3 times) by standard procedures for the following parameters; ....c^"^061 10- A'4 53^'" po^ "------ Cofl*?^; H-24921, H-26313, and H-26225: Evaluation of the Interference of the Test Substances in the Analysis of Rat Serum Lipids_______DuPont-15372 Triglyceride Method: Enzymatic (lipases, kinase, oxidase, and peroxidase), with colorimetric detection (Olympus Diagnostics, CAT # OSR6116) Total cholesterol Method: enzymatic (esterase and oxidase), with colorimetric detection (Olympus Diagnostics, CAT # OSR6133) High-density lipoprotein cholesterol (HDL) Method: Accelerator Selective Detergent methodology, with colorimetric detection (Equal Diagnostics, CAT #6121) Non-high-density lipoprotein cholesterol (non-HDL) Method: Calculated Calculations: Mean values were calculated for the clinical chemistry parameters for all control and test samples. Calculation of interference at each concentration of test substance was not conducted, because there was no interference detected. - complysanu^' .Doe^co^ RESULTS AND DISCUSSION A. Clinical Chemistry Analyses (Tables 1-6, Appendix A) The values for the measured lipid concentrations did not change despite a thousand-fold change in test substance concentration. Therefore, the test substances did not have any effect on the measurement oftriglycerides, total cholesterol, HDL cholesterol, and non-HDL cholesterol in pooled normal rat serum or in phosphate buffered saline. CONCLUSIONS Neither H-24921, H-26313, nor H-26225, at concentrations up to 720 /xg/mL, interfered with the determination of concentration oftriglycerides, total cholesterol, HDL cholesterol, or non-HDL cholesterol in phosphate-buffered saline or in pooled control rat serum. RECORDS AND SAMPLE STORAGE Specimens (if applicable), raw data, and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware. REFERENCES 1. DuPont Haskell Laboratory unpublished data < 2. DuPont Haskell Laboratory unpublished data .liu>.n'"TSCACBl -12- Con^a*^00"- H-24921, H-26313, and H-26225: Evaluation of the Interference of the Test Substances in the Analysis of Rat Serum Lipids ____DuPont-15372 TABLES ~ T - A ________________n_o_ss_"_^1_"'.^nTSC^l CoW^P3S^a"^66 TABLES ABBREVIATIONS: EXPLANATORY NOTES PBS - CHOL TRIG HDL non-HDL - phosphate buffered saline cholesterol triglycerides high-density lipoprotein cholesterol non-high-density lipoprotein cholesterol ^ ^ C03-' -14- co^-5--3'"^ H-24921, H-26313, and H-26225: Evaluation of the Interference of the Test Substances in the Analysis of Rat Serum Lipids TABLE 1 SUMMARY OF CLINICAL