EPA 560/6-81-002
EPIDEMIOLOGY STUDIES
SCREENING FOR THE EARLY DETECTION OF DISEASE
IN INDIVIDUALS EXPOSED TO VINYL CHLORIDE
JANUARY 1981
FINAL REPORT
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDES AND
TOXIC SUBSTANCES
WASHINGTON, D.C.
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EPA 560/6-81-002
January 1981
SCREENING FOR THE EARLY DETECTION OF DISEASE
IN INDIVIDUALS EXPOSED TO VINYL CHLORIDE
Carlos H. Tamburro
Charles Kupchella1
3
Kenneth Taylor
Emanuel Landau
1
by
Richard Greenberg
2
Hildegarde Maricq
Joseph Whelan, Jr.
Joseph Seifter
1
1. University of Louisville
Louisville, Kentucky
2. University of South Carolina
Charleston, South Carolina
3. Yale University
New Haven, Connecticut
4. American Public Health Association
Washington, D. C.
5. U.S. Environmental Protection Agency
Washington, D. C.
Project Officer
Jane Keller
Office of Pesticides and
Toxic Substances
Washington, D.C.
U.S. ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
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DISCLAIMER
This project has been funded with Federal Funds from the
Environmental Protection Agency under contract number
68-01-3859. The content of this publication does not
necessarilyreflect the views or policies of the U.S.
Environmental Protection Agency, nor does mention of trade
names, commercial products, or organizations imply
endorsement by the U.S. Government.
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ABSTRACT
A prospective collaborative study was conducted to compare the effectiveness
of four clinical techniques in the detection of liver damage due to vinyl
chloride monomer exposure. A chemically exposed and medically monitored worker
population was identified by histopathological and biochemical documentation.
Three techniques were non-invasive: a) grey scale ultrasonography of the liver,
b) microvascular skin capillary assessment, and c) urinary analysis of glyco-
99
saminoglycan excretion. The fourth technique was the standard mTc sulfur
colloid radionucleotide liver spleen scan. The screening studies were performed
on a randomly selected single cohort of chemical workers; some of whom were known
to have disease. All four techniques were analyzed for their sensitivity and
specificity as compared to results of the liver biopsy and biochemical blood
test classification. Although all four screen-ing techniques had a sensitivity
and specificity sum greater than one, none were significantly better than could
be explained by chance or the use of a biased coin. Reclassification of the
population into those with more severe biochemical abnormalities improved the
sensitivity of all screening tests, but only the sensitivity and specificity sum.
for the GAG test were statistically significant at the 0.05 level, there was no
significant correlation between any pair of screening tests. None of the four
screening tests agreed with the biopsy results better than might be obtained by
biased coin or chance. These screening studies as presently constituted, do not
provide sufficient sensitivity and specificity to warrant their use in community
screening for subclinical asymptomatic hepatic injury due to chemical exposure.
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INTRODUCTION
The initial reports of primary liver cancers (angiosarcoma) in rats exposed
to vinyl chloride by Maltoni, et al (1) and the discovery of similar liver tumors
s
in vinyl chloride polymerization workers by Johnson and Creech (2) has lead to
considerable environmental concern regarding communities surrounding chemical
industries which utilize potentially carcinogenic agents such as vinyl chloride.
Several investigators have reported on various screening .techniques as effective
indicators of vinyl chloride chemicel injury. Four such techniques - ultrasono-
graphy (3), radionucleotide scanning (4), nailbed capillary visualization (5),
and glycosaminoglycan (GAG) (6) excretion - were reported to have some possible
usefulness in detecting early chemical injury to the liver. In order to determine
the useability of these techniques for community screening, the American Public
Health Association (APHA) and Environmental Protection Agency (EPA) funded a
multi-center collaborative study designed to determine the comparative sensitivity
and specificity of these various techniques in detecting and identifying chemical
related hepatic injury in asymptomatic individuals.
