Bulletin BoardOctober 14, 2005

EnvironmentalBrominated flame retardants - status quo in risk discussion2005-09-27Brominated flame retardants (BFR) are a group of chemicals which are produced in large quantities and occur in many consumer products. The BFR which are currently quantitative most dominant in Europe are tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD) and the polybrominated di-Ph ether (PBDE). BFR are predominantly used as additives. They are released into the environment by using products and through depositing waste, as well as other means. In the meantime they are ubiquitously detectable. Their lipophilicity and persistence encourage bioaccumulation. Besides occupational exposure, humans assimilate these substances primarily via ingestion. At present the internal exposure and the concentrations in foodstuff are very low. It is known that acute toxicity of the BFR is marginal, but they can disrupt the thyroid hormone system and the neurological development. Overall the insights about the behavior in the environment, in the organism and the effects in particular of TBBPA and HBCD are still rudimental. Due to the existent knowledge about potential risks from PBDE two of the three used commercial mixtures (penta-BDE and octa-BDE) are already regulated in Europe. The usage of deca-BDE is still in discussion. The bioaccumulative and toxic potential of this congener is very low, but there is strong evidence that it is transformed in the environment to more toxic compounds.Authors: Salomon, MarkusFull source: Umweltmedizin in Forschung und Praxis 2005, 10(3), 183-197 (German)Hexavalent chromium remediation using MRC injection and monitored natural attenuation2005-09-27A hexavalent chromium [Cr(VI)] plume in shallow groundwater, located in an industrial area of Berkeley, California near San Francisco Bay, is being remediated through a combined strategy of source reduction, monitored natural attenuation (MNA), and “hot spot” treatment by injection of a recently-developed Metals Remediation Compound (MRC). The use of MRC at the site is one of the first field-scale tests of the new compound. Shallow groundwater at the site became contaminated due to releases of plating wastes during the late 1970s. Groundwater monitoring since 1993 shows an elongated plume extending downgradient of the source area. Chromium (Cr) and geochemical sampling data indicate that natural attenuation is occurring, with a significant fraction of Cr(VI) speciation to Cr(III). Isotopic analysis has also been conducted to confirm conversion of Cr(VI) to Cr(III). Measurements of stable Cr isotope fractionation in groundwater samples from the site wells corroborate the conclusion that geochemical reduction of Cr(VI) is occurring. Hydropunch sampling in 2002 revealed “hot spot” areas farther downgradient of the source area than predicted by a solute transport model, due to previously undiscovered ancestral channels. After 9 months of measurements subsequent to injection, decreases in Cr(VI) concentrations in downgradient monitoring wells-from 47% to 69%-were observed, but unexpectedly no metabolic acids were detected. Follow-up sampling was subsequently conducted, which confirmed a correlation did exist between metabolic acid concentrations and lower Cr(VI) chromium concentrations and suggested that localized groundwater flow direction differences and breakthrough between injection points were likely responsible for previously uncorrelated results.Authors: Makdisi, Richard S.; Phelps, Michael B.Full source: Remediation of Chlorinated and Recalcitrant Compounds--2004, Proceedings of the International Conference on Remediation of Chlorinated and Recalcitrant Compounds, 4th, Monterey, CA, United States, May 24-27, 2004Environmental health physics: 50 years of progress2005-09-27Environmental health physics is an interdisciplinary field, involving study of the release, transport, and fate of radioactive material in the environment. Further, it addresses the interaction of humans with radioactive materials within the ambient (outdoor) environment and with the environments associated with modern technology and lifestyles. It also involves both naturally occurring and artificially produced radionuclides with the former generally being by far the highest source of exposure. In fact, doses from naturally occurring radionuclides are increasingly being used as a benchmark for the establishment of dose rate limits for