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Environmental specimen banking and poisons control — a new challenge
The Science of the Total Environment, 139/140 (1993) 507-514 Elsevier Science Publishers B.V., Amsterdam
507
Environmental specimen banking and poisons c o n t r o l - a new challenge Friedrich W. Jekat, Rolf Eckard and Fritz H. Kemper Institute of Pharmacology and Toxicology, Environmental Specimen Bank for Human Tissue, Poisons Control Centre, University of Miinster, Domagkstrafle 11-12, D-4400 Miinster, Germany ABSTRACT Today clinical toxicology and poisons control are widely lacking objective criteria, e.g., analytical data, figures of kinetics and metabolism in acute and chronic poisoning. Cooperation between clinical toxicology and an environmental specimen bank for human tissue will help to overcome many difficulties and complement one another. The possible power of such a co-operation is demonstrated by the example of the institutions in Miinster, Germany. The successful strategies used for setting-up an environmental specimen bank for human tissue may also be applied in clinical toxicology and experimental toxicology. The frame of a university medical clinic seems to be the ideal basis of an effective co-operation of an Environmental Specimen Bank for Human Tissue, a Poisons Control Centre and clinical toxicology. In general a co-operation of an environmental specimen bank for human tissue and a poisons control centre will be cost-saving and beneficial to both and an environmental specimen bank for human tissue will gain the status of a unique tool for risk assessment of xenobiotics.
Key words: clinical toxicology; environmental specimen bank; human body-burdens; poisons control
1. INTRODUCTION A N D PRESENT STATUS
1.1. Clinical toxicology and poisons control Clinical toxicology reflects the biologic response of a human being to a substance which either has been administered in toxic quantities or has met extraordinary metabolic conditions. Under these circumstances a patient's response depends on numerous factors, which may extend or limit the reaction to a particular toxic agent. The majority of organic xenobiotics undergo extensive metabolic alterations in the organism. As a consequence the concentrations attained in the distribution compartment blood, as well as in the target organs of toxicity depend on biotransformation processes which deter-
508
F.W JEKAT ET AL
mine to a large extent the duration and intensity of toxic action in addition to elimination processes. A sufficient understanding of kinetics and metabolism of toxicants in acute and chronic poisoning is urgently required because it is well known that in many cases poisonings do not follow textbook descriptions and signs and symptoms listed as pathognomonic are absent while the victim reveals an uncommon clinical status [1]. Under these circumstances toxicological analysis is the one and only objective criterion of diagnosis, evaluation, prediction of outcome and therapy in acute and chronic poisoning. Even though a proper knowledge of metabolism of drugs or toxicants is essential in clinical pharmacology and toxicology and moreover a basic requirement for a rational therapy, and even though there are sufficient data on pharmacokinetics and the metabolic fate of drugs in normal conditions, there is a lack of reliable figures in acute and chronic poisoning. There seems to be clear reasons for this fact: • studies under controlled conditions are impossible, • the situation of a severely poisoned patient in an emergency room seems to foil any academic study, • in general patients presumably suffering from chronic intoxications reveal only minor or uncharacteristic symptoms. An extrapolation of the data from normal conditions may be misleading, because in poisoning the routes of absorption, distribution, metabolic changes and excretion may be very complex and moreover everything may be altered by the patient's general state of health, his age and sex. At present poisons control means clinically well documented cases, but in most cases analytical information is limited because of various reasons, e.g., inadequate sampling, lack of experienced laboratories and the application of insufficient or wrong analytical methods as well as the absence of established reference values. Thus the interpretation and comparability of the results is difficult or impossible and as a consequence, there is a lack of reliable figures for acute and chronic poisonings with respect to xenobiotic body burden and clinical symptoms. The establishing of 'normal' or 'reference values' of trace elements and other chemical compounds in human tissues is very important for risk assessment, but literature data show fluctuations, which very often preclude their use as baseline data for toxicologic evaluation. Bertram [2] gave an example both for constancy and fluctuation of 'normal values' of trace elements in time. While published 'normal values' of zinc are constant since the late 1950s, there are remarkable differences for other trace elements, e.g., chromium. The fluctuations are mainly ascribed to analytical factors and in general the values are falling due to improved analytical techniques [3].
