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Environmental Health Perspech Vol. JAPP, S5-88, 1981
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'y/Wurmation Center
Results of Sputum Cytology among Workers Exposed to Vinyl Chloride Monomer and to Poly(vinyl Chloride)
by Cesare Maltoni* and Paola Lodi*
The results of systematic cytological sputum examinations of 3,380 Italian VC-PVC industry workers and of 2,287 workers in other industries at different potential risk and chosen as control groups are reported.
The results indicate an increase in cellular abnormalities and dysplasias in the epithelium of the respiratory tract among VC-PVC workers. These data are in line with experimental results showing that VC produces lung tumors in mice and with early epidemiological evidence among exposed workers.
Introduction
In 1975, it was decided to include the cytological examination of sputum in the protocol of systematic medical surveillance of the workers in all the Italian plastic factories exposed to vinyl chloride (VC) and pcly(vinyl chloride) (PVC).
This program was co-sponsored by the Italian Federation of Unions of Chemical Workers (FULC) and by the Public Health Service of the Italian regions where the factories were located.
The decision to investigate cytologically all Ital ian VC-PVC industry workers was taken on the basis of the following facts: (1) the observation of a marked increase in the incidence of lung adenomas in mice exposed by inhalatory route, to a spectrum of doses of VC ranging from 10,000 down to 250 ppm (1-S); (2) the unusual finding of cellular ab normalities in a high portion of the lung adenomas of exposed mice (1-3); (3) the observation of fre quent severe abnormalities (squamous dysplasia and atypical adenomatous hyperplasia) in the sputa of a small group of heavily exposed workers (3); (4) the report of some increase in lung carcinomas among workers from two VC-PVC factories U); (5) the finding that the majority of lung carcinomas
Institute of Oncology and Tumor Center, Bologna, Italy.
observed among exposed workers were not of a common histotype i.e., giant cell carcinomas (5).
Planning and Methods
The investigation was carried out on workers from 13 Italian VC-PVC factories located in the northern, central and southern parts of Italy, namely, in Villadossola (1), Portomarghera (3), Bollate (1), Ferrara (1), Ravenna (1), Rosignano (1), Temi (1), Brindisi (1), Ferrandina (1), Porto Torres (1) and Cagliari (1).
A total of 3380 workers was examined. These workers have been and/or are exposed to the monomer and part of them also to PVC dust. For comparison 2287 workers in other industries at different potential risk were examined: namely, workers manufacturing PVC products, workers in chemical industries not dealing with plastics, metal workers, miners and workers in the chromium industry.
For each sputum examination four cytological slides were prepared. The smears were stained by the Papanicolaou technique.
The slides were screened and evaluated indepen dently by the pathologists of the hospitals in the area where the factories were located, then by a trained cytologist in our institute. All abnormal smears were reviewed by the senior pathologist of
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Table 1. Type, sequence and classification of local changes in the genesis of the various histotypes of pulmonary carcinomas.
