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Table 1. Tumors induced in B6C3F 1 mice by gavage administration of chlorinated paraffins (NTP, 1986) Dose (mg/kg bw) Hepatocellular adenomas Hepatocellular adenomas and carcinomas Alveolar/bronchiolar carcinomas Thyroid follicular-cell tumors Males 0 11/50 20/50 0/50 125 20/50 34/50 3/50 250 29/50 38/50 6/50 Females 0 0/50 3/50 8/50 125 18/50 22/50 12/49 250 22/50 28/50 13/49 Table 2. Tumors induced in Fischer 344 rats by gavage administration of chlorinated paraffins (NTP, 1986) Dose (mg/kg bw) Hepatocellular carcinomas Hepatocellular adenomas and carcinomas Mononuclear cell leukemia Thyroid follicular-cell tumors Males 0 0/50 0/50 7/50 312 10/50 13/50 12/50 625 16/48 16/50 14/50 Females 0 0/50 0/50 0/50 312 4/50 5/50 6/50 625 7/50 7/50 6/50 IV. DERIVATION OF CANCER POTENCY Basis for Cancer Potency Results of the NTP (1986) gavage study of chlorinated paraffins in male and female B6C3F 1 mice and F344 rats are listed in Gold et al. (1990). Benign and malignant liver tumors were observed in both sexes and species; significant elevations in tumor incidences at other sites were also observed. Estimates of cancer potency are similar for male and female mice and male rats. Cancer potency is 189
ased on dose-response data for benign and malignant liver tumors in female mice (see Table 1) (<strong>OEHHA</strong>, 1992). Methodology Expedited Proposition 65 methodology (with cross-route extrapolation) was used to derive a cancer potency factor. A unit risk factor was then calculated by <strong>OEHHA</strong>/ATES from the cancer potency factor using a reference human body weight of 70 kg and an inspiration rate of 20 m 3 /day. V. REFERENCES California Environmental Protection Agency (Cal/EPA) 1992. Expedited Cancer Potency Values and Proposed Regulatory Levels for Certain Proposition 65 Carcinogens. Office of Environmental Health Hazard Assessment, Reproductive and Cancer Hazard Assessment Section, Berkeley, CA. Gold L, Slone T, Backman G, Eisenberg S, Da Costa M, Wong M, Manley N and Ames, B. 1990. Third chronological supplement to the Carcinogenic Potency Database; Standardized results of animal bioassays published through December 1986 and by the National Toxicology Program through June 1987. Environ Health Perspect 84:215-285. Hazardous Substance Data Bank (HSDB) 1994. National Library of Medicine, Bethesda MD (CD- ROM Version). Micromedix, Inc., Denver CO, Edition 22. National Toxicology Program (NTP) 1986. Toxicology and Carcinogenesis Studies of Chlorinated Paraffins (C12, 60% Chlorine) in F344/N Rats and B6C3F 1 Mice (Gavage Studies). Technical Report Series No. 308. NIH Publication No. 86-2564. U.S. Department of Health and Human Services, NTP, Research Triangle Park, NC. 190
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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
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
Page 179 and 180: cancers, were less than expected. T
Page 181 and 182: and no cases of cancer (although cl
Page 183 and 184: There was a statistically significa
Page 185 and 186: NTP (1982a) also conducted an carci
Page 187 and 188: Several pathologists have independe
Page 189 and 190: hepatocellular adenoma/carcinoma tu
Page 191 and 192: carcinogenic potency may decline in
Page 193 and 194: Cochrane W, Singh J and Miles W. 19
Page 195 and 196: North Atlantic Treaty Organization,
Page 197: CHLORINATED PARAFFINS (average chai
Page 201 and 202: chloroform in drinking water with k
Page 203 and 204: Overall, the present epidemiologica
Page 205 and 206: female dogs received toothpaste bas
Page 207 and 208: Calculated q 1 * values from the ab
Page 209 and 210: Hogan MD, Chi Py, Hoel DG and Mitch
Page 211 and 212: Table 1. Study design summary for N
Page 213 and 214: V. REFERENCES California Environmen
Page 215 and 216: toluidine. Followup of this subcoho
Page 217 and 218: feeding studies on by NCI (1979) us
Page 219 and 220: CHROMIUM (HEXAVALENT) CAS No: 18540
Page 221 and 222: expected rate may be inflated becau
Page 223 and 224: Oral Borneff et al. (1968) exposed
Page 225 and 226: CREOSOTE (COAL TAR-DERIVED) CAS No:
Page 227 and 228: from an inhalation exposure study (
Page 229 and 230: U.S. Environmental Protection Agenc
Page 231 and 232: Table 1. Study design summary for N
Page 233 and 234: Methodology Expedited Proposition 6
Page 235 and 236: 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: 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
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Page 251 and 252:
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
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In an inhalation study, Torkelson e
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V. REFERENCES American Conference o
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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
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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.
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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
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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
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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
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
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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
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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
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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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