ENVIRONMENTAL SPECIMEN BANKING AND POISONS CONTROL
509
1.2. Environmental specimen banking Environmental specimen banking has stimulated progress in many fields of science, especially for the development and handling of analytical techniques in the scope of principles of 'Good Laboratory Practice' (GLP) using 'Standard Operating Procedures' (SOP), that guarantee reliable and reproducible results and thus provide the possibility to draw up reference values and ranges in 'normal' human subjects, which have not been established up to now. In the same way key indicator tissues have been determined for a large number of xenobiotics. At the University of Mfinster (Germany) an Environmental Specimen Bank for Human Tissue has been established in the early 1970s and it is linked to the Institute of Pharmacology and Toxicology. An official Poisons Control Centre, which is accepted by the 'Bundesgesundheitsamt' (German Federal Health Authority), is also part of the Institute of Pharmacology and Toxicology. 2. OBJECTIVES
The objectives of the Environmental Specimen Bank for Human Tissue in Miinster are: •
• • • • •
•
collection of information regarding the integrated past and recent exposure of humans to certain chemicals (reference or normal values). This information is important for the determination of trends of pollutant levels, for the development of adequate criteria (dose-effect relationship) and for the definition of quality guides, objectives and standards for pollutants; evaluation of the effectiveness of existing guides, standards and control measures on changing pollutant burdens; detection of populations at risk before serious effects occur; determination of the presence and extent of hazards from exposure to pollutants; determination of 'key indicator tissue' for toxicologic analysis; building-up of a data bank with comparable results; establishing of priorities for research.
It is striking that the objectives of the Environmental Specimen Bank for Human Tissue are in line with the analytical fields of clinical toxicology and the 'Real Time Monitoring'-programme (RTM) established in Mfinster is a valuable tool not only for specimen banking, but also for poisons control.
510
F.W. JEKAT ET AL.
2.1. Real time monitoring
The first real time monitoring programme was carried out in 1977, and it is still performed to provide a continuous surveillance on possible changes in patterns and trends of xenobiotics in man. At least twice a year samples of whole blood, plasma, urine, saliva, scalp and body hair - - and human milk in special cases - - are collected from about 150 healthy Caucasians of both sexes in the age range 20-40 years. Detailed information about personal habits and individual sources of acute or chronic exposure patterns are recorded by a comprehensive questionnaire. Basic analysis of more than 50 selected organic and inorganic substances are made for all samples according to standard operating procedures. For chemical analysis, recent equipment is used: atomic absorption spectroscopy (AAS), inductively coupled plasmaatomic emission spectroscopy (ICP-AES) or gaschromatographic/mass spectroscopy (GC/MS) are very sensitive methods for reliable determination of trace amounts. In the following, three examples may demonstrate the power of a cooperation of poisons control and environmental specimen banking [4]. 3. C L I N I C A L B E N E F I T S
3.1. Metal intoxication
Chelating agents, e.g., EDTA, deferoxamine, d-penicillamine and especially dimercaprol, are often applied for therapeutic purposes in metal poisoning. The clinical value of dimercaprol, however, is limited because of its considerable toxicity and very low therapeutic range. Nowadays DMPS, 2,3-dimercapto-l-propanesulfonic acid, a water-soluble derivative of dimercaprol is available as a drug both for oral and parenteral application. Due to the large number of published case reports the clinical efficacy of DMPS in cases of mercury poisoning seems to be well established. The good clinical efficacy combined with a low toxicity of DMPS seemed to justify its application in non-mercury poisoning instead of dimercaprol. The clinical investigation was carried out under an extensive toxicologic monitoring. 3.1.1 Chronic intoxication. The first case deals with a 55-year-old man suffering from an analytically confirmed argyrosis. Silver deposits were most striking in the skin, whereas silver levels in hair, blood and urine tended to be normal. The oral application of 300 mg DMPS per day clearly enhanced renal silver excretion. The increase was about 100-fold and was noticed throughout the therapeutic period. In a second therapeutical trial dpenicillamine, at an oral daily dose of 600 mg, failed to increase the basal rate of renal silver excretion in the same patient.