CHEMISTRY PARAMETERS FOR SERIAL DIUTIONS OF H-2492 SERIAL DILUTIONS NEGATIVE (jLtg/mL) CONTROL" 720 360 180 90 45 22.5 11.3 5.6 2.8 1 CHOL (mg/dL) TRIG (mg/dL) HDL (mg/dL) non-HDL (mg/dL) Data arranged as: 0 0.00 0000000000 0 0.00 0000000000 0 0.00 0000000000 0 00.00000000 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0 Mean Standard deviation -15- Oompa1^ San.tee H-24921, H-26313, and H-26225: Evaluation of the Interference of the Test Substances in the Analysis of Rat Serum Lipids TABLE 2 SUMMARY OF CLINICAL CHEMISTRY PARAMETERS FOR SERIAL DIUTIONS OF H-24921 SERIAL DILUTIONS NEGATIVE7_2_0___3_60___1_8_0___9_0 ___4_5_(^2g2/.5mL1)_1._3 __5_._6 ___2._8___1 ____________CONTROL CHOL(mg/dL) 54 0.00 51 0.58 53 0.58 53 0.00 54 0.00 54 0.58 55 2.00 57 3.06 55 54 1.00 0.00 0 TRIG(mg/dL) 48 0.58 46 48 49 49 49 50 49 49 49 0.58 0.58 0.58 0.00 0.00 1.53 0.58 1.00 0.00 0 HDL(mg/dL) 23 0.58 21 22 23 23 23 24 23 23 23 0.00 0.00 0.58 0.00 0.00 1.53 0.58 0.58 0.58 0 non-HDL (mg/dL) 31 0.58 30 31 30 31 31 31 33 32 31 0.58 0.58 0.58 0.00 0.58 0.58 3.21 0.58 0.58 0 Data arranged as: Mean Standard deviation H-24921, H-26313, and H-26225: Evaluation of the Interference of the Test Substances in the Analysis of Rat Serum Lipids TABLES SUMMARY OF CLINICAL CHEMISTRY PARAMETERS FOR SERIAL DIUTIONS OF H-2631 SERIAL DILUTIONS NEGATIVE (^g/mL) CONTROL' 720 360 180 90 45 22.5 11.3 5.6 2.8 1 CHOL (mg/dL) TRIG (mg/dL) HDL (mg/dL) non-HDL (mg/dL) Data arranged as: 0 0.00 0000000000 0 0.00 0000000000 0 0.00 0000000000 0 0000000000 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0 Mean Standard deviation 17- ^^cdpo 1 H-24921, H-26313, and H-26225: Evaluation of the Interference of the Test Substances in the Analysis of Rat Serum Lipids TABLE 4 SUMMARY OF CLINICAL CHEMISTRY PARAMETERS FOR SERIAL DIUTIONS OF H-26313 I SERIAL DILUTIONS NEGATIVE_72_0___3_6_0 ___18_0___9_0____45_(At2g2./5mL1)1_.3___5_.6____2._8 ___1_ ____________CONTROL CHOL(mg/dL) 54 0.00 52 53 54 54 55 55 55 56 55 5 0.58 0.00 0.58 0.58 1.53 0.58 0.58 1.15 0.00 0. TRIG(mg/dL) 49 0.58 47 48 48 49 49 49 49 49 49 4 0.58 0.00 0.00 0.58 1.00 1.73 0.00 0.58 0.58 0. HDL(mg/dL) 23 0.58 21 22 23 23 23 24 23 23 23 2 0.00 0.00 0.00 0.00 0.58 0.58 0.58 0.58 0.58 0. non-HDL (mg/dL) 31 0.58 31 31 31 31 31 32 31 32 32 3 0.58 0.00 0.58 0.58 1.15 0.58 0.58 0.58 0.58 0. Data arranged as: Mean Standard deviation eo^^^ AOO ,VZ.0- 18- H-24921, H-26313, and H-26225: Evaluation of the Interference of the Test Substances in the Analysis of Rat Serum Lipids TABLE 5 SUMMARY OF CLINICAL CHEMISTRY PARAMETERS FOR SERIAL DIUTIONS OF H-2622 SERIAL DILUTIONS NEGATIVE^ (jug/mL) CONTROL" 720 360 180 90 45 22.5 11.3 5.6 2.8 CHOL (mg/dL) TRIG (mg/dL) HDL (mg/dL) non-HDL (mg/dL) Data arranged as: 0 0.00 0000000000 0 0.00 0000000000 0 0.00 0000000000 0 0000000000 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0 Mean Standard deviation 19- e.