Abstract  Propylene oxide (PO), a simple alkylating agent used in the chemical industry, is weakly genotoxic and induces nasal cavity tumors in rodents on inhalation at high air concentrations. DNA adducts, hemoglobin adducts, and sister chromatid exchanges (SCE) were analyzed as biomarkers of exposure in a group of eight PO-exposed workers and eight nonexposed subjects. 1-2-Hydroxypropyladenine (1-HP-adenine) in DNA of WBCs was analyzed using a hypersensitive (32)P-postlabeling assay. HP-valine in hemoglobin was measured using gas chromatography/tandem mass spectrometry. Air measurements indicated PO levels in the range of 1-7 ppm. All three biomarkers showed significantly increased levels in the exposed workers. 1-HP-adenine was recorded in seven of the exposed workers (mean 0.66 mol/10(9) mol nucleotides) but was not detected in any of the control subjects. HP-valine was found in all subjects (means of 2.7 and 0.006 pmol/mg globin in exposed workers and controls, respectively). The average frequencies of SCE were 3.7/cell in exposed workers and 2.0/cell in controls, respectively. DNA and hemoglobin adducts were correlated (r = 0.887), as well as DNA adducts and SCE (r = 0.792) and hemoglobin adducts and SCE (r = 0.762). The present study is the first demonstrating PO-DNA adducts in human individuals. It is also the first study indicating cytogenetic effects in humans from PO exposure, although confounding effects from other sources cannot be excluded.

Abstract  In this study we aimed to identify cancers where there is a consistent sex disparity, with the goal of identifying unexplained sex disparities that may offer promising opportunities for etiologic research. Age- and sex-specific cancer incidence data from Cancer Incidence in Five Continents, provided by the International Agency for Research on Cancer, were used to calculate incidence rate ratios for 35 cancer sites, comparing men to women, adjusting for attained age, gross domestic product (GDP), and geographical region. Genital cancers and breast cancer were excluded. The consistency of relative risks was examined by GDP and geographical region and, in a subset of longstanding cancer registers, by calendar year. For each cancer site, the sex disparity was broadly classified as plausibly explained by established environmental risk factors, partly explained, or unexplained. Cancer incidence was statistically significantly higher in men than women at 32 of 35 sites, with disparities >2-fold for 15 sites and >4-fold for 5 sites. For nearly all sites, the sex disparity was consistent across GDP groups and geographical regions. However, the incidence rate ratios varied considerably by age at diagnosis. The sex disparity for 13 cancer sites was considered to be entirely unexplained by known risk factors; these sites showed strikingly little variation in the incidence rate ratios over decades. Thus, the basis of many of the largest sex disparities in cancer incidence seems mostly unknown, highlighting the need for intensified research into its origins.

Abstract  BACKGROUND: Cancer epidemiology articles often point out that cancer rates tend to be higher among males than females yet rarely is this theme the subject of investigation.

METHODS: We used the Surveillance, Epidemiology and End Results program data to compute age-adjusted (2000 U.S. standard population) sex-specific incidence rates and male-to-female incidence rate ratios (IRR) for specific cancer sites and histologies for the period 1975 to 2004.

RESULTS: The 10 cancers with the largest male-to-female IRR were Kaposi sarcoma (28.73), lip (7.16), larynx (5.17), mesothelioma (4.88), hypopharynx (4.13), urinary bladder (3.92), esophagus (3.49), tonsil (3.07), oropharynx (3.06), and other urinary organs (2.92). Only 5 cancers had a higher incidence in females compared with males: breast (0.01), peritoneum, omentum, and mesentery (0.18), thyroid (0.39), gallbladder (0.57), and anus, anal canal, and anorectum (0.81). Between 1975 and 2004, the largest consistent increases in male-to-female IRR were for cancers of the tonsil, oropharynx, skin excluding basal and squamous, and esophagus, whereas the largest consistent decreases in IRR were for cancers of the lip and lung and bronchus. Male-to-female IRRs varied considerably by age, the largest increases of which were for ages 40 to 59 years for tonsil cancer and hepatocellular carcinoma. The largest decreases in male-to-female IRR by age, meanwhile, were for ages 30 to 49 years for thyroid cancer, ages >70 years for esophageal squamous cell carcinoma, and ages >30 years for lung and bronchus cancer.

