Document wDb3dMMQVX4bjLEdKVJErw7E

4 /, ITEM 1 COPIED BY MCA FOR DISTRIBUTION TO THE VCjNYL CHLORID^ TECHNICAL PANEL, AUGUST 27, 1976, MR. M- FREIFELD FOR ADMINISTRATIVE USE LIMITED DISTRIBUTION NOT FOR PUBLICATION PUBLIC HEALTH SERVICE-CDC-Atlanta EPI-76-60-2 July 26, 1976 TO : Director, Center for Disease Control FROM : Cancer and Birth Defects Division Bureau of Epidemiology SUBJECT: Congenital Central Nervous System Malformations, Kanawha County, West Virginia SUMMARY Data available through the Birth Defects Monitoring Program (BDMP) revealed that from 1970 through 1974, Kanawha County, West Virginia-- where 1 of the 40 polyvinyl chloride production plants in the United States la located--had rates of congenital central nervous system defects that were significantly higher than national BDMP races for those years. In February 1976 an Investigation was undertaken because of the possibility that theaa higher than expected rates nay have been related to parents' occupational or residential exposure to vinyl chloride. The study confirmed that an Increase In CKS defect rates had occurred in Kanawha County, and cases clustered primarily in Che area east of the plant; however, no relationship between Infants with malformations and parents' exposure to vinyl chloride could be established, INTRODUCTION Because of continuing concern regarding the possibility thst birth defects of the central nervous system (CNS) may be caused by parents' occupational or residential expoeure to vinyl chloride, CDf.'s Birth Defects Branch, Cancer and Birth Defects Division, Bureau of Epidemiology, reviewed 1970-1974 dete available through the Birth Defects Monitoring Program (BDMP), a hoapltal-baead ayaten for monitoring the inci dence of birth defects end other newborn eondltlona noted in infants discharged fron approximately 1,200 United States hospitals (1). Of the 40 polyvinyl chloride (PVC) pro duction plants In the United States (2), 17 ere located in counties which have at least 1 hospital that woe participating in the BDMP In 1974 and thus could ba Included In the review. In 10 of rhe J7 counties, BDMP data are reported on loss than 501 of tho total renorted Mrthe: therefore, even though higher than normal CNS rstes ware notsd in 2 of these counties, they were not Included In this study bscsuse of the low pcrcentaga of total births they represented. In the 7 counties where the majority of births are reported to the BDMP, 2 had rates of CNS dofects in infants born from 1970 through 1974 that wore significantly higher than national BDMP rates for those yasrs: Lake County, Ohio (Palnesville), the site of a previous investigation (3), and Kan.r.hn County, West Vi-glr.io. '- The Kanawha Co'ii'ty findings (Table I) were discussed with William L. Cooke, M.D., Wast Virginia State. EM.demio1 and Peter Infante, D.D.S., Dr.P.H., National Institute RKt.v.,, J. B. JOHNSCbj ucc 001585 for Occupational Safety and Health (NIOSH), who agreed with the need for further Investigation. On February 10, Larry Edmonds, M.S.P.H., and Carol E. Anderson, M.D., met with Dr. Cooke In Charleston, West Virginia, and began an Investigation. Others who participated In the investigation and in the preparation of this report Included Joseph Carney, Director, and Lucas Neas, Statistician, West Virginia State Department of Health, Division of Vital Statistics; Paul Seekford, M.D., Director, and Edna Smith, R.N., Charleston-Kanawha County Health Department; and Carl Beard, II, Director, West Virginia Air Pollution Control Commission. BACKGROUND The principal centers of population In Kanawha County (1970 population 229,113) are Charleston, South Charleston, Dunbar, St. Albans, and Nitro. All are located along the Kanawha River, which flows from southeast to northwest through the valley's hilly terrain. In 1970 the chemical industry employed 121 of the county's work force. There are 7 major chemical plants and several smaller ones In the Kanawha River Valley within 10 miles of Charleston. Only 1 of these plants produces pvc. This plant, which beean production In 1935, uses the solvent, emission, and modified emulsion processes. Vinyl chloride monomer (VCM) is released Into the atmosphere as part of the production process, METHODS Two data sources were used in this investigation: 1) BDMP listing of infants born with CNS defects from Jsnuary 1, 1970, through December 31, 1974, and 2) West Virginia Department of Vital Statistics recorls (birth and fecal death certificates) on