6 - A bs tract- Chromium in Erythrocytes as a Biological Marker of Worker Expos ed to Hexavalent Chromium Ui- Seoung Yoon, Kw ang- Jong Kim Departm ent of Preventive M edicine & Institute for Occupational and E nvironm ental H ealth, Colleg e of M edicine, K orea U niversity Objective - T o evaluate the usefulness of chromium in erythrocytes as a biological marker of exposure to hexavalent chromium in chromate producers and chrome platers Methods - Blood and urine samples were ramdomly obtained from chromate prodecers (n=34) and chrome platers (n=35), and non- exposed workers (n=75). chromium level in erythrocytes and plasma, and urine were measured. Different chromium exposure workers were assessed through measurements of airborne hexavalent chromium concentrations using a personal air sampler. Linear associations between variables were evaluated with correlation analysis. Results - T he chromate producers had mean chromium levels in erythrocytes five fold as higher than the chrome platers, and fifteen fold higher than non- exposed group. Among the chromium exposed workers, airborne hexavalent chromium was positively and strongly correlated with in erythrocytes (r=0.689. p< 0.01), and erythrocytes chromium was inversely correlated with hematocrit (r=- 0.441, p< 0.01), hemoglobin (r=- 0.465, p< 0.01) and the number of red blood cells (r=- 0.28, p< 0.05). Conclusions - In conclusion, this study suggests that chromium in erythrocytes is a good indicator of the chromium body burden caused by exposure to hexava.lent chromium. Key Word : chromeplater, biological marker, erythrocytes, hexavalent chromium 2000 4 7, 2000 4 24 : 5 126-1 T el) 02-920- 6169, Fax) 02-927- 7220, E- mail) kkjo@mail.korea.ac.kr
1..,,,,,, (Ladou, 1997)., 3 6 3 6.,, (WHO, 1988; Langard, 1990) (Wetterhan, 1989; Ryberg Alexander, 1990; Capellmann Bolt, 1992). (1998) (American Conference of Governmental Industrial Hygienists, ACGIH, 1999) 6 0.05 /, ACGIH A1". (National Institute for Occupational Safety and Health, NIOSH) 6 0.001 / (NIOSH, 1994).... 3 6 6 (Lukanova, 1996 ; Miksche Lewalter, 1997 ; Harzdorf Lewalter, 1997). 6 3 6. 6 (Wiegand, 1985; Alexander Aaseth, 1995). (WHO, 1988 ; Miksche Lewalter, 1997; Harzdorf Lewalter, 1997). 6 6. 6 6,, 6. 2. 1 ) 9
1 6 69 75.,, 1,,,,,. 1999 3 1999 10 7. 2 ) (2) 2.5 5 1 isotonic saline solution 1,200rpm 5. 2. 2.5 isotonic saline. 5 2.5ml ultra water. (1) 6 6 NIOSH Manual of Analytical Methods No.7600 (NIOSH, 1994). PVC (pore size 5.0, 37mm) (Gilian, USA) 1.5 /min 8. 6 Wang (1997, 1999) ultrasonication and strong anion- exchange solid phase extraction method., 15 10 0.05M(NH4)2SO4/0.05M NH4 OH(pH8) 10 (< 40 ) 30. 3 strong anion- exchange. 3 6 2 /min 0.5M(NH4)2SO4/0.1M NH4OH(pH8) 3 3 9. 37% HCl 100. 20mM diphenylcarbazide 2 6 540nm (Ceil 3000, England). 1.25%(NH4)2HPO4 1% T riton X- 100 600 1% HNO3 200 200 (GF- AAS, Hitachi Z- 8100, Japan). GF- AAS 3 [1 : 50 80 (40 ), 2 : 80 120 (10 ), 3 : 120 400 (30 )], 3 [1 : 400 600 (40 ), 2 : 600 (10 ), 3 : 700 (5 )}, 2,900 (5 ) 357.9nm. 1000ppm 1% HNO3 0.5, 1.0, 1.5 /.. 0.085 /, 0.010 /.. (3) 30
