A Practical Approach, Second Edition=Ronald D. Ho.pdf

222 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITIONWhen catheters are used, the dosing compound is drawn directly into the syringe. Then theadapter with the catheter is attached to the syringe, and the catheter is fed through the bit completelyinto the stomach. If the tube is guided into the trachea, the rabbit will twitch its ears and cough,signaling the technician to withdraw the tube and try again. Steady movement of the nostrils shouldbe apparent while the compound is being injected by use of a rubber catheter. With this method,it is necessary to “wash” the catheter with approximately 1 ml of vehicle after dosing, to administerthe last milliliter of compound remaining in the catheter.2) Dosing via the Diet — The test compound may be introduced directly into ground rodent orrabbit feed, depending on the characteristics of the compound, including its palatability and solubility.The test compound may be mixed with a solvent prior to mixing with the feed, or it may bemicroencapsulated to limit release to a particular part of the intestines or to ensure that unpalatablecompounds will be eaten.Ground feed for rodents is made available in the home cage in glass feed jars that are chemicallyresistant, easily sanitized, and transparent (allowing cage-side observation of the feeder). The jarsare typically fitted with a stainless-steel lid. Mouse feed jars are also fitted with a wire cylinderthat