people. Because of the pioneering work of early environmental health physicists, models exist today that can be used to assess the potential impacts of new nuclear facilities prior to their operation. In fact, these people represent the branch of the health physics profession who conducted environmental monitoring programs and performed the associated research studies that led to the identification of the principal radionuclides of interest, the major pathways and mechanisms through which they expose people, and the doses that may result from radioactive materials in the natural and technological enhanced environments. One of their most important contributions was the identification and quantification of many of the key parameters that serve as input to such models. Monitoring of nuclear weapons development facilities used during and after World War II was the initial stimulus for the establishment of environmental health physics programs. Thereafter, these programs were expanded both nationally and globally, as a result of the atmospheric weapons testing programs of nations such as France, the People’s Republic of China, the former Soviet Union, the United Kingdom, and the United States. Additional stimuli were provided by the development of the commercial nuclear power industry. Current environmental programs, particularly within the U.S., focus on decontamination and decommissioning of dormant facilities from these earlier defense and commercial programs. The range of the environmental health physics aspects of these activities is the subject of this paper.Authors: Moeller, Dade W.Full source: Health Physics 2005, 88(6), 676-696 (Eng)Selected Volatile Organic Compounds in Residential Air in the City of Ottawa, Canada2005-09-27Airborne levels of selected volatile organic chemicals (VOCs) that are priorities for exposure assessment under the Canadian Environmental Protection Act (CEPA) 1999 were measured in both indoor air and outdoor air of 75 residential houses, in the city of Ottawa, Ontario, during the winter of 2002/2003. Among 37 chemicals monitored, 17 were detected with a frequency greater than 80% in indoor air; 9 were between 30% and 80%; 7 were between 1% and 30%; and 4 were not detected. Virtually all of the target VOCs were detected more frequently and were present at significantly higher levels in indoor air than in outdoor air. Compared with earlier published studies, including a 1991/1992 Canadian national survey of VOCs in residential air, levels of target analytes in indoor air in this study were lower for a number of chemicals, indicating a possible trend toward decreased inhalation exposure to these chemicals in residential environments. This study has yielded up-to-date information on levels of a variety of priority airborne chemicals in residential air, which is being used to estimate current exposure to these substances as input to health risk assessments and risk management actions under CEPA 1999. Authors: Zhu, Jiping; Newhook, Ron; Marro, Leonora; Chan, Cecilia C.Full source: Environmental Science and Technology 2005, 39(11), 3964-3971 (Eng)Evaluation of the size and type of free particulates collected from unused asbestos-containing brake components as related to potential for respirability2005-09-27Chrysotile asbestos has found multiple applications in the production of friction products. At one point it comprised 40-50% of the composition of brake linings thus generating the potential for the development of asbestos related diseases in millions of workers involved in vehicle repairs. While some attention has been given to the health status of workers involved in the handling of worn components, little has been given to the potential for exposure during the handling and fitting of new (unused) components as replacement parts. Unused brake linings or brake shoes with attached linings from four different sources were gently rinsed with prefiltered water that was then collected on filters for analysis. Large numbers of chrysotile asbestos containing structures, the majority of respirable size, were present in each sample. Authors conclude that any manipulation of new asbestos containing brake components would be expected to yield free dust containing chrysotile asbestos of respirable size. That the vast majority of these fibers and particulates would not be counted as regulated fibers rendering assessment of potential exposures in the workplace, based on data of