Day 039 - 20 Oct 94 - Page 75
1
2 Q. Then we find monkeys?
3 A. Yes.
4
5 Q. Something called cynomogus monkeys, whatever they may be?
6 A. Yes.
7
8 Q. Then may we read the conclusion, Comments, on the
9 right-hand side on page 17. This is JECFA, who shortly go
10 to recommend an ADI of 0.5 mg/kg: "Studies have been
11 conducted that provide additional information on the
12 proliferative changes observed in the forestomach of rats
13 fed BHA. No new studies on the effect of BHA on the
14 stomach and oesophagus of species that do not have a
15 forestomach, e.g., pigs or monkeys, were conducted. The
16 data show that continuous exposure of the rat forestomach
17 to 2% BHA in the diet for 6-12 months is necessary to
18 produce squamous cell carcinoma. The data also show that
19 the induction of mild hyperplasia can occur at levels of
20 0.125% of BHA in the diet but not at a level of 0.1% BHA.
21 After reevaluating the data in pigs, it was concluded that
22 the evidence that BHA produces hyperplasia in the esophagus
23 of the pig is questionable. Moreover, these presumptive
24 effects in pigs were reported to occur at levels of BHA
25 significantly higher than those that produced the confirmed
26 effects in the rat forestomach. Considering the absence of
27 any significant adverse effects in two dog studies, it was
28 concluded that further investigations in animals without
29 forestomachs are not required. The human relevance of the
30 rat studies, while inherently questionable because the
31 target tissue in the rat has no human counterpart, cannot
32 readily be ignored. Based on the dose dependence and
33 reversibility of the lesions produced in the rat, discussed
34 previously in the 1986 monograph ... and since confirmed by
35 more recent studies, it was concluded that an ADI can be
36 established."
37
38 Now that I have read that, Dr. Millstone, do you still
39 assert that the ADI proposed by this body was irresponsibly
40 high?
41 A. Oh, I certainly do and I would be happy to go through
42 that paragraph sentence by sentence and indicate precisely
43 where my doubts and concerns lie, if you would like me to
44 do that?
45
46 Q. I think you had better do it because then we can put this
47 away until tomorrow.
48 A. OK. "Studies have been conducted", OK. No new
49 studies on the effect of species that do not have a stomach
50 were conducted. Now, clearly, the initial tumours reported
51 by Ito et al in the rats were in rat forestomachs.
52 Elsewhere in the body of this document they state that the
53 tissue in the humans which most closely resembles the rat
54 forestomach is the oesophagus, and imply elsewhere that it
55 -- several things; firstly, it is important to look at
56 species that do not have forestomachs and that, insofar as
57 we are looking for lesions that might be triggered by BHA
58 in tissue similar to the forestomach, the oesophagus would
59 be the place to look, but studies in species that do not
60 have forestomachs were not conducted. "No new studies were
