Opinion on Cadmium - The Final Report by WS Atkins International Ltd based on : The Final Report (September 1998) and Additional Assessment (September 1998): "Assessment of the risks to health and to the environment of Cadmium contained in certain products and of the effects of further restrictions on their marketing and use". Expressed at the 7th CSTEE plenary meeting, Brussels, 18 January 1999.
Title of Opinion:
On the WS Atkins "Assessment of the risks to health and to the environment of Cadmium contained in certain products and of the effects of further restrictions on their marketing and use", Report September 1998 and Additional Assessment of the risks to health and to the environment of Cadmium contained in certain products and of the effects of further restrictions on their marketing and use, Report September 1998.
- The CSTEE has been asked to express its opinion on the adequacy of the above named reports:
(1) Whether the degree of risk to the environment and man, as assessed by the WS Atkins Reports, is sufficiently justified?
(2) To comment on the general quality of the Reports.
Executive Summary
Question: Whether the assessment of the degree of risk to the environment and man, as assessed by the WS Atkins Report "Assessment of the risks to health and to the environment of Cadmium contained in certain products and of the effects of further restrictions on their marketing and use" and the Report "Additional Assessment of the risks to health and to the environment of Cadmium contained in certain products and of the effects of further restrictions on their marketing and use" are sufficiently justified and to provide a comment on the general quality of the Reports.
- Answer: The reports are not of an acceptable quality.
The present reports have inadequacies in that there are some major areas in need of further clarification or amendment. These inadequacies render parts of the reports unacceptable. In particular, some of the methodologies used in the reports have been incorrectly used and others present difficulties for interpretation. The opinion of the CSTEE given below presents the main criticisms of the report.
- The main basis of the scientific justification of the Report's conclusions has been the use of a wide range of information from published literature, industry and trade associations, regulatory authorities and member states of the EU and on the application of the principles laid down in the Technical Guidance Document (TGD) in support of Directive 96/67/EEC and Commission Regulation (EC) No 1488/94. However, it is not always clear which particular source of information has been used to provide specific data.
Conclusions of the WS Atkins Reports, September 1998
1. Report Part 1, P6-1, 6.1 & 6.3
The report found that the regional risks for man and the environment arising from all three products involving cadmium as pigment in polymers, as stabilisers in PVC and for metal plating for the acidic environment were acceptable.
2. Additional Assessment P6-1, 6.3
The report found that the regional risks to man and the environment arising from all three products for both the generalised EU region and acidic regions were acceptable.
3. Report Part 1, P6-1, 6.3
The report found that it was not possible to provide the risk characterisation for the local risks from pigment production because regional PECs for the generalised EU environment have not been derived.
4. Additional Assessment P6-1, 6.4
The risks to man and the environment arising from one of the three pigment production facilities through the atmosphere were considered unacceptable.
5. Additional Assessment P6-1, 6.4
The local risks to man and the environment arising through the environment in the vicinity of facilities mixing and using pigments were considered to be acceptable.
6. Report Part 1, P6-1, 6.3
It was not possible to provide the risk characterisation for the local risks from stabiliser production because regional PECs for the generalised EU environment have not been derived.
7. Additional Assessment P6-1, 6.4
The local risks to man and the environment arising through the atmosphere in the vicinity of two of the six stabiliser production facilities were considered to be unacceptable.
8. Report Part 1, P6-2, 6.5 & Additional Assessment P6-2, 6.6
Health risks in the workplace associated with pigment production, plating, stabiliser mixing and use were considered acceptable.
9. Report Part 1, P6-2, 6.5 & Additional Assessment P6-2, 6.6
Stabiliser preparation may present unacceptable health risks in the workplace.
10. Report Part 1, P6-1, 6.3
For plating facilities it was only possible to provide risk characterisation for local risks to the environment for the acidic environment again because regional PECs for the generalised EU environment have not been derived. These local risks for the acidic regions were considered acceptable.
11. Additional Assessment P6-1, 6.4
The local risks to man and the environment arising from plating facilities for both the generalised EU environment and the acidic environment were considered to be acceptable.
