Document zQ6oND8jJ5oKEXYDq1EgEzwYg

MANUFACTURING CHEMISTS ASSOCIATION 1825 CONNECTICUT AVENUE, N.W. WASHINGTON, D.C. 20009 (202) 483-6126 April 14, 1976 URL 1719, TO: Vinyl Chloride Technical Panel SUBJECT: Protocol for Birth Defect Study by Center for Disease Control and Other Items Gentlemen: Enclosed are the following: 1. Subject protocol entitled "Proposed Study of Increased Rates of Central Nervous System Defects in Kanawha Co. West Virginia" and cover letter of March 25 from Dr. Flynt. In compliance with his request, names of participating hospitals have been blocked out. In a telecon with Dr. Flynt on March 25, I learned the field work was nearly complete and a report was targeted for about one month from then. Their study includes fifty cases (interviews) and a like number of controls. Key aspects of the program are to try to locate residence at conception and occupational history of both parents. 2. Summary of article "Pharmacodynamics and Uptake of Vinyl Chloride Monomer Administered by Various Routes to Rats" by J. R,, Withey in Journal of Toxicology and Environmental Health, 1:381-394, 1976. 3. First page, containing summary, of V. J. Feron et al. article "Observations on the Oral Administration and Toxicity of Vinyl Chloride in Rats", in Food and Cosmetic Toxicology. Volume 13, pages 633-638. 4. "Morbidity and Mortality" article of February 28, 1976 citing arsenic and thorium dioxide in addition to vinyl chloride as suspect causative agents of angiosarcoma of the liver in Wisconsin cases. 5. Letter of April 1, 1976 from Mr. G. L. McCowin, Assis tant to the Director, Division of Food and Color Additives of FDA indicating that so far they have been unable to detect any migration of vinyl chloride at a sensitivity of 1 ppb, from polyvinyl chloride articles. 6. Citations of vinyl chloride research (pages 130, 147; Appendix II, pages V, VI) from Information Bulletin on the Survey of Chemicals Being Tested for Carcinogenicity, No. 6, March 1976, by the International Agency for Research on Cancer. 7. Dr. Torkelson's letter of April 5 to Dr. Warren R. Muir, without attachments, regarding the Tabershaw-Cooper Associates epidemiology study. Information 1. The last paragraph of my March 17 letter to the Panel reported on a transplacental study on vinyl chloride at Midwest Research Institute, (MRI). I have since learned this particular study was with vinylidene chloride (VDC), not vinyl chloride. MRI is working with both monomers. 2. NIOSH has published a Recommended Standard for Occupational Exposure to Vinyl Chloride, PB-246-691/OGA. Copies are available at $3.50 each from: Office of Technical Publications National Institute for Occupational Safety and Health Post Office Building Cincinnati, Ohio 45202 (513/684-2723) Please include a self-addressed mail ing label to assist in answering your request. Sincerely, MF:ec Enclosure Milton Freifeld^ >"- Project Manager Vinyl Chloride Research DEPARTMENT OT lEALTH. EDUCATION. AND WELFARE f-'.JCLIC HEALTH TCPVIf.L ' O W DICTATE CONTROL March 25, 1976 Mr. Milton Freifeld Manufacturer's Chemist Association 1825 Connecticut Avenue Washington, D. C. 20009 Dear Mr. Freifeld: Enclosed is a copy of the protocol for the study presently underway in Charleston, West Virginia. I have made a few marginal notes where changes were made. The main change was the decision from the outset to interview cases and controls (regardless of exposures among the case group). We had at one time considered searching occupational records at the plant for names of cases and controls, but discarded the idea in favor of the interviews. If you have questions about this, do not hesitate to contact me. I would like to emphasize our desire to maintain the confidentiality of hospitals that participate in the BDMP. This includes, according to our agreement with the Commission on Professional and Hospital Activities, no mention of the number of hospitals