4 2 microwave oven. 0.2 10% 200 1% T riton X- 100 600,. 1000ppm 1% HNO3 4, 8, 16, 24 /. /, /g creatinine. (UCT - 1, Japan), (Olympus AU 400, Japan) Jaffe method. 0.10 /. (4),, 2 (Nion Kohden, MEK- 6108K, Japan),,. (5) SPSS 8.0.,. t- test, ANOVA.,,,,,,,,,. 3. 69 75,,, T able 1. 34.3, 4.1, 1.2, 1 17.6,,,. 6 T able 2. T able 1. General characteristics of exposed and non- exposed group. Exposed (n=69) Non- exposed (n=75) mean(sd) p- value* Age(year) 34.3( 8.1) 32.3(8.9) 0.16 Work duration(year) 4.1( 3.4) 4.2(3.3) 0.87 Alcohol consumption(bottle /week) 1.2( 1.4) 1.4(1.6) 0.54 Smoking amount(cigarettes/day) 17.6(10.7) 19.3(8.6) 0.20 SD: Standard Deviation * : t- test : 24% alcohol, 360 volume
T able 2. Airborne hexavalent chromium concentrations in exposed group Industry No. of workers Hexavalent chromium( / ) GM GSD Range p- value* Chromate producing 34 10.7 0.7 6.0 35.2 Chrome plating 35 7.2 0.4 3.0 20.0 0.003 T otal 69 8.7 0.6 3.0 35.2 GM(GSD): Geometric Mean(Geometric Standard Deviation) * : t- test 6 10.7 / (6.0 35.2 / ) 7.2 / (3.0 20.0 / ). 6. 50 / (, 1998 ). T able 3. 24.32 / (7.14 100.02 / ) 4.81 / (1.40 23.93 / ), 1.64 / (0.20 16.20 / ) 5, 15. 2.11 /1012cells (0.64 18.73 /1012cells) 0.48 /1012cells (0.13 2.34 /1012cells), 0.15 /1012cells (0.02 1.48 /1012cells), 4, 14. 6.80 /ghb (2.10 59.89 /g T able 3. Mean chromium concentrations in erythrocytes among exposed and non- exposed group. Variable Erythrocytes( /, corrected for Hct) Chromate producers Chrome platers Non- exposed N 34 GM (GSD) 24.32 (1.04) Range N GM (GSD) 7.14 100.02 35 4.81 (0.67) Range 1.40 23.93 N 75 GM (GSD) 1.64 (1.33) Range 0.20 16.20 p- value* 0.001 Erythrocytes ( /1012 cells) 34 2.11 (0.88) 0.64 18.73 35 0.48 (0.87) 0.13 2.34 75 0.15 (1.33) 0.02 1.48 0.001 Erythrocytes ( /ghb) 34 6.80 (0.90) 2.10 59.89 35 1.31 (0.70) 0.41 6.96 75 0.47 (1.33) 0.06 4.36 0.001 GM(GSD): Geometric Mean(Geometric Standard Deviation) * : ANOVA test : Variable is corrected with hematocrit, number of red blood cells, and hemoglobin.
Hb) 1.31 /ghb (0.41 6.96 /ghb), 0.47 /ghb (0.06 4.36 /ghb) 5, 14. T able 4. 5.70 / (0.80 93.69 / ) 2.13 / (0.20 26.05 / ), 0.65 / (0.0 3 15.80 / ), (P< 0.001). 45.88 /g creatinine (6.17 379.3 /g creatinine) 38.05 /g creatinine (9.68 298.87 /g creatinine), 13.14 /g creatinine (1.92 42.95 /g creatinine) (P< 0.001). 6,, T able 5. 6, 6 6. 6 (A- cr), (U- cr), (P- cr) (E- cr),,, T able 4. Mean chromium concentrations in plasma and in urine among exposed and non- exposed group Group Exposed group chromate producers chrome platers Non- exposed group No. of Workers 34 35 75 Chromium in plasma( / ) Chromium in urine ( /g creatinine) GM(GSD) Range GM(GSD) Range 5.70(1.38) 2.13(1.36) 0.65(1.52) 0.80 93.69 0.20 26.05 0.03 15.80 45.88(0.87) 38.05(0.91) 13.14(0.70) 6.17 379.93 9.68 298.87 1.92 42.95 p- value=0.000* p- value=0.000* GM(GSD) : Geometric Mean(Geometric Standard Deviation) * : ANOVA