Document ZJNmrmK3knKORX9aaG7wJeO5O

attachment IV MRH) REPORT Polychlorina ed Dibenzo-p-Dioxins (PCDDs) and Polylchlorinated Dibenzofurans (PCDFs) Ar alysis of Chlorinated PVC Samples For The BF Goodrich Company Technical Center Moore and Walker Road P.O. Box 122 Avon Lake, OH 44012 Attn: Dr. John Nikora MRI Project No. 6415-A December 17, 1991 SPl-01397 MIDWEST RESEARCH INSTITUTE ` 25 Volker Boulevard, Kansas City, MO 64110-2299 (816) 753-7600 PREFACE This report provides the boiychlorinated dibenzo-p-dioxins (PCODs) and polychlorinated dibenzofurans (PCDFs) results from the analysis of five chlorinated PVC samples. The results for corresponding quality control samples including a laboratory method blank and duplicate matrix spikes are also presented. The samples were prepa d for analysis by Mr. Mark Clapp under the direction of Ms. Kathy Boggess, ai the HRGC/HRMS analyses were performed by Mr. Mark Horrigan. Ms. Boggess performed the data reduction and prepared this report. MIDWEST RESEARCH INSTITUTE Kathly E. IBogaess Chemist John S. Stanley, Ph.D. Head Analytical Chemistry Section Chemical Sciences Departrr ent UR)-A'A641S Sp|.0l398 CONTENTS Preface Tables 1. 2. 3. 4. Introduction Sample Reseipt Experimental Approach................ Parti le size reduction .... SolvA nt compatibility studies Sami )le preparation............ HRG 7HRMS analysis .... Data reduction..................... Results ii iv 1 MW-ANAMIS SPI-01399 iii LIST OF TABLES Number 1 Page 1 Internal quantitation standard spiking solution ................................... 8 2 Native standard (spiking solution......................................................... 9 3 PCDD and PCDF calibration standards............................................ 10 4 Concentrations (bg/g) of PCDDs and PCDFs in chlorinated PVC samples.........I................................................................................ 11 5 Quality control sample results........................................................... 12 6 Absolute recoveries (%) of 1aC12- internal quantitation standards ... 13 Mft^A\A64t6 Spl-01400 SECTION 1 INTRODUCTION Midwest Research Institi te (MRI) was contracted by the BF Goodrich Company to determine the levels o 2,3,7,8-substituted tetra- through octachlorinated polychlorinated dibenzo-; -dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in five chlorinate d PVC samples. The samples included bar stock, compound cubes, pipe, a id two chlorinated PVC resins. This report presents the simple receipt, experimental approach, and results of the PCDDs and PCDFs analysis of the chlorinated PVC samples and corresponding quality control samples. UFU-A\fl64lS 1 SPI-014Q1 SECTION 2 SAMPLE RECEIPT MRI received the five ch orinated PVC samples on August 27, 1991, enclosed in a cardboard shipping co itainer at ambient temperature. The samples were stored at room temperatjj re in a locked facility until sample preparation was initiated. The samples were designated as follows, as described in a letter to Kathy Boggess from Dr. John Nikora, dated August 22, 1991. Sample Code 163-90-86-1 163-90-86-2 163-90-86-3 163-90-86-4 163-90-86-5 Description Bar Stock (grey color) Compound Cubes (grey color) Chlorinated PVC Resin (white) Pipe (ivory color) Chlorinated PVC Resin (white) MR1-AVA&415 2 SPI-01402 SECTION 3 EXPERIMENTAL APPROACH This section of the repoi t describes the experimental approach used to prepare and analyze the sample for PCDDs and PCDFs. The analytical procedures used for sample prepar^ ion included particle size reduction of the bar stock and pipe samples. Solvent Compatibility studies were conducted to determine the most appropriate solven for extracting the PCDDs and PCDFs from the various matrices. Hexane was chosen as he most appropriate solvent and the five chlorinated PVC samples were Soxljliet-extracted with hexane. The subsequent extract cleanup procedures and high resolution gas chromatography/high resolution mass spectrometry (HRCjiC/HRMS) analysis procedures were modifications of EPA Method 8290. PARTICLE SIZE REDUCTION Particle size reduction of the bar stock (163-90-86-1) and pipe (163-90-82-4) samples was necessary before the samples were extracted. These samples were received in three s ctions with lengths from 3 to 4 in. The resin samples (163-90-86-3 and 163-90-86-5) were a powder consistency and required no further size reduction pric r to their extraction. The particle sizes of the compound cubes (163-9C -86-2) were approximately 3 mm x 3 mm x 3 mm, and further particle size reduc tion was not necessary. The bar stock and pipe samples were reduced on a lathe and shaved particles were collected in a plastic bag. The metal parts of the lathe were precleaned with hexane before conta A with the samples. The approximate size of the shaved particles was 1 m m x 5 mm. SOLVENT COMPATIBIL TY STUDIES Before samples were prepared for PCDDs and PCDFs analyses, solvent compatibility studies were conducted. The objective of these studies was to identify an extraction soK ent that would accomplish a slight swelling of the MR1/WW415 SPl-01403 material without dissolving the material in the sample extract. Ideally, a solvent that met this objective wi|)uld accomplish a more exhaustive extraction than if only the surface areas o the various materials were extracted. At ambient temperatures methylene chloride and toluene appeared to be appropriate extraction so vents. However, initial attempts to extract the five chlorinated PVC samples with a mixture of toluene and methylene chloride proved unsuccessful. Th 3 resins were partially dissolved by the solvent, and attempts to solvent-exch* nge the extracts to hoxane for extract cleanup resulted in precipitation of a white solid mass. This observation was attributed to the presence of methylene chloride which was used to promote swelling of the materials. Subsequent attempts to extract the resin samples with toluene and with hexane/methylene ct loride mixtures were also unsuccessful. The resin material fused into a solid mass in the extraction thimble. The first steps of the cleajiup procedures, including partitioning with concentrated sulfuric acid and concentrkted base solutions, did not remove the precipitated material from the sample jxtracts. Extraction of the samples vith hexane was then evaluated and no problems were encountered with the matrj; MRI's plans to extract the samples with hexane were discussed with Dr. John Nikora on