in a community which participate in BDMP. We would appreciate your cooperation in this respect. Also note that the data contained in this protocol are preliminary and were corapiLed only as background for planning of the study. Final data will be part of the finished report. Sincerely yours, C 33 &VLV Enclosure t cc: Dr. John Finklea Mr. Larry Edmonds JWFtcrs J. William Flynt, Jr., M.D. Chief, Birth Defects Branch Bureau of Epidemiology Proposed Study of Increased Rates of Central Nervous System Defects in Kanawha Co. West Virginia Introduction A recent report noted higher rates of CNS defects in Painesville, Ohio, a city with a vinyl chloride polymerization (VCP) plant. This report suggested a causal association between the PVC plant and the higher CNS rate. We conducted a follow-up investigation, including interviews of parents of cases, and found no current or past occupational exposures to vinyl chloride among parents of cases. Comparison of cases with controls suggested no differences in distances of family residence from the vinyl chloride plant. The latter finding has been questioned because cases and , controls were based on hospital births rather than resident births in the t community. The continuing concern about a causal association prompted a review of all 36 counties with VCP plants to determine those with BDMP hospitals. A C :0 r~ ^ similar determination had been done previously selecting for analysis those ^ communities with a VCP plant and most likely served by a single hospital also in the BDMP (and having a VCP plant). Painesville, Ohio, and Pottstown, Pennsylvania, were identified in this manner. Pottstown had no excess of malformations while Painesville was noticed to have a twofold Increase in * -, CNS defectsr On the second review, a total of 17 counties with VCP plants also have at least 1 BDMP hospital. Four of the 17 counties have a significantly higher number of CNS defects than expected, based on a total U.S. rate 1970-73. In two counties BDMP monitors less than 50 percent of the total reported births (Table 1). The 2 remaining counties are Lake Co., Ohio (Painesville), 2 the site of previous investigation, and Kanawha County (Charleston), West Virginia. There are 4 hospitals in Kanawha County reporting 4,476 births in 1973 (Table 2). The 2 largest hospitals are enrolled in the BDMP; 1 is located in Charleston and the other in South Charleston, the site of the VCP plant. The current BDMP data show for Kanawha County a signifi cantly higher number of CNS defects than expected (59 observed vs. 37_ expected). The expected number of cases are based on the total U.S. rates for 1970-74 (Table 3). In light of continuing concern regarding the possible teratogenicity of VC monomer; the Kanawha County setting was selected for a second inves tigation concerning the possible association of increased rates of CNS defects with parental occupation or residential exposure to the S. Charleston VCP plant. Additional background data on Kanawha County vital statistics are pro vided in the appendix. Objectives The objective of this study will be to further investigate the possible relationship of parental exposure to vinyl chloride and the increased incidence of central nervous system defects. The case-control study method will' be .used to compare the frequency of maternal and paternal occupational exposure to VCP. Similarly, residential exposure will be examined by comparing distances of parental residences at birth from the VCP plant in South Charleston. s e v H iw n 3 Methods A. Case Ascertainment All cases of Central Nervous System (ICDA NO. 740.0-743.9) defects that occurred among resident live births and fetal deaths in Kanawha County between January 1, 1970 and December 31, 1974 will be identified. Two sources of case identifications will be employed: 1. Birth and fetal death certificates will be reviewed in the West Virginia Department of VitaL Statistics. 