TH9507, an analogue of human growth hormone-releasing factor (hGRF(1-44)NH 2 ) minimally modified by addition of a trans -3-hexenoyl moiety to Tyr 1 of the amino acid sequence, was found to be resistant to dipeptidyl aminopeptidase-IV deactivation. Compared to natural hGRF(1-44)NH 2 , the modification slowed the in vitro degradation of the peptide in rat, dog and human plasma and prolonged the in vivo plasma elimination kinetics of immunoreactive TH9507. Plasma growth hormone and insulin-like growth factor-1 (IGF-1) markedly increased in pigs, rats and dogs after daily repeat intravenous or subcutaneous injections of TH9507 at doses up to 600 µ g /kg. Subchronic toxicity studies in rats and dogs with TH9507 treatment for up to 4 months showed a significant, but not dose-related, increase in body weight gain associated with increased biomarker response. Although TH9507 was well tolerated by both rats and dogs, a more pronounced anabolic effect and more evident (reversible) adverse effects (liver and kidney findings, anaemia, clinical chemistry changes, organ weight effects) were observed in dogs after repeat daily subcutaneous injections, which were attributed to prolonged exposure to supraphysiological levels of growth hormone and/or IGF-1. In both rats and dogs, toxicokinetic evaluations indicated that exposure to immunoreactive TH9507 was dose related after both routes of administration. The apparent elimination t 1/2 in dogs ranged from 21 to 45 min. In conclusion, TH9507 is a modified hGRF peptide having enhanced potency and duration of action. The adverse treatment-related effects in dogs appear to be associated with sustained exposure to supraphysiological levels of growth hormone and IGF-1 induced by prolonged TH9507 treatment.
National legislation, which implements European Council Directive 96/29/EURATOM in Ireland, sets a reference level of 400 Bq m(-3) averaged over any 3 month period for radon exposure in the workplace and also empowers the Radiological Protection Institute of Ireland to direct employers to have radon measurements carried out. This legislation came into effect in May 2000. Radon measurements have already been completed in show caves and other underground workplaces. Between 1998 and 2001, over 33 800 individual radon measurements were carried out in all ground floor offices and classrooms in 3444 schools nationwide as part of a programme undertaken jointly with the Department of Education and Science. Where the average indoor radon concentration in one or more rooms exceeded 200 Bq m(-3), remedial measures were implemented. For concentrations up to 400 Bq m(-3) this involved increased ventilation while for higher concentrations an active sump was normally installed. The results of the survey, as well as the effectiveness of the different remedial strategies, are discussed. In the case of other above ground workplaces, different approaches have been adopted. As a first step, workplaces in two known high radon areas were directed to have radon measurements carried out. This programme had limited success because of problems in obtaining accurate workplace databases and a general lack of awareness on the part of employers of the issues involved. From a sample of 2610 employers directed to measure radon, only 408 actually completed measurements and 37 workplaces were identified as having average 3 month average radon concentrations above 400 Bq m(-3). A total of 1356 employers ignored all correspondence, some of which was sent by registered post and signed for on receipt. Current initiatives are focused on the provision of information and include newspaper advertising as well as publications aimed specifically at both employer and employee representative groups. The ability to provide accurate information that encourages both measurement and remediation is seen as central to an effective radon workplace programme.
Until the end of 2012, the Radiological Protection Institute of Ireland (RPII) operated a personal dosimetry service for workers in the medical, industrial, education and research sectors in Ireland. The data recorded by the RPII service were used to generate national dose statistics and as such acted as a National Dose Register (NDR). In preparation for the closure of the RPII dosimetry service in 2012, a formal NDR was introduced for the first time in Ireland and data on all monitored workers are now supplied to it annually by Approved Dosimetry Services. A new system for approving dosimetry services operating in Ireland was also introduced in 2012. The criteria for approval are based on the recommendations given in the European Commission's publication, 'Radiation Protection No. 160'. This paper describes the steps involved and the operational experience gained in establishing both the NDR and the system for approval of dosimetry services.
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