Handbook of Solvents - George Wypych - ChemTech - Ventech!

15.2.1 Use of breath monitoring 1079
tive dose) that is related to toxicity and/or damage. In general, the dose at the receptor can
not be measured because, at this time, available methodology is unacceptably invasive to be
employed. On the other hand, biological monitoring allows measurements to be made on
body fluids or tissues that would serve as surrogate measurements of the dose at the receptor.
Certain conditions, however, are required for meaningful interpretations of the analytical
results.
1. There should be adequate information on the absorption, distribution,
biotransformation, metabolism and elimination of the chemical in the body. This type of information
will indicate what tissues to sample, for what compound (parent chemical or a
metabolite) and at what time. The latter issue is very important with chemicals that are eliminated
rapidly (i.e., those with short half-lives).
2. The concentration of the chemical (or its metabolite) to be measured in the selected
medium (breath, blood, urine) must be in equilibrium with the concentration of the chemical
at the target organ.
3. The assay has to be sensitive, in order to detect low levels of the compound before
any adverse effects take place; specific, in order to link exposure to dose; and accurate and
precise, in order to be reliable.
Very few chemicals have been adequately studied to allow biological monitoring according
to the above criteria. This is, however, an expanding area, as indicated by the number
of substances for which Biological Exposure Indices (BEIs) have been proposed by the
American Conference of Governmental Industrial Hygienists (ACGIH). In the 1984-85
Threshold Limit Value (TLV) booklet there were BEIs for 10 chemicals; in the 1998 booklet
there were 37 compounds with adopted BEIs. 2 BEIs are considered reference values intended
as guidelines and do not determine whether the worker is at risk of disease. They are
supplementary to TLVs in evaluating workers’ exposures to workplace hazardous agents.
The recommended values of BEIs are based on data correlating exposure intensity and biological
effects from field studies and/or on pharmacokinetic treatment of data obtained from
controlled human exposures. The BEIs developed by the ACGIH, assume 8-hour exposures
for 5 days, followed by 2 days of non-exposure, and they strictly specify the time of sample
collection.
A clear advantage of biological monitoring over environmental or personal monitoring
is that the estimate of the internal dose takes into account all possible routes of entry (inhalation,
ingestion and dermal exposure). In addition, exposures other than occupational,
such as through diet, hobbies or residential air, all contribute to the internal dose, which is
related to adverse effects. When the effect of occupational exposure alone needs to be evaluated,
non-occupational exposures need to be assessed and controlled to allow interpretation
of biological monitoring results. A special case is the evaluation of protective
equipment in reducing workplace exposures.
Biological monitoring is limited by parameters that can affect the exposure and dose
relationship. Such parameters include the following: biological conditions (age, sex, obesity,
pregnancy, disease), physical workload, or exposure to other agents (other chemicals,
tobacco smoking, dietary components) that in some way interfere with the uptake, distribution,
metabolism or elimination of the chemical in the body. 3-6 Such parameters may introduce
large inter-individual variation in the resulting dose. When simulation techniques
were used to evaluate the influence of these parameters, it was shown 6 that up to 100% bias
may result from inter-individual variation in the metabolism of aromatic compounds. If
these differences occur randomly, they will widen the confidence limits of the biological
monitoring results, decreasing the statistical power of a study. This is just one example illustrating
the care that must be taken when interpreting biological monitoring results.