Safety dogs

South Africa does not require the use of safety dogs, whereas they are required in other countries. There are thus no load requirements for safety dogs in SANS 10208, but activation of safety dogs will apply high vertical loads to mine shaft guides. 

In 1854 Elisha Otis was at the Crystal Palace exposition in New York. After being hauled up in an elevator in an open-sided shaft, haUw up he had the rope cut with an axe, calling All safe, gentlemen . The shaft conveyance safety arrest mechanism (safety dogs) then took over. 

Health and Safety Factors. Butyrolactone is neither a skin irritant nor a sensiti2er however, it is judged to be a severe eye irritant in white rabbits. The acute oral LD q is 1.5 ml,/kg for white rats or guinea pigs. Subacute oral feeding studies were carried out with rats and with dogs. At levels up... 

Initial safety tests were carried out in beagle dogs and subsequently in cynomolgus monkeys. Single bolus i.v. doses of up to 100 mg kg-1 were used and were found to exert no negative effect upon general condition, blood pressure, heart or cardiovascular parameters, respiration rate or body temperature. No safety tests evaluating potential product effects upon the central nervous system were undertaken, as the protein is considered unlikely to cross the blood-brain barrier. 

With the aim of developing animal models appropriate for safety assessment of allergenic potential a number of species has been considered, including swine [94,99] and dogs [94,100-102], Although these species have their advantages, discussion here... 

Desfluorositagliptin was clean in a 2-week exploratory safety study in rats and in an acute dog tolerability study, as described above. This compound did show some effects in the anesthetized, vagotomized cardiovascular (CV) dog model... 

The safety tests look remarkably similar to those for traditional tests. Most have been done on three species the rat, the dog, or the monkey. The big difference has to do with the length of the test. It is rare for a safety test on a protein to be more than 13 weeks long. 

Toxicity studies traditionally are conducted using normal animals. However, studies in animal disease models may provide additional safety information regarding the possibility of disease exacerbation. For example, the administration of human recombinant erythropoietin was associated with hypertension in patients with chronic renal failure, and also in uraemic dogs, but not in normal dogs. 

In addition to rodent studies, regulatory guidelines for pharmaceuticals require that repeated dose safety studies of up to nine months (in the United States, six months elsewhere) in duration be conducted in a nonrodent species. The most commonly used nonrodent species is the dog, followed by the monkey and pig. Another nonrodent model used to a limited extent in systemic safety evaluation is the ferret. The major objectives of this chapter are (1) to discuss differences in rodent and nonrodent experimental design, (2) to examine the feasibility of using the dog, monkey, pig, and ferret in safety assessment testing, and (3) to identify the advantages and limitations associated with each species. 

This section is devoted to the definition and comparison of the three nonrodent animal models (dog, ferret, and monkey) in terms of experimental procedures, environmental and dietary requirements, as well as advantages and disadvantages of use in safety assessment testing. 

While the dog is a carnivore, it is able to adapt to an omnivorous diet. Requirements for dietary sources of energy, amino acids, glucose precursors, fatty acids, minerals, vitamins, and water have been established based on recommendations by the National Research Council (NRC, 1985). Adult beagles maintained in a laboratory environment function well with one feeding of standard laboratory chow per day. In safety assessment testing, however, some compounds may induce serious dietary deficiencies through induced loss of appetite, malabsorption, or vomiting, and, in these cases, it may be advisable to provide a dietary supplement. 

Common Study Protocols. The dog is the most commonly used nonrodent species in safety assessment testing (i.e., acute, subchronic, and chronic studies). The exception to this is its use in developmental toxicity and reproductive studies. For developmental toxicity studies, the dog does not appear to be as sensitive an indicator of teratogens as other nonrodent species such as the monkey (Earl et al., 1973) or the ferret (Gulamhusein et al., 1980), and, for reproductive studies, the dog is not the species of choice because fertility testing is difficult to conduct (due to prolonged anestrus and the unpredictability of the onset of proestrus) and there is no reliable procedure for induction of estrus or ovulation. 

Dosing Techniques. The most frequently used route of administration in dog safety assessment studies is oral. Dosing by capsule is usually the preferred oral route in... 

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

Clinical Observations and Physical Examinations. Daily clinical observations in dog safety studies, usually conducted pretreatment (prior to cage cleaning) and at a specified time(s) after dosing, consist of a home cage observation with notation of clinical signs indicative of poor health (such as salivation, weight loss, abnormal feces and vomitus) or abnormal behavior (such as reduced activity or increased aggression). 

Advantages and Disadvantages. Advantages of using monkeys in safety assessment studies include their phylogenetic proximity, as well as their physiological, behavioral, and, often, metabolic similarities, to humans (Table 16.13). An example is the similarity between the ovarian cycle of female monkeys and women (Mazue and Richez, 1982), which makes the monkey the ideal animal model for reproductive studies. Another advantage associated with most species of monkeys used in safety assessment studies is that they are much smaller than nonrodents such as the dog and, thus like the ferret, require less test compound. 

While there are advantages and disadvantages associated with all three nonrodent species, the dog is probably the nonrodent species most frequently used in safety assessment studies. This is because dogs are relatively docile and even tempered,... 

Study Type. Metabolic and pharmacokinetic data from a rodent species and a nonrodent species (usually the dog) used for repeat dose safety assessments (14 days, 28 days, 90 days or six months) are recommended. If a dose dependency is observed in metabolic and pharmacokinetic or toxicity studies with one species, the same range of doses should be used in metabolic and pharmacokinetic studies with other species. If human metabolism and pharmacokinetic data also are available, this information should be used to help select test species for the full range of toxicity tests, and may help to justify using data from a particular species as a human surrogate in safety assessment and risk assessment. 

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