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Safe Levels (safe + level)
Selected AbstractsSURGEON GENERAL: NO SAFE LEVEL FOR SECONDHAND SMOKECA: A CANCER JOURNAL FOR CLINICIANS, Issue 6 2006Article first published online: 31 DEC 200 No abstract is available for this article. [source] Low-level lead exposure and childrenJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 5 2001NR Wigg Abstract: The adverse effects of environmental lead exposure on the mental development of young children are well established. There is no safe level of blood lead below which children are not affected. Recent research expands our understanding of the impact of lead exposure continuing into later childhood, as well as its effects on children's behaviour. However, social and other environmental factors also contribute to variance in measures of developmental and behavioural outcomes. Lead is associated with only modest effects on children's development, but is a potentially modifiable risk factor. As environmental exposure to lead declines for the whole population, continued specific attention is needed for children living in industrial areas. [source] Successful treatment of severe recalcitrant erosive oral lichen planus with topical tacrolimusJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2006R Shichinohe Abstract Oral lichen planus (LP) is a severe, painful form of LP, and is often resistant to topical corticosteroid therapy. Recently, open trials demonstrated that topical tacrolimus therapy was effective for the treatment of chronic erosive oral LP. We report two cases with severe recalcitrant erosive oral LP, who dramatically benefited from topical tacrolimus therapy. In case 1, a 64-year-old man presented with a 5-month history of painful erosions on his entire lower lip and buccal mucosa. Physical and histological examination confirmed a diagnosis of LP. He experienced rapid relief from pain and a dramatic improvement was obtained within 5 weeks of topical tacrolimus treatment. No significant irritation was observed and blood tacrolimus level was kept within a safe level (2.5 ng/mL). In case 2, a 68-year-old man developed painful erosions on his right lower lip and buccal mucosa 2 months before his arrival at our hospital. Histopathological analysis confirmed a diagnosis of oral LP. He experienced a rapid dramatic improvement of both lesions within 4 weeks of the start of tacrolimus application. No significant irritation or recurrence was observed. Thus, topical tacrolimus is suggested as a well-tolerated, effective therapy for oral LP. [source] Eradication of the invasive Pseudorasbora parva results in increased growth and production of native fishesECOLOGY OF FRESHWATER FISH, Issue 1 2009J. R. Britton Abstract,,, The topmouth gudgeon, Pseudorasbora parva, has been described as Europe's most invasive fish. To control their UK invasion, some lentic populations at risk of causing fluvial dispersal have been eradicated. The first of these operations was from a lake in north-west UK in March 2005 using rotenone application; prior to eradication, their mean density was estimated as 6.1 m,2 whereas since eradication, no P. parva have been recorded. Prior to rotenone application, the majority of native fishes were removed, held off-site and reintroduced following degradation of rotenone to safe levels. In the three growth seasons since their reintroduction and P. parva eradication, the abundance, somatic growth rate and production of roach Rutilus rutilus and common bream Abramis brama have increased significantly; production is now driven by a lower number of comparatively larger, faster growing individuals. These data suggest that the eradication of this P. parva population has been highly beneficial for the growth, recruitment and production of these native species. [source] Impact of inter-individual differences in drug metabolism and pharmacokinetics on safety evaluationFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2004J.L.C.M. Dorne Abstract Safety evaluation aims to assess the dose,response relationship to determine a dose/level of exposure for food contaminants below which no deleterious effect is measurable that is ,without appreciable health risk' when consumed daily over a lifetime. These safe levels, such as the acceptable daily intake (ADI) have been derived from animal studies using surrogates for the threshold such as the no-observed-adverse-effect-level (NOAEL). The extrapolation from the NOAEL to the human safe intake uses a 100-fold uncertainty factor, defined as the product of two 10-fold factors allowing for human variability and interspecies differences. The 10-fold factor for human variability has been further subdivided into two factors of 100.5 (3.16) to cover toxicokinetics and toxicodynamics and this subdivsion allows for the replacement of an uncertainty factor with a chemical-specific adjustment factor (CSAF) when compound-specific data are available. Recently, an analysis of human variability in pharmacokinetics for phase I metabolism (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, hydrolysis, alcohol dehydrogenase), phase II metabolism (N-acetyltransferase, glucuronidation, glycine conjugation, sulphation) and renal excretion was used to derive pathway-related uncertainty factors in subgroups of the human population (healthy adults, effects of ethnicity and age). Overall, the pathway-related uncertainty factors (99th centile) were above the toxicokinetic uncertainty factor for healthy adults exposed to xenobiotics handled by polymorphic metabolic pathways (and assuming the parent compound was the proximate toxicant) such as CYP2D6 poor metabolizers (26), CYP2C19 poor metabolizers (52) and NAT-2 slow acetylators (5.2). Neonates were the most susceptible subgroup of the population for pathways with available data [CYP1A2 and glucuronidation (12), CYP3A4 (14), glycine conjugation (28)]. Data for polymorphic pathways were not available in neonates but uncertainty factors of up to 45 and 9 would allow for the variability observed in children for CYP2D6 and CYP2C19 metabolism, respectively. This review presents an overview on the history of uncertainty factors, the main conclusions drawn from the analysis of inter-individual differences in metabolism and