Benzene exposure is well demonstrated as a cause of acute myelogenous leukemia, but not of chronic myelogenous leukemia. Previous literature reviews based on case series and cohort studies have not shown an association. We have now conducted a literature search for case–control studies that examine the association between benzene exposure and chronic myelogenous leukemia. Six case–control studies have been found. These derive from occupational groups, cancer registries, and a clinical laboratory. Their exposure ascertainments are all based on job histories, job-exposure matricies, or industrial hygiene data. The odds ratios (ORs) for individual studies range from 0.73 to 1.2. The pooled OR is 1.003 with 95% confidence interval (CI) of 0.94–1.07 (p = 0.98) for both a fixed effects model and a random effects model. The case–control literature indicates that chronic myelogenous leukemia does not appear to be related to benzene exposure.

4561 We conducted a cross-sectional epidemiological study of skin cancer and other skin lesions (keratoses and dyspigmentation) among 3,719 residents exposed to inorganic arsenic from drinking water from 184 wells in three villages in Huhhot, Inner Mongolia, China. The study area came to the attention of medical personnel, because of an unusually high number of requests for dermatological medications. The study population received complete dermatological examinations and provided life histories of well usage. The Chinese government measured arsenic levels in a nationwide survey. Geological processes, not industrial or agricultural sources, accounted for the arsenic. Arsenic levels ranged from non-detectable ( 35% of the study population ingested well waters with peak arsenic concentrations of

We examined the overall results of 124 consecutive rodent carcinogenesis assays carried out at the maximum tolerated dose on 37 chemicals reported recently by the Toxicology Program of the United States. In 31 experiments each in male and female F-344 rats and in male and female B6C3F1 mice, tumor increases and decreases occurred in 41 and 46% of the experiments, respectively. In 22 experiments both increases and decreases in tumor incidence were reported. Of the experiments with decreases in tumor incidence, about 70% were associated with lower body weights of the treated animals. However, of the 30 chemicals producing some tumor decreases, 12 showed decreases in some experiments without any association with bodyweight. Ten chemicals that were Salmonella positive produced increases and decreases in tumor incidences and three produced only decreases in tumor incidence. If it is considered that the bioassay provides information relevant to the carcinogenic potential of a chemical, then logically it must also be considered that information about the cancer-preventive potential of a chemical is provided. When a chemical causes increases and decreases in tumors, several questions follow. First, which are more relevant to the health of an exposed individual: tumor increases or tumor decreases? Second, should such a chemical be stigmatized as a "carcinogen," in view of all the legal and economic implications that ensue from such a label? Third, how should one define a carcinogen?

During the American College of Toxicology's Symposium on Endocrine Modulators (Valley Forge, PA, November 1996), the speakers evaluated relevant scientific information and discussed three general ideas, as follows: (1) The available epidem iological data are inconsistent with significant increases in observed human health effects that might relate to the modulation of the endocrine system. (2) Environm ental contarn in ants have produced toxic effects in wildlife at specific locations. In select instances, the adverse effects observed may involve modulation of endocrine pathways. (3) Additional research focused on endocrine modulation is desirable in order to address this issue within a sound, scientificframework.

Recent events have drawn attention to the hypothesis that some xenobiotics in the environment may elicit toxicities in humans by modulating endocrine pathways. From the perspective of regulatory toxicology, pursuit of this hypothesis w ill prove difficult, because current risk assessment m ethods do not readily apply to substances with very high potencies, reversibility, transgener-ational effects, and subtle biological outcomes. Such xenobiotics typically persist in the body and bioaccumulate in the food chain. Yet the exposures are important only during critical periods of vulnerability, and no sustained bio-markers of these important exposures currently exist. This article describes some recent efforts by federal agencies to pursue the hypothesis, including research planning and screening of potential endocrine modulating xenobiotics and risk assessment of dioxin conflicts with its policy for substances that cause thyroid follicular carcinomas.

