Biomonitoring of 30 trace elements in urine of children and adults by ICP-MS

Clinica Chimica Acta 365 (2006) 310 – 318 www.elsevier.com/locate/clinchim

Biomonitoring of 30 trace elements in urine of children and adults by ICP-MS Peter Heitland*, Helmut D. Ko¨ster Medical Laboratory Bremen, Haferwende 12, D-28357 Bremen, Germany Received 15 August 2005; received in revised form 14 September 2005; accepted 14 September 2005 Available online 24 October 2005

Abstract The paper provides physicians and clinical chemists with statistical data (concentration ranges, geometric mean values, selected percentiles, etc.) about 30 urinary trace elements in order to determine whether people have trace element deficiencies or have been exposed to higher elemental concentrations. Morning urine samples of 72 children and 87 adults from two geographical areas of Germany were collected and the elements Li, Be, V, Cr, Mn, Ni, Co, Cu, Zn, Ga, As, Se, Rb, Sr, Mo, Rh, Pd, Ag, Cd, In, Sn, Sb, Cs, Ba, Pt, Au, Pb, Tl, Bi and U were determined by inductively coupled plasma mass spectrometry (ICP-MS) with a new octopole based collision/reaction cell. The urine samples were analysed directly after a simple 1 / 5 (V/V) dilution with deionised water and nitric acid. Information on exposure conditions of all human subjects were collected by questionnaire-based interviews. The described concentration data down to the ng/l range are very useful for the formulation of reference values. For some elements either new data are described (e.g., for V, Ga, In, Bi, Rh, Mn) or differences to earlier studies were found (e.g., for Be, As). For other elements (e.g., Sb, Se, Mo, Ba, Cu, Zn, Li) our results are in good correlation with previous studies and also complemented with urinary trace element concentrations for children. D 2005 Elsevier B.V. All rights reserved. Keywords: Trace elements; Urine; ICP-MS; Toxic metals

1. Introduction Multi-element determinations in biological samples have been described in the literature with focus on the analytical method development [1 –22]. These papers are dealing with the analyses of blood [1 –4], serum [4– 12], urine [1,4,6,13– 18], hair [19,20] nails [19] bones [21] or saliva [22]. Only a few papers describe both, the method development for the determination of a large number of elements and the analysis of a statistically relevant number of real samples [2,23 –26]. Rodushkin et al. [3] developed a method for the determination of 60 elements in whole blood by sector field ICP-MS. In another paper [2] of this author 50 elements were determined in blood samples of 31 non-exposed * Corresponding author. Tel.: +49 421 2072 261; fax: +49 421 2072 7261. E-mail address: [email protected] (P. Heitland). 0009-8981/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.cca.2005.09.013

human subjects. Minoia et al. [24] determined 46 elements in urine, blood and serum by graphite furnace atomic absorption spectrometry (GF-AAS) and inductively coupled plasma optical emission spectrometry (ICP-OES). For many elements the power of detection of these two methods is not sufficient to determine elemental background concentrations. In general, lower limits of detection (LODs) are possible by inductively coupled plasma mass spectrometry (ICP-MS). To avoid spectral interferences, which are often described as the major disadvantage in ICP-MS, highresolution sector field ICP-MS was suggested for the analysis of biological materials [2 –6,11,12,16,17]. In our approach the application of a new ICP-MS instrument with the collision/reaction cell technology was used to remove spectral interferences but keeping all other unique capabilities of ICP-MS, such as low detection limits, multi-element capability and a wide linear calibration range. Compared with sector field ICP-MS it is also lower in