2. Records at all Kanawha County hospitals will be reviewed. This will include cases reported through the Birth Defects Monitoring Program. A consolidated list of unduplicated cases will be compiled and diag nosis verified according to hospital records. Non-residential and unverified cases will be retained for further comparative analysis, but not matched with controls. B. Selection of Controls Controls will be selected from Kanawha County resident birth certificates after all cases have been identified. Two controls will be selected for each case of CNS defects. The controls selected will be the next notched normal live birth preceding and following. The cases and controls will A be matched for maternal age (15-19, 20-24, etc.), paternal education (0-8, t 9-12, 13 over), and race. A maximum of twenty-five birth certificates will be reviewed preceding and following the case to find the two matching controls. If a preceding (following) age-education-race matched control is not found, then the first preceding (following) birth matched on race URL 17196 4 and either education or age will be chosen, education being the first choice. If there is still no-match, then the first preceding (following) birth matched only on race will be selected. Data Collection A. Birth Certificates and Fetal Death Certificates The information to be collected on case and controls from the birth certificates is contained on page 1 of the work sheet. B. Hospital Record The information to be collected on cases from hospital charts is listed on page 2 of the work sheet. Hospital records will be reviewed for controls only in cases where birth certificates information is incomplete. C. Interview Parents of cases will be interviewed in standard fashion regarding prior residences and occupations. The information to be obtained is listed on Worksheets 3-5. v .1 Parents of controls will not be interviewed unless 1 or more parents of v ,.yjr leases are found to be employed in the vinyl chloride plant or a signifi- r*' L;^ cantly greater proportion of the parents of cases live near the vinyl chloride plant. In the event that 1 or more parents of cases works at vinyl chlo'ride plant, only 1 control will be interviewed- for each matching case. The control chosen for interview will be the closest match. URL 17197 5 Data Analysis t' An analysis of matched trlpTEs will be nade using the method of Mantel and Haenszel. The possible relationship between parents* occupational exposure and CNS defects in their children will be analyzed 3 ways by dichotomizing cases and controls on employment of mother, father, and either parent in a vinyl chloride plant. Only current employment will be used for controls unless significance is attained. Then past employment data will be otained from the controls in the same manner as for acses and the resulting data re analyzed. ^ r The effect of distance of residence from the vinyl chloride plant will be ' analyzed by dichotomizing on distance in increments of 1 mile in the range 1-10 miles. C -o a URL 19649 i Oklahoma Co., Oklahoma New Castle Co. Delaware Lake Co. Ohio Kanawha Co. West Virginia Table I Counties with Significant Increases in CNS Defects 1970-73 and Reported Births in 1973 fl CNS Defects in BDMP obs. exp. tfBirths In AHA* 68 44.9 8,718 (9 hospitals) '9 4 5,634 (3 hospitals) 31 18 1,851 (2 hospitals) 53 31 4,476 (4 hospitals) %'Monitored in BDMP 47.0 6.5 98.4 94.8 American Hospital Association Guide to the health care field (1974 edition) 66ti nan Table II Reported Hospital Births in Kanawha County, W. Virginia from AHA Guide Total birth Kanawha County Charleston. " " South Charleston 3488 148 93 757 4476 *BDMP Hospital 95% of reported hospital births are monitored by BDMP Vital Statistics Data from West Virginia Vital Statistics Reports 1974 for Kanawha County ) Total Births 3348 Hospital Births 3341 White Births (male) 1616 (female) 1471 Non-white Births (male) 126 . (female) 135 r-- Xr~I --4. --J NQCJ5 Table III Total Central Nervous System Defects - 1970-1974 Kanawha County Total U.S. Relative risk = 1.58 OBS. 43 16 59 7655 EXP.