Risk AnalysisVolume 18, Issue 1 p. 1-2 The Dose—Response Model for Dioxin Daniel M. Byrd III, Daniel M. Byrd III Federal Focus, Inc. Washington, D.C.Search for more papers by this authorDonald O. Allen, Donald O. Allen Department of Pharmacology University of South Carolina School of Medicine Columbia, South CarolinaSearch for more papers by this authorRobert L. Beamer, Robert L. Beamer Department of Basic Pharmaceutical Sciences College of Pharmacy University of South Carolina Columbia, South CarolinaSearch for more papers by this authorHenry R. Besch Jr., Henry R. Besch Jr. Department of Pharmacology and Toxicology School of Medicine Indiana University Indianapolis, IndianaSearch for more papers by this authorDavid B. Bylund, David B. Bylund Department of Pharmacology College of Medicine The University of Nebraska Omaha, NebraskaSearch for more papers by this authorJohn Doull, John Doull Department of Pharmacology, Toxicology and Therapeutics University of Kansas Medical Center Kansas City, KansasSearch for more papers by this authorWilliam W. Fleming, William W. Fleming Department of Pharmacology and Toxicology School of Medicine West Virginia University Morgantown, West VirginiaSearch for more papers by this authorArthur Fries, Arthur Fries Institute for Defenses Analysis Alexandria, VirginiaSearch for more papers by this authorF. Peter Guengerich, F. Peter Guengerich Department of Biochemistry and Center in Molecular Toxicology School of Medicine Vanderbilt University Nashville, TennesseeSearch for more papers by this authorRoger Hornbrook, Roger Hornbrook Department of Pharmacology and Toxicology College of Pharmacy University of Oklahoma Oklahoma, OklahomaSearch for more papers by this authorLouis Lasagna, Louis Lasagna Department of Pharmacology and Experimental Therapeutics Sackler School of Graduate Biomedical Sciences School of Medicine Tufts University Boston, MassachusettsSearch for more papers by this authorBert K. B. Lum, Bert K. B. Lum Department of Pharmacology School of Medicine University of Hawaii Honolulu, HawaiiSearch for more papers by this authorElias K. Michaelis, Elias K. Michaelis Department of Pharmacology and Toxicology School of Pharmacy The University of Kansas Lawrence, KansasSearch for more papers by this authorEdward T. Morgan, Edward T. Morgan Department of Pharmacology School of Medicine Emory University Atlanta, GeorgiaSearch for more papers by this authorAlan Poland, Alan Poland McArdle Laboratory for Cancer Research University of Wisconsin Madison, WisconsinSearch for more papers by this authorKarl K. Rozman, Karl K. Rozman Department of Pharmacology, Toxicology and Therapeutics University of Kansas Medical Center Kansas City, KansasSearch for more papers by this authorJ. Bryan Smith, J. Bryan Smith Department of Pharmacology School of Medicine Temple University Philadelphia, PennsylvaniaSearch for more papers by this authorHollie I. Swanson, Hollie I. Swanson Department of Pharmacology University of Kentucky Lexington, KentuckySearch for more papers by this authorWilliam Waddell, William Waddell Department of Toxicology and Pharmacology University of Louisville Medical Center Louisville, KentuckySearch for more papers by this authorJames D. Wilson, James D. Wilson Resources for the Future Washington, D.C.Search for more papers by this author Daniel M. Byrd III, Daniel M. Byrd III Federal Focus, Inc. Washington, D.C.Search for more papers by this authorDonald O. Allen, Donald O. Allen Department of Pharmacology University of South Carolina School of Medicine Columbia, South CarolinaSearch for more papers by this authorRobert L. Beamer, Robert L. Beamer Department of Basic Pharmaceutical Sciences College of Pharmacy University of South Carolina Columbia, South CarolinaSearch for more papers by this authorHenry R. Besch Jr., Henry R. Besch Jr. Department of Pharmacology and Toxicology School of Medicine Indiana University Indianapolis, IndianaSearch for more papers by this authorDavid B. Bylund, David B. Bylund Department of