^^-00'  H-24921, H-26313, and H-26225: Evaluation of the Interference of the Test Substances in the Analysis of Rat Serum Lipids TABLE 6 SUMMARY OF CLINICAL CHEMISTRY PARAMETERS FOR SERIAL DIUTIONS OF H-26225 I SERIAL DILUTIONS NEGATIVE (lig/mL) CONTROL' 720 360 180 90 45 22.5 11.3 5.6 2.8 1 CHOL (mg/dL) 54 0.00 51 53 54 54 54 54 55 54 55 5 0.58 0.00 0.58 0.00 0.58 0.58 1.15 0.58 1.15 0. TRIG (mg/dL) 49 0.00 47 48 49 49 49 49 49 49 50 4 0.00 0.58 0.58 0.58 0.58 0.00 1.00 0.00 0.58 0. HDL (mg/dL) 23 0.00 21 22 23 23 23 23 23 23 23 2 0.58 0.00 0.00 0.00 0.00 0.00 0.58 0.00 0.00 0. non-HDL (mg/dL) 31 0.00 31 31 31 31 31 31 32 31 32 3 0.58 0.00 0.58 0.00 0.58 0.58 1.00 0.58 1.15 0. Data arranged as: Mean Standard deviation ^.^ww -20- Company APPENDICES -21- i Company Sanitized. Does not contain TSCA CBi APPENDIX A Clinical Chemistry Data "^^p^iSi^^1^^ CLINICAL CHEMISTRY DATA EXPLANATORY NOTES ABBREVIATIONS: CHOL TRIG - HDL non-HDL PBS - cholesterol triglycerides high-density lipoprotein cholesterol non-high-density lipoprotein cholesterol phosphate buffered saline -23- Company Sanitized. Doss net conuun . o.A CB' H-24921, H-26313, and H-26225: Evaluation of the Interference of the Test Substances in the Analysis of Rat Serum Lipids Clinical Chemistry Data for H-24921 in PBS CHOL (nig/dL) Negative Run Control 720 ^g/inL 360 tig/mL ISO iig/mL 50 iig/mL 45 ^g/mL 22.5 ^g/mL 11.3 ^g/mL 5.6 lig/mL 2.8 Iig/mL 1.4 0 0 0 0 0 0 0 10 0 0 0 0 0 TRIG (mg/dL) 230000000 000 Negative Run Control 720 iig/iaL, 360 ^ig/mL 180 ng/mL 90 iig/mL 45 iig/mL, 22.5 ^g/mL 11.3 ing/mL, 5.6 iig/mL 2.8 p.g/ivL 1.4 0 0 0 HDL (mg/dL) 12300000000000000 0000 Negative Run Control 720 ig/mL 360 (xg/mL 180 ug/mL 90 iig/mL, 45 ng/mL, 22.5 ng/mL 11.3 iig/mL, 5.6 ^g/mL 2.8 ^ig/mL 1.4 0 0 0 2130000000 000 non-HDL (mg/dL) 0 0 0 Negative Run Control 720 iig/mL, 360 fig/mL 180 iig/niL, 90 yg/inL 45 (tg/niL 22.5 ^g/mL 11.3 (ig/mL 5.6 iig/mL 2.8 4g/mL 1.4 0 120 00000000 0 000 0 0 0 0 0 0 0 .24- COtWp'^ Sa^8 OO5r'0.