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Archives of Environmental Health: An International Journal Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/vzeh20
Chromium in Biological Samples from Low-Level Exposed Stainless Steel and Mild Steel Welders a
Jens Peter Bonde M.D. & Jytte Molin Christensen a
b
Department of Occupational , Medicine Hospital , Aalborg, Denmark
b
Danish National Institute of Occupational Health , Copenhagen, Denmark Published online: 03 Aug 2010.
To cite this article: Jens Peter Bonde M.D. & Jytte Molin Christensen (1991) Chromium in Biological Samples from Low-Level Exposed Stainless Steel and Mild Steel Welders, Archives of Environmental Health: An International Journal, 46:4, 225-229, DOI: 10.1080/00039896.1991.9937453 To link to this article: http://dx.doi.org/10.1080/00039896.1991.9937453
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Chromium in Biological Samples from Low-Level Exposed Stainless Steel and Mild Steel Welders
JENS PETER BONDE, M.D. Department of Occupational Medicine Hospital of Aalborg Denmark
J U T E MOLIN CHRISTENSEN Danish National Institute of Occupational Health Copenhagen, Denmark
ABSTRACT. Occupational exposure to hexavalent chromium i s of concern because of the carcinogenic action of this metal. The purpose of this study was to evaluate internal exposure to chromium in welders who were exposed to low levels of chromium. Chromium in urine, blood, and seminal fluid was determined among 60 welders and 45 referents. The concentration of chromium in urine and blood did not change across a workshift or across a 3-wk break in exposure. However, stainless-steel and mild-steel welders who were exposed to low levels of chromium and steel welders who were mildly exposed had significantly increased levels of chromium in post-shift urine (mean 2.1 nmol/mmol creatinine [standard deviation (SD) = 1.01 and 1.3 nmol/mmol creatinine [SD = 0.51, respectively) compared with referents (mean 0.7 nmol/mmol creatinine [SD = 0.31). Pre-shift blood chromium concentrations showed a similar variation between exposed workers and referents. Subgroups of stainless-steel welders had very high levels of chromium in seminal fluid. This finding may, however, be explained by nonoccupational factors and, therefore, warrants further study. Attention should focus on the potential risk of delayed health effects among stainless-steel and mild-steel welders who heretofore were not thought to be at risk from chromium exposure.
OCCUPATIONAL EXPOSURE to hexavalent chromium is of concern because of its mutagenic and carcinogenic actions.’’2 Welding of stainless steel ( S S ) with the manual metal arc (MMA) method may be associated with substantial pulmonal absorption and urinary excretion of ~ h r o m i u m . ” ~ The emission of hexavalent chromium at tungsten inert gas (TIG) SS and mild-steel (MS) welding is much lower compared with MMAlSS welding. (Stainless steel is an alloy of iron, nickel, and chromium. Mild steel is an alloy of iron, carbon, and silicon.) Knowledge of the magnitude of internal exposure to chromium associated with TlGlSS and MS weldjuly/August 1991 [VO~. 46 (NO.4
1
ing is, however, very limited. Two studies found urine chromium concentrations of TlGlSS welders in the range of population-based normal value^.^'^ Although the risk for delayed health effects from long-term, lowlevel exposure to chromium i s questionable, it should be recognized that the number of TIGlSS and MS welders throughout the world i s high and i s increasing relative to the number of SS welders who use the MMA methods. The aim of this study was to examine the internal exposure to chromium among TIGlSS and MS welders who, to date, have not been considered to be at risk from chromium exposure. 225
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Subjects and methods Subjects. The study was conducted at 6 plants in Aalborg, Denmark. The plants manufacture SS equipment, pumps, boilers, and many different steel constructions in MS. A total of 105 metal workers and electricians were enrolled in the study. Information about occupational experience during the 6 mo that preceded the study and through adult life was gathered by structured interview. The study population consisted of 30 TlGlSS welders, 30 MMA andlor metal active gas (MAG) MS welders, 29 non-welder metal workers (i.e., drillers, fitters, crane drivers, storemen), and 16 electricians. Welding fume exposure. Ambient air measurements of welding fume particulates were taken among randomly selected TlGlSS welders (n = 151, MMAlMS welders (n = 14), and MAGlMS welders (n = 15). Air was sampled on filters (Millipore Filter AAWPO 37-mm; mean pore size, 