October 24,1991. Dr. Nikora suggested an evaluation of a mixture of isopropyl alcohol and hexane. The swelling potential of a hexane and sopropyl alcohol mixture was evaluated with a cube of sample 163-90-86-2 and np swelling was observed. Because the hexane/isopropyl mixture sppeared to have no advantages over hexane, the samples were prepared foi analysis using hexane as the extraction solvent. SAMPLE PREPARATION Sample aliquots (10 g weighed to the nearest 0.0001 g) of the bar stock and pipe- shaved particles, the compound cubes, and the resin samples were mixed with 10 g quartz sand and ransferred to Soxhlet extraction thimbles. The samples were spiked with < in internal quantitation standard (IQS) spiking solution containing 15 13C12-labeled PCDDs and PCDFs at the concentrations shown in Table 1. For matrix spike samples, duplicate aliquots of resin sample 163-90-86-3 were prepared and spiked with native 2,3,7,8-substituted PCDDs and PCDFs at the concentrations shown in Table 2 in addition to the IQS spiking solution. The samples were Soxhlet-extracted for 24 hr with hexane. The hexane extracts were concentrated, and ma rix interferences were removed by partitioning against 20% (w/v) aqueous K0H and concentrated sulfuric add followed by SPI-01404 elution through a series of chromatography columns including acid/neutral silica gel, neutral alumina, and Carbopack C/Celite. After the final cleanup, each extract was concentrated under prepurified nitrogen to 100 pi, and 10 pi of a recovery standard (RS) was added that contained 13C12-1,2,3,4-TCDD am 1,2,3,7,8,9-HxCDD at concentrations of 10 pg/pl in tridecane. The evaporation was continued until a final volume of 10 pJ was reached. The extracts were transferred to refrigerated storage until ready for HRGC/HRMS analysis. Matrix interferences were observed during the preliminary analysis of the bar stock sample and additional cleanup was necessary. The sample extract was put through a second Cprbopack C/Celite column cleanup for reanalysis by HRGC/HRMS. HRGC/HRMS ANALYSE The sample extracts wen> analyzed using a 60-m DB-5 fused silica chromatography column and VG70 250S HRMS with mass resolution > 10,000. The day that samples were analyzed began with mass calibration of the mass spectrometer followed by the analysis of a window-defining mix which was used to set appropriate retention times for the PCDD and PCDF analytes and to calculate the separation or the 2,3,7,8-TCDD isomer from other closely eluting TCDD isomers. The 2,3,4,8 isomer was resolved from other TCDD isomers with a valley of < 25%. The initial calibration of th< i instrument consisted of a series of seven standards over the concentration ranges shown in Table 3. The criterion for an acceptable calibration curve was a rel, itive standard deviation of < 20%. The criterion for continuing daily calibration was that the daily response factor (RF) must be within 20% of the mean from the initial calibration curve. The initial calibration curve and continuing calibration qriteria were met. After the analysis of the dai y calibration standard, a tridecane solvent blank was analyzed to ensure a clean system. The chlorinated PVC samples and quality control samples were then i