The Science of the Total Environment, 105 (! 991 ) 87-99 Elsevier Science Publishers B.V., Amsterdam
87
Estimated dietary intake of lead and cadmium and their concentration in blood K. Louekari a'*, S. Valkonen h, S.
P o u s i c a n d L. V i r t a n e n c
a National Finnish Board of Waters and Environment, P.O. Box 250. SF-O0101 Helsinki, Finland b Institute of Occupational Health, Laboratory of Biochemists),, Arinatie 1, SF-00370 Helsinki 37, bYnland University of Helsinki, Department of Nutrition, SF-O0710 Helsinki 71, Finland (Received March 20th, 1990; accepted July 8th, 1990)
ABSTRACT
Dietary intake of lead and cadmium and the concentration of Pb and Cd in blood were determined for 42 non-smoking subjects not occupationally exposed to Pb or Cd. The aim of the study was to analyze: (i) the relation between calculated dietary intake of Pb and Cd and the concentra:ion of these metals in blood; and (ii) the methodological problems associated with these two measurements of exposure. The mean dietary intakes of Cd and Pb were 14.5 (SD, 3.1) and 5?.9 (SD, 17.9) Fg day- ~, respectively. The concentrations of Pb and Cd in blood were 0.28 Fmol 1- ~(SD, 0.12) and < 0. I Fg I-J, respectively. The relation between dietary intake and concentration in blood was similar to that found in other countries. However, the distributions of these two variables were quite different. Thi~ suggests that dietary intake does not accurately reflect the concentration of lead in blood. The methodological problems associated with estimating the dietary intake of toxic metals were: mistakes in keeping food diaries: errors in transferring data from diaries to the computer; invalid food composition or recipe data in the data base used in the calculations. The concentration of Pb and Cd in blood is not necessarily a good indicator of exposure, since only a small proportion of the total body burden is in the blood, and interactions of Pb and Cd with other food con,~tituents during absorption are possible. INTRODUCTION
Several methods are available to estimate the intake ot food contaminants. They are based on food consumption data and analysis of contaminants in food items. The methods can be inaccurate for several reasons: (a) reliable food consumption data is difficult to obtain; (b) the analysis of heavy metals at trace levels is: characterized by sensitivity and contamination problems; (c) * Author to whom correspondence and reprint requests should be addressed.
0048-9697/91/$03.50
© 1991 - - Elsevier Science Publishers B.V.
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K. LOUEKARI ET AL.
representative sampling and coverage of all relevant food items is usually not possible (Louekari and Salminen, 1986; Louekari et al., 1988). Therefore, the estimated intakes do not necessarily reflect the actual exposure or the internal dose of the contaminant. Biological monitoring of exposure to heavy metals can be undertaken by measuring the concentration of the metals in blood or urine. Samples from tissues such as kidney and liver are normally not available. However, the concentration of lead and cadmium in blood of non-occupationally exposed people kas not been correlated with recent or chronic exposure. Therefore, information concerning the relation between dietary intake of Pb and Cd and their concentrations in blood is scarce. In some studies, smoking data and age of the cohort has been presented, but not the dietary intake (Brockhaus et al., 1983; Telisman et al., 1986). Populations living near polluting smelters have also been studied (Carvalho et al., 1986). Children were exposed to approximately 10-50 times higher concentrations of cadmium in food as compared, for example, with those in Scandinavian countries, and an alarmingly high concentration of cadmium was found in their blood (mean, l0/~g 1-1; maximum, 55/zg 1-~ ). This r,~flects extreme pollution of food and drinking water. Estimated average intakes have been correlated with average concentrations of cadmium in kidney using valules reported in the literature from different countries; a statistically significant relationship was reported by Morgan and Sherlock (1984). Kowal (1988) reported a positive correlation between urinary cadmium and smoking, and a negative correlation between urinary cadmium and dietary iron and calcium. The dietary intake of cadmium was not estimated in that st~dy. Correlations between dietary selenium and plasma selenium levels were studied by Mutanen et al. (1985). A reasonable correlation (r = 0.67) was found when the 2-week recall method was used, but the 24-h recall method did not show any correlation. For lead and cadmium there are also toxicokinetie factors which potentially impair the correlation between the dietary intake and blood levels of Pb and Cd; for example, Fe, Ca and Zn in the diet may interact with Pb and Cd during absorption (Hathcock, 1976; Mykk~inen and Humaloja, 1984). Urban air and drinking water can significantly affect the exposure to lead and cadmium for those living in contaminated areas. Also, smoking and the habit of pica can significantly increase the intake of toxic metals (Telisman et al., 1986; Morgan et al., 1988; Louekari et al., 1989). However, in the cohort of the present study, the possibility of additional expasures from these sources was very limited. The subjects were non-smokers, respiratory exposure to lead was estimated to be 5/~g day -I and the exposure from drinking water was negligible (Louekari et al., 1989).
DIETARY INTAKE OF LEAD AND CADMIUM
89
The aims of the present study were: (i) to study the relationship between estimated dietary intake and levels of lead and cadmium in the blood of a non-occupationally exposed population (ii) to consider the methodological factors, and (iii) to compare the present results with earlier results on the relationship between dietary intake and concentration of Pb and Cd in blood. MATERIAL AND MI:q HODS
Lead in blood samples of 42 female students was analyzed by graphite furnace atomic absorption spectrophotometvy (AAS). Food diaries of the subjects and food composition tables were used to provide an estimate of lead and cadmium intake (Koivistoinen, 1980). Material was collected from subjects at the Department of Nutrition, University of Helsinki, in 1985.
Analysis of lead in blood The analyses were performed with a polarized Zeeman AAS. (Hitachi, Model 7000) equipped with a graphffe furnace, an automatic sampling system, and a data processor. The samples were diluted five-fold with an aqueous solution of diammoniumhydrogen phosphate and Triton-X-100. A 20-pl aliquot was injected into a graphite furnace cup cuve~te. Lead con-. centrations were obtained by direct comparison with matrix-matched working curves from a data processor. The analytical method, including instrumental parameters and temperature programme, was modified from the method described by Subramanian and Meranger (198 l). The reliability of the method was monitored by the use of internal quality control procedures in addition to participating in external quality assurance schemes. Our laboratory has participated regularly, with good res~Jlts, in a UK External Quality Assurance Scheme (UKEQAS) for Pb in blood (Bullock et al., 1986). The detection limit of the method is 20 pg Pb l -~ . The within-run coefficient of variation (calculated from l0 consecutive measurements) was 0.7 and 1.5% at 100 and 700pgl -~, respectively. The day-to-day coefficient of variation calculated on the basis of l0 determinations over 2 weeks was 2.8% at a concentration of 400 #g l-~. Determinations were made on haemolyzed blood and the result calculated for whole blood by taking the dilution into account, assuming that 99% of the blood lead is in the erythrocytes (Manton and Cook, 1984) and using the mean haematocrit value of the subjects (40%). The cadmium concentration of blood samples was determined using AAS and mild ashing techniques (Kiilunen and Aitio, 1990).