0.8 p) from the breathing zone with portable pumps. The sampling time was approximately 6 h. The filters were analyzed for welding fume particulates (filter weight) and particular metals (atomic absorption spectrometry). The concentration of hexavalent chromium was determined by the carbonate method’’ from one-half of the filter. Biological samples. The participants were given written and oral instruction to avoid contamination of urine and semen samples. The samples were delivered outside the working room after change of dress and washing of hands and arms. Specimens were obtained in acid-washed polyethylene bottles (urine and semen) and tubes (blood) delivered and controlled for contamination by the laboratory. Chromium in urine. A post-shift urine sample (PS urine sample) was obtained from all participants the fourth day of work in a week. From TlGlSS welders and electricians were collected a morning spot urine sample (second void in the morning) before-shift the first day of work (BS urine sample), and a before-shift urine sample the first day after 3 wk vacation (AV urine sample). Seven SS welders from 1 of the plants (n = 14) were asked to deliver the AV urine samples. All samples, including blood and semen samples, were stored at -80 “C until analysis. Chromium concentration in urine was determined by Zeeman atomic absorption spectrometry (Z-AAS).” Creatinine concentration in urine samples was determined by the Jaffe reaction with a Beckman 42 spectrophotometer. Chromium in blood. From subgroups of all participants, a blood sample was taken by venipuncture (elbow) before workshift the first day of work. TIGlSS welders from 1 plant had another blood sample taken before workshift on the first day after a 3-wk vacation. Chromium concentration in blood was determined by Z-AAS. Blood (250 pl), water (0.50ml), and 0.04 ml subtilisin A (40 g/l, NOVO, Bagsvaerd, Denmark) were pipetted into a set of 4 Minisorb tubes. Each tube was stoppered, and after 36 h at 50 “C the samples were cooled and to each tube 0.75 ml 0.1 M nitric acid with triton containing chromium in concentrations of 0, 1.5, 3, and 6 pgll were added. After mixing, the samples were centrifuged at 12 OOO rpm for 15 min, and super226
natants were transferred to sample cups, of which 0.06 ml were pipetted into graphite tubes and analyzed by Z-AAS. We used linear regression on the four samples to calculate chromium concentration in blood. Quality control samples and samples from a blood pool were assayed in each run. Imprecision of the method, estimated as total and within-assay coefficients of variation, was 7%. Chromium in semen. Chromium in seminal fluid was examined within a subgroup of participants (TIG/SS welders from one plant, MMAlMS welders from another plant, and electricians). Semen samples were collected at home by masturbation (preferably after 3 d of sexual abstinence) into an acid-washed polyethylene jar. The chromium concentration in seminal fluid was determined by Z-AAS. Seminal fluid (0.3 ml) was mixed with 1 ml of 20% tetramethylammonium hydroxide in methanol in Minisorb tubes followed by incubation for 30 min in an ultrasonic water bath at room temperature. Subsequently, 0.4 ml of the digests was diluted with 0.3 ml 2 M nitric acid, mixed, and was allowed to stand for 1 h before the Z-AAS, assay.” Transformation of units may be obtained as follows: 1 nmol Crll = 0.052 pg Crll, and 1 nmol C r h m o l creatinine = 0.46 pg/g creatinine. Analysis and statistical methods. Chromium concentration in urine was adjusted by the creatinine concentration in urine. Eleven urine samples that had creatinine concentrations below 3 mmol/l were excluded. If the chromium concentration was less than the detection limit of 3.8 nmolll, the result was replaced by a value of half the detection limit (31 of 82 blood samples and 6 of 50 semen samples). Two-sided paired t test was applied to examine within-person change of chromium concentration over time. One-way analysis of variance was applied for comparisons of mean values between groups. Dependent variables were transformed by the logarithmic function to obtain equality of variances. Wilcoxon rank sum test was applied to compare chromium concentration in semen among exposed and unexposed subjects.”
