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Kanisawa M and Schroeder H. 1967. Life term studies on the effects of arsenic, germanium, tin, and vanadium on spontaneous tumors in mice. Cancer Res 27:1192-1195. Knoth W. 1966. [Psoriasis vulgaris. Arsenic therapy]. Arch Klin Exp Dermatol 227:228-234. Lee-Feldstein A. 1983. Arsenic and respiratory cancer in humans: follow-up of copper smelter employees in Montana. J Natl Cancer Inst 70:601-609. Lee-Feldstein A. 1986. Cumulative exposure to arsenic and its relationship to respiratory cancer among copper smelter employees. J Occup Med 28:296-302. Mabuchi K, Lilienfeld A and Snell L. 1979. Lung cancer among pesticide workers exposed to inorganic arsenicals. Arch Environ Health 17:312-320. Hazardous Substance Data Bank (HSDB) (Internet version) 1998. National Library of Medicine, Bethesda MD. Ohyama S, Ishinishi N, Hisanaga A and Yamamoto A. 1988. Comparative chronic toxicity, including tumorigenicity, of gallium arsenide and arsenic trioxide intratracheally instilled into hamsters. Appl Organometallic Chem 2:333-337. Osswald H and Goerttler K. 1971. [Arsenic-induced leucoses in mice after diaplacental and postnatal application]. Verh Dtsch Ges Pathol 55:289-293. Ott M, Holder B and Gordon H. 1974. Respiratory cancer and occupational exposure to arsenicals. Arch Environ Health 29:250-255. Pershagen G, Wall S, Taube A and Linnman L. 1981. On the interaction between occupational arsenic exposure and smoking and its relationship to lung cancer. Scand J Work Environ Health 7:302-309. Pershagen G, Nordberg G and Björklund N. 1984. Carcinomas of the respiratory tract in hamsters given arsenic trioxide and/or benzo[a]pyrene by the pulmonary route. Environ Res 34:227-241. Pershagen G and Björklund N. 1985. On the pulmonary tumorigenicity of arsenic trisulfide and calcium arsenate in hamsters. Cancer Lett 27:99-104. Rencher A, Carter M and McKee D.A retrospective epidemiological study of mortality at a large western copper smelter. J Occup Med 19:754-758. Sandstrom A, Wall S and Taube A. 1989. Cancer incidence and mortality among Swedish smelter workers. Br J Ind Med 46:82-89. Schrauzer G and Ishmael D. 1974. Effects of selenium and of arsenic on the genesis of spontaneous mammary tumors in inbred C3H mice. Ann Clin Lab Sci 4:441-447. 71
Schrauzer G, White D, McGinness J, Schneider C and Bell L. 1977. Arsenic and cancer: effects of joint administration of arsenite and selenite on the genesis of mammary adenocarcinoma in inbred female C3H/St mice. Bioinorganic Chem 7:245-253. Sobel W, Bond G, Baldwin C and Ducommun D. 1988. An update of respiratory cancer and occupational exposure to arsenicals. Am J Ind Med 13:263-270. Taylor P, Qiao Y, Schatzkin A, Yao S, Lubin J, Mao B, Rao J, McAdams M, Xuan X and Li J. 1989. Relation of arsenic exposure to lung cancer among tin miners in Yunnan Province, China. Br J Ind Med 46:881-888. Tokudome S and Kuratsune M. 1976. A cohort study on mortality from cancer and other causes among workers at a metal refinery. Int J Cancer 17:310-317. Tseng W. 1977. Effects and Dose--Response Relationships of Skin Cancer and Blackfoot Disease with Arsenic. Environ Health Perspect 19:109-119. Tseng W, Chu H, How S, Fong J, Lin C and Yeh S. 1968. Prevalence of skin cancer in an endemic area of chronic arsenicism in Taiwan. J Natl Cancer Inst 40:453-463. U.S. Environmental Protection Agency (US EPA) 1988. Special Report on Ingested Inorganic Arsenic. Skin Cancer; Nutritional Essentiality. EPA/625/3-87/013. Risk Assessment Forum, US EPA, Washington, DC. U.S. Environmental Protection Agency 1995. Integrated Risk In<strong>format</strong>ion System: Arsenic, inorganic. Office of Research and Development, National Center for Environmental Assessment, Washington, DC. Wall S. 1980. Survival and mortality pattern among Swedish smelter workers. Int J Epidemiol 9:73-87. Welch K, Higgins I, Oh M and Burchfiel C. 1982. Arsenic exposure, smoking, and respiratory cancer in copper smelter workers. Arch Environ Health 37:325-335. Wicklund K, Daling J, Allard J and Weiss N. 1988. Respiratory cancer among orchardists in Washington State, 1968 to 1980. J Occup Med 30:561-564. Wu W. 1988. Occupational cancer epidemiology in the People's Republic of China. J Occup Med 30:968-974. Yue-zhen H, Xu-chun Q, Guo-quan W, Bi-yu E, Dun-ding R, Zhao-yue F, Ji-yao W, Rong-jiang X and Feng-e Z. 1985. Endemic chronic arsenicism in Xinjiang. Chin Med J (Engl) 98:219-222. 72
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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 15 and 16:
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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
Page 29 and 30: Comparison of Hot Spots Cancer Unit
Page 31 and 32: Gold, L., de Veciana, M., Backman,
Page 33 and 34: Animal Studies Rats Woutersen et al
Page 35 and 36: ased on sufficient evidence of carc
Page 37 and 38: ACETAMIDE CAS No: 60-35-5 I. PHYSIC
Page 39 and 40: Methodology Expedited Proposition 6
Page 41 and 42: cancer mortality. However, US EPA (
Page 43 and 44: Table 2. Lung adenoma incidence in
Page 45 and 46: Table 3 (continued). Acrylamide-ind
Page 47 and 48: Robinson M, Bull RJ, Knutsen GL, Sh
Page 49 and 50: Also, a trend was observed correlat
Page 51 and 52: eported. Cause-specific expected de
Page 53 and 54: Bio/Dynamics Inc. conducted a study
Page 55 and 56: examination. Interim sacrifices wer
Page 57 and 58: Table 8. Tumor incidence in male an
Page 59 and 60: Gaffey WR and Strauss ME. 1981. A m
Page 61 and 62: (technical grade; 98% pure) by gava
Page 63 and 64: International Agency for Research o
Page 65 and 66: still alive in the low-dose control
Page 67 and 68: ANILINE CAS No: 62-53-3 I. PHYSICAL
Page 69 and 70: fibrosarcomas, stromal sarcomas, ca
Page 71 and 72: ARSENIC (INORGANIC) CAS No: 7440-38
Page 73 and 74: 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: Chen C, Chuang Y, You S, Lin T and