9O
K. LOUEKAR! ET AL.
Estimation of intakes The dietary intake of Pd and Cd was estimated by using two sets of data: the amounts of food recorded in food diaries were multiplied by the respective concentration of heavy metals in that food, giving the dietary intake. It was not possible to corfsider inter-individual variation in absorption. The subjects, 42 volunteer, healthy female students, of average age 25 years, kept food diaries for 14 days after the donation of blood samples. Written instructions for recording food consumption, including also guidance for converting household measures to grams, were given to the subjects. Seven days of those 2 weeks were considered to represent the habitual food consumption of each individual and, consequently, also the dietary intake of lead and cadmium. Between the entry of data by the subjects into their dairies and calculation of intakes by the computer, there were the following phases which are sources of possible errors; keeping of the food diaries; coding of the food items, including division of the meals into particular food items; converting household measures to grams; conversion of the codes and amounts of foods to machine-readable form; program-driven coding check; manual check of stored data; correction of coding errors; and calculation of intakes. In a review of the possible errors associated with diary records, the following estimates are given: coding errors of the investigator, 3-17%; and estimation of food weights, 20-50% (Bingham, 1985). The contribution of other phases to the total error is not known. Because the subjects were students of nutrition and consequently, rather conscious of their food habits, it is considered likely that recording of food consumption was reliat)le. The coding scheme was as follows. In most cases, there was a code for all food items recorded in the diaries. If there was no adequate code, the code of the most similar food item was used (23 cases). A general code was used for some food items, for example average mushroom instead of specific mushrooms and average juice instead of apple juice (27 cases). Some foods were divided into ingredients, for example instant cocoa drink was divided into cocoa, sugar and milk powder (15 cases). New food items were also added to the data base, for example mango and coconut (five cases). Some food items were not coded, since it was assessed that their effect on the intake of toxic metals was minimal, for example herbal tea and some spices (seven cases). Some new recipes and food items were added to the respective files in case they contributed significantly to the food consumption of a subject. The codes for foods and meals and the respective amounts in grams were stored in the system for calculation.
91
DIETARY INTAKE OF LEAD AND C A D M I U M
There is a difference between the present mainframe computer system (VAX/VMS) and microcomputers or mainframe systems with a different use~ interface. When a ~-aic~ocomputer or a direct access system is used, the user selects the appropriate food from the list displayed, and thus coding and typing errors do not occur. The coded food consumption data were used as input to the food composition system maintained at the Department of Nutrition of the University of Helsinki. The average intake of Pb and Cd in seven of the 14 days, covering all weekdays, was calculated. .m-
RESULTS AND DISCUSSION
In the present study, techniques were found to solve the problem of incompatibility between data in the food diaries and that in the data base. If the data base did not contain the food or the meal that was recorded in the diary, the coding scheme presented above was applied. Also, some new food codes and recipes were stored in the data base. A person who formulates new recipes should have an appropriate education, preferably in nutrition, and use up-todate reference material on the composition of meals and dishes. If new analytical data became available, the composition data base was updated accordingly. The mean dietary intake of Pb and Cd in the study group was 52.9 and 14.5/tg d a y - ' , respectively, values fairly similar to recent estimates for nonoccupationally exposed non-smoking subjects (Table 1). The correlation coefficient between intake of energy (kJ d a y - ' ) and intake of lead (pg day -~) was 0.61 and that between intake of energy and intake of cadmium was 0.65. Although the foods contributing most to the intake of lead and cadmium are different, there was also a positive correlation between the intakes of Pb and Cd (0.52). Thus, energy intake appears to be one factor affecting the intake of Pb and Cd. This has also been suggested in previous studies (Louekari et al., 1989). "[ABLE I Intake of energy, iron. calcium, lead and cadmium according to food diaries Component
Unit
Mean intake ( +_SD)
Energy Iron Calcium Lead Cadmium
kJ day ' mg day-' mg day-i l~g day t /,g d a y '
7665 ( + 1381 ) 13.5 (+2.7) 1138 ( + 358) 52.9 (+ 17.0) 14.5 (+ 3.1)
Range
4358-10554 7.7-21.4 498-1937 25.7-105.3 7.2-23.8
Mean intake per 5 MJ
34.4 9.5
92
K. L O U E K A R I E T A L
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60
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100
110
of lead (?,g/Coy)
Fig. !. Distribution of calculated lead intake (.ug d a y - I ) .
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55
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70
93
DIETARY INTAKE OF LEAD AND CADMIUM
If energy intake is the major factor explaining the distribution of the intake of these two elements, one would assume that when intake is calculated per energy unit the range covered by the distribution would be smaller. When the distribution of energy-related intake of the metals (/~g/day/5 MJ) and the skewness were compared, there was no remarkable difference between uncorrected and energy-related intake (Figs 1 and 2). Skewness factors for the distribution of Pb and Cd intake were 1.58 and 0.44, respectively, and the skewness factors for energy-related intake were 1.70 and 0.69, respectively. For comparison, the skewness factor of energy intake was - 0.16. Consumption of food items which have high concentrations of cadmium or lead, but do not contribute significantly to energy intake, has a remarkable effect on the energy-related intak~ (/tg/day/5 M J). The mean concentration of Pb in blood was 61/~g l ~ or 0.28 :,tool l- ~(SD, 0.12). The range of concentrations (0.08-0.531~moll -~) is wide when compared with the estimated intakes. The mean concentration of Cd in blood was below the limit of detection, l nmol l -~. The form of the distribution curve for blood lead (Fig. 3) differs from that for estimated lead intake. Comparison of the distribution curves (Figs l and 3) suggests that the two methods do not result in consistent estimates of exposure. Therefore, estimation of Pb intake via food by the calculation method (even when there is no other significant sources of exposure) does not reliably predict con"/'# J
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K. LOUEKAR| ET AL.