51 1
ENVIRONMENTAL SPECIMEN BANKING AND POISONS CONTROL
3.1.2 Acute intoxication. Tartar emetic, potassium antimony(III) oxide tartrate, is widely used to kill ants in households. Thus antimony poisoning is a quite frequent source of unintended intoxication in children. This 'antimony' case deals with a 16-month-old boy who ingested tartar emetic. Except for spontaneous vomiting the boy did not reveal any acute signs of intoxication. Urine concentration of antimony, however, was 8000 #g/1. Beside supportive care DMPS was applied orally at a dosage of 50 mg every 12 h. During chelation therapy the antimony level in urine decreased. In this case toxicologic monitoring was not restricted only to antimony. Indeed an 'element scan' [5] was performed and provided valuable clinical information on the patient and therapy effects (Fig. 1). Both renal iron loss and zinc loss were obviously not effected by DMPS. Analytical monitoring by the 'element scan' detected a marginal increased renal copper loss, that is probably due to chelation, but did not cause any additional clinical intervention. pg/I 10000
[] 1000
N
100
z~.................. " A
A
~" -- . ..... • ...... ~ " - 4
-~
~ ~
"A
.~ •
10
L
L []
0
Sb
•
Fe
"~"
Zn
~
DMPS
Cu
I
I
I
I
I
I
I
48
96
144
192
240
time after intoxication [hours]
Fig. 1. 'Element Scan' in an acute antimony intoxication and treatment by chelation (DMPS).
512
v.w. JEKAT ET AL.
No other side effects were noticed. This little boy was discharged in good health. 3.2. Element scan
The technique of 'element scan', which means a simultaneous quantification of several elements in the same sample, was established at the Environmental Specimen Bank for Human Tissue in Mfinster and provides valuable clinical information on the patient, and the effects and side effects of chelation therapy, especially for the early detection of a developing deficiency of trace elements. In some way acute heavy metal intoxication is quite an easy task for analysts because serum and urine levels are increased ten-, hundred- or thousandfold. In many cases of poisoning, however, it is not certain what the toxicologic marker is and what metabolite has to be searched for. Going deeper into biotransformation processes will lead into a 'jungle'. 4. EXPERIMENTAL TOXICOLOGY
But there are pathways in this jungle: in mammals biotransformation occurs primarily in the liver. Thus metabolites of toxicants may be predicted qualitatively and quantitatively to a great extent by more knowledge of the substance-specific metabolism by the intact liver. One of these pathways through the jungle has led us to the 'Isolated perfused rat liver'. 4.1. Isolated perfused rat liver
The technique of isolated liver perfusion is more than 100 years old. With such a long period for development, it should have reached a level of technical perfection beyond improvement. If the primary objective of isolated organ perfusion technique is to simulate exactly the status of the organ in the living animal for long intervals, then it is clear that it is still short of this goal [61. But the technique of isolated liver perfusion has been improved at our institute, using the strategy of 'standard operating procedures' and 'good laboratory practice', which was successful before in the environmental specimen banking programme. This technique was applied to study the liver's metabolic response under controlled conditions, e.g., to investigate metabolic patterns and to elucidate the interaction of toxicants and the potential antidotes in the perfused organ.
