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Reprinted from AMERICAN INDUSTRIAL HYGIENE ASSOCIATION JOURNAL Volume 30, Novcmber-Dccember, 1969 J Monitoring Exposures to Vinyl Chloride Vapor: Breath Analysis and Continuous Air Sampling EDWARD D. BARETTA,* RICHARD D. STEWART, M.D.* and JOHN E. MUTCHLERf Department of Environmental Medicine, Marquette School of Medicine, Milwaukee, Wisconsin, and Environmental Health Section, Biochemical Research Laboratory, The Dow Chemical Company, Midland, Michigan @ An environmental survey was conducted to determine the time-weighted average exposure (TWA) of a group of chemical plant workers to vinyl chloride (VC1) vapor. This survey featured continuous multipoint air sampling and analysis using an infrared spectrophotometer. The inhalation exposure data were digitized and record ed on paper tape for subsequent computer analysis and derivation of daily TWA values for each worker. A breath sampling program was conducted concurrently with the environmental survey, and a series of breath decay curves relating post exposure breath concentration to vapor exposure were derived from the data. To validate the breath curves derived from on-the-job data, postexposure breath curves were also constructed from breath data obtained following experimental human exposures to carefully controlled concentrations of VC1 vapor. The close agreement between postexposure breath concentrations at the corresponding TWA's obtained by each of the methods suggests that cither continuous air monitoring or breath analysis is valid for estimating the worker's indi-'lual daily exposure to VC1, and provides further evidence that breath analysis is a useful industrial hygiene technique for evaluating vapor exposure. Introduction npHE QUESTION THAT MAY ARISE following an mvimninenlal survey is whether the rhemiral vapor concentrations measured are truly representative of the ex posure being experienced by the workmen. Evaluation of the ranges of atmospheric con centrations and estimates of time-weighted average concentration (TWA) are all too often based on a few spot samples obtained under conditions which are not representa tive of all phases of a given operation. A more exact measurement of vapor exposure would have to be based on continuous moni toring of air in the workman's breathing zone during his entire work shift. Obviously this task is made difficult and often impossible This paper was presented at the American Industrial Hyiriene Conference, St, Loub; Missouri, May 13-17, 1968. Marquette School of Medicine, Milwaukee, Wisconsin. tThe Dow Chemical Company, Midland, Michigan, by the large number and variety of tasks per formed by today's modern chemical plant worker. Recent improvements in automatic moni toring and data processing equipment have provided a means for a more satisfactory so lution. Sequential samplers and automatic analyzers and recorders can now be used to continuously monitor several locations or operations to provide more valid data on which to base estimates of chemical exposure. Computers can be utilized to manage the large volume of data generated by continu ous monitoring.1 Meanwhile a technique has been under de velopment which more precisely defines the level of individual exposure. The realization that the total body burden of a volatile chem ical is directly related to its concentration in expired air led to the development of tech niques for collecting and analyzing breath samples useful in estimating the more indi- 537 f, 00 CO o o o> <o v I 53H Novetnbcr-December, I069 vidualized exposure experience of each work man. Studies by Stewart et at. have shown that the excretion or "`decay" of vapor in the breath can be used to characterize the ex posure. Breath decay curves constructed for several chemical solvents have proved clin ically useful as an index to chemical expo sure. These breath decay curves, for the most part_. were constructed from postexposure breath data obtained from experimental hu man exposures to carefully controlled and relatively constant vapor concentrations. However, breath decay curves have recently been constructed from breath data collected from workers whose work environment was being continuously monitored/ In this study of human exposure to vinyl chloride (VC11 vapor, breath decay curves constructed from data obtained during ex perimental exposures to the relatively uni form concentration within an exposure cham ber were compared with those derived at the theoretically equal, but broadly fluctuating, concentrations encountered in a chemical plant atmosphere. A measure of the validity of continuous monitoring data and the use fulness of breath analysis in assessing timeweighted average exposure was reflected by a close similarity between the two sets of breath decav curves. I WORK AREA | STATION 3 STATION 5 ?