Document 1wQkDn2zDRGn2LGMO19Knap5

OBSERVATIONS ON THE VINYL CHLOSILKciSTi^'SiY^EROM. Produced Pursuant A STATISTICAL VIEWPOINT To Pra'ecikj OrLr R(ks v. i>!W , r?1 337 Caic:"L-.` The Objective and Scope of the Study t->i'?3nY Case Nc. S-i-CV-uJ&'i LH) Western District of New York Jt ' The vinyl chloride study was undertaken to define an acceptable career exposure level to vinyl and vinylidene chloride in light of data collected from a human population exposed over a period of years to these chemicals. The study was retrospective in that the data analyzed was assembled from informa tion already available. Ninety-seven employees working within the area of concern were declared in-scope of the study on the basis of having experienced no serious acute exposures and having had little or no contact with other toxic chemicals. For many of these employees, complete medical information was not available. Physical exams had been given on a voluntary basis in 1958, 1959-60, 1961, and 1965-66. A summary of lab procedures under investigation and the number of employees examined is shown in Table A. The non-response rate is high for some tests and must be considered in the final interpretation of results. The procedures appearing in Table A were selected from a broader list of lab tests available from the medical records because these showed promise of correlation with exposure variables based on a preliminary analysis of the more complete set of data. R&S 000403 The Industrial Hygiene section of the Bio-Chem Department was responsible for determining exposure levels experienced by plant workers in the study population. The time-weighted average concentrations of VC1 and VC12 were measured for each job classification on a yearly basis. It was necessary in several cases to project backwards in order to estimate the exposure levels in years prior to installation of the monitoring devices. Thus, the exposure data for the i th. individual consists of a 1 X n. matrix of yearly TWA exposure levels for the n.. years preceding the date of medical exam. The details of measuring these yearly time-weighted averages will not be discussed here. The Method of Analysis The question posed by this study and the methods of data collection made it rather difficult to specify a statistical model for which all assumptions of the model could be met. Since definite medical diagnoses were not available, R&S 000404 7j ?!'c;act:;'j Orisr 'roaucsd Pursuant j-S8 Na. 90-4837 c? ... .,A':r(rU ^ l --. ; j^H'i^A'csl Company 2- - Ciss ?jo. 94-07-0333 S(H) Western District of New York the strategy of analysis was to attempt to explain variation in the observed At clinical variables by first removing effects resulting from non-environmental factors such as age, and then to see if the unexplained variation could be further reduced by the introduction of variables representing some function of the exposure levels to VC1 and VC12. This led to the use of multiple regression analysis. Obviously, there was no way of arbitrarily selecting the levels of the independent variables. As a result,very few observations occurred at the higher exposure levels which were of most interest. The assumptions that the errors were independently normally distributed with constant variance was not rigorously tested. However, these assumptions appear to be reason ably satisfied. Findings (1) Six lab procedures of the eleven under study showed correlations with one or more exposure variables for at least one periodic exam series at the . 05 level. These were BSP, B Protein, Icterus Index, Hemoglobin, Systolic and Diastolic Blood Pressure. (2) All six of these lab tests showed correlations during the 1965-66 period, while only hemoglobin showed a significant correlation at the . 05 level prior to this date; that being in 1958. However, two tests, B Protein and Icterus Index, were administered only in 1965-66 and one, the BSP, was obtained only on a limited basis prior to 1965. (3) In the final analysis much weight is placed on the readings ob served for those few employees who experienced high exposure levels, especially in the 1949-58 period of their careers. For example, the average exposure level in 1950 was 153 ppm, whereas the average exposure level for 1965 was 29 ppm. (4) The BSP test showed the most pronounced correlation with one or more exposure variables. (5) Three individuals in the study had Time-Weighted-Averages of 595 ppm in 1953. Two of these were given physicals in 1965. The weight of their relatively high exposure levels in the early 50's is evident from Figure I where they represent the two highest time-weighted averages despite average exposure levels in the 60`s. R&S 0004$5 -3- (6) The correlation between age and TWA concentration of chemical exposure increased as exam dates became more recent with 1965-66 showing the highest correlations. Year Correlation 1958 1959-60 1961 1965-66 . 048 . 125 . 153 . 361 (7) The average career length as of the 1965-66 physicals was 14.4 years. (8) A number of interrelated exposure measures were examined, such as dose, number of years of TWA greater than 50, 100, or 200 ppm and several interactions between exposure measures and age or ^ weight. However, TWA was relied upon where possible because of the ease in presenting and inter preting results. (9) Although no significant correlations in the 1958-61 BSP readings were detected after removing the weight affect, the mean BSP value for the 16 observations was a high 4. 06 and the average exposure level was 120 ppm. (Tentative) Conclusions There is strong evidence that several clinical results were influenced by the amount of exposure to VC1 and VC12 experienced by study subjects. It is not known if the effects are the result of accumulative action over the entire career of the individual or the result of the higher exposure levels experienced prior to 1958. The latter possibility seems more plausible at this time. Effects were detected in 1958 and 1965-66; none were observed in 1959-60 or 1961. A delayed response would account for the effects detected in 1965-66 after the over-all exposure levels had been lowered con siderably. Assuming this explanation to be correct, the upper exposure limit could then be set by following back on the careers of those subjects showing effect in 1965 to their exposure levels prior to 1958, M , Ge raid Ott Corporate Medical Department 4/22/68