Stage
Cytologic classes
Initial nonspecific stage
4
Adenomatous hyperplasia 1
Normal respiratory epithelium
Nonciliated cuboid epithelium
Squamous metaplasia
4
___ ^ <--
4
Basal cell hyperplasia
4
II. IKIII) Il-III
Intermediate specific state
Atypical adenomatous proliferation
*
Tumor stage
Predinical tumor Clinical tumor
| In situ adenocarcinoma
r+ Invasive
[adenocarcinoma
--^
Squamous dysplasia
In situ squamous carcinoma
Invasive squamous carcinoma
<-- Basaloid cell dysplasia
I.n4s'.itu ' anaplastic carcinoma
'i'
Invasive anaplastic > carcinoma
(ID-III, III, III-IV
IV and V
Table 2. Classification, characterization, distribution by classes and code of sputum cytology findings. Cell character
Class
Type*
Degree Quantity
Code
Not performed
I Normal epithelium (LRE, URE, OCA) Histocytes
I-II Normal epithelium (LRE, URE, OCA) Histocytes
II Squamous metaplasia LRE Hypersecretive mucous cells
II-(III) Squamous metaplasia LRE Adenomatous hyperplasia LRE
II-III Mild atypical adenomatous hyperplasia LRE Mild squamous dysplasia LRE Mild dysplasia URE, OCA
(ID-III Mild atypical adenomatous hyperplasia LRE Mild squamous dysplasia LRE Mild dysplasia URE, OCA
III Well defined atypical adenomatous hyperplasia LRE Well defined squamous dysplasia LRE Well defined dysplasia URE, OCA
III-IV Grave atypical adenomatous hyperplasia LRE Grave squamous dysplasia LRE Grave dysplasia URE, OCA
IV Adenocarcinoma Suspected Squamous carcinoma Undifferentiated carcinoma
V Adenocarcinoma Squamous carcinoma Undifferentiated carcinoma
Not evaluable
+/+ + +++
*LRE = lower respiratory epithelium; URE = upper respiratory epithelium; OCA = oral cavity.
1, 2, 3 1, 2 1, 2, 3
3 lf 2, 3
1, 2, 3
1 1 1
2, 3 2, 3 2, 3
99 01 02 03 04 05 06
07
08
09
10 11
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Table 3. Incidence of various types of cytological changes in sputa: comparison of results among VC-PVC workers and workers of the reference groups.
Cytological changes
Group
Non-
Hyper-
eval-
secretive
uable
mucous Squamous
cases
Cases cells and meta-
(in without squamous plasia
suf- epithelial metaplasia LRE
No. ficientEval- changes LRE+/+ + + + +
of mate- uable---------------- --------------
cases rial) cases No. % No. % No. %
Squamous
Atypical
metaplasia Adenoma- adenoma-
with horn tous hyper- tous hyper- Squamous
pearls
plasia
plasia dvsplasia
LRE
LRE
LRE
LRE
No. % No. % No. % No. %
Dysplasia URE, OCA
No. %
Workers of VC- 3380 822 2558 799 31.2 1153 45.1 374 14.6 70 2.7 794 31.0 38 1.5 219 8.6 44 1.7
PVC industry
PVC manu
422 79 343 99 28.9 253 73.8 36 10.5 1 0.3 74 21.6 4 1.2
4 1.2 1 0.3
facturers
Workers of 1019 130 889 165 18.6 604 66.9 83 9.3 various chem
3 0.3 227 25.5
8 0.9
10 1.1
'
~
ical industries*
Metal workers 264 54 210 73 34.8 109 51.9 30 14.3 1 0.5 5 2.4 - -
6 2.8 _
_
Miners1*
402 48 354 47 13.3 254 71.7 41 11.6 1 0.3 59 16.7 5 1.4
4 1.1 1 0.3
Workers of
180 28 152 9 5.9 89 58.5 69 45.4 1 0.6
7 4.6 6 3.9 28 18.4 -
-
chromium
industry
Other than VC-PVC and chromium industries and not exposed to a known risk. bNot exposed to a known risk.
Table 4. Distribution, by classes of cytological changes in sputa: comparison of results among VC-PVC workers and workers of the reference groups.
Group
Not Classes
evaluable
---------------------------------------------------------------------------------------------------------------------------------
No. cases Eval- !, I-Il
II II-(III) II-III (II)-III III III-IV IV
V
of (insufficient uable ------------ ------------ ----------- ----------- ----------- ------------ ------------ ---------- -----
cases material) cases No. % No. % No. % No. % No. . % No. % No. % No. % No. %
Workers of 3380 822 2558 799 31.2 705 27.5 780 30.4 211 8.6 21 0.8 35 1.3 7 0.2 VC-PVC
-
industry
PVC manu 422 79 343 99 28.9 135 39.3 102 29.7 4 1.2 1 0.3 1 0.3 1 0.3 - ~
-
facturers
Workers of 1019 various chem
130
889 165 18.6 399 44.8 313 35.2 6 0.7 6 0.7
""----
ical industries*
Metal workers 264 54 210 73 34.8 102 48.6 28 13.3 6 2.8 _ _ 1 0.5
Miners1*
402 48 354 47 13.3 220 62.1 82 23.1 2 0.6 1 0.3 1 0.3 1 0.3
------
Workers of
180
28
152 9 5.9 63 41.5 51 33.6 18 11.8 2 1.3 5 3.3 4 2.6
chromium
industry
Other than VC-PVC and chromium industries and not exposed to a known risk. bNot exposed to a known risk.
