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Hazardous Substance Data Bank (HSDB) (Internet version) 1998. National Library of Medicine, Bethesda MD. Hecht SS, Loy M, Maronpot RR and Hoffman D. 1976. A study of chemical carcinogenesis: comparative carcinogenicity of 5-methylchrysene, benzo(a)pyrene, and modified chrysenes. Cancer Lett 1:147-154. Hemminki K, Randerath K, Reddy MV, Putman KL, Santella RM, Perera FP, Young TL, Phillips DH, Hewer A and Savela K. 1990. Postlabeling and immunoassay analysis of polycyclic aromatic hydrocarbons - adducts of deoxyribonucleic acid in white blood cells of foundry workers. Scand J Work Environ Health 16:158-162. Hoffman D and Wynder EL. 1966. Beitrag zur carcinogen wirkung von dibenzopyrenen. Z Krebsforsch 68:137-149. Howe RB, Crump KS and Van Landingham C 1986. GLOBAL86: a computer program to extrapolate quantal animal toxicity data to low doses. KS Crump and Company, Ruston, LA. International Agency for Research on Cancer (IARC). 1983. Benzo[a]pyrene. In: Polynuclear Aromatic Compounds, Part 1, Chemical, Environmental and Experimental Data. Vol. 32. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. pp. 211-224. International Agency for Research on Cancer (IARC). 1984a. Polynuclear Aromatic Compounds, Part 2, Carbon Blacks, Mineral Oils and Some Nitroarenes. Vol. 33. International Agency for Research on Cancer (IARC). 1984b. Polynuclear Aromatic Compounds, Part 3, Industrial Exposures in Aluminum Production, Coal Gasification, Coke Production, and Iron and Steel Founding. Vol. 34. International Agency for Research on Cancer (IARC). 1985. Polynuclear Aromatic Compounds Part 4, Bitumens, Caoal-Tars and Derived Products, Shale-Oils and Soots. Vol. 35. International Agency for Research on Cancer (IARC). 1987. In: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Vol. Suppl. 7. pp. 42. International Agency for Research on Cancer (IARC). 1989. Summary of final evaluations. In: Diesel and Gasoline Exhausts and Some Nitroarenes. Vol. 46. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. pp. 375. Iwagawa M, Maeda T, Izumi K, Otsuka H, Nishifuji K, Ohnishi Y and Aoki S. 1989. Comparative dose-response study on the pulmonary carcinogenicity of 1,6-dinitropyrene and benzo[a]pyrene in F344 rats. Carcinogenesis 10:1285-1290. 117
Krewski D, Thorslund T and Withey J. 1989. Carcinogenic risk assessment of complex mixtures. Tox Indust Health 5:851-867. Lee BM, Yin BY, Herbert R, Hemminki K, Perera FP and Santella RM. 1991. Immunologic measurement of polycyclic aromatic hydrocarbon-albumin adducts in foundry workers and roofers. Scand J Work Environ Health 17:190-194. Manchester D and Jacoby E. 1984. Decreased placental monoxygenase activities associated with birth defects. Teratology 30:31-37. Miller JA, Sandin RB, Miller EC and Rusch HP. 1955. The carcinogenicity of compounds related to 2- acetylaminofluorene. Cancer Res 15:188-199. National Cancer Institute (NCI) 1978. Bioassay of 5-Nitroacenaphthene for Possible Carcinogenicity. Carcinogenesis Technical Report Series No. 118. NTIS Pub No. PB 287347. U.S. Department of Health, Education and Welfare (DHEW), NCI Carcinogenesis Testing Program, Bethesda, MD. Neal J and Rigdon RH. 1967. Gastric tumors in mice fed benzo[a]pyrene: a quantitative study. Texas Reports Biol Med 25:553-557. Nisbet ICT and LaGoy PK. 1992. Toxic equivalency factors (TEFs) for polycyclic aromatic hydrocarbons (PAHs). Reg Toxicol Pharmacol 16:290-300. Office of Environmental Health Hazard Assessment (<strong>OEHHA</strong>) 1993. Benzo[a]pyrene as a Toxic Air Contaminant. Part B. Health Effects of Benzo[a]pyrene. Air Toxicology and Epidemiology Section, Berkeley, CA. Ovrebo S, Haugen A, Phillips DH and Hewer A. 1992. Detection of polycyclic aromatic hydrocarbon- DNA adducts in white blood cells from coke oven workers: correlation with job categories. Cancer Res 52:1510-1514. Perera FP, Hemminki K, Young TL, Brenner D, Kelly G and Santella RM. 1988. Detection of polycyclic aromatic hydrocarbon-DNA adducts in white blood cells of foundry workers. Cancer Res 48:2288-2291. Perera FP, Tang DL, O'Neill JP and et al. 1993. HPRT and glycophorin mutations in foundry workers: relationship to PAH exposure and to PAH-DNA adducts. Carcinogenesis 14:969-973. Reddy MV, Hemminki K and Randerath K. 1991. Postlabeling analysis of polycyclic aromatic hydrocarbon-DNA adducts in white blood cells of foundry workers. J Toxicol Environ Health 34:177- 185. Rigdon RH and Neal J. 1966. Gastric carcinomas and pulmonary adenomas in mice fed benzo[a]pyrene. Texas Reports Biol Med 24:195-207. 118
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Air Toxics Hot Spots Program Risk A
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Prepared by: John D. Budroe, Ph.D.