Infants born with CNS defects from January 1, 1968, through December 31, 1974, Data obtained from these 2 sources were not entirely comparable (4), since BDMP data represented 95X of all hospital births in Kanawha County wiLhout regard to parents' realdencs, and vital statistics records represented only those infants born to county residents. The data were examined separately for trends, end then both sets were combined to deter mine sll CNS defects incidence for 1970 through 1974. A esse was defined as a hospitalconfirmed CNS defect in an infent born between January 1, 1970, and December 31, 1974, to parents who were residents of Kanawha County at the time of the Infant's birth. We reviewed hospital records to confirm diagnoses, rule out miscoding, and check each mother's piece of residence. For each confirmed caac, we selected 2 controls from vital statistics records. These controls, all with parents \/ho resided in Kanawha County, were the first llvebom infants without malformations bora iaediately before and after an infant with a CNS defect and were matched according to the following criteria: 1) month of birth, 2) race, 3) paternal education (nuAer of yeara: 0-8, 9-12, and 13 and over), and 4) maternal age within 2 years. With the permission of the attending physicians, we interviewed by telephone the families of effected infants and 1 randomly chosen control. The following information was obtained: 1) history of previous pregnancies, including information about miscarriages, stillbirths, and children with malformations in their family, 2) 5-year residential history before and including the year of birth of the child in question, and 3) 5-year occupational history for both parents, including location of work and exposure to chemicals. Case and control families could not be interviewed blindly, since the families often remarked about either the malformation or the normal development of their child. The Kanawha County Health Department and the NT0SH staff assisted in locating families who had changed residences and/or jobs and those who did not have telephones. 2 ucc 001586 RESULTS Except for 1974, Kanawha County rates shown in the BDMP for total CMS, as well ss the particular defects anencephaly and hydrocephaly, were higher then U.S. rates (Table 1). A decline in total CNS defect rates in Kanawha County was noted in both data seta (Tables 1 and 2). In both data sourcea, the total rates in 1974 were distinctly lower than those in previous years, although the decline waa also evident in the 1973 vital records data. Earlier data were available only for 1968 and 1969 froa vital records. In both years, there were fewer cases than there were in 1970. The highest BDMP rates for all defects occurred in 1971. Preliminary BDMP data obtained for 1975, the year following the study period, showed that total CNS rates were similar to U.S. rates. Table 1 Reported Incidence* of CNS Malformations in Kanawha County, West Virginia, and the United States Birth Defects Monitoring Progrsm, 1970-1975 Anencenhalv Kanawha Co. U.S. 1970 1971 1972 1973 1974 Casaa Rata Caats Rata Cases Rate Caaea Rate Ceaee Rate 3 9.0 6 16.3 6 16.6 2 5.2 4 9.6 5.6 5.4 4.9 4.9 4.4 Spina bifida Kanawha Co. U.S. 4 12.0 8 21.8 1 7.2 7.9 2.8 4 10.5 2 7.4 6.4 4.8 6.0 Hydrocephalus** Kanawha Co. U.S. 2 6.0 4 10.9 2 4.8 4.9 5.5 4 10.5 0 4.9 4.5 0.0 3.8 Othar CNS Kanawlia Co. U.S. 3 9.0 1 4.2 2.7 2 3.9 5.5 1 4.4 2.6 0 4.1 0.0 4.2 Total CNS Kanawha Co. U.S. 12 35.9 19 51.7 11 30.5 11 28.9 21.8 22.1 21.6 19.9 6 14.4 18.4 Rates per 10,000 total births Excludes eases with spina bifida Table 1 f OH Malfonstlses Inserted thee** Vita leeeids--. Ceenty, Meet Virginia, laaleasts, IMS-1974 Aaaeeaphaly s1s 1999 Cases late 19 TO Cease !SS J2ZL Cease late J32L. Cease lata 3 13.9 3 7.9 9 24.1 3 13.2 9 17.3 Spine bifida 9 19.3 3 7.9 3 13.4 4 13.2 2 3.0 * Hydrocephalus z 3.4 2 3.1 2 3.3 3 7.9 3 14.9 2 Other CM Total cm - 0.0 - 0.0 _ 0.0 1 2.7 - 0.0 13 33.4 1 28.3 19 41.S 13 34.4 13 37.9 3 Sates par 10,000 total blnbe M>lrth ead fatal death certificates, Hast Virginia State Oepartneat of gsalth 0.0 1 9.0 0.0 13.0 . 