12. Report Part 1, P6-2, 6.4
For incinerators it was only possible to comment on the local risks to man and the environment for the acidic environment again because regional PECs for the generalised EU environment have not been derived. These local risks for the acidic environment were found to be acceptable.
13. Additional Assessment P6-2, 6.5
The local risks to man and the environment arising from incineration were considered to be acceptable.
14. Report Part 1, P6-2, 6.4 & Additional Assessment P6-2, 6.5
The risks from municipal landfill sites were considered to be potentially unacceptable. It was not possible to apportion the cadmium present in a landfill or leachate from such a site between cadmium arising from components associated with the products and cadmium arising from other sources.
15. Report Part 1, P6-2, 6.4 & Additional Assessment P6-2, 6.5
The risks from hazardous waste landfill sites in the long term, assuming good practice, were considered to be small.
16. Report Part 1, P6-2, 6.4 & Additional Assessment P6-2, 6.5
The risks and long term risks from monofill landfill sites, construction and demolition waste landfill sites were considered to be broadly acceptable.
Opinion of the Scientific Committee for Toxicity, Ecotoxicity and the Environment
The opinion of the CSTEE is that the conclusions of the Reports were not substantiated and are doubtful.
(I) The derivation of PEC values for the regional environment is most likely incorrect in terms of the methodology used and probably in terms of the data used in the input.
Examples of this are:
a. The release estimation of cadmium from plastics and PVC does not properly take account of release during the entire period in which the material is used.
b. The emissions from cadmium plated material are averaged out over the environment, both aquatic and terrestrial. They do not take account of the specific uses of the plated materials and emissions arising from these uses.
c. PEC values are not calculated for the steady-state situation but for a specific residence time in a compartment, thereby ignoring the potential long-term accumulation of cadmium in soil and sediment.
No clear distinction is made in the report between the concentrations arising from anthropogenic sources and natural sources, nor is it always clear whether the values used for the natural background are in fact not also influenced by anthropogenic emissions.
PEC values associated with the three specific uses, were derived by a fundamentally incorrect procedure in that the regional, continental and background concentrations were simply added together.
(II) The calculated daily intakes of Cadmium, 110 µg d-1 for the acidic environment and 114 µg d-1 for the generalised environment, are substituted by "measured values", 15 µg d-1 for the acidic and 45 µg d-1 for the generalised environments, since it was considered impossible that the calculated intake values could be higher than the measured values. What the measured values represent or what they are based on, is not clear. It seems likely that they are population average values.
The reported estimated average dietary intake of cadmium in European countries varies between 8 and about 50 µg d-1 (European Commission 1996; IPCS, 1992; Cuardo et al., 1995; Louekari et al., 1991; Buchet et al., 1983; Vahter et al., 1996; Berglund et al., 1994; Muller et al., 1993). Although it is known that there are great individual variations due to differences in dietary habits and energy intake, there is a lack of information on the distribution of the daily dietary intake of cadmium in the various European populations. Still it is obvious that the distribution often is very skewed and that a part of the population has an intake far exceeding the average. Thus even in a population having a fairly low average daily intake of cadmium, a fraction of the population is likely to exceed even the present PTWI of about 70 µg d-1. For example in Swedish studies of cadmium in collected duplicate diets, the individual daily intake of cadmium among 74 women varied from 5 to 70 µg d-1, Berglund et al. 1994; Vahter et al. 1996). In a Belgian duplicate diet study (21 hospital diets and three meals a day from 30 individuals from three areas) the total range of cadmium in the duplicate diets was 2 - 88 µg d-1, median 15 µg d-1 (Buchet et al, 1983).
In conclusion, the values of daily intakes employed in the risk calculations are lower that those found in the general population. Thus, the PEC/TDI ratios are in fact much higher.
(III) The TDI (PTWI in the WHO document), like the WHO water and air quality guidelines, or the blood cadmium concentration limit for occupational exposed people, represents the maximum (tolerable) intake. Thus, the dietary intake of all individuals should be below this value.
