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1,4-DICHLOROBENZENE CAS No: 106-46-7 I. PHYSICAL AND CHEMICAL PROPERTIES (From HSDB, 1995) Molecular weight 147.01 Boiling point 174°C Melting point 53.1°C Vapor pressure 10 mm Hg @ 25°C Air concentration conversion 1 ppm = 6 mg/m 3 II. HEALTH ASSESSMENT VALUES Unit Risk Factor: 1.1 E-5 (µg/m 3 ) -1 Slope Factor: 4.0 E-2 (mg/kg-day) -1 [Calculated from a cancer potency factor derived by CDHS (1988)] III. CARCINOGENIC EFFECTS Human Studies There are several case reports of human leukemia associated with occupational exposure to chlorinated benzenes, including 1,4 - dichlorobenzene (1,4-DCB) (Girard et al., 1969). One case of chronic lymphocytic leukemia involved exposure to a solvent mixture of 80% ortho-, 2% meta-, and 15% paradichlorobenzene. The association between leukemia and 1,4 - dichlorobenzene exposure was confounded by multiple chemical exposure. Animal Studies Loeser and Litchfield (1983) conducted a chronic inhalation carcinogenicity bioassay in male and female Alderly Park rats. In this study, groups of 76-79 rats were exposed to 0, 75, or 500 ppm p-DCB 5 hours/day, 5 days/week for 76 weeks. Control rats exhibited a high mortality rate and did not differ significantly from treated rats in overall tumor incidence (Table 1) or in the incidence of animals with multiple tumors and malignant tumors. 243
Table 1. Tumor incidence in rats exposed to 1,4-dichlorobenzene (DCB) in air for 76 weeks (Loeser and Litchfield, 1983) Concentration of 1,4-DCB Combined Tumors (males) Combined Tumors (females) 0 ppm 39/60 55/61 75 ppm 31/60 54/61 500 ppm 35/60 53/58 A parallel experiment was conducted using groups of 75 Swiss mice of either sex (Loeser and Litchfield, 1983). In this experiment, female mice were exposed to 0, 75, or 500 ppm 1,4 – DCB for 5 hours/day, 5 days/week, for 57 weeks. A similar experiment in male mice was terminated due to high mortality due to fighting and respiratory infections. As with the rats, no significant increase in any tumor type was detected. The National Toxicology Program (NTP, 1987) studied the carcinogenicity of 1,4 - DCB in male and female F344 rats and B6C3F1 mice via chronic (103 week) oral intubation. Male rats were given 0, 150, or 300 mg/kg 1,4 - DCB for 5 days/week for 103 weeks. Male and female mice, and female rats were given 0, 300, or 600 mg/kg for the same duration. Sentinel animals were killed periodically to test for infectious pathogenic agents. The survival of male rats given 300 mg/kg was significantly lower than controls after 97 weeks, but the survival of treated female rats was unchanged from controls. The timeweighted average doses in the study were 0, 214, and 428 mg/kg/day for the mice, and 0, 107, and 214 mg/kg/day for the rats. Male rats treated with 1,4-DCB displayed nephropathy and mineralization and hyperplasia of renal tubules. The incidence of renal tubular adenocarcinomas was also dosedependently increased in the male rats (1/50, 3/50, or 7/50 for the 0, 107, or 214 mg/kg groups, respectively). A significant dose-dependent increase in the incidence of mononuclear cell leukemia (5/50, 7/50, or 11/50 for the 0, 107, or 214 mg/kg groups, respectively) was observed in the male rats. Additionally, an increasing trend in the incidence of mesothelioma was observed in the male rats (1/50, 0/50, 4/50, for the 0, 107, or 214 mg/kg groups, respectively). Mice of both sexes exposed to 1,4 - DCB had significantly increased incidence of hepatocellular adenomas and carcinomas (NTP, 1987). In addition, four male mice exposed to 428 mg/kg were found to have hepatoblastomas, a rare hepatocellular carcinoma. The incidence of follicular thyroid cell adenomas was increased in female mice exposed to 428 mg/kg (p < 0.038). As with the male rats, male mice showed evidence of kidney tubule damage when treated with 1,4 - DCB. Females were not similarly affected. NTP concluded from these data that 1,4 - DCB was carcinogenic to male rats, but not female rats. In addition, NTP concluded that the increased incidence of hepatocellular adenomas and carcinomas was evidence of carcinogenicity in male and female mice. 244
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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
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
Page 249 and 250: IV. DERIVATION OF CANCER POTENCY Ba
Page 251: Jackson RJ, Greene CJ, Thomas JT, M
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 and 290: Table 4. Epichlorohydrin-induced fo
Page 291 and 292: Konishi Y, Kawabata A, Denda A, Ike
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
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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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U.S. Environmental Protection Agenc
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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
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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
Page 495 and 496:
POLYCHLORINATED BIPHENYLS (PCBs) CA
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several benign adenomatous lesions
Page 499 and 500:
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
Page 505 and 506:
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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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-
Page 525 and 526:
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
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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
Page 573 and 574:
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
Page 585 and 586:
Table 4 A Comparison of CTEF- and I
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Office of Environmental Health Haza
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Group 4: The agent is probably not
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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
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Chemical Exposure Route Study Type
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Page 603 and 604:
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Methyl tert-butyl ether p. 5: Added
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