Permissible Exposure Limits or Regulated Fibers, questionable. Authors: Atkinson, Mark A. L.; O’Sullivan, Michael; Zuber, Sylvia; Dodson, Ronald F.Full source: American Journal of Industrial Medicine 2004, 46(6), 545-553 (Eng)MedicalCyclo-oxygenase-2 inhibitors: when should they be used in the elderly?2005-09-27Chronic pain in the elderly is frequently a result of arthritic disorders, particularly osteoarthritis. The cyclo-oxygenase (COX)-2 inhibitors are as effective as standard NSAIDs for the relief of pain and for improving function in elderly patients with osteoarthritis and rheumatoid arthritis. In order to minimize the risk of gastroduodenal disorders COX-2 inhibitors may be prescribed over standard NSAIDs. COX-2 inhibitors are responsible for dose-related adverse reactions involving renal function, salt and water homeostasis and the vascular endothelium resulting in renal failure, hypertension, and cardiac failure. Thus, there are good reasons to avoid high doses of COX-2 inhibitors in the elderly. Recent research indicates that COX-2 inhibitors have a thrombotic potential, especially in high doses and when use is prolonged, and this further limits the extent to which they can be used in the elderly. Important interactions with COX-2 inhibitors in the elderly include those with warfarin, ACE inhibitors, angiotensin II type 1 receptor antagonists, and diuretics. A standard NSAID plus a proton pump inhibitor may be equally effective as a COX-2 inhibitor in reducing the risk of gastroduodenal toxicity and if used the same prescribing advice applies. Current knowledge concerning the thrombotic potential of COX-2 inhibitors suggests that this combination, if tolerated, may be preferable to a COX-2 inhibitor, particularly where prolonged use is required. This knowledge also indicates that for patients with or at high risk of ischemic heart disease or stroke, COX-2 inhibitors are contraindicated.Authors: Savage, RuthFull source: Drugs & Aging 2005, 22(3), 185-200 (Eng)An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment2005-09-27R112 inhibits Syk kinase, a transducer of signaling through the Fcepsilon receptor of mast cells, blocking mast cell responses to allergic stimuli. This study examines the efficacy and safety of intranasal R112 in volunteers with symptomatic seasonal allergic rhinitis compared with a placebo in a park setting. After 8 h (dosing 3 mg/nostril every 4 h • 2), R112 significantly reduced the GSC compared with placebo. Each individual symptom combined to form the GSC was also significantly improved in the R112 group compared with control. As early as 45 min after dosing, R112 showed a significant improvement in symptoms over placebo, and the duration of action exceeded 4 h. Adverse effects were indistinguishable between the groups and clinical insignificant. Intranasal R112 was effective in this park study and is a promising new treatment for seasonal allergic rhinitis.Authors: Meltzer, Eli O.; Berkowitz, Robert B.; Grossbard, Elliott B.Full source: Journal of Allergy and Clinical Immunology 2005, 115(4), 791-796 (Eng)The Refinement of Uncertainty/Safety Factors in Risk Assessment by the Incorporation of Data on Toxicokinetic Variability in Humans2005-09-27The derivation of safe levels of exposure in humans for compounds that are assumed to cause threshold toxicity has relied on the application of a 100-fold uncertainty factor to a measure for the threshold, such as the no observed adverse effect level (NOAEL) or the benchmark dose (BMD). This 100-fold safety factor consists of the product of 2 10-fold factors allowing for human variability and interspecies differences. The International Program on Chemical Safety has suggested the subdivision of these 10-fold factors to allow for variability in toxicokinetics and toxicodynamics. This subdivision allows the replacement of the default uncertainty factors with a chemical-specific adjustment factor (CSAF) when suitable data are available. This short review describes potential options to refine safety factors used in risk assessment, with particular emphasis on pathway-related uncertainty factors associated with variability in kinetics. These pathway-related factors were derived from a database that quantified interspecies differences and human variability in phase I metabolism, phase II metabolism, and renal excretion. This approach allows metabolism and pharmacokinetic data in healthy adults and subgroups of the population