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Envi-ronmental Health © Springer-Verlag 1991

Urinary excretion of proteins and enzymes in workers exposed to hydrocarbons in a shoe factory Adolf Vyskocil l , Albert Popler 2, Iva Skutilova 2 , Milena Ciharova 2, Eva Ettlerova 3 , Robert R Lauwerys 4 , and Alfred M Bernard4 'Department of Hygiene, Medical Faculty, Charles University, Simkova 870, 50038 Hradec Kralov 6, Czechoslovakia

2 District Institute of National Health, Kyjevska 44, 53203 Pardubice, Czechoslovakia 3 Computer Centre, Medical Faculty, Charles University, Simkova 870, 50038 Hradec 4

Kralovd, Czechoslovakia Unit of Industrial Toxicology and Occupational Medicine, School of Medicine, Catholic University of Louvain, Clos Chapelle-aux-Champs, 30 54, 1200 Bruxelles, Belgium Received November 16, 1990 / Accepted March 20, 1990

Summary A cross-sectional study was conducted to determine whether exposure to hydrocarbons in a shoe factory may produce renal effects that can be detected by determination of the urinary excretion of proteins and enzymes The study population included 59 women who had been exposed to petroleum naphtha and toluene and 24 age-matched control women The time-weighted average exposure to petroleum naphtha, toluene and ethylacetate was 1,619, 81 and 160 mg/m 3, respectively The integrity of the renal structures or functions was assessed by measuring the urinary excretion of total protein, beta 2microglobulin, retinol-binding protein, albumin, transferrin, lysozyme, lactate dehydrogenase and beta-Nacetylglucosaminidase (NAG) The only parameter that was significantly influenced by hydrocarbon exposure was the urinary activity of beta-N-acetylglucosaminidase. Although the health significance of this renal change, which was not accompanied by changes in the urinary excretion of low or high-molecular-weight proteins, is unclear, the results of the present study are in agreement with our previous observations suggesting that long-term moderate exposure to solvents does not entail a significant risk for the development of nephrotoxicity.

which are well documented, have been attributed to the interference of the hydrocarbons with the renal disposal of the male-rat-specific alpha 2 ,-globulin. In humans, the potential of hydrocarbons to induce renal effects or diseases during chronic exposure remains unclear An association between hydrocarbon exposure and the development of glomerulonephritis has been suggested on the basis of case reports and case-control studies l4, 9 l Cross-sectional studies carried out in several countries l1, 5, 9, 12, 13, 16 l have provided some evidence indicating that chronic exposure to hydrocarbons might cause subclinical renal disturbances involving the glomerular or tubular function The solvent(s) or mixtures of solvents and the exposure levels responsible for these effects are unknown However, it does not seem likely that exposure to styrene at levels of up to 50 ppm would cause nephrotoxicity l17, 18l The aim of the present study was to determine whether exposure to relatively high concentrations of petroleum-derived hydrocarbons in a shoe factory might lead to renal effects that are detectable on the basis of an increased urinary excretion of proteins or enzymes, which are considered to be very sensitive indicators of renal disturbances.

Key words: Hydrocarbon nephrotoxicity Enzymuria

Subjects and methods

Proteinuria -

Introduction Petroleum naphtha or mixed distillates are complex blends of aromatic hydrocarbons, alkanes, cycloalkanes and olefins The exact composition of naphtha varies with the crude oil source and the refining conditions Petroleum naphtha and numberous other petroleum-derived hydrocarbons can produce renal tubular lesions and tumors in male rats exposed by inhalation l 11l These effects, Offprint requests to: A Vysocil

