Document ZJamdQY8Own0ROrDpKmB4g4XO

ITEM 1 COPIED BY MCA FOR DISTRIBUTION TO THE VINYL CHLORIDE . - -.'0 TECHNICAL PANEL, AUGUST 27, 1976, MR. M. FREIFELD ' FOR ADMINISTRATIVE USE LIMITED DISTRIBUTION NOT FOR PUBLICATION PUBLIC HEALTH SERVICE-CDC-Atlaata EPI-76-60-2 July 26, 1976 TO : Director, Center for Disease Control FROM : Cancer and Birrh Defects Division Bureau of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 Is located--had rates of congenital central nervous system defects chat were significantly higher than national BDMP rates for those years. In February 1976 an investigation was undertaken because of the possibility that these higher than expected rates may have been related to parents' occupational or residential exposure to vinyl chloride. The study confirmed that an Increase in CHS defect rates had occurred In Kanawha County, and cases clustered primarily in the area east of the plant; however, no relationship between Infants vlth malformations and parents* exposure to vinyl chloride could be established. INTRODUCTION Because of continuing concern regarding the possibility that birth defects of the central nervous system (CNS) may be caused by parents' occupational or residential exposure to vinyl chloride, CDC*s Birth Defects Branch, Cancer and Birth Defects Division, Bureau of Epidemiology, reviewed 1970-1974 data available through the Birth Defects Monitoring Program (BDMP), a hospital-based system for monitoring the inci dence of birth defects end other newborn conditions noted In Infants discharged from approximately 1,200 United States hospitals (1). Of the 40 polyvinyl chloride (PVC) pro duction plants in the United States (2), 17 are located in counties which have at least ] hospital that vo? participating in the BDMP in 1974 and thus could be Included in the review. In 10 of the 17 counties, BDMP data are reported on lees than 50Z of the total reported births: therefore, even though higher than normal CNS rates were noted in 2 of these counties, they were not included in this study because of the low percentage of total births they represented. In the 7 counties where the majority of births are reported to the BDMP, 2 had rates of CNS defects in infants bom from 1970 through 1974 that were significantly higher than national BDMP rates for these years: Lake County, Ohio (Painesvllle), the site of a previous investigation (3), and Kan.*v./ha County, West Virginia. The Kanawha Courty findings (Table 1) were discussed with William L. Cooke, M.D., West Virginia State Epidemioiogis?-, and Peter Infante, D.D.S., Dr.P.H., National Institute RSV 0012223 for Occupational Safety and Health (HIOSB), who agreed with the need for further Investigation. On February 10, Larry Edmonds, M.S.P.H., end Carol E. Anderson, H.D., met with Or. 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, end Edna Smith, R.N., Charleston-Kanavha County Health Department, and Carl Beard, II, Director, West Virginia Air Pollution Control Commission. BACKGROUND The principal center# 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 122 of the county's work force. There sre 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 olant, which besan 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 boro with CNS defects from January 1, 197R, through December 31, 1974, and 2) West Virginia Department of Vital Statistics records (birth and fetal death certificates) on infants boro with CNS defects from January 1, 1968, through December 31, 1974. Data obtained from these 2 sources were not entirely comparable (4), since BDKP data represented 952 of all hospital births is Kanawha County without regard to parents' residence, and vital statistics records represented only those infants born to county residents. The data were examined separately for trends, and then both sets were combined to deter mine all CNS defect# incidence for 1970 through 1974. A case was defined as a hospitalconfirmed CNS defect in an infant 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. Ve reviewed hospital records to confirm diagnoses, rule out miscoding, and check each mother's place of residence. For each confirmed case, we selected 2 controls from vital statistics records. These controls, all with parents Vho resided in Kanawha County, were the