* 29.2 8.2 37.4 RATE+ 31.3 41.3 33.5 21.2 Anencephalus-Spina Bifida - 1970-1974 Charleston S. Charleston Kanawha County Total U.S. Relative risk * 1.77 OBS. 27 13 40 4604 EXP. 17.6 5.0 22.6 RATE 19.6 33.5 22.7 12.8 BDMP Births - 1970-1974 f Charleston 13,754 S. Charleston 3,877 Kanawha County 17,631 Total U.S. 3,606,848 * Expected calculated on BDMP total white U.S. rate 1970-1974 + Rates per 10,000 total births for whites APPENDIX VITAL STATISTICS, KANAWHA COUNTY, WEST VIRGINIA S. Charleston Charleston St. Albans County POPULATION Census Population, Kanawha County 1970 16,330 1971 1972 1973 71,505 14,356 229,515 230,400 230,300 226,800 1974 223,700 Kanawha County West Virginia 1970 16.3 17.3 BIRTH RATE 1971 1972 16.5 15.0 17.8 16.7 1973 14.4 15.4 1974 15.0 15.4 t eh URL 1 7202 White Male White Female TOTAL 1970 1724 1726 3450 BIRTHS, KANAWHA COUNTY 1971 1972 1805 1658 1694 1535 3499 3193 1973 1624 1436 3060 1974 1616 1471 3087 " 1 Nonwhite Male 148 116 134 120 126 Nonwhite FeriTale 137 162 107 147 135 TOTAL 285 278 241 267 261 City Charleston S. Charleston St. Albans 1970 NUMBER OF BIRTHS 1971 1972 1035 245 200 1973 972 240 218 1974 1031 227 198 1970 1971 1972 1973 1974 10-14 7 9 6 14 10 BIRTHS BY AGE OF MOTHER, KANAWHA COUNTY 15-19 20-24 25-34 35-44 45 711 1504 1309 201 3 761 1553 1274 180 723 1360 1186 156 3 743 1247 1186 136 1 671 1290 1252 124 1 Unk l C fo'O Fetal Deaths Congenital Anomaly Premature Births RESIDENT DEATHS , KANAWHA COUNTY 1970 1971 1972 59 (15.8) 60 (15.9) 53 (15.4) 25 (10.9) 25 (10.9) 20 (8.7) 12 (5.2) 3 (1.3) 8 (3.5) 1973 37 (11.1) 15 (6.5) 9 (3.9) 1974 28 (8.4) 11 (4.9) 7 (3.1) FAMILIES WITH INCOME LESS THAN POVERTY LEVEL IN 1969' BY COUNTY if Families % Of All Families Kanawha County 8020 13.0 West Virginia 81697 18.0 PHARMACODYNAMICS AND UPTAKE OF VINYL CHLORIDE MONOMER ADMINISTERED BY VARIOUS ROUTES TO RATS Jim R. Withcy Toxicology Division, Bureau of Chemical Safety (Foods), Health Protection Branch, Ottawa, Canada Finding at toast 2-3 ppm and occasionally as much as 10-20 ppm Of vinyl chloride monomer in o wide range of foodstuffs has prompted concern lor 0 possible human health hazard. 7he recognition of vinyl chloride as a carcinogen to humans in April 1974, following the discovery of angiosarcoma as the cause of death in at least 25 workers who hod been engaged in the manufacture of polyvinyl chloride, enhanced this concern with respect to ihe presence of vinyl chloride monomer in foods. To assess the hazard presented by the ora! ingestion of vinyl chloride monomer, rats that had been surgically prepared with an indwelling jugular cannula were dosed by intrugastric intubation with aqueous solutions containing up to 2.0 mqjml vinyl chloride. Time-concentration curves were obtained from sequential samples of blood. The uptake of vinyl chloride by this route was found to he extremely rapid: peak concentrations were achieved less than 10 min after administration of the dose, tliminalion from the blood compartment appeared fo he bicxponential. Studies with the same animal model in a single restraint cage that allowed a "head only " exposure fo concentrations of vinyl chloride up to 7,000 ppm in the gas phase have shown a similar rapid uptake followed by a plateau blood concentration during several hours of exposure. On removal from the vinyl chloride atmosphere, blood levels fell rapidly to barely detectable concentrations after 2 hr. The precise kinetic coefficients that describe the distribution and elimination rates of vinyl chloride from the blood com/sartment were also determined from the blood concentration data after the administration of on intravenous dose of aqueous or vegetable oil solution. INTRODUCTION Prior to the discovery of a