P. Heitland, H.D. Ko¨ster / Clinica Chimica Acta 365 (2006) 310 – 318

investment costs. For the rapid and reliable routine analysis with high sample throughput collision/reaction cell ICP-MS was established for urine analysis [26]. Biomonitoring of trace elements in urine samples of healthy humans has been published for many elements at different geographical locations. Many of these papers deal with elements described as toxic or carcinogenic, such as As [24,26 –28,33], Cr [24,26,29 – 33], Ni [24,26,30– 33], Hg [24,32,33] or Pb [13,24,26,32,33]. Other publications deal with biomonitoring of essential trace elements, for example, for Se [24,26,32– 34], Cu [24,26,33], Mo [24,26,33,35] or Zn [24,26,33]. For some elements (e.g., Se or Mn) other biological fluids (serum or blood) are preferred for analyses to investigate the essential trace element concentrations, however, in the case of intoxications urine is often used. For As, Cd, Cr, Cu and Hg in urine a representative population study was performed in the German Environmental Survey in 1992 [36] and this was repeated 6 years later with Pb, Cd, Hg, Au, Ir and Pt in urine [37,38]. Reference values for Cd, Hg, As in urine were derived from this survey [39]. For the US population urinary concentrations of the elements Pb, Cd, Hg, Co, U, Sb, Ba, Be, Cs, Mo, Pt, Tl, W were published in the Second National Report on Human Exposure to Environmental Chemicals [40]. Both surveys, in Germany and in the US, provide results for children. Other Reference values for youngsters in the urban area of Rome were described for Ni, Cr and V [41]. Even though concentration ranges of many urinary trace elements (e.g., Se, Cu, Zn, Pb) are well investigated for healthy humans for other elements (e.g., Be, Ga, V, Bi, Rh, W, In) reference values and background concentrations in urine of children and adults are not described or have to be critically reviewed. For children in general only limited data about urinary trace element concentrations are available or were not found. In this paper the analysis results of 159 real urine samples from non-exposed humans are presented. 30 elements were determined in morning urine samples of 72 children and 87 adults by ICP-MS. The major goal of the analyses was to determine background concentrations of those elements for which only little data are available in the literature. Another goal of this biomonitoring survey was to investigate differences between children and adults, smokers and non-smokers, people with and without fish consumption and geographical locations. A comparison with previous studies was carried out for elements with well investigated concentration ranges in urine.

2. Materials and methods 2.1. Study population and samples Urine samples of 87 occupationally non-exposed adults and 72 children were collected in the surrounding areas of Aachen and Erkelenz in western Germany and in Bremen in northern Germany in January 2005. Both areas have a

311

population density with more than 500 inhabitants/km2 and are located close to a few industrial regions. Near to Aachen and Erkelenz are vast brown coal mining areas and Bremen has car, steel and food industry. The following information about these 159 human subjects is available: age, gender, place of residence, smoking habits, medication and fish consumption prior to sample collection. The children were divided into 3 age groups: 2– 6 years, 7 –11 years and 12– 17 years. For each age group 12 samples were collected in both geographic areas (n = 72). The ratio male / female is 1 / 1 in each age group and in both areas. The age of adults was in the range 18 –65 years. 40 adults are male and 43 are female. 17 adults are smokers. 2.2. Apparatus An Agilent 7500c (Agilent Technologies, Waldbronn, Germany) ICP mass spectrometer with an octopole based collision/reaction cell was used for the analysis of urine samples. For sample introduction a robust Babington nebulizer with a Scott spray chamber (Agilent Technologies) was used. This system does not clog in the case of small particles in the urine. Details about instrumentation, experimental parameters and automation have been described before [26]. 2.3. Sample collection Morning middlestream urine samples were collected in 30 ml polyethylene containers (Sarstedt, Nu¨mbrecht, Germany) and were transported to the laboratory at room temperature. Prior to collection the containers were cleaned with 5% (V/V) HNO3 (Merck, Darmstadt, Germany) in ultrapure quality. The samples were acidified with 100 Al of 65% (V/V) HNO3 per 20 ml urine and were stored in a refrigerator at 5 -C. 2.4. Sample preparation, control materials and calibration Sample preparation and calibration were described before [26]. Prior to dilution the sample were shaken vigorously. In a simple procedure 1 ml of the urine sample was diluted with nitric acid, internal standard solution and deionised water up to 5 ml. Only for seven elements the ICP-MS method was not developed in our earlier paper. For those elements Cs, Ga, Ag, Pd and Au the concentrations in the calibration solutions are 0, 0.005, 0.05, 0.1, 0.2, 0.5 and 2 Ag/l, respectively, while for Rb and Sr the concentrations in each calibration solution are 0, 0.5, 1, 2, 5 and 20 Ag/l, respectively. Control materials used for internal quality assurance for those 7 elements were Seronorm\ (LOT 2525, Sero AS, Billingstad, Norway), Medisafe\ (LOT 001314, Medichem, Steinenbronn, Germany) and also a pooled urine control sample with spiked concentrations for the elements (Pd, Au, Ga) which are not certified in the commercially

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available control samples. Prior to analysis the commercial control materials were diluted according to the recommendation of the manufacturer. After this dilution 1 mL of the freshly prepared control material was filled up with nitric acid, internal standard solution and deionised water in the same way as described for the real samples. The control samples were analysed for each element after calibration and after every 20th sample.

