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Dement JM, Harris RL, Symons MJ and Shy C. 1982. Estimates of dose-response for respiratory cancer among chrysotile asbestos textile workers. Ann Occup Hyg 26:869-87. Dement JM, Harris RL, Symons MJ and Shy CM. 1983a. Exposures and mortality among chrysotile asbestos workers. Part I: exposure estimates. Am J Ind Med 4:399-419. Donham KJ, Berg JW, Will LA and Leininger JR. 1980. The effects of long-term ingestion of asbestos on the colon of F344 rats. Cancer 45:1073-1084. Donna A. 1970. [Experimental tumors induced by chrysotile, crocidolite and amosite asbestos in Sprague-Dawley rats] (Ital.). Med Lav 61:1. Finkelstein MM. 1983. Mortality among long-term employees of an Ontario asbestos-cement factory. Br J Ind Med 40:138-44. Gross P, de Treville RTP, Tolker EB, Kaschak M and Babyak MA. 1967. Experimental asbestosis. The development of lung cancer in rats with pulmonary deposits of chrysotile asbestos dust. Arch Environ Health 15:343-355. Hammond EC, Selikoff IJ and Seidman H. (1979). Asbestos exposure, cigarette smoking and death rates. Ann NY Acad Sci 330:473-90. Henderson VL and Enterline PE. (1979). Asbestos exposure: factors associated with excess cancer and respiratory disease mortality. Ann NY Acad Sci 330:117. International Agency for Research on Cancer (IARC). 1977. Asbestos. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. Vol. 14. International Agency for Research on Cancer, Lyon, France. Maltoni C and Annoscia C. 1974. Mesotheliomas in rats following the intraperitoneal injection of crocidolite. In: Advances in Tumour Prevention, Detection, and Characterization. Vol 1: Characterization of Human Tumours. Davis W and Maltoni C, eds. Excerpta Medica, Amsterdam, pp. 115. McConnell EE, Rutter HA, Ulland BM and Moore JA. (1983b). Chronic effects of dietary exposure to amosite asbestos and tremolite in F344 rats. Environ Health Perspect 53:27-44. McConnell EE, Shefner AM, Rust JH and Moore JA. 1983a. Chronic effects of dietary exposure to amosite and chrysotile asbestos in Syrian golden hamsters. Environ Health Perspect 53:11-25. McDonald AD, Fry JS, Woolley AJ and McDonald JC. (1984). Dust exposure and mortality in an American chrysotile asbestos friction products plant. Br J Ind Med 41:151-57. McDonald JC, Liddell FDK, Gibbs GW, Eyssen GE and McDonald AD. (1980). Dust exposure and mortality in chrysotile mining, 1910-75. Br J Ind Med 37:11-24. 79
National Institute for Occupational Safety and Health (NIOSH) 1994. NIOSH Pocket Guide to Chemical Hazards. Washington, DC. Hazardous Substance Data Bank (HSDB) (Internet version) 1998. National Library of Medicine, Bethesda MD. National Research Council Committee on Nonoccupational Health Risks of Asbestiform Fibers (NRC). 1984. Asbestiform Fibers. Nonoccupational Health Risks. National Academy Press, Washington D.C. National Toxicology Program (NTP) 1985. Toxicology and Carcinogenesis Studies of Chrysotile Asbestos (CAS No. 12001-29-5) in F344/N Rats (Feed Studies). TR295. Research Triangle Park, NC. Newhouse ML and Berry G. (1979). Patterns of mortality in asbestos factory workers in Longdon. Ann NY Acad Sci 330:53-60. Nicholson WJ. 1985. Asbestos Health Effects Update. U.S. Environmental Protection Agency, Washington, DC. Nicholson WJ, Selikoff IJ, Seidman H, Lilis R and Formby P. 1979. Long-term mortality experience of chrysotile miners and millers in Thetford Mines, Quebec. Ann NY Acad Sci 330:11-21. Ontario Royal Commission 1984. Report of the Royal Commission on Matters of Health and Safety Arising from the Use of Asbestos in Ontario. Ontario Ministry of Government Services, Publication Services Branch, Toronto, Ontario, Canada. Peto J. 1980a. Lung cancer mortality in relation to measured dust levels in an asbestos textile factory. In: Biological Effects of Mineral Fibres. Wagner JC, ed. International Agency for Research on Cancer (IARC), Lyon, France, pp. 829-36. Peto J. 1980b. The incidence of pleural mesothelioma in chrysotile asbestos textile workers. In: Biological Effects of Mineral Fibres. Wagner JC, ed. International Agency for Research on Cancer (IARC), Lyon, France, pp. 703-11. Pott F, Friedrichs KH and Huth F. 1976. Results of animal experiments concerning the carcinogenic effect of fibrous dusts and their interpretation with regard to the carcinogenesis in humans. Zentralbl Bakteriol [Orig B] 162:467-505. Pott F, Huth F and Friedrichs KH. 1972. Tumors of rats after i.p. injection of powdered chrysotile and benzo(a)pyrene. Zentralbl Bakteriol [Orig B] 155:463-469. Pylev LN and Shabad LM. 1973. Some results of experimental studies in asbestos carcinogenesis. In: Biological Effects of Mineral Fibres. Bogovski P, Timbrell V, Gilson JD and Wagner JC, eds. Sci. Pub. No. 30. International Agency for Research on Cancer (IARC), Lyon, France, pp. 99. 80
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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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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
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 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: mesothelioma, recommended lifetime
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
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
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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
Page 237 and 238:
Hazardous Substance Data Bank (HSDB
Page 239 and 240:
Table 1: Tumor induction in Fischer
Page 241 and 242:
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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
Page 249 and 250:
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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
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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
Page 327 and 328:
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
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
Page 349 and 350:
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
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
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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
Page 383 and 384:
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 .
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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
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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
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
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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
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
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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
Page 467 and 468:
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
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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