connection between the induction of angiosarcoma in humans and the exposure to vinyl chloride monomer (VCM) in January J974 {Falk et al., 1974; Thomas et at., 1975), the U.S. Food and Drug Administration had already withdrawn their prior sanctioned use of This paper was presented in part at the 14th Annual Meeting of The Society of Toxicology, Williamsburg, Virginia, March 9-13, 197S. It is a pleasure to acknowledge the technical assistance ol Mr. Peter Collins in this work. The interest, skill, and dedication of Mr. Henry James, who surgically prepared the animals used in this study, is also appreciated. Requests for reprints should be sent to Jim R. Withcy, Toxicology Division, Bureau of Chemical Safety (Foods), Health Protection Branch, Octawa, Canada. 381 Journal of Toxicology and Environmental Health, V.361-394,1976 Copyright 1976 by Hemisphere Publishing Corporation />/ FJ \N M. pp M* A.H Pcr^umon Pro* 1*^5 PrtrTetf in Grc./ Britain , y 9 *v* -HoUluu: voor V-:;.;U;p:ondvr7Xt 1- - Ptzblik*uii Nr l Q^|r_ OBSERVATIONS ON THE ORAL ADMINISTRATION AND TOXICITY OF VINYL CHLORIDE IN RATS* V. J. Fl KOV A. J. Sf'U K. Maki.wm I. WII.[.IMS. D. van Battlm and A. P. Dt. Gki>ot Centra/ fiKfifi'fo ]or Si<rntu>ii a/ui four/ Rcscuuh iCH 0\ T\0. Vircchtu.Mi.il 4S, Zcist. 1 he \etfurLuuls {Rccand \ April 19751 Abstract Various rMssihiltties wore studied for administering tnyI chloride monomer (VCM) orally U> rats. Upon 'k-r.ijc. solutions of Y( M in mh,i-k.-.ui oil appeared to he viable with respect to their \'CM content and the fatty acid composition of the oil. In addition no oln'orncrs of vmvl chloruic or reaction products of \C M with components of the oil acre detected, Stomach imuhation of such solutions was considered an acceptable method of oral administration of Yt M to rats tn short-lerm toxicity studies. Within a period of 4 hr following ir.t.-ne.tsine mtahation of VCM in oya-hc.m oil me VCM kg hods weight). over 9J",, of t!ic VCM administered was recovered from the gases excreted imainK exhaled') bv the animals. Eructation did not appear to he involved in the excretion of VCM. VCM dissolved in soya-bean oil was administered b> guv-age to male and female rats at levels of 0 (controls), at) Mm and .MX) me kc body weight, once daily on t> days uk for a period of 13 wk. Several haenwtological. btoeliemit.il and organ weight values differed to a statistically significant degree from those of the controls, hut these UwVercr.ccv were considered to have only minor, if any. toxicological significance. A slight increase :n li'er-to-body weight ratio occurred in males and females on the highest dose let el. This increase was not accompanied bv (ivor damage, as was evident from histologieai evaimnaiio'i. cti/yine iii'ioehemistry and electron micro-cops. The no-effect level in this 90-day study was ciMi.scrv.imel> placed at ,'n mg VCM kg bodv weight. but was probably iiicher since the effects oecuinng at MX) and ytKi mg kg body weight were of doubtful toxicological significance. Indications were obtained that the (coding oi rats on diets containing polyvinyl chloride iPVCi powder with a Inch Y(. \1 content is a mote practical method for the long-term oral exposure of rai> to VCM than is stomach intubation of VCVI in ml. VCM was almost completely released from PVC powder during passage through the digestive tract. INTROOV. (TION Vinyl chloride monomer (VCM) is used m the manufacture of the resin, polyvinyl chloride ll'VCi. Industrial exposure to VCM has Iven associated with several disorder?., including acro-ustcoly.sis (Dirmun. Cook. Wliitehouse. Mneuuson Si Ditcheefc. 1971; Harris vt Adam*. I sift?; I.atige. JUhe. Stein A Vehman. 19"4-. Markowit?. McDonald. Fethiere & Kcrmer. /9?2i and non-malignant liver diseases (Kramer & Mutelder. 1972; .Marstellcr. Lelhach. Mtilier. Jultc. Lange. Rohncr & Veltman. 197.3; Suciu. Drejman & Valaskai. I9ft7t and. only recertify, also with angiiuvarcoma of (lie liter I Block. 