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Vinyl Chloride Cytogenetics *)
Dante |. Picciano, Ph.D.; Ray E. Flake, M.D.; Peter C. Cay, M.D.; and D. Jack Kilian, M.D.
Thi* report present* cytogenetic findings from a group of
Vinyl chloride monomer has been produced at the Texas Dlvi-t > e ~<(l
204 workers employed for up to 28 years in the manufacture of vinyl chloride monomer at the Texas Division of Dow Chemical
sion of Dow Chemical U.S.A. since 1948. There are no vinyl chloride polymerization operations. Average exposure levels, as is
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U.S.A. Cytogenetic evaluation results from this group were the case for almost all vinyl chloride monomer plants, have been
compared to results found in examination of individuals being generally lower than those reported for facilities involved in
considered for employment. Statistical analyses were per* polymerization operations.14 Although the threshold limit values
formed on a group basis for chromatid aberrations, chromo for vinyl chloride had been 500 parts per million (ppm) until 1974,
some aberrations and proportion of abnormal cells; no Dow had established a goal of 50 ppm or below in 1959." The
statistical difference of significance was found between the current Occupational Health and Safety Administration (OSHA)
two groups. Comparison of these results with reported studies standard for vinyl chloride is one ppm as a time-weighted-average
suggests that the level of cytogenetic aberrations in vinyl over an eight-hour workday. We have found that the TWA con
chloride workers is probably related to the length and level of exposure, and that risk of adverse genetic effect can be avoided in cohtrolled, minimal-exposure environments.
centration of vinyl chloride for all VC-related job classifications was approximately 5 ppm from 1968 to 1973; in 1974, TWA con centrations were 1 to 2 ppm. Since 1975, average levels of expo sure have been lowered to less than 1 ppm. Estimates of average
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Vmyl chloride (VC) has been reported to be carcinogenic in
exposure levels for the years prior to 1968 are less reliable. For the purposes of this study, estimates of exposure were calculated for'
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animals' 1 and human beings' and mutagenic in bacterial test specific job classifications, based on records of both personnel
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t systems.4 ' ` There have been reports of increased frequencies of chromosomal aberrations in workers exposed to vinyl chloride at
and area monitoring (Table 1). However, actual exposure may vary from individual to individual within the same job classification and
polyvinyl chloride (PVO facilities.' * * Similar increases were not accidental, short-term exposures of some workers to concentra
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found upon cytogenetic evaluation of German PVC workers'" nor in our own preliminary investigation of a group of American VC workers." One study based on interviews with male employees has indicated an increased rate of fetal wastage among wives of VC-exposed workmen involved in polymerization operations.'1
We have recently completed cytogenetic evaluation of all currently-employed workers exposed to vinyl chloride at the Dow (Freeport) Texas Division. Both vinyl chloride and vmylidone chloride are produced in this plant. Vinylidene chloride has also been reported as mutagenic in bacterial test systems." However, while these Dow workers are involved with the production of both compounds, the degree of contact with vinylidene chloride is far less than the exposure to vinyl chloride.
Ffom Octii04tttn.il Health *n<1 MedicAl
h Dow Chomu ,iM i S A 0 P*--
t i4ho And Killin' And Depertmcnt of InduMrul Mrdtfinp Dow i hemdl USA Tng.i*
Oivition 'Dr* Fl.ike jnd Ciy* Ffoepnrt rx
MAitful trnm thn report w,i* prpg4-nird jt the Sth loMvn.ttmn.vl Cnl Hum,in
OnnhM Mettco C'tv Oclohm td-IS 107ft
tions m excess of the standard probably occur from time to time. Documentation of such incidents is difficult.
Methods Our studv group was composed of 209 workers who had
worked in the vinyl chloride plant for periods ranging between one and 332 months (average. 48.3 months) at thg.tiqte of this in vestigation. As part of the medical surveillance program for this group, peripheral blood samples were obtained, and evaluation of lymphocyte chromosomes was performed. Lymphocytes were cultured using a modification of the Moorhead technique." Stan dard procedures, as previously described.'' were used for incuba tion processing, and analysis.
Findings wore compared to cytogenetic data from a group of 295 "proemploymont examinees'- who had chromosome evalua tion done as part of routine preemployment examination and who. at that time, had no known exposure to chromosome-break-
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Journal of Occupational Medicine/Vol. 19. No. 8/August 1977
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' ' Tali 1. -- Btfmatad Expom ta Vinyl Cblerida (VC) for Vinyl ChtorWeRalrtad Jab Claofflcatlaia.
Ettsnated Eipawrx In Party aar Minien. *1 Tknt-WnflrTaa-Aisfafa 1973-1974 1940.1977 Baton 1990
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u 17 l7 05 12 87 13 U 03 0.7 09 24 0.0 13 09 1J '44 52 09 28 1 23 0.7
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82 82 82 05 77 15.2 70 79 \ 03 07 09 89 06 78 05 78 109 711.7 09' ' 93 ' . 80 07 11 1
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Table 2. -- Cyteianatic Study at 209 WorinraEqwnrf -. (*
ta Vinyl CMadda.
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percent aberrations, and the vinyl chloride workers were
separated into those with estimated TWA exposure levels of less-
than-1 ppm, from 1-to-9 ppm, and greater-than-5 ppm. The
estimated exposure levels were based on calculations for specific
|ob classifications to which members of the vinyl chloride study
group were assigned Three categories of aberration were chosen
for this analysis: chromatid breaks, chromosome breaks, and the
proportion of abnormal cells.
