Ulrich Ewers

Results from the European multicenter study on lead neurotoxicity in children: Implications for risk assessment

In order to improve dose-response information on neurobehavioral effects of environmental lead exposure in children, the World Health Organization, Regional Office for Europe (WHO/EURO), in collaboration with the Commission of the European Communities, initiated this international study which was planned, executed and evaluated between 1984 and 1989. Eight groups from eight European countries (Bulgaria, Denmark, Greece, Hungary, Italy, Roumania, W. Germany and Yugoslavia) took part. A common study protocol with inherent quality assurance elements was developed to achieve comparability. Blood-lead concentrations (PbB) were the main markers of exposure. The WISC (4 subtests) for psychometric intelligence, the Bender Gestalt test (GFT version) and the Trail-Making test for visual-motor integration, the Vienna Reaction Device and a delayed RT task for reaction performance, and the Needleman scales for behavior ratings served as behavioral endpoints. All individual studies taken together represent a sample size of 1879 school-age children and cover a PbB range from below 5 to about 60 micrograms/100 ml. Overall statistical evaluation of outcome was done by multiple regression analysis using a uniform confounder model. The strongest and most consistent effects occurred for the Bender Gestalt test (GFT version) and for serial choice reaction performance (Vienna Device). The degree of association with PbB was significant for these variables, although the contribution of PbB to the observed variance never exceeded 0.8%. Psychometric intelligence was also negatively affected, although the consistency of outcome between studies was poor, and the association with PbB only borderline. An effort towards risk assessment was made by calculating the proportion of children at risk, using the observed regression coefficients as well as means and standard deviations.

Teil 3: PCDD/F im Blutfett ausgewählter Personen

ZusammenfassungIm Zusammenhang mit der im Jahre 1991 aufgedeckten hohen Belastung der Rückstandshalden und des Umfeldes einer früheren Kupferhütte in Marsberg (Nordrhein-Westfalen) mit polychlorierten Dibenzo-p-dioxinen und Dibenzofuranen (PCDD/F) wurden die Konzentrationen dieser Schadstoffe im Blut von 56 ausgewählten Probanden aus Marsberg untersucht. Es handelte sich dabei um direkte Anwohner der Halden bzw. der früheren Kupferhütte und um Personen, die in besonderer Weise mit Haldenmaterial in Kontakt gekommen waren. Parallel dazu wurde eine gleichgroße Gruppe von alters- (±3 Jahre) und geschlechtsgleichen Personen aus dem Kreis Steinfurt (Münsterland, Nordrhein-Westfalen) untersucht.Die Belastung der Marsberger Probanden betrug im Mittel 28,5 pg BGA-TE/g Blutfett (52,7 pg NATO/CCMS-TE/g Blutfett), die des Steinfurter Kollektivs 23,9 pg BGA-TE/g Blutfett (44,4 pg NATO/CCMS-TE/g Blutfett) (Medianwerte: Kollektiv Marsberg: 24,4 pg BGA-TE/g Blutfett (43,2 pg NATO/CCMS-TE/g Blutfett), Kollektiv Steinfurt: 23,4 pg BGA-TE/g Blutfett (43,0 pg NATO/CCMS-TE/g Blutfett). Die Konzentrations-Spannweiten betrugen 11,3–103 pg BGA-TE/g Blutfett (22,1–231 pg NATO/CCMS-TE/g Blutfett) [Marsberg] bzw. 9,1–48,9 pg BGA-TE/g Blutfett (16,9–98 pg NATO/CCMS-TE/g Blutfett) [Steinfurt]. Die in Relation zu dem Steinfurter Kollektiv im Mittel höheren TE-Blutfettgehalte der Marsberger Probanden waren vornehmlich durch erhöhte Penta- und HexaCDF-Konzentrationen bedingt. Es ist zu vermuten, daß diese bei mehreren Probanden erkennbaren Auffälligkeiten des Kongenerenmusters durch Aufnahme von PCDD/F aus dem belasteten Haldenmaterial bzw. Boden zustande gekommen sind. Eine eindeutige Klärung dieser Frage ist aufgrund der vorliegenden Untersuchungsergebnisse nicht möglich.AbstractThis study was designed to assess the degree of exposure to PCDD/F in 56 selected persons living in the vicinity of a former copper smelter located in Marsberg, Germany. The copper smelter was in operation until 1945. In 1991, high levels of PCDD/F were found particularly in materials from the slag dumps (10 000 – 100 000 ng TE/kg).The levels of PCDD/F in blood fat were used as parameters for individual PCDD/F exposure.Since only limited reference data for PCDD/F in human blood were available, blood samples of a reference group were analyzed in the same way. The criteria were collected from a group matched for sex, age (±3 years) and body mass.The median NATO/CCMS-Toxicity equivalency values (NATO/CCMS-TE-values) of the Marsberg group (43,2 pg NATO/CCMS-TE/g blood fat) and the reference group (43,0 pg NATO/CCMS-TE/g blood fat) were similar, whereas the arithmetic mean of the Marsberg group (52,7 pg NATO/CCMS-TE/g blood fat) was higher than that of the reference group (44,4 pg NATO/CCMS-TE/g blood fat). The frequency distribution of the individual TE-values of the Marsberg group was slightly shifted toward higher values. The individuals of the Marsberg group had significantly higher levels of PentaCDF, HexaCDF and HeptaCDF on average than the individuals of the reference group.On the basis of TE-values, the majority of the individuals from Marsberg did not have an increased body burden of PCDD/F. However, some individuals could be identified with TE-values exceeding background levels ranging up to 231 pg NATO/CCMS-TE/g blood fat. Although it must be assumed that the unusual congener pattern found in many of the test subjects is a result of ingestion of contaminated slag material or soil, the findings of this study could not verify this fact.