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This document is one of five docume
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TABLE OF CONTENTS PREFACE i INTRODU
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N-Nitrosodimethylamine 401 N-Nitros
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Hot Spots Unit Risk and Cancer Pote
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Page 17 and 18:
Additional ATES and PETS documents
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data. If several data sets (dose an
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US EPA Calculation of Carcinogenic
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exposure to a concentration of 1 µ
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incidences for each of the dose lev
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computes the surface area of a sphe
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Comparison of Hot Spots Cancer Unit
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Gold, L., de Veciana, M., Backman,
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Animal Studies Rats Woutersen et al
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ased on sufficient evidence of carc
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ACETAMIDE CAS No: 60-35-5 I. PHYSIC
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Methodology Expedited Proposition 6
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cancer mortality. However, US EPA (
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Table 2. Lung adenoma incidence in
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Table 3 (continued). Acrylamide-ind
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Robinson M, Bull RJ, Knutsen GL, Sh
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Also, a trend was observed correlat
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eported. Cause-specific expected de
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Bio/Dynamics Inc. conducted a study
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examination. Interim sacrifices wer
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Table 8. Tumor incidence in male an
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Gaffey WR and Strauss ME. 1981. A m
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(technical grade; 98% pure) by gava
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International Agency for Research o
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still alive in the low-dose control
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ANILINE CAS No: 62-53-3 I. PHYSICAL
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fibrosarcomas, stromal sarcomas, ca
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ARSENIC (INORGANIC) CAS No: 7440-38
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elationship between arsenic exposur
Page 75 and 76: al. (1988) did not induce lung tumo
Page 77 and 78: A risk assessment was also conducte
Page 79 and 80: Chen C, Chuang Y, You S, Lin T and
Page 81 and 82: Schrauzer G, White D, McGinness J,
Page 83 and 84: Table 1: Summary of epidemiologic s
Page 85 and 86: had at least one animal demonstrati
Page 87 and 88: mesothelioma, recommended lifetime
Page 89 and 90: National Institute for Occupational
Page 91 and 92: BENZENE CAS No: 71-43-2 I. PHYSICAL
Page 93 and 94: Animal Studies Available experiment
Page 95 and 96: Table 3: Summary of NTP bioassay re
Page 97 and 98: Table 4: Summary of benzene low-dos
Page 99 and 100: Maltoni C, Conti B and Cotti G. 198
Page 101 and 102: a benign tumor of the kidney. No ba
Page 103 and 104: al. (1968) found no tumors in lifet
Page 105 and 106: following relationship, where C(t 1
Page 107 and 108: Miakawa M. and Yoshida O. 1975. Pro
Page 109 and 110: human population and that BPDE-DNA
Page 111 and 112: demonstrated the tumor initiating a
Page 113 and 114: Table 4: Bronchoalveolar tumors fro
Page 115 and 116: Table 5: IARC groupings of PAHs, mi
Page 117 and 118: Table 6 (continued): IARC Group 3 P
Page 119 and 120: Potency Equivalency Factors (PEF) f
Page 121 and 122: This was rounded to a PEF of 0.1. 1
Page 123 and 124: experiment (Takayama et al., 1985)
Page 125: Deutsch-Wenzel RP, Brune H, Grimmer
Page 129 and 130: U.S. Environmental Protection Agenc
Page 131 and 132: Sorahan et al. (1983) studied cance
Page 133 and 134: Lijinsky W. 1986. Chronic bioassay
Page 135 and 136: the drinking water (Schroeder and M
Page 137 and 138: Table II. Effective dose, upper-bou
Page 139 and 140: BIS(2-CHLOROETHYL)ETHER CAS No: 111
Page 141 and 142: IV. DERIVATION OF CANCER POTENCY Ba
Page 143 and 144: BIS(CHLOROMETHYL)ETHER CAS No: 542-
Page 145 and 146: Table 1. Bis(chloromethyl)ether-ind
Page 147 and 148: Drew RT, Laskin S, Kuschner M and N
Page 149 and 150: ates for the 1968 U.S. male populat
Page 151 and 152: Table 1: Incidence of primary tumor
Page 153 and 154: IV. DERIVATION OF CANCER POTENCY Ba
Page 155 and 156: National Institute of Occupational
Page 157 and 158: was less than 0.05 when controlling
Page 159 and 160: up period. The final cohort include
Page 161 and 162: If the cadmium-exposed workers incl
Page 163 and 164: on personnel records (20%); (3) eva
Page 165 and 166: were exposed to a continuous (23.5
Page 167 and 168: procedure (NLIN), the parameters we
Page 169 and 170: International Agency for Research o
Page 171 and 172: Two reports were published on cance
Page 173 and 174: Mendel rats, respectively), and sub
Page 175 and 176: Eschenbrenner A and Miller E. 1946.
