Toxicology of Industrial Compounds

F.A.DE WOLFF ET AL. 3
health surveillance. The latter is a major task for the occupational health
physician, but biological monitoring and biological effect monitoring are
fields of interest to the occupational toxicologist. In this contribution, only
biological monitoring will be expounded upon.
Biological monitoring (BM) is defined as the ‘measurement and
assessment of workplace agents or their metabolites either in tissues,
secreta, excreta or any combination of these to evaluate exposure and
health risk compared to an appropriate reference’ (Zielhuis & Henderson,
1986). This means that a biological monitoring programme is not limited
to the assay of xenobiotics in biological samples. As in clinical laboratory
medicine, the pre-analytical phase of the process is very important, and
even more so the post-analytical phase of the laboratory analysis, which
means the interpretation of the analytical data in biomedical terms. The
ultimate goal of biological monitoring is the evaluation of the health risk of
workers by estimation of the internal dose of a chemical. This is not limited
to measurement of the quantity of the substance absorbed by the body, but
may also include the assay of metabolites of toxicological interest, if
possible in or near a critical organ (Monster & van Hemmen, 1988).
This implies that the absorption, metabolism and elimination of a
substance in man should be known before a biological monitoring
programme can be performed in practice. Animal experiments are of
limited value; volunteer studies in order to determine pulmonary and
dermal uptake of organic solvents provide more relevant data for this
purpose.
Owing to the existence of very sensitive analytical methods it is possible
to study the kinetics and metabolism of solvents in volunteers who are
experimentally exposed to levels at or far below the official threshold limit
values, so that any health risk for the volunteers can almost totally be
excluded.
As with biological monitoring of most other substances, in the case of
organic solvents the compound itself and/or its metabolite in blood or urine
can be measured. Studies with volatile, rather lipophilic, substances have an
additional advantage, namely that the solvent can also be measured in
expired air. Analytically this has the advantage of an extremely clean
matrix in comparison with body fluids, whereas biologically, air samples
provide us with information on the blood concentration of a volatile
compound. Moreover, collection of expired air is non-invasive and large
volumes are readily available (Droz & Guillemin, 1986).
An example of a study on solvents in volunteers is the one carried out in
our laboratory on the biokinetics of n-hexane and its neurotoxic metabolite
2,5-hexanedione (Van Engelen et al., in preparation). Volunteers are
exposed during 15 min to 60 ppm hexane by inhalation. The minute volume
and the respiratory rate are measured and blood and exhaled air sampled
frequently for determination of 2,5-hexanedione and n-hexane,