Results The median values of the time-weighted average exposure to welding fume particulates, total chromium, and hexavalent chromium in ambient air were 0.94 mg/m3 (standard deviation [SD] = 0.83 mg/m’), 0.011 mg/m3 (SD = 0.011 mg/m3), and 0.003 mg/m3 (SD = 0.002 mg/m3), respectively, among TlGlSS welders; and 3.1 mg/m3 (SD = 1.7 mg/m3), 0.003 mg/m3 (SD = 0.008 mg/m3), and 0.001 mg/m3 (SD = 0.001 mg/m3), respectively, among MS welders. All determinations of fume particulates from TlGlSS welding were below the Danish Process-Specific Occupational Exposure Limit (OEL; 2.6 mg/m3), with the exception of one outlying observation, whereas fume particulates from MMAl MAG MS welding were in the range of the ProcessSpecific OEL (2.8-3.1 mg/m3). Pulmonary uptake of water-soluble hexavalent chromium associated with TlGlSS welding during 4 workArchives of Environmental Health
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shifts was estimated by comparing chromium concentrations in urine samples voided before (first day) and after workshifts (fourth day). The average paired difference of creatinine-adjusted urine chromium concentration was 0.05 nmollmmol creatinine (SD = 1.5, p > .05) among current TIG/SS welders and 0.06 nmoll mmol creatinine (SD = 0.4, p > .05) among non-welding participants. This indicated that no detectable increase in urine chromium concentration in urine and blood occurred across a 3-wk break in welding exposure (i.e., summer vacation). The average paired difference of chromium concentration in urine and blood was 0.23 nmollmmol creatinine (SD = 0.9, p > .05) and -0.60 nmol/l (SD = 6.5 nmol/l, p > .05), respectively, among TIGlSS welders; and 0.10 nmollmmol creatinine (SD = 0.1, p > .05) and 2.15 nmolll (SD = 8.1 nmolll, p > .05), respectively, among non-welding participants. Another approach to the study of internal exposure to chromium associated with welding was to compare never-welders with ever-welders, who were grouped by lifetime exposure to welding (Table 1). This classification was adopted in response to learning that generally, no uptake of chromium occurred across a workshift. The average concentration of chromium in urine and blood was increased among welders who had ever-welded SS using the TIG method but never with the MMA method and among welders who had ever welded MS but never SS (Table 1.) Also, the chromium concentration was slightly increased among former MMAlSS welders. The concentration of chromi-
um in urine and blood was not related to age, smoking habits, year of welding, or years of welding SS and MS, respectively. All of these results were confirmed when crude urine chromium concentrations were analyzed instead of the creatinine-adjusted values. The concentration of chromium in seminal fluid was significantly elevated among ever-MMAISS welders compared with never-welders (Table 1). The distribution of concentrations showed, however, an extremely wide variation within the subgroup of ever-MMA/SS welders. Discussion
This study was undertaken to examine the internal exposure to chromium in welders who were exposed to low levels of chromium and who had never used welding methods (MMA/SS welding) for which there was well-documented high exposure to water-soluble hexavalent chromium. In general, low exposure TIGlSS welders had no detectable increase of urine or blood chromium concentration 'across workshifts nor did their blood chromium concentration decline during a 3-wk period during which there was no exposure. This accords with the very low concentrations of chromium measured in ambient work room air and with the findings reported in other studies.Br9 Nevertheless, chromium concentration in urine and blood was very significantly increased among never-MMAlSS welding SS welders and among never-SS welding MS welders compared with never-welders. That the chromium concen-
Table 1.-Chromium in Urine, Blood, and Seminal Plasma in Metal Workers Who Were Classified according to Welding Experience Throughout Working Life and Regardless of Current Welding Exposure
Welding experience Number of subjects
x
(Y) Min. Max.
Urine chromium* (nmollrnmol creati nine)
n
x*
SD
Blood chromiumt
Seminal chrorniurn (nmolll)
(nmolll)
x
n
x
10 17.31§§11.9
14
672
260tt
2
2830
n
SD
Medians Min.
Max.
MMAlSS welders// (ever MMAlSS welding)
19
3.6
0.1
11.5
15
TlGlSS welders (ever TICISS, never MMA/SS welding)
29
6.7
0.3
30.0
24 2.07-H 1.03
18
17.25tt10.35
14
365
18**
2
3 908
MS welders (ever MS, never SS
29
10.6
0.5
30.0
25
17
14.46§§10.48
3
26
22**
15
39
4 15
280 16
9 2
1063 93
1.38tt1.12
1.31H 0.53
welding) Never-welders Metal workers Electricians
28 12 16
12 0.76 16 0.68
0.49 0.23
5 12
8.77 8.17
2.65 2.46
24 19
-
Notes: SS = stainless steel, MA = manual metal arc method, MS = mild-steel welding, and TIC tungsten inert gas. * End-of-shift sample. tPre-shift sample. *Exposed versus never-welders (t test). §Exposed versus never-welders (Wilcoxon rank sum test). //All former MMAISS welders: no ever-MMAISS welders welded SS with the MMA method during the study period. * * p > .05, not significant (ns).
ttp < . O l . **p < ,001. §Sp < .05.
