Abstract: Exposure levels, noncancer effect s and su scep t ib ility facto rs can all be assessed in hum an s expo sed to envi2 ronm en tal carcinogen s. A dded to the vast arm am en tarium of t radit ional b iom arkers cu rren t ly availab le fo r these purpo ses are novel ones con stan t ly em erging f rom the rap idly develop ing areas of tox icogenom ics and p ro2 teom ics. The b iom arker arm am en tarium w ill be b rief ly review ed. T ran sit ional studies w ill even tually validate (o r fail to validate) each b iom arker fo r it s in tended app licat ion. O nce validated, b iom arkers of expo su re, effect and su scep t ib ilitym ay be u sed to relate studies in hum an popu lat ion s to tox ico logical evaluat ion s in test an im als fo r the pu rpo se of u sing the non2cancer endpo in t s in hum an s to bet ter def ine the hum an cancer risk. The N at ional Research Council’s paradigm fo r the induct ion of cancer by geno tox ic chem icals po rt rays the step s in the p rogression to m alignancy f rom ex ternal expo su re to f inal cancer p roduct ion. The in term ediate step s in the p rogression are in ternal do se, b io logically effect ive do se, early b io logical effect s and altered st ruc2 tu re and funct ion. These m ay all be m easu red by b iom arker respon ses, con st itu t ing the noncancer data that m ay be u sed fo r mode of act ion modeling and hum an cancer risk assessm en t. Comparison s of these endpo in betw een test an im als and hum an s, w ich cancer ou tcom es being assessed in the fo rm er, relate the endpo in t s cancer ou tcom es. A n examp le app licat ion of hum an b iom arker data to the cancer risk assessm en t p rocess w ill be con sidered u sing resu lt s of recen t studies of the chem ical agen t 1, 32bu tadiene (BD). BD is an impo rtan t, h igh2p roduct ion indu st rial chem ical. It is a po ten t carcinogen in m ice bu t m uch less so in rat s. Ep idem io logical studies in hum an wo rkers indicate an ino rease in leukem ia bu t the resu lt s are open to in terp retat ion. Fo r th is reason, BD w as classif ied by the In ternat ional A gency fo r Cancer Research ( IARC) as a“p robab le hum an carcinogen”(Class 2A ) bo th in 1992 and on reevaluat ion in 1999. The elect roph ilic m etabo lites of BD are unquest ionab ly geno tox ic in all species. BD’s roden t carcinogen i2 city, therefo re, has a geno tox ic mode of act ion. The elect roph ilic m etabo lites of BD are p roduced in v ivo w ith differen t eff iciencies in the differen t species, suggest ing that their rates of p roduct ion m ay determ ine the rela2 t ive carcinogen ic po tencies of BD. There is an abundance of non tumo r data, i. e. b iom arker respon ses, in m ice, rat s and hum an s that are in2 fo rm at ive as to the comparat ive m etabo lism and geno tox icity of BD. These w ill be review ed. Sub set s of these data have been ob tained under comparab le condit ion s in all th ree species, allow ing the direct comparison of re2 su lt s. These comparat ive resu lt s w ill be p resen ted in detail. In b rief, in th is sub set of studies, the mou se and rat expo su re BD concen t rat ion s ranged f rom 3 to 1, 250 ppm , w h ile the h ighest m ean hum an occupat ional expo2 su re w as～ 0. 8 ppm (eigh t2hou r t im e w eigh ted average). Desp ite these differences in ex ternal expo su re levels, there w as overlap in the concen t rat ion s of hemoglob in adduct s of BD m etabo lites betw een the hum an s and the reden t s at the low er expo su re levels. M easu rem en t s of u rinary concen t rat ion s of the differen t BD m etabo lites show ed clear differences in the detox if icat ion pathw ays u sed by the th ree species, w ith con jugat ion p redom inat2 ing in m ice and hydro lysis in hum an s. O f greatest relevance, the geno tox ic po tency of BD expo su re by inhala2 t ion w asm uch greater in m ice that in rat s, and no geno tox icity asm an ifest by increases in H PR T m u tat ion s in lymphocytesw ere seen in hum an s. These sub set comparison sw ill be con sidered in the con tex t of the overallBD b iom arker dataset. D irect ion s fo r fu tu re studies w ill be ou t lined and ten tat ive conclu sion s draw n.