CONCLUSION: These observations emphasize the importance of sex in cancer etiopathogenesis and may suggest novel avenues of investigation.

Abstract  Compositional variability of the new fluorine fibrous amphiboles (fluoro-edenite) from the volcanic area of Biancavilla (Sicily, Italy) is reported here for the first time. Quantitative chemical analysis of a suite of four samples was performed by a standardized SEM-EDS microanalysis method, previously developed and tested on different typologies of fibrous amphiboles. The results highlighted compositional differences, especially concerning Si, Ca, Fe, and Na contents, both within the same and among the different samples. Compared to the previously investigated fluoro-edenite prismatic variety, the fluorine fibrous amphiboles showed average values of Si and Fe contents always higher, whereas Ca was significantly lower, which we consider a distinctive character for the fluorine fibrous variety. The Fe(3+)/Fe(tot) ratios, evaluated by Mossbauer spectroscopy, reflected different iron oxidation states: Fe(3+) was always more prevalent than Fe(2+), which was very low for two of the four samples analyzed. Employing the Leake classification, all the analyzed fluorine amphibole fibers showed an edenite-winchite trend, with a non negligible content of tremolite component. Both the fluorine amphibole fibers and the prismatic fluoro-edenite from Biancavilla may be correlated with the same genetic process, but the compositional variability reflect different growth conditions. The large variation observed for Fe(3+)/Fe(tot) ratios in the amphibole fibers is probably due to local variations of oxygen fugacity during crystallization. A workable hypothesis is that a hot metasomatizing fluid, enriched in fluorine and other incompatible elements, altered the volcanic rocks and caused the crystallization of either the fibrous fluorine amphiboles, by a very fast cooling, or the prismatic fluoro-edenite, by slow cooling.

Abstract  The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for 2-bromopropane to cause adverse effects on reproduction and development in humans. 2-Bromopropane was selected for evaluation due to documented evidence of worker exposures and published evidence of reproductive toxicity in both rodents and humans. 2-Bromopropane may be used as an intermediate in the synthesis of pharmaceuticals, dyes, and other organic chemicals. In Asia, 2-bromopropane was also used as a replacement for chlorofluorocarbons and 1,1,1-trichloroethane, and is used as a solvent/cleaner for microelectronics. The results of this evaluation on 2-brompropane are published in a NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of 2-Bromopropane, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to 2-bromopropane on human development and reproduction. No data were available on environmental exposure of the general public to 2-bromopropane. However, occupational exposure data indicate workplace exposures to 2-bromopropane range from

Abstract  2-Bromopropane and hydrochlorofluorocarbons (HCFCs), whose toxicity has scarcely been known, have recently been introduced as main substitutes for chlorofluorocarbons (CFCs). A major corporation in Korea replaced CFCs with 2-bromopropane and this actually led 23 Korean workers to be the world's first 2-bromopropane intoxication victims. Out of 25 female workers in the tactile switch assembling section, 17 (68%) were diagnosed as having ovarian failure. Two affected female workers showed marked pancytopenia with markedly hypoplastic marrow. In the same section, two out of eight male workers showed azoospermia and four some degree of oligospermia. The above toxicity of 2-bromopropane was reproduced in experimental animal studies. Recently, health effects of HCFC 123, including toxic hepatitis, have been reported by several authors. The principle of replacement of toxic substances with non-toxic or less toxic chemicals is important in risk management, but substances still poorly known should not be confused with non-toxic or less toxic substances. Measures aimed at reducing exposure to chemicals with known toxicity rather than using new unknown alternatives may be a rational and effective approach to risk management.