first liveboro Infants without malformations^born immediately 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 (number of years: 0-8, 9-12, and 13 and over), and 4) maternal age within 2 years. With the permission of the attending physicians, ve interviewed by telephone the families of affected infants and 1 randomly chosen control. The following information was obtained: 1) history of previous pregnancies. Including information about miscarriages, stillbirths, snd children with malformations in their family, 2) 5-year residential history before and including Che year of birth of the child in question, and 3) 5-year occupational history for both pareats, Including location of work and exposure to chemicals. Case and control families could net 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 NI0SH staff assisted in locating families vho had changed residences and/or Jobs and those who did not have telephones. 2 RSV 0012224 7+ RESULTS Except for 1974, Kanawha County rataa shown in the BDMP for total CNS, as well as the particular defects anencephaly and hydrocephaly, were higher than U.S. rates (Table 1). A decline In total CNS defect rates In Kanawha County was noted In both data sets (Tables 1 and 2). In both data sources, the total rates in 1974 were distinctly lover than those In previous years, although Che decline was also evident in Che 1973 vital records data. Earlier data were available only for 1968 and 1969 from vital records. In both years, there were fever cases chan 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, shoved that total CNS rates were similar to U.S. rates. Table 1 Reported Incidence* of QIS Malformatlone In Kanawha County, West Virginia, and the United Statea Birth Defects Monitoring Program, 1970-1975 Anencephalv Kanawha Co. U.S. 1970 1971 1972 1973 1974 Cases Rste Cases Rate Cases Rate Cases Rate Cases 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 Other CNS Kanawha Co. U.S. 3 . 9.0 4.2 1 2.7 2 3.9 5.5 1 4.4 2.6 0 4.1 0.0 4.2 Total CNS Kanawha Co. 12 35.9 19 51.7 11 30.5 11 28.9 6 14.4 U.S. 21.8 22.1 21.6 19.9 18.4 Rates per 10,000 total births Excludes cases with spina bifida Table 2 Incidence* of OS Malfonatlons Imported through Vital lecorda**, baedu County, Vest Virginia* Residents, 196^1974 1968 1969 1970 1971 1972 1973 1974 Cases late Caeca Kate Cases Rate Casee Kate Cases Kate Cases Kate Case* Kate Ansneephaly S 13.6 3 7.6 9 24.1 5 13.2 6 17.5 3 9.0 - 0.0 Spin* bifida c 16.3 3 7.6 5 13.4 4 13.2 2 5.8 - 0.0 1 3.0 Hydrocephalus 2 5.4 2 5.1 2 5.3 3 7.9 5 14.6 2 6.0 - 0.0 Other Qts - 0.0 - 0.0 - 0.0 1 2.7 - 0.0 - 0.0 - 0.0 Total CHS 13 35.4 6 20.3 16 42.8 13 34.4 13 37.9 5 15.0 . 1 3.0 Kates per 10 .000 total births **llrth and fecal death certificates. Vest Virginia State Department of Health 3 RSV 0012225 Combined races for Kan aa County for the hospital and vita* statistics data are given in Table 3. The rates were high fro* 1970 through 1972, with a decline in 1973 and only 1 ease reported in 1974, giving a 1974 rate veil below expected. Forty-seven confined CHS defeet cases were in infants born to residents of Kanawha County at tine of tile 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 time of conception and were excluded from further analysis. All mal formed Infants 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 end Rates* of CNS Malformations, Kanawha County Residents, 1970-1974 Malformation 1970- 1974 1970 1971 1972 1973 1974 Cases Rate Cases Rate Cases Rate Cases Rate Cases Rate Cases Rate Anencephaly 23 13.0 9 24.1 5 13.2 6 17.5 3 9.0 - 0.0 Spina bifida 15 8.5 4 10.7 6 15.9 3 8.7 1 3.0 1 3.0 Hydrocephalus 7 4.0 - 0.0 3 8.7 3 8.7 1 3.0 - 0.0 Other CNS "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 *?er 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 ease 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, CNS Defect Cases and Controls, By Malformation Matching Variables Paternal education* Maternal age* Total CNS Anencephaly Spina Bifida Other CNS Cases Controls Cases Controls Cases Controls Cases Controls 12.6 12.8 12.6 12.2 13.7 14.1 10.9 12.0 24.3 23.9 24.8 24.4 25.8 25.1 24.3 20.3 Non-matching variables - Paternal age* Maternal education* 27.3 12.1 25.8 12.0 26.8 11.9 26.4 11.9 29.2 12.7 26.5 12.5 25.4 12.1 22.7 11.9 Hollingshead