_____________9_________ i1 STATION 2 ('STATION 4 {STATION 6 o t J--1-- i1___9l____ Procedures Monitoring the Plant Atmosphere The chemical installation surveyed was a closed structure housing several separate chemical processing operations. First, a job survey was conducted for each of four job classifications to determine the work areas frequented by the workmen and the time they spent in each area. For each job classification, five sampling probes were strategically placed in the work area. A sixth probe was placed outside the building, and charcoal and silica gel filters were placed in the sampling line to assure a clean air reference. The sample probes were 5/16-inch I.D. Saran tubing through which air samples were drawn by a vacuum pump at a rate of 17.5 liters/min to a centrally located infrared spectrophotom eter. The spectrophotometer was equipped with a 10-meter path-length gas cell sensi tive to 5 ppm of VC1 at a wavelength of 10,63 microns. The VC1 concentration was linearly related to absorbance up to approx imately 1000 ppm. A schematic diagram of the sampling sys^ tern is shown in Figure 1. Sampling was e ecuted sequentially with a set of six two-wa^ solenoid valves controlled by a timer which advanced the sampling location every 5 min utes. A visual account of transmittance was recorded on a. strip charl recorder. Mean while the data were recorded in digital form on paper tape by a tape punch and digitizerprogrammed to record three equally spaced transmittances during the last half of each 5-minute sampling period. The transmittance data furnished by the spectrophotometer was converted to absorb ance and reduced to concentration according to Beer's law: a, (x-x") L ,0(x1-x"; R&S 100698 7fV- WEIGHTED MEAN EXPOSURE O.OI Whrt Ci mtoo coneMrotion ol Station i - Pj * ptf ttnf of time tptnt of location j during normal work detivitj Fioure 1. Schematic diagram of the infrared continuous monitoring system. where A X\ Jf* Xi i = absorbance = base-line response. = response at total absorption. = response at location i. = 2, 3, 4, 5, 6. American Industrial Hygiene Association Journal 539 R&S 100699 Finally, C= KA where K = a proportionality constant, C = concentration The taped data were processed by a Bur roughs 5500 computer at The Dow Chemi cal Company Computation Research Labora tory. The computer was used to calculate the mean and standard deviation of concen trations at each location for each 8-hour work shift. Finally, time-weighted average concentrations were calculated for each job classification using the time-location data obtained from the job surveys. As described elsewhere,1 the weighted percentage of time during which concentrations exceeded sev eral prechosen levels was also computed for use in establishing exposure profiles. Figure 2 describes the exposure profiles (frequency distributions) for the four job classifications studied during this survey. These profiles show the percentage of time hat concentrations exceeded the levels hown. They summarize several tens of thou sands of individually measured concentra tions and reduce them to single curves. Fig ure 3 shows the corrective trend brought about by actions undertaken to reduce the atmospheric concentration of VC1 over the 7-month period during which the study was conducted. Only two job classifications war ranted extensive study, but men in all four classifications were asked to participate in the breath sampling program. TIHC-WCI6NTI0 1. 01 TWf T-t COMCENTUriOf* CXCEOtO that shown Figure 2. Exposure profiles expressed as VC1 vapor concentration versus the exposure frequencydistribution for the four job classifications. cap glass vial (Figure 4). The overall length of the pipet was about 9 inches, so it could be conveniently and inconspicuously trans ported to and from work in a lunch bucket. The plastic caps were lined with six layers of Saran film identical to that used for the construction of Saran air sampling bags. A 3/32-inch hole predrilled through one of the caps provided an access for withdrawing samples. The Saran liners provided an ef fective gas barrier so that vapor losses were held to less than 10^2 for a holding period of 3 days. When collecting a sample the subject was asked to remove the caps, place the pipet to his lips, and breathe normally in through his nose and exhale through the pipet three On-lhe-Job Breath Sampling Three separate breath sampling programs were conducted concurrently with the envir onmental plant survey, designated by the boxed portions in Figure 3. Each worker collected three breath samples daily--the first on his arrival home from work, the second 5 to 10 hours later, and a final sample be fore returning to work the following day The samples were collected in pipets constructed from short lengths of 20-mm soft glass tubing to which had been welded at each end the threaded portion af a 2-dram (8-ml) screw- Figure 3. Weekly mean vapor exposure concen trations measured during the survey. Periods dur ing which breath sampling was conducted are rep resented by the hoxed-in areas. 