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Methodology A linearized multistage procedure (CDHS, 1985) was applied to male Wistar rat forestomach papilloma and carcinoma incidence data (Konishi et al., 1980). US EPA (1984) lists the half-life of ECH in water as 0.69 days. Assuming first order decay due to hydrolysis, this corresponds to an average concentration throughout the day of 63% of the concentration of the freshly prepared solution. The control, low, mid and high dose groups were reported to have received cumulative doses of 0, 5.0, 8.9 and 15.1 grams (Konishi et al., 1980); however, these data do not compensate for hydrolysis loss of ECH. CDHS (1988) estimated the actual daily exposures after hydrolysis compensation for the low, mid and high dose groups to be 15.1, 31.9 and 76.1 mg/kg-day, respectively. This assumes a body weight of 400 grams for a control Wistar rat, and utilizes the body weight data supplied by Konishi et al. (1980) which indicated that the low, mid and high dose animals weighed 7.7, 22.4 and 44.9% less than the controls, respectively. Upper 95% confidence bounds on carcinogenic potency (q 1 * ) were estimated using the incidences of forestomach tumors in animals surviving to the end of the study (81 weeks) and the above dose estimates. Estimates of lifetime potency values (q animal ) were calculated from the q 1 * derived from the 81 week study using the relationship q animal = q 1 * * (104/81) 3 . Estimates for q animal of 0.015 and 0.011 (mg/kg-day) -1 were obtained for the benign squamous cell papillomas and malignant squamous cell carcinomas, respectively. The fitted dose response functions associated with these potency estimates exhibited significant upward curvature (p = 0.03). Surface area scaling was employed to transform animal cancer potency factors to human cancer potency factors, using the relationship (q human = q animal * (bw h / bw a ) 1/3 ), where q human is the human potency, q animal is the animal potency, and bw h and bw a are the human and animal body weights, respectively. Human carcinogenic potency values (q human ) of 0.08 and 0.06 mg/kg-day -1 were derived from the q animal values for benign squamous cell papillomas and malignant squamous cell carcinomas, respectively. A unit risk factor was calculated by <strong>OEHHA</strong>/ATES from the benign squamous cell papilloma data-derived q human value using a reference human body weight of 70 kg and an inspiration rate of 20 m 3 /day. V. REFERENCES California Department of Health Services (CDHS) 1985. Guidelines for Chemical Carcinogen Risk Assessment and Their Scientific Rationale. CDHS, Health and Welfare Agency, Sacramento, CA. California Department of Health Services (CDHS) 1988. Proposition 65 Risk-Specific Levels: Epichlorohydrin. Reproductive and Cancer Hazard Assessment Section, Office of Environmental Health Hazard Assessment. Hazardous Substance Data Bank (HSDB) 1994. National Library of Medicine, Bethesda MD (CD- ROM Version). Micromedix, Inc., Denver CO, Edition 22. Henschler D, Elsässer H, Romen W and Eder E. 1984. Carcinogenicity study of trichloroethylene, with and without epoxide stablizers, in mice. J Cancer Res Clin Oncol 107:149-156. 281
Konishi Y, Kawabata A, Denda A, Ikeda T, Katada H, Maruyama H and Higashiguchi R. 1980. Forestomach tumors induced by orally administered epichlorohydrin in male Wistar rats. Gann 71:922- 923. Laskin S, Sellakumar AR, Kuschner M, Nelson N, La Mendola S, Rusch GM, Katz GV, Dulak NC and Albert RC. 1980. Inhalation carcinogenicity of epichlorohydrin in noninbred Sprague-Dawley rats. J Natl Cancer Inst 65:751-757. Tassignon JP, Bos GD, Craigen AA, Jacquet B, Kueng HL, Lanouziere-Simon C, and Pierre C. 1983. Mortality in an European cohort occupationally exposed to epichlorohydrin (ECH). Int. Arch Occup Environ Health 51:325-336. U.S. Environmental Protection Agency 1984. Health Assessment Document for Epichlorohydrin. EPA/600/8-83-032F. Environmental Criteria And Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Research Triangle Park, NC. Van Duuren BL, Goldschmidt BM, Katz C, Seidman I and Paul JS. 1974. Carcinogenic activity of alkylating agents. J Natl Cancer Inst 53:695-700. Wester PW, Van der Heijden CA, Bisschop A and Van Esch GJ. 1985. Carcinogenicity study with epichlorohydrin (CEP) by gavage in rats. Toxicol 36:325-339. 282
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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
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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
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al. (1988) did not induce lung tumo
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A risk assessment was also conducte
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Chen C, Chuang Y, You S, Lin T and
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Schrauzer G, White D, McGinness J,
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Table 1: Summary of epidemiologic s
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had at least one animal demonstrati
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mesothelioma, recommended lifetime
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National Institute for Occupational
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BENZENE CAS No: 71-43-2 I. PHYSICAL
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Animal Studies Available experiment