nalyzed followed by an end-of-the-day calibration standard to ensure instrume nt stability. DATA REDUCTION The data reduction procedures for the analysis of the chlorinated PVC samples included qualitative criteria far identification of a peak as a 2,3,7,8-substituted PCDD or PCDF isomer and quantitation procedures for peaks positively MR4-AVR6415 5 SP1-01405 identified. The quantitation ions, theoretical ion abundance ratio criteria, and calculation formulas are specified in EPA Method 8290. An automatic data reduction program was used to calculate the responses of analytes in the appropriat) mass windows with ion abundance ratios within 15% of the theoretical ratios. (detected peaks were also required to be within relative retention time windows established from the analysis of the calibration standards. The retention times of the native 2,3,7,8-substituted PCDD or PCDF analytes were required to be within 3 sec of the corresponding "C12-2,3,7,8 substituted internal quantitation stand, irds. For peaks that passed the qualitative criteria, the computer program calculated an extract concentration, a id then sample weights and extract volumes were taken into account to arriv at a final sample concentration. For compounds not positive ly identified, a calculated detection limit (cdt) was determined based on the c rncentration of the lowest instrument calibration standard. In some cases re sponses were noted at retention times characteristic of 2,3,7,8- substituted PCD Ds or PCDFs, but the qualitative ratio criteria were not met. For these situations, a detection limit was determined based on the maximum possible concentration (MPC) for the observed peak. UAMVA641S 6 SPI-01406 SECTION 4 RESULTS The preliminary results from the analysis of the resin samples, the compound cubes, and the pipe sampl js were, discussed with Dr. John Nikora on November 12, 1991. Duri ig that discussion, the results for the bar stock sample were not available because the bar stock sample required additional cleanup. Additional cleanu 3 was performed for the bar stock sample, and the results for this sample and the other chlorinated PVC samples are summarized in Table 4. The 2,3,7,8-substtuted PCDDs and PCDFs are presented first followed by the total homolog conce itrations. Resin sample 163-099-86-3 contained higher concentrations of PC DFs than the other samples, and concentrations of PCDDs were much lower tf an the PCDFs. Quality control (QC) sample s prepared and analyzed with the chlorinated PVC samples including a laborat >ry method blank and duplicate resin matrix spikes Table 5. Background levels of 1,2,3,4,6,7,8-HpCDD and OCDD were detected ir the method blank at concentrations slightly above the calculated detection limits. The accuracy and precision of the duplicate matrix spike samples are also summarized in Table 5. Th< spike levels, concentrations in unspiked samples, and concentrations found in matrix spike samples are shown followed by the percent accuracy and relativ i percent difference precision. The accuracy of the matrix spike was determined by subtracting the amount found in the unspiked sample from the amount foui id in the spiked sample and then dividing the difference by the theoretical