Interrelationships between cadmium, zinc and copper in human kidney cortex

The concentrations of cadmium, copper, and zinc have been determined in tissue samples of kidney cortex collected from 399 deceased persons autopsied in Dusseldorf and Duisburg, West Germany. The mean concentrations (geometric means) were: Cd: 17.0 μg/g wet weight (range <0.4–94.3 μg/g); Cu: 1.6/ μg/g (range 0.5–8.7 μg/g); Zn: 29.1 μg/g (range 6.3–91.6 μg/g). Zinc was shown to accumulate with age in the kidney cortex in a way similar to cadmium with peak concentrations at ages between 30 and 50 years. In contrast to cadmium and zinc, the copper content did not increase with age. The calculation of the regression line between individual cadmium and zinc concentrations, expressed as μmol/g wet weight, gave a slope constant 0.723 (regression equation: ZnKc = 0.723 CdKc + 0.342; r=0.46, P <0.001), which corresponds to a somewhat less than equimolar increase of zinc. There was a significant increase of the Cd/Zn ratio in kidney cortex during the first decades of life followed by a decrease at ages over 70 year...

Exposure to Cadmium of the West-German Population - Results of Biological Monitoring Studies 1980-1986

This article reviews recent studies concerning the current situation of cadmium exposure of the West-German population. The normal levels of cadmium in blood, urine and kidney cortex as measured by modern analytical techniques applying careful quality control are discussed. Moreover, recent results concerning the normal levels of urinary proteins as indicators of cadmium nephrotoxicity are presented. The knowledge of the normal levels of indicators of exposure and effect is an essential prerequisite to detect undue exposures and nephrotoxic effects of cadmium in the general population as well as in occupationally exposed groups of workers.

Blei- und Cadmiumbelastung Zähne als Indikatoren der Blei- und Cadmiumbelastung des Menschen

ZusammenfassungEs wurden die Blei- und Cadmiumgehalte in Milchschneidezähnen von Kindern aus verschiedenen Gebieten Nordrhein-Westfalens bestimmt. Die Kinder entstammten den Geburtsjahrgängen 1968–1973 und 1979–1986. Die Gegenüberstellung der Blei- und Cadmiumgehalte in den Milchzähnen dieser Kinder läßt erkennen, daß die Blei- und Cadmiumgehalte in Kinderzähnen in den 70er und 80er Jahren stark abgenommen haben. Der Rückgang beträgt im Mittel 50–60 %. Da die Blei- und Cadmiumgehalte in Zähnen als Indikatoren der Langzeit-Blei- und Cadmiumbelastung des Organismus angesehen werden können, zeigen die Untersuchungsergebnisse, daß die Blei- und Cadmiumbelastung von Kindern und wahrscheinlich auch der Bevölkerung insgesamt in den 70er und 80er Jahren erheblich abgenommen hat. Der Rückgang der Belastung setzt sich offenbar in den 90er Jahren fort. Verschiedene Studien zeigen, daß die Blei- und Cadmiumbelastung der Bevölkerung im Zuge der Industrialisierung stark zugenommen hat. Die Spitze der Belastung scheint überwunden und die Belastung nunmehr rückläufig zu sein.AbstractThe levels of lead and cadmium were determined in deciduous teeth of children from different areas of Northrhine-Westfalia, Germany. The children were born in 1968–1973 and 1979–1986. The levels of lead and cadmium in deciduous teeth show a significant decrease within this time interval. Lead decreases about 50 %, cadmium about 60 %. Since tooth lead and tooth cadmium may be used as indicators of the lead and cadmium body burden, the results of this study indicate a significant decrease of population exposure to lead and cadmium in West-Germany during the past 20–25 years, which is a consequence of pollution control and the increasing use of unleaded fuel.