At the time when the present PTWI (WHO 1989) was evaluated, most dose- response relationships for cadmium were based on relatively crude methods to detect the renal damage or on studies of occupationally exposed male workers. During the last ten years much more sensitive methods, to detect renal damage, have become available. A number of recent studies of population groups, including elderly and individuals who are particularly susceptible to cadmium, exposed to relatively low levels of cadmium indicate that kidney tubular damage may develop at much lower levels than previously believed. Thus, most likely the true daily intake/TDI ratio is lower than that calculated based on a PTWI of 70 µg/d (Elinder et al 1985; Buchet et al, 1990; Bernard et al 1992; Chia et al 1992; Roels et al 1993; Fels et al 1994; Jarup et al 1995; Berglund et al, 1997; Jarup et al, 1998). In the risk assessment, it is also crucial to consider the individual variation in toxicokinetics and sensitivity.
(IV) The estimation of the PNEC values is incorrect.
The use of probabilistic approaches, although not yet included in the TGD, is considered valid and scientifically sound. However, there are some basic requirements for probabilistic methods that have not been fulfilled in the report calculations. Therefore the values presented in the report cannot be accepted.
Some major problems observed in the PNEC estimations are:
a. The toxicity data set must be large enough (use of probabilistic approach for n=5 is inappropriate).
b. Several NOEC and LOEC values obtained for different endpoints in a single study on the same species have been considered as individual data.
c. The probabilistic curves and the statistical values have not been included.
d. The taxonomic distribution and representativity of the data set have not been presented.
e. The uncertainty of the results and the need of additional safety factors have not been discussed.
(V) The effects of environmental characteristics on cadmium toxicity are not addressed. This is a major weakness, particularly for local risk characterisation which can be markedly over-estimated if toxicity data are not corrected for the real bioavailability of cadmium in the receiving environment.
In addition, regional and continental risk characterisations should be improved by the inclusion of PNEC values adapted to the water/soil conditions using probabilistic approaches for European water/soil characteristics.
(VI) The present report does make the comparison between exposure and effects for individual uses but the total picture of the risks of cadmium is not given. Although the summation of the risks from the three uses is now given in this report the implications of the other sources of cadmium are not addressed. For a substance with a diffuse emission pattern like cadmium, this may lead to the conclusion that the emissions from the three use-types investigated may not lead to unacceptable levels but, if these are added to the emissions from other sources, the acceptable levels may well be exceeded. This remains a serious omission in the report and is not in line with common practice in performing risk assessments for substances. The present report does not provide the means to assess the relative risks from these uses compared with the other uses of cadmium.
References:
Bernard A, Roels H, Thielemans N, Van Lierde M, Lauwerys R:
Assessment of the causality of the cadmium--protein relationships in the urine of the general population with reference to the Cadmibel study. IARC Scientific Publications 1992; 118, 341-6
Berglund M, Åkesson A, Nermell B, and Vahter M:
Intestinal absorption of dietary cadmium in women is dependent on body iron stores and fibre intake. Environ. Health Perspect. 1994; 102 (12), 1058-1067.
Buchet JP, Lauwerys R, Roels H, Bernard A, Bruaux P, Claeys F, Ducoffre G, De Plaen P, Staessen J, Amery A, Lijnen P, Thijs L, Rondia D, Sartor F, Saint Remy A, Nick L:
Renal effects of cadmium body burden of the general population. Lancet 1990; 336, 699-702.
Buchet JP., Lauwerys R, Vandevoorde A, Pycke J M:
Oral daily intake of cadmium, lead, manganese, copper, chromium, mercury, calcium, zinc and arsenic in Belgium: a duplicate meal study. Food Chem. Toxicol 1983; 21, 19-24.
Chia KS, Tan AL, Chia SE, Ong CN, Jeyaratnam J:
Renal tubular function of cadmium exposed workers. Annals of the Academy of Medicine, Singapore 1992; 21, 756-9.
Cuadrado C, Kumpalainen J, Moreiras O: Contaminants and nutrients in total diets in Spain. Eur. J. Clin. Nutr. 1995; 49, 767-778.