1 3 3.0 0.0 0.0 3.0 ucc 001587 Contained rates for Kanawha County for the hospital and vital statistics data are given In Table 3. The races were high from 1970 through 1972, with a decline in 1973 and only 1 case reported in 1974, giving a 1974 rate well below expected. Forty-seven confirmed CHS defect cases were in infants born to residents of Kanawha County at time of the child's birth. Families of 46 of these Infants and of their matched controls were located and Interviewed. Five infants' parents were not residents of Kanawha County at the tiiM of conception and were excluded from further analysis. All mal formed Infanta were white, and females predominated (25:16), as usual in anencephaly and spina bifida cases. No seasonal variation was noted in the rates. Of the spe cific defects, anencephaly had the highest rate. Table 3 Confirmed Cases and Kates* of CNS Malformations, Kanawha County Residents, 1970-1974 1970-1974 1970 1971 1972 1973 1974 Malformation Cases Rate Caaea Rate Cases Rate Cases Rate Cases Rate Cases Rate Anencephaly 23 13.0 9 24.1 5 13.2 6 17.5 3 Spina bifida 15 8.5 4 10.7 6 15.9 3 8.7 1 9.0 3.0 1 0.0 3.0 Hydrocephalus 7 4.0 - 0.0 3 8.7 3 8.7 1 3.0 - 0.0 Other CHS 2 1.1 1 2.7 1 2.7 - 0.0 - 0.0 - 0.0 Total CNS 47 26.7 14 37.5 15 39.7 12 34.9 5 15.0 1 3.0 spar 10,000 total births Age. Education, and Socioeconomic Index - Close case-control matching was achieved for paternal education, maternal age, and Hollingshead Index, an indicator of socioeconomic status (Table 4). Case and control groups were also comparable regarding maternal edu cation (12.4 and 12.0 years, respectively). Paternal age was slightly older in the case group (27.3 years) than in the control group (25.8 years), but the difference was not statistically significant. Table 4 Age, Education, and Socioeconomic Index, CHS Defect Cases and Controls, By Malformation Matching Variables Total CNS Anencephaly Spina Bifida Other CNS Cases Controls Cases Controls Cases Controls Cases Controls Paternal education* 12.6 12.8 12.6 12.2 13.7 14.1 10.9 12.0 Maternal age* 24.3 23.9 24.8 24.4 25.8 25.1 24.3 20.3 Non-matching variables Paternal age* 27.3 25.8 26.8 26.4 29.2 26.5 25.4 22.7 Maternal education* 12.1 12.0 11.9 11.9 12.7 12.5 12.1 11.9 Hollingshead Index Mean score Class sMean number of years 47.5 IV 45.5 IV 49.3 IV 48.5 IV 4 38.9 38.6 III III 58.3 IV 49.4 IV ucc 001588 Generally, caeca and controla were similar In the specific deface categories. Among the specific defect categories, parents in the spina bifida group (both case and control) had the highest education and were the oldest; in the "Other CHS" category (mainly hydrocephalus), parents had the least education and were the youngest. Reproductive History - The total number of previous pregnendea of mothers in the case group (49) was almost the same as that observed for mothers in the control group (48). Other similarities included live births (cases 78Z, controls 77X), fetal deaths' (cases 22Z, controls 23Z), and other children with congenital anomalies (1 in each group). The fetal death rates among cases and controls were higher than the rate of 16.1Z reported by Uarburton and Fraser (5). A family history of birth defects was reported by 11 of 41 families in the case group but by only 4 of 41 in the control group. Five "case" parents and no "control" par ents reported a family history of CHS defects. A possible explanation for the differ ence is that parental recall is affected by the birth of a child with a congenital malformation (6). Occupation - Two "case" fathers and 2 "control" fathers were employed in the FVC plant at the time their affected Infants were conceived. Fathers of 3 additional controls had worked in the plant on a contract basis for a short time and therefore also had had possible exposures. Hone of the mothers in either group had ever worked at the FVC plant. One other occupational category is worth noting. In the case group, 2 mothers were employed in dental laboratories when they became pregnant, and 2 fathers had worked in dental laboratories before their Infanta were conceived. Parents in the case and control groups were asked about the location of their place of work at the time of their infant's conception. Only parents with a permanent work location were counted, thus excluding workers such as truck drivers and salasmen. The homes of housewives and uneafloyed parents were considered to be their place of employment. On this basis, distance from work place to the FVC plant was calculated. No difference was observed between case and control groups for either parent regard ing distance of work place from the FVC plant. Residence - Parents' place of residence at elms of their Infant's conception was plotted on county maps, and we then calculated distances from the FVC plant. Table 5 presents the mileage from the plant by 1-mlle increments