July/August1991 [Vol. 46 (No.4)]
227
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tration in welders differed from both never-welding metal workers (i.e., internal referents) and electricians (external referents) suggests that the findings are related to the welding process. Several studies of exposure and toxicokinetics of chromium among highly exposed MMA/SS welders have shown significant increases in excretion of chromium in urine during a workshift, which is strongly correlated to the current exposure to hexavalent chromium measured in air sample^.^,^,^ The water-soluble fraction of hexavalent chromium is distributed to at least two different compartments in the body. The major portion of currently absorbed chromium is distributed to a fast compartment from which elimination occurs with a biological half-time of 7 to 48 h, and the remainder is eliminated from a slow Compartment with a half-time ranging from 14 days to infinity. The apparent discrepancy between finding no detectable uptake of chromium across a workshift and observing elevated chromi um concent rat ions in biological samples of welders compared with non-welders might, in accordance with the toxicokinetics of chromium outlined above, be understood to be the result of a gradual build up of chromium during long-term welding exposure. The lack of a relationship between number of welding years and current level of chromium i s not surprising when the crudeness of this cumulative exposure index (welding years) and the small range of changes in chromium concentration i s accounted for. A urine sample may be contaminated easily by metals in work room dust. Precautions were taken to avoid this error. No obvious outlying concentrations were observed, and the very same range of concentrations were observed among internal referents (from the same occupational setting as welders) and external referents. In addition, the validity is supported by the consistency of the comparisons with two different reference groups, and the consistency of urine and blood measurements of the samples obtained at different times relative to exposure. Two earlier studies have found urine chromium concentrations in TlClSS welders within the populationbased normal This does not contradict the results of our study because the small difference observed may only be detectable in designs where both exposed and unexposed individuals are investigated with the same sensitive and accurate analytical methods. Reference values for chromium in biological fluids of healthy, nonoccupationally exposed individuals have diminished considerably recently because of improved analytical techniques. The average internal exposure of exposed groups in this study i s higher than the latest published range of normal values (range of urine concentration: 0.38-1.90 nmollmmol creatinine”; mean and 1 SD of blood chromium: 3.04 f 0.31 nmol/l blood”). A recent study revealed a small increase in chromium across workshifts among SS welders-even when the welding process was mostly TIC.” Perhaps this is explained by extreme exposures to fumes and gases in this group of welders. The findings concerning ever-MS welders (Table 1) were unexpected. None of the welders had ever manu228
factured or welded stainless steel or other kinds of chromium alloys. Although the content of chromium in construction steel is usually very low (less than 1”/0), the concentration in welding fumes may be higher. This is because some elements are preferentially vaporized and are enriched in the fumes over their concentrations in the consumable or parent metal.’ Some studies suggest that welding contributes to the deterioration of the male reproductive ~apacity.’~.’’In this context, the observation that ever-MMAISS welders had very high levels of chromium in seminal fluid is of interest. However, this finding was not consisfent. Only some welders had elevated levels of chromium, and these welders’ occupational exposures did not differ from ever-MMA/SS welders who had normal levels of seminal chromium. This discrepancy could be explained if marked differences in chromium metabolism and secretion occurred among individuals. Contamination of semen during the delivery process i s a more likely explanation. However, the concentration of manganese in seminal plasma (not reported) varied only slightly among individuals. The seminal chromium concentration might vary with the sexual abstinence period, which influences glandular secretions and sperm count. However, the abstinence period was similar in subjects who had high and in those who had normal seminal chromium concentrations (mean 4.3 d [SD = 3.21 and 4.8 d [SD = 3.91, respectively). These results warrant further examination before any conclusions can be drawn. We concluded that long-term TlGlSS and MS welding is associated with increased internal exposure to chromium, even though no uptake across a workshift was measurable. The magnitude of internal exposure among welders i s approximately 2-3 times the level found in nonoccupationally exposed populations. Whether welding is associated with increased levels of chromium in seminal fluid warrants further study. Attention should be focused on the potential risk for delayed health effects among SS and MS welders who are usually not considered to be at-risk from exposure to hexavalent chromium.
********** This study was supported by a grant from the Danish Working Environment Fund. Submitted for publication August 27, 1990; accepted for publication December 4, 1990. Requests for reprints should be sent to: ]ens Peter Bonde, M.D., Department of Occupational Medicine, University Hospital of Aarhus, Norrebrogade 37-39, 8000 Aarhur C, DK.
********** References 1. Stern RM. Process-dependent risk of delayed health effects for welders. Environ Health Perspect 1981; 41:235-53. 2. Langard S. Biological and environmental aspects of chromium. Elsevier Biomedical, 1982. 3. international Agency for Research on Cancer. IARC monographs on the evaluation of carcinogenic risks to humans. Chromium, nickel and welding, vol. 49. Lyon, 1990. 4. Tola S, Kilpio J, Virtamo M, Haapa K. Urinary chromium as an indicator of the exposure of welders to chromium. Scand I Environ
Archives of EnvironmentalHealth
Health 1977; 3:192-202.
5. Mutti A, Cavatoro A, Pedroni C , Borghi A, Giaroli C, Franchini I.
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The role of chromium accumulation in the relationship between airborne and urinary chromium in welders. Int Arch Occup Environ Health 1979; 43:123-33. 6. Sjogren B, Hedstrom L, Ulfvarson U. Urine chromium as an estimator of air exposure to stainless steel welding fumes. Int Arch Occup Environ Health 1983; 51:347-54. 7. Welinder H, Littorin M, Gullberg B, Skerfving S. Elimination of chromium in urine after stainless steel welding. Scand J Work Environ Health 1983; 9:397-403. 8. Angerer J, Amin W, Heinrich-Ramm R, Szadkowski D, Lehnert G. Occupational chronic exposure to metals. Int Arch Environ Health 1987; 59503-12. 9. Kalliomaki PL, Rahkonen E, Vaaranen V, Kalliomaki K, Aittoniemi K. Lung-retained contaminants, urinary chromium and nickel among stainless steel welders. Int Arch &cup Environ Health 1984; 49:67-75. 10 Zober A, Shaller KH, Weltle D. lnhalative belastnung und beanspruchnung von WIG-Schweibern durch crom-nickelhaltige zusatszwerkstoffe. StaubReinhalt: Luft, .1984;11:465-68. 11 Thomsen E, Sterm RM. A simple analytical technique for the determination of hexavalent chromium in welding fumes and other complex matrices. Scand j Work Environ Health 1979; 5:386-403.