3. Results and discussion 3.1. Analytical characteristics The complete method validation was described before for 23 elements, including all relevant parameters, such as the determination of linear calibration ranges and detection limits, the evaluation of short-term and long-term stability of the spectrometer, the analysis of several reference materials and the discussion of precision and accuracy in internal and external quality assurance [26]. For the other 7 elements Cs, Ga, Ag, Pd, Au, Rb and Sr this method validation was repeated and relevant analytical figures of merit (recoveries for control materials, inter-day and intraday variation coefficients, spike recoveries, etc.) are summarized in Table 1. Measured concentrations in the control materials are in good agreement with certified values. Intra-day variation coefficients (one sample preparation, 10 measurements of the same sample) are in the range 1.9– 4.4%, whereas inter-day variation coefficients (10 different sample preparations, 10 measurements at different days by different people) range from 6.5 – 14.2%. Spike recoveries are in the range 95– 104%. For these 7 elements there is a need for more urine reference materials and higher quality of analytical data (application of different analytical methods and information about uncertainty) and to our knowledge only for Ag a multi-element external quality assement scheme was possible. We found 1.1 Ag/l Ag in a urine of an external quality assement scheme organized by the Institut National de Sante Publique du Quebec in Canada. The average and median concentration (n = 16 participants) are 1.1 and 1.2 Ag/l, respectively, which is agreement with our result.

Table 2 Selected isotopes and limits of quantification (LOQ) calculated to the undiluted urine for routine analysis Isotope

LOQ (Ag/l undiluted urine)

7

0.02 0.009 0.056 0.055 0.073 0.032 0.017 0.41 0.30 0.019 0.26 0.39 0.11 0.060 0.090 0.007 0.09 0.008 0.028 0.014 0.060 0.021 0.030 0.028 0.009 0.024 0.010 0.007 0.009 0.004

Li Be 51 V 52 Cr 55 Mn 58 Ni 59 Co 63 Cu 66 Zn 69 Ga 75 As 78 Se 85 Rb 88 Sr 98 Mo 103 Rh 106 Pd 107 Ag 111 Cd 115 In 118 Sn 121 Sb 133 Cs 138 Ba 195 Pt 197 Au 205 Tl 208 Pb 209 Bi 238 U 9

Isotope selection and the limits of quantification (LOQs) for all elements are listed in Table 2. LOQs were determined from LOQ = 10 RSDb c/SBR as proposed by Boumans [42], where RSDb is the relative standard deviation of the background intensity of 10 measurements, c the concentration of the element in solution and SBR the signal-tobackground ratio. The LOQs are in the range 0.004 Ag/l (for U) to 0.4 Ag/l (for Cu) calculated to the undiluted urine. For many elements the LOQs are mainly limited by blanks and therefore careful control of impurities in all reagents and in water was applied. For most essential trace elements, such as Co, Cu, Zn, Se, Mo, the LOQs are significantly below the

Table 1 Comparison of measured and certified concentrations, intra-day and inter-day variation coefficients (VCs) and spike recoveries of 1 Ag/L (for Au, Ag, Cs, Ga, Pd) and 50 Ag/L (for Rb, Sr) Element

Control material

Au Ag Cs Ga Pd Rb Sr

Pool Pool Seronorm\ Pool Medisafe\, level 1 Seronorm\ Seronorm\

Concentration (Ag/L)

VC (%)

Certified

Measured

Intra-day

Inter-day

Spike recovery (%)

1 T 0.14 0.8 T 0.15 6.8 T 0.5 1 T 0.15 5 T 1.7 1510T 91.3T

0.9 T 0.1 0.9 T 0.1 6.3 T 0.3 1.1 T 0.1 4.7 T 0.3 1487 T 53 93 T 7

3.4 4.1 3.0 3.4 4.4 2.8 1.9

11.4 9.8 6.8 13.1 14.2 6.5 7.4

99 104 102 97 95 99 99

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3.2. Study results

Ag/g creatinine (Table 5). For the young children (2 –6 years) higher values were found either for essential trace elements (Mn, Co, Cu, Zn, Se, Mo) or for toxic elements (Pb, Cd, Tl) compared with older children (12 – 17 years). Significant local differences between the areas of Bremen or Aachen were not found. In the following all urinary trace elements determined in this study are discussed.

