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· Undertake occupational studies of persons exposed to high concentrations of PAHs. These studies would record detailed information on job histories and smoking habits of all persons studied, so that the effects attributable to occupational PAR exposure and cigarette-smoking could be assessed. · Study the relationship of PAH measurements to the various defined job categories. A studied control group (non-PAH-exposed) must be included. 9-5 ~ . - .. .
To answer these questions, developed for detecting PAH me antibod ies . Such as says would metabolite-DNA adduct formatio ~ , r ~ 0 -~~ ~ ~ such as the lung, after in vivo experimental exposure to PAHs, especially low-dose, long-term exposure. With appropriately designed cell-model systems that use various cell types, the relationship of in vivo repair of PAH metabolite-DNA adducts should be examined and an activity profile developed for the individual known active PAHs. Animals other than mice and rats should be used to examine PAH metabolite-DNA adduct formation and the mechanisms by which phenolic antioxidants and inducers of aryl hydrocarbon hydroxylase (AHH) inhibit the formation of adducts. more sensitive and specific assays must be tabolite-DNA adducts, e.g., with monoclonal be used to determine rates of PAH n in individual cell tvoes and in organs Can the PAH metabolite-DNA systems be quantified and further developed for use in monitoring exposure to specific PAHs? The feasibility of using adducts as a measure of effective biologic dose should be studied for low-dose extrapolation of bioassay findings to dose-response curves that show the rate of adduct formation and its relationship to PAH-induced neoplasia in animal-model systems. The importance of the findings will depend on a careful analysis of the background concentrations of PAM-DNA adducts in tissues--i.e., "noise." HUMAN STUD IE S Obviously, all health-related research findings are useful in improving the protection of human health. Although research that uses human beings directly poses difficult problems,.there are various kinds of human studies that avoid those problems. For instance, human tissues can be used to study the relationship of specific biotransformations of PAHs to findings of carcinogenicity in animals. To determine the PAH dose absorbed from human lung tissue, there is a need to know-the chemical form and binding of PAHs on particles, particle size, composition, clearance rates, and ultimate fate of inhaled particle-adsorbed PAHs. These findings would be essential in studying the relationship of formation of PAR metabolite-DNA adducts and the incidences of adverse health effects found in animal studies. Progress in understanding research findings could be greatly improved if an "inventory" of PAHs identified and measured in normal and diseased human tissues could be developed. Perhaps samples of appropriate tissues could be analyzed specifically for this purpose, and biologic and historical information on the donors could be accumulated. The tissue profiles of PAH metabolite-DNA adducts or other indicators could be compared with those derived from environmental sampling or air monitoring. The findings ;n this report show that a high fraction of human exposure to PAHs is attributable to dietary intake. The possible relationship of ingested PAHs to increased incidences of gastrointestinal (or other) malignancies should be included in epidemiologic analyses.
APPEND IX A LISTS OF POLYCYCLIC AROMATIC HYDROCARBONS lhis appendix consists of four tables. The first is an alphabetical list of polycyclic aromatic hydrocarbons (PAHs) di.sc,~ssed in the report and close chemical relatives, with molecular formulas and CAS numbers . The second is a list of structural formulas (ordered according to structural complex- ity) and ratings of carcinogenic activity; these ratings indicate only relative activity. The third table lists nitro- arenes that have been detected in particulate extracts of diesel exhaust, and the fourth shows their structural formulas. A-1
