Document rpwVpa2pD3g2j9RpXvkm7RveE

9*uJLuUid BIO-TEST laAotofoue*, Dnc. 1810 FRONTAGE ROAD NORTHBROOK. ILLINOIS 60062 A R A CODE 312 TELEPHONE 272-3030 April 10, 1969 ^ 14 19$$ Mr. Elmer Wheeler Monsanto Company 800 N. Lindbergh Boulevard St, Louis, Missouri 63166 Dear Elmer: I am enclosing a revised protocol for a chicken study with the Aroclors. After much discussion among ourselves, we have concluded that a relatively conventional study should be conducted with the addition of certain specific parameters which might be of importance in reproduction and mineral metabolism. The study has been made flexible at the end to allow for the possibility of mechanistic studies, should these be indicated, based on gross findings. It seems to us irrational to attempt definition of mechanism until we have demon strated an effect. It is our opinion that the studies to elucidate mechanisms, to determine rate of accumulation, and to define no-effect levels for enzyme induction might best be done as separate studies specifically designed for the purpose. Although these Btudies would require the utilization of more refined techniques, the duration of treatment and the numbers of animals required would not be excessive. To attempt to combine all things in one study would introduce massive complications and, in our opinion, would be excessively expensive and wasteful if it should be that the significant effects are not observed with the species selected for study. We have also elected to recommend dietary levels of 1. 0, 10 and 100 ppm. We feel that 100 ppm is high enough since, if effects are not observed at this level, it is probable that the test material does not cause the effect of concern or that the chosen species is unresponsive. DSW 034689 STLCOPCB4018516 Mr. Elmer Wheeler, April 10, 1969 Page 2 Since 2 ppm has already been found to be a no-effect level of DDT for microsomal enzyme induction in rats, we see little virtue in going below 1.0ppm at this stage. If effects are observed at this level, our shorter term mechanistic studies can be confined to lower levels. The mallard duck study would be conducted according to the same protocol except for the change in species. . The cost for these studies, exclusive of Part E and the other detailed studies, would be: Chicken or duck study using 3 dosage levels plus controls One material $ 9,000 Two materials (common controls) 15,750 Three materials (common controls) 22,500 %O(rt>0 Four materials (common controls) 29,250 I am in the process of acquiring more insight into the biochemistry which might be involved, and will develop cost estimates for other studies which might be indicated. We see no cause to modify the fundamental design of the mammalian studies which, in our opinion, should be conducted as classical toxico logical studies to define no-effect levels. We will, however, propose the addition of certain biochemical parameters which might be significant to the overall purpose of the program. I will forward to you our thoughts on this (including consideration of the suggestions of Drs. Mehler and Metcalf) together with revised cost estimates in the very near future. Since duck egg production is somewhat seasonal, the fowl studies should be started soon. Because of the time involved, the chronic feeding studies, and the rat reproduction study should be initiated at an early date. Sincerely yours, OEF/JM Enel. Otis E. Fancher, Ph. D. Director DSM 034690 STLCOPCB4018517