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Human & Experimental Toxicology (1990), 9 , 377-380
@ Macmillan Press Ltd 1990
cs wns: 232: ~ 2 - 9
& Fowler BA A low molecular cin in brain attenuates lead inhibrcvulanic aad dehydratase corn. lcad binding protein. Journal of
~~rrmcnruTl herapeutics 1986: a?.
xepted 15 June 1990)
,
Study on Kidney Function in Female Workers Exposed to Perchlorethylene
A. Vyskoeil,' S. Emminger,' J. Tejral,' Z. Fiala,' E. Ettlerova3& A. CermanovA2
'Department of Hygiene, Medical Faculty, Charles University, Simkova 870,500 38 Hradec Kralove, 2Departmentof Occupational Hygiene, Regional Hygiene Station, Ba!binova 821, 500 31 Hradec Kralovk and 'Computer Centre, Medical Faculty, Charles University, Simkova 870, 500 38 Hradec KrilovC, Czechoslovakia.
1 Biochemical markers of kidney damage were examined in 16 female workers chrsnically exposed t o tetrachlorethylene (TCE) in five dry-cleaning shops. T h e results were compared with those obtained in 13 females non-occupationally exposed t o organic solvents. 2 The intensity of exposure was monitored by personal environmental monitoring. The time-weighed average exposure to TCE amounted to 157 mg m-3 (range 9-799 mg m-3). A satisfactory agreement was found between the concentration of T C E in ambient air
sampled with the charcoal tube method and with a passive dosimeter.
3 The urinary excretion of lysozyme was increased in the exposed group. No difference was found in the urinary excretion of albumin, f12-microglobulin, lactate dehydrogenase, total proteins or glucose. The prevalence of abnormal values of biochemical parameters in the exposed group did not differ from that observed in the control group. No correlation was found between the level of TCE exposure and biochemical parameters. 4 The present study suggests that chronic exposure to TCE does not lead to renal damage.
Introduction
Tetrachlorethylene (TCE), an unsaturated chlorinated hydrocarbon is extensively used as an industrial organic solvent for metal degreasing and dry-cleaning. Many studies report the effects
of TCE on various organs. The most commonly studied organ is the liver.'**So far, very limited
information has been available regarding its
effects on renal function. In recent studies
Goldsworthy er ai.?4 found nephrotoxicity and renal tumours in male rats gavaged with TCE (loo0 mg kg-'). Lauwerys et af.' did not find any
adverse effects of TCE on the kidneys of workers. On the contrary, Franchini et al.' found
increased lysozymuria and activity of urinary p-
glucuronidase in workers exposed to TCE. The aim of the present investigation was to re-
examine the nephrotoxic potential of TCE. We measured sensitive markers of tubular and glomerular toxicity in a group of female workers with an average exposure 157 mg m-3 TCE.
Methods
-1
The study was conducted on two groups of female subjects working in five dry-cleaning
shops. The exposed group consisted of 22 workers inhaling TCE. Their working conditions had always remained identical. It was compared with a group of 15 females with only administrative function and with no known exposure to organic solvents.
All participants were asked to answer a selfadministered questionnaire in which information
was obtained on occupational, demographic and health history. Subjects with a present or past history of kidney disease or systemic diseases known for their renal involvement (e.g. diabetes mellitus) were excluded from the statistical analysis of the results.
Exposure of each worker was monitored on the third or fourth day of the week over a whole day. Two absorbing systems, namely passive diffusion samplers (HK85/CKD-Czechoslovakia) and active charcoal tube samplers (Charcoal tubesconnectedto a personal SKC-222-4sampling
pump - USA, with a flow rate of 55 ml min-')
were positioned in the worker's beathing area, on the left lapel, at 10 cm distance from each other. One-hundred-and-sixty TCE samples (80 coincidental pairs) were carried out on 16workers
378 A. WSKOCIL et al.
during 1 year. Analyses of TCE were carried out using a gas chromatograph Chrom 61 (Czechoslovakia) equipped with a flame ionization detector after desorption with carbon disulphide.6
After the last TCE monitoring, at the end of the working day, a sample of urine from each subject was collected over phosphate buffer (pH 7.4) containing sodium azide as a preservative. All the samples were stored at 4C until the analyses were performed.