to be incorporated in the risk-assessment process and constitutes an intermediate approach between simple default factors and chemical-specific adjustment factors.Authors: Dorne, J. L. C. M.; Renwick, A. G.Full source: Toxicological Sciences 2005, 86(1), 20-26 (Eng)Cardiovascular Manifestations of Moderate to Severe Carbon Monoxide Poisoning2005-09-27The authors describe the cardiovascular manifestations of CO poisoning. Carbon monoxide poisoning is a common cause of toxicological morbidity and mortality. Although the neurological sequelae of CO poisoning have been well described, the cardiovascular consequences are limited to isolated case reports. The authors reviewed the cardiovascular manifestations of 230 consecutive patients treated for moderate to severe CO poisoning in the hyperbaric oxygen chamber at Hennepin County Medical Center (HCMC), a regional center for treatment of CO poisoning. The mean age was 47.2 years with 72% men. Ischemic ECG changes were present in 30% of the patients, whereas only 16% had a normal ECG. Cardiac biomarkers (creatine kinase-MB fraction or troponin I) were elevated in 35% of patients. In-hospital mortality was 5%. Cardiovascular sequelae of CO poisoning are frequent, with myocardial injury assessed by biomarkers or ECG in 37% of the patients. Patients admitted to the hospital with CO poisoning should have a baseline ECG and serial cardiac biomarkers.Authors: Satran, Daniel; Henry, Christopher R.; Adkinson, Cheryl; Nicholson, Caren I.; Bracha, Yiscah; Henry, Timothy D.Full source: Journal of the American College of Cardiology 2005, 45(9), 1513-1516 (Eng)Airway inflammatory and immunological events in a rat model exposed to toluene diisocyanate2005-09-27This study investigates the inflammatory and immunological events in the airway induced by a short period of repeated exposure to toluene diisocyanate (TDI), an animal model was established, which resembled the industrial field exposure. The TDI vapor exposure resulted in airway symptoms similar to those in occupational asthma. BAL fluid cellular analysis and lung histophathological examination revealed that inflammatory response was characterized by marked eosinophil infiltration of the airways. The cytokine assay revealed significant production of IL-4 in the airways of the TDI exposed rats as compared to the control rats. These findings indicated that a short period of repeated exposure to TDI vapor may cause respiratory hypersensitivity in which airway inflammatory and immunological events represented by eosinophil infiltration and Th2 cytokines may play an important role. Also, this animal model may be suitable for exploring the mechanism underlying TDI-induced occupational asthma.Authors: Kouadio, Kouame; Zheng, Kui-Cheng; Tuekpe, Mallet K.-N.; Todoriki, Hidemi; Ariizumi, MakotoFull source: Food and Chemical Toxicology 2005, 43(8), 1281-1288 (Eng)A study on the relationship between the mutation of p53 gene and skin cancer in patients with arsenism caused by coal-burning using PCR-SSCP, cloning and sequencing2005-09-27This study examines the mutation of p53 gene in peripheral blood white cells of patients with arsenism caused by coal-burning pollution. p53 gene mutations were found in 30% of cases in carcinoma group (3/10), 16.67% of cases with pre-carcinoma group (2/12), there was no p53 gene mutation found in 38 cases in general pathological group. The results of cloning and sequencing indicated that mutation types were G:C .fwdarw. A:T transition, located at codons 143, 146 and 151. Detection of p53 mutation in peripheral blood white cells is very important with theoretical values to reveal the mechanism of arsenic carcinogenicity.Authors: Pan, Xue-li; Zhang, Ai-hua; Huang, Xiao-xin; Jiang, xian-yaoFull source: Huanjing Yu Zhiye Yixue 2004, 21(5), 360-363 (Ch)Antigenotoxic effect of allicin against methyl methanesulfonate-induced genotoxic damage2005-09-27Allicin, one of the S compounds especially thiosulfonates of garlic (Allium sativum), possesses antioxidant and thioldisulfide exchange activity and is also shown to cause a variety of actions potentially useful for human health. In this investigation, the authors determined its antigenotoxic potential using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) induced by Me methanesulfonate (MMS) as genotoxic end points both in the presence as well as the absence of rat liver microsomal activation system (S9 mix) in cultured human lymphocytes. The