Route Safety Studies

Road Safety Audits are not carried out on existing roads in the UK although they are routinely carried out in other countries (see Chapter 7). This type of work is carried out as Route Safety Studies in the UK with an emphasis on historic accident and casualty data. 

Road Safety Audit of existing roads is not carried out in the UK. Instead, route safety studies are routinely carried out based on an analysis of historical injury accident records, and the definition of problems arising from those records. Local Safety Schemes have produced significant casualty reductions and excellent cost-benefit returns at single sites and along routes in the UK for the past 35 years. 

Road Safety Audits are not carried out on existing roads in the UK, although they are often carried out in other countries (see Chapters 8 and 10). In the UK, this type of work is carried out routinely by local highway authorities as route safety studies using historic collision data to identify problem routes and to establish common types of collisions. In addition, since 2002, the Road Safety Foundation has produced an annual report mapping the risks on motorways and major A roads in the UK as part of the EuroRAP project (Road Safety Foundation, 2013). The report compares risks on roads in different areas of the UK, and shows how risks on roads have changed over time. 

Almost 30 routes exist for administration of drugs to patients, but only a handfbl of these are commonly used in preclinical safety studies (Gad, 1994). The most common deviation from what is to be done in clinical trials is the use of parenteral (injected) routes such as IV (intravenous) and SC (subcutaneous) deliveries. Such injections are loosely characterized as bolus (all at once or over a very short period, such as five minutes) and infusion (over a protracted period of hours, days, or even months). The term continuous infusion implies a steady rate over a protracted period, requiring some form of setup such as an implanted venous catheter or infusion port. 

Pharmacokinetics and Metabolism. Pharmaceutical subchronic toxicity studies are always accompanied by a parallel determination of the pharmacokinetics of the material of interest administered by the same route as that used in the safety study. 

Other routes of administration used less commonly in dog safety studies are subcutaneous, intramuscular, intraperitoneal, rectal, and vaginal. 

Although no biopharmaceutical product delivered to the bloodstream via the pulmonary route has been approved to date, several companies continue to pursue active research and development programmes in the area. Amongst the leading product candidates is Exubera , an inhalable dry powder insulin formulation currently being evaluated by Pfizer and Aventis Pharma in Phase III clinical studies. The inhaled insulin is actually more rapidly absorbed than if administered subcutaneously and appears to achieve equivalent glycaemic control. While promising, final approval or otherwise of this product also depends upon additional safety studies which are currently under way. 

The design of a nonclinical safety study should use the most appropriate species and take into account the clinical route of administration, the dose, and the dosing schedule. In the clinic, the dosing schedule is usually episodic, either weeks or months apart. In the animal studies, this dosing period can be reduced to approximately 2 to 3 weekly intervals (see Sections 19.2.4 and 19.2.5). 

Many of the procedures used in conventional toxicity testing with animals have arisen by an apparently empirical process (e.g., period of exposure and selection of dose levels). Safety studies are performed with a variety of experimental animals, including rodents, rabbits, nonhuman primates, and farm animals, before progressing to studies with human volunteers, and other animals in the case of veterinary medicines. The individual study designs vary with the chosen animal species, route of administration, duration (dependent on the proposed or estimated exposure in... 

Where sufficient toxicologic information is available, we have derived minimal risk levels (MRLs) for inhalation and oral routes of entry at each duration of exposure (acute, intermediate, and chronic). These MRLs are not meant to support regulatory action but to acquaint health professionals with exposure levels at which adverse health effects are not expected to occur in humans. They should help physicians and public health officials determine the safety of a community living near a chemical emission, given the concentration of a contaminant in air or the estimated daily dose in water. MRLs are based largely on toxicological studies in animals and on reports of human occupational exposure. 

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