up to 13 miles. Using a chi-square test at 1-mile intervals, we found no significant difference between the 2 groups. Hatched peirs of cases and controla were also tested by using the matched pair t-tast of significance; no differences were noted. Table 5 Residential Distance from FVC Plant, Controls, By Malformation e 8 1 Distance from Total CHS Anencaohalv Spina Bifida Other CMS Plant (Milas) Casas Controls Casas Controls Cases 'Controls Caste Controls <1 3200 3200 <2 4400 3 4 10 <3 9 10 1 5 5 4 3 1 < 4 14 14 4 6 6 5 4 3 < 5 17 15 6 7 7 5 4 3 < 6 21 16 9 a 8 5 4 3 < 7 23 17 9 8 10 6 4 3 < 8 24 22 10 10 10 9 4 3 < 9 27 24 12 11 11 9 4 4 < 10 30 30 15 13 11 11 4 6 < 15 35 34 19 16 12 12 4 0 TOTAL 41 41 21 21 13 13 7 7 5 UCC 001589 Although no differences were observed in measured distance within concentric circles, within the 3-Mile rone of the PVC plant, there were more case family residences In the ares northeast of the river and more control family residences in the area south of the river (Figure 1), Fig l CONGENITAL CNS DEFECTS CASES AND CONTROLS, CHARLESTON-SOUTH CHARLESTON, WEST VIRGINIA, AREA Using the PVC plant as the origin, we determined x and y coordinates for parents' residence at time of each infant'a conception (case and control groups). Four cumulative groups were defined for both cases and controls based on distance of residence from the PVC plant: <3 miles, <5 miles, ^10 miles, and the total group. Case and control groups were then compared for statistically significant differences in their respective centers of gravity (average position), using multivariate extensions of the Wilcoxon matched-pairs signed-ranks teat and the Kruskal-Wallis teat (_7). The matched-pairs test was used to test the total group (all case-control pairs). Since in the distance-defined groups case-control pairs were split, these 3 groups were analysed by the (unpaired) Kruskal-Wallis analysis of variance. The only significant difference was for infants in the case and control groups whose families resided within 3 miles of the plant (p <.02) (Table 6). 6 ucc 001590 Table 6 Significance Testing of Differences In Centers of Gravity, CNS Defect Cases and Controls Distance from Plant X2 (2 Degrees of Freedom) Probability <3 miles <3 miles <10 miles All distances 8.72 3.06 1.09 0.91 <.02 >.20 >.30 >.50 The case and control parents who resided within 3 miles of the PVC plant at their child's conception had a higher socioeconomic status than those who resided more than 3 miles from the plant, as reflected by a class III Hollingshead Index; the remaining group had a class IV. The distribution of this group by date of birth was similar to the remaining group. There were 9 Infants in the case group: 5 with spina bifida, 2 with congenital hydrocephalus, 1 with microcephaly, and 1 with anenccphely. Tn at least 3 cases there was evidence of a familial co^xment to the defect occurrence. One mother gave birth to 2 of the Infants: 1 with spine bifida and another with anencephaly. Another case mother reported chat her sister had spina bifida, and a third mother had a cousin with a heart defect. Although familial components do not exclude an environmental cause, they do suggest the possibility of genetic causation. There was no difference in previous stillbirths or abortions between case and control parents who lived within 3 miles of the PVC plant or between these parents and those who lived more than 3 miles from the plant. No difference was noted between the mean years of residence of case parents (1.9) and control parents (2.0) who lived within 3 mllea of the PVC plant. environmental Studies - Atmospheric and environmental data related to VCM and ocher emissions in Kanawha County are limited. Data on VCM emissions provided by the South Charleston plant at the request of the West Virginia Air Pollution Cosmisslon are provided in Table 7. The data included the average amount (pounds per hour) of each year's emissions from 1967 through 1975 and the muter of abnormally heavy emissions. On October l, 1974, after the largest known single emission in the years 1967-1975, measurements were made by plant personnel in the cogenticy. The wind was blowing from the southwest, and the highest atmospheric VCM levels (grab samples) were to the northeast (.1 - .2 ppmv). The wind patterns in Kanawha Valley are variable according to the season of the year, time of day, and place of measurement. Monthly wind measurements also made at the plant indicated that the wind was blowing out of the south and west 421 of the time, and north and east 331 of the tlM during the months the infanta with CMS defects were conceived. 