1974: Creech A Johii.-on# N74; Lee A: Harry. 19741 and tumours of (beTrain and lungs (Monsou. Peters & Johnson. 1974). Degenerative chances in the iivvi. kidneys, hone and brain were detected in rnt> md labbils fol lowing exposure to \CM innal.itioi' iliactiacv. Va/in & Kochetkov. i'->T- Lieger. Reynolds. Couolk. Moslem S/a ho <Xl Mutidiv .974; Torkclson. ((yen & Rowe. I4ft|; Viola. !9"(b. Moreover. VCM ittli ilalion was found to induce rumours m noil; rats and mice fMuhoni .V l.eleniiite. .974. Viola. Bicotl) & Cuputu. 197', | 1l"v st.isle was s| ims,ireu by a groan of ci'-<MXT.iting I uropean ii.dvtstr.es. iitclu tmg V.-Knut Kiuvistoffcr/ruucinlc Indir'ri.' .A' il cdc..u Republic of < iernuny) Shell Ned.iff.imi C hi mi--. Dutrli Slate Mines. \k/o /out t hemic Nederland It.\ and Dow C henvic.il 1 mope SA. Certain formulations of PVC arc used widely as food-packaging materials. Residual VCM present in the extruded polymeric product was shown to ho liable to migration into PVC-packod loodx and drinks. especially distilled spirits (Randolph. 1973). Since no data oil the oral toxicity of VCM appeared to be available, studies were initiated to examine the suhacme toxic properties of this compound when admin istered orally to rats. Oral administration is greatly hampered by the fact that VCM is a gas at room temperature |b.p. c - Ox ("j and therefore preliminary experiments were earned out to find an acceptable way of administering the compound orally to rats. Administration in the drinking-water was consi dered m this respect hut was rejected because of the rather poor solubility of VCM in water (Hard'c. |9M) and. more sjymiieanilv. because oi the difficulties to he expected tn handling the solutions and in estimat ing the quantities of VCM actually ingested by the animals. As VCM is lipophilic, we investigated the possibi lity of administering VCM as a solution in edible oil either by gastric intubation or hy incorporation into the diet. Another possibility studied was the addition to the diet of a f*VC jv-wder containing an unusually high concentration of VCM. The present report describes' tentative experiments on the oral administration of VCM and presents some observations on the fate of VCM in rats. In addition, the results are given of a subacute toxtcity \ k tv C TO -J q ^ DEPARTMENT OF HEALTH. EDUCATION. AND WELFARE PUBLIC HEALTH SERVICE FOOD AND DRUG ADMINISTRATION WASHINGTON. DC. 20204 April 1, 1976 APR 7 m/fi Hr. Albert C. Clark Manufacturing Chemists Assn. 1825 Connecticut Avenue, N.W. Washington, DC 20009 Dear Mr. Clark: This is to acknowledge receipt of your letter of March 23, 1976, transmitting the final report entitled, "The Effects of Maternally Inhaled Vinyl Chloride on Embroyonal and Fetal Development in Mice, Rats and Rabbits." This information will be considered in our evaluation of the use of vinyl chloride polymers in contact with food. Accordingly, as you are aware, it may be necessary to place this report on public display at the Hearing Clerk when final regulations are published. i r We have not been conducting any animal studies on the potential toxicity of FD&C Red Ho. 2. We have been analyzing various samples of PVC coatings, gasket material, plasticized film, and flexible tubing. To date, we have been unable to detect any migration of vinyl chloride from these types of articles at a level of sensitivity of 1 part per billion. We are looking forward to the receipt of further reports of the studies being sponsored by MCA. Sincerely yours, Gerad L. McCowin Assistant to the Director Division of Food and f Color Additives, HFF-334 URL 17206 Noma of iubitanc* ;Synonyms) Spci (Strain) E vpoiuro Slag* of xpftr imnt 5. Furfural Hamster (CAS Reg. No.: 98-01-1; 2Furaldehyde; 2-Furancarbonal; (Syrian Golden) a-Furole) 6. Iron oxide Hamster (CAS Reg. No.: 1309-37-1; Ferric (Syrian Golden) oxide; C.I. 77491; Ferric* sequioxide; Jeweler's rouge; Hanaaite) ?. y-Irradiated chicken $ , Methylbenzocyanate Rat (Wistar) Rat (Wistar) 9. 