The analyses results for 72 children and 87 adults are summarized in Tables 3 –6, which describe mean concentrations, concentration ranges, geometric mean concentrations, selected percentiles and number of values below the limit of quantification of ICP-MS. The concentrations were expressed in Ag/l urine and also in Ag/g creatinine to adjust for effects of urinary dilution. For children the results were presented in three age groups (Tables 5,6). Compared with adults (Table 4) most of the geometric mean concentrations of the elements are higher for children (Table 3) with some exceptions (Cd, Sn, Cs, Au). Those higher Cd and Au concentrations for adults are due to smoking and a higher number of dental Au alloys, respectively. The elemental concentrations in urine of children decrease with age, when the geometric mean values are expressed in

3.2.1. Alkaline and earth alkaline elements Li, Rb, Cs, Be, Ba, Sr Except of Be all elements were found in the urine samples above the LOQs. Compared with concentrations for children urinary trace element concentrations for adults are at a similar level for Sr, Cs and Ba and lower for Li and Rb (Tables 3, 4). Geometric mean values for Li and Rb for children are 40 and 1421 Ag/l, respectively. Both elements are companions of either Na or K in the nature. Lower geometric mean values were found for Cs and Ba at 4.1 and 1.5 Ag/l, respectively (Table 3), which is in very good agreement with a representative survey in the US [40], where geometric mean values of 4.4 Ag/l for Cs and 1.5 Ag/l for Ba were reported for the whole population. Be and its compounds are toxic and may cause lung diseases. In a recent paper by Infante [43] Be exposure and

normal range in urine of healthy humans. For a few ultratrace elements (Be, Ga, Rh, Pd, Pt) most of the concentrations were found to be below the LOQ, though ICP-MS is one of the most sensitive methods for multi-element determinations in liquid samples.

Table 3 Elemental concentrations in urine for 72 children Element

Li Be V Cr Mn Ni Co Cu Zn Ga As Se Rb Sr Mo Rh Pd Ag Cd In Sn Sb Cs Ba Pt Au Tl Pb Bi U a

a

Mean (Ag/l)

77
Range (Ag/l)

7 – 580
Concentrations below the LOQ were calculated as LOQ / 2.

a

Geometric mean (Ag/l)

a

Geometric mean (Ag/g creatinine)

% < LOQ

40
33
0 100 79 3 65 2 0 0 0 89 0 0 0 0 0 96 100 93 0 95 16 21 0 0 95 94 15 0 84 80

Percentiles (Ag/l) 60%

95%

35
306
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Table 4 Elemental concentrations in urine for 87 adults Element

a

Range (Ag/l)

a

Geometric mean (Ag/l)

a Geometric mean (Ag/l creatinine)

% < LOQ

Percentiles (Ag/l) 60%

95%

Li Be V Cr Mn Ni Co Cu Zn Ga As Se Rb Sr Mo Rh Pd Ag Cd In Sn Sb Cs Ba Pt Au Tl Pb Bi U

35
4 – 237
23
22
0 100 69 6 65 9 0 0 0 92 0 0 0 0 0 95 100 92 2 95 16 21 0 0 93 92 15 0 86 82

24
115
Mean (Ag/l)

a

Concentrations below the LOQ were calculated as LOQ / 2.

chronic Be disease are discussed. Only a few data about urinary Be concentrations of non-exposed people are available [24,40,44]. The measured Be concentrations in our study were below the LOQ of 0.009 Ag/l. This is in agreement with the survey in the US [40], where all 2465 humans had Be concentrations below a LOQ of 0.09 Ag/l. Compared to this study our LOQ was improved by a factor 10 and it seems to be that urinary Be concentrations are lower as expected. In earlier studies [24,44] significantly higher average values (0.9 Ag/l in the US and 0.4 Ag/l in Italy) were reported for non-exposed subjects, however, these results should be reviewed critically, because in both papers less sensitive GF-AAS was used for the determination and the reported mean Be concentration was close to the limit of quantification.

samples, because all measured Pd concentrations were found below the LOQ of 90 ng/l. In general, for adults higher geometric mean values for the precious metals were found, probably due to the higher number of dental alloys. The highest concentrations are 120 ng/l for Pt, 50 ng/l for Ag, 20 ng/l for Rh and 340 ng/l for Au (Table 4). The two people with the highest urinary Au concentrations reported about more than 4 gold fillings in their teeth. A correlation between the number of Au dental inlays and the Au concentration in urine was also found in the German Environmental Survey from 1998 [37], where geometric mean values of 2 ng/l for Pt and 45 ng/l for Au were calculated for adults of the general population. In the US survey [40] all measured concentrations for Pt were below an LOQ of 30 ng/l.