July/August1991 [Vol. 46 (No.411
12. Westgaard JO, Berry P, Hunt MR. Multirule xhewhart chart for quality control in clinical chemistry. Clin Chem 1981; 3:493-501. 13. Christensen JM, Petersen LM. Enzymatic digestion of whole blood for improved determination of cadmium, nickel and chromium by electrothermal atomic absorption spectrophotometry measurement in rheumatoid arthritis and normal humans. Acta Pharmacol 1986 59399-402. 14. SAS Institute, Inc. SAS users guide: statistics. Version 5. Cary, NC: SAS Institute, Inc., 1985. 15. Franchini R, Mutti A, Cavatota E. Chromium. In: Biological indicators for the assessment of human exposure to industrial chemicals. Luxembourg: Commission of the European Communities, 1984; pp. 31-52. 16. Aggarival SK, Kinter M, Wills RM, Sovary J, Herold DA. Determination of chromium in urine by stable isotope dilution gas chromatographylmass spectrometry using lithium bis (trifluore ethyl) dithiocarbamate as a chelating agent. Anal Chem 1990; 62: 111-15, 17. Kilburn KH, Warshaw R, Boylen CT, Thornton JC, Hopfer SM, Sunderman W, Finklea J. Cross-shift and chronic effects of stainless-steel welding related to internal dosimetry of chromium and nickel. Am J Ind Med 1990; 17507-15. 18. Mortensen JT. Risk for reduced sperm quality among metal workers, with special reference to welders. %and J Environ Health 1988; 14:27-30.
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Archives of Environmental Health: An International Journal Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/vzeh20
Chromium in Biological Samples from Low-Level Exposed Stainless Steel and Mild Steel Welders a
Jens Peter Bonde M.D. & Jytte Molin Christensen a
b
Department of Occupational , Medicine Hospital , Aalborg, Denmark
b
Danish National Institute of Occupational Health , Copenhagen, Denmark Published online: 03 Aug 2010.
To cite this article: Jens Peter Bonde M.D. & Jytte Molin Christensen (1991) Chromium in Biological Samples from Low-Level Exposed Stainless Steel and Mild Steel Welders, Archives of Environmental Health: An International Journal, 46:4, 225-229, DOI: 10.1080/00039896.1991.9937453 To link to this article: http://dx.doi.org/10.1080/00039896.1991.9937453
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
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Chromium in Biological Samples from Low-Level Exposed Stainless Steel and Mild Steel Welders
JENS PETER BONDE, M.D. Department of Occupational Medicine Hospital of Aalborg Denmark
J U T E MOLIN CHRISTENSEN Danish National Institute of Occupational Health Copenhagen, Denmark
ABSTRACT. Occupational exposure to hexavalent chromium i s of concern because of the carcinogenic action of this metal. The purpose of this study was to evaluate internal exposure to chromium in welders who were exposed to low levels of chromium. Chromium in urine, blood, and seminal fluid was determined among 60 welders and 45 referents. The concentration of chromium in urine and blood did not change across a workshift or across a 3-wk break in exposure. However, stainless-steel and mild-steel welders who were exposed to low levels of chromium and steel welders who were mildly exposed had significantly increased levels of chromium in post-shift urine (mean 2.1 nmol/mmol creatinine [standard deviation (SD) = 1.01 and 1.3 nmol/mmol creatinine [SD = 0.51, respectively) compared with referents (mean 0.7 nmol/mmol creatinine [SD = 0.31). Pre-shift blood chromium concentrations showed a similar variation between exposed workers and referents. Subgroups of stainless-steel welders had very high levels of chromium in seminal fluid. This finding may, however, be explained by nonoccupational factors and, therefore, warrants further study. Attention should focus on the potential risk of delayed health effects among stainless-steel and mild-steel welders who heretofore were not thought to be at risk from chromium exposure.
