Document jm2LDkqKzQqmEb55M5eXkX2YR

AUG-12-1992 16=19 FROM TO 912164476459 P.04 r 1 1 uNrrEO spates environmental protection agency ' WASHINGTON, OX. Z0*0 FILE COPY C ^Tieecs AXITCutf *** Or* Kenneth Olden Direeter# National Toxicology Program p.o. box mss Research Triangle Park# KC 27709 Dear or* olden * The National Toxicology Program (NTP) has rasponsibility tor developing the Annual Report on ciret^ogewg. % liat of substance* that are either known pr reasonably anticipated to be human carcinogens- Given the general leek of adequate information in humans to impact these determinations# the bulk of the chemicals listed are based upon cancer findings in experimental animals# where the underlying premise is that agents that produce cancer in animal# are likely to do so in humans* Although it is reasonable to presume that animal carcinogens are human carcinogens# the position is rebuttable, mechanistic and exposure information may modulate significantly the case for human carcinogenicity* several of the chemicals listed in the 6th ymuqi Report demonstrate the problem with relying exclusively on animal tumor studies* Some of them include the following! (i) butylated hydroxyanisole# nltrllotriacetie sold and saccharin seem to cause tumors at laboratory doses associated with target organ toxicity and far beyond expected human exposure; (2) chloroform production of hepatic and renal tumors is greatly affected by specific pharmacokinetic considerations; (9) diethylhexylphthalate may produce tumors by processes not relevant to humans; and (4) Iron dextrsn complex may present a hazard from parenteral exposure but Should pose little or none via dermal. Inhalation and oral exposure* Although these cases do not necessarily demonstrate the absence of any human cancer potential# they illustrate the complexities that are part of such decisions and point to the problems of using animal cancar data alone. UO0T8F; AUG 12 '92 15=06 BFG27345 PAGc.004 AUG-i2-i9S2 16;20 Q 9i2:S4476459 p_as Without developing eon* appreciation or the uncertainties Cor human cancer potential tor each chemical in the fttcfiss* the naive reader is forced to conclude that til listed substaneei have the same hazard potential* Certainly that la not the case Likewise, the listing of chemical* in the Report has implication for potential regulatory action by states and certain federal authorities* Therefore, ve urge you to produce more analytical evaluations of listed chemicals. This Agency has learned over the years the importance of going beyond the animal cancer studies in maxing hazard determinations, and the International Agency for Research on Cancer la beginning to recognise the significance of mechanistic information in their classification decisions* We urge the HTP to do llkevise. 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 maxe outputs mors meaningful to regulatory agancies and the public* Sincerely, Victor J. Mkim* Deputy Assistant Administrator Office of Prevention, Pesticides and Toxic Substances ' William H* Farland, PhTD. Director, office of Health and Environmental. Assessment Office of Research and Development z o o z is e , BFG27346 TT TOTAL P,05 PAGE.005