centration of Pb in blood. The form of the distribution of dietary lead intake was in agreement with two recent studies (Morgan et al., 1988; Louekari et al., 1989). The sources of error in the calculation of dietary intakes (based on food diaries) are considered to be: (i) errors in some phase of data entry, including wrong generalizations in some phase of the coding scheme; (ii) out-of-date data in the food composition or recipe data bases used in the calculations. Al~o, the effect of fond preparation is not usually taken into account; (iii) memory lapse while participants are keeping the food diary. In addition, the two methods can result in different estimates of exposure, because the concentration ot' Pb in blood does not faithfully reflect the estimated intake of Pb, since absorption and distribution of Pb are affected by other dietary factors. A crucial factor is also the duration of recording required to estimate the long-term dietary intake of Pb and Cd reliably. For selenium, a 7-day record gave an estimate which varied within 35% of that obtained for long-term selenium intake (Mutanen, 1984). Selenium and heavy metals are similar in that trace amounts are found in every food item, and their concentration in foods does not affect the consmaers' choice. Consequently, some of the inter-individual variation in the dietary intake of Pb and Cd observed in the present study seems to be caused by inaccuracy in the method of the food consumption study. However, inter-individual variation (26-105 #g day -m for lead) is about four-fold the uncontrolled intra-individual variation (18 l~g day -~ for lead) (Table 1). The reliability of the calculation method can also be improved by maintaining an adequate food composition data base. National data bases should be coordinated and regularly updated. Changes in Pb concentrations of blood samples may take place during storage due to adsorption onto walls of cuvettes. The effects of storage time and temperature have been studied, but the results are contradictory: M6ranger et al. (1981) found a significant decrease in the Pb concentration after only 1 week when stored at - 10°C, while Subramanian et al. (1983) found no significant changes after 60 days at the same temperature. Lind et al. (1987) found that the decrease in Pb concentration was 7-15% after 5-6 years of storage at -20°C. Consequently, concentration changes during storage could affect the reliability of biological monitoring based on blood analysis, although the significance of this effect remains unclear. In studies where the concentrations of Pb and Cd in the blood of nonoccupationally exposed people have been analysed, the dietary intake of these metals has not been estimated. In Tables 2 and 3, recorded dietary intake data for various countries are compared with reported concentrations of Pb and Cd in blood for the same countries. Lead and Cd concentrations in blood of
60 218 27 179 82 82 52
UK FRG Sweden Belgium Japan USA Finland
Morgan et al., 1988 Weigert et al., 1984 Slorach et al., 1983 Buchet and Lauwerys, 1983 GEMS, 1982 GEMS, 1982 Present study
Reference
122 82 67 140 49" 92 61
(ttg !- I )
Concentration in blood
Elwood, 1983 Brockhaus et al., 1983 Friberg and Vahter, 1983 Friberg and Vahter, 1983 Watanabe et al., 1985 Annest et ai., 1983 Present study
Reference
The estimates for the USA and Japan are from market basket studies, including 117 and 90 food items, respectively; for the Swedish and Belgian studies, duplicate portions were analysed; the-estimate for the FRG is based on a calculation method. Subjects of this study were farmers and the aim was to establish the baseline level and not a representative mean level.
Dietary intake of Pb (/~g day- i )
Country
Relation between the dietary intake of Pb and the concentration of Pb in blood among non-smoking, non-occupationally exposed subjects
TABLE 2
Dietary intake of Cd (pg day-~ )
53 10 42 33 15 !5
Country
FRG Sweden Japan USA USA Finland
Weigert et al., 1984 Slorach et ai., 1983 GEMS, 1982 GEMS, 1982 Kowal et al., 1979 Present study
Reference
1.6 0.2 1.0 0.55 1.0 < 0. !
Concentrat irm in whole blood (#g ! -~)
Kraus et al., 1988 Friberg end Vahter. 1983 Friberg and Vahter, 1983 Friberg and Vahter, 1983 Kowal et al., 1979 Present study
Reference
Relation between the dietary intake of Cd and the concentration of cadmium in blood among non-smoking, non-occupationally exposed subjects
TABLE 3
DIETARY INTAKE OF LEAD AND CADMIUM
97
non-occupgfionally exposed individuals are reported to be 49-140 and < 0.11.6#gl -I, respectively. Occupational exposure can increase the level of cadmium in blood, for example to 7.2/~gl -~ in phosphate workers and to 14.1 #gl -I in workers in an alkaline battery factory (Sharma, 1981; Hassler et al., 1983). From Tables 2 and 3 it is evident that correlations between estimated dietary intakes and concentrations of heavy metals in blood are not as good as the correlation between dietary cadmium intake and concentration of Jv"r]. cadmium in kidney found by Morgan and Sherlock (1 aQA~ CONCLUSIONS
The analytical difficulties and the need for quality control in the analysis of blood Pb and Cd have recently been demonstrated by Vahter and Friberg (1988)~ When analytical quality control is applied, blood analysis can be reliable. However, it is not clear whether the concentrations of Pb and Cd in blood reliably reflect the total body burden of these metals or the dietary intake. It seems that dietary intake of Pb and Cd is an indicator of body burden rather than an indicator of concentrations in blood. However, the concentration of Cd in urine Js positively correlated with both total body burden and also with exposure from cigarette smoke (Elinder et al., 1976; Kowal, 1988). This present study suggests that blood Pb analysis should not be used as a substitute for reliable estimates of Pb intake. The reliability of the calculation method can be improved by eliminating unnecessary phases in data entry and using updated files of heavy metal concentrations in food items. The duplicate portion method for intake estimation may be more reliable than calculated estimates (Louekari et al., 1988). Therefore, the correlation between this latter type of estimate and concentrations of heavy metals in blood could also be studied. ACKNOWLEDGEMENTS
We are grateful to Dr Marj~ Mutanen for her assistance during the design of the study, and to Dr Kai Savolainen, National Public Health Institute, and Dr Antero Aitio, Occupational Health Institute, for constructive comments on the manuscript. This study was supported by a grant from the Finnish Culture Fund. REFERENCES Annest, J.L., J.L. Pirkle, D. Makuc, J.W. Neese, D.D. Bayse and M.G. Kovar, 1983. Chronological trend in blood lead levels between 1976 and 1980. N. Engi. J. Med., 308: 1373-1377.