OCCUPATIONAL EXPOSURE to hexavalent chromium is of concern because of its mutagenic and carcinogenic actions.’’2 Welding of stainless steel ( S S ) with the manual metal arc (MMA) method may be associated with substantial pulmonal absorption and urinary excretion of ~ h r o m i u m . ” ~ The emission of hexavalent chromium at tungsten inert gas (TIG) SS and mild-steel (MS) welding is much lower compared with MMAlSS welding. (Stainless steel is an alloy of iron, nickel, and chromium. Mild steel is an alloy of iron, carbon, and silicon.) Knowledge of the magnitude of internal exposure to chromium associated with TlGlSS and MS weldjuly/August 1991 [VO~. 46 (NO.4
1
ing is, however, very limited. Two studies found urine chromium concentrations of TlGlSS welders in the range of population-based normal value^.^'^ Although the risk for delayed health effects from long-term, lowlevel exposure to chromium i s questionable, it should be recognized that the number of TIGlSS and MS welders throughout the world i s high and i s increasing relative to the number of SS welders who use the MMA methods. The aim of this study was to examine the internal exposure to chromium among TIGlSS and MS welders who, to date, have not been considered to be at risk from chromium exposure. 225
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Subjects and methods Subjects. The study was conducted at 6 plants in Aalborg, Denmark. The plants manufacture SS equipment, pumps, boilers, and many different steel constructions in MS. A total of 105 metal workers and electricians were enrolled in the study. Information about occupational experience during the 6 mo that preceded the study and through adult life was gathered by structured interview. The study population consisted of 30 TlGlSS welders, 30 MMA andlor metal active gas (MAG) MS welders, 29 non-welder metal workers (i.e., drillers, fitters, crane drivers, storemen), and 16 electricians. Welding fume exposure. Ambient air measurements of welding fume particulates were taken among randomly selected TlGlSS welders (n = 151, MMAlMS welders (n = 14), and MAGlMS welders (n = 15). Air was sampled on filters (Millipore Filter AAWPO 37-mm; mean pore size, 0.8 p) from the breathing zone with portable pumps. The sampling time was approximately 6 h. The filters were analyzed for welding fume particulates (filter weight) and particular metals (atomic absorption spectrometry). The concentration of hexavalent chromium was determined by the carbonate method’’ from one-half of the filter. Biological samples. The participants were given written and oral instruction to avoid contamination of urine and semen samples. The samples were delivered outside the working room after change of dress and washing of hands and arms. Specimens were obtained in acid-washed polyethylene bottles (urine and semen) and tubes (blood) delivered and controlled for contamination by the laboratory. Chromium in urine. A post-shift urine sample (PS urine sample) was obtained from all participants the fourth day of work in a week. From TlGlSS welders and electricians were collected a morning spot urine sample (second void in the morning) before-shift the first day of work (BS urine sample), and a before-shift urine sample the first day after 3 wk vacation (AV urine sample). Seven SS welders from 1 of the plants (n = 14) were asked to deliver the AV urine samples. All samples, including blood and semen samples, were stored at -80 “C until analysis. Chromium concentration in urine was determined by Zeeman atomic absorption spectrometry (Z-AAS).” Creatinine concentration in urine samples was determined by the Jaffe reaction with a Beckman 42 spectrophotometer. Chromium in blood. From subgroups of all participants, a blood sample was taken by venipuncture (elbow) before workshift the first day of work. TIGlSS welders from 1 plant had another blood sample taken before workshift on the first day after a 3-wk vacation. Chromium concentration in blood was determined by Z-AAS. Blood (250 pl), water (0.50ml), and 0.04 ml subtilisin A (40 g/l, NOVO, Bagsvaerd, Denmark) were pipetted into a set of 4 Minisorb tubes. Each tube was stoppered, and after 36 h at 50 “C the samples were cooled and to each tube 0.75 ml 0.1 M nitric acid with triton containing chromium in concentrations of 0, 1.5, 3, and 6 pgll were added. After mixing, the samples were centrifuged at 12 OOO rpm for 15 min, and super226
natants were transferred to sample cups, of which 0.06 ml were pipetted into graphite tubes and analyzed by Z-AAS. We used linear regression on the four samples to calculate chromium concentration in blood. Quality control samples and samples from a blood pool were assayed in each run. Imprecision of the method, estimated as total and within-assay coefficients of variation, was 7%. Chromium in semen. Chromium in seminal fluid was examined within a subgroup of participants (TIG/SS welders from one plant, MMAlMS welders from another plant, and electricians). Semen samples were collected at home by masturbation (preferably after 3 d of sexual abstinence) into an acid-washed polyethylene jar. The chromium concentration in seminal fluid was determined by Z-AAS. Seminal fluid (0.3 ml) was mixed with 1 ml of 20% tetramethylammonium hydroxide in methanol in Minisorb tubes followed by incubation for 30 min in an ultrasonic water bath at room temperature. Subsequently, 0.4 ml of the digests was diluted with 0.3 ml 2 M nitric acid, mixed, and was allowed to stand for 1 h before the Z-AAS, assay.” Transformation of units may be obtained as follows: 1 nmol Crll = 0.052 pg Crll, and 1 nmol C r h m o l creatinine = 0.46 pg/g creatinine. Analysis and statistical methods. Chromium concentration in urine was adjusted by the creatinine concentration in urine. Eleven urine samples that had creatinine concentrations below 3 mmol/l were excluded. If the chromium concentration was less than the detection limit of 3.8 nmolll, the result was replaced by a value of half the detection limit (31 of 82 blood samples and 6 of 50 semen samples). Two-sided paired t test was applied to examine within-person change of chromium concentration over time. One-way analysis of variance was applied for comparisons of mean values between groups. Dependent variables were transformed by the logarithmic function to obtain equality of variances. Wilcoxon rank sum test was applied to compare chromium concentration in semen among exposed and unexposed subjects.”
