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Hazardous Substance Data Bank (HSDB) (Internet version) 1998. National Library of Medicine, Bethesda MD. National Research Council (NRC) 1986. Environmental tobacco smoke. Measuring exposures and assessing health effects. National Academy Press, Washington, DC. 1-12, 223-249. Netterström B. 1988. Cancer incidence among urban bus drivers in Denmark. Int Arch Occup Environ Health 61:217-221. Nielsen P, Andreassen Å, Farmer P, Ovrebo S and Autrup H. 1996. Biomonitoring of diesel exhaustexposed workers. DNA and hemoglobin adducts and urinary 1-hydroxypyrene as markers of exposure. Toxicol Lett 86:27-37. Nikula K, Snipes M, Barr E, Griffith W, Henderson R and Mauderly J. 1995. Comparative pulmonary toxicities and carcinogenicities of chronically inhaled diesel exhaust and carbon black in F344 rats. Fundam Appl Toxicol 25:80-94. Nokso-Koivisto P and Pukkala E. 1994. Past exposure to asbestos and combustion products and incidence of cancer among Finnish locomotive drivers. Occup Environ Med 51:330-334. Office of Environmental Health Hazard Assessment (<strong>OEHHA</strong>) 1998. Proposed Identification of Diesel Exhaust as a Toxic Air Contaminant. Part B: Health Risk Assessment for Diesel Exhaust. Air Toxicology and Epidemiology Section, Berkeley, CA. Pepelko WE PW. 1983. Health effects of exposure to diesel engine emissions: a summary of animal studies conducted by the US Environmental Protection Agency’s Health Effects Research Laboratories at Cincinnati, Ohio. Journal of the American College of Toxicology 2:253-306. Petitti DB. 1994. Meta-analysis, decision analysis, and cost-effectiveness analysis. In: Methods for Quantitative Synthesis in Medicine. Monographs in Epidemiology and Biostatistics. Vol. 24. Oxford University Press, New York, pp. 15-20, 90-114. Pfluger D and Minder C. 1994. A mortality study of lung cancer among Swiss professional drivers: accounting for the smoking related fraction by a multivariate approach. Soz Praventivmed 39:372-378. Pott F and Heinrich U. 1990. Relative significance of different hydrocarbons for the carcinogenic potency of emissions from various incomplete combustion processes. In: Complex mixtures and cancer risk. Vol. Scientific publication 104. Vainio H, Sorsa M and McMichael A, eds. Lyon, France, pp. 288-297. Raffle P. 1957. The health of the worker. Br J Ind Med 14:73-80. Rafnsson V and Gunnarsdottir H. 1991. Mortality among professional drivers. Scand J Work Environ Health 17:312-317. 473
Rothman K. 1986. Modern epidemiology. Little, Brown and Company, Boston. p. 19. Rushton L, Alderson M and Nagarajah C. 1983. Epidemiological survey of maintenance workers in London Transport Executive bus garages and Chiswick Works. Br J Ind Med 40:340-345. Sawyer R and Johnson J. 1995. Diesel emissions and control technology. In: Diesel exhaust: a critical analysis of emissions, exposure, and health effects. A special report of the Institute’s Diesel Working Group. Health Effects Institute (HEI), Cambridge, MA, pp. 65-82. Sera N, Fukuhara K, Miyata N and Tokiwa H. 1994. Detection of nitro-azabenzo[a]pyrene derivatives in the semivolatile phase originating from airborne particulate matter, diesel and gasoline vehicles. Mutagenesis 9:47-52. Siemiatycki J, Gerin, SP SP, Nadon L, Dewar R and Richardson L. 1988. Associations between several sites of cancer and ten types of exhaust and combustion products. Scand J Work Environ Health 14:79-90. Steenland N, Silverman D and Hornung R. 1990. Case-control study of lung cancer and truck driving in the Teamsters Union. Am J Public Health 80:670-674. Steenland K, Silverman D and Zaebst D. 1992. Exposure to diesel exhaust in the trucking industry and possible relationships with lung cancer. Am J Ind Med 21:887-890. Stöber W and Abel U. 1996. Lung cancer due to diesel soot particles in ambient air? A critical appraisal of epidemiological studies addressing this question. Int Arch Occup Environ Health 68:S3- S61. Swanson G, Lin C and Burns P. 1993. Diversity in the association between occupation and lung cancer among black and white men. Cancer Epidemiol Biomarkers Prev 31:313-320. Takemoto K, Yosimura H and Katayama H. 1986. Effects of chronic inhalation exposure to diesel exhaust on the development of lung tumors in di-isopropanol-nitrosamine-treated F344 rats and newborn C57Bl and ICR mice. In: Carcinogenic and mutagenic effects of diesel engine exhaust. Ishinishi N, Koizumi A, McClellan R and Stöber W, eds. Elsevier Science Publishers, Amsterdam, pp. 311- 327. U.S. Environmental Protection Agency (US EPA) 1994. Health Assessment Document for Diesel Emissions. EPA/600/8-90/057BA. Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Research Triangle Park, NC. US Department of Health and Human Services (DHHS) 1989. Reducing the health consequences of smoking. 25 years of progress. A report of the Surgeon General. DHHS, Washington, DC. p. 39. Waller R. 1981. Trends in lung cancer in London in relation to exposure to diesel fumes. Environment International 5:479-483. 474
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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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Table 1. Experimental design for ca
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Hazardous Substance Data Bank (HSDB
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Table 1: Tumor induction in Fischer
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Table 1. Experimental design of 2,4
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Additional analysis of these data b
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Jackson RJ, Greene CJ, Thomas JT, M
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Table 1. Tumor incidence in rats ex
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Girard R, Tolot F, Martin P and Bou
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exposed more than 16 years before t
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interpretation of dose extrapolatio
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1, 1-DICHLOROETHANE CAS No: 75-34-3
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Table 1b. Study design for carcinog
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National Cancer Institute (NCI) 197
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mice, hepatocellular carcinoma inci
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V. REFERENCES California Department
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DAB/day by gavage for the life of t
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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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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-
Page 431 and 432: Table 3. N-Nitrosopiperidine-induce
Page 433 and 434: Crump KS, Howe RB, Van Landingham C
Page 435 and 436: testicular tumors were noted in the
Page 437 and 438: PARTICULATE MATTER FROM DIESEL-FUEL
Page 439 and 440: 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
Page 447 and 448: Table 1 (continued): Reference Damb
Page 449 and 450: Table 1 (continued): Reference Burn
Page 451 and 452: Table 1 (continued): Reference Raff
Page 453 and 454: Table 1 (continued): Epidemiologica
Page 455 and 456: Table 1 (continued): Epidemiologica
Page 457 and 458: 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
Page 471 and 472: 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: Lewis T, Green, FH MW, Burg J and L
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: IV. DERIVATION OF CANCER POTENCY Ba
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
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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
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
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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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