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Bingham, S., 1985. Aspects of dietary survey methodology. Br. Nutr. Found. Bull., 10(2): 90-103. Brockhaus, A., I. FreJer, U. Ewers, E. Jerman and R. Dolgner, 1983. Levels of cadmium and lead in blood in relation to smoking, sex, occupation, and other factors in an adult population of the FRG. Int. Arch. Occup. Health, 52: 167-175. Buchet, J.P. and R. Lauwerys, 1983. Oral daily intake of cadmium, lead, manganese, copper, chromium, mercury, calcium, zinc and arsenic in Belgium: a duplicate meal study. Food Chem. Toxicol., 2 i: 19-24. Bullock, D.G., N.J. Smith and T.P. Whitehead, 1986. External quality assessment of assays of lead in blood. Clin. Chem., 32: 1884-1889. Carvalho, F.M., T.M. Tavares, A.M. Siivany .Netc, M.E.C. Lima and F. Alt, 1986. Cadmium concentrations in blood ofchildren living near a lead smelter in Bahia, Brazil. Environ. Res., 40; 437-449. Elinder, C-G., T. KjellstrSn, L. Linnman and G. Pershagen, 1976. Urinary excretion of cadmium and zinc among persons from Sweden. Environ. Res~, 15: 473-484. Elwood, P.C., 1983. Changes in blood lead concentrations in women in Walcs 1972-1982. Med. Pract. 286:1553-1555. Friberg, L. and M. Vahter, 1983. Assessment of exposure to lead and cadmium through biological monitoring: results of a UNEP/WHO Global Study. Environ. Res. 30: 95-128. GEMS, 1982. Joint FAO/WHO Food and Animal Feed Monitoring Programme. Summary and assessment of data received form the FAO/WHO collaborating centres for food contamination monitoring. National Food Administration, Uppsala. Hassler, E., B. Lind and M. Piscator, 1983. Cadmium in blood and urine related to present and past exposure. A study of workers in an alkaline battery factory. Br. J. Ind. Med., 40: 420425. Hathcock, J.N., 1976. Nutrition: toxicology and pharmacology. Nutr. Rev., 34: 65-70. Kiilunen, M. and A. Aitio, 1990. Dilution and mild ashing technique for the routine determination of cadmium in blood and urine. In: int. Symp. Trace Elements in Health and Disease, Espoo, Finland, 5-8 June 1990 (Abstr.). Koivistoinen, P. (Ed.), 1980. Mineral element composition of Finnish foods. Acta Agric. Stand. Suppl., 22: i- 17 i. Kowai, N.E., 1988. Urinary cadmium and beta-microglobulin: correlation with nutrition and smoking history. J. Toxicol. Environ. Health, 2b: 179-183. Kowal, N.E., D.E. Johnson, D.F. Kraemer and H.R. Pahren, 1979. Normal levels ofcadmium in diet, urine, blood, and tissues of inhabitants of United States. J. Toxicol, Environ. Health, 5:995-1014. Kraus, G., K.H, Schaller and L. Winter, 1988. The influence of occupational cadmiumexposure on various element levels in human blood. Zentralbl. Bakteriol. Hyg. B, 186: 95-107. Lind, B., C.G. Elinder, L. Friberg, B. Nilsson, M. Svartengren and M. Vahter, 1987. Quality control in the analysis for lead and cadmium in blood. Fresenius Z. Anal. Chem., 326: 647655. Louekari, K. and S. Salminen, 1986. Intake of heavy metals in Finland, West Germany and Japan. Food Addit. Contain., 3: 355-362. Louekari, K., L. Joikkonen and P. Varo, 1988. Exposure to cadmium from foods, estimated by analysis and calculation - - comparison of methods. Food Addit. Contam., 5: ! ! !-I 17. Louekari, K., U. Uusitalo and P. Pietinen, 1989. Variation and modifying factors of the exposure to lead and cad~llium based on an epidemiologicai study. Sci. Total Environ., 84: i-12.
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Manton, W.I. and J.D. Cook, 1984. High accuracy (stable isotope dilution) measurements of lead in serum and cerebrospinal fluid. Br. J. Ind. Med. 41: 313-319. M6ranger, J.C., B.R. Hollebone and G.A. Blanchetta, 1981. The effects of storage times, temperatuies and container types on the accuracy of atomic absorption determinations of Cd, Cu, Hg, Pb, and Zn in whole heparinized blood. J. Anal. Toxicoi., 5: 33-41. Morgan, H. and J.C. Sherlock, 1984. Cadmium intake and cadmium in the human kidney. Food Addit. Contam., !: 45-5 I. Morgan, H., G.A. Smart and J.C. Sherlock, 1988. Intakes of metal. Sci. Total Environ., 75: 71-100. Mutanen, M., 1984. Dietary intake and sources of selenium in young Finnish women. Hum. Nutr. Appl. Nutr., 38A: 265-269. Mutanen, M., G. Alfihan, H. Arvilommi, P. Koivistoinen and P. Varo, 1985. Correlation between dietary selenium, platelet, GSH-Px and plasma seleniam level. N/iringsforskning, 29: 135-138. Mykk~nen, H.M. and T. Humaloja, 1984. Effect of lead on the intestinal absorption of sodium selenite and selenomethionine (7"~Se)in chicks. Biol. Trace Elem. Res., 6:11-17. Sharma, R.P., 1981. High blood and urine levels of cadmium in phosphate workers' a preliminary investigation. Bull. Environ. Contam. Toxicol., 27: 806-809. Slorach, S., I-B. Gustafsson, L. Jorhem and P. Mattson, 1983. Intake of lead, cadmium and certain other metals via a typical Swedish weekly diet. Vfir Foeda, Suppl. I, 35: 3-16. Subramanian, K.S. and J.C. Meranger, 1981. A rapid electrothermal atomic absorption spectrophotometric method for cadmium and lead in human whole blood. Clin. Chem., 27/i1: 1866-1871. Subramanian, K.S., J.C. Meranger and J. Connor, 1983. The effect of container material, storage time and temperature on cadmium and lead levels in heparinized human whole blood. J. Anal. Toxl~:ol., 7: 15-19. Telisman, S., J. Azaric and D. Prpic-Majic 1986. Cadmium in blood as an indicator of integrated exposure to cadmium in ,he urban population. Bull. Environ. Co,tam. Toxicol., 36:491--495. Vahter, M. and L. Friberg, 1988. Quality control in integrated human expor,ure monitoring of lead and cadmium. Fresenius Z. Anal. Chem., 332: 726-731. Watanabe, T., H. Fujita, A. Koizumi, K. Chiba, M. Miyasaka and M. Ikeda, 1985. Baseline level of blood lead concentrations among Japanese farmers. Arch. Environ. Health. 40:170176. Weigert, P., J. Muller, H. Klein, K. Zufelde and J. Hillebrandt, 1984. Arsen, Blei, Cadmium and Quecksilber in und auf Lebensmitteln. Zentrale Erfassungs- und Bewertungsstelle ftir Umwelt-Chemicalien des Bundesgesund-Keitsamtes, ZEBS Hal16 !/1984.