amount spiked. For some of the analytes, including 2,3,7,8-TCDF, 1,2,3,7,8-PeC OF, 2,3,4.7,8-PeCDF, and 1,2.3,6,7,8-HxCDF, the amounts found in the unspiki id sample were significantly higher than the amount spiked by a factor ranging frc m 3 to 30 and these results are footnoted. For the remaining analytes, the accuracy and precision results were very good. An additional quality control e ctivity included monitoring the absolute method recoveries of the 13C12-labelecl IQSs that were added to the samples before extraction. The IQS recoveries shown in Table 6 indicate very good precision for the analytical method (14% tc 27% relative standard deviation), and recoveries were generally within the Metiod 8290 suggested range of 40% to 120%. Some recoveries were slightly outsice the 40% to 120% range, and these data are footnoted in Table 6. UfU-MR4l6 7 SPI-01407 Table 1. INTERNAL QUANTITATION STANDARD SPIKING SOLUTION Compoui id Concentration* (pg/p.L) Amount spiked (total pg) ,3C12-2,3.7,8-TCD = 0.5 100 '3C12-2,3,7,8-TCD D 0.5 100 ,3C12-1,2,3,7,8-PeODF 0.5 100 13C,2-2,3,4,7,8-PeODF 0.5 100 13C12-1,2,3,7,8-Pe( )DD 0.5 100 13C12-1,2,3,4,7,8-H <CDF 0.5 100 13C12-1,2,3,6,7,8-H cCDF 0.5 100 13C12-2,3,4,6,7,8-H: :CDF 0.5 100 13C12-1,2,3,7,8,9-Hi:CDF 0.5 100 ,3C12-1,2,3,4,7,8-H> CDD 0.5 100 ,3C,2-1,2,3,6,7,8-H) CDD 0.5 100 13C12-1,2,3,4,6,7,8-HpCDF 0.5 100 ,3C12-1,2,3(4f7f8f9-HpCDF 0.5 100 13C12-1,2,3,4,6,7,8-HpCDD 0.5 100 13,c12-ocdd 1.0 200 Prepared in isoo^tane, 200 pL was added to each sample before extractor. SPI-01408 Table 2. NATIVE STANDARD SPIKING SOLUTION Compoun Concentration* (pg/pL) Amount spiked (total pg) 2,3,7,8-TCDF 0.77 31 2,3,7,8-TCDD 0.76 30 1,2,3,7,8-PeCDF 0.70 28 2,3,4,7,8-PeCDF 0.57 23 1,2,3,7,8-PeCDD 0.75 30 1,2,3,4,7,8-HxCD 1.9 76 1,2,3,6,7,8-HxCD 1.7 66 2,3,4,6,7,8-HxCD 1,2,3,7,8,9-HxCDI : 1.8 2.0 73 79 1,2,3,4,7,8-HxCDl ) 2.0 79 1,2,3,6,7,8-HxCDt ) 1.8 71 1,2,3,7,8,9-HxCDI ) 1.9 75 1,2,3,4,6,7,8-HpC )F 1.8 74 1,2,3,4,7,8,9-HpC )F 1,2,3,4,6,7,8-HpC )D 1.9 1.8 75 71 1,2,3,4,6,7,8,9-OC,DF 1,2,3,4,6,7,8,9-OC DD 3.5 3.6 140 145 * Prepared in iscnctane, 40 pL was added to method spike sample before jxtraction. URIA\A6416 SPI-01409 Tabli 3. PCDO AND PCOF CALIBRATION STANDARDS Compound Concentration (pg/pl) Native analyte* 2,3.7,8-TCDF 0 1 0.25 0.5 2.5 10 2.3,7.8-TCDD ) t 0.25 0.5 2.5 10 1,2,3,7,8-PeCDF 2.3,4.7.8-PeCDF } 1 0.25 0.5 2.5 10 ) 1 0.25 0.5 2.5 to 1,2,3.7,8-PeCDD 1 1 0.2S 0.5 2.5 10 1.2.3.4.7.8-HxCDF t ,2,3,6,7,8-HxCOF 25 ' (i 25 0.625 0.625 1.25 1.25 - 6.25 625 25 25 2,3,4,6,7,8-HxCDF t ,2,3,7,8,9-HxCOF ( 25 C 25 0.625 0.625 1.25 1.25 6.25 6.25 25 25 1,2.3.4.7,8-HxCDD t ,2,3,6,7,8-HxCOD < 25 0 25 0.625 0.625 1.25 1.25 6.25 625 25 25 1,2,3,7,8,9-HxCDD 0 25 0.625 1.25 6.25 25 1,2,3,4,6.7.8-HpCDF 0 25 0.625 1.25 6.25 25 1,2,3,4,7.8,9-HpCDF 1.2.3,4,6.7,8-HpCDD 0 25 0 25 0.625 0.625 1.25 1.25 6.25 6.25 25 25 OCDF OCOD 0 5 1.25 0. > 1.25 2.5 12.5 2.5 12.5 SO 50 Internal Quantitation Standard* "C-2.3.7.8-TCOF to "C-2.3.7.8-TCDO uC-1.2,3,7,8-PoCDF "C-2,3,4,7,8-PeCDF to to to "C-1,2,3,7,8-PCOD 10 "C-t,2.3,4,7.8-HxCOF "C-1.2.3.6.7.8-HxCDF "C-2,3,4,6,7,8-HxCDF **C-t ,2,3,7,8,9-HxCOF "C-1.2.3.4.7,8-HxCOD "C-1,2,3,6,7,8-HxCOO C-1,2,3,4,6,7,8-HpCOF 10 to to to to to to "C-1,2,3,4,7,8,9-HpCOF 10 "C-1.2.3,4.6,7.8-HpCDO 10 'C-OCOO 20 to to 10 10 to 10 10 to to to 10 to to 10 20 to 10 10 10 10 10 10 to 10 10 to 10 10 to 10 to to 10 10 to 10 10 to 10 to to 10 10 20 20 10 to to to to 10 10 10 to 10 10 10 10 10 20 Recovery Standards "C-l ,2.3,4-TCQO l*C-t,2.3,7.8,9-HxCOD to 10 10 10 to to to 10 10 to 25 25 25 25 25 62.5 62.5 62.5 62.5 625 625 62.5 625 62.5 62.5 125 125 to to 10 to to 10 10 10 to to to 10 10 to 20 to to 50 SO 50 SO 50 125 125 125 12S 125 125 125 12S 125 125 250 250 to to to to 10 to to 10 10 10 to 10 to 10 20 10 10 URl-A\ft64tS 10 f 163-90-86-4 163-90-86-3 163-90-86-2 T a b le 4. C O N C EN TR ATIO N S (PG/G) OF PCDDs AND PCDFs IN CHLO RINATED PVC SAM PLES U) *b CO c 8| 8 e i* H w oo 9 QQ zZZ is if I OZ QZ QZ 9Z o z Kco co n*" O^o> ^^^ N ^ cni, <o CM . cn co CM icfOO^CMn Ol E ^w OO. E co JQIcAj eIeee^e^ I _^^.<0<^E'Jc>4jQ<Vj<'iC4^j-<Sif-T_-<0 cm in E ?i r* 2 ^ <__ ^___ _ ^ ci cm - a> CM CO cl Q Q Z7 ~Q o O o --nn_Q_^--- --/Q-i. --Q n--Q o zzz --- o --co Q M Q CM Q o J, o Z ZQ Z Z Sample ID Method Blank a 163-90-86-1 c *<5s5> GC EE EEEE ^ ^ <C4) rr-- <tj-> ^CM QwSlcQSiqS*- ^cqtocq5 Ol__CM t-___ r- CO ^ J. J. -- o N n OO OQQa - \V SSI ^io,c5 zz zzzz zz J0wO3 E H.EEEfEEEEEE E E E in Scm 5cSo w*CM- Pc o*,,-. n,,N C^M. 0*<1 iflCMuiwoogios; CMCMNNWnCIcO jfJgcgo ^OcoNcCnMoCJOSS I o S' d ^ wwQ wQ Q Q Q Q O Q Q o O y O222 zzzzzz z z2 a z go a a zzzz 8 Ec03 CO CM r- CM O Art * ^ ^ S *- w co U) j Q 2 CM 00 o N O) in o oS o> o & <D CM o CM CO CO to CO O) o CO u w**--' Xz uW 00 CM r" 2 2^2 o CO CM CM o CM CM CO CO d 0) 00 o CO CO d CO od cd f EEEEEEEEEEEEE,,E l-.Sl-.aaassisasa^ss w^ ^ . - W-* * - /A * * x-QqqOooq 3 q q q q a Q ^Zzzzzzzpzzzzz z ifEE-gf f CO oo a z o z Q z O z o z a z a z -Xc <5 2 a z Z3 o Q_ 2 O o LL LL u. O o.CO o Q o.CO LL Q UOJ Oc00-. u. 0q 01 a. tCxO a oa UJ a. r0-0 Q o X X CO rm->- a o X X 00 cCn' f- N CO M. CO co co m v, CM CCMMCCMMcncs r- r- W r __,,U-U-QU-Q QQQqqqqq QQQOOOOO OOOa.o_a.XX ,, O) <omoisSsS2 U.QU.QU.Q tfeSSSSXS oluooooooo CcW5MvSCycNMwo(cCvMoyMcWw?Wcv(oyMtcMso*(yCcMvoyJNWAEw/WoSISQP-- PPQQtcp5.OCtiQ.,OO-.wX?^O^^X-OOX--OXO- a- For comparison to samples concentrations in method blank were based on alO g sample size. b- Compound not detected. Value In parenthesis is calculated detection limit (cdl) based on lowest calibration standard. c- Compound not detected. Value in parenthesis is maximum possible concentration (mpc) for a peak that did not meet the qualitative ratio criteria. i Q Table 5. QUALITY CONTROL SAMPLE RESULTS SPI-01412 aQ Woj^ {oij|U^)Winrfl^(j w o co n <\i oi oi c] in n <6 co <n O) cv cvi <6 tri cc ssls co <3 "q. 2 oO> 2c Q3 og n<0 B1 o <^ CC ^ oS.sH oSSo-r?^o5*"*j Z *22 ^Z * OHOlAIOrXOMN^1 t- N0)O)flOCOOO)flON c<ob ~s|-SS|'i S5, -i CC <<8 3 CO * 5cQ=-2g 2 8J "Co. CO o<5 S* CO ^ n o c tO 5<D2 05 *o CO "O *o pou)(0r;rs.<o5rcoc| gSggSgSfc NcbO<oO<Q7>lcD>Ofl0CuSO*-O*clnQcrN> (\J O) ^ ^ <o o ^ N^ CIs* itwo ^-o^wcvim* ciS(O.<coNcOscjOcyj ot-^NinonNoco^t-c^ro- ioOrriJ^^W^ccCovMcaoT^-^oOWcINWojrc-^C; O^_.MW. ^-O-3--<-O--O---l-WC- --Ji----CN---<-nOOVrN-C^O -_<c0 jsO a__ Jsfc cr^oTc^occqvcicoiQcocrq-'ccqdcrq^ qq'rW^qt-^m a. *0 oW cd e CO CO c Z3 o X> ceg i8 M C QCO. 3--u<0 1_ <9 <g sft go2 2_-%^- b*- s2~i8s 88|*J fr c S) c O ,, c .8=. 