3-Methylthio-2-butanone-O l (Methylainino) carbonyl ]codme Rat (Wistar) 20. N-Nitroscdiethylamine Hamster (CAS Reg . No,: 55-18-5 ; (Syrian Golden) Diethylnitrosamine? DEN; OEJ*A) 12. Vinyl chlDride JCAS Reg. No,: 75-01-4; Chlor- Rat (Wistar) ethene; Chloethylene; Chloro- ethene; Chleroethylene; Ethylene monochloride; 1C; VCM) 22. Yeast (qrewn on qas-oil) Rat Mouse 16. Yeast (grown on pure n-paraffins) Rat (Wistar) Mouse inhalation histology in progress i.tr. alone & in combination with DieLhylnitrosini Lno (inhal. & i.tr.) canpietod published1 p.o. in the dier. completed to be published p.o. in the diet in progress p.o. in the diet in progress i.t. ccrpiti ted publ ished1 p.o. in the diet & inhal. in progress p.o. -d i t z cp.o. -a i t i completed ~d i t z ocouplered -d i t t o- Principal i n vo * t i go tor Feran, V.J. & Kruysse, a. Feron, V.J. Til, H.P. Til, H.P. Til, H.P. Feron, V.J. Feron, V.J. Til, H.P. & Kruysse, A. Feran, V.J. Feron, V.J. 1 See Appendix I Noma of aubilonco [Synonyms I 20, Span 60 (CAS Reg. No.: 1338-41-6; Sorbitan mcnostearate) Sp*eCcili (Strain) MDuse (TFI) Stearoyl lactic acid, sodium & calcium salt Rat Tartrazine (CAS Reg. No.: 1934-21-0; C.I. Acid Yellow 23, trisodium salt; 5-Hydroxy-l-(p-sulphophenyl)-4-[(p-sulphophenyl)azoJpyrazole-3-carboxylic acid, trisodium salt; C.I. 19140; C.I. Food yellow 4? FD & C yellow 5; Tartar yellow N) Mouse (CSI) y-Urdecalactone (CAS Reg. No.: 104-67-6) Mouse Vinyl chloric (CAS Reg.-No.; 75-01-4; Chlorethene; Chlorethylene; Chloroethane; Chloroethylene; ethylene monochloride; VC; YCM) Rat (Wistar) URL 19658 Expoiuro Slag* of xportmonl Principal invotligatora p.o. in the diet p.o. in the diet histopathological exami nation to be carried out planned ccmpleted to be published1 BIBRA staff BIBRA staff p.o. in drinking water discontinued in progress BIBRA staff See Appendix I Chemical Principal Investigator 29. Testosterone & dihyrotestosterone Habib, F.K. 20. Titanium dioxide (CAS fteg, No.: 13463-67-7? Titanium oxide; Illmenite; Rutiox cr; Titania; Unitane) Selikoff, I.J. 22. Trichloroethylene (CAS Reg. No.: 79-01-6? 1Chloro-2,2-dichloroethylene; Ethinyl trichloride; Trichloroe.thene; Algylen? Germalgene? Trichloran; Triclene; Westrosol) Axel sen, 0. 22. Vinyl chloride Thiess, A.M. (CAS Reg. No.: 75-01-4; Chlor- ethene; Chlorethylene; Chloro- j ethene; Chloroethylene? Ethylene monochloride; VC; Bartalini, E. VCM) Duncan, K.D, Selikoff, I.J. 602*. nan Appendix II page v Name of Department/laboratory & Address Division of Steroid Endocrinology, 26-28 Hyde Terrace, Heeds 1S2 9LAJ, UK Environmental Sciences Laboratory, Mount Sinai School of Medicine, The City University of New York, 100th Street & 5th Avenue, New York, N.Y. 10029, USA Department of Occupational Medicine, Regional Hospital, S-70185 Orebro, Svasden Medical Department, Badische Anilin- und Sodafabrik, BASF-AG, Brunchstrasse, Uidwigshafen, Federal Republic of Germany Medicina e Igiene del Lavoro, Montedison & Consociate, Via A. Appiani, 12, 201212 Milan, Italy Deployment Medical Advisory Service, Health & Safety Executive, Baynard's House, Chepstow Place, London W2, UK Environmental Sciences laboratory. Mount Sinai School of Medicine, The City University of New York, 100th Street & 5th Avenue, New York, N.Y. 10029, USA Chemical 22. Cant'd Principal Investigator Berta22i, P.A. 23, Vinyl chloride polymers (CAS Peg. No. fPM9002-86-2; Chloroethylene polymer; Poly vinyl chloride; Blacar; Opalon; Vynon) Berta2zi, P.A. Ottevanger, C.F. Duncan, K.D. 24. Vinylidene chloride (CAS Reg". No.: 75-35-4; 1,1- Dichloroethylene; asynDichloroethylene) Pell, S. Name of Department/Laboratory & Address Clinica del Iavoro "L.Devoto", University degli Studi, via S. Bamaba 8, Milan, Italy Clinica del lavoro "L, Devoto", University degli Studi, via S. Bamaba 