So, there are a number of proposals to improve toxicity-testing strategies,
of the committee felt that the system has reached a turning point,
it's reached saturation.
There's not much else that can be done to increase its output its accuracy
in detecting chemicals, that at very low doses, through which humans
are normally exposed, as to whether or not they're having any adverse health effects.
So, the regulatory agencies, as I've mentioned previously, have responded to
the scientific advances and challenges, by altering the tests or adding tests.
And it's really been a patchwork approach that is not really fully satisfactory.
So there are four objectives of toxicity-testing, one is depth.
So down at the bottom, you can see that we want a detailed mechanistic
understanding and dose information for human health risk assessment.
And we want to be able to have this for a number of compounds in great depth.
So we really understand what kinds of effects these chemicals may be having
on cells and tissues and organ systems.
Up at the top, you can see we want breadth,
we want the broadest coverage of chemicals and end points and life stages.
We don't only get exposed as adults,
we get exposed throughout our life beginning in utero.
So the developing fetus and embryo is exposed through the mother, and
then from birth on, we're exposed to a variety of chemicals.
And sure, the chemicals that we're exposed to may change over time, but
exposure to environmental chemicals is continuous.
There are also animal welfare issues, we want to cause the least suffering possible
and use the fewest number of animals.
This requires that we have well designed toxicity-tests
when we need to use animals.
And that we would only use animals when absolutely necessary,
because we would have alternative testing strategies that could be used first.
And we need endpoints, such that we can detect an adverse effect in the animal
before the animal begins to suffer from that adverse effect.
And we also need conservation, we need the lowest cost and the least time,
we have to minimize the expenditure of resources.
So there can be disagreements as to which of the four of these is most important.
For instance, with the endocrine disruptor screening program,
the primary objective was breadth.
Wanted to be able to test many different environmental chemicals as to whether or
not they could have adverse health effects mediated through
altering the hormonal systems in our bodies.
That was a primary driving factor, and
some of the protocols that were developed were very animal intensive for instance.
And so there was less attention to that objective of toxicity-testings, so
there's this conflict between these four objectives.
So this concludes the second section of this lecture.