3.2.2. Precious metals Ag, Rh, Pd, Pt, Au Main sources of environmental exposure of the precious metals are dental alloys and catalysts from cars. The measured concentrations of Rh, Pt, Au and Ag were below the LOQ for more than 90% of the samples (Tables 3, 4). The LOQs range from 8 ng/l for Ag to 24 ng/l for Au (Table 1). Spectral interferences on 106Pd have been reported [12] but were not observed or are negliable for our 159 real

3.2.3. Essential trace elements Se, Co, Mn, Cu, Zn, Mo, V, Cr, Ni For some of these elements (e.g., Se, Zn or Mn) other biological fluids (serum or blood) are preferred to determine the essential trace element concentrations, however, in the case of intoxications urine is often used for analysis. Among children, urinary concentrations of these essential trace elements calculated in Ag/g creatinine decrease with age

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315

Table 5 Geometric mean values, ranges and 95% percentiles of elemental concentrations in urine (Ag/g creatinine) for children of three age groups (each with n = 24 human subjects) Element

Concentration (Ag/g creatinine) Geometric meana

95% Percentilea

Range

Age group

2–6

7 – 11

12 – 17

2–6

7 – 11

12 – 17

2–6

7 – 11

12 – 17

Li Be V Cr Mn Ni Co Cu Zn Ga As Se Rb Sr Mo Rh Pd Ag Cd In Sn Sb Cs Ba Pt Au Tl Pb Bi U

31
39
35
66
428
285
17 – 179
11 – 521
7 – 477
a

Concentrations below the LOQ were assumed as LOQ / 2.

(Table 4). Urinary concentration ranges of Mo (1 –126 Ag/l) and Zn (60 – 1142 Ag/l) are higher than for Se (4 –39 Ag/l) and Cu (4 –53 Ag/l) and significantly higher than for Ni (0.1 –20 Ag/l). Geometric mean values for Mo, Zn, Se, Cu and Ni are 48, 405, 15, 12 and 1.7 Ag/l, respectively (Table 3). For the other trace elements Co, V, Cr and Mn the geometric mean values are below 0.2 Ag/l. Co, Ni, Cr and Mn were also described as toxic or carcinogenic at higher concentration levels and therefore maximum concentration values (MAK) and biological tolerance values (BAT) were expressed for occupational medicine [46]. The geometric mean values for Zn and Se calculated to creatinine are 335 and 12 Ag/g, respectively, which is roughly similar to 399 and 10 Ag/g creatinine, respectively, which was found in a study in the Czech Republic for children [45]. For adults the concentrations of all these trace elements are generally lower (Table 4). 3.2.4. Toxic elements Cd, Pb, Tl, U Previous studies reporting urinary concentrations of Cd, Pb, Tl and U in other countries have found values similar to those reported in Tables 3 and 4 [24,40]. In the biomonitor-

ing survey for the whole US population [40] geometric mean values of 0.31, 0.71, 0.17 and 0.007 Ag/g creatinine were reported for Pb, Cd, Tl, U, respectively, which are slightly higher than our values for adults of 0.16, 0.5, 0.07 and 0.004 Ag/g creatinine, respectively. Children aged 2– 6 years have higher urinary concentrations of all 4 elements than older children (Table 5). Cd concentrations for the age group 7– 11 years are lower than either for children aged 2– 6 years or adults aged 18 years and older due to the higher number of smokers in the group of adults. Geometric mean and 95% percentile for adults are 0.16 and 0.42 Ag/g creatinine, respectively (Table 4). For adults we have compared smokers (n = 17) and non-smokers (n = 70) and for smokers the Cd concentrations increases by a factor 2– 3 (Fig. 1). 3.2.5. Other elements of group 13 –15: As, Sb, Bi, Sn, Ga, In In this group of elements As has the highest background concentration in the environment. Non-occupational exposure to As is easy possible by the oral pathway, especially when sea food is consumed regularly. In our study selected percentiles of arsenic concentrations of people eating fish in

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Table 6 Geometric mean values, ranges and 95% percentiles of elemental concentrations in urine (Ag/l) for children divided in three age groups (each with n = 24 human subjects) Element

Concentration (Ag/l) Geometric meana

95% Percentilea

Age group

Li Be V Cr Mn Ni Co Cu Zn Ga As Se Rb Sr Mo Rh Pd Ag Cd In Sn Sb Cs Ba Pt Au Tl Pb Bi U