authors tested the effect of 5, 10, and 20 muM allicin on the damage exerted by 60 muM MMS. The levels of CAs and SCEs were lowered suggesting an antigenotoxic role of allicin against genotoxic damage both in the presence as well as the absence of metabolic activation.Authors: Siddique, Yasir Hasan; Afzal, MohammadFull source: Journal of Environmental Biology 2005, 26(3), 547-550 (Eng)Functionality changes of natural antioxidants during food processing and storage2005-09-27Food raw materials and products contain inhibitors of oxidation reactions, both in the lipidic phase and the aquatic phase. The most important inhibitors are phenolic antioxidants. During food processing and storage, concentrations of antioxidants in the two phases reach an equilibrium. Phenolics react with lipidic free radicals, being converted into antioxidant free radicals, quinones, polymers and copolymers. Some degradation products possess an antioxidant activity, too. The relative antioxidant activity decreases with decreasing concentration of oxygen in the system and with increasing temp. Antioxidants are more rapidly decomposed in surface layers. Health aspects of antioxidant degradation products are often neglected as the safety of antioxidant degradation products is mostly unknow

.Authors: Pokorny, J.; Schmidt, S.; Nguyen, H. T. T.Full source: Czech Journal of Food Sciences 2004, 22(Spec. Iss.), 80-83 (Eng)Ambient Carbon Monoxide May Influence Heart Rate Variability in Subjects With Coronary Artery Disease2005-09-27Days with high ambient CO have been associated with increased hospital admissions for cardiac disease. This work determined if daily CO and fine particulate (PM2.5) concentrations were associated with daily changes in heart rate variability. Each of 36 adults with coronary artery disease were personally exposed to PM2.5 and CO; heart rate variability was measured for one, 24-h period each week for up to 10 week. Among those not taking beta-receptor blockers, there was a positive association between the standard deviation of the R-to-R intervals and CO; no effect was observed for PM2.5. Urban exposure to CO may exert a biological effect on the heart, which may be modified by medications.Authors: Dales, RobertFull source: Journal of Occupational and Environmental Medicine 2004, 46(12), 1217-1221 (Eng)NSAID-induced peptic ulcers and Helicobacter pylori infection: implications for patient management2005-09-27The conflicting data about the influence of Helicobacter pylori infection on the ulcer risk in patients receiving NSAIDs can be accounted for by the heterogeneity of study designs and the diversified host response to H. pylori. Factors that will affect the outcome include the choice of H. pylori diagnostic tests, previous ulcer complications, concurrent use of acid suppressants, NSAID-naive versus long-term users, low-dose aspirin (acetylsalicylic acid) versus non-aspirin NSAIDs and whether the result was derived from a pre-specified endpoint or post hoc subgroup analysis. Current evidence suggests that H. pylori eradication reduces the ulcer risk for patients who are about to start receiving NSAIDs but not for those who are already on long-term NSAID therapy. Since treatment with a proton pump inhibitor (PPI) worsens H. pylori-associated corpus gastritis, H. pylori should be tested for, and eradicated if present, before starting long-term prophylaxis with PPIs. Patients with H. pylori infection and a history of ulcer complications who require NSAIDs should receive concomitant PPIs or misoprostol after curing the infection. Among patients receiving low-dose aspirin, who have H. pylori infection and previous ulcer complications, long-term treatment with a PPI further reduces the risk of complicated ulcers if H. pylori eradication fails or if patients use concomitant non-aspirin NSAIDs. Current data on the gastric safety of COX-2 selective NSAIDs in H. pylori-infected patients are conflicting. Limited data suggest that the gastroduodenal sparing effect of rofecoxib is negated by H. pylori infection in patients who have had prior upper gastrointestinal events.Authors: Chan, Francis K. L.Full sources: Drug Safety 2005, 28(4), 287-300 (Eng)Hepatic findings in long-term clinical trials of ximelagatran2005-09-27In clinical trials, the efficacy and safety of the oral direct thrombin inhibitor ximelagatran have been evaluated in the prevention or treatment of thromboembolic conditions known to have high