The concentration of µglobulin &), and albumin were determined by the RIA-test (UVVVR Prague, Czechoslovakia). Creatinine was measured by the method of Jaffk.' The urinary activity of lysozyme was measured by the method of Litwack.8 Urinary glucose was determined by the Oxochromglucose BIOLA-Test (Lachema, Czechoslovakia). LDH in urine was assayed by the UV-test (Sevac, Czechoslovakia). Total proteins were determined by the BIOLATest (Lachema, Czechoslovakia). All urinary parameters were corrected for the creatinine contents. The results of the analysis of the urine samples with creatinine of less than 0.4 g I-' were discarded.
The Kolmogorov-Smirnov test was applied to check if a distribution or its logarithmic transformation was normal. The homogeneity of variances was checked by the F-test. Student's t test was used to compare arithmetic or geometric means. The comparison of prevalence of elevated
values was performed with 2 X 2 x2 test (with
Yates correction) using XI? in the control group as a cut-off where x is the geometric mean and s is the geometric standard deviation. The level of
significance was taken as P < 0.05.
Results
The characteristics of both groups are summarized in Table 1. They are well matched for the listed criteria (number of subjects, duration of exposure, age, smoking habits, alcohol and analgesic consumption).
There was no appreciable non-occupational exposure to organic solvents in either group.
The mean value and the range of individual values of TCE time-weighed average exposure in five dry-cleaning shops are presented in Table 2. Laboratory tests showed that both the adsorption charcoal tube and the charcoal collector of the passive dozimcter measured TCE with an accuracy t 20% of the concentration present. This level of accuracy corresponds to the performance of these techniques in industrial pollution control. On average, the exposure level was below the Czechoslovak TWA (250 rng ~ I I -b~u)t
in three dry-cleaning shops 2040% of individual values exceeded 250 mg m-3.
Data on the urinary excretion of proteins and enzymes in control and exposed subjects are presented in Table 3. Only lysozyme was significantly increased in the exposed group. There were no statistically significant differences in the
urinary excretion of albumin. Pz-,, LDH or total
proteins. No elevated concentrations of glucose were found in control or exposed group (results
not shown). The prevalence of abnormal values in the
urinary excretion of proteins or enzymes in the exposed group did not differ from those observed in the control group (Table 4).
Figures 1 and 2 show the distribution of Pz-,
and lysozyme. The overall distribution of lysozyme is shifted to higher values in exposed workers.
We did not find any significant correlation between the level of TCE exposure and biochemical parameters (results not shown).
I II 12 34
Lysozyme in urine
I 5mg creat.
Figure 1 Cumulative frequency distribution of lysozyme in the urine of control (C) and exposed (E)
workers.
150 300 BETA,-M in urine
'1
450 pg g creat.
Figure 2 Cumulative frequency distribution of betaz ,,, in the urine of control (C) and exposed (E) workers.
Table 1 Charactt
Number voluntec -Number retaineu
Agelyearlmean I
Number of smoL Regular alcohol . Regular analgem Non-occupationa Duration of empi
Mean (range)
'I More than five
week, More Lh significant: Studt
Table 2 Time-weighed averag
Number Number pairs OJ Shop of workers measuremi
1 2 20 2 4 14 3 5 22 4 2 12 5 3 12
Total 16
80
a &,Pi . . . individual values
Table 3 Urin and total prott
Albumin (mg I
µglobul Lysozyme (mg LDH (Ug-' c` Total proteins
Data are ex1
Student's r-tes
Table4 Prc and cnzym
Urinary pa,
Albumin
&-micro& Lysozyme LDH
Total protc
a Highertt NS: not stil
shops 20430% of individual mg ry excretion of proteins and and exposed subjects are Only lysozyme was significexposed group. There were ificant differences in the
tlbumin, pZ-,,,,LDHor total
d concentrations of glucose )I or exposed group (results )f abnormal values in the proteins or enzymes in the I t differ from those observed (Table 4).
low the distribution of p2-,.,,
.werail distribution of lysohigher values in exposed any significant correlation b f TCE exposure and bio(results not shown).
