Toxicology of Industrial Compounds

20
Testing and Evaluation for Reproductive Toxicity
ANTHONY K.PALMER
Huntingdon Research Centre, Huntingdon
Introduction
Most of the presentations at this meeting refer to high level, scientific
investigations of one or two, highly important, high production volume
chemicals, for which an adverse effect has been demonstrated. They are
studies of characterisation, because they elaborate on known effects using a
wealth of available information. But, how were the adverse effects of these
few substances first discovered, what were the initial clues? Sadly, for
many, the observation of adverse effects in humans was the trigger to
intensive investigations, which is akin to ‘shutting the stable door after the
horse has bolted’.
This presentation is concerned with detecting effects of substances for
which little or no information is available and, preferably, before they
cause harm to humans. This requires a different kind of science, for which
the main asset is the ability to predict, with reasonable accuracy, possible
activity from minimal information. It requires wide experience and a
balance between imagination and pragmatism. These attributes are
especially important for toxicity to reproduction, which triggers instinctive
reactions in even the coolest and most objective scientist.
Identifying the cause of adverse effects on human reproduction has long
been surrounded by controversy and uncertainty. In respect of the
evaluation of substances for reproductive toxicity this state of affairs seems
likely to persist for years to come. The main obstacle to any attempt to
rationalise the situation is that any discussion on evaluation almost
inevitably gravitates to the black hole of regulatory guidelines. All
guidelines are flawed because science fact is compromised by bureaucracy
and science fiction. For many reasons, but especially the unwillingness of
any establishment to change the status quo, guidelines provide the worst
starting point for developing a strategy for evaluation.
Most guidelines are concerned only with methods for gathering specified
information. On its own this information (on hazard) is insufficient and
needs to be supplemented with other information, from other sources, to