540 Nouember-December, 1969 R&s 100700 Figure 4. Glass pipet (50 ml) used for collect ing breath samples. One cap has a predrilled hole for gas sampling. Both caps have Saran liners which seal the pipet chamber. times. After expelling the fourth breath he quickly caps the tube, trapping a portion of alveolar air. The importance of writing the name, date, exact time of sampling, and the workshift most recently completed, on the label attached to each pipet, was stressed. Aliquots were drawn from the pipets with a 1-ml Hamilton gas-tight syringe and ana lyzed in an Aerograph A-600B gas chromato graph using N- carrier gas and a hydrogen flame detector. Separations were made with a 6-foot, j4-inch I.D. stainless-steel column packed with Carbowax 20M alkaline on Chromosorb YV 60/80 mesh acid-washed. Exposure Chamber Operation Three experimental human exposures to VC1 were conducted at nominal vapor concentrauons of 50, 250, and 500 ppm. The exposure chamber was a room measuring 41 feet by 6 feet wide by 7.5 feet high. The room had a continuous positive air supply and exhaust system capable of maintaining a slight negative pressure within the cham ber. Continuous distribution of the cham ber air was achieved by recirculating the air with a squirrel cage fan through a series of inlet and outlet ducts spanning the length of the chamber. The VC1 was metered into the duct carrying air exhausted by the squirrel cage fan and entered the room atmosphere via the recirculation system at a rate sufficient to maintain the desired atmospheric concen tration. The vapors were introduced from a pressurized storage cylinder through 6 feet of j4-inch I.D. stainless-steel tubing into a rotometer prior to entering the circulating air duct. A heating tape wrapped around the stainless-steel tubing prevented condensation of the VCI and stabilized the How of the vapor. The concentration of VCI in the chamber was constantly monitored with, a. Perkin-El- mer infrared spectrophotometer equipped with a 10-meter path-length gas cell. A sam pling probe, consisting of 5/16-inch I.D. Sa ran tubing, was centrally located during the exposure to represent the breathing zone of all subjects within the chamber. The probe was moved about prior to each exposure to detect imbalance of vapor concentrations within the chamber so that necessary cor rections in the recirculating system could be made. Air samples collected periodically within the chamber throughout the exposure day were analyzed by gas chromatography for added assurance of analytical accuracy. Both the infrared spectrophotometer and the gas chromatograph were calibrated before each experiment and at intervals throughout the exposure day. Each 7.5-hour exposure day included a 0.5-hour lunch period in an uncontaminated area outside the exposure chamber. The TWA concentration was calculated on the basis of 7.5 hours of exposure. Clinical and Laboratory Procedures Each subject had been under careful medi cal surveillance by the medical department for a number of years, and each was given a complete medical examination a few days prior to the VCI exposures. Included were a complete urinalysis and 24-hour urine for urobilinogen, complete blood count with sed imentation rate, reticulocyte count, SGOT, SGPT, LDH, alkaline phosphatase, BUN, creatinine, and bilirubin. Each subject received a repeat physical examination 1 hour before entering the ex posure chamber. This examination included measurement of temperature, blood pressure, and pulse rate, a neurological examination, and collection of blood and breath samples. A questionnaire noting the presence of any symptoms of illness (for example, headache, nausea, dry throat) completed e pre-ex posure medical evaluation. After the subject entered the chamber, total expired breath samples were collected every hour by having him breathe out through a Saran tube leading to a Saran plastic col lection bag located outside the chamber. Tidal volume and total expiratory capacity erican Industrial Hygiene Association Journal 541 R&S 100701 wWc measured in the morning and again late in the afternoon exposure periods. Subjective and neurological responses were measured before the subject entered the chamber. 15 minutes after entrance, and at 1-hour intervals thereafter. Flannagan Co ordination and Crawford Manual Dexterity Tests were conducted at midmorning and again in the afternoon. Breath sampling be gan immediately after the subject left the exposure chamber. A 24-hour postexposure urine sample was collected and a blood sampie was drawn the following morning for SGPT, LDH, alkaline phosphatase, BUN, creatinine, and bilirubin determinations. Analysts of Breath Data The decay curves for the breath vinyl chlo ride concentrations were constructed by step wise multiple regression using a digital com puter. An empirical relationship of the form Concentration = / (TWA, time) was select ed from a choice of several terms, each based on TWA and/or time. The resulting regres sion equation best represents the ordered re lationship