test T able 5. Chromium concentrations in erythrocytes, plasma, and urine by hexavalent chromium exposure level Hexavalent chromium level in air( / ) 9.99 10.00 14.99 15.00 No. of Workers 43 11 15 Cr in erythrocytes ( / ) Cr in plasma ( / ) Cr in Urine ( /g crea.) GM(GSD) GM(GSD) GM(GSD) 6.24(0.96) 12.03( 0.32) 39.33(0.62) 2.20(1.38) 5.09(1.35) 9.55(1.13) 35.37(0.86) 47.66(0.93) 60.81(0.87) p- value=0.000* p- value=0.001* p- value=0.109* GM(GSD): Geometric Mean(Geometric Standard Deviation) * : ANOVA test
T able 6. T he correlation coefficients matrix of selected study variables Age Age 1.000 Work duration work duration 0.482** 1.000 Smoking amount smoking amount 0.115 0.150 1.000 Log P- cr Log P- cr - 0.140-0.089-0.049 1.000 Log U- cr Log U- cr - 0.341** - 0.238* - 0.172 0.346** 1.000 Log U- cr/ crea. Log U- cr/crea. - 0.168-0.060 0.108 0.209 0.774** 1.000 Log A- cr - 0.156 0.093-0.038 0.359** 0.279* 0.219* 1.000 Log A- cr Log E- cr Log E- cr - 0.202-0.006-0.221 0.400** 0.423** 0.259* 0.689** 1.000 Log P- cr: Log plasma chromium Log U- cr: Log urinary chromium corrected specific gravity Log U- cr/crea.: Log urinary chromium corrected for creatinine Log A- cr: Log airborne hexavalent chromium Log E- cr : Log erythrocyte chromium * : p< 0.05, ** : p< 0.01 T able 6. 6 (r=0.689, p< 0.01) 6, 0.359 (p< 0.01), 0.279 (0< 0.05)., 0.423 (p< 0.01), 0.400 (p< 0.01) 0.346(p< 0.01). 0.259 (0< 0.05). (r=- 0.238, P< 0.05). 6,,, T able 7. 6 (r=- 0.367, p< 0.01) (r=- 0.358, p< 0.01). T able 7. Correlation coefficients between hexavalent chromium in air, chromium in erythrocytes and hemoglobin, hematocrit, and the number of red blood cells Hemoglobin Hematocrit RBCs * : p< 0.05, ** : p< 0.01 Log hexavalent chromium in air correlation coefficient(r) - 0.367** - 0.358** - 0.223 Log chromium in erythrocytes correlation coefficient(r) - 0.465** - 0.441** - 0.238*
Fig. 1. Scatterplot between Cr in air and in erythrocytes Fig. 2. Scatterplot between Cr in urine and in erythrocytes
(r=- 0.465, P 0.01) (r=- 0.441, P 0.01), (r=- 0.238, P 0.05). 6, 1, 2. 6 Log Y=- 5.14 + 1.32 Log X (r2=0.475, p=0.000). Log Y=- 4.574 + 0.79 Log X (r2=0.179, p=0.000). 4.,. 6 3. 6 3 (Yoshikawa Hara, 1980), 6 3 (Nomiyama, 1980) transferrin. 6 (WHO, 1988) (real risk) (Gao, 1993; Finley, 1996; Lukanova, 1996). 24.32 /, 5, 15,.. 4.81 /, 1.64 /, Lukanova (1996) 14 22.82 /, 18 2.50 /. 5.70 / 2.13 /, 0.65 /, Gao (1994) 10 2.8 / 6 0.65 /. 45.88 /g creatinine (1995) 6 5-39 / 25.4 /g creatinine, 38.5 /g creatinine Lai (1998) 14 14.7 /g creatinine.,,,. 6, 10.7 / (6.0 35.2) 7.2
/ (3.0 20.0 / ) 1.5, 50.0 /. 6, 6,,. 6 (Boeniger, 1993). 6,... 6 (subclinical anemia),, 6,. Lukanova (1996) 14 6 0.5-130 / (r=- 0.66, p< 0.01) (r=- 0.62, P< 0.02), (r=- 0.55, P< 0.04). 6 6. 6 (, 1997). 6. 5. 6 6 34 35, 75 6,,. 1) 6 10.7 / (6.0 35.2 / ) 7.2 /. 2) 24.32 / (7.14 100.02 / ) 5, 15. 3) 5.70 / (0.80 93.69 / ), 45.88 /g creatinine (6.17 379.93 /g creatinine)
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