pharmacokinetics, the development of pathway-related uncertainty factors and their use in chemical risk assessment. [source] Low-flow anaesthesia at a fixed flow rateACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2009A. CHERIAN Aims and Objectives: This study attempts to assess the safety of low-flow anaesthesia (LFA) at fixed flow rates with particular reference to the incidence of a decline in FiO2 below safe levels of 0.3 and to determine whether LFA can be used safely in the absence of an FiO2 monitor. Methods: A total of 100 patients undergoing procedures under general anaesthesia at fresh gas flows of 300 ml/min of O2 and 300 ml/min of N2O were monitored while maintaining the dial setting of isoflurane at 1.5% for 2 h. The changes in gas composition were analysed and even a single recording of FiO2 of <0.3 was considered sufficient to render the technique unsafe in the absence of gas monitors. Results: The lowest recorded value of FiO2 was 31% (v/v%). There was no incidence of adverse events necessitating the conversion from low flows to conventional flows. Conclusions: We conclude that low flows of 300 ml/min of N2O and 300 ml/min of oxygen can be used safely for a period of 2 h without the use of monitors for gas analysis of oxygen and agent in adult patients weighing between 40 and 75 kgs. [source] An overview of factors affecting the disposition of intramammary preparations used to treat bovine mastitisJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2006R. GEHRING The administration of antimicrobial drugs by the intramammary route offers a convenient option for the treatment of bovine mastitis. The goal of antimicrobial treatment is to achieve effective drug concentrations at the site of infection. Drug concentrations must also decrease to safe levels before the milk is harvested for human consumption. The rate of change of drug concentrations in the milk and udder tissues over time is dependent on the physicochemical characteristics of the drug and how these interact with the biological environment, affecting the rate and extent of absorption, distribution and elimination. Studies reported in the literature have identified various pathophysiological and pharmaceutical factors that may influence these processes. This review summarizes current understanding of factors affecting the disposition of drugs following intramammary administration. Areas of incomplete knowledge requiring further research have been identified. [source] Quantitative Structure,Activity Relationship Study on Fish Toxicity of Substituted BenzenesMOLECULAR INFORMATICS, Issue 8 2008Zhiguo Gong Abstract Many chemicals cause latent harm, such as erratic diseases and change of climate, and therefore it is necessary to evaluate environmentally safe levels of dangerous chemicals. Quantitative Structure,Toxicity Relationship (QSTR) analysis has become an indispensable tool in ecotoxicological risk assessments. Our paper used QSTR to deal with the modeling of the acute toxicity of 92 substituted benzenes. The molecular descriptors representing the structural features of the compounds were calculated by CODESSA program. Heuristic Method (HM) and Radial Basis Function Neural Networks (RBFNNs) were utilized to construct the linear and the nonlinear QSTR models, respectively. The predictive results were in agreement with the experimental values. The optimal QSTR model which was established based on RBFNNs gave a correlation coefficient (R2) of 0.893, 0.876, 0.889 and Root-Mean-Square Error (RMSE) of 0.220, 0.205, 0.218 for the training set, the test set, and the whole set, respectively. RBFNNs proved to be a very good method to assess acute aquatic toxicity of these compounds, and more importantly, the RBFNNs model established in this paper has fewer descriptors and better results than other models reported in previous literatures. The current model allows a more transparent chemical interpretation of the acute toxicity in terms of intermolecular interactions. [source] Principles of risk assessment for determining the safety of chemicals: Recent assessment of residual solvents in drugs and di(2-ethylhexyl) phthalateCONGENITAL ANOMALIES, Issue 2 2004Ryuichi Hasegawa ABSTRACT Risk assessment of chemicals is essential for the estimation of chemical safety, and animal toxicity data are typically used in the evaluation process, which consists of hazard identification, dose,response assessment, exposure assessment, and risk characterization. Hazard identification entails the collection of all available toxicity data and assessment of toxicity endpoints based on findings for repeated dose toxicity, carcinogenicity or genotoxicity and species-specificity. Once a review is compiled, the allowable lifetime exposure level of a chemical is estimated from a dose,response assessment based on several measures. For non-carcinogens and non-genotoxic carcinogens, the no-observed-adverse-effect-level (NOAEL) is divided by uncertainty factors (e.g. with environmental pollutants) or safety factors (e.g. with food additives) to derive a tolerable daily intake (TDI) or acceptable daily intake (ADI), respectively. These factors include interspecies and individual differences, duration of exposure, quality of data, and nature of toxicity such as carcinogenicity or neurotoxicity. For genotoxic carcinogens, low dose extrapolation is accomplished with mathematical modeling (e.g. linearized multistage model) from the point of departure to obtain exposure levels that will be associated with an excess lifetime cancer risk of a certain level. Data for levels of chemicals in food, water and air, are routinely used for exposure assessment. Finally, risk characterization is performed to ensure that the established ,safe' level of exposure exceeds the estimated level of actual exposure. These principles have led to the evaluation of several existing chemicals. To establish a guideline for residual solvents in medicine, the permitted daily exposure (PDE), equivalent to TDI, of N,N-dimethylformamide was derived on the basis of developmental toxicity (malformation) and of N-methylpyrrolidone on the basis of the developmental neurotoxicity. A TDI for di(2-ethylhexyl)phthalate was derived from assessment of testicular toxicity. [source] | |||||||||||||