Day 038 - 19 Oct 94 - Page 30
1 For that group of 18 compounds, a man called David
2 Zaltsberg took those known human carcinogens, carcinogens
3 known to cause cancer in humans, from occupational
4 epidemiological studies. He then looked at the
5 corresponding rat feeding studies and asked the question:
6 How often do the rat studies correctly pick up the
7 carcinogenicity? He claimed the rat studies then got it
8 right. I think his figure was something like 38 per cent
9 at the time, which indicates that they are extremely
10 unreliable.
11
12 It perhaps will not surprise you to know that this provoked
13 a lot of concern and further work. Some of the compounds
14 were studied again in different species, at higher doses,
15 scrutinised more thoroughly. By the late 80s, the most
16 recent figure I have seen suggested that for known human
17 carcinogens the rat feeding studies picked up the
18 carcinogenicity maybe 80 per cent of the time, which is an
19 improvement in the science but still a relatively poor
20 basis of policy making, because it implies that the rat
21 feeding studies were missing, on average, 20 per cent of
22 all carcinogens.
23
24 Since we know more about carcinogenicity than anything
25 else, than other toxic end points, we might reasonably
26 suppose that carcinogenic toxicology is a more developed
27 science than other parts of toxicology. We therefore might
28 plausibly think that animal feeding studies in respect of
29 other end points are even less reliable.
30
31 So, I think the answer is, the relatively brief answer to
32 your question is there have been all too few studies
33 estimating the relative reliability of different kinds of
34 animals; even less has there been the kind of research,
35 which I have long been advocating, which is research
36 intended to estimate the reliability of different kinds of
37 animal studies, and, better still, to develop new kinds of
38 studies which are demonstrably more reliable. So, we know
39 very, very little about the reliability of these studies.
40
41 Q. As regarding when setting ADI's, are they set with
42 reference to results in the most sensitive animal species?
43 A. Not always.
44
45 Q. Should they?
46 A. There is a marked disparity between the theoretical
47 literature in which the ADI concept was defined and the way
48 it is used in practice. All the early definitions said --
49 firstly, all the early definitions said the concept of the
50 ADI should not be used in respect of carcinogens at all.
51 There was then a retreat from that and they decided they
52 would not use it in respect of genotoxic carcinogens and
53 might use it for non-genotoxic carcinogens.
54
55 But normally the rule is supposed to be that the ADI is set
56 by reference to the most sensitive species of those tested,
57 not of all known species, because which species the tests
58 are conducted in is itself something determined at the
59 discretion of those conducting or sponsoring the tests.
60 But, even where we have data in the public domain