Index Mean score 47.5 45.5 49.3 48.5 38.9 36.6 58.3 49.4 Class etfean number of years IV IV IV IV III III IV IV 4 RSV 0012226 Generally* cases and controls were similar in the specific defeet 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 CSS" category (mainly hydrocephalus)* parents had the least education and were the youngest. Reproductive History - The total number of previous pregnancies of mothers In the case group (49) vas almost the same aa that observed for mothers In the control group (48). Other similarities included live births (cases 78Z* controls 77Z) fetel deaths (esses 22%, controls 23%), and other children with congenital anomalies (1 In each group). The fetal death rates among cases and controls were higher then the rate of 16.IX reported by Warburton and Fraser (5). A family history of birth defects vas 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 CNS 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 Che plant on a contract basis for a short time and therefore also had had possible exposures. None of the mothers in either group had ever worked at the PVC plant. One other occupational category is worth noting. In the ease group* 2 mothers were employed in dental laboratories when they became pregnant* and 2 fathers had worked in dental laboratories before their infants were conceived. Parents in the case and control groups were asked about the location of their place of work sc the time of their infant's conception. Only parents with a permanent work location were counted* thus excluding workers such as truck drivers and salesmen. The homes of housewives and unemployed parents were considered to be their piece of employment. On this basis* distance from work place to the PVC plant was calculated. No difference was observed between case and control groups for either parent regard ing distance of work place from the PVC plant'. Residence - Parents' place of residence at time of their infant's conception vas plotted on county maps* and we then calculated distances from the PVC plant. Table 3 presents the mileage from the plant by 1-mile increments up to 15 miles. Using a chi-square test at 1-mile intervals, we found no significant difference between the 2 groups. Matched pairs of cases and controls were also tested by using the matched pair t-test of significance; no differences were noted. Table 5 Residential Distance from PVC Plant* Cases end Controls* By Malformation Distance from Total CNS Plant (Miles) Cases Controls Anencephaly Cases Controls Spina Bifida Cases Controls Other CNS Cases Controls <1 3200 32 0 0 <2 4400 34 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 8 8 5 4 3 <7 23 17 9 8 10 6 4 3 < 6 24 22 10 10 10 9 4 3 <9 27 24 12 11 11 9 4 4 < 10 30 30 15 13 11 U 4 6 < 15 35 34 19 16 12 12 4 0 TOTAL 41 41 * 21 21 13 13 7 7 5 RSV 0012227 Although no difference* were observed In measured distance within concentric circles, within the 3-mlle zone of the PVC plant, there were nore case family residences In the area northeast of the river and more control family residences In the area south of the river (Figure 1). Fig. / CONGENITAL CNS DEFECTS CASES AND CONTROLS. CHARLESTON-SOUTH CHARLESTON, WEST VIRGINIA, AREA Using the PVC plant aa the origin, ve determined x and y coordinates for parents* residence at time of each Infant's 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 test and the Kruskal-Wallis test (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 ware split, these 3 groups were analyzed 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 RSV 0012228 Table 6 Significance Testing of Differences in Centers of Gravity* CMS Defect Cases and Controls Distance from Plant X2 (2 Degrees of Freedom) Probability <3 miles <5 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 ?VC plant at their child*8 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 anencephsly. In at least 3 cases there was evidence of a familial component to the defect occurrence. One mother gave birth to 2 of the infants: 1 with spina bifida and another with anencephaly. Another case mother reported that 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 waa no difference in previous stillbirths or abortions between case and control parents who lived within 3 miies 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 miles of the PVC plant. Environmental Studies - Atmospheric and environmental data related to VCM and other emissions in Kanawha County are limited. Data on VQ4 emissions provided by the South Charleston plant at the request of the West Virginia Air Pollution Comnisslon 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 number of abnormally heavy emissions. On October 1, 1974, after the largest known single emission in the years 1967-1975* measurements were made by plant personnel in the comsunlty. 