^^^^o^^o^ d. H-24921, H-26313, and H-26225: Evaluation of the Interference of the Test Substances in the Analysis of Rat Serum Lipids CHOL (mg/dL) Clinical Chemistry Data for H-24921 in Serum Negative Run Control 720 (ig/mL 360 iig/mL 180 (ig/mL 90 (xg/mL 45 ^g/mL 22.5 fig/mL 11.3 ;ig/mL 5.6 ^g/mL 2.8 ^g/mL 1.4 1 5^ 4 ^572 52 53 54 54 53 60 55 54 5 2 54 51 53 53 54 55 57 56 56 54 5 3 54 51 53 53 54 54 55 54 54 54 5 TRIG (mg/dL) Negative Run Control 720 (ig/mL 360 tig/mL 180 ^g/mL 90 4g/mL 45 itg/mL 22.5 yg/mL 11.3 fig/mL 5.6 ^g/mL 2.8 ig/mL 1.4 1 44Q9 47 47 49 4Q9 44Q9 4lif8t 409 A48S 409 /4 2 48 46 48 48 49 49 51 50 50 49 4 3 48 46 48 49 49 49 50 49 49 49 4 HDL (mg/dL) Negative Run control 720 iig/mL, 360 ig/mL 180 lig/mL 90 iig/inL 45 fig/mL 22.5 iig/mL, 11.3 iig/mL 5.6 Aig/mL 2.8 fig/mL 1.4 1 24 21 22 23 23 23 22 23 23 23 2 2 23 21 22 22 23 23 25 24 24 24 2 3 23 21 22 23 23 23 24 23 23 23 2 non-HDL (mg/dL) Negative Run Control 1 30 1 3a1i 31 720 yg/mL 31 3-a0n 30 360 iig/mL 31 3-a1i 30 180 ^g/mL, 30 3a1i 30 90 iig/mL, 31 3111 31 45 ^ig/mL 31 3-n2 31 22.5 iig/mL 31 -3n2 31 11.3 fig/mi, 37 3a2i 31 5.6 Hg/mL 32 3n2 31 2.8 (ig/inL 31 i3n0 31 1.4 3 3 3 -25- Company Sanitized. Does not conta H-24921, H-26313, and H-26225: Evaluation of the Interference of the Test Substances in the Analysis of Rat Serum Lipids Clinical Chemistry Data for H-26313 in PBS CHOL (mg/dL) Negative i n Run Control TRIG (mg/dL) 720 (ig/mL n 360 (ig/mL n 180 (ig/mL n 0 0 90 fig/mL 45 fig/mL 22.5 ^g/mL 0 11.3 Atg/mL 0 5.6 iig/mL 0 2.8 0(ig/mL 01.4 Negative Run Control 720 ng/mL 360 p.g/n\L 180 fig/mL 90 iig/mL 45 ^g/mL 22.5 ^g/mL 11.3 ^g/mL 5.6 (ig/mL 2.8 ^g/mL 1.4 0 0 0 HDL (mg/dL) 12300000000000000 000000 Negative Run Control 720 ^g/rnL 360 yg/mL 180 ^g/rnL 90 ^g/inL 45 ng/mL 22.5 iig/mL, 11.3 ^g/mL 5.6 ^ig/mL 2.8 (ig/mL 1.4 0 0 0 non-HDL (mg/dL) 12300000000000000 000000 Negative Run Control 720 ^g/mL 360 fig/mL 180 (ig/mL 90 tig/mi, 45 fig/mL 22.5 fig/mL 11.3 fig/mL 5.6 xg/mL 2.8 fig/mL 1.4 inrt nnn n n n n n , ^ Sani11'.^.^n39 .26- oWP^^ H-24921, H-26313, and H-26225: Evaluation of the Interference of the Test Substances in the Analysis of Rat Serum Lipids CHOL (mg/dL) Clinical Chemistry Data for H-26313 in Serum Negative Run Control 720 Iig/mL 360 iig/mL 180 ^g/mL 90 fig/iaL 45 ^ig/mL 22.5 (ig/mL 11.3 4g/mL 5.6 ^g/mL 2.8 ^g/mL 1.4 ' 1 54 51 53 54 54 55 55 55 55 55 5 2 54 52 53 53 55 56 56 54 57 55 5 3 54 52 53 54 54 53 55 55 55 55 5 TRIG (mg/dL) Negative Run Control 720 iig/mL 360 iig/mL 180 Iig/mL 90 Iig/mL 45 Iig/mL 22.5 4g/mL 11.3 iig/mL 5.6 Aig/mL 2.8 ig/mL 1.4 1 48 46 48 48 49 48 47 49 49 49 4 2 49 47 48 48 49 50 50 49 50 49 4 3 49 47 48 48 48 49 50 49 49 50 5 HDL (mg/dL) ft ft Negative Run Control 720 iig/mL 360 iig/mL, 