Document zMvw7GR9BY12xZkGgYM9xz8z

AR 26 _ O&T! PFOS Repeat Dose - 000101 INCORPORATED 200 Girard Street, Suite 200, Gaithersburg, MD 20877 301-921-0168 Fax:301-977-0433 Client: 3M MEDICAL DEPARTMENT 3M CENTER BUILDING 220-2E-02 ST. PAUL, MN 55133-3220 (651) 575-3161 Attention: ANDREW SEACAT Date Collected: 02/20/1999-02/26/200C Date Received: 04/18/2000 Date Reported: 05/02/2000 Client No. 1492 Study: 6 MONTH PFOS STUDY Species: CYNOMOLGUS Accession Spec. No. ID A 0098138 I05508M A 0098139 I05519M A 0098140 I05527M A 0098141 I05530F A 0098142 I05531F A 0098143 I05535F A 0098144 I05544F Mean S.D. Group 1 Gp Sex Age 1 1 1 1 1 1 1 TSH, SI UIU/ML 0.45 0.32 0.42 0.43 0.19 0.59 0.80 .457 .195 CHOLEST MG/DL 105 145 143 124 116 171 99 129 25.4 HDL-DIR MG/DL 50 72 44 56 47 42 32 49 12.6 LDL-DIR MG/DL 53 73 97 68 66 128 65 78.6 25.6 VLDL MG/DL 2 0 2 0 3 1 2 1.4 1.1 A 0098145 I05514M A 0098146 I05515M A 0098147 I05516M A 0098148 105521M A 0098149 I05541F A 0098150 I05547F A 0098151 I05550F Mean S.D. Group 2 2 2 2 2 2 2 2 0.64 0.69 0.49 0.41 0.51 0.43 0.34 .501 .125 115 80 73 67 92 84 82 84.7 15.6 43 37 32 34 48 36 25 36.4 7.5 72 41 36 33 40 48 51 45.9 13.1 0 2 5 0 4 0 6 2.4 2.6 Reference Range .2 - 2.6 101 - 240 Page l + 0- 0 0 0 0- 0 000102 INCORPORATED 200 Girard Street, Suite 200, Gaithersburg, MD 20877 301-921-0168 Fax:301-977-0433 Client: 3M MEDICAL DEPARTMENT 3M CENTER BUILDING 220-2E-02 ST. PAUL, MN 55133-3220 (651) 575-3161 Attention: ANDREW SEACAT Date Collected: 02/20/1999-02/26/200C Date Received: 04/18/2000 Date Reported: 05/02/2000 Client No. 1492 Study: 6 MONTH PFOS STUDY Species: CYNOMOLGUS Accession Sgec. No. A 0098152 I05510M A 0098153 I05518M A 0098154 I05524M A 0098155 I05528M A 0098156 I05532F A 0098157 I05538F A 0098158 I05545F A 0098159 I05548F Mean S.D. Group 3 Gp Sex Age 3 3 3 3 3 3 3 3 TSH, SI UIU/ML 0.83 0.83 0.54 0.60 0.76 0.46 0.34 0.32 .585 .207 CHOLEST MG/DL 115 98 110 116 91 88 74 74 95.8 17 HDL-DIR MG/DL 48 44 37 31 23 32 24 31 33.8 8.8 LDL-DIR MG/DL 66 54 72 76 68 53 50 42 60.1 12 VLDL MG/DL 1 0 1 9 0 3 0 1 1.9 3 A 0098160 I05506M A 0098161 I05507M A 0098162 I05512M A 0098163 I05534F A 0098164 I05536F A 0098165 I05540F A 0098166 I05551F Mean S.D. Group 4 4 4 4 4 4 4 4 0.73 0.72 1.15 1.25 1.75 0.89 0.86 1.05 .368 56 25 27 59 53 57 61 48.3 15.4 14 8 11 16 18 16 22 15 4.6 42 16 16 40 31 41 35 31.6 11.3 0 1 0 3 4 0 4 1.7 1.9 Reference Range .2 - 101 - 0 - 0- 0- 2.6 240 0 0 0 Page 2 + 000103 INCORPORATED 200 Girard Street, Suite 200, Gaithersburg, MD 20877 301 -921 -0168 Fax: 301 -977-0433 Client: 3M MEDICAL DEPARTMENT 3M CENTER BUILDING 220-2E-02 ST. PAUL, MN 55133-3220 (651) 575-3161 Attention: ANDREW SEACAT Date Collected: 02/20/1999--02/26/200( Date Received: 04/18/2000 Date Reported: 05/02/2000 Client No. 1492 Study: 6 MONTH PFOS STUDY Species: CYNOMOLGUS Accession Spec. No. ID Gp Sex Age A 0098167 I05533F A 0098168 I05542F A 0098169 I05511M A 0098170 I05522M 4R 4R 4R 4R Mean S.D. r-oup 4 WK52 RECOVERY TSH, SI UIU/ML 0.85 0.60 0.65 0.93 .758 .158 CHOLEST MG/DL 117 124 89 106 109 15.3 HDL-DIR MG/DL 51 50 45 37 45.8 6.4 LDL-DIR MG/DL 61 46 44 68 54.8 11.6 VLDL MG/DL 5 28 0 1 8.5 13.2 Reference Range .2 - 101 - 0 - 0- 0- 2.6 240 0 0 0 Approved --- - zf--------- oat ..