87
Estimated dietary intake of lead and cadmium and their concentration in blood K. Louekari a'*, S. Valkonen h, S.
P o u s i c a n d L. V i r t a n e n c
a National Finnish Board of Waters and Environment, P.O. Box 250. SF-O0101 Helsinki, Finland b Institute of Occupational Health, Laboratory of Biochemists),, Arinatie 1, SF-00370 Helsinki 37, bYnland University of Helsinki, Department of Nutrition, SF-O0710 Helsinki 71, Finland (Received March 20th, 1990; accepted July 8th, 1990)
ABSTRACT
Dietary intake of lead and cadmium and the concentration of Pb and Cd in blood were determined for 42 non-smoking subjects not occupationally exposed to Pb or Cd. The aim of the study was to analyze: (i) the relation between calculated dietary intake of Pb and Cd and the concentra:ion of these metals in blood; and (ii) the methodological problems associated with these two measurements of exposure. The mean dietary intakes of Cd and Pb were 14.5 (SD, 3.1) and 5?.9 (SD, 17.9) Fg day- ~, respectively. The concentrations of Pb and Cd in blood were 0.28 Fmol 1- ~(SD, 0.12) and < 0. I Fg I-J, respectively. The relation between dietary intake and concentration in blood was similar to that found in other countries. However, the distributions of these two variables were quite different. Thi~ suggests that dietary intake does not accurately reflect the concentration of lead in blood. The methodological problems associated with estimating the dietary intake of toxic metals were: mistakes in keeping food diaries: errors in transferring data from diaries to the computer; invalid food composition or recipe data in the data base used in the calculations. The concentration of Pb and Cd in blood is not necessarily a good indicator of exposure, since only a small proportion of the total body burden is in the blood, and interactions of Pb and Cd with other food con,~tituents during absorption are possible. INTRODUCTION
Several methods are available to estimate the intake ot food contaminants. They are based on food consumption data and analysis of contaminants in food items. The methods can be inaccurate for several reasons: (a) reliable food consumption data is difficult to obtain; (b) the analysis of heavy metals at trace levels is: characterized by sensitivity and contamination problems; (c) * Author to whom correspondence and reprint requests should be addressed.
0048-9697/91/$03.50
© 1991 - - Elsevier Science Publishers B.V.
88
K. LOUEKARI ET AL.
representative sampling and coverage of all relevant food items is usually not possible (Louekari and Salminen, 1986; Louekari et al., 1988). Therefore, the estimated intakes do not necessarily reflect the actual exposure or the internal dose of the contaminant. Biological monitoring of exposure to heavy metals can be undertaken by measuring the concentration of the metals in blood or urine. Samples from tissues such as kidney and liver are normally not available. However, the concentration of lead and cadmium in blood of non-occupationally exposed people kas not been correlated with recent or chronic exposure. Therefore, information concerning the relation between dietary intake of Pb and Cd and their concentrations in blood is scarce. In some studies, smoking data and age of the cohort has been presented, but not the dietary intake (Brockhaus et al., 1983; Telisman et al., 1986). Populations living near polluting smelters have also been studied (Carvalho et al., 1986). Children were exposed to approximately 10-50 times higher concentrations of cadmium in food as compared, for example, with those in Scandinavian countries, and an alarmingly high concentration of cadmium was found in their blood (mean, l0/~g 1-1; maximum, 55/zg 1-~ ). This r,~flects extreme pollution of food and drinking water. Estimated average intakes have been correlated with average concentrations of cadmium in kidney using valules reported in the literature from different countries; a statistically significant relationship was reported by Morgan and Sherlock (1984). Kowal (1988) reported a positive correlation between urinary cadmium and smoking, and a negative correlation between urinary cadmium and dietary iron and calcium. The dietary intake of cadmium was not estimated in that st~dy. Correlations between dietary selenium and plasma selenium levels were studied by Mutanen et al. (1985). A reasonable correlation (r = 0.67) was found when the 2-week recall method was used, but the 24-h recall method did not show any correlation. For lead and cadmium there are also toxicokinetie factors which potentially impair the correlation between the dietary intake and blood levels of Pb and Cd; for example, Fe, Ca and Zn in the diet may interact with Pb and Cd during absorption (Hathcock, 1976; Mykk~inen and Humaloja, 1984). Urban air and drinking water can significantly affect the exposure to lead and cadmium for those living in contaminated areas. Also, smoking and the habit of pica can significantly increase the intake of toxic metals (Telisman et al., 1986; Morgan et al., 1988; Louekari et al., 1989). However, in the cohort of the present study, the possibility of additional expasures from these sources was very limited. The subjects were non-smokers, respiratory exposure to lead was estimated to be 5/~g day -I and the exposure from drinking water was negligible (Louekari et al., 1989).
DIETARY INTAKE OF LEAD AND CADMIUM
89
The aims of the present study were: (i) to study the relationship between estimated dietary intake and levels of lead and cadmium in the blood of a non-occupationally exposed population (ii) to consider the methodological factors, and (iii) to compare the present results with earlier results on the relationship between dietary intake and concentration of Pb and Cd in blood. MATERIAL AND MI:q HODS
Lead in blood samples of 42 female students was analyzed by graphite furnace atomic absorption spectrophotometvy (AAS). Food diaries of the subjects and food composition tables were used to provide an estimate of lead and cadmium intake (Koivistoinen, 1980). Material was collected from subjects at the Department of Nutrition, University of Helsinki, in 1985.
Analysis of lead in blood The analyses were performed with a polarized Zeeman AAS. (Hitachi, Model 7000) equipped with a graphffe furnace, an automatic sampling system, and a data processor. The samples were diluted five-fold with an aqueous solution of diammoniumhydrogen phosphate and Triton-X-100. A 20-pl aliquot was injected into a graphite furnace cup cuve~te. Lead con-. centrations were obtained by direct comparison with matrix-matched working curves from a data processor. The analytical method, including instrumental parameters and temperature programme, was modified from the method described by Subramanian and Meranger (198 l). The reliability of the method was monitored by the use of internal quality control procedures in addition to participating in external quality assurance schemes. Our laboratory has participated regularly, with good res~Jlts, in a UK External Quality Assurance Scheme (UKEQAS) for Pb in blood (Bullock et al., 1986). The detection limit of the method is 20 pg Pb l -~ . The within-run coefficient of variation (calculated from l0 consecutive measurements) was 0.7 and 1.5% at 100 and 700pgl -~, respectively. The day-to-day coefficient of variation calculated on the basis of l0 determinations over 2 weeks was 2.8% at a concentration of 400 #g l-~. Determinations were made on haemolyzed blood and the result calculated for whole blood by taking the dilution into account, assuming that 99% of the blood lead is in the erythrocytes (Manton and Cook, 1984) and using the mean haematocrit value of the subjects (40%). The cadmium concentration of blood samples was determined using AAS and mild ashing techniques (Kiilunen and Aitio, 1990).