Elinder, C-G, Edling, C, Lindberg, E, Kågedal B, Vesterberg, O: Assessment of renal function among workers previously exposed to cadmium. Brit J Ind Med. 1985; 42,754-60.
Fels LM, Bundschuh I, Gwinner W, Jung K, Pergande M, Graubaum HJ, Price RG, Taylor SA, De Broe ME, Nuyts GD:
Early urinary markers of target nephron segments as studied in cadmium toxicity. Kidney International. 1994; 46 (Suppl. 47), 81-8.
Jarup L, Carlsson MD, Elinder CG, Hellstrom L, Persson B, Schutz A:
Enzymuria in a population living near a cadmium battery plant. Occupational & Environmental Medicine 1995; 52, 770-2.
Louekari, K., Valkonen S, Pousi S, Virtanen L:
Estimated dietary intake of lead and cadmium and their concentrations in blood. Science Total. Environ. 1991; 105, 87-99.
Muller M, Thiel C, Anke M, Harmann E., Arnold, W:
Cadmium intake of adults in Germany. In Trace elements in man and animals - TEMA 8, 1993 (M Anke, D Meissner, and CF Mills, Eds.) pp. 211-215. Verlag Media Touristik, Gersdorf.
Nordberg GF, Jin T, Kong Q, Ye T, Cai S, Wang Z, Zhuang F, Wu X:
Biological monitoring of cadmium exposure and renal effects in a population group residing in a polluted area of China. Sci Total Environment 1997; 19, 111-114.
Roels H, Bernard AM, Cardenas A, Buchet JP, Lauwerys RR, Hotter G, Ramis I, Mutti A, Franchini I, Bundschuh I:
Markers of early renal changes induced by industrial pollutants. III. Application to workers exposed to cadmium. British Journal of Industrial Medicine. 1993; 50, 37-48.
Vahter M, Berglund M, Nermell B, Åkesson A:
Bioavailability of cadmium from shellfish and mixed diet in women. Toxicol. Appl. Pharmacol. 1996; 136, 332-341,.
WHO. 1992:
Cadmium. Environmental Health Criteria. WHO, Geneva. 280 p
Title of Opinion:
On the WS Atkins "Assessment of the risks to health and to the environment of Cadmium contained in certain products and of the effects of further restrictions on their marketing and use", Report September 1998 and Additional Assessment of the risks to health and to the environment of Cadmium contained in certain products and of the effects of further restrictions on their marketing and use, Report September 1998.
- The CSTEE has been asked to express its opinion on the adequacy of the above named reports:
(1) Whether the degree of risk to the environment and man, as assessed by the WS Atkins Reports, is sufficiently justified?
(2) To comment on the general quality of the Reports.
Executive Summary
Question: Whether the assessment of the degree of risk to the environment and man, as assessed by the WS Atkins Report "Assessment of the risks to health and to the environment of Cadmium contained in certain products and of the effects of further restrictions on their marketing and use" and the Report "Additional Assessment of the risks to health and to the environment of Cadmium contained in certain products and of the effects of further restrictions on their marketing and use" are sufficiently justified and to provide a comment on the general quality of the Reports.
- Answer: The reports are not of an acceptable quality.
The present reports have inadequacies in that there are some major areas in need of further clarification or amendment. These inadequacies render parts of the reports unacceptable. In particular, some of the methodologies used in the reports have been incorrectly used and others present difficulties for interpretation. The opinion of the CSTEE given below presents the main criticisms of the report.
- The main basis of the scientific justification of the Report's conclusions has been the use of a wide range of information from published literature, industry and trade associations, regulatory authorities and member states of the EU and on the application of the principles laid down in the Technical Guidance Document (TGD) in support of Directive 96/67/EEC and Commission Regulation (EC) No 1488/94. However, it is not always clear which particular source of information has been used to provide specific data.
Conclusions of the WS Atkins Reports, September 1998
1. Report Part 1, P6-1, 6.1 & 6.3
The report found that the regional risks for man and the environment arising from all three products involving cadmium as pigment in polymers, as stabilisers in PVC and for metal plating for the acidic environment were acceptable.
