Cancer risk estimation for mixtures of coal tars and benzo(a)pyrene.
Two-year chronic bioassays were conducted by using B6C3F1 female mice fed several concentrations of two different mixtures of coal tars from manufactured gas waste sites or benzo(a)pyrene (BaP). The purpose of the study was to obtain estimates of cancer potency of coal tar mixtures, by using conventional regulatory methods, for use in manufactured gas waste site remediation. A secondary purpose was to investigate the validity of using the concentration of a single potent carcinogen, in this case benzo(a)pyrene, to estimate the relative risk for a coal tar mixture. The study has shown that BaP dominates the cancer risk when its concentration is greater than 6,300 ppm in the coal tar mixture. In this case the most sensitive tissue site is the forestomach. Using low-dose linear extrapolation, the lifetime cancer risk for humans is estimated to be: Risk < 1.03 x 10(-4) (ppm coal tar in total diet) + 240 x 10(-4) (ppm BaP in total diet), based on forestomach tumors. If the BaP concentration in the coal tar mixture is less than 6,300 ppm, the more likely case, then lung tumors provide the largest estimated upper limit of risk, Risk < 2.55 x 10(-4) (ppm coal tar in total diet), with no contribution of BaP to lung tumors. The upper limit of the cancer potency (slope factor) for lifetime oral exposure to benzo(a)pyrene is 1.2 x 10(-3) per microgram per kg body weight per day from this Good Laboratory Practice (GLP) study compared with the current value of 7.3 x 10(-3) per microgram per kg body weight per day listed in the U.S. EPA Integrated Risk Information System.
Gaylor
D W
DW
National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
Culp
S J
SJ
Goldstein
L S
LS
Beland
F A
FA
D000818:Animals; D001564:Benzo(a)pyrene / Q000009:adverse effects*; D001835:Body Weight; D002273:Carcinogens / Q000009:adverse effects*; D003033:Coal Tar / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D005260:Female; D005740:Gases; D006801:Humans; D015994:Incidence; D007220:Industrial Waste / Q000009:adverse effects*; D008175:Lung Neoplasms / Q000139:chemically induced; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D015203:Reproducibility of Results; D012306:Risk; D018570:Risk Assessment; D013274:Stomach Neoplasms / Q000139:chemically induced; D014481:United States; D014484:United States Environmental Protection Agency
D002273:Carcinogens; D005740:Gases; D007220:Industrial Waste; D001564:Benzo(a)pyrene; D003033:Coal Tar