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In the study of the association between lead exposure and both- renal insuf- ficiency and hypertension, it was also considered that renal impairment might be responsible for the elevation of blood lead concentrations by decreasing the urinary excretion of the met- al.

But even in patients with severe renal failure, the renal clearance of lead was not affected, which suggests that the in- creased lead body burden could be an etiologic factor rather than a mere consequence of these diseases [10], The association between a chemical and a health effect may also be secondary i.

A typical example of such an association is the presence of high levels of cadmium in tissues e. This associ- ation, which was reported in the past as possibly causal, is better explained by the fact that tobacco smoke may contain high levels of cadmium, and tobacco consumption is a well known etiologic factor in these diseases [6]. Establishment of Dose-response Relationships Dose-response or dose-effect relationships i. The greatest interest of these relationships is the fact that they allow the suggestion of biological limit values BLY.

Cross- sectional studies performed among populations at risk and using sensitive indicators of health effects represent the most prag- matic approach to establish dose-response relationships. Prolonged exposure to cad- mium results in the progressive accumulation of this metal in the organism, mainly in the liver and the kidneys. The latter Is usually considered as the critical organ, I. Renal dysfunction induced by cadmium can be detected at an early stage by measuring specific urinary proteins such as albumin, retino!

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The accumulation of cadmium in the kidneys can be directly assessed in vivo by neutron activation analysis or indirectly from the urinary excretion of cadmium. The kidneys and the central nervous system are the two critical organs during chronic exposure to inorganic mercury. At ex- posure levels below this threshold, the risk of central nervous system disturbances e.

In those cases, the BLV is derived indirectly from the TLV by means of toxicokinetic data usually collected in controlled human studies [2], Identification of Groups at Risk BH may also be used for the Identification of groups of workers exposed to certain chemicals or groups of chemicals e. This information, however, may be useful for designing appropriate epidemiological studies. A similar approach may also be ap- plied to the general population. The doubling of chemical con- sumption every seven years in industrialized societies neces- sarily entails a global pollution of the ecosystem with persis- tent hazardous chemicals such as PCB derivatives or heavy rat- als.

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In the case of cadmium, the results show that the mean concentration of this matal in the renal cortex i. In Belgium, cadmium pol- lution is mainly localized in areas e. To determine whether this environmental pollution by cadmium may have led to a higher uptake of cadmium by the In- habitants, we have compared the cadmium level in the blood and urine of aged women who have spent the major part of their lives in the Liege area with that of a control group of women matched for age and socio-economic status and selected in an industrial area not polluted by cadmium.

The urinary excretion of cadmium was found to be, on the average, twice as high in the Liege area than In the control area. Since the cadmium level in urine mair. The concentration of cadmium in blood was also higher in the Liege area than in the control area, which is in agreement with the current environ- mental pollution by cadmium [13].

These results were confirmed by a recent autopsy study in which liver and 44 J kidney cortex samples from the l. In all age groups, the persons who had lived in the contaminated area had stored more cadmium in their livers and renal cortexes than did residents from other areas of Belgium.

The same trend was found in males and females, which strengthens the hypothesis of an environmental factor. Toxicokinetic Studies on Human Subjects As indicated above, the knowledge of the metabolic fate of chemicals is a prerequisite for developing biological tests of exposure. Such information is usually collected on volunteer subjects in industry or under experimental exposure condi- tions. When the results suggest that the tests are potentially useful, additional kinetic studies may be relevant to identify possible confounding factors.

Such studies have shown that ethanol can competitively inhibit the enzymatic oxidation of substances such as styrene [15] or toluene [16]. Diseases may also be a source of confounding in BM. Studies among patients with liver diseases have shown that the proportions of mono- methylarsenic and dimethyl arsenic acid excreted in urine fol- lowing exposure to inorganic arsenic are closely related to the functional integrity of the liver [17].

Toxicokinetic studies have also shown that physical activity, body fat, site of skin contact, and drug consumption may also act as confounding fac- tors in some BM tests []. We have tested on volunteers the ef- fect of two barrier creams containing glycerol or sillcone on the percutaneous absorption of m-xylene [21]. The absorption of the solvent was evaluated by measuring the amount of m- xylene eliminated in exhaled air and the 24 h urinary excretion of methylhypurlc acid. Although these creams had been vali- dated 1n vitro by the manufacturers; In volunteers, they sur- prisingly had no significant effect on the skin absorption of m-xylene [ In a similar study conducted among workers ex- posed to dimethylformamlde CHF In an acryl 1c.

Furthermore, the comparison of NMF excretion 1n. However, the removal of gloves led to a marked increase of the urinary excretion of NMF. This observation demonstrated that the skin was the main route of exposure to DMF.

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For other chemicals e. It 1s, however, likely that 1n many situations the information provided by both monitoring approaches is complementary. However, the potential of BM is far from being completely realized, and it can be ex- pected that 1n the future this approach will further develop in both quantitative and qualitative terms. The steady Improve- ment of the sensitivity and specificity of analytical methods broadens the spectrum of chemicals which can be analyzed in biological media.

Increasing automation, by reducing the dura- tion and cost of chemical determinations, makes them more suit- able to routine application. Analytical advances also improve the quality of information which can be obtained from BM tests. The steady progress 1n the understanding of the metabolic fate and of the mode of action of occupational or environmental pollu- tants may also suggest new biological Indicators potentially applicable for BH.

But these promising perspectives should not let us forget that BH of exposure uses man as an Integrator of exposure.

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The ethical aspects must receive a great deal of at- tention, and 1n particular, BM must always be applied under conditions which respect some basic rights of the examined sub- ject, such as the right to the confidentiality of the results end the right to be informed of the risks, benefits, and re- sults of the test. Lauwerys, R. Bernard, A. Ho and H. Dillon, Eds. New York:John Wiley and Sons, , in press. Roels, M. Regnier, J.

Buchet, A. Ber- nard, and A. Research Hassler, E. L1nd, and H. Brown and J. Foulkes, Ed. Drucke, T. Wedeen, R.


Mallik, and V. Roels, P. Genet, G. Toussaint, A. Bouck- aert, and S. De Cooman. A Questionnaire Study. Campbell, B. Ellitt, and P. Letters, Roels, H. Gennart, R. Lauwerys, J. Buchet, J. Malchaire, and A. Vcthter, M. Roels, J. Bernard, and Ph. Wilson and R.

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