Materials and Methods
Population Selection
The chemical worker population consisted of 1,178 active (Group B, Figure 1)
employees as of September 1, 1977, and 70 employees who had had liver biopsies
regardless of current employment status (Group A, Figure 1); they were undergoing
annual medical screening for the identification of work-related disorders. The
medical screening consisted of an annual or semi-annual (for those employees with
10 or more years of employment) comprehensive history and physical examinations,
laboratory screening studies consisting of 35 biochemical tests, chest and abdomi-
nal X-rays, and radionucleotide liver-spleen scan.
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This population was selected for the collaborative study to determine the
comparative effectiveness of four screening techniques in detecting liver damage
as indicated by 1) past histopathological documentation of liver injury of
2) current hepatic dysfunction identified biochemically.
Three of the four techniques were included as potential non-invasive pro-
cedures suitable for determining the effects of vinyl chloride in a community
population. These included 1) grey scale ultrasonography of the liver as devel-
oped by Taylor and colleagues (7, 13, 14), 2) a nailbed skin capillary evaluation
of the middle and distal phalanges of the fingers as developed by Maricq and
associates (8), and 3) urinary analysis of glycosaminoglycan excretions (GAG)
as published by Kupchella and associates (9).
The fourth method included for comparison purposes was the standard radio-
99
nucleotide liver-spleen scan utilizying mTc colloid and interpreted by Whelan
and associates (10).
The non-invasive screening studies were performed during a single week on a
group randomly selected from all chemical company employees. The workers were
selected on the basis of complete medical and work data for 1976-1977, and all
those employees who had investigative liver biopsies performed during the
screening program (1974-1977). The selection process for these workers is
illustrated in Figure 1. The biochemical data and radioisotopic scans were part
of the routine medical surveillance system for the employees. The pathological
data was based on the last or most recent liver biopsy (s) which were performed
for medical reasons, both related and not related to their work. Positive and
negative results were determined as defined in Table 1 which list the technique,
v
the evaluation or evaluators, and the criteria used. The employees targeted for
examination were selected by simple random sampling from all available employees.
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One hundred and twenty one of the targeted 170 employees (71 percent) participated.
Twenty six declined to participate or could riot be scheduled; 13 did not keep
their scheduled appointment. After participation, nine employees were discovered
to have been misclassified as biochemically abnormal. They had some biochemical
./'
abnormalities but not all (classified intermediate) and have been eliminated from
the final analysis. Four biochemically abnormal individuals had abnormally low
test values and they were included in the analysis.
Liver Biopsies
Liver biopsies were performed by the transjugular technique (11) and pro-
vided two to five biopsies from various areas of the liver. In addition, some
individuals had second biopsies performed by the percutaneous or wedge biopsy
via mini-laparotomy procedures. Pathological data was recorded in a computerized
format identifying all histological abnormalities in a semi-quantitative fashion.
Biopsies were read without knowledge of the individual's medical history or
chemical exposure by two pathologists and a hepatologist with extensive experience
in hepatic chemical injury. All biopsies were classified as 1) normal, 2)
abnormal, a) chemical injury, and b) non-chemical injury.
. The non-biopsy groups were drawn from those currently employed, and based on
biochemical liver "function tests" individuals were sorted into positive,
negative and indeterminate for hepatic disease. Only the positive and negative
are included in this study.
The ultrasonic evaluation and its relative ability to identify hepatic
damage due to vinyl chloride has been published elsewhere (3).
Microvascular techniques and the method of evaluation by Dr. Maricq and
co-workers are also published in part (8).
The experimental work on GAG excretion in vinyl chloride workers and the
techniques for differentiating the electrophoretic patterns in patients with
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angiosarcoma and connective tissue damage of the liver has been published else-
where (9). The effectiveness of radioisotopic (radionucleotide) scanning as a
technique for identifying anatomical lesions in vinyl chloride workers is in
preparation (12).