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Table 3: Summary of NTP bioassay re
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Table 4: Summary of benzene low-dos
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Maltoni C, Conti B and Cotti G. 198
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a benign tumor of the kidney. No ba
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al. (1968) found no tumors in lifet
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following relationship, where C(t 1
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Miakawa M. and Yoshida O. 1975. Pro
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human population and that BPDE-DNA
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demonstrated the tumor initiating a
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Table 4: Bronchoalveolar tumors fro
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Table 5: IARC groupings of PAHs, mi
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Table 6 (continued): IARC Group 3 P
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Potency Equivalency Factors (PEF) f
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This was rounded to a PEF of 0.1. 1
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experiment (Takayama et al., 1985)
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Deutsch-Wenzel RP, Brune H, Grimmer
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Krewski D, Thorslund T and Withey J
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U.S. Environmental Protection Agenc
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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
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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
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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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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
Page 241 and 242: Hazardous Substance Data Bank (HSDB
Page 243 and 244: Table 1. Experimental design of 2,4
Page 245 and 246: Methodology Expedited Proposition 6
Page 247 and 248: Additional analysis of these data b
Page 249 and 250: IV. DERIVATION OF CANCER POTENCY Ba
Page 251 and 252: Jackson RJ, Greene CJ, Thomas JT, M
Page 253 and 254: Table 1. Tumor incidence in rats ex
Page 255 and 256: Girard R, Tolot F, Martin P and Bou
Page 257 and 258: exposed more than 16 years before t
Page 259 and 260: interpretation of dose extrapolatio
Page 261 and 262: 1, 1-DICHLOROETHANE CAS No: 75-34-3
Page 263 and 264: Table 1b. Study design for carcinog
Page 265 and 266: National Cancer Institute (NCI) 197
Page 267 and 268: mice, hepatocellular carcinoma inci
Page 269 and 270: V. REFERENCES California Department
Page 271 and 272: DAB/day by gavage for the life of t
Page 273 and 274: 2,4-DINITROTOLUENE CAS No: 121-14-2
Page 275 and 276: Ellis et al.(1979) (also reported b
Page 277 and 278: Final Statement of Reasons for OAL,
Page 279 and 280: 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.
Page 287 and 288: espiratory tumors were noted in the
Page 289: Table 4. Epichlorohydrin-induced fo
Page 293 and 294: exposed to arsenicals for 20 months
Page 295 and 296: espectively (all statistically sign
Page 297 and 298: ETHYLENE DICHLORIDE CAS No: 107-06-
Page 299 and 300: Several factors have been suggested
Page 301 and 302: U.S. Environmental Protection Agenc
Page 303 and 304: myelogenous leukemias (4 and 8 year
Page 305 and 306: statistically significant. CDHS not
Page 307 and 308: combined with the incidence in the
Page 309 and 310: incidence of primary brain tumors.
Page 311 and 312: Table 6 (continued): Organ/Sex Mali
Page 313 and 314: An Upper 95% Confidence Limit (UCL)
Page 315 and 316: ETHYLENE THIOUREA (ETU) CAS No: 96-
Page 317 and 318: male and female rats. Tumor inciden
Page 319 and 320: FORMALDEHYDE CAS No: 50-00-0 I. PHY
Page 321 and 322: presented an extension of a previou
Page 323 and 324: 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
Page 331 and 332: 50 pups (F 1 ) of each sex were ran
Page 333 and 334: Ertürk E, Lambrecht RW, Peters HA,
Page 335 and 336: Table 1. Liver hepatoma incidence i
Page 337 and 338: 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
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Using these relationships, a human
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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
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Interspecies scaling for oral doses
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Table 4 (continued): Dose Response
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Experimental Pathology Laboratories
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Animal Studies Male and female HaM/
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Gold L, Sawyer C, Magaw R, Backman
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Using the statistical tests (one-ta
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Table 1: Methylene chloride-induced
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Significant treatment-related incre
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National Toxicology Program (NTP) 1
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noted; however, the study duration
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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 .