-3L-$--Jsmg g- 1 creat.
in urine frequency distribution of ' control (C) and exposed (E)
---+---'450 r g g creat.
: on urine quency distribution of beta2-, 2) and exposed (E) workers.
RENAL FUNCTION IN FEMALES EXPOSED TO TCE 379
Tabk 1 Characteristics of the control and exposed group.
Number volunteered Number retained for study
Agdyearlmean f s.d.
Number of smokers Regular alcohol consumption' Regular analgesics consumption2 Non-occupational exposure3
Duration of employment/year/ Mean (range)
Control
15 13 36 f 6 6 3 1 0
9 (1-18)
Exposed
22 16 42 f 10 7 2 0 0
11 (1-25)
P
-
-
NS NS NS NS NS
NS
I More than five glasses of wine. beer or liquor per week, More than one tablet per week, More than 1 h week-' domestic-use of organic solvents, NS: not satistically
significant: Student's r-test or xz test with Yates correction.
Tabk 2 Time-weighed average exposure to TCE on the third or fourth working day.
~~ ~
~
Exposure level (mg mA3)
Number of Number pairs of
Shop of workers mrasurernenU
Charcoal tube
Mcpn
Range
(A)
Parsive sampler
Mean
Range
(P)
1
2
20
319
129-799
262
11S752
2 4 14
a4 9-249 72 11-231
3
5
22
283
1-1 1
276
23427
4 2 12
41 31-113 34 21-162
5 3 12
60 13-351 51 1P-360
Total 16
80
157
9-799
139
11-752
-~
a A,,P, . . .individual values
% of samples"
A.. + P,.
2 AJP
1.22 70 1.17 0 1.03 80 1.21 0 1.18 20
Tabk 3 Urinary excretion of albumin, P,-microglobulin, lysozyme, LDH
and total proteins in control workers and workers exposed to TCE'.
~
Control (n = 13) Exposed (n = 16) P
Albumin (mg g-' creat) µglobulin (~rgg-' creat) Lysozyme (mg g-' creat)
LDH (Ug-' creat)
Total proteins (mg g-' creat)
18.9 (5.7-61.4) 45.0 (11.7-153.6) 0.15 (0-1.49) 14.9 (2.7-47.1) 103 (32-254)
19.1 (7.7-97.2) 63.9 (9.9-333.3) 0.56 (04.16) 13.5 (2.7-67.1) 125 (49-535)
NS NS
< 0.05 NS
NS
~~~ ~ ~
~~ ~~ ~
a Data are expressed as geometric mean (range), NS: not statistically significant. Student's r-test; creat: creatinine
Tab& 4 Prevalence of abnormal values' in the urinary excretion of proteins and enzymes in TCEtxposed workers and in their controls.
Urinary parameter
Connol
Exposed
P
Albumin P,-microglobulin Lysozyme
LDH Total proteins
W13 1/16 NS W13 2/16 NS 0113 3/16 NS
W13 1/16 NS 1113 2.46 NS
a Higher than the 95th percentile of the values found in the control group.
NS: not statistically significant, x' test with Yates correction
380 A. WSKOCIL ef ul.
Discussion
In the present study the level of TCE was generally below the current TLV (250 mg m-3), but in three dry-cleaning shops 2040% of
individual values exceeded 250 mg w3.A satis-
factory agreement was found between the two sampling methods.
Glomerular permeability did not appear to be affected by TCE exposure as shown by unchanged
albumin excretion. No statistically significant differences were found in the urinary excretion of LDH, glucose or p2+,, which were used as
markers of tubular dysfunction. Only lysozyme, was significantly increased in the exposed group. Its distributionwas shifted to higher values in the exposed group.
Decreased tubular reabsorption of lysozyme leads to high concentrations of lysozyme in the urine of leukemic patients, patients who have been treated with aminoglycoside antibiotics and patients who have received kidney transplants. Consequently, lysozyme has become a largely used tool in the diagnosis of tubulopathies and
nephrotoxicity.e" Nevertheless, as the urinary excretion of other sensitive markers of tubular dysfunction were normal, it is difficult to interpret the increased lysozymuria as a result of tubular damage due to TCE.