between breath vinyl chloride con- ration, time-weighted average exposures, postexposure time. Each breath decay curve lias an associated standard error of regression which can be used to compute the confidence band for any chosen level of significance. The 95% con fidence band for the mean of a group of ob servations was chosen in this case to describe the statistical error associated with the breath data and the regression technique. Table I Experimental Human Exposure to Vinyl Chloride Chamber Concentration (ppm) X S.D. 59 2 261 8 493 7 491 5 Range (ppm) 65- 53 289-243 5ift-m 525-475 1WA* ippm) 43 243 459 491** Xuuibtft' of Subjects `Time-weighted average concentration based on 7.5 houn including a 0.5-hour lunch period ia an unconuminated area. K Table I shows the analyzed concentration to which the subjects were exposed. Calcu lations of the mean and standard deviation of exposure concentration are based on chart readings from the infrared spectrophotometer taken at 5-minute intervals over the two 3.5hour exposure periods. The TWA is based on the total 7.5 hours which included a 0,5hour lunch period in an uncontaminated area. The final breath decay curves intended for use as an index to VC1 exposures were ad justed to TWA concentrauons of 50, 250, Results Experimental Breath Curves A total of 13 men participated in the three experimental chamber exposures at nominal concentrations of 50, 250, and 500 ppm pro ducing a total of 160 valid breath data points. Five of the six subjects exposed to 50 ppm were re-exposed at 500 ppm 2 days later. There was no measurable residual vinyl chloride detected on the breaths of the sub jects prior to the second exposure. Serial breath sampling was initiated immediately after the subjects left the exposure chamber and continued up to 20 hours following the exposures. Figure 5. Breath decay curves based on experi mental human exposures to 50, 250, and 500 ppm of VC1 (7.5-hour TWA). R&S 100702 542 November-December, 196 daily variation in exposure to vcl vapor (8 hr TWA) with confidence bands only slightly wider than those from controlled human experi ments. The close similarity between these curves and those constructed from controlled exposure data are further illustrated in Fig ure 8. Human Responses 2- 2? 2S 2' I; 29 Ocys Of the Month c- cZJSto't Figure 6. Variation in VC1 vapor exposure for three shifts. and 500 ppm (Figure 5), A 100-ppm decay curve was interpolated from the available data using regression analysis. These curves are presented with the calculated 95con fidence bands for the mean of a group of ob servations. On-the-job Breath Curves Ten workmen participated in the on-thejob breath sampling program, producing a total of 91 usable sets of data. Ten percent of the breath samples collected were discard ed because of pipet leakage or poor sampling techniques. Absolute breath levels ranged from about 20 ppm in one sample taken less than 1 hour after an 8-hour TWA of 250 ppm, to barely detectable levels (<0.05 ppm) in samples taken after exposures at TWA's below 50 ppm. The extremely broad variation in the TWA's experienced by workmen during one of the periods in which breath sampling was being conducted is demonstrated for three shifts of men bearing the job classification "coagulator operator" (Figure 6). Minute, hourly, and daily fluctuations in the concen tration of a contaminant are most descriptive ly revealed by continuous monitoring. This method of sampling quickly points out the fallacy of judging TWA and peak exposure concentrations on the basis of spot sampling or periodic surveys of brief duration. The remarkable correlation between breath concentration and corresponding TWA val ues made it possible to construct the series of breath decay curves shown in Figure 7, From a subjective standpoint no significant untoward affects were noted at any of the exposure concentrations. The only complaints were those of two subjects who reported mild headache and some dryness of their eyes and nose during the 500-ppm exposure experi ments. No odor was detected by anyone entering the exposure chamber at 50 ppm. At 250 ppm all four subjects entering the chamber initially reported that they could detect a very slight odor of the chemical. Five of the seven subjects entering the exposure cham ber at 500 ppm were able to detect the odor of VC1, but after 5 minutes of exposure those five were unable to detect it even with forced inspiration. Three of the four subjects re-J entering the chamber after lunch were abl^ Figure 7. Breath decay curves derived from breath data collected from workers following onthe-job exposures to VC1 vapor (8-hour TWA). >- 'r Tfi'7> AS- American Industrial Hygiene Association Journal to^J^ct a faint odor of VCI. One subject 543 could detect a faint odor on deep inspiration for approximately 15 minutes after entering the exposure chamber. The exposure had no noticeable effect on neurological responses, nor did it produce sig nificant changes in the