ENVIRONMENTAL SPECIMEN BANKING AND POISONS CONTROL
513
5. CONCLUSIONS
The experience gained by operating a specimen bank for human tissue and a poisons control centre is of striking benefit for both sides. The opportunities of an Environmental Specimen Bank for Human Tissue are: • determination of base-line trends and potential hazards of new or previously unrecognized exposures to different substances; • retrospective studies that may contribute to our knowledge of relationship between chemicals and effects including possible antagonistic or synergistic effects; • retrospective close estimates for chronic disturbances, damages or other adverse effects with long latent periods; • subsequent comparison with previous analytical data. These are in line with the needs of clinical toxicology. An Environmental Specimen Bank for Human Tissue will provide an analytical technique (including guidelines for sampling) and 'normal values' or 'reference ranges' in non-exposed humans. Textbook figures are not suitable in cases of chronic poisonings, because normal ranges are not static, but changing - - sometimes in a few years - - and they may differ in populations or sub-groups. Thus only data gained in real time may be applied for a proper evaluation. Co-operation between a Poisons Control Centre and an Environmental Specimen Bank for Human Tissue is not only useful from a scientific point of view, but it is also cost-saving, because parallel work and double infrastructures are avoided. Clinical toxicology and poisons control will provide well documented cases for setting up a comprehensive data base, which may help to find the analytical borderline for chronic poisonings. In such a co-operation an Environmental Specimen Bank for Human Tissue is not only a tool for biological monitoring, but also a unique institution for evaluating and assessing risks of xenobiotics to human health. REFERENCES 1 T.A. Gossel and J.D. Bricker, Principles of Clinical Toxicology, Raven Press, New York, 2nd Edn., 1990, pp. 19-21. 2 H.P. Bertram, in H. Zumkley (Ed), Spurenelemente, G. Thieme Verlag, Stuttgart, 1983, pp. 1-11. 3 E. Sabbioni and M.T. van der Venne, Trace Element Reference Values in Tissues from Inhabitants of the European Community. Commission of the European Communities, Joint Research Centre (1990) SP-1.90.06. 4 F.W. Jekat, H.P. Bertram, F.H. Kemper and C. M/iller, The clinical application of 2,3-
514
F.W. J E K A T ET AL
dimercapto-l-propanesulfonic acid (DMPS) in non-mercury metal poisoning. Bull. Soc. Sci. Med. Grand-Duch6 Luxembourg, (S) 127 (1990) 193-197. 5 H.P. Bertram, F.W. Jekat, F.H. Kemper and C. M/iller, Analytical "Element Scan" for Toxicologic Monitoring of Thallium Intoxication. Bull. Soc. Sci. Med. Grand-Duch6 Luxembourg, (S) 127 (1990) PO 3.06. 6 L.L. Miller, in I. Bartos~lk, A. Guaitani and L.L. Miller (Ed), Isolated Liver Perfusion and its Application, Raven Press, New York, 1973, Ch. 1, pp. 1-11.
507
Environmental specimen banking and poisons c o n t r o l - a new challenge Friedrich W. Jekat, Rolf Eckard and Fritz H. Kemper Institute of Pharmacology and Toxicology, Environmental Specimen Bank for Human Tissue, Poisons Control Centre, University of Miinster, Domagkstrafle 11-12, D-4400 Miinster, Germany ABSTRACT Today clinical toxicology and poisons control are widely lacking objective criteria, e.g., analytical data, figures of kinetics and metabolism in acute and chronic poisoning. Cooperation between clinical toxicology and an environmental specimen bank for human tissue will help to overcome many difficulties and complement one another. The possible power of such a co-operation is demonstrated by the example of the institutions in Miinster, Germany. The successful strategies used for setting-up an environmental specimen bank for human tissue may also be applied in clinical toxicology and experimental toxicology. The frame of a university medical clinic seems to be the ideal basis of an effective co-operation of an Environmental Specimen Bank for Human Tissue, a Poisons Control Centre and clinical toxicology. In general a co-operation of an environmental specimen bank for human tissue and a poisons control centre will be cost-saving and beneficial to both and an environmental specimen bank for human tissue will gain the status of a unique tool for risk assessment of xenobiotics.