Our results are in agreement with the results of
Franchini et who found a significantly increased lysozymuria and activity of urinary Jglucuronidase and no differencesin total proteinuria or albuminuria in female workers exposed to 68.9 mg m-3 TCE. Lauwerys et al.' did not find any significant differences in urinary excretion of
albumin and B2-,,i,n female workek exposed to 145 mg m-3 TCE.
The renal effects observed in our study seem to be very weak and their occurrence does not
correlate with the intensity of exposure. In view
of these limitationsand results of other authors,'J the existence of a chronic nephrotoxicity of TCE at low exposure levels remains very hypothetical. This conclusion is reinforced by the fact that
prolonged exposure to TCE in our study was not associated with an increased prevalence of sub-
clinical renal effects.
-.
References
' Lauwerys R, Herbrand J, Buchet JP, Bernard A & Caussin I. Health surveillance of worken exposed to tetrachlorethylene in dry-cleaning shops. Inwnational Archives of Occupational and Environmental H d t h 1983; 5 2 69-l7. Manh E. Metabolic changer following oral expourre to tetrachlorcthylene in subtoxic concentrations. Archives of
' Torieology 1987; 60: 293-9.
Goldsworthy TL,Lyght 0.Martin JT & Popp JA. Chlorin-
ated hydrocarbon nephrotoxicity and cell proliferation.
' PhrYmocob@r 1986;m:180.
Coldnvoihy TL. Lyght 0.Burnett VL & Popp JA.
Potential role of alfa-2pgjobuli, protein -let lecumulation and cell replication in the renal carcinogenicity of rats exposed to trichlorethylene, perchlorethylene and pentachlorethane. Toxicology and Applied Phomrocology 1988;
' % 367-79. Franchini I. Cavatona A, F a h i M. Lucenini S k Mutti A. Early indicators of renal damage in worken exposed to organic solvents. IntemaiiOM1Archives of Occupational and
Environmental Health 1983; 5 2 W7l.
Standard Czechoslovak methods. A m Hygienica Epidcmio-
' logica CI Microbwlogica. 1974; Suppl. 1 7 1-10. Henry RJ, Cannon DC & Winhelman JW. Clinical
chemistry: princQles and techniques. 2nd Ed. New York:
*
Harper and Row, 1974. Litwack G. Photometric determinationof
lysozyme activity.
Proceedings of Society for Experimental Biology and
Medicine 195.5; 3):401-3.
Cojocel C & Baumann K. Renal handling of endogenous
lysozyme in the rat. R e d Physbbgy 1983; 6: 38-65
lo Brouwer J. On the stability of urinary lysozyme. Clinical
Chemistry 1986; 32: 1.331.
" Ohata H, Hashimoto T, MOWK K. Takahashi A & Terao
T. Urinalysis for detection of chemically induced renal
damage (3) Establishment and application of radioimmuno-
assay for lysozyme of rat urine. Archivesof Toxicology 1%;
62: 60-5.
Human & Experimental Toxi
Pre-embarkment I
Hiroshi Yamaguchi. '
'Department of Anesthesiol of Anesthesia, Tsuchiura K Hospital, Japan
1 In order to assess wh, patients with acute p a r a
who had ingested paraqu
2 Serum creatinine and excess levels, arterial bl(
urinary paraquat qualitat
surviving patients were s' 48 h of ingestion. 3 The relationship of the
Eq, =
against the interval of tirr
-with prognosis (P C 0.01 )
rate, Eq,: (930 399 X Lc LOgT) 3%, P C 0.01.
Introduction
As intensive therapeutic mc with acute paraquat pisor. lavage followed by a numbc of activated charcoal, len: haemoperfusion, plasmapt diuresis have been attemptel elabwate and costly tre improved the survival rate. point of cost performance predict the prognosis prior t other hand, the quality of patients who have ingested amount of paraquat as we shouldbe emphasized.' It is i both physical and mental IT early as possible to avoid US) able treatment for the 1 prognosis quod vitam'.
Until now there have be nostic indicators besides I paraquat concentration.'0index.I6 Since it is not poss
Correspondence: Shigehito Sat(
Manabc-Shinmachi, Tsuchiura-c