2. Additional Assessment P6-1, 6.3
The report found that the regional risks to man and the environment arising from all three products for both the generalised EU region and acidic regions were acceptable.
3. Report Part 1, P6-1, 6.3
The report found that it was not possible to provide the risk characterisation for the local risks from pigment production because regional PECs for the generalised EU environment have not been derived.
4. Additional Assessment P6-1, 6.4
The risks to man and the environment arising from one of the three pigment production facilities through the atmosphere were considered unacceptable.
5. Additional Assessment P6-1, 6.4
The local risks to man and the environment arising through the environment in the vicinity of facilities mixing and using pigments were considered to be acceptable.
6. Report Part 1, P6-1, 6.3
It was not possible to provide the risk characterisation for the local risks from stabiliser production because regional PECs for the generalised EU environment have not been derived.
7. Additional Assessment P6-1, 6.4
The local risks to man and the environment arising through the atmosphere in the vicinity of two of the six stabiliser production facilities were considered to be unacceptable.
8. Report Part 1, P6-2, 6.5 & Additional Assessment P6-2, 6.6
Health risks in the workplace associated with pigment production, plating, stabiliser mixing and use were considered acceptable.
9. Report Part 1, P6-2, 6.5 & Additional Assessment P6-2, 6.6
Stabiliser preparation may present unacceptable health risks in the workplace.
10. Report Part 1, P6-1, 6.3
For plating facilities it was only possible to provide risk characterisation for local risks to the environment for the acidic environment again because regional PECs for the generalised EU environment have not been derived. These local risks for the acidic regions were considered acceptable.
11. Additional Assessment P6-1, 6.4
The local risks to man and the environment arising from plating facilities for both the generalised EU environment and the acidic environment were considered to be acceptable.
12. Report Part 1, P6-2, 6.4
For incinerators it was only possible to comment on the local risks to man and the environment for the acidic environment again because regional PECs for the generalised EU environment have not been derived. These local risks for the acidic environment were found to be acceptable.
13. Additional Assessment P6-2, 6.5
The local risks to man and the environment arising from incineration were considered to be acceptable.
14. Report Part 1, P6-2, 6.4 & Additional Assessment P6-2, 6.5
The risks from municipal landfill sites were considered to be potentially unacceptable. It was not possible to apportion the cadmium present in a landfill or leachate from such a site between cadmium arising from components associated with the products and cadmium arising from other sources.
15. Report Part 1, P6-2, 6.4 & Additional Assessment P6-2, 6.5
The risks from hazardous waste landfill sites in the long term, assuming good practice, were considered to be small.
16. Report Part 1, P6-2, 6.4 & Additional Assessment P6-2, 6.5
The risks and long term risks from monofill landfill sites, construction and demolition waste landfill sites were considered to be broadly acceptable.
Opinion of the Scientific Committee for Toxicity, Ecotoxicity and the Environment
The opinion of the CSTEE is that the conclusions of the Reports were not substantiated and are doubtful.
(I) The derivation of PEC values for the regional environment is most likely incorrect in terms of the methodology used and probably in terms of the data used in the input.
Examples of this are:
a. The release estimation of cadmium from plastics and PVC does not properly take account of release during the entire period in which the material is used.
b. The emissions from cadmium plated material are averaged out over the environment, both aquatic and terrestrial. They do not take account of the specific uses of the plated materials and emissions arising from these uses.
c. PEC values are not calculated for the steady-state situation but for a specific residence time in a compartment, thereby ignoring the potential long-term accumulation of cadmium in soil and sediment.
No clear distinction is made in the report between the concentrations arising from anthropogenic sources and natural sources, nor is it always clear whether the values used for the natural background are in fact not also influenced by anthropogenic emissions.
PEC values associated with the three specific uses, were derived by a fundamentally incorrect procedure in that the regional, continental and background concentrations were simply added together.