9O
K. LOUEKAR! ET AL.
Estimation of intakes The dietary intake of Pd and Cd was estimated by using two sets of data: the amounts of food recorded in food diaries were multiplied by the respective concentration of heavy metals in that food, giving the dietary intake. It was not possible to corfsider inter-individual variation in absorption. The subjects, 42 volunteer, healthy female students, of average age 25 years, kept food diaries for 14 days after the donation of blood samples. Written instructions for recording food consumption, including also guidance for converting household measures to grams, were given to the subjects. Seven days of those 2 weeks were considered to represent the habitual food consumption of each individual and, consequently, also the dietary intake of lead and cadmium. Between the entry of data by the subjects into their dairies and calculation of intakes by the computer, there were the following phases which are sources of possible errors; keeping of the food diaries; coding of the food items, including division of the meals into particular food items; converting household measures to grams; conversion of the codes and amounts of foods to machine-readable form; program-driven coding check; manual check of stored data; correction of coding errors; and calculation of intakes. In a review of the possible errors associated with diary records, the following estimates are given: coding errors of the investigator, 3-17%; and estimation of food weights, 20-50% (Bingham, 1985). The contribution of other phases to the total error is not known. Because the subjects were students of nutrition and consequently, rather conscious of their food habits, it is considered likely that recording of food consumption was reliat)le. The coding scheme was as follows. In most cases, there was a code for all food items recorded in the diaries. If there was no adequate code, the code of the most similar food item was used (23 cases). A general code was used for some food items, for example average mushroom instead of specific mushrooms and average juice instead of apple juice (27 cases). Some foods were divided into ingredients, for example instant cocoa drink was divided into cocoa, sugar and milk powder (15 cases). New food items were also added to the data base, for example mango and coconut (five cases). Some food items were not coded, since it was assessed that their effect on the intake of toxic metals was minimal, for example herbal tea and some spices (seven cases). Some new recipes and food items were added to the respective files in case they contributed significantly to the food consumption of a subject. The codes for foods and meals and the respective amounts in grams were stored in the system for calculation.
91
DIETARY INTAKE OF LEAD AND C A D M I U M
There is a difference between the present mainframe computer system (VAX/VMS) and microcomputers or mainframe systems with a different use~ interface. When a ~-aic~ocomputer or a direct access system is used, the user selects the appropriate food from the list displayed, and thus coding and typing errors do not occur. The coded food consumption data were used as input to the food composition system maintained at the Department of Nutrition of the University of Helsinki. The average intake of Pb and Cd in seven of the 14 days, covering all weekdays, was calculated. .m-
RESULTS AND DISCUSSION
In the present study, techniques were found to solve the problem of incompatibility between data in the food diaries and that in the data base. If the data base did not contain the food or the meal that was recorded in the diary, the coding scheme presented above was applied. Also, some new food codes and recipes were stored in the data base. A person who formulates new recipes should have an appropriate education, preferably in nutrition, and use up-todate reference material on the composition of meals and dishes. If new analytical data became available, the composition data base was updated accordingly. The mean dietary intake of Pb and Cd in the study group was 52.9 and 14.5/tg d a y - ' , respectively, values fairly similar to recent estimates for nonoccupationally exposed non-smoking subjects (Table 1). The correlation coefficient between intake of energy (kJ d a y - ' ) and intake of lead (pg day -~) was 0.61 and that between intake of energy and intake of cadmium was 0.65. Although the foods contributing most to the intake of lead and cadmium are different, there was also a positive correlation between the intakes of Pb and Cd (0.52). Thus, energy intake appears to be one factor affecting the intake of Pb and Cd. This has also been suggested in previous studies (Louekari et al., 1989). "[ABLE I Intake of energy, iron. calcium, lead and cadmium according to food diaries Component
Unit
Mean intake ( +_SD)
Energy Iron Calcium Lead Cadmium
kJ day ' mg day-' mg day-i l~g day t /,g d a y '
7665 ( + 1381 ) 13.5 (+2.7) 1138 ( + 358) 52.9 (+ 17.0) 14.5 (+ 3.1)
Range
4358-10554 7.7-21.4 498-1937 25.7-105.3 7.2-23.8
Mean intake per 5 MJ
34.4 9.5
92
K. L O U E K A R I E T A L
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0 10
20
30
4.0
50 Intake
60
70
80
90
100
110
of lead (?,g/Coy)
Fig. !. Distribution of calculated lead intake (.ug d a y - I ) .
13 1211 1098>., U ;: u
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25
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40 lead
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Fig, 2, Distribution or energy-related lead intake (14g/day/5 M J).
55
60
65
70
93
DIETARY INTAKE OF LEAD AND CADMIUM
If energy intake is the major factor explaining the distribution of the intake of these two elements, one would assume that when intake is calculated per energy unit the range covered by the distribution would be smaller. When the distribution of energy-related intake of the metals (/~g/day/5 MJ) and the skewness were compared, there was no remarkable difference between uncorrected and energy-related intake (Figs 1 and 2). Skewness factors for the distribution of Pb and Cd intake were 1.58 and 0.44, respectively, and the skewness factors for energy-related intake were 1.70 and 0.69, respectively. For comparison, the skewness factor of energy intake was - 0.16. Consumption of food items which have high concentrations of cadmium or lead, but do not contribute significantly to energy intake, has a remarkable effect on the energy-related intak~ (/tg/day/5 M J). The mean concentration of Pb in blood was 61/~g l ~ or 0.28 :,tool l- ~(SD, 0.12). The range of concentrations (0.08-0.531~moll -~) is wide when compared with the estimated intakes. The mean concentration of Cd in blood was below the limit of detection, l nmol l -~. The form of the distribution curve for blood lead (Fig. 3) differs from that for estimated lead intake. Comparison of the distribution curves (Figs l and 3) suggests that the two methods do not result in consistent estimates of exposure. Therefore, estimation of Pb intake via food by the calculation method (even when there is no other significant sources of exposure) does not reliably predict con"/'# J