Method of Analysis
The biopsied group and the non-biopsied (biochemical) group were analyzed
independently. For the biopsied group sensitivity and specificity were estimated
for each screening test by assuming that the biopsy was correct. For the bio-
chemical group the biochemical classification was assumed to be correct. For
each analysis the data consisted of a simple cross classification. In a perfect
screening test, the sum of sensitivity and specificity would be two. In a
screening test which provided results no better than could be obtained by using
a biased coin, the sum of sensitivity and specificity would be equal to one. We,
therefore, estimated 95% confidence limits for the sum of sensitivity and spec-
ificity and observed whether or not one is included within these limits. As a
2
test of statistical significance this is equivalent to the usual X test for
independent proportions.
Finally, in Table 4 we looked at the association (as measured by the phi
coefficient) between each pair of screening tests. For these comparisons we
used all employees who received both screening tests regardless of their biopsy
status. In this case, we assumed both tests were subject to error and estimated
the phi coefficient (r$) between them. Finally, for completeness, we give the
biochemical classification for the 51 employees included in the biopsy group.
Results
Table 2 compares the histological and biochemical results for the 51
biopsied employees included in the study. Twenty-two of these employees had
biochemical abnormalities as defined in Table 1. There was no significant
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correlation between the biochemical and biopsy classification for the 29
employees with positive or negative biochemical classifications (r$ = 0.21; Xf =
0.20). The biochemical studies used in this analysis were those determined at
the time of this and not at the time the biopsy was/performed. In all instances
s
of disagreement, the biopsy was positive and the biochemical results negative
(P< O.OOT).
Figure 2 provides the sensitivity and specificity for each of the screening
tests when compared to biopsy results. In no case is the sum significantly
greater than one, indicating that the results are not statistically significantly
better than could be obtained using the biased coin. With the exception of the
GAG studies, similar results are obtained when comparing the sum of sensitivity
and specificity in the biochemical group (Figure 3). The sum of sensitivity and
specificity for the GAG studies are just statistically significant with 95 percent
confidence limits of 1.06 to 1.52. Table 3 gives the frequency distribution of
the results of the GAG test for employees with normal and abnormal biochemical
results. The distributions differ in their spread (variance) and not in their
location (means).
Finally, the correlation matrix for the four tests are given in Table 4.
There is no significant correlation, as measured by r$, between any pair of the
screening tests. This is also true when they are sorted by biopsy status.
After reviewing the results, a reclassification of the 51 employees who had
biopsies was assessed in regard to whether there was chemically induced liver
damage. Ultrasonographic evaluation was reclassified by Dr. Taylor and the liver
biopsies by Drs. Tamburro and Popper. Table 5 gives the results of this additional
analysis which demonstrates that there was no agreement that could not be explained
by chance (P = 0.60).
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Discussion
The increasing industrialization in highly developed Western countries, such
as the United States, continues to provide concern, not only for the health and
safety of the industrial workers, but also for the surrounding communities in the
areas of these industries. It is highly desirable to identify and validate the
reliability of screening and diagnostic techniques which will identify the early
development of injury due to the exposure of a variety of chemicals such as
vinyl chloride. The assessment of newly developing techniques on a high-risk,
exposed worker population, who have been carefully screened and prospectively
followed, provide the most reliable method for determing both the sensitivity and
specificity of these technical procedures in the asymptomatic subclinical high-
risk exposed community population. The failure of such techniques to provide
sufficient sensitivity in the presence of a required specificity is of critical
clinical importance. This is especially so where the incidence of disease is
relatively low and the population exposed large. Tests which provide a high
sensitivity but of low specificity can and do medically stigmatize the population
under surveillance leading to unnecessary anxiety and socioeconomic disturbances
which can far outweigh the benefit of early detection of even serious disease in
a smaller population.
Far too often screening techniques which have been developed in a highly
diseased, clinically overt, hospitalized population are applied to an asymptomatic,
clinically well-working populations without adequate determination of the sensi-
tivity and specificity at this earlier stage of disease development.
