Document jmdg4X89Yax2ZMaDnvpbovgVQ

3/5/87 Don Barnes COMMENTS ON REPRO/DEVELOPMENTAL and IMMUNOTOX 1. I did not review these documents in detail, since I thought the first drafts and the associated discussions were pretty much in hand. 2. Apparently, the repro position has been altered somewhat beyond our previous considerations. This changes seem to be related to hearing testimony (e.g., Bailar and recent data (Abbott). I would like to discuss this information so that I am sure that I understand the arguments -- which appear to be suggestive, rather than definitive. 3. It appears, however, that we end up using the rat data, rather than the monkey data as CDC did. What is the rationale for this selection? 4. We calculate the RfD using a LOAEL/NOAEL and an uncertainty factor of 1000. There is passing reference to an "additional modifying factor" being possible. Why would this be? It might be useful to discuss the RfD concept and its interpretation; i.e., it is not a "line in the dirt" between "acceptable" and "unacceptable". Its "accuracy", is likely to be inversely related to the size of the UF. How does this estimate stack up against the CDC value of #1 pg/kg-d for a comparable quantity? 5. How should one estimate the risk associated with a bolus dose during pregnancy; cf., eating fish? I understand from the page on DEVELOPMENT that an appropriate NOAEL should be 1 ug/kg-d ^in rats, mice and rabbits. What would be the appropriate RfD to use for the human condition? quick glance at the immunotox document suggests that things have not changed much. How about responses to my earlier comments? I note that the somewhat questionable final sentences have been modified...to the better. v