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 and 126: Deutsch-Wenzel RP, Brune H, Grimmer
Page 127 and 128: Krewski D, Thorslund T and Withey J
Page 129 and 130: U.S. Environmental Protection Agenc
Page 131 and 132:
Sorahan et al. (1983) studied cance
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Lijinsky W. 1986. Chronic bioassay
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the drinking water (Schroeder and M
Page 137 and 138:
Table II. Effective dose, upper-bou
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BIS(2-CHLOROETHYL)ETHER CAS No: 111
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IV. DERIVATION OF CANCER POTENCY Ba
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BIS(CHLOROMETHYL)ETHER CAS No: 542-
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Table 1. Bis(chloromethyl)ether-ind
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Drew RT, Laskin S, Kuschner M and N
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ates for the 1968 U.S. male populat
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Table 1: Incidence of primary tumor
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National Institute of Occupational
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was less than 0.05 when controlling
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up period. The final cohort include
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If the cadmium-exposed workers incl
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on personnel records (20%); (3) eva
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were exposed to a continuous (23.5
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procedure (NLIN), the parameters we
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International Agency for Research o
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Two reports were published on cance
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Mendel rats, respectively), and sub
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Eschenbrenner A and Miller E. 1946.
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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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Methodology Expedited Proposition 6
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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
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Page 243 and 244:
Table 1. Experimental design of 2,4
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Methodology Expedited Proposition 6
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Additional analysis of these data b
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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
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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)
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ETHYLENE THIOUREA (ETU) CAS No: 96-
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male and female rats. Tumor inciden
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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
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Tobe M, Kaneko T, Uchida Y, Kamata
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Table 1. Hexachlorobenzene-induced
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50 pups (F 1 ) of each sex were ran
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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
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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
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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
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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
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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
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Table 1. Michler’s ketone-induced
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NICKEL AND NICKEL COMPOUNDS CAS No:
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the high exposure group was 14.0. A
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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.
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N-NITROSODIETHYLAMINE CAS No: 55-18
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Table 2. Treatment groups, concentr
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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
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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
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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
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etired railroad workers who had had
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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
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Table 1 (continued): Reference Damb
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Table 1 (continued): Reference Burn
Page 451 and 452:
Table 1 (continued): Reference Raff
Page 453 and 454:
Table 1 (continued): Epidemiologica
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Table 1 (continued): Epidemiologica
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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
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q 1 * = Excess relative risk × CA
Page 469 and 470:
Table 3: Number of Workers in the E
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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
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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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