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94
K. LOUEKAR| ET AL.
centration of Pb in blood. The form of the distribution of dietary lead intake was in agreement with two recent studies (Morgan et al., 1988; Louekari et al., 1989). The sources of error in the calculation of dietary intakes (based on food diaries) are considered to be: (i) errors in some phase of data entry, including wrong generalizations in some phase of the coding scheme; (ii) out-of-date data in the food composition or recipe data bases used in the calculations. Al~o, the effect of fond preparation is not usually taken into account; (iii) memory lapse while participants are keeping the food diary. In addition, the two methods can result in different estimates of exposure, because the concentration ot' Pb in blood does not faithfully reflect the estimated intake of Pb, since absorption and distribution of Pb are affected by other dietary factors. A crucial factor is also the duration of recording required to estimate the long-term dietary intake of Pb and Cd reliably. For selenium, a 7-day record gave an estimate which varied within 35% of that obtained for long-term selenium intake (Mutanen, 1984). Selenium and heavy metals are similar in that trace amounts are found in every food item, and their concentration in foods does not affect the consmaers' choice. Consequently, some of the inter-individual variation in the dietary intake of Pb and Cd observed in the present study seems to be caused by inaccuracy in the method of the food consumption study. However, inter-individual variation (26-105 #g day -m for lead) is about four-fold the uncontrolled intra-individual variation (18 l~g day -~ for lead) (Table 1). The reliability of the calculation method can also be improved by maintaining an adequate food composition data base. National data bases should be coordinated and regularly updated. Changes in Pb concentrations of blood samples may take place during storage due to adsorption onto walls of cuvettes. The effects of storage time and temperature have been studied, but the results are contradictory: M6ranger et al. (1981) found a significant decrease in the Pb concentration after only 1 week when stored at - 10°C, while Subramanian et al. (1983) found no significant changes after 60 days at the same temperature. Lind et al. (1987) found that the decrease in Pb concentration was 7-15% after 5-6 years of storage at -20°C. Consequently, concentration changes during storage could affect the reliability of biological monitoring based on blood analysis, although the significance of this effect remains unclear. In studies where the concentrations of Pb and Cd in the blood of nonoccupationally exposed people have been analysed, the dietary intake of these metals has not been estimated. In Tables 2 and 3, recorded dietary intake data for various countries are compared with reported concentrations of Pb and Cd in blood for the same countries. Lead and Cd concentrations in blood of
60 218 27 179 82 82 52
UK FRG Sweden Belgium Japan USA Finland
Morgan et al., 1988 Weigert et al., 1984 Slorach et al., 1983 Buchet and Lauwerys, 1983 GEMS, 1982 GEMS, 1982 Present study
Reference
122 82 67 140 49" 92 61
(ttg !- I )
Concentration in blood
Elwood, 1983 Brockhaus et al., 1983 Friberg and Vahter, 1983 Friberg and Vahter, 1983 Watanabe et al., 1985 Annest et ai., 1983 Present study
Reference
The estimates for the USA and Japan are from market basket studies, including 117 and 90 food items, respectively; for the Swedish and Belgian studies, duplicate portions were analysed; the-estimate for the FRG is based on a calculation method. Subjects of this study were farmers and the aim was to establish the baseline level and not a representative mean level.
Dietary intake of Pb (/~g day- i )
Country
Relation between the dietary intake of Pb and the concentration of Pb in blood among non-smoking, non-occupationally exposed subjects
TABLE 2
Dietary intake of Cd (pg day-~ )
53 10 42 33 15 !5
Country
FRG Sweden Japan USA USA Finland
Weigert et al., 1984 Slorach et ai., 1983 GEMS, 1982 GEMS, 1982 Kowal et al., 1979 Present study
Reference
1.6 0.2 1.0 0.55 1.0 < 0. !
Concentrat irm in whole blood (#g ! -~)
Kraus et al., 1988 Friberg end Vahter. 1983 Friberg and Vahter, 1983 Friberg and Vahter, 1983 Kowal et al., 1979 Present study
Reference
Relation between the dietary intake of Cd and the concentration of cadmium in blood among non-smoking, non-occupationally exposed subjects
TABLE 3
DIETARY INTAKE OF LEAD AND CADMIUM
97
non-occupgfionally exposed individuals are reported to be 49-140 and < 0.11.6#gl -I, respectively. Occupational exposure can increase the level of cadmium in blood, for example to 7.2/~gl -~ in phosphate workers and to 14.1 #gl -I in workers in an alkaline battery factory (Sharma, 1981; Hassler et al., 1983). From Tables 2 and 3 it is evident that correlations between estimated dietary intakes and concentrations of heavy metals in blood are not as good as the correlation between dietary cadmium intake and concentration of Jv"r]. cadmium in kidney found by Morgan and Sherlock (1 aQA~ CONCLUSIONS
The analytical difficulties and the need for quality control in the analysis of blood Pb and Cd have recently been demonstrated by Vahter and Friberg (1988)~ When analytical quality control is applied, blood analysis can be reliable. However, it is not clear whether the concentrations of Pb and Cd in blood reliably reflect the total body burden of these metals or the dietary intake. It seems that dietary intake of Pb and Cd is an indicator of body burden rather than an indicator of concentrations in blood. However, the concentration of Cd in urine Js positively correlated with both total body burden and also with exposure from cigarette smoke (Elinder et al., 1976; Kowal, 1988). This present study suggests that blood Pb analysis should not be used as a substitute for reliable estimates of Pb intake. The reliability of the calculation method can be improved by eliminating unnecessary phases in data entry and using updated files of heavy metal concentrations in food items. The duplicate portion method for intake estimation may be more reliable than calculated estimates (Louekari et al., 1988). Therefore, the correlation between this latter type of estimate and concentrations of heavy metals in blood could also be studied. ACKNOWLEDGEMENTS
We are grateful to Dr Marj~ Mutanen for her assistance during the design of the study, and to Dr Kai Savolainen, National Public Health Institute, and Dr Antero Aitio, Occupational Health Institute, for constructive comments on the manuscript. This study was supported by a grant from the Finnish Culture Fund. REFERENCES Annest, J.L., J.L. Pirkle, D. Makuc, J.W. Neese, D.D. Bayse and M.G. Kovar, 1983. Chronological trend in blood lead levels between 1976 and 1980. N. Engi. J. Med., 308: 1373-1377.