Key words: clinical toxicology; environmental specimen bank; human body-burdens; poisons control
1. INTRODUCTION A N D PRESENT STATUS
1.1. Clinical toxicology and poisons control Clinical toxicology reflects the biologic response of a human being to a substance which either has been administered in toxic quantities or has met extraordinary metabolic conditions. Under these circumstances a patient's response depends on numerous factors, which may extend or limit the reaction to a particular toxic agent. The majority of organic xenobiotics undergo extensive metabolic alterations in the organism. As a consequence the concentrations attained in the distribution compartment blood, as well as in the target organs of toxicity depend on biotransformation processes which deter-
508
F.W JEKAT ET AL
mine to a large extent the duration and intensity of toxic action in addition to elimination processes. A sufficient understanding of kinetics and metabolism of toxicants in acute and chronic poisoning is urgently required because it is well known that in many cases poisonings do not follow textbook descriptions and signs and symptoms listed as pathognomonic are absent while the victim reveals an uncommon clinical status [1]. Under these circumstances toxicological analysis is the one and only objective criterion of diagnosis, evaluation, prediction of outcome and therapy in acute and chronic poisoning. Even though a proper knowledge of metabolism of drugs or toxicants is essential in clinical pharmacology and toxicology and moreover a basic requirement for a rational therapy, and even though there are sufficient data on pharmacokinetics and the metabolic fate of drugs in normal conditions, there is a lack of reliable figures in acute and chronic poisoning. There seems to be clear reasons for this fact: • studies under controlled conditions are impossible, • the situation of a severely poisoned patient in an emergency room seems to foil any academic study, • in general patients presumably suffering from chronic intoxications reveal only minor or uncharacteristic symptoms. An extrapolation of the data from normal conditions may be misleading, because in poisoning the routes of absorption, distribution, metabolic changes and excretion may be very complex and moreover everything may be altered by the patient's general state of health, his age and sex. At present poisons control means clinically well documented cases, but in most cases analytical information is limited because of various reasons, e.g., inadequate sampling, lack of experienced laboratories and the application of insufficient or wrong analytical methods as well as the absence of established reference values. Thus the interpretation and comparability of the results is difficult or impossible and as a consequence, there is a lack of reliable figures for acute and chronic poisonings with respect to xenobiotic body burden and clinical symptoms. The establishing of 'normal' or 'reference values' of trace elements and other chemical compounds in human tissues is very important for risk assessment, but literature data show fluctuations, which very often preclude their use as baseline data for toxicologic evaluation. Bertram [2] gave an example both for constancy and fluctuation of 'normal values' of trace elements in time. While published 'normal values' of zinc are constant since the late 1950s, there are remarkable differences for other trace elements, e.g., chromium. The fluctuations are mainly ascribed to analytical factors and in general the values are falling due to improved analytical techniques [3].
ENVIRONMENTAL SPECIMEN BANKING AND POISONS CONTROL
509
1.2. Environmental specimen banking Environmental specimen banking has stimulated progress in many fields of science, especially for the development and handling of analytical techniques in the scope of principles of 'Good Laboratory Practice' (GLP) using 'Standard Operating Procedures' (SOP), that guarantee reliable and reproducible results and thus provide the possibility to draw up reference values and ranges in 'normal' human subjects, which have not been established up to now. In the same way key indicator tissues have been determined for a large number of xenobiotics. At the University of Mfinster (Germany) an Environmental Specimen Bank for Human Tissue has been established in the early 1970s and it is linked to the Institute of Pharmacology and Toxicology. An official Poisons Control Centre, which is accepted by the 'Bundesgesundheitsamt' (German Federal Health Authority), is also part of the Institute of Pharmacology and Toxicology. 2. OBJECTIVES
The objectives of the Environmental Specimen Bank for Human Tissue in Miinster are: •
• • • • •
•
collection of information regarding the integrated past and recent exposure of humans to certain chemicals (reference or normal values). This information is important for the determination of trends of pollutant levels, for the development of adequate criteria (dose-effect relationship) and for the definition of quality guides, objectives and standards for pollutants; evaluation of the effectiveness of existing guides, standards and control measures on changing pollutant burdens; detection of populations at risk before serious effects occur; determination of the presence and extent of hazards from exposure to pollutants; determination of 'key indicator tissue' for toxicologic analysis; building-up of a data bank with comparable results; establishing of priorities for research.
It is striking that the objectives of the Environmental Specimen Bank for Human Tissue are in line with the analytical fields of clinical toxicology and the 'Real Time Monitoring'-programme (RTM) established in Mfinster is a valuable tool not only for specimen banking, but also for poisons control.
510
F.W. JEKAT ET AL.