7 UCC 001591 Table 7 Annual Average Vinyl Chloride Mononer Emit*Iona, South Charlescon Plant, Ueat Virginia Year Ealaaiona (lba/hr) Eatlaated Nwber of Abnoraallv Heavy Ealaaiona* 1967 1968 1969 1970 1971 1972 1973 1974 1975 240 260 250 260 270 235 265 180 76 28 18 12 5 2 0 *Anounta ranged from 1,000-8,000 pounda, vlch an eaclmated average of 2,000 Source: Polyvinyl chloride plant, at the requeat of the Wcct Virginia Air Pollution Coalaalon Should the releaae of ealaaion coincide with the eouthwaat wlnda, then one night expect that acre ealaaiona could be blown froa the plant to the northeaat. The Meat Virginia Air Pollution Control Coaalaalon aeaaured auapended and aettleable particulate natter, another Indicator of wind direction, at varloua polnta within the coaaiailty (Table 8). The reported levele ware greater in the aouthveat, auggeatlng a prevailing wind froa the northeaat. Table 8 Mean Annual Levele of Suapended and Settleable Particulate Matter, 1963-1979 Year 1965 1967 1968 1969 1970 1971 1972 1973 1974 1975 1970-1973 1967-1973 Geoaatrlc Mean Suepended Particulate Matter (alcroaraa/cublc aeter) 12 203 160 171 150 136 102 105 123.2 113 131 107 107 93 94 114.3 Arlthaetlc Mean Settleable Particulate Matter (toae/eeuare alla/aonth) 11 92.2 133.2 82.3 68.6 47.6 30.0 24.0 18.0 62.0 68.9 63.6 35.4 35.9 24.0 24.0 15.0 18.5 13.3 57.7 38.1 `South Charleaton High School (aouthveat) `Federal Building, Quarrler Street (northeaat) `North Charlaaton Fire Departaent (northeaat) Source: Weet Virginia Air Pollution Control CoMttaaion 8 ucc 001592 DISCUSSION The investigation In Kanawha County confirmed that an increase had occurred In total congenital CNS malformation rates in 1970-1974. Rates were highest in 1970-1972 and dropped In 1>)73 to he Low national rates and In 1974 to only 1 confirmed case. Such a decline was not unique to Kanawha County. A similar, though less marked, trend was also present in BDMP data for other parts of the country. Furthermore, preliminary 1973 BDMt' data on CNS defects for the county were higher than 1974 data, suggesting that the apparent low Incidence for that year may reflact the variability of small numbers. As in the Paineavllle study (3), there were no differences between case and control groups regarding parents' po- sihle occupational exposure to VCM or to other environmental agents at time of their child's conception or for 5 years before conception. On this hip is. there was no evidence that the high CNS defect rate for Kanawha County was related to parental occupation in Industries producing PVC or other chemicals. A difference bctwcci. .he locations of residences of the case and control groups within a 3--mile radius of the plant was noted. Although approximately the same number from each group resided within the 3-mlle araa, those In the case group tended to live cist of the plant, and those in the control group lived across the river and south of the plant. Such a pattern might be chance distribution, or it could be related in some way to an environmental axposure ilmitad to the part of the city lying east of the plant. Aside from a slightly higher socioeconomic status, theri was nothing to distinguish the families of easaa and controls from other families who lived within the 3-mlle area. Furthermore, there was no difference in 'bo d.strihution of the types of defects or the years of birth (or conception!. SWc the investigation vis undertaken because of s possible association between the high CNS defect, rates observed in Kanawha County and the presence of s PVC plant, we gave pjrt.icu'ar attention to the possibility that the cluster may have been caused pv increased VCM emlaslons. To explain the case cluatvi on the basis of a teratogenic effect of atmospheric VCM exposure, one woul'* also expect an approximate correlation between s decrease in atmospheric v.M levels and a fall In CNS defact rates. The decreese In CNS raLes which occurred In 1973 preceded the decline in measured VCM emissions and lagged consider.il ly behind the overall decrease in particulates noted in the late J960s. This investigation did not reveal an association batween the case clustering within 3 miles of the plant, and exposure to VCM or other chemicals. Available data suggest that atmospheric and metoornlogic conditions along ths Kanawha River are