Pharmacology College of Medicine The University of Nebraska Omaha, NebraskaSearch for more papers by this authorJohn Doull, John Doull Department of Pharmacology, Toxicology and Therapeutics University of Kansas Medical Center Kansas City, KansasSearch for more papers by this authorWilliam W. Fleming, William W. Fleming Department of Pharmacology and Toxicology School of Medicine West Virginia University Morgantown, West VirginiaSearch for more papers by this authorArthur Fries, Arthur Fries Institute for Defenses Analysis Alexandria, VirginiaSearch for more papers by this authorF. Peter Guengerich, F. Peter Guengerich Department of Biochemistry and Center in Molecular Toxicology School of Medicine Vanderbilt University Nashville, TennesseeSearch for more papers by this authorRoger Hornbrook, Roger Hornbrook Department of Pharmacology and Toxicology College of Pharmacy University of Oklahoma Oklahoma, OklahomaSearch for more papers by this authorLouis Lasagna, Louis Lasagna Department of Pharmacology and Experimental Therapeutics Sackler School of Graduate Biomedical Sciences School of Medicine Tufts University Boston, MassachusettsSearch for more papers by this authorBert K. B. Lum, Bert K. B. Lum Department of Pharmacology School of Medicine University of Hawaii Honolulu, HawaiiSearch for more papers by this authorElias K. Michaelis, Elias K. Michaelis Department of Pharmacology and Toxicology School of Pharmacy The University of Kansas Lawrence, KansasSearch for more papers by this authorEdward T. Morgan, Edward T. Morgan Department of Pharmacology School of Medicine Emory University Atlanta, GeorgiaSearch for more papers by this authorAlan Poland, Alan Poland McArdle Laboratory for Cancer Research University of Wisconsin Madison, WisconsinSearch for more papers by this authorKarl K. Rozman, Karl K. Rozman Department of Pharmacology, Toxicology and Therapeutics University of Kansas Medical Center Kansas City, KansasSearch for more papers by this authorJ. Bryan Smith, J. Bryan Smith Department of Pharmacology School of Medicine Temple University Philadelphia, PennsylvaniaSearch for more papers by this authorHollie I. Swanson, Hollie I. Swanson Department of Pharmacology University of Kentucky Lexington, KentuckySearch for more papers by this authorWilliam Waddell, William Waddell Department of Toxicology and Pharmacology University of Louisville Medical Center Louisville, KentuckySearch for more papers by this authorJames D. Wilson, James D. Wilson Resources for the Future Washington, D.C.Search for more papers by this author First published: 29 May 2006 https://doi.org/10.1111/j.1539-6924.1998.tb00907.xCitations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume18, Issue1February 1998Pages 1-2 RelatedInformation

Induction of cancer by inorganic arsenic occurs inconsistently between species and between routes of exposure, and it exhibits different dose-response relationships between different target organs. Inhaled or ingested arsenic causes cancer in humans but not in other species. Inhaled arsenic primarily induces lung cancer, whereas ingested arsenic induces cancer at multiple sites, including the skin and various other organs. Cancer potency appears to vary by route of exposure (ingestion or inhalation) and by organ site, and increases markedly at higher exposures in some instances. To understand what might explain these inconsistencies, we reviewed several hypotheses about the mechanism of cancer induction by arsenic. Arsenic disposition does not provide satisfactory explanations. Induction of cell proliferation by arsenic is a mechanism of carcinogenesis that is biologically plausible and compatible with differential effects for species or differential dose rates for organ sites. The presence of other carcinogens, or risk modifiers, at levels that correlate with arsenic in drinking water supplies, may be a factor in all three inconsistencies: interspecies specificity, organ sensitivity to route of administration, and organ sensitivity to dose rate.