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 plane indicated that the wind was blowing out of the south and west 42Z of the time, and north and east 33X of the time during the months the infants with CNS defects were conceived. 7 RSV 0012229 Tabic 7 Annual Average Vinyl Chloride Monomer Ealaelone South Charleston Plant, West Virginia Tear Emissions (lbs/hr) Estimated Humber of Abnormally Hi 1967 1968 1969 1970 1971 1972 1973 19 74 1975 240 260 250 260 270 235 265 180 76 28 18 12 5 2 0 ^Amounts ranged from 1,000-8,000 potmds, with an estimated average of 2,000 Source; Polyvinyl chloride plant, at the request of the Vest Virginia Air Pollution Commission Should the release of emission coincide vlth the southwest winds, then one might expect that more emissions could be blown from the plant to the northeast. The Vest Virginia Air Pollution Control Cosaslssion measured suspended and aettleable particulate matter, another indicator of wind direction, at various points within the community (Table 6). The reported levels were greater In the southwest, suggesting e prevailing wind from the northeast. Table 8 Mean Annual Levels of Suspended and Settleable Particulate Matter, 1965-1975 Tear Geometric Mean Suspended Particulate Matter (microRTam/cubic meter)__ 12 Arithmetic Mean Settleable Particulate Matter (tons/sauare mlle/aoneh) 13 1965 1967 1968 1969 1970 1971 1972 1973 1974 1975 1970-1973 1967-1973 205 171 150 136 102 105 123.2 160 113 131 107 107 93 94 114.5 92.2 133.2 82.3 6B.6 47.6 30.0 24.0 18.0 57.7 62.0 66.9 63.6 35.4 35.9* 24.0 24.0 15.0 18.5 13.3 38.1 1 South Charleston High School (southwest) *Federal Building, Quarrler Street (northeast) *Horth Charleston Fire Department (northeast) Source: Vest Virginia Air Pollution Control Commission 8 RSV 0012230 DISCUSSION The Investigation In Kanawha County confined that an increase had occurred in total congenital QJS malformation rates in 1970-1974. Rates were highest in 1970-1972 and dropped in 1973 to below 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 1975 BDMP data on CNS defects for the county were higher than 1974 -data, suggesting that the apparent low incidence for that year may reflect the variability of small, numbers. As in the Painesville study (3), there were no differences between case and control groups regarding parents' passible occupational exposure to VCM or to other environmental agents at time of their child's conception or for 5 years before conception. On this basis, 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 butweci. the locations of residences of the case nnd control groups within a 3--miK- radius of the plant was noted. Although approximately the same number from each group resided within the 3-mile area, 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 exposure limited to the part of the city lying cast of the plant. Aside from a slightly higher socioeconomic status, then was nothing to distinguish the families of cases and controls from other families who lived within the 3-mile area. Furthermore, there was no 'difference in the distribution of the types of defects or the years of birth (or conception} . Since the investigation was undertaken because of a possible association between the high CNS deicer, rates observed in Kanawha County and the presence of a PVC plant, we gave particular attention to the possibility that the cluster may have been caused ny increased VCM emissions. To explain the case cluster on the basis of a teratogenic effect of atmospheric VCM exposure, one wouJ^ also expect an approximate correlation between a decrease in atmespher:r. v-'M levels and a fall in CNS defect rates. The decrease in CNS rat.es which occurred in 1973 preceded the decline in measured VCM emissions