variable. To proposs that some wind-born teratogen had settled In e particular location in the community, one would have to postulate alao the timing of plant emissions with the appropriate wind direction and other atmospheric conditions. No data are available to reconstruct such circumstances. Furthermore, it n.ust be noted that over 100 co^iounds other then VCM have been associated with omissions from the plants in the Kanawha Vallay area. One study estimated rhat 5^,457 tons of organic compounds. Including VCM, were emitted each yea- by Charleston chemical plants (8). Seme of these comnounds have baen identified as toxic to animals and humans; their Individual and combined teratogenic potentials are not known. 9 ucc 001593 Although there was a cluster of CNS defect cases to the east of the PVC plant In Kanawha County, the role of VCM or other compounds In explaining this cluster Is conjectural at present. REFERENCES 1. Center for Disease Control: Congenital Malformations Surveillance, Annual . Suamary 1974. Atlanta, CDC, 1975 2. Environmental Protection Agency: Scientific and Technical Assessment Report on Vinyl Chloride and Polyvinyl Chloride. Issued June 1975 3. Edmonds LD, Falk H, Nlsslm JE: Congenital malformations and vinyl chloride. Lancet, 1098, Nov 1975 4. Hay S: Variables in underreporting of clefts on birth certificates. Public Health Rep 82:985, 1967 5. Warburton D, Fraser C: Spontaneous abortion risks in man: Data from reproductive histories collected In a medical genetics unit. Am J Human Genet 16:1, 1964 6. Fraser FC, Warburton D: No association of emotional stress or vltsmln supplement during pregnancy to cleft lip or palate in man. Plastic and Recon structive Surgery 33:395-399, 1964 7. Purl ML, Sen PK: Nonparametric Methods In Multivariate Analysis. New York, John Wiley, 1971, pp 184-193 8. Department of Health, Education, and Welfare: Kanawha Valley Air Pollution Study. Washington Government Printing Office, 1970 Larry D. Edmonds, M.S.F.H. Birth Defects Branch Cancer and Birth Defects Division Buresu of Epidemiology 1L ^?tuOlsur) Carol E. Anderson, M.D. Birth Defects Branch Cancer and Birth Defects Division Bureau of Epidemiology J.'William Flynti Jr.,\jf.D. Chief, Birth Defects Branch Cancer and Birth Defects Division Epidemiology Clark W. Heath, Jr., M.D., Director Cancer and Birth Defects Division Bureau of Epidemiology DISTRIBUTION Mailing keys 53-1,2,3 William L. Cooke, M.D., State Epidemiologist, State Department of Health, State House, Building 3, 1800 Washington Street E., Charleston, West Virginia 25305 Joseph Carney, Director, Department of Vital Statistics, State Department of Health, Building 3, 1800 Washington Street E., Charleston, West Vlrslnla 25305 Page H. Seekford, M.D., Director, Kanawha County-Charleston Health Depertment, 1426 Kanewha Boulevard E., Charleston, West Virginia 25301 Carl G. Beard, II, Director, West Virginia Air Pollution Control Comlasion, 1558 Washington Street E., Charleston, West Virginia 25311 Ralph Rhodes, Director, Toxic Substances, Environmental Protection Agency, Region III Sixth end Welnut Streets, Philadelphia. Pennsylvania 19106 H`D'' Dlr,ctor* National Institute for Occupational Safety and Health, 12420 Parklawn Drive, Rockville, Maryland 20852 Bobby F. Craft, Ph.D., Deputy Associate Director for Cincinnati Operations, National Institute for Occupational Safety and Health, U.S. Post Office Building, Room 543, 1014 Broadway, Cincinnati, Ohio 45202 Infante, D.D.S., Dr.F.H., Biometry Branch, Division of Field Studies and Chemical Investigations, National Institute for Occupational Safety and Health, U.S, Post Office Building, Cincinnati, Ohio 45202 10 UCC 001594 Robert W. Hiller, M.D., Chief, Epidemiology Breach, National Cancer Institute, National Institutes of Health, A-521 Landov Building, Bechesda, Maryland 20014 Lawrence A. Plumlee, M.D., Medical Science Advisor, Environmental Protection Agency, 401 "M" Street, S.U., Room 905, West Tower (RD 678), Washington, D.C. 20460 Arnold H. Spellman, Manager, Project Development Group, Information Services, Coimnisslon on Professional and Hospital Activities, 1968 Green Road, Ann Arbor, Michigan 48105 Gabriel Stickle, Vice-President for Program, National Foundation-March of Dimes, 1275 Mamaronack Avenue, White Plains, New York 10605 Daniel G. Seigel, S.D., Chief, Blostatlstics Section, Epidemiology and Biometry Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 31, Room 2A10, Bechesda, Maryland 20014 11 UCC 001595