Range

Age group

Age group

2–6

7 – 11

12 – 17

2–6

7 – 11

12 – 17

2–6

7 – 11

12 – 17

27
45
61
70
172
522 0.004 0.123 0.38 0.202 7.3 2.21 23.8 929 0.072 103.0 29.9 3023 310 122
7 – 257 <0.004 LOQ—0.162 LOQ—0.83 LOQ—1.15 0.13 – 6.5 0.04 – 2.7 4 – 33 115 – 1142
11 – 486
12 – 580
a

Concentrations below the (LOQ) were assumed as LOQ / 2.

the last 48 h prior to sample collection are 2 –4 times higher compared with non-fish eaters for the same time period (Fig. 2). A toxicological conclusion for urinary As determined by ICP-MS is difficult because As compounds have significant differences in their toxicological behaviour and ICP-MS is

determining the total As concentration. It is not possible to determine the toxicologically relevant species of As by ICPMS directly without a seperation technique, however, it is possible to investigate if people have been exposed to total arsenic. Because the total As concentration is measured in 100

100 80

Percentile (%)

Percentile (%)

80

60 smoker non-smoker

40

fish consumption 40

without fish consumption

20

20

0 0,0

60

0,1

0,2

0,3

0,4

0,5

0,6

Cd-concentration (µg/l) Fig. 1. Comparison of selected percentiles of urinary Cd concentrations of smokers and non-smokers.

0 0

50

100

150

200

As-concentration (µg/l) Fig. 2. Comparison of selected percentiles of urinary As concentrations of people with and without fish consumption.

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our study it is also clear why our results are higher compared to earlier studies [36,38], where only selected species of arsenic were determined. As ranges in the urine samples from 1– 375 Ag/l with a geometric mean of 13 Ag/l. Differences of the geometric mean for As concentrations between children and adults were not found (Tables 3,4). For Sn the mean concentration is higher for adults due to some outliers. Geometric mean concentrations are 0.4 and 0.8 Ag/l for children and adults, respectively (Tables 3,4). The concentrations of Bi, Ga and In in urine were found to be extremely low. For Ga, In and Bi more than 80% of all measured concentrations are below the LOQ. Sb was found in 80% of all samples with a maximum concentration of 0.72 Ag/l for children and 0.57 Ag/l for adults (Tables 3,4).

[6]

[7]

[8]

[9]

[10]

4. Conclusions We have demonstrated the application of ICP-MS for the biomonitoring of trace elements in human urine in the ng/l concentration range. The concentration data of 30 elements serve as a basis for the formulation of reference values for essential and toxic trace elements. The data will also help scientists planning research about exposition to metals and health effects. For many trace elements discussed in this paper (e.g., Ba, Cs, Co, Sb, Sn, Pt) more research is required for the investigation of health effects at our reported concentration ranges.

Acknowledgements We gratefully acknowledge Dirk Gipperich and Walter Woltery (Gymnasium der Stadt Hu¨ckelhoven, Germany) and Jo¨rg Platthaus (Soest, Germany) for sample collection and our excellent team in the trace element laboratory for analytical assistance and routine measurements.

References [1] Nixon DE, Moyer TP. Routine clinical determination of lead, arsenic, cadmium and thallium in urine and whole blood by inductively coupled plasma mass spectrometry. Spectrochim Acta Part B Atom Spectrosc 1996;51:13 – 25. ¨ dman F, Branth S. Multielement analysis of whole [2] Rodushkin I, O blood by high resolution inductively coupled plasma mass spectrometry. Fresenius’ J Anal Chem 1999;364:338 – 46. ¨ dman F, Olofsson R, Axelsson MD. Determination of [3] Rodushkin I, O 60 elements in whole blood by sector field inductively coupled plasma mass spectrometry. J Anal At Spectrom 2000;15:937 – 44. [4] Marchante-Gayo´n JM, Muniz CS, Garcia Alonso JI, Sanz-Medel A. Multielemental trace analysis of biological materials using double focusing inductively coupled plasma mass spectrometry detection. Anal Chim Acta 1999;400:307 – 20. [5] Barany E, Bergdahl IA, Schu¨tz A, Skerfving S, Oskarsson A. Inductively coupled plasma mass spectrometry for direct multi-