2.1. Real time monitoring
The first real time monitoring programme was carried out in 1977, and it is still performed to provide a continuous surveillance on possible changes in patterns and trends of xenobiotics in man. At least twice a year samples of whole blood, plasma, urine, saliva, scalp and body hair - - and human milk in special cases - - are collected from about 150 healthy Caucasians of both sexes in the age range 20-40 years. Detailed information about personal habits and individual sources of acute or chronic exposure patterns are recorded by a comprehensive questionnaire. Basic analysis of more than 50 selected organic and inorganic substances are made for all samples according to standard operating procedures. For chemical analysis, recent equipment is used: atomic absorption spectroscopy (AAS), inductively coupled plasmaatomic emission spectroscopy (ICP-AES) or gaschromatographic/mass spectroscopy (GC/MS) are very sensitive methods for reliable determination of trace amounts. In the following, three examples may demonstrate the power of a cooperation of poisons control and environmental specimen banking [4]. 3. C L I N I C A L B E N E F I T S
3.1. Metal intoxication
Chelating agents, e.g., EDTA, deferoxamine, d-penicillamine and especially dimercaprol, are often applied for therapeutic purposes in metal poisoning. The clinical value of dimercaprol, however, is limited because of its considerable toxicity and very low therapeutic range. Nowadays DMPS, 2,3-dimercapto-l-propanesulfonic acid, a water-soluble derivative of dimercaprol is available as a drug both for oral and parenteral application. Due to the large number of published case reports the clinical efficacy of DMPS in cases of mercury poisoning seems to be well established. The good clinical efficacy combined with a low toxicity of DMPS seemed to justify its application in non-mercury poisoning instead of dimercaprol. The clinical investigation was carried out under an extensive toxicologic monitoring. 3.1.1 Chronic intoxication. The first case deals with a 55-year-old man suffering from an analytically confirmed argyrosis. Silver deposits were most striking in the skin, whereas silver levels in hair, blood and urine tended to be normal. The oral application of 300 mg DMPS per day clearly enhanced renal silver excretion. The increase was about 100-fold and was noticed throughout the therapeutic period. In a second therapeutical trial dpenicillamine, at an oral daily dose of 600 mg, failed to increase the basal rate of renal silver excretion in the same patient.
51 1
ENVIRONMENTAL SPECIMEN BANKING AND POISONS CONTROL
3.1.2 Acute intoxication. Tartar emetic, potassium antimony(III) oxide tartrate, is widely used to kill ants in households. Thus antimony poisoning is a quite frequent source of unintended intoxication in children. This 'antimony' case deals with a 16-month-old boy who ingested tartar emetic. Except for spontaneous vomiting the boy did not reveal any acute signs of intoxication. Urine concentration of antimony, however, was 8000 #g/1. Beside supportive care DMPS was applied orally at a dosage of 50 mg every 12 h. During chelation therapy the antimony level in urine decreased. In this case toxicologic monitoring was not restricted only to antimony. Indeed an 'element scan' [5] was performed and provided valuable clinical information on the patient and therapy effects (Fig. 1). Both renal iron loss and zinc loss were obviously not effected by DMPS. Analytical monitoring by the 'element scan' detected a marginal increased renal copper loss, that is probably due to chelation, but did not cause any additional clinical intervention. pg/I 10000
[] 1000
N
100
z~.................. " A
A
~" -- . ..... • ...... ~ " - 4
-~
~ ~
"A
.~ •
10
L
L []
0
Sb
•
Fe
"~"
Zn
~
DMPS
Cu
I
I
I
I
I
I
I
48
96
144
192
240
time after intoxication [hours]
Fig. 1. 'Element Scan' in an acute antimony intoxication and treatment by chelation (DMPS).
512
v.w. JEKAT ET AL.