Results The median values of the time-weighted average exposure to welding fume particulates, total chromium, and hexavalent chromium in ambient air were 0.94 mg/m3 (standard deviation [SD] = 0.83 mg/m’), 0.011 mg/m3 (SD = 0.011 mg/m3), and 0.003 mg/m3 (SD = 0.002 mg/m3), respectively, among TlGlSS welders; and 3.1 mg/m3 (SD = 1.7 mg/m3), 0.003 mg/m3 (SD = 0.008 mg/m3), and 0.001 mg/m3 (SD = 0.001 mg/m3), respectively, among MS welders. All determinations of fume particulates from TlGlSS welding were below the Danish Process-Specific Occupational Exposure Limit (OEL; 2.6 mg/m3), with the exception of one outlying observation, whereas fume particulates from MMAl MAG MS welding were in the range of the ProcessSpecific OEL (2.8-3.1 mg/m3). Pulmonary uptake of water-soluble hexavalent chromium associated with TlGlSS welding during 4 workArchives of Environmental Health
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shifts was estimated by comparing chromium concentrations in urine samples voided before (first day) and after workshifts (fourth day). The average paired difference of creatinine-adjusted urine chromium concentration was 0.05 nmollmmol creatinine (SD = 1.5, p > .05) among current TIG/SS welders and 0.06 nmoll mmol creatinine (SD = 0.4, p > .05) among non-welding participants. This indicated that no detectable increase in urine chromium concentration in urine and blood occurred across a 3-wk break in welding exposure (i.e., summer vacation). The average paired difference of chromium concentration in urine and blood was 0.23 nmollmmol creatinine (SD = 0.9, p > .05) and -0.60 nmol/l (SD = 6.5 nmol/l, p > .05), respectively, among TIGlSS welders; and 0.10 nmollmmol creatinine (SD = 0.1, p > .05) and 2.15 nmolll (SD = 8.1 nmolll, p > .05), respectively, among non-welding participants. Another approach to the study of internal exposure to chromium associated with welding was to compare never-welders with ever-welders, who were grouped by lifetime exposure to welding (Table 1). This classification was adopted in response to learning that generally, no uptake of chromium occurred across a workshift. The average concentration of chromium in urine and blood was increased among welders who had ever-welded SS using the TIG method but never with the MMA method and among welders who had ever welded MS but never SS (Table 1.) Also, the chromium concentration was slightly increased among former MMAlSS welders. The concentration of chromi-
um in urine and blood was not related to age, smoking habits, year of welding, or years of welding SS and MS, respectively. All of these results were confirmed when crude urine chromium concentrations were analyzed instead of the creatinine-adjusted values. The concentration of chromium in seminal fluid was significantly elevated among ever-MMAISS welders compared with never-welders (Table 1). The distribution of concentrations showed, however, an extremely wide variation within the subgroup of ever-MMA/SS welders. Discussion
This study was undertaken to examine the internal exposure to chromium in welders who were exposed to low levels of chromium and who had never used welding methods (MMA/SS welding) for which there was well-documented high exposure to water-soluble hexavalent chromium. In general, low exposure TIGlSS welders had no detectable increase of urine or blood chromium concentration 'across workshifts nor did their blood chromium concentration decline during a 3-wk period during which there was no exposure. This accords with the very low concentrations of chromium measured in ambient work room air and with the findings reported in other studies.Br9 Nevertheless, chromium concentration in urine and blood was very significantly increased among never-MMAlSS welding SS welders and among never-SS welding MS welders compared with never-welders. That the chromium concen-
Table 1.-Chromium in Urine, Blood, and Seminal Plasma in Metal Workers Who Were Classified according to Welding Experience Throughout Working Life and Regardless of Current Welding Exposure
Welding experience Number of subjects
x
(Y) Min. Max.
Urine chromium* (nmollrnmol creati nine)
n
x*
SD
Blood chromiumt
Seminal chrorniurn (nmolll)
(nmolll)
x
n
x
10 17.31§§11.9
14
672
260tt
2
2830
n
SD
Medians Min.
Max.
MMAlSS welders// (ever MMAlSS welding)
19
3.6
0.1
11.5
15
TlGlSS welders (ever TICISS, never MMA/SS welding)
29
6.7
0.3
30.0
24 2.07-H 1.03
18
17.25tt10.35
14
365
18**
2
3 908
MS welders (ever MS, never SS
29
10.6
0.5
30.0
25
17
14.46§§10.48
3
26
22**
15
39
4 15
280 16
9 2
1063 93
1.38tt1.12
1.31H 0.53
welding) Never-welders Metal workers Electricians
28 12 16
12 0.76 16 0.68
0.49 0.23
5 12
8.77 8.17
2.65 2.46
24 19
-
Notes: SS = stainless steel, MA = manual metal arc method, MS = mild-steel welding, and TIC tungsten inert gas. * End-of-shift sample. tPre-shift sample. *Exposed versus never-welders (t test). §Exposed versus never-welders (Wilcoxon rank sum test). //All former MMAISS welders: no ever-MMAISS welders welded SS with the MMA method during the study period. * * p > .05, not significant (ns).
ttp < . O l . **p < ,001. §Sp < .05.