The present study was conducted on two groups of women The exposed group was composed of 59 women who had been exposed to petroleum naphtha and toluene in a shoe factory The main source of exposure was solvent evaporation from glued surfaces. Two types of glues were used: naphtha "Robinol", containing technical-grade petroleum 50/110 (Czechoslovakia), with 3% being aromatics, and "Vukolep" containing toluene, ethyl acetate, and petroleum naphtha The characteristics of the former glue are listed in Table 1 A total of 24 age-matched women with no history of exposure to nephrotoxic chemicals were selected from a textile factory located near the shoe factory All participants filled out a questionnaire requesting information on their occupational, demographic and health history Subjects who had a current or prior history of diseases that could have affected the kidney or the urinary tract were excluded from the study On the basis of these

360

Table 1 Specifications of technical-grade petroleum naphtha 50/160 Initial boiling point 5 vol % 97 vol % Aromatics, wt % Benzene, wt %

50°C 70 °C 110 °C 3 05

Table 2 Characteristics of the control and exposed groups Control group

Exposed group

Number volunteering

24

59

Number retained for study

23

48

Age (year, mean + SD)

34 + 11

38 + 11

Number of smokers criteria, 48 exposed workers and 23 control subjects were retained for the study. The exposure of each worker was monitored on the 3rd and 4th days of the week using personal passive samplers (P4, Czechoslovakia) worn throughout the work shift The solvents adsorbed on the charcoal layer were extracted with C52 Petroleum naphtha compounds and toluene were analyzed by gas chromatography using a column packed with Chromaton N Super (Lachema, Czechoslovakia) coated with 20 M 15% Carbowax and a Chrom V chromatograph (Laboratorni pristroje, Prague, Czechoslovakia) equipped with a flame ionisation detector One urine sample was collected from each subject at the end of the work day over 1 mol/l phosphate buffer (p H 7 4) containing sodium azide (1%) as a preservative All samples were stored at 4 C until their analysis, which was performed within 1 month. Concentrations of albumin, transferrin and retinol-binding protein (RBP) were measured by an automated latex-particle assay l 2l, whereas those of beta 2 -microglobulin (beta 2-m) were determined by the RIA-test (UVVVR, Prague, Czechoslovakia) Creatinine levels were measured using the method of Jaffd l 6l The urinary activity of beta-N-acetylglucosaminidase (NAG) and that of lysozyme were determined by the methods of Tucker et al l15 l and Litwack l 10l, respectively Urinary glucose content was determined using the oxochromglucose BIOLA-Test (Lachema, Czechoslovakia) Levels of lactate dehydrogenase (LDH) in urine were assayed by the UV-test (Sevac, Czechoslovakia) All urinary parameters were corrected for creatinine content The results of the analysis of urine samples that showed creatinine levels of < 0.4 g/l were discarded. The Kolmogorov-Smirnov test was applied to check the normality of the distributions The homogeneity of variance was ascertained by the F-test Student's t-test was used to compare arithmetic or geometric means Comparisons of the prevalence of elevated values were performed according to a 2 x 2 chi-square test (with Yates correction), with the cut-off being the geometric mean + 2 geometric SD of the results found for the control group Spearman correlation coefficients were also calculated The level of significance was taken as P < 0 05.

Results The characteristics of the control and exposed groups are summarized in Table 2 The control and exposed groups did not differ significantly with respect to age and smoking habits None of the control or exposed subjects reported a regular consumption of alcohol (more than five glasses of wine, beer or liquor per week) or of analgesics (more than one tablet per day) Non-occupational exposure to organic solvents was negligible in both groups. The mean value and the range of individual values for the time-weighted average exposures to solvents are presented in Table 3 The levels of exposure to toluene and ethyl acetate were on average below the threshold limit values (TLVs) For ethyl acetate, all individual values were below the TLV, whereas 4 2% of individual values for toluene exceeded the TLV The time-weighted aver-

2

Duration of employment (years): Mean + SD Range

5

13 + 10 1 31

13 + 8 1 29

Table 3 Hydrocarbon concentrations in the breathing zone (TWA) of the exposed workersa Solvents