(II) The calculated daily intakes of Cadmium, 110 µg d-1 for the acidic environment and 114 µg d-1 for the generalised environment, are substituted by "measured values", 15 µg d-1 for the acidic and 45 µg d-1 for the generalised environments, since it was considered impossible that the calculated intake values could be higher than the measured values. What the measured values represent or what they are based on, is not clear. It seems likely that they are population average values.
The reported estimated average dietary intake of cadmium in European countries varies between 8 and about 50 µg d-1 (European Commission 1996; IPCS, 1992; Cuardo et al., 1995; Louekari et al., 1991; Buchet et al., 1983; Vahter et al., 1996; Berglund et al., 1994; Muller et al., 1993). Although it is known that there are great individual variations due to differences in dietary habits and energy intake, there is a lack of information on the distribution of the daily dietary intake of cadmium in the various European populations. Still it is obvious that the distribution often is very skewed and that a part of the population has an intake far exceeding the average. Thus even in a population having a fairly low average daily intake of cadmium, a fraction of the population is likely to exceed even the present PTWI of about 70 µg d-1. For example in Swedish studies of cadmium in collected duplicate diets, the individual daily intake of cadmium among 74 women varied from 5 to 70 µg d-1, Berglund et al. 1994; Vahter et al. 1996). In a Belgian duplicate diet study (21 hospital diets and three meals a day from 30 individuals from three areas) the total range of cadmium in the duplicate diets was 2 - 88 µg d-1, median 15 µg d-1 (Buchet et al, 1983).
In conclusion, the values of daily intakes employed in the risk calculations are lower that those found in the general population. Thus, the PEC/TDI ratios are in fact much higher.
(III) The TDI (PTWI in the WHO document), like the WHO water and air quality guidelines, or the blood cadmium concentration limit for occupational exposed people, represents the maximum (tolerable) intake. Thus, the dietary intake of all individuals should be below this value.
At the time when the present PTWI (WHO 1989) was evaluated, most dose- response relationships for cadmium were based on relatively crude methods to detect the renal damage or on studies of occupationally exposed male workers. During the last ten years much more sensitive methods, to detect renal damage, have become available. A number of recent studies of population groups, including elderly and individuals who are particularly susceptible to cadmium, exposed to relatively low levels of cadmium indicate that kidney tubular damage may develop at much lower levels than previously believed. Thus, most likely the true daily intake/TDI ratio is lower than that calculated based on a PTWI of 70 µg/d (Elinder et al 1985; Buchet et al, 1990; Bernard et al 1992; Chia et al 1992; Roels et al 1993; Fels et al 1994; Jarup et al 1995; Berglund et al, 1997; Jarup et al, 1998). In the risk assessment, it is also crucial to consider the individual variation in toxicokinetics and sensitivity.
(IV) The estimation of the PNEC values is incorrect.
The use of probabilistic approaches, although not yet included in the TGD, is considered valid and scientifically sound. However, there are some basic requirements for probabilistic methods that have not been fulfilled in the report calculations. Therefore the values presented in the report cannot be accepted.
Some major problems observed in the PNEC estimations are:
a. The toxicity data set must be large enough (use of probabilistic approach for n=5 is inappropriate).
b. Several NOEC and LOEC values obtained for different endpoints in a single study on the same species have been considered as individual data.
c. The probabilistic curves and the statistical values have not been included.
d. The taxonomic distribution and representativity of the data set have not been presented.
e. The uncertainty of the results and the need of additional safety factors have not been discussed.
(V) The effects of environmental characteristics on cadmium toxicity are not addressed. This is a major weakness, particularly for local risk characterisation which can be markedly over-estimated if toxicity data are not corrected for the real bioavailability of cadmium in the receiving environment.
In addition, regional and continental risk characterisations should be improved by the inclusion of PNEC values adapted to the water/soil conditions using probabilistic approaches for European water/soil characteristics.