Page 177 and 178:
III. CARCINOGENIC EFFECTS Human Stu
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cancers, were less than expected. T
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and no cases of cancer (although cl
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There was a statistically significa
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NTP (1982a) also conducted an carci
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Several pathologists have independe
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hepatocellular adenoma/carcinoma tu
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carcinogenic potency may decline in
Page 193 and 194:
Cochrane W, Singh J and Miles W. 19
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North Atlantic Treaty Organization,
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CHLORINATED PARAFFINS (average chai
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ased on dose-response data for beni
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chloroform in drinking water with k
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Overall, the present epidemiologica
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female dogs received toothpaste bas
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Calculated q 1 * values from the ab
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Hogan MD, Chi Py, Hoel DG and Mitch
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Table 1. Study design summary for N
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V. REFERENCES California Environmen
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toluidine. Followup of this subcoho
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feeding studies on by NCI (1979) us
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CHROMIUM (HEXAVALENT) CAS No: 18540
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expected rate may be inflated becau
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Oral Borneff et al. (1968) exposed
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CREOSOTE (COAL TAR-DERIVED) CAS No:
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from an inhalation exposure study (
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U.S. Environmental Protection Agenc
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Table 1. Study design summary for N
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Page 235 and 236:
Table 1. Experimental design for ca
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Hazardous Substance Data Bank (HSDB
Page 239 and 240:
Table 1: Tumor induction in Fischer
Page 241 and 242:
Page 243 and 244:
Table 1. Experimental design of 2,4
Page 245 and 246:
Page 247 and 248:
Additional analysis of these data b
Page 249 and 250:
IV. DERIVATION OF CANCER POTENCY Ba
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Jackson RJ, Greene CJ, Thomas JT, M
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Table 1. Tumor incidence in rats ex
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Girard R, Tolot F, Martin P and Bou
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exposed more than 16 years before t
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interpretation of dose extrapolatio
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1, 1-DICHLOROETHANE CAS No: 75-34-3
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Table 1b. Study design for carcinog
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National Cancer Institute (NCI) 197
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mice, hepatocellular carcinoma inci
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V. REFERENCES California Department
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DAB/day by gavage for the life of t
Page 273 and 274:
2,4-DINITROTOLUENE CAS No: 121-14-2
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Ellis et al.(1979) (also reported b
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Final Statement of Reasons for OAL,
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to the small sample size and short
Page 281 and 282:
In an inhalation study, Torkelson e
Page 283 and 284:
V. REFERENCES American Conference o
Page 285 and 286:
EPICHLOROHYDRIN CAS No: 106-89-8 I.
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espiratory tumors were noted in the
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Table 4. Epichlorohydrin-induced fo
Page 291 and 292:
Konishi Y, Kawabata A, Denda A, Ike
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exposed to arsenicals for 20 months
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espectively (all statistically sign
Page 297 and 298:
ETHYLENE DICHLORIDE CAS No: 107-06-
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Several factors have been suggested
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myelogenous leukemias (4 and 8 year
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statistically significant. CDHS not
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combined with the incidence in the
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incidence of primary brain tumors.