No other side effects were noticed. This little boy was discharged in good health. 3.2. Element scan
The technique of 'element scan', which means a simultaneous quantification of several elements in the same sample, was established at the Environmental Specimen Bank for Human Tissue in Mfinster and provides valuable clinical information on the patient, and the effects and side effects of chelation therapy, especially for the early detection of a developing deficiency of trace elements. In some way acute heavy metal intoxication is quite an easy task for analysts because serum and urine levels are increased ten-, hundred- or thousandfold. In many cases of poisoning, however, it is not certain what the toxicologic marker is and what metabolite has to be searched for. Going deeper into biotransformation processes will lead into a 'jungle'. 4. EXPERIMENTAL TOXICOLOGY
But there are pathways in this jungle: in mammals biotransformation occurs primarily in the liver. Thus metabolites of toxicants may be predicted qualitatively and quantitatively to a great extent by more knowledge of the substance-specific metabolism by the intact liver. One of these pathways through the jungle has led us to the 'Isolated perfused rat liver'. 4.1. Isolated perfused rat liver
The technique of isolated liver perfusion is more than 100 years old. With such a long period for development, it should have reached a level of technical perfection beyond improvement. If the primary objective of isolated organ perfusion technique is to simulate exactly the status of the organ in the living animal for long intervals, then it is clear that it is still short of this goal [61. But the technique of isolated liver perfusion has been improved at our institute, using the strategy of 'standard operating procedures' and 'good laboratory practice', which was successful before in the environmental specimen banking programme. This technique was applied to study the liver's metabolic response under controlled conditions, e.g., to investigate metabolic patterns and to elucidate the interaction of toxicants and the potential antidotes in the perfused organ.
ENVIRONMENTAL SPECIMEN BANKING AND POISONS CONTROL
513
5. CONCLUSIONS
The experience gained by operating a specimen bank for human tissue and a poisons control centre is of striking benefit for both sides. The opportunities of an Environmental Specimen Bank for Human Tissue are: • determination of base-line trends and potential hazards of new or previously unrecognized exposures to different substances; • retrospective studies that may contribute to our knowledge of relationship between chemicals and effects including possible antagonistic or synergistic effects; • retrospective close estimates for chronic disturbances, damages or other adverse effects with long latent periods; • subsequent comparison with previous analytical data. These are in line with the needs of clinical toxicology. An Environmental Specimen Bank for Human Tissue will provide an analytical technique (including guidelines for sampling) and 'normal values' or 'reference ranges' in non-exposed humans. Textbook figures are not suitable in cases of chronic poisonings, because normal ranges are not static, but changing - - sometimes in a few years - - and they may differ in populations or sub-groups. Thus only data gained in real time may be applied for a proper evaluation. Co-operation between a Poisons Control Centre and an Environmental Specimen Bank for Human Tissue is not only useful from a scientific point of view, but it is also cost-saving, because parallel work and double infrastructures are avoided. Clinical toxicology and poisons control will provide well documented cases for setting up a comprehensive data base, which may help to find the analytical borderline for chronic poisonings. In such a co-operation an Environmental Specimen Bank for Human Tissue is not only a tool for biological monitoring, but also a unique institution for evaluating and assessing risks of xenobiotics to human health. REFERENCES 1 T.A. Gossel and J.D. Bricker, Principles of Clinical Toxicology, Raven Press, New York, 2nd Edn., 1990, pp. 19-21. 2 H.P. Bertram, in H. Zumkley (Ed), Spurenelemente, G. Thieme Verlag, Stuttgart, 1983, pp. 1-11. 3 E. Sabbioni and M.T. van der Venne, Trace Element Reference Values in Tissues from Inhabitants of the European Community. Commission of the European Communities, Joint Research Centre (1990) SP-1.90.06. 4 F.W. Jekat, H.P. Bertram, F.H. Kemper and C. M/iller, The clinical application of 2,3-
514
F.W. J E K A T ET AL
dimercapto-l-propanesulfonic acid (DMPS) in non-mercury metal poisoning. Bull. Soc. Sci. Med. Grand-Duch6 Luxembourg, (S) 127 (1990) 193-197. 5 H.P. Bertram, F.W. Jekat, F.H. Kemper and C. M/iller, Analytical "Element Scan" for Toxicologic Monitoring of Thallium Intoxication. Bull. Soc. Sci. Med. Grand-Duch6 Luxembourg, (S) 127 (1990) PO 3.06. 6 L.L. Miller, in I. Bartos~lk, A. Guaitani and L.L. Miller (Ed), Isolated Liver Perfusion and its Application, Raven Press, New York, 1973, Ch. 1, pp. 1-11.