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

317

element analysis of diluted human blood and serum. J Anal At Spectrom 1997;12:1005 – 9. Bocca B, Alimonti A, Petrucci F, et al. Quantification of trace elements by sector field inductively coupled plasma mass spectrometry in urine, serum, blood and cerebrospinal fluid of patients with Parkinson’s disease. Spectrochim Acta Part A Mol Spectrosc 2004;59: 559 – 66. Alimonti A, Petrucci F, Laurenti F, Papoff P, Caroli S. Reference values for selected trace elements in serum of term newborns from the urban area of Rome. Clin Chim Acta 2000;292:163 – 73. Hsiung CS, Andrade JD, Costa R, Ash KO. Minimizing spectral interferences in the quantitative multielement analysis of trace elements in biological fluids by inductively coupled plasma mass spectrometry. Clin Chem 1997;43:2303 – 11. Yu L, Koirtyohann SR, Rueppel ML, Skipor AK, Jacobs JJ. Simultaneous determination of aluminium, titanium and vanadium in serum by electrothermal vaporization-inductively coupled plasma mass spectrometry. J Anal At Spectrom 1997;12:69 – 74. Huang C, Beauchemin D. Direct multielement analysis of human serum by ICP-MS with on-line standard addition using flow injection. J Anal At Spectrom 2003;18:951 – 2. Muniz CS, Marchante-Gayo´n JM, Garcia Alonso JI, Sanz-Medel. Accurate determination of iron, copper and zinc in human serum by isotope dilution analysis using double focusing ICP-MS. J Anal At Spectrom 1999;14:1505 – 10. Begerow J, Turfeld M, Dunemann L. New horizons in human biomonitoring of environmentally and occupationally relevant metals — sector field ICP-MS versus electrothermal AAS. J Anal At Spectrom 2000;15:347 – 52. Schramel P, Wendler I, Angerer J. The determination of metals (antimony, bismuth, lead cadmium, mercury, palladium, platinum, tellurium, thallium, tin and tungsten) in urine samples by inductively coupled plasma mass spectrometry. Int Arch Occup Environ Health 1997;69:219 – 23. Townsend AT, Miller KA, McLean S, Aldous S. The determination of copper, zinc, cadmium and lead in urine by high resolution ICP-MS. J Anal At Spectrom 1998;13:1213 – 9. Schramel P, Wendler I. Antimony, lead, cadmium, platinum, mercury, tellurium, thallium, bismuth, tungsten, tin. In: Angerer J, Schaller KH, editors. Analyses of hazardous substances in biological materials, vol. 6. Weinheim’ Wiley-VCH; 1999. p. 79 – 109. Schramel P, Dunemann L. Aluminum, chromium, cobalt copper, manganese, molybdenum, nickel, vanadium. In: Angerer J, Schaller KH, editors. Analyses of hazardous substances in biological materials, vol. 7. Weinheim’ Wiley-VCH; 2001. p. 73 – 96. Towsend AT. The accurate determination of the first row transition metals in water, urine, plant, tissue and rock samples by sector field ICP-MS. J Anal At Spectrom 2000;15:307 – 14. Centineo G, Montes Bayo´n M, Sanz-Medel A. Flow injection analysis with inductively coupled plasma time-of-flight mass spectrometry for the simultaneous determination of elements forming hydrides and its application to urine. J Anal At Spectrom 2000;15:1357 – 62. Rodushkin I, Axelsson D. Application of double focusing sector field ICP-MS for multielement characterization of human hair and nails: Part 1. Analytical methodology. Sci Total Environ 2000;250: 83 – 100. Yoshinaga J, Shibata J, Morita M. Trace elements determined along single strands of hair by inductively coupled plasma mass spectrometry. Clin Chem 1993;39:1650 – 5. D´Haese P, Couttenye MM, Lamberts LV, et al. Aluminum, iron, lead, cadmium, copper zinc, chromium, magnesium, strontium and calcium content in bone of end-stage renal failure patients. Clin Chem 1999; 45:1548 – 56. Vaughan MA, Baines AD, Templeton DM. Multielement analysis of biological samples by inductively coupled plasma mass spectrometry: II. Rapid survey method for profiling trace elements in body fluids. Clin Chem 1991;37:210 – 5.