88 *8 o g 1 cA 5 0 5 2S 1?JC 8l8**13 8Sl|tj8]8f|S C ctcooo ^cm 2O^g CJ> jg 2 8- T" ZC) 4m3 . o Qz o a. 2 OO 88 18`BEE <-'-'r(0'_oiN. ^ 0> ^,04 *- _- CO <M 8|.*l*l Oo <^q|S^ueqlQ55 -<r r-joiri aa 2Z QQQ Z22 ffffffff 888888 '-,OOr.^N o1 rfQZnn^ZQ2QZQ7O?Q'TQ-Q-Q'-'Q'' o Q 2 CO CO *J|33 llilfi 2 CL x a. 8 18 Ugs* JS JL *s - e -e 41S . --C & eaJ &5- - S ? " -C H- w 1I 5^81o38a- S^cf| o -2 -o 2 <o <0 > ic fS' i l e|Ic| SI!2 f -stf?! fi^if *lMf E o P 3 "I a!6 j*5oc co ib 12 <Q0 CC 3* a (0 Q Ac 2 OC < o 9Q z < Sc (" CO 2| z o H< o CO <CO>2$g O<? *c3> CO <0 CE < <000 C 3 6 <g O _i oSC<O>0 CC < z CE LU <o S 8. H 9 51 Z C<O0 O n u. O CO 6C0O.O0) C"c0C* CO Co" 9 " CO UJ CoO?O) *Oc3o 0C IU S| >o O i-s LU CC cn 1U 3H o ss c CQ CO CQ < 23oo <d o -Q fC--O St3 2 iC2 a 1z3 22 (ONQOQOOONNtOOON i- i- r* W r- W N ----*-<MCMCMCM CM ^ cn I/) CM CM to >COo40>r^<00<,J CO <T) (O* o 09 40 CO O) O O) ^ CO 0 o ' (o0 O*" WO)) o NK oOl <Co) 0 O (0 O r. s r w wrr 01 ai o> *- co 0>O C ^W O) CQ CD O <0 <o <0 O r 3 ^ o < ^ 9 9 1 o(3J w WCO WT* O'fMNJ> O^ oojOfnfl tNOl'dN r-rti^-fl0fl)r-O CM O CO CO CO ^O)n(OI u0S)aOd }CNO* 0U9)0C)MO04) <J> CO CO N " 00 6 CO oi O P) <0 ffl CT r- o <D CO 0 CO O O hO (OC0) *T*- cn o*-- ^ oo CO Or- *0f*s*: Or-horOto9-worc-nONO'5O^r^;9. irflPffl **CI"*-''-^ ,,^OCOCOOMO co in w '-'9 u) <ni * C\| U) r- f*. ^ o OOOcmCMOOO ' ai rl oi nW ^ o> co to at n CONN^COMOCOU 6 o cn o> s co n w (OU)COCOCOiACO CM N* CO W0) S. <D N ' CO CM 9cv9^"0^^; ^ u) i- w 0 eo dciOT-oJoOoiN >" N O 6 o (\( 0> O) ** *" 0O *" ^ O) Ol ^ 0 CO O) <D _ a. u. Uu u_ Ua. o Qa o o o 0) a a o <D Ol 9 9 O CL a o x X 03 a o x I CO Q o O o X O* H 09 H 03 ao n- co r- CN'* N<0 CO r- fN. CO ^ CO CO CO CO CO CO CM CO CM CM CM CM oooCM CM CM ooo o CM *oo co co CO CO co CO CO CO CO _ LL. UL Q 9000 o >< X I go X0 I co _ Q O N ffl NO N tO N <0 o SSSSo CM CM CM CM CM 00000 CO CO CO co co 13 > sa 8 CC O CO C Ca 1! 2 -O a> o> y o so 2O) -- *r (SI o > =3 n M u 1-si S -S 2S 35 s> 5 c OAA >>0Q a -o OC >6 8-d SOU) CCS CC AA 6 SPI-01413 fciUOi October 4, 1991 Chuck Bush SUBJECT: VCM CANCER RISK ASSESSMENT -ERQEQSAL The proposal from Peter Vcytex (Clement International) is exactly the direction we need to go. However, the elements of this proposal needs to be reordered and supplemented as follows: 1. Review the pharmacoki netic data on vcm. .2 Review the animal dat a on VCM which indicates that the young (fetus) is more sensitive than adults Determine whether a Plj-PX model can be developed for VCM based on existing data. recommend what additi anal pharmacokinetic studies are needed (if appropriate). 5. Develop risk assessment based ^on PB-PK mode>/ 6. Review epidemiology dita, compare it"with animal data. 7. Assess the feasibility, and if possible, develop a risk assessment based on a combination of human and animal data. I think this group can do fhe job. The only question I would ask them is whether they feo 1 that they will need to identify additional resources (add snother person) to cover the additional items. Furthermore, I don t know whether the EH&S Committee has addressed the value of gett ;.ng a competitive bid. However, I don't feel strongly that one is r eeded. Bob Hinderer 0924-6/mn \ "T SPI-01414 OCT 8199);