results of mental, co ordination. or manual dexterity tests conduct ed during the exposure period. All clinical laboratory studies performed in the post exposure period were normal and not signifi cantly different from pre-exposure values. R&S 100703 Discussion ' The object of the environmental health survey is to identify the atmospheric contam inant, determine the exposure level, and re late this to the health hazard it presents. If one is to judge hazard by ambient concen tration measurements, then those measure ments must accurately describe the exposure on a continuing individual basis. A carefully conducted survey combining continuous anal ysis of the work room atmosphere with a comprehensive job study will provide data valid for estimating time-weighted average c^^wre. the other hand, breath decay curves constructed from breath data collected dur ing continuous plant monitoring are in close agreement with those obtained from exposure chamber experiments with VCI. These curves should therefore be useful as a second meth od for assessing exposure to VCI vapor. The choice of whether one or both meth ods should be used depends on prevailing circumstances and on the thoroughness de sired. For example, data useful in describ ing peak exposures are obtained from con tinuous monitoring. Concurrently, exposure trends and concentration gradients may help identify plant operational inefficiencies and equipment malfunctions by revealing specific sources of emission. Correcting these prob lems not only restores a healthful work en vironment but often results in bonus savings by reducing losses of raw' material and prod uct. Continuous monitoring, however, is ex tremely costly both in time and in the equip ment required. The scope of data acquired is Figure 8. Comparison of breath decay curves derived from the on-the-job data and the experi mental human exposure data. limited by the number of sampling probes, and these probes are not always capable of accurately measuring the individual's daily exposure experiences, especially should these involve unusual incidences such as chemical spills or exposures outside the monitored area. Breath analysis has the advantage of in dividualizing each worker's integrated daily exposure. Breath decay curves, as an index of exposure, offer a means of estimating the average daily individual exposure on the basis of a few breath samples taken serially in the postexposure period. Consequently breath analysis can be used to diagnose as well as quantitate an exposure which has already occurred. It is a relatively inexpensive and simple method which can be put into opera tion without extensive and costly preliminary preparations. However, postexposure breath analysis does not provide information on the daily fluctua tions of exposure, and the peak exposure con centrations are not made evident by breath data. Finally, breath analysis is not applica- 544 Sovrtnbi-r-Di'rcuihrr. 196!) ble to all chemicals, and breath decay curves established for one chemical are not useful as an index of exposure to any other chem ical. The decay curves presented here are in tended to serve as an index of exposure to vinyl chloride vapor and are based on an exposure duration of 7.5 hours for the experi mental exposures, and 8 hours for the on-thejob study. The close agreement between the two sets of curves and the narrow confidence bands obtained in each case demonstrate the usefulness and accuracy of both methods for estimating TWA exposures and indicate the importance of breath analysis and the need for expanding its use in evaluating ex posures to other widely used volatile organic chemicals. References 1. Peterson. J. E., H. X. Hoyle, and E. J. Schnkidkr: The Application of Computer Science to Industrial Hy gienc. Amcr. /nd. Hyg. Assoc, 1. 27: 160-185 (March 1966). 2. Stewart. R. D. H. H. Gay, D. S. Erley, C. L, Hake, and A. W. Schaffer; Human Exposure to Tctrachloro* ethylene Vapor; Relationship of Expired Air and Blood Concentrations to Exposure and Toxicity. Arch. Environ, Health 2: 516*522 (May 1961)* 3. Stewart, R. D., H. H. Gay, D. S. Erley, C. L. Hake, and J. E. Peterson: Observations on the Concentration of Trichloroethylene in Blood and Expired Air follow* ing Exposure of Humans. Amtr, Ind, Hyg. Assoc. J.23; 167-170 (April 1962;, 4. Stewart, R. 0.. and V, K. Rowe: Quinzc An* d'Etudes sur 1c l.l,l*Trichlornethane. Arch. Mafodin Profits. 28: 194-201 (1967). j. Stewart, R. D. H. C. Dodd, E. D. Barett*. and A. \V. Schaffer: Human Exposure to Styrene Vapor. Arch, Environ. Health 16: No. 5 (May 1968). 6. Stewart. R. D-. E. D. Baretta, H, C. Dodo, and T. R. Torkelsoh; Experimental Human Exposure to Tetrachloroethylene. AMA Arch. Environ. Health, (In print). 7. Stewart, R. D.. H, C. Dodd, E, D. Baretta. A. W. Schaffer, and J. E. Mutghler; Chronic Overexposure to Benzene Vapor. Presented at the Sixth Annual Meet ing of the Society of Toxicology, March 23-25, 1967, Atlanta, Georgia. Received May 26, 1968 R&S 100704