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Table 1. Tumor incidence in yellow mice exposed to γ-HCH (lindane) (Wolff et al., 1987) Dietary Concentration of Tumor Type and Incidence γ-HCH (ppm) Lung Carcinomas Liver Adenomas 0 4/95 8/93 160 18/95 33/94 Thorpe and Walker (1973) showed an increase in liver tumors of male CF1 mice fed 400 ppm lindane for 110 weeks, compared with controls. The time-weighted dose was estimated as 52 mg/kg/day by US EPA (1988). In this experiment, control mice exhibited an incidence of 11/45 for liver tumors, compared to 27/29 for the 52 mg/kg/day group. A study by Goto et al. (1972) showed a positive effect of lindane on cancer in mice. However, this experiment used only 10 animals per treatment group and was of a short duration. The NCI (1977) study on male mice showed a significant increase in cancer incidence in mice exposed to 80, but not 160 ppm γ-HCH. The absence of a clear dose-response precluded this data from use in determining the cancer potency for lindane. IV. DERIVATION OF CANCER POTENCY Basis for Cancer Potency The US EPA (1988) selected the study by Thorpe and Walker (1973) as the basis for the cancer potency for lindane. This was considered to be the best study for development of a cancer potency factor for lindane because of the large sample size of mice surviving for a full lifespan, and the large numbers of tumors in the treatment group. Thorpe and Walker (1973) showed an increase in liver tumors in male CF1 mice fed 400 ppm lindane in the diet for 110 weeks, compared with controls. Control mice exhibited an incidence of 11/45 for liver tumors, compared to 27/29 for the lindanetreated group (p < 0.01). Some lung metastases were also reported in the male and female mice treated with lindane. Methodology A linearized multistage procedure was used to estimate the cancer potency of lindane from the Thorpe and Walker (1973) data in male CF1 mice (Crump et al., 1982). The concentrations of lindane given in the feed were 0 or 160 ppm. The 95% upper confidence bound on the dose-response slope was used to derive the human cancer potency value for lindane. The animal cancer potency, q animal , was calculated from the linear slope using the lifetime scaling factor q animal = q 1 * × (T/T e ) 3 , where T/T e is the ratio of the experimental duration to the lifetime of the animal. An estimated value for the human cancer potency was determined using the relationship q human = q animal × (bw h /bw a ) 1/3 , where bw is the default body weight of human or animal (mouse). 343
Using these relationships, a human cancer potency (q human ) of 1.1 [mg/kg-day] -1 was reported (US EPA, 1987). An airborne unit risk factor of 3.1E-4 (µg/m 3 ) -1 was calculated from the q human value by <strong>OEHHA</strong>/ATES using the default parameters of 70 kg human body weight and 20 m 3 /day breathing rate. V. REFERENCES California Department of Health Services (CDHS). Guidelines for Chemical Carcinogen Risk Assessment and their Scientific Rationale. State of California Health and Welfare Agency, Department of Health Services, 2151 Berkeley Way, Berkeley, CA. 1985. California Department of Health Services (CDHS). 1988. Risk-Specific Intake Levels for the Proposition 65 Carcinogen Technical Grade Hexachlorocyclohexane. Reproductive and Cancer Hazard Assessment Section, Office of Environmental Health Hazard Assessment. 2151 Berkeley Way, Annex 11, Berkeley, CA. Crump KS. 1982. An improved procedure for low-dose carcinogenic risk assessment from animal data. J Environ Path Toxicol 5(2):675-684. Goto M, et al. 1972. Ecological chemistry. Toxizitat von a-HCH in mausen. Chemosphere 1:153. as cited in: California Department of Health Services (CDHS). 1988. Risk-Specific Intake Levels for the Proposition 65 Carcinogen Technical Grade Hexachlorocyclohexane. Reproductive and Cancer Hazard Assessment Section, Office of Environmental Health Hazard Assessment. 2151 Berkeley Way, Annex 11, Berkeley, CA. Hazardous Substances Data Bank (HSDB) 1995. National Library of Medicine, Bethesda, MD (CD- ROM version) Micromedex, Inc., Denver, CO. International Agency for Research on Cancer (IARC). 1987. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Supplement 7. pp.220. National Cancer Institute (NCI). Bioassay of Lindane for Posssible Carcinogenicity (Technical Report Series No. 14), Department of Health, Education, and Welfare Publication No. (NIH) 77-814. 1977. Thorpe E and Walker AIT. 1973. The toxicology of dieldrin (HEOD). II. Comparative long-term oral toxicity studies in mice with dieldrin, DDT, phenobarbitone, β-BHC and γ-BHC. Food Cosmet Toxicol 11:433-442. U.S. Environmental Protection Agency (US EPA). 1987. Health Assessment Document for Beryllium. Office of Health and Environmental Assessment, Washington DC.7-84. 344
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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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U.S. Environmental Protection Agenc
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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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Hazardous Substance Data Bank (HSDB
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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
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
Page 341 and 342: Methodology Inhalation A linearized
Page 343 and 344: LEAD AND LEAD COMPOUNDS (INORGANIC)
Page 345 and 346: and other occupational carcinogens
Page 347 and 348: y inhalation is similar for rats an
Page 349 and 350: Goyer RA. 1992. Nephrotoxicity and
Page 351: LINDANE (g-Hexachlorocyclohexane) C
Page 355 and 356: METHYL TERT-BUTYL ETHER (MTBE) CAS
Page 357 and 358: Tumor incidences according to the r
Page 359 and 360: kidney changes indicative of chroni
Page 361 and 362: Interspecies scaling for oral doses
Page 363 and 364: Table 4 (continued): Dose Response
Page 365 and 366: Experimental Pathology Laboratories
Page 367 and 368: Animal Studies Male and female HaM/
Page 369 and 370: Gold L, Sawyer C, Magaw R, Backman
Page 371 and 372: Using the statistical tests (one-ta
Page 373 and 374: Table 1: Methylene chloride-induced
Page 375 and 376: Significant treatment-related incre
Page 377 and 378: National Toxicology Program (NTP) 1
Page 379 and 380: noted; however, the study duration
Page 381 and 382: Crump KS, Howe RB, Van Landingham C
Page 383 and 384: Table 1. Michler’s ketone-induced
Page 385 and 386: NICKEL AND NICKEL COMPOUNDS CAS No:
Page 387 and 388: the high exposure group was 14.0. A
Page 389 and 390: male and 121 female rats, was expos
Page 391 and 392: 2.1 - 2.6 × 10 -4 (µg/m 3 ) -1 .
Page 393 and 394: U.S. Environmental Protection Agenc
Page 395 and 396: The increased incidence of bladder
Page 397 and 398: A linearized multistage procedure w
Page 399 and 400: N-NITROSO-N-METHYLETHYLAMINE CAS No
Page 401 and 402: 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
Page 475 and 476:
Table 4: Values from Unit Risk for
Page 477 and 478:
their findings that a reasonable es
Page 479 and 480:
Garshick E, Schenker M, Woskie S an
Page 481 and 482:
Lewis T, Green, FH MW, Burg J and L
Page 483 and 484:
Rothman K. 1986. Modern epidemiolog
Page 485 and 486:
PENTACHLOROPHENOL CAS No: 87-86-5 I
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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
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
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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-
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
Page 535 and 536:
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
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
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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
Page 567 and 568:
Experiment BT1 Most previous risk a
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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
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Page 603 and 604:
Page 605 and 606:
Methyl tert-butyl ether p. 5: Added
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