and lagged consider.]: '.y behind the overall decrease in particulates noted in the late 1960s. This investigation did not reveal an association between the case clustering within 3 miles of the plant and exposure to VCM or other chemicals. Available data suggest that atmospheric and metoorologic conditions along the Kanawha River are variable. To propose that some wind-bnrn teratogen had settled in a particular location in the community, one v^uld have to postulate also the timing of plant emissions with the appropriate wind direction and other atmospheric conditions. No data are available to reconstruct such circumstances. Furthermore, it most he noted that over 100 compounds other than VCM have been associated with emissions from the plants in the Kanawha Valley area. One study estimated that 52,457 tons of organic compounds, Including VCM, were emitted each year hy Charleston rheir.lral plants (jl) . Some of these corsDOunds have been identified as toxic to animals and humans; their individual and combined teratogenic potentials are not known. 9 RSV 0012231 Although there vm a duster of CMS defect esses to the east of the PVC plant In Kanawha County, the role of VQI or other compounds in explaining this cluster is conjectural at present* REFERENCES 1. Center for Disease Control: Congenital Malformations Surveillance. Annual Sunmary 1974. Atlanta. CDC, 1975 2* Environmental Protection Agency: Scientific and Technical Assessment Report on Vinyl Chloride and Polyvinyl Chloride. Issued June 1975 3. Edmonds ID, Falk H. Nissla JE: Congenital malformations and vinyl chloride. Lancet, 1098, Nov 1975 4. Hay S: Variables in underreporting of clefts on birth certificates. Public Health Rep 82:965, 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 vitamin supplement during pregnancy to cleft lip or palate in man. Plastic and Recon* structive Surgery 33:395-399, 1964 7. Purl ML, Sen PK: NonparaMtrie Methods in Multivariate Analysis. New York, John Wiley, 1971, pp 184-193 6. Department of Health, Education, and Welfare: Kanawha Valley Air Pollution Study. Washington Government Printing Office, 1970 Larry D. Edmonds, M.S.P.H. Birth Defects Branch Cancer and Birth Defects Division Bureau of Epidemiology Ca/i erf Q** Carol E. Anderson, M.D. Birth Defects Branch Cancer and Birth Defects Division Bureau of Epidemiology J. william Flynd, Jr.,\^.D. Chief, Birth Defects Branch Cancer and Birth Defects Division Bureau of Epidemiology ($ul 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 Statistice, State Department of Health, Building 3, 1800 Washington Street E., Charleston, West Virginia 25305 Page H. Seekford, M.D., Director, Kanawha County-Charleston Health Department, 1426 Kanawha Boulevard E., Charleston, West Virginia 25301 Carl G. Beard, II, Director, West Virginia Air Pollution Control Commission, 1558 Washington Street E., Charleston, West Virginia 25311 Ralph Rhodes, Director, Toxic Substances, Environmental Protection Agency, Region III, Sixth and Walnut Streets, Philadelphia, Pennsylvania 19106 John Finklea, M.D., Director, National Institute for Occupational Safety and Health, 12420 Parklavn Drive, Rockville, Maryland 20852 Bobby F. Craft, Ph.D., Deputy Associate Director for Cincinnati Operations, National Institute for Occupational Safety and Health, U.S. Poet Office Building, Room 543, 1014 Broadway, Cincinnati, Ohio 45202 Peter Infante, D.D.S., Dr.P.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 RSV 0012232 Robert V. Miller, M.D., Chief, Epidemiology Branch, National Cancer Institute, National Institutes of Health, A-S21 Landov Building, Bethesda, Maryland 20014 Lawrence A. Plunlee, M.D., Medical Science Advisor, Environmental Protection Agency, 401 "M" Street, S.W., Boom 905, Vest Tower (RD 676), Washington, D.C. 20460 Arnold H. Spellman, Manager, Project Development Croup, Information Services, Commission on Professional and Hospital Activities, 1968 Green Hoed, Ann Arbor, Michigan 48105 Gabriel Stickle, Vice-President for Program, National Foundation-March of Dimes, 1275 Mamaroneck Avenue, White Plains, New York 10605 Daniel G. Selgel, S.D., Chief, Blostatlstlcs Section, Epidemiology and Biometry Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 31, Room 2A10, Bethesda, Maryland 20014 11 RSV 0012233