< U ^ L Page 3 of 3 000104 Andrew M. Seacat, Ph.D. 3M Medical Dept. 3M Center, Building 220-2E-02 St. Paul, MN 55133-3220 Phone: (6 1 2 ) 575-3161 FAX: (6 1 2 )7 3 3 -1 7 7 3 e-mail: amseacatl@mmm.com 3/6/2000 Peter J. Thomford, Ph.D. Study Director, Toxicology Covance Laboratories Inc. 3301 Kinsman Blvd. Madison WI 53704 Phone: 608-241-7202 Fax: 608-242-2736 Re: 26-week capsule toxicity study with perfluorooctane sulfonic acid potassium salt (PFOS; T -6295) in Cynomolgus Monkeys. Covance Study Number: 6329-223, Peter, 3M requests information from the study records of 6329-223 for the methods used and the dates of specific hormone determinations conducted by Ani Lytics Incorporated, Gaithersburg, MD. Specifically, we need more information on the methods of determination for T3, T4, free T3, free T4 and TSH. An explanation of the zero values for TSH is requested. What is the limit of detection (LOD) and limit of quantitation (LOQ) for TSH in the method used, and should the zero values be replaced with <LOD or < LOQ. Furthermore, we need to understand the high T3 values reported for the day 37 samples (reference, appendix 6 of Draft interim Report from Covance), for which the T3 values were high in all dose groups. The date that the tests were performed on each sample is also requested. Ani Lytics is being copied on this request in order to expedite the transfer of information. Sincerely, Andrew M. Seacat Ph.D. Study Monitor cc: Dr. Saroj Das Ani Lytics 200 Girard Street, Suite 200 Gaithersburg, Maryland 20877 Telephone No.: 301-921-0168 Facsimile No.: 301-977-0433 000105 INCORPORATED 200 Girard Street, Suite 200, Gaithersburg, MD 20877 301-921-0168 800-237-2815 05 April 2000 Andrew Seacat, Ph.D. 3M Medical Department 3M Center, Building 220-2E-02 St. Paul, MN 55133-3220 Dear Dr. Seacat, REF: Fax dated 3/20/00 TSH analysis in Cynos I want to bring to your attention that primate TSH analysis at Ani Lytics, Inc. has always been performed using anti-human TSH polyclonal antibody. During our telephone conversation I told you that as of 1998 all human TSH testing is being done using monoclonal antibody, therefore these test reagents can not be used in primates. For this reason we initiated an inhouse TSH assay procedure utilizing polyclonal antibody. The reagent source and other information on each of the assays mentioned in your letter along with result reporting policy are inclosed. As I indicated to you, primates in general have quite low TSH levels. Therefore it will be necessary to increase the specimen volume in the TSH test system. At