98
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Bingham, S., 1985. Aspects of dietary survey methodology. Br. Nutr. Found. Bull., 10(2): 90-103. Brockhaus, A., I. FreJer, U. Ewers, E. Jerman and R. Dolgner, 1983. Levels of cadmium and lead in blood in relation to smoking, sex, occupation, and other factors in an adult population of the FRG. Int. Arch. Occup. Health, 52: 167-175. Buchet, J.P. and R. Lauwerys, 1983. Oral daily intake of cadmium, lead, manganese, copper, chromium, mercury, calcium, zinc and arsenic in Belgium: a duplicate meal study. Food Chem. Toxicol., 2 i: 19-24. Bullock, D.G., N.J. Smith and T.P. Whitehead, 1986. External quality assessment of assays of lead in blood. Clin. Chem., 32: 1884-1889. Carvalho, F.M., T.M. Tavares, A.M. Siivany .Netc, M.E.C. Lima and F. Alt, 1986. Cadmium concentrations in blood ofchildren living near a lead smelter in Bahia, Brazil. Environ. Res., 40; 437-449. Elinder, C-G., T. KjellstrSn, L. Linnman and G. Pershagen, 1976. Urinary excretion of cadmium and zinc among persons from Sweden. Environ. Res~, 15: 473-484. Elwood, P.C., 1983. Changes in blood lead concentrations in women in Walcs 1972-1982. Med. Pract. 286:1553-1555. Friberg, L. and M. Vahter, 1983. Assessment of exposure to lead and cadmium through biological monitoring: results of a UNEP/WHO Global Study. Environ. Res. 30: 95-128. GEMS, 1982. Joint FAO/WHO Food and Animal Feed Monitoring Programme. Summary and assessment of data received form the FAO/WHO collaborating centres for food contamination monitoring. National Food Administration, Uppsala. Hassler, E., B. Lind and M. Piscator, 1983. Cadmium in blood and urine related to present and past exposure. A study of workers in an alkaline battery factory. Br. J. Ind. Med., 40: 420425. Hathcock, J.N., 1976. Nutrition: toxicology and pharmacology. Nutr. Rev., 34: 65-70. Kiilunen, M. and A. Aitio, 1990. Dilution and mild ashing technique for the routine determination of cadmium in blood and urine. In: int. Symp. Trace Elements in Health and Disease, Espoo, Finland, 5-8 June 1990 (Abstr.). Koivistoinen, P. (Ed.), 1980. Mineral element composition of Finnish foods. Acta Agric. Stand. Suppl., 22: i- 17 i. Kowai, N.E., 1988. Urinary cadmium and beta-microglobulin: correlation with nutrition and smoking history. J. Toxicol. Environ. Health, 2b: 179-183. Kowal, N.E., D.E. Johnson, D.F. Kraemer and H.R. Pahren, 1979. Normal levels ofcadmium in diet, urine, blood, and tissues of inhabitants of United States. J. Toxicol, Environ. Health, 5:995-1014. Kraus, G., K.H, Schaller and L. Winter, 1988. The influence of occupational cadmiumexposure on various element levels in human blood. Zentralbl. Bakteriol. Hyg. B, 186: 95-107. Lind, B., C.G. Elinder, L. Friberg, B. Nilsson, M. Svartengren and M. Vahter, 1987. Quality control in the analysis for lead and cadmium in blood. Fresenius Z. Anal. Chem., 326: 647655. Louekari, K. and S. Salminen, 1986. Intake of heavy metals in Finland, West Germany and Japan. Food Addit. Contain., 3: 355-362. Louekari, K., L. Joikkonen and P. Varo, 1988. Exposure to cadmium from foods, estimated by analysis and calculation - - comparison of methods. Food Addit. Contam., 5: ! ! !-I 17. Louekari, K., U. Uusitalo and P. Pietinen, 1989. Variation and modifying factors of the exposure to lead and cad~llium based on an epidemiologicai study. Sci. Total Environ., 84: i-12.
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Manton, W.I. and J.D. Cook, 1984. High accuracy (stable isotope dilution) measurements of lead in serum and cerebrospinal fluid. Br. J. Ind. Med. 41: 313-319. M6ranger, J.C., B.R. Hollebone and G.A. Blanchetta, 1981. The effects of storage times, temperatuies and container types on the accuracy of atomic absorption determinations of Cd, Cu, Hg, Pb, and Zn in whole heparinized blood. J. Anal. Toxicoi., 5: 33-41. Morgan, H. and J.C. Sherlock, 1984. Cadmium intake and cadmium in the human kidney. Food Addit. Contam., !: 45-5 I. Morgan, H., G.A. Smart and J.C. Sherlock, 1988. Intakes of metal. Sci. Total Environ., 75: 71-100. Mutanen, M., 1984. Dietary intake and sources of selenium in young Finnish women. Hum. Nutr. Appl. Nutr., 38A: 265-269. Mutanen, M., G. Alfihan, H. Arvilommi, P. Koivistoinen and P. Varo, 1985. Correlation between dietary selenium, platelet, GSH-Px and plasma seleniam level. N/iringsforskning, 29: 135-138. Mykk~nen, H.M. and T. Humaloja, 1984. Effect of lead on the intestinal absorption of sodium selenite and selenomethionine (7"~Se)in chicks. Biol. Trace Elem. Res., 6:11-17. Sharma, R.P., 1981. High blood and urine levels of cadmium in phosphate workers' a preliminary investigation. Bull. Environ. Contam. Toxicol., 27: 806-809. Slorach, S., I-B. Gustafsson, L. Jorhem and P. Mattson, 1983. Intake of lead, cadmium and certain other metals via a typical Swedish weekly diet. Vfir Foeda, Suppl. I, 35: 3-16. Subramanian, K.S. and J.C. Meranger, 1981. A rapid electrothermal atomic absorption spectrophotometric method for cadmium and lead in human whole blood. Clin. Chem., 27/i1: 1866-1871. Subramanian, K.S., J.C. Meranger and J. Connor, 1983. The effect of container material, storage time and temperature on cadmium and lead levels in heparinized human whole blood. J. Anal. Toxl~:ol., 7: 15-19. Telisman, S., J. Azaric and D. Prpic-Majic 1986. Cadmium in blood as an indicator of integrated exposure to cadmium in ,he urban population. Bull. Environ. Co,tam. Toxicol., 36:491--495. Vahter, M. and L. Friberg, 1988. Quality control in integrated human expor,ure monitoring of lead and cadmium. Fresenius Z. Anal. Chem., 332: 726-731. Watanabe, T., H. Fujita, A. Koizumi, K. Chiba, M. Miyasaka and M. Ikeda, 1985. Baseline level of blood lead concentrations among Japanese farmers. Arch. Environ. Health. 40:170176. Weigert, P., J. Muller, H. Klein, K. Zufelde and J. Hillebrandt, 1984. Arsen, Blei, Cadmium and Quecksilber in und auf Lebensmitteln. Zentrale Erfassungs- und Bewertungsstelle ftir Umwelt-Chemicalien des Bundesgesund-Keitsamtes, ZEBS Hal16 !/1984.