318

P. Heitland, H.D. Ko¨ster / Clinica Chimica Acta 365 (2006) 310 – 318

[23] Sabbioni E, Minoia C, Pietra R, Fortaner S, Gallorini M, Saltelli A. Trace element reference values in tissues from inhabitants of the European Community: II. Examples of strategy adopted and trace element analysis of blood, lymph nodes and cerebrospinal fluid of Italian subjects. Sci Total Environ 1992;120:39 – 62. [24] Minoia C, Sabbioni E, Apostoli P, et al. Trace element reference values in tissues from inhabitants of the European Community: I. A study of 46 elements in urine blood and serum of italian subjects. Sci Total Environ 1990;95:89 – 105. [25] Rukgauer M, Klein J, Kruse-Jarres JD. Reference values for the trace elements copper, manganese, selenium and zinc in serum/plasma of children, adolescents and adults. J Trace Elem Med Biol 1997;11: 92 – 98. [26] Heitland P, Ko¨ster HD. Fast, simple and reliable routine determination of 23 elements in urine by ICP-MS. J Anal At Spectrom 2004;19: 1552 – 8. [27] Speˇva´*kova´ V, Cˇejchanova´ M, Cˇerna´ M, Speˇva´*ek V, Sˇmı´d J, Benex B. Population based biomonitoring in the Czech Republic: urinary arsenic. J Environ Monit 2002;4:796 – 8. [28] Milton AH, Hasan Z, Rahman A, Rahman M. Chronic arsenic poisoning and respiratory effects in Bangladesh. J Occup Health 2001;43:136 – 40. [29] Chen JL, Guo YL, Tsai PJ, Su LF. Use of inhalable Cr(VI) exposures to characterize urinary chromium concentrations in plating industry workers. J Occup Health 2002;44:46 – 52. [30] Eikmann T, Makropoulus V, Eikmann S, Krieger T. Cross-sectional epidemiological study on chromium, manganese mercury nickel, selenium excretion in urine of populations in areas with with different air pollution. Fresenius Environ Bull 1992;1:706 – 11. [31] Kiilunen M, Jarvisalo J, Makitie O, Aitio A. Analysis, storage stability and reference values for urinary chromium and nickel. Int Arch Occup Environ Health 1987;59:43 – 50. [32] Herber RFM. Review of trace element concentrations in biological specimens according to the TRACY protocol. Int Arch Occup Environ Health 1999;72:279 – 83. [33] Iyengar V, Woittiez J. Trace elements in human clinical specimen: evaluation of literatire data to identify reference values. Clin Chem 1988;34:474 – 81. [34] Gammelgaard B, Jons O. Determination of selenite and selenate in human urine by ion chromatography and inductively coupled plasma mass spectrometry. J Anal At Spectrom 2000;15:945 – 9.

[35] Iversen BS, Menne´ C, White MA, Kristiansen J, Molin Christensen J, Sabbioni E. Inductively coupled plasma mass spectrometric determination of molybdenum in urine from a Danish population. Analyst 1998;123:81 – 5. [36] Krause C, Babisch W, Becker K, et al. Umwelt-Survey 1990/92 Band 1a: Studienbeschreibung und Human-Biomonitoring. Umweltbundesamt, ed., 1996. [37] Becker K, Kaus S, Krause C, et al. Umwelt-Survey 1998 Band III: human-biomonitoring. Umweltbundesamt, ed., Berlin, 2002. [38] Becker K, Schulz C, Kaus S, Seiwert M, Seifert B. German Environmental Survey 1998 (GerES III): environmental pollutants in the urine of the German population. Int J Hyg Environ Health 2003; 206:15 – 24. [39] Wilhelm M, Ewers U, Schulz C. Revised and new reference values for some trace elements in blood and urine for human biomonitoring in environmental medicine. Int J Hyg Environ Health 2004;207:69 – 73. [40] Second national report on human exposure to environmental chemicals. NCEH Pub, vol. 02-0716. Atlanta, Georgia’ Department of Health and Human Services; 2003. [41] Alimonti A, Petrucci F, Krachler M, Bocca B, Caroli S. Reference values for chromium, nickel and vanadium in urine of youngsters from the urban area of Rome. J Environ Monit 2000;2:351 – 4. [42] Boumans PWJM. Measuring detection limits in inductively coupled plasma emission spectrometry using the SBR-RSDB approach. I. A tutorial discussion of the theory. Spectrochim Acta 1991;46B:431 – 45. [43] Infante PF, Newman LS. Beryllium exposure and chronic beryllium disease. The Lancet 2004;363:415 – 6. [44] Grewal DS, Kearns FX. A simple and rapid determination of small amounts of beryllium in urine by flameless atomic absorption spectrometry. At Absorpt Newsl 1977;16:131 – 2. [45] Benex B, Speˇva´*kova´ V, Sˇmı´d J, et al. Determination of normal concentration levels of Cd, Pb, Hg, Cu, Zn and Se in urine of the population in the Czech Republic. Cent Eur J Publ Health 2002;10: 3 – 5. [46] List of MAK and BAT values 2003. Maximum concentrations and biological tolerance values at the workplace, Report 39. Deutsche Forschungsgemeinschaft, ed., Wiley-VCH, Weinheim; 2003.