July/August1991 [Vol. 46 (No.4)]
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tration in welders differed from both never-welding metal workers (i.e., internal referents) and electricians (external referents) suggests that the findings are related to the welding process. Several studies of exposure and toxicokinetics of chromium among highly exposed MMA/SS welders have shown significant increases in excretion of chromium in urine during a workshift, which is strongly correlated to the current exposure to hexavalent chromium measured in air sample^.^,^,^ The water-soluble fraction of hexavalent chromium is distributed to at least two different compartments in the body. The major portion of currently absorbed chromium is distributed to a fast compartment from which elimination occurs with a biological half-time of 7 to 48 h, and the remainder is eliminated from a slow Compartment with a half-time ranging from 14 days to infinity. The apparent discrepancy between finding no detectable uptake of chromium across a workshift and observing elevated chromi um concent rat ions in biological samples of welders compared with non-welders might, in accordance with the toxicokinetics of chromium outlined above, be understood to be the result of a gradual build up of chromium during long-term welding exposure. The lack of a relationship between number of welding years and current level of chromium i s not surprising when the crudeness of this cumulative exposure index (welding years) and the small range of changes in chromium concentration i s accounted for. A urine sample may be contaminated easily by metals in work room dust. Precautions were taken to avoid this error. No obvious outlying concentrations were observed, and the very same range of concentrations were observed among internal referents (from the same occupational setting as welders) and external referents. In addition, the validity is supported by the consistency of the comparisons with two different reference groups, and the consistency of urine and blood measurements of the samples obtained at different times relative to exposure. Two earlier studies have found urine chromium concentrations in TlClSS welders within the populationbased normal This does not contradict the results of our study because the small difference observed may only be detectable in designs where both exposed and unexposed individuals are investigated with the same sensitive and accurate analytical methods. Reference values for chromium in biological fluids of healthy, nonoccupationally exposed individuals have diminished considerably recently because of improved analytical techniques. The average internal exposure of exposed groups in this study i s higher than the latest published range of normal values (range of urine concentration: 0.38-1.90 nmollmmol creatinine”; mean and 1 SD of blood chromium: 3.04 f 0.31 nmol/l blood”). A recent study revealed a small increase in chromium across workshifts among SS welders-even when the welding process was mostly TIC.” Perhaps this is explained by extreme exposures to fumes and gases in this group of welders. The findings concerning ever-MS welders (Table 1) were unexpected. None of the welders had ever manu228
factured or welded stainless steel or other kinds of chromium alloys. Although the content of chromium in construction steel is usually very low (less than 1”/0), the concentration in welding fumes may be higher. This is because some elements are preferentially vaporized and are enriched in the fumes over their concentrations in the consumable or parent metal.’ Some studies suggest that welding contributes to the deterioration of the male reproductive ~apacity.’~.’’In this context, the observation that ever-MMAISS welders had very high levels of chromium in seminal fluid is of interest. However, this finding was not consisfent. Only some welders had elevated levels of chromium, and these welders’ occupational exposures did not differ from ever-MMA/SS welders who had normal levels of seminal chromium. This discrepancy could be explained if marked differences in chromium metabolism and secretion occurred among individuals. Contamination of semen during the delivery process i s a more likely explanation. However, the concentration of manganese in seminal plasma (not reported) varied only slightly among individuals. The seminal chromium concentration might vary with the sexual abstinence period, which influences glandular secretions and sperm count. However, the abstinence period was similar in subjects who had high and in those who had normal seminal chromium concentrations (mean 4.3 d [SD = 3.21 and 4.8 d [SD = 3.91, respectively). These results warrant further examination before any conclusions can be drawn. We concluded that long-term TlGlSS and MS welding is associated with increased internal exposure to chromium, even though no uptake across a workshift was measurable. The magnitude of internal exposure among welders i s approximately 2-3 times the level found in nonoccupationally exposed populations. Whether welding is associated with increased levels of chromium in seminal fluid warrants further study. Attention should be focused on the potential risk for delayed health effects among SS and MS welders who are usually not considered to be at-risk from exposure to hexavalent chromium.
********** This study was supported by a grant from the Danish Working Environment Fund. Submitted for publication August 27, 1990; accepted for publication December 4, 1990. Requests for reprints should be sent to: ]ens Peter Bonde, M.D., Department of Occupational Medicine, University Hospital of Aarhus, Norrebrogade 37-39, 8000 Aarhur C, DK.
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