TABLE A- 1 Polycyclic Aromatic Hydrocarbons and Related Compounds: 1\Iolecular Formulas and CAS Numbers Name Molecular Formula CAS No. . . Acenaptlthylene C 12H8 208-96-8 Acephenanthrylene C16Hlo 201-06-9 Acr~d~ne C13HgN 260-94-6 Anthanthrene see Dibenzo~def,mno~chrysene Anthracene C14H10 120-12-7 9,10-Anthracenedione C14H~O2 84-65-1 9~10H)-Anthracenone C14HloO 90-44-8 Anthraquinone see 9,10-Anthracenedione Anthrone see 9~10_~-Anthracenone Benz[elacephenanthrylene C20H12 205-99-2 Benz[c]acridine C17Hll 225-51-4 Benz~alanthracene Cl8H12 56-55-3 7H-Benz~deJanthracen-7-one C17HloO 82-05-3 Benzanthrone see 7H-Benz~deJanthracen-7-one Benzotb~chrysene C22H14 214-17-5 Benzotc~chrysene C22H14 194-69-4 Benzo~g~chrysene C22H14 196-78-1 Benzotc~cinnoline C12H8N2 230-17-1 Benzota~dibenzothiophene see Benzotbinaphthot2,1-d] thiophene Benzotbifluoranthene see Benz~eJacephenanthrylene Benzotghilfluoranthene ClgHlo ~ 203-12-3 Benzo~jlfluoranthene C20H12 205-82-3 Benzo~k~fluoranthene C20H12 207-08-9 llH-Benzofa~fluorene 017H12 238-84-6 11~-Benzotbifluorene C17Hl2 243-17-4 7~-Benzotc~fluorene C17Hl2 205-12-9 Benzoth~nap~tho[1,2-fJquinolene C21Hl3 196-79-2 8enzo !6 ~ naphthof2,l-d~thiophene C16Hlo 239-35-0 Benzotrst~pentaphene C24H14 189-55-9 Benzo~ghi~perylene C22H12 191-24-2 Benzotclphenanthrene Cl8H12 195-19-7 Benzota~pyrene C20H12 -50-32-8 Benzo~elpyrene C20H12 192-97-2 Benzo~flquinoline Cl3H9 85-02-9 Benzoth~quinoline C13Hg 230-27-3 Benzotbitriphenylene C22H14 215-58-7 Biphenylene C12Hg 259-79-0 9H-Carhazole C12H9 86-74-8 Chrysene C18H12 218-01-9 Coronene C24H12 . 191-07-1 4H-Cyclopenta~def]phenanthrene C15H10 203-64-5 Cyclopenta[cd~pyrene C18Hlo 27208-37-3 Dibenz[a,6]acridine C21Hl3 226-36-8 Dibenz~a,j]acridine C21Hl3 224-42-0 Dibenz[c,h]acridine C2lHl3 224-53-3 A-2 ~....
Table A-1 (continued) Name Molecular Fonmula CAS No. Dibenz~a,c~anthracene see Benzotb~triphenylene Dibenz~a,h~anthracene C22H14 53-07-3 D~benz~a,J]anthracene C22H14 224-41-9 7H-Dibenzota,gicarbazole C20H13 207-84-1 13H-Dibenzo~a,iicarbazole C20H13 239-64-5 7H-Dibenzotc,gicarbazole C20H13 194-59-2 Dibenzo~b,defichrysene C24H14 189-64-0 Dibenzo~def,mnoichrysene C22H.12 191-26-4 Dibenzo~def,p~chrysene C24H14 191-30-0 Dibenzotb,h~phenanthrene see Pentaphene Dibenzo~a,e~pyrene see Naphthot1,2,3,4-def~chrysene Dibenzota,h~pyrene see Dibenzotb,def~chrysene Dibenzota,i~pyrene see Benzotrst~pentaphene Dibenzota,l~pyrene see Dibenzo~def,p~chrysene Dibenzothiophene C12H8S 132-65-0 Fluoranthene C16Hlo 206-44-0 9H-Fluorene C13H10 86-73-7 9H-Fluoren-9-one C13H8° 484-25-9 Indenot1,2,3-cd~pyrene C22H12 - 193-39-5 lH-Indole C8H7N 120-72-9 Isoquinoline CgH7N 119-65-3 Naphthacene C18H12 92-24-0 Naphthalene ClOH8 ~ 91-20-3 Naphthot1,2, 3,4-clef ~ chrysene C24H14 192-65-4 Naphtho[2, 3-f ~ quinol ine C17Hll 224-98-6 Pentaphene C22H14 222-93-5 Perylene C20H12 198-55-0 lH-Phenalene C13H10 203-80-5 Phenanthraquinone see 9,10-Phenanthrenedione Phenanthrene C14H10 85-01-8 9,10-Phenanthrenedione C14HgO2 84-11-7 Phenanthridine C13HgN 229-87-8 1,10-Phenanthroline C12HgN2 66-71-7 Phenanthrot4,5-bcd~thiophene C14HgS 30796-92-0 Phenazine C12HgN2 92-82-0 Phenazone see Benzotcicinnoline Picene C22H14 213-46-7 Pyrene C16Hlo 129-00-0 Quinoline CgH7N 91-22-5 Triphenylene C18H12 217-59-4 9H-Xanthene C13HloO 92-83-1 A-3 ~;
TABLE A-2 Polycyclic Aromatic Hydrocarbons and Related Compounds: Structural Formulas, Molecular Weights, and Carcinogenic Activity Structural Formula Name Molecular Carcinogenic Weight Activitya 7 H lH-Indole 117.0578 0 4 8 1 6~13 Quinoline 129.0578 5 4 8 1 7X12 Isoquinoline ~ 129.0578 0 5 4 8 1 6W~J3 Naphthalene 128.0626 0 !5 4 I. ~ 8~):`3 7~4 6 S Acenaphthylene 152.0626 0 8 1 7~2 Biphenylene 152.0626 NA 5 ~ A-4