Toxicology of Industrial Compounds

medicines, agrochemicals and food additives. They may be sufficient to
detect potent toxicity but not comprehensive enough to allow presumption
of the absence of hazard, especially as the base set does not include tests
for reproductive toxicity (Table 20.2).
As production volume increases, more extensive testing should be
undertaken. Often, this has been neglected, prompting the development of
the OECD guidelines 421 and 422. These tests were intended to recover a
situation that never should have arisen.
A better approach?
There is no question that evaluation for reproductive toxicity could be
improved considerably. The question is whether industry and agencies are
willing to do so. It would require a change of attitude in industry and
agencies alike. Industry’s ‘passive avoidance’ of testing would need to be
replaced by ‘active participation’. For a new substance the first step should
be an integrated assessment of commercial prospects and potential toxicity
over a broad spectrum (Figure 20.1). Early identification of ‘serious bad
actors’, which tend to effect many systems, can save time and effort. Given
the prognosis of problems ahead, it may be better to devote resources to
finding safer alternatives, or to risk management, rather than to endless
testing. For materials with a high commercial potential, the aim should be
to get to full scale tests by the quickest route. Following the EC levels by rote
is very inefficient since there is duplication with successive steps.
Methods
With an active participation policy, a much broader scope of methodology
can and should be considered, ranging from searches for structure-activity
relationships, through various in vitro methods, whole animal tests, wild
life surveys and human surveys (Table 20.3). Due to time constraints I will
concentrate on whole animal test systems.
Structure-activity databases
Structure and activity relationships are an obvious place to start any
evaluation, despite the fact that currently available databases are far from
perfect. Their reliability could be improved dramatically by adding unused
information currently hidden in industry and agency archives.
Entire mammalian tests
A.K.PALMER 283
Tests in entire mammals provide the only way of assessing what effects a
substance may evoke in the complex, integrated and dynamic process of