(VI) The present report does make the comparison between exposure and effects for individual uses but the total picture of the risks of cadmium is not given. Although the summation of the risks from the three uses is now given in this report the implications of the other sources of cadmium are not addressed. For a substance with a diffuse emission pattern like cadmium, this may lead to the conclusion that the emissions from the three use-types investigated may not lead to unacceptable levels but, if these are added to the emissions from other sources, the acceptable levels may well be exceeded. This remains a serious omission in the report and is not in line with common practice in performing risk assessments for substances. The present report does not provide the means to assess the relative risks from these uses compared with the other uses of cadmium.
References:
Bernard A, Roels H, Thielemans N, Van Lierde M, Lauwerys R:
Assessment of the causality of the cadmium--protein relationships in the urine of the general population with reference to the Cadmibel study. IARC Scientific Publications 1992; 118, 341-6
Berglund M, Åkesson A, Nermell B, and Vahter M:
Intestinal absorption of dietary cadmium in women is dependent on body iron stores and fibre intake. Environ. Health Perspect. 1994; 102 (12), 1058-1067.
Buchet JP, Lauwerys R, Roels H, Bernard A, Bruaux P, Claeys F, Ducoffre G, De Plaen P, Staessen J, Amery A, Lijnen P, Thijs L, Rondia D, Sartor F, Saint Remy A, Nick L:
Renal effects of cadmium body burden of the general population. Lancet 1990; 336, 699-702.
Buchet JP., Lauwerys R, Vandevoorde A, Pycke J M:
Oral daily intake of cadmium, lead, manganese, copper, chromium, mercury, calcium, zinc and arsenic in Belgium: a duplicate meal study. Food Chem. Toxicol 1983; 21, 19-24.
Chia KS, Tan AL, Chia SE, Ong CN, Jeyaratnam J:
Renal tubular function of cadmium exposed workers. Annals of the Academy of Medicine, Singapore 1992; 21, 756-9.
Cuadrado C, Kumpalainen J, Moreiras O: Contaminants and nutrients in total diets in Spain. Eur. J. Clin. Nutr. 1995; 49, 767-778.
Elinder, C-G, Edling, C, Lindberg, E, Kågedal B, Vesterberg, O: Assessment of renal function among workers previously exposed to cadmium. Brit J Ind Med. 1985; 42,754-60.
Fels LM, Bundschuh I, Gwinner W, Jung K, Pergande M, Graubaum HJ, Price RG, Taylor SA, De Broe ME, Nuyts GD:
Early urinary markers of target nephron segments as studied in cadmium toxicity. Kidney International. 1994; 46 (Suppl. 47), 81-8.
Jarup L, Carlsson MD, Elinder CG, Hellstrom L, Persson B, Schutz A:
Enzymuria in a population living near a cadmium battery plant. Occupational & Environmental Medicine 1995; 52, 770-2.
Louekari, K., Valkonen S, Pousi S, Virtanen L:
Estimated dietary intake of lead and cadmium and their concentrations in blood. Science Total. Environ. 1991; 105, 87-99.
Muller M, Thiel C, Anke M, Harmann E., Arnold, W:
Cadmium intake of adults in Germany. In Trace elements in man and animals - TEMA 8, 1993 (M Anke, D Meissner, and CF Mills, Eds.) pp. 211-215. Verlag Media Touristik, Gersdorf.
Nordberg GF, Jin T, Kong Q, Ye T, Cai S, Wang Z, Zhuang F, Wu X:
Biological monitoring of cadmium exposure and renal effects in a population group residing in a polluted area of China. Sci Total Environment 1997; 19, 111-114.
Roels H, Bernard AM, Cardenas A, Buchet JP, Lauwerys RR, Hotter G, Ramis I, Mutti A, Franchini I, Bundschuh I:
Markers of early renal changes induced by industrial pollutants. III. Application to workers exposed to cadmium. British Journal of Industrial Medicine. 1993; 50, 37-48.
Vahter M, Berglund M, Nermell B, Åkesson A:
Bioavailability of cadmium from shellfish and mixed diet in women. Toxicol. Appl. Pharmacol. 1996; 136, 332-341,.
WHO. 1992:
Cadmium. Environmental Health Criteria. WHO, Geneva. 280 p