morbidity and mortality. In these studies, raised aminotransferase levels were observed during long-term use (>35 days). The aim of this analysis is to review the data regarding these hepatic findings in the long-term trials of ximelagatran. Treatment with ximelagatran has been associated with mainly asymptomatic elevation of ALT levels in a mean of 7.9% of patients in the long-term clinical trial program and nearly all of the cases occurred within the first 6 months of therapy. Rare symptomatic cases have been observed. An algorithm has been developed for testing ALT to ensure appropriate management of patients with elevated ALT levels. Regular ALT testing should allow the clinical benefits of ximelagatran to reach the widest population of patients while minimizing the risk of hepatic adverse effects.Authors: Lee, William M.; Larrey, Dominique; Olsson, Rolf; Lewis, James H.; Keisu, Marianne; Auclert, Laurent; Sheth, SunitaFull source: Drug Safety 2005, 28(4), 351-370 (Eng)OccupationalEffects of Occupational Trichloroethylene Exposure on Cytokine Levels in Workers2005-09-27The authors sought to investigate trichloroethylene-induced alterations of the immune system in humans. The levels of interleukin 2, interleukin 4, and interferon gamma in sera obtained from workers exposed to trichloroethylene were determined and compared with those of internal and external control subjects. This study provides the first report on quantitative immune changes induced by occupational exposure to low levels of trichloroethylene and strongly suggests that exposure to this substance alters immunohomeostasis in humans with possible effects on health.Authors: Iavicoli, Ivo; Marinaccio, Alessandro; Carelli, GiovanniFull source: Journal of Occupational and Environmental Medicine 2005, 47(5), 453-457 (Eng)Protein adducts as biomarkers of human benzene metabolism2005-09-27Authors used cysteinyl adducts of serum albumin (Alb) to investigate the production of 2 reactive benzene metabolites, namely, benzene oxide (BO) and 1,4-benzoquinone (1,4-BQ) in workers exposed to benzene. Adducts were measured in 160 benzene-exposed workers who did not use respiratory protection and 101 local controls, from populations in Shanghai and Tianjin, China. Although BO-Alb and 1,4-BQ-Alb were measured in all subjects, levels of both adducts were 2.4-fold greater (median value) in exposed subjects than in controls. Log-log plots of the individual adduct levels versus exposure were quasi-linear with straight-line slopes of about 0.3 for both BO-Alb and 1,4-BQ-Alb. Since these log-space slopes were significantly less than one, Authors infer that adduct production was nonlinear, i.e., less-than proportional to benzene exposure, over the indicated range. This behavior points to saturation of CYP2E1 as a critical metabolic consequence of high exposure to benzene in humans. Thus, the biological ED of BO and 1,4-BQ should be proportionally greater in persons exposed to low rather than high levels of benzene.Authors: Rappaport, Stephen M.; Waidyanatha, Suramya; Yeowell-O’Connell, Karen; Rothman, Nathaniel; Smith, Martyn T.; Zhang, Luoping; Qu, Qingshan; Shore, Roy; Li, Guilan; Yin, SongnianFull source: Chemico-Biological Interactions 2005, 153-154, 103-109 (Eng)The use of S-phenylmercapturic acid as a biomarker in molecular epidemiology studies of benzene2005-09-27S-Phenylmercapturic acid (S-PMA), is a urinary metabolite of benzene, thought to be derived from the condensation product of benzene oxide with glutathione. S-PMA may be determined by GC, HPLC (UV or fluorescence detection), GC-MS, LC-MS/MS or immunoassays. Urinary benzene was the most discriminatory biomarker and showed a relationship with airborne benzene at all levels of exposure studied (including groups exposed to <0.1 ppm benzene), whereas t,t-MA and S-PMA, as determined by immunoassay, were suitable only in the highest exposed workers (petrochemical industry, geometric mean 1765 mug/m3 (0.55 ppm) benzene). All 3 biomarkers were positively correlated with smoking as measured by urinary cotinine.Authors: Farmer, Peter B.; Kaur, Balvinder; Roach, Jonathan; Levy, Len; Consonni, Dario; Bertazzi, Pietro A.; Pesatori, Angela; Fustinoni, Silvia; Buratti, Marina; Bonzini, Matteo; Colombi, Antonio; Popov, Todor; Cavallo, Domenico; Desideri, Arianna; Valerio, Federico; Pala, Mauro; Bolognesi, Claudia; Merlo, FrancoFull source: Chemico-Biological Interactions 2005, 153-154, 97-102 (Eng)