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The increased incidence of bladder
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A linearized multistage procedure w
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N-NITROSO-N-METHYLETHYLAMINE CAS No
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Hazardous Substance Data Bank (HSDB
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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
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N-NITROSODIPHENYLAMINE CAS No: 86-3
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Methodology Dosage estimates of NDP
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Crump KS, Howe RB. 1984. The multis
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Table 1. P-Nitrosodiphenylamine-ind
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N-NITROSOMORPHOLINE CAS No: 59-89-2
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N-NITROSOPIPERIDINE CAS No: 100-75-
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Table 3. N-Nitrosopiperidine-induce
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Crump KS, Howe RB, Van Landingham C
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testicular tumors were noted in the
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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
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elevated smoking-adjusted risk esti
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Table 1 (continued): Reference Miln
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Table 1 (continued): Reference Damb
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Table 1 (continued): Reference Burn
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Table 1 (continued): Reference Raff
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Table 1 (continued): Epidemiologica
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Table 1 (continued): Epidemiologica
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Table 1 (continued): Reference Wegm
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Animal Studies Section 6.1 (Animal
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The variability, or heterogeneity,
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estimate for those studies for whic
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Figure 1: Estimates of Relative Ris
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q 1 * = Excess relative risk × CA
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Table 3: Number of Workers in the E
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u nexposed workers at zero concentr
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for each µg/m 3 of diesel exhaust
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Table 4: Values from Unit Risk for
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their findings that a reasonable es
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Garshick E, Schenker M, Woskie S an
Page 481 and 482:
Lewis T, Green, FH MW, Burg J and L
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Rothman K. 1986. Modern epidemiolog
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PENTACHLOROPHENOL CAS No: 87-86-5 I
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The default lifespan for mice is 10
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documented. An excess risk from ski
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B6C3F 1 mice and F344/N rats were e
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This model, rather than a time depe
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POLYCHLORINATED BIPHENYLS (PCBs) CA
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several benign adenomatous lesions
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Ito et al. (1973) exposed groups of
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could not be characterized by chlor
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exposure (all pathways and mixtures
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National Toxicology Program 1993. T
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Table 1. Potassium bromate-induced
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1,3-PROPANE SULTONE CAS No: 1120-71
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Page 513 and 514:
PROPYLENE OXIDE CAS No: 75-56-9 I.
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oxide. In the NTP carcinogenicity s
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1,1,2,2-TETRACHLOROETHANE CAS No: 7
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assumed a body weight of 70 kg and
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total); an untreated control group
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TOLUENE DIISOCYANATE CAS No: 26471-
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Animal Studies The National Toxicol
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Mortillaro PT and Schiavon M. 1982.
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male or female rats. Increases in h
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TRICHLOROETHYLENE CAS No: 79-01-6 I
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A mortality analysis of a cohort of
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elative to that of the controls whi
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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
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control; females: 6/10 exposed, 0/1
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over controls (p < 0.04). Other tum
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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
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Table 1 (continued): A Summary of E
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al., 1983). Histopathology of all o
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Table 3: Tumor incidences in 100 pp
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experiment, animals were exposed to
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Experiment BT1 Most previous risk a
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No statistical analyses of mortalit
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Table 11 gives unit risk estimates
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Bertazzi PA, Villa A, Foa V, Saia B
Page 575 and 576:
Nicholson WJ, Hammond EC, Seidman H
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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
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Table 4 A Comparison of CTEF- and I
Page 587 and 588:
Office of Environmental Health Haza
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Group 4: The agent is probably not
Page 591 and 592:
TECHNICAL SUPPORT DOCUMENT FOR DESC
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US EPA IRIS Inhalation Unit Risk an
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TECHNICAL SUPPORT DOCUMENT FOR DESC
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as appropriate, and revise IRIS fil
Page 599 and 600:
Chemical Exposure Route Study Type
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Page 603 and 604:
Page 605 and 606:
Methyl tert-butyl ether p. 5: Added
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