Objectives-Benzene has long been recognised as a carcinogen and recent concern has centred on the eVects of continuous exposure to low concentrations of benzene both occupationally and environmentally. This paper presents an overview of the current knowledge about human exposure to benzene in the United Kingdom population based on recently published data, summarises the known human health eVects, and uses this information to provide a risk evaluation for sections of the general United Kingdom population. Method-Given the minor contribution that non-inhalation sources make to the overall daily intake of benzene to humans, only exposure from inhalation has been considered when estimating the daily exposure of the general population to benzene. Exposure of adults, children, and infants to benzene has been estimated for diVerent exposure scenarios with timeactivity patterns and inhalation and absorption rates in conjunction with measured benzene concentrations for a range of relevant microenvironments. Exposures during refuelling and driving, as well as the contribution of active and passive tobacco smoke, have been considered as part of the characterisation of risk of the general population. Results-Infants (<1 years old), the average child (11 years old), and nonoccupationally exposed adults, receive average daily doses in the range of 15-26, 29-50, and 75-522 µg of benzene, respectively, which correspond to average ranges to benzene in air of 3.40-5.76 µg/m 3 , 3.37-5.67 µg/m 3 , and 3.7-41 µg/m 3 for infants, children, and adults, respectively. Infants and children exposed to environmental tobacco smoke have concentrations of exposure to benzene comparable with those of an adult passive smoker. This is a significant source of exposure as a 1995 United Kingdom survey has shown that 47% of children aged 2-15 years live in households where at least one person smokes. The consequence of exposure to benzene in infants is more significant than for children or adults owing to their lower body weight, resulting in a higher daily intake for infants compared with children or non-smoking adults. A worst case scenario for exposure to benzene in the general population is that of an urban smoker who works adjacent to a busy road for 8 hours/day-for example, a maintenance worker-who can receive a mean daily exposure of about 820 µg (equal to an estimated exposure of 41 µg/m 3 ). The major health risk associated with low concentrations of exposure to benzene has been shown to be leukaemia, in particular acute non-lymphocytic leukaemia. The lowest concentration of exposure at which an increased incidence of acute nonlymphocytic leukaemia among occupationally exposed workers has been reliably detected, has been estimated to be in the range of 32-80 mg/m 3 . Although some studies have suggested that eVects may occur at lower concentrations, clear estimates of risk have not been determined, partly because of the inadequacy of exposure data and the few cases. Conclusions-Overall the evidence from human studies suggests that ...
This paper reviews research on attitudes and behaviours towards environmental tobacco smoke (ETS), with a special focus on child health and the indoor environment. Research needs and ways forward to encourage reductions in domestic ETS levels are discussed. Published material was identified through online literature searches (Medline, Toxline, Cancerlit, Biosis, Embase, Enviroline, Sociological Abstracts, Social Science Citation Index, Academic Index and Psychinfo). The literature search strategy employed search terms such as "passive smoking" or "environmental tobacco smoke" with "attitude" or "awareness" and other synonyms. Additional publications were identified by citation chasing and expert advice. Focusing on the UK, studies that provided survey-derived data about attitudes and behaviours in relation to ETS exposure in the indoor environment were selected for review. Published studies from other countries were also included when they provided information pertinent to this review. Most people are aware of the health risks associated with ETS exposure, and there is a high level of support for smoking restrictions in public places to protect non-smokers from ETS. However, although there is concern among both non-smoking and smoking parents about children and second-hand smoke, many people allow children to be exposed to ETS in the home. The review suggests that traditional health promotion campaigns have had only limited success in encouraging ETS risk reduction measures in the home. Because ETS is a public health priority, particularly in relation to child health, the barriers to the uptake of such measures need to be explored in detail to inform the future promotion of reductions in domestic levels of ETS.
In this paper, the population attributable risk (PAR), a measure of the excess risk of disease associated with a risk factor, is calculated for some of the common adverse health effects that have been associated with exposure of children to environmental tobacco smoke (ETS): childhood lower respiratory illness, chronic middle ear disease, asthma and sudden infant death syndrome (SIDS). Published data on both risk estimates and the percentage of children exposed to ETS in the home (prevalence of ETS) have been utilised. The percentage of childhood lower respiratory illness and middle ear disease typically attributable to ETS from either parent smoking ranged from 9% for asthma prevalence and for referral for glue ear, to 25% for hospital admission for lower respiratory illness. Where data were available to calculate PARs separately for mother only smoking and father only smoking, the PARs were generally larger for mothers only smoking, due mainly to higher odds ratios for mothers only smoking. The PAR for SIDS attributable to ETS from mother only smoking was 11%. Although based on a small number of studies, the PAR for SIDS attributable to smoking of fathers only was similar to that attributable to the smoking of mothers only, largely due to the higher prevalence of households where only the father smokes. This study has shown that the impact of ETS on childhood illness can be considerable, emphasising the importance of the need to develop effective strategies for reducing the risk of ETS exposure in the home and elsewhere.
Summary Staurosporine is a potent but non-specific kinase inhibitor. It has served as synthetic template for a variety of analogues with high specificity for protein kinase C (PKC). Here staurosporine and four PKCselective analogues, the indolocarbazoles, UCN-01 and CGP 41251, and the bisindolylmaleimides, Ro 31-8220 and GF 109203X, were investigated as growth inhibitors of human-derived A549 human lung adenocarcinoma cells. They were compared with respect to (1) effect on the cell cycle, (2) time dependency of growth arrest and (3) cytotoxic potency. Cells were exposed for 1, 2 and 4 days, or for 6, 12 and 24 h in the case of cyclesynchronised cells, to staurosporine analogues at concentrations at which they inhibited growth by 80% after 4 day exposure. Staurosporine and UCN-01 retarded cells in Go/, and CGP 41251 appeared to inhibit cell growth without cell cycle specificity. Ro 31-8220 slowed progression of synchronised cells through the cycle; over a longer time period it induced a weak block in G2/M. GF 109203X induced potent G2/M arrest in synchronised cells. This was not so apparent in asynchronous cells, which by day 4 were slowed in Go/, instead.Growth arrest induced by these inhibitors was more potent after incubation for 4 rather than 2 days. Incubation for 1 day followed by maintenance in drug-free medium for 3 days was sufficient to exert some cytostasis. The differences between cytotoxic and cytostatic concentrations, the former measured by release from cells of lactate dehydrogenase, were 15 000-fold for staurosporine, 300-fold for UCN-01, -400-fold for CGP 41251, 25-fold for Ro 31-8220 and -4-fold for GF 109203X. The results show that PKC-selective staurosporine analogues differ with respect to the mechanisms by which they interfere with the cell cycle. The necessity of long-term exposure for effective growth inhibition and the considerable margin between cytostatic and acute cytotoxic indolocarbazole concentrations are findings which might influence the planning and interpretation of clinical trials of these kinase inhibitors.
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