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As shown in Table 3. no significant differences -vyere found
when these groupings were compared on the basis of chromatid
aberrations. Results from those workers with estimated exposures
of greater than 5 parts per million are almost identical to those of
the control group.
Similar conclusions were reached upon evaluation of the data
for chromosome breaks (Table 4) and the proportion of abnormal
cells (Table S). In all three cases, most of both groups were found
to have zero-to-hvo percent aberrations, and the vinyl chloride
workers with the highest level of estimated exposure showed
aberration rates not significantly different than those of the con
trol group. Findings for both groups, workers and controls.-are
considered to be within the range of normal variation as seen m this- laboratory
tng agents The records selected for inclusion in the control group were matched to those of the study group, insofar as possible, for sex. number of cells analyzed, and time period during which the culture was initiated.
Age variation between the two groups could not be completely eliminated' the average age of the vtnvl chloride workers was 19 9 years (range. 18 to 67 years), and the average age of the preemployment control group was 29 1 years (range 18 to 90 vearsi
Discussion The reports that have appeared, to date, concerning
chromosome aberrations in vinyl chloride workers have not been in agreement This conflict may be due either to the small number of workers studied or to differences in exposure levels, or both. The Swedish group studied by Funes-Cravioto et al'* was com posed of seven PVC workers who had been exposed for nine to 29 years and who wete found to have an increased frequency of chromosome hreakage The level of exposure for this group was
Results
As shown in Table 2. data from both groups -- vinyl chloride workers and preemployment controls -- were scored and com pared on the basis of chromatid breaks: chromosome breaksrings, dicentrics, and exchange figures; and the proportion of ab normal cells. The proportion of abnormal cells was calculated to show the overall frequency of aberrant cells, that is. the ratio ol cells with at least one aberration to the total numher of sells examined. Results expressed in terms ot ihe mean percentage for these categories of aberration, sliowed no ma|or cfitlerences betsveen the tsvo groups tor anv ol the classifications
Using Chi-square analysis, it was derided to see it diiferent es in various aberration rates tould he tb-tected within the* tsvo groups Acs ordinglv hulh groups were divided into those showing zerolo live percent aberrations ami those shewing greater-th,in-live
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reported to have continuously decreased over a period of years until immediately prior to the study when VC concentrations in the polymerization department were estimated to be 20 to 30 ppm.
The U.S. group of 11 PVC workers surveyed by Ducatman et al" was also reported to show an increased rate of chromosome breakage following exposures estimated to have been in excess of 300 ppm at times. The group of ten German workers investigated by Fleig and Thiess10 worked with either VC or PVC or both for periods ranging between six and 34 years and with exposures esti mated to have decreased from greater than 500 ppm in 1945 to between 10 and 25 ppm in 1974. Evaluation of this group for in creased aberration rates was negative.
The study of British PVC workers by Purchase et a/.11 concluded that the frequency of cytogenetic aberrations was increased in 56 exposed workers as compared to 24 nonexposed individuals. Esti mates of the levels of exposure were not given in this report. The medical director of the surveyed group, however, has informed us that while further analyses of the data confirmed the findings of in creased aberrations in workers exposed to "higher" levels of vinyl chloride, no differences between worker and control groups were detected upon evaluation of the data for workers exposed to "lower" levels.
An earlier report from our laboratory21 concluded that there were no cytogenetic differences of statistical significance be tween a group of 121 workers exposed to vinyl chloride and a 75person control group. As in the work reported here, there was a discrepancy in the age composition of the two groups, because applicants seeking employment tend to be younger than those already settled into jobs. We do not believe, however, that this difference is a confounding factor in our comparison since the dif ference is not great and because it has been shown2' that the cytogenetic change most often associated with aging is chromosome loss, rather than chromosome breakage.
On the basis of our negative findings and the conflicting find ings reported by others, we believe that the level of chromosome aberrations in workers exposed to vinyl chloride is probably re lated to the length and level of exposure and that the risk of ad verse cytogenetic effects can be avoided in controlled, minimalexposure environments. Cytogenetic dose-response curves, similar to that suggested here, have been reported for x-irradiated ankylosing spondylitics.2* A-bomb survivors.2' radium dial paint ers,2* persons exposed to Thorotrast.2'' and workers exposed to lead.2* it has also been noted that the groups exposed to radiation (ater demonstrated significant increases in neoplastic incidence A-bomb survivors, for example, have shown increased .rates of leukemia and thyroid carcinoma;radium dial painters were found to be at increased risk of osteogenic sarcoma; '* and
thorium dioxide-exposed persons have an increased rate of liver tumors." This relationship between chromosomal breakage and neoplasia strongly suggests that cytogenetic analyses may be a useful tool for detecting environmental situations which may be associated with increased cancer risks to the workers.
The present study is one of several involving Texas plant em ployees to investigate the possibility that increased rates of fetal loss or birth defects in offspring are experienced by wiv^s of vinyl chloride workmen and to determine the morbidity-mortality ex perience of all past and present VC workers. A search has been made for cases of angiosarcoma of the liver; none have been found in our study group (533 individuals) which includes all past and present VC workers. Current workers are also being monitored as part of the continuing medical surveillance program.
The author* acknowledge with appieclation the technical assntence of Mr*. A. Lin* scombe and Mr* D Mentik. the tuggestiom of Mn. M. Benge, the editing of Mt T. 8. Lloyd, and the adwce of Or C. 0 Jacobson
References
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