TLV Measured values (mg/m3 ) (mg/m3 ) Mean Range

Petroleum naphta

500b

1,619

Toluene

380 c

81

28

578

42

1,440 c

160

10

398

0

Ethyl acetated

243-3,736

% of samples > TLV 94

Number of samples = 48 Czechoslovakian TLV c ACGIH 1990 TLVs, German 1989 MAK values d Only 11 workers were exposed to ethyl acetate a b

age values for petroleum naphtha concentrations varied between O 5 and 7 times the TLV, with 94 % of individual values exceeding the TLV. Data on the urinary excretion of proteins and enzymes in control and exposed subjects are presented in Table 4. Exposed workers were divided into these groups according to the petroleum naphtha concentrations in their breathing zone No statistically significant difference was found in the urinary excretion of albumin, transferrin, RBP, beta 2 -m, LDH or lysozyme Total proteinuria was significantly higher in groups that had been exposed to petroleum naphtha concentrations of > 1,001 mg/m 3 , and the urinary excretion of NAG was significantly increased in all exposed groups No elevated value for glucosuria was detected in control or exposed subjects (results not shown). Table 5 shows the results of the same parameters in terms of the prevalence of increased values Elevated values for NAG activity in urine were found significantly more frequently in the exposed group The prevalence of abnormal values for the urinary excretion of other parameters did not differ significantly between the two groups Figure 1 clearly shows that the distribution of urinary NAG is shifted to higher values in exposed workers, with the difference being statistically significant We found no correlation between the duration of exposure or the concentrations of hydrocarbons in air and the various biochemical parameters, the exception being a slight correlation between total proteinuria and the concentration of petroleum naphtha in air (r = 0 31, P < O 05).

361 Table 4 Urinary excretion of albumin, beta2 -m, LDH, lysozyme, total proteins and NAG in control workers and hydrocarbonexposed worders divided into 3 groups according to the petroleum naphta concentration in air

Petroleum naphta concentration in air (mg/m3 )

Albumin (mg/g creatinine) Transferrin (pg/g creatinine) Beta 2-m (pg/gcreatinine) RBP (pg/g creatinine) LDH (U/g creatinine) Lysozyme (mg/g creatinine) Total proteins (mg/g cratinine) NAG (U/g creatinine)

Control workers

Exposed workers

0 (n = 23)

< 1,000 (n = 18)

1,001-2,000 (n = 13)

> 2,000 (n = 17)

Total (n = 48)

8 (1 9-36 1) 297 (33-2,920) 33 3 (4 6-231) 81 (20-1,300) 11 8 (2 9-36 8) 0 58 (0 09-2 25) 96 (25-270) 1 61 (0 2-6 4)

11 21 (6 8-57 4) 260 (52-890) 34 1 (11 5-110 2) 44 (11 8-250) 16 5 (3 1-35 7) 0 61 (0 1-5) 99 (25-280) 4 03 ** (0 3-18 9)

9 51 ( 2 4-39 2) 277 (41-1,550) 57 6 (26 8-235 3) 49 5 (18-180) 13 1 (6 7-36 8) 0 52 (0 17-1 8) 142 * (93-310) 3 93 * ( 1 1-21 9)

9 13 (3 1-65 3) 299 (98-2,640) 53 8 (18-166 2) 58 (21-126) 16 6 (7 9-28) 0 42 (0 11-0 83) 134 (70-280) 2 96* (0 6-16 3)

9 96 (2 4-65 3) 278 (41-2,640) 46 6 (11 5-235 3) 50 (12-250) 15 5 (3 1-36 7) 0 51 (0 1-5) 121 (25-310) 3 55 ** (0 3-21 9)

Data are expressed as geometric means; ranges are indicated in parentheses * P < 0 05, ** P

Urinary excretion of proteins and enzymes in workers exposed to hydrocarbons in a shoe factory.

A cross-sectional study was conducted to determine whether exposure to hydrocarbons in a shoe factory may produce renal effects that can be detected b...
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