In this study, all four techniques had, in the highly diseased hospitalized
population, demonstrated either a sensitivity or specificity suggestive for the
identification of underlying chemically related liver disease. Some techniques
(Maricq and Kupchella) appeared ideal for community studies since they were non-
invasive, relatively inexpensive, and provided a means of screening which would be
highly accepted by a community.
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This prospective!./ designed study has allowed us to estimate the ability of
ultrasonography, nailbed capillary assessments, radioisotopic scanning, and
glycosaminoglycan excretions to correctly predict the presence and absence of
hepatic disease as documented by an exposed population. These studies clearly
show that none of the four screening techniques sufficiently agree with either
the biopsy, the biochemical results, or each other in a well defined population;
they do not provide sufficient sensitivity or specificity to be useful as early
indicators of chemical exposure injury.
The inclusion of nine individuals with intermediate biochemical results,
who were originally misclassified as abnormal, would decrease the sum of sensi-
tivity and specificity in all three screening tests. With their exclusion only
the GAG tests provided results better than might be expected by chance (P< 0.05).
Even the GAGs, from a pragmatic point of view, provide too high a false positive
rate to be useful in its present stage. Possibly, with increased refinement and
further study, this might provide a simple non-invasive technique for the
identification of increased collagen changes related to chemical injury. More
immediately, it should be duplicated to rule out chance.
Had we eliminated the four employees with an abnormally low biochemical
test values, the sum of sensitivity and specificity for the GAGs and nailbed
skin capillary screening tests would have been slightly reduced and that for the
scan slightly increased. The GAG would still be of bordering significant
(xf = 3.73), and the scan not significant (X^ = 1.46).
Finally, the tests not only disagree with each other, but within the biopsy
group there was no agreement.between the biopsies and biochemical results. It
should be noted, however, that the biochemical studies used in analysis were
those chronologically closest to September, 1977, and not to the date of biopsy.
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8
The test determinations and the biopsies may have been as long as three years
apart. An analysis of the biochemical tests value done at the time of the
biopsy would have more accurrately reflected the liver status, as shown by
histology (15). It has been shown, in previously published studies, that
biochemical and histological findings each correlate with chemical injury and
chemical exposure (16, 17).
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References
1. Mai torn', C. and Lefemine, G. Carcinogenicity to bioassays of vinyl chloride
I. Research plan and early results. Environmental Perpectives, 7/.387-405,
1974.
2. Creech, J. L. and Johnson, M. N. Angiosarcoma of the liver in the manufac-
ture of polyvinyl chloride. Journal of Occupational Medicine, 16:150-151,
1974. ~
3. Taylor, K. J. W., Williams, D. M. J., Smith, P. M. and Dach, B. W. Grey
scale ultrasonogrephy for monitoring industrial exposure to hepatotoxic
agents. Lancet, jr.1222-1224, 1975.
4. Whelan, J. G. Jr., Creech, J. L. and Tamburro, C. H. Angiographic and iso-
topic characteristics of hepatic angiosarcoma found in vinyl chloride
workers. Radiology, 1JJ3:549-557, March 1976.
5. Maricq, H. R., Johnson, M. N., Whitstone, C. L. and LeRoy, E. C. Capillary
abnormalities in polyvinyl chloride production workers. JAMA, 236, 1368-
1371, 1976.
6. Kupchella, C. E. and Tamburro, C. H. Urinary and tissue glycosaminoglycan
patterns in angiosarcoma and oth«;r vinyl chloride exposure - associated liver
injury. In Prevention and Detection of Cancer, Part I, 1:915-926, ed.
Niebergs, H., Marcel Dekker, Inc., 1977.
7. Taylor, K. J. W., Carpenter, D. A., Hill, C. R. and McCready, V. R. Grey scale
ultrasound imaging the anatomy and pathology of the liver. Radiology, 119;
415-423, 1976.
