Document kGe9bMB0kJMDb2jVLqekX7yb

RUG-12-1992 16:19 FROM TO 912164476459 P.04 r UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, O.C. 20460 FILE COPY tetTeet} mtoi toasTANct* Dr. Kenneth olden Director, National Toxicology Program P.O. Sox 12233 Research Triangle Park, NO 27702 Dear Dr.Oldens The National Toxicology Progress (NT?) bee responsibility tor developing the Annual Report on carcinogens, a liet of eubstanees that are either Xnovn >r reasonably antictpatad to be human carcinogens. Given the general lack of adequate information in humans to ispact these determinations, the bulk of the chemicals listed are based upon cancer findings in experimental animals, where the underlying premise is that agsnte that produca cancer in animals ars likely to do eo in humans* Although it is reasonebls to presume that animal carcinogans are human carcinogens, the position it rebuttable. Mechanistic and expocurs information may modulate significantly the case for human carcinogenicity, several of the ehemicele listed in the 6th Annual Report demonstrate the problem with relying exclusively on animal tumor studies. Some of them include the following* (1) butylated hydroxyanisole, nltrilotriecetic acid and saccharin seem to cause tumors et laboratory doses associated with target organ toxicity and far beyond expeeted human exposure; (2) chloroform production of hepatic end renal tumors is greatly effected by specific pharmacokinetic consideratlone; (3) diethylhexylphthaiate may produce tumors by processes not relevant to humane; end (4) iron dextran complex may present e hazard from parenteral exposure but should pose little or none via dermal, inhalation and oral axpoaure. Although these caaee do not necessarily demonstrate the absence of any human cancer potential, they illustrate the complexities that ere part of such decisions and point to the problems of using animal cancer data alone. nn7Too AUG 12 '92 15=06 BFG27345 PAGE.004 1 AUG-12-1992 16:20 FROM TO 912164476459 p.05 2 Without developing appreciation of the uncertainties for human eancer potential for etch chemical in the htEcrt, the naive reader is forced to conclude that ell listed substances have the sane hazard potential, certainly that is not the case. Likewise, the listing of chemicals in the BtpgCti has implications for potential regulatory action by states and certain federal authorities. Therefore, ve urge you to produce acre analytical evaluations of listed chemicals. This Agency has learned over the years the importance of going beyond the animal cancer studies in making hazard determinations, and the International Agency for Research on Cancer is beginning to recognise the significance of mechanistic information in their classification decisions. Wo urge tha HTP to do likewise. Implementing these recommendations are in keeping with your laudable desire to strengthen the National Toxicology Program by conducting mechanistic studies to augment results from chronic studies and make outputs more meaningful to regulatory agencies and the public. Sincerely, Deputy Assistant Administrator Office of Prevention, pesticides and Toxic Substances ' william H. Farland, PbT*. Director, office of Health and environmental.Assessment Office of Research and Development 38X2002 AUG 12 '92 15=07 BFG27346 TOTAL p.05 PAGE.005