Page 311 and 312:
Table 6 (continued): Organ/Sex Mali
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An Upper 95% Confidence Limit (UCL)
Page 315 and 316:
ETHYLENE THIOUREA (ETU) CAS No: 96-
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male and female rats. Tumor inciden
Page 319 and 320:
FORMALDEHYDE CAS No: 50-00-0 I. PHY
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presented an extension of a previou
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Methodology In developing a spectru
Page 325 and 326:
Casanova M, Morgan KT, Steinhagen W
Page 327 and 328:
Tobe M, Kaneko T, Uchida Y, Kamata
Page 329 and 330:
Table 1. Hexachlorobenzene-induced
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50 pups (F 1 ) of each sex were ran
Page 333 and 334:
Ertürk E, Lambrecht RW, Peters HA,
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Table 1. Liver hepatoma incidence i
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1988). An airborne unit risk factor
Page 339 and 340:
HYDRAZINE CAS No: 302-01-2 I. PHYSI
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Methodology Inhalation A linearized
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LEAD AND LEAD COMPOUNDS (INORGANIC)
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and other occupational carcinogens
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y inhalation is similar for rats an
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Goyer RA. 1992. Nephrotoxicity and
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LINDANE (g-Hexachlorocyclohexane) C
Page 353 and 354:
Using these relationships, a human
Page 355 and 356:
METHYL TERT-BUTYL ETHER (MTBE) CAS
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Tumor incidences according to the r
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kidney changes indicative of chroni
Page 361 and 362:
Interspecies scaling for oral doses
Page 363 and 364:
Table 4 (continued): Dose Response
Page 365 and 366:
Experimental Pathology Laboratories
Page 367 and 368:
Animal Studies Male and female HaM/
Page 369 and 370:
Gold L, Sawyer C, Magaw R, Backman
Page 371 and 372:
Using the statistical tests (one-ta
Page 373 and 374:
Table 1: Methylene chloride-induced
Page 375 and 376:
Significant treatment-related incre
Page 377 and 378:
National Toxicology Program (NTP) 1
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noted; however, the study duration
Page 381 and 382:
Crump KS, Howe RB, Van Landingham C
Page 383 and 384:
Table 1. Michler’s ketone-induced
Page 385 and 386:
NICKEL AND NICKEL COMPOUNDS CAS No:
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the high exposure group was 14.0. A
Page 389 and 390:
male and 121 female rats, was expos
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2.1 - 2.6 × 10 -4 (µg/m 3 ) -1 .
Page 393 and 394:
Page 395 and 396:
The increased incidence of bladder
Page 397 and 398:
A linearized multistage procedure w
Page 399 and 400:
N-NITROSO-N-METHYLETHYLAMINE CAS No
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propylamine in drinking water at 0.
Page 405 and 406:
N-NITROSODIETHYLAMINE CAS No: 55-18
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Table 2. Treatment groups, concentr
Page 409 and 410:
California Department of Health Ser
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animals and the second generation t
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ationale for selection of the OEHHA
Page 415 and 416:
A unit risk value based upon air co
Page 417 and 418:
N-NITROSODIPHENYLAMINE CAS No: 86-3
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Methodology Dosage estimates of NDP
Page 421 and 422:
Crump KS, Howe RB. 1984. The multis
Page 423 and 424:
Table 1. P-Nitrosodiphenylamine-ind
Page 425 and 426:
N-NITROSOMORPHOLINE CAS No: 59-89-2
Page 427 and 428:
Page 429 and 430:
N-NITROSOPIPERIDINE CAS No: 100-75-
Page 431 and 432:
Table 3. N-Nitrosopiperidine-induce
Page 433 and 434:
Crump KS, Howe RB, Van Landingham C
Page 435 and 436:
testicular tumors were noted in the
Page 437 and 438:
PARTICULATE MATTER FROM DIESEL-FUEL
Page 439 and 440:
etired railroad workers who had had
Page 441 and 442:
employment (χ 2 test for trend: p
Page 443 and 444:
elevated smoking-adjusted risk esti