8. Maricq, H. R. and LeRoy, E. C. Patterns of finger capillary abnormalities
in connective tissue disease by wide field microscopy arthritis pheum, 16:
619-629, 1973. ~
9. Curran, K. L., Kupchella, C. E. and Tamburro, C. H. Urinary glycosaminoglycan
patterns in angiosarcoma of the liver. Cancer, 40_: 3050-3053, 1977.
10. Whelan, J. G. Jr., Greenberg, R. and Tamburro, C. H. The effectiveness of
radioisotopic scans and grey scale ultrasonography in. the detection of liver
damage. Gastroenterology, 79:1129, 1980.
11. Rosch, J., Antonovic, R. and Dotter, C.T. Transjugular approach to the
Itver, biliary system and portal circulation. American Journal of
-Roentgenology, 1^:602-608, 1975.
12. Whelan, J. G. Jr., Creech, J. L. and Tamburro, C. H. Primary liver, cancer
detection in vinyl chloride workers by radioisotopic scanning (In Preparation).
13. Taylor, K. J. W», Glees,J. P., Smith, T. A. and Carpenter, D. A. Ultrasonic
examination of the liver. In Ultrasound in Medicine, Vol. 2., pp. 173-174
(Eds.) White, D. N. and Barnes, R., Plenum Press, New York, 1976.
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10
14. Taylor, K. J. W. and Carpenter, D. A. Comparison of radioisotopic and ultra-
sound examination in the investigation of hepatobiliary disease. In Ultra-
sound in Medicine, Vol. 1, pp. 159-167 (Ed.) White, D. N., Plenum Press,
New York, 1976.~~
15. Clarmont, R.J. and Chalmers, T.C. The transaminase tests in liver disease.
Medicine, 46:197-207, 1967.
16. Tamburro, C.H. and Greenberg, R. Effectiveness of federally-required
medical laboratory screening in the detection of chemical liver injury.
Environmental Perspectives, 1980. In Press.
17. Tamburro, C.H. and Greenberg, R.A. Identification of human toxicity and
carcinogenicity by ethylene derivatives in mechanisms of toxicology and
hazard evaluation (eds. Holmstedt, B., et al) Elsevier/North-Holland
Biomedical Press, New York, New York, pp. 319-334, 1980.
18. Tamburro, C.H., Makk, L. and Popper, H. Early hepatic histological
alterations among chemical (vinyl monomer) workers. Gastroenterology,
77:A43, 1979.
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Table 1
CLASSIFICATION
DETERMINED
BY
CRITERIA
Biopsy
1) Dr. Popper, Pathologist
2) Dr. Makk, Pathologist
3) Dr. Tamburro, Hepatologist
a) Positive by consensus agreement
if medically significant pathology
i is present. Negative otherwise.
b) Pathology is of chemical or non-
chemical origin. (18)
Biochemical
Liver "Function" Tests
Group 1
SGPT
ICG
SCOT
ALK. PHOSPHATASE
Group 2
GGTP
BILIRUBIN
Positive if two or more Group
tests were abnormal or if one
Group 1 and both Group 2 tests
were abnormal. Negative if all
six tests were normal.
Intermediate otherwise.
Ultrasound
Dr. Taylor
Defined as negative if the over-
all impression was normal. Posi-
tive otherwise.
Microvascular
Dr. Maricq
Defined as negative if there were
no microvascular abnormalities.
Positive otherwise.
Glycosaminoglycans
Uronic
acid
UG Uronic Acid
MG Creatinine
Defined as positive for values
less than 2.0 or greater than 4.8
Negative otherwise.
Liver Scan
Dr. Whelan
Defined as positive if any patho-
logical defect was detected.
Negative Otherwise.
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12
TABLE 2
COMPARISON OF BIOPSY AND BIOCHEMICAL
DETERMINATIONS OF THE PRESENCE
OF LIVER DISEASE
BIOPSY
POSITIVE
NEGATIVE
SUM
BIOCHEMICAL
POSITIVE .
3
0
3
' NEGATIVE
18
8
26
SUM
21
8
29
BIOCHEMICALtY.
INDETERMINATE
15
7
22
TOTAL
36
15
51
r = 0.20966 X2 = 0.200 N.S.
Matched
= (18 1} /18 = 16.
1 P < 0.001
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13
TABLE 3
FREQUENCY (F) AND RELATIVE FREQUENCY (R.F.)
OF GAGS FOR NORMAL AND ABNORMAL
>
... BIOCHEMICAL RESULTS
Normal Abnormal
GAG
< 2
2 < 3
3 < 4
4 < 5
5+
Sum
Mean
Variance
f
4
16
13
1
2
36
2.886
0.746
R.F.
0.111
0.444
0.361
0.028
0.056
1.000
f
6
7
6
1
4
24
3.160
1.776
R.F.
0.250
0.292
0.250
0.042
0.167
1.000
t = 0.968 N.S. T Test Independent Means
58
F =2.381 P < 0.05 F Test Independent
23'3S Variances ( Two Tailed)
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TABLE 4
CORRELATION MATRIX (Ro) BETWEEN FOUR SCREENING
TESTS USED TO PREDICT THE PRESENCE OR
ABSENCE OF LIVER DISEASE
14
GAG ANALYSIS
CAPILLARY ASSESSMENT
ULTRASOUND STUDY
RADIOISOTOPIC SCAN
GAG CAPILLARY ULTRASOUND RADIOISOTOPIC
ANALYSIS ASSESSMENT STUDY SCAN
(113)
(87)
(120)
0.08
(84)
(114)
-0.03
0.03
(88)
0.005
0.07
0.06
None of the correlations are statistically significant (a = 0.05)
The correlations are given above the diagonal.
The sample size is given in parenthesis below the diagonal.
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TABLE 5
FECLASSIFICATION OF BIOPSIED EMPLOYEES
FOR CHEMICALLY INDUCED ABNORMALITIES
15
Biopsy
Chemical
Abnormality
Other
SUM
Ultra Sound
Chemical ru-K-r-
Abnormality utner
7 5
26 13
33 18
SUM
12
39
51
Specificity = 13/39 = 0.333
Sensitivity = 7/12 = 0.583
Sum = 0.916
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FIGURE 1
16
GROUP A
GROUP B
All employees who
underwent investigative
Biopsys
(70)
Current employees
>dthout Biopsies
on 9/1/77
(1178)
Scan
(1011)
Based
on last Biocha
No Scan
(167)
mical Test
Positive
Biochemical
(81)
Targeted
(70)
Negative
Biochemical
(95)
Targeted
(50)
Scheduled
(57)
Indeterminate
Group
(835)
Targeted
(50)
Scheduled
(38)
Scheduled
(39)
Participated
(51)
Participated
(33)*
I
Chemical
Injury
(12)
Non-
Chemical
Injury
(39)
Participated
(37)
Biochemically
Abnormal
(24)
1
Reclassified
Biochemically
Indeterminate
(9)
*Not seen by Doctor Taylor
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FIGURE 2
SENSITIVITY AND SPECIFICITY. FOR FOUR.SCREENING
TESTS FOR THE PREDICTION OF LIVER ABNORMALITIES
(AS DETERMINED BY BIOPSY)
GO
-P
H
O
H
H
P
H
CO
C
0)
CO
Ntnrber Errployees
Positive Biopsies
Negative Biopsies
,22
80
.02
1.13
BS
i
Specificity
Sum: Sensitivity
plus
.53
.60
75
40
.64
.40
95% Limits
1.04
I Sensitivity
[Specificity
GAG
(51)
36
15
Microvascular Ultrasound Scan
(49)
34
15
(51)
36
15
(51)
36
15
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Figure 3
00
SENSITIVITY AND SPECIFICITY FOR FOUR SCREENING
TESTS FOR THE PREDICTION OF LIVER ABNORMALITIES
(AS DETERMINED BY REVIEWED BIOCHEMICAL TESTS)
-p
rl
O
H
«H
i-l
O
>
p
P
H
W
ti
(U
w
1.29
,46
83
Sum: Specificity
plus sensitivity
1.16
.57
.35
.. 95% Limits
1.15
.58
.57
Sensitivity
Specificity
GAG Microvascular Ultrasound Scan
Number Employees
Positive Biochemical
Negative Biochemical
(60)
24
36
(57)
22
35
(37)
(61)
24
37
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TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
1. REPORT NO.
5fin/fi-ai-nn?
2.
3. RECIPIENT'S ACCESSION NO.
4. TITLE AND SUBTITLE
SCREENING FOR THE EAfcLY DETECTION OF DISEASE
IN INDIVIDUALS EXPOSED TO VINYL CHLORIDE
S. REPORT DATE
January.
1981
6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S) Carlo H.Tamburro* Richard Greenberg* Charles Kupchella*
Hildegarde Maricq0 Kenneth Taylor' Joseph Whelan, Jr.* Emanuel Landau
Joseph Seifter++ '
8. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND ADDRESS
American Public Health Association "
1015 Fifteenth Street, N.W. *
Washington, D.C. ^000.5 . '....
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
68-01-3859
12. SPONSORING AGENCY NAME AND ADDRESS
Office of Pesticides and Toxic Substances
U.S. Environmental Protection Agency .
401 M Street, S.W.
Washington, D.C. 20460 ' ."
13. TYPE OF REPORT AND PERIOD COVERED
Final Report
14. SPONSORING AGENCY CODE
15. SUPPLEMENTARY NOTES . . .
University of Louisville* University of South Carolina0 Yale University' American Public Health Association*
U.S. Environmental Protection Agency ++
16. ABSTRACT A prospective collaborative study was conducted to compare the effectiveness of four clinical techniques in tjie
detection of l;ver damage due to vinyl chloride mj'nomer.exposure. A chemically exposed and medically monitored worker
population was identified by histo-p.athological and;biochemical documentation . Jhree techniques were non -invasive: a)
grey scale ultrasonography of the liver, b) microvainlar skin capillary assessment, and c) ujjnary analysis of glycosaminoglycan
excretion. The fourth techniques was the standard 99mTc sulfur colloid radionucleotide liver spleen scan. The screening studies
were performed on a randomly selected single cohort of chemical workers. All four techniques were analyzed for their sensitivity
and-specificity as compared to results of the liver biopsy and biochemical blood test classification. Although all four screening
techniques had a sensitivity and specificity sum greater than one,'none-were significantly.better than could be explained by
chance or the use of the biased coin. R classification of the population into those with more severe biochemical abnormalities
^mproved the sensitivity of all screening te.sts, but only the sensitivity and specificity sum for the GAG test were statistically
. significant at the 0..05 level. There was n'o significant correlation between any pair of screening test. None of the four screening
tests agreed with the biopsy results better than might be obtained-by biased coin or chance. These screening studies as presently
constituted,do not provide sufficient-sensitivity and specificity to warrant their use in community screening for subclinical
asymptomatic hepatic injury due to chemical exposure. .
7.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS
c. COSATl Field/Group
Vinyl chloride
Vinyl monomer
Occupational exposure
Community exposure .
Ultrasonography
Radionucleotide liver spleen scan
Microvascular skin capillary assessment
.Glycosaminoglycan excretion
Screening techniques-sensitivity and
specificity
Occupational study . CommunityStudy
8. DISTRIBUTION STATEMENT
Unlimited
19. SECURITY CLASS (ThisReport)
Unclassified
20. SECURITY CLASS (This page)
21. NO. OF PAGES
18
22. PRICE
EPA Form 2220-1 (R.r. 4-77) PREVIOUS COITION is oesouerc
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