180 fig/mL 90 iig/mL 45 fig/mi, 22.5 iig/mL 11.3 iig/mL 5.6 fig/mL 2.8 Iig/mL 1.4 1 23 '2111 1202 7213 7213 0213 23 23 T23a m23 m2 2 24 21 22 23 23 24 24 23 24 23 2 3 23 21 22 23 23 23 24 24 23 24 2 non-HDL (mg/dL) Negative Run control 720 ig/mL 360 iig/mL 180 iig/mL 90 4g/mL 45 xg/mL 22.5 (ig/mL 11.3 (ig/mL 5.6 p.g/mL 2.8 ig/mL 1.4 1 31 30 31 31 31 32 32 32 32 32 3 2 30 3111 3n1 3in0 3127 3127 3127 3 31 31 31 31 31 30 31 n31 3131 3n 2 n3 31 32 31 3 .27- Cpmpa"y- ^ ^ . ^ ^ S H-24921, H-26313, and H-26225: Evaluation of the Interference of the Test Substances in the Analysis of Rat Serum Lipids Clinical Chemistry Data for H-26225 in PBS CHOL (mg/dL) Negative Run Control 720 ug/mL 360 ng/mL 180 fig/mL 90 tig/mL 45 ^ig/mL 22.5 iig/iaL, 0 0 0 0 0 0 0 0 10 0 0 0 0 2300 00000 TRIG (mg/dL) 0 Negative Run Control 720 ig/mL 360 iig/mL 180 yg/mL 90 lig/mL 45 ng/mL 22.5 yg/mL 0 0 0 0 0 0 1230000 0 0 0 HDL (mg/dL) Negative Run Control 720 (ig/mL 360 iig/mL 180 yg/mL 90 ng/mL, 45 (ig/mL 22.5 lig/mL, non-HDL (mg/dL) 12 0 0 0 0 0 0 0 Negative 3 0 0 0 0 0 0 0 Run Control 720 yg/mL 360 ^ig/mL 180 tig/mi, 90 (ig/mL 45 (xg/mL 22.5 yg/mL 1o0o0o0o0o0o0o0 7. 11.3 fig/mL 5.6 (ig/mL 2.8 fig/mL 1.4 4 00 00 00 00 11.3 fig/mL 5.6 ng/mL 2.8 4g/mL 1.4 f 0 0 0 0 11.3 yg/mL 5.6 ^g/mL 2.8 yg/mL 1.4 0 0 0 00 00 00 11.3 ^ig/mL 5.6 Mg/mL 2.8 (ig/mL 1.4 0 0o0o0n o no ^ed,^ -28- cepp* .,, fiani H-24921, H-26313, and H-26225: Evaluation of the Interference of the Test Substances in the Analysis of Rat Serum Lipids Clinical Chemistry Data for H-26225 in Serum CHOL (mg/dL) Negative Run Control 720 yg/mL 360 fxg/mL 180 (ig/mL 90 (xg/mL 45 iig/mL 22.5 ^g/mL 11.3 (xg/mL 5.6 (xg/mL 2.8 ng/mL 1.4 1 54 51 53 53 54 54 54 56 54 54 2 54 52 53 54 54 55 54 56 54 56 3 54 51 53 54 54 54 55 54 55 54 TRIG (mg/dL) Negative Run Control 720 ng/mL 360 iig/mL 180 ng/mL 90 ng/mL 45 iig/mL 22.5 iig/mL 11-3 ig/mL 5.6 ^ig/mL 2.8 iig/mL 1.4 1 49 47 47 48 49 48 49 49 49 49 2 49 47 48 49 49 49 49 50 49 50 3 49 47 48 49 48 49 49 48 49 50 HDL (mg/dL) Negative Run Control 720 p.g/mL 360 iig/mL. 180 iig/mL, 90 tig/mL 45 4g/mL 22-5 iig/mL 11.3 iig/mL 5.6 ng/mL 2.8 p.g/mL 1.4 1 23 21 22 23 23 23 23 23 23 23 II 1 23 1211 23 20 '2)'2) 22 '2531 2331 2331 23 23 23 2 3 ">< 23 12H4 '2)'3>. 2331 23 23 23 non-HDL (mg/dL) Negative Run Control 720 iig/mL 360 xg/mL 180 ig/mL 90 fig/mL 45 Aig/mL 22.5 (xg/mL 11.3 iig/mL 5.6 iig/mL, 2.8 yg/inL 1. i 1311 3a0n 1311 3"a0n 3'311 . "3n1 3n 1 3a3'a 3a1i 31 "a 1 31 31 31 31 31 32 31 31 31 31 31 31 31 32 32 31 33 31 32 31 .29. Company Sanifesd. D