least 0.5ml but preferably 1.0ml serum will be good. Sincerely, 0^ ai u j xv. u a o , M.S., Ph.D. Director cc: Peter J. Thomford, Ph.D. Study Director, Toxicology Covance Laboratories, Inc. 3301 Kinsman Blvd. Madison, WI 53704 000106 INCORPORATED 200 Girard Street, Suite 200, Gaithersburg, MD 20877 301-921-0168 800-237-2815 RESULT REPORTING POLICY Linear regression curve correlation coefficient of 0.99 or greater accepted. Results observed over the highest calibrator concentration repeated on appropriate dilution. Lowest limit of quantitation is the lowest calibrator concentration. Values below this concentration are computer generated based on the standard curve. These values are reported. In some assays the exact calibration range is kit lot number specific. A zero value indicates that the counts bound for the sample/s were same as or close to or > zero standard counts. 000107 INCORPORATED 200 Girard Street, Suite 200, Gaithersburg, MD 20877 301-921-0168 800-237-2815 ANALYTE : NonHuman Primate Thyroid Stimulating Hormone (TSH) PROCEDURE: Double Antibody RIA Inhouse Procedure REAGENTS: Human TSH standard (Ref WHO standard 68/38) Sigma-Aldrich Inc. Cat. #T-4651 Rabbit-anti human TSH (polyclonal) Sigma-Aldrich Inc. Cat. #T-4651 Radiolabeled HTSH Covance Laboratories, Inc., Vienna, VA CALIBRATION RANGE: 0.4 to 50 mlu/ml. (Low end sensitivity is dependent upon the integrity of the iodinated hormone.) RESULTS: mlu/ml Computer generated values reported below low end sensitivity of the curve. COMMENT: Overall TSH levels in NHP are extremely low so it is difficult to know if this test offers significant clinical information. 000108 INCORPORATED 200 Girard Street, Suite 200, Gaithersburg, MD 20877 301-921-0168 800-237-2815 ANALYTE : Free T4 PROCEDURE: Coat-A-Count RIA REAGENT SOURCE: Diagnostic Products Corporation, CA. CALIBRATION RANGE: 0.1 to 10 ng/dl (kit lot # specific) RESULTS : ng/dl Computer generated values reported below the standard. 000109 INCORPORATED 200 Girard Street, Suite 200, Gaithersburg, MD 20877 301-921-0168 800-237-2815 ANALYTE : Total T4 PROCEDURE: RIA Coated Tube Assay REAGENT SOURCE: DPC, CA. CALIBRATION RANGE: 1 to 24 ug/dl RESULTS : ug/dl Computer generated values reported below 1 ug/dl. oom INCORPORATED 200 Girard Street, Suite 200, Gaithersburg, MD 20877 301-921-0168 800-237-2815 ANALYTE: Free T3 PROCEDURE: Coat-A-Count RIA REAGENT SOURCE: DPC, CA. CALIBRATION RANGE: 0.5 - 42 pg/ml (kit lot # specific) RESULTS: pg/ml computer generated values reported below the lowest standard curve calibrator concentration. 000111 INCORPORATED 200 Girard Street, Suite 200, Gaithersburg, MD 20877 301-921-0168 800-237-2815 ANALYTE: Total T3 PROCEDURE: Radioimmunoassay (RIA) Coated Tube Assay REAGENT SOURCE: Diagnostic Products Corporation (DPC), CA. CALIBRATION RANGE: 20 to 600 ng/dl RESULTS: ng/dl Computer generated values reported below 20 ng/dl 000112