Expositionsabschätzung: Human-Biomonitoring vs. Modellrechnungen

ZusammenfassungDie Expositionsabschätzung stellt einen wesentlichen Bestandteil der umweltmedizinisch-toxikologischen Gefährdungs- und Risikoabschätzung dar. Ziel der Expositionsabschätzung ist es, die über verschiedene Pfade aufgenommenen Schadstoffmengen und die daraus resultierende innere Schadstoffbelastung exponierter Personen abzuschätzen. Hierzu werden einerseits szenarische Modellbetrachtungen und -rechnungen durchgeführt, andererseits Messungen der Schadstoffkonzentrationen in menschlichen Untersuchungsmaterialien (Human-Biomonitoring). In dem vorliegenden Beitrag werden die Möglichkeiten und Grenzen der beiden v.g. Untersuchungsansätze erörtert. In bezug auf den modelltheoretischen Ansatz ist kritisch anzumerken, daß je nach Wahl der Eingangsparameter und Grundannahmen stark divergierende Ergebnisse bezüglich der Expositionsabschätzung erhalten werden. In Hinsicht auf die Bewertung von Gefährdungspotentialen ergeben sich hieraus erhebliche Unsicherheiten. Das Human-Biomonitoring stellt demgegenüber ein empirisches Verfahren zur Abschätzung der inneren Schadstoffbelastung exponierter Personen dar. Die großen Unsicherheiten der rechnerischen Abschätzung der Schadstoffbelastung werden umgangen. Die Meßwerte spiegeln die individuelle Belastung der jeweiligen Personen wider und können daher zum Ausschluß oder zur Feststellung einer im Einzelfall bestehenden Gesundheitsgefährdung herangezogen werden. Sofern geeignete Parameter zur Verfügung stehen, sind bei der Expositionsabschätzung daher Human-Biomonitoring-Untersuchungen gegenüber Modellrechnungen grundsätzlich zu bevorzugen.Wenn Human-Biomonitoring-Untersuchungen nicht durchführbar sind, können Modellrechnungen zur Expositionsabschätzung sinnvoll sein. Die Validität der Modellrechnungen bedarf allerdings einer empirischen Überprüfung. Aus umweltmedizinisch-toxikologischer Sicht ist zu fordern, daß die diagnostischen Möglichkeiten des Human-Biomonitoring stärker als bisher bei umweltmedizinisch-toxikologischen Gefährdungsabschätzungen genutzt werden.AbstractExposure assessment represents an important and integral part of the assessment of health risks associated with the human exposure to toxic substances in soil and other environmental media. In recent times model calculations are widely used to assess the doses of toxic substances which have been incorporated into the human body via different routes of exposure. The present paper discusses the possibilities and limitations of such model calculations with regard to exposure and risk assessment. A critical point is that the results largely depend on the basic assumptions introduced into the model calculations. Moreover, the results refer to a more or less typical scenario of exposure, although they do not allow any conclusion with regard to individual exposure levels. In contrast, the use of biomarkers of exposure (human biological monitoring) represents a methodological approach to estimate individual exposure levels of subjects exposed to toxic substances in a given situation. In practice, the identification of persons at risk and the exclusion of individual health risks can only be based on human biological monitoring studies.Exposure assessment based on theoretical calculations and exposure assessment based on biomarkers of exposure and effects should be regarded as complementary approaches in exposure and risk assessment.

Chapter 18 Lead

Publisher Summary This chapter discusses the problems of determination of lead in whole blood (PbB) as it is considered to be the best indicator of current lead exposure in humans and mammals. The techniques and problems of lead determination in other biological matrices, such as teeth, bones, plant, and animal tissues are also reviewed. The determination of PbB is of prime importance with respect to the diagnosis of lead poisoning and to the assessment of hazardous conditions, both in occupationally exposed people and in the general population. Blood contains lead in three forms: a major fraction bound to erythrocytes; a protein-bound fraction in plasma; and a diffusible fraction that represents the metabolically active form of circulating blood. The PbB level as an index of the absorbed amount of lead depends on a variety of environmental factors as well as biological factors. The correct performance of PbB determination must include the correct sampling of blood; and an internal and external quality control within each set of PbB determinations. The methods used to provide accurate and precise PbB determinations in routine use include anodic stripping voltammetry (ASV), flame atomic absorption spectrophotometry (FAAS), discrete sampling FAAS, and graphite furnace AAS (GF-AAS).