Page 445 and 446:
Table 1 (continued): Reference Miln
Page 447 and 448:
Table 1 (continued): Reference Damb
Page 449 and 450:
Table 1 (continued): Reference Burn
Page 451 and 452:
Table 1 (continued): Reference Raff
Page 453 and 454:
Table 1 (continued): Epidemiologica
Page 455 and 456:
Table 1 (continued): Epidemiologica
Page 457 and 458:
Table 1 (continued): Reference Wegm
Page 459 and 460:
Animal Studies Section 6.1 (Animal
Page 461 and 462:
The variability, or heterogeneity,
Page 463 and 464:
estimate for those studies for whic
Page 465 and 466:
Figure 1: Estimates of Relative Ris
Page 467 and 468:
q 1 * = Excess relative risk × CA
Page 469 and 470:
Table 3: Number of Workers in the E
Page 471 and 472:
u nexposed workers at zero concentr
Page 473 and 474:
for each µg/m 3 of diesel exhaust
Page 475 and 476:
Table 4: Values from Unit Risk for
Page 477 and 478:
their findings that a reasonable es
Page 479 and 480:
Garshick E, Schenker M, Woskie S an
Page 481 and 482:
Lewis T, Green, FH MW, Burg J and L
Page 483 and 484:
Rothman K. 1986. Modern epidemiolog
Page 485 and 486:
PENTACHLOROPHENOL CAS No: 87-86-5 I
Page 487 and 488:
The default lifespan for mice is 10
Page 489 and 490:
documented. An excess risk from ski
Page 491 and 492:
B6C3F 1 mice and F344/N rats were e
Page 493 and 494:
This model, rather than a time depe
Page 495 and 496:
POLYCHLORINATED BIPHENYLS (PCBs) CA
Page 497 and 498:
several benign adenomatous lesions
Page 499 and 500:
Ito et al. (1973) exposed groups of
Page 501 and 502:
could not be characterized by chlor
Page 503 and 504:
exposure (all pathways and mixtures
Page 505 and 506:
National Toxicology Program 1993. T
Page 507 and 508:
Table 1. Potassium bromate-induced
Page 509 and 510:
1,3-PROPANE SULTONE CAS No: 1120-71
Page 511 and 512:
Page 513 and 514:
PROPYLENE OXIDE CAS No: 75-56-9 I.
Page 515 and 516:
oxide. In the NTP carcinogenicity s
Page 517 and 518:
1,1,2,2-TETRACHLOROETHANE CAS No: 7
Page 519 and 520:
assumed a body weight of 70 kg and
Page 521 and 522:
total); an untreated control group
Page 523 and 524:
TOLUENE DIISOCYANATE CAS No: 26471-
Page 525 and 526:
Animal Studies The National Toxicol
Page 527 and 528:
Mortillaro PT and Schiavon M. 1982.
Page 529 and 530:
male or female rats. Increases in h
Page 531 and 532:
TRICHLOROETHYLENE CAS No: 79-01-6 I
Page 533 and 534:
A mortality analysis of a cohort of
Page 535 and 536:
elative to that of the controls whi
Page 537 and 538:
applied or metabolized. The range o
Page 539 and 540:
Katz RM and Jowett D. 1981. Female
Page 541 and 542:
10,000 ppm 2,4,6-trichlorophenol in
Page 543 and 544:
Page 545 and 546:
Bionetics Research Laboratories. 19
Page 547 and 548:
control; females: 6/10 exposed, 0/1
Page 549 and 550:
over controls (p < 0.04). Other tum
Page 551 and 552:
was increased (100/314 exposed vs.
Page 553 and 554:
Table 3. Cancer potency estimates f
Page 555 and 556:
Crouch E. 1983. Uncertainties in in
Page 557 and 558:
VINYL CHLORIDE CAS No: 75-01-4 I. P
Page 559 and 560:
Table 1 (continued): A Summary of E
Page 561 and 562:
al., 1983). Histopathology of all o
Page 563 and 564:
Table 3: Tumor incidences in 100 pp
Page 565 and 566:
experiment, animals were exposed to
Page 567 and 568:
Experiment BT1 Most previous risk a
Page 569 and 570:
No statistical analyses of mortalit
Page 571 and 572:
Table 11 gives unit risk estimates
Page 573 and 574:
Bertazzi PA, Villa A, Foa V, Saia B
Page 575 and 576:
Nicholson WJ, Hammond EC, Seidman H
Page 577 and 578:
immunotoxicity, reproductive toxici
Page 579 and 580:
scheme. TEFs for two major noncance
Page 581 and 582:
NATO/CCMS (1988a) Pilot Study on In
Page 583 and 584:
Table 2 Toxicity Equivalency Factor
Page 585 and 586:
Table 4 A Comparison of CTEF- and I
Page 587 and 588:
Office of Environmental Health Haza
Page 589 and 590:
Group 4: The agent is probably not
Page 591 and 592:
TECHNICAL SUPPORT DOCUMENT FOR DESC
Page 593 and 594:
US EPA IRIS Inhalation Unit Risk an
Page 595 and 596:
TECHNICAL SUPPORT DOCUMENT FOR DESC
Page 597 and 598:
as appropriate, and revise IRIS fil
Page 599 and 600:
Chemical Exposure Route Study Type
Page 601 and 602:
Page 603 and 604:
Page 605 and 606:
Methyl tert-butyl ether p. 5: Added
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