8, Milan, Italy Department of Industrial Health, Shell Co., P.0. Box 7000, Rotterdam, The Netherlands Employment Medical Advisory Service, Health & Safety Executive, Baynard's House, Chepstcw Place, London W2, UK Medical Division, E.I. du Pont de Nanours & Co., 11400 Nemours Building, Wilmington, Delaware 19898, USA 0996T IHn April 5, 1976 THE DOW CHEMICAL COMPANY BENNETT BUILDING 2030 DOW CENTER MIDLAND, MICHIGAN 49640 Warren R. Muir, Ph.D. Senior Staff Member for Environmental Health Executive Office of the President Council on Environmental Quality 722 Jackson Place, N.W. Washington, D.C. 20006 i.( .A _ t----------- Dear Dr. Muir: The attached correspondence is relative to reanalysis of the July 1974 Tabershaw-Cooper study conducted for the companies sponsoring research on vinyl chloride administered by the Manufacturing Chemists Association. We discussed this at the SOT meeting in Atlanta and you requested replacement copies for your files. * I personally feel that this study has been unjustly criticized.. Because? of their great importance, the available data were pulled together for j the New York Academy of Science meeting in May 1974. They were subsequently published in the Journal of Occupational Medicine to make them publicly available while the Work was being c:rtended and reanalyzed. Industry has been damned on one hand for withholding data and on the other for releasing it before it is completed. It is not possible to do both. Industry has been accused of "diluting" the data by including workers with only one years exposure or more. Since the study was a study of all causes of death it was essential that the study include these workers. Without them, deaths due to non-cancerous causes could not have been studied. As would be expected, table 9 of Dr. Gaffey*s letter of July 12 illustrates the problem of most epidemologicial studies; that is, the total number of workers is small. In this study the number is so small that when the total is split into a lot of cells, the number per cell is minute? It is expected that when the total study is completed this spring we may have enough older workers exposed long ago (15-25 years ago) to draw some conclusions. This was among the first studies of this type conducted by such a large group of companies. It was admittedly incomplete when it was thought necessary to release the data. There was no intent to dilute the data URL 17211 or minimize the problem. In fact the authors concluded that "by these criteria, mortality from digestive cancer, respiratory cancer, cancer of other and unspecified sites and lymphomas, appear to be related to exposure as defined in the study" p 513, JOM, Aug 1974. (copy attached). The MCA panel has expressed concern for these other possible cancers and acknowledged the limitation of the data. It is further of interest that the MCA has received little guidance from government in this study. Several persons and agencies have been asked to comment on the table that I included in my letter to you dated August 12, 1975. To my knowledge no one has done so. Industry has attempted to maintain the open communications and scientific.cooperation necessary for society to deal with these important problems. I suggest your office do all it can to encourage the government agencies and organization to be more understanding of the limitations under which we all work and to foster a better spirit of cooperation. ^ .. URL 19662 Sincerely yours, f. T. R. Torkelson APR 3 0 1976 MEDICAL DEPARTMENT eg Attachment - Letter from T.R.Torkelson to W. R. Muir dated Aug 12, 1975 -Letter from W.R. Muir to K. D. Johnson dated June 21, 1974 Letter from K.D. Johnson to W.R. Gaffey dated July 2, 1974 Letter from K.D. Johnson to W. R. Muir dated July 3, 1974 Letter from K.D. Johnson to Tech Task Group on VC Res Mgmt dated July 22, 1974 Letter from W. R. Gaffey to W. R. Muir dated July 12, 1974 ft *' k ti fO URL 1721