Table 5. Distribution of classes II-(III) and over among VC-PVC workers and the workers in reference groups.
Groups
Workers of VC-PVC industry PVC manufacturers Workers of various chemical industries Metal workers Miners Workers in chromium industry
Classes II-(III), %
30.4 29.7 35.2 13.3 23.1 33.6
Classes II-III, (II)-III, %
9.4 1.5 1.4 2.8 0.9 13.1
Classes III, III-IV, %
1.5 0.6
0.5 0.6 5.9
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the same institute. A joint critical reevaluation was carried out for those cases where there was not full agreement.
The same criteria of classification of the lesions and their distribution by classes were adopted by all pathologists.
Such criteria are based on our knowledge of the local cytological changes and of their sequence in the genesis of the various histotypes of pulmonary carcinomas (Table 1).
The list of the most relevant changes correlated with environmental and occupational exposure, their distribution by classes following qualitative and quantitative parameters, and the code, are given in Table 2. This list takes into account not only cells from the pulmonary tree, but also cells from the upper respiratory tract and oral cavity.
Results
The number of valuable cases, the distribution of the cytological changes and the distribution of the results expressed by classes in the group of work ers in the VC-PVC industries and in the control groups, are given in Tables 3 and 4. The incidence of dysplastic changes is particularly high in the plastics industry workers when compared to the other control groups, with the exception of chro mium workers, which can be considered a positive control. The situation is well illustrated by the distribution of classes II-(III) and above (Table 5).
It may be stated that, in relation to the incidence of respiratory cell abnormalities, the workers in the VC-PVC industries can be placed halfway between chromium workers and other groups.
A finding which deserves attention is the occur rence of atypical cells in the oral cavity and upper respiratory tract in 44 workers (17%) among VC-PVC workers (Table 3).
The results were highly homogeneous in differ ent factories, suggesting that variations in climate, which may affect the incidence of common pneu mopathies, is not a determining factor.
The difference in the distribution of the patholog ical findings was not dependent on tobacco smok ing.
Conclusions
The results presented are consistent with exper imental data and early epidemiological evidence on the potential oncogenic effects of VC exposure on the lungs.
Furthermore, our data suggest a possible onco genic risk for the upper respiratory tract which should now be explored by proper epidemiological investigation.
Much remains to be done to clarify the part played by the monomer and by polymer dust in determining the observed cytological changes. Our data are now being re-examined, on the basis of the complete exposure history of single workers, to better establish the role played by PVC particles.
REFERENCES
1. Maltoni C., and Lefemine G. Carcinogenicity bioassays of vinyl chloride. I. Research plan and early results. Environ. Res. 7: 387-405 (1974).
2. Maltoni, C., and Lefemine, G. Carcinogenicity bioassays of vinyl chloride: current results. In: Toxicity of Vinyl ChloridePolwinyl Chloride, New York Academy of Sciences, New York, 1975, pp. 195-218.
3. Maltoni, C., Lefemine, G., Chieco, P., and Carretti, D. La cancerogenesi ambientale e professionale: nuove prospettive alia luce della cancerogenesi da cloruro di vinile. 0spedali Vita, 1 (5-6): 4-66 (1974).
4. Wagoner, J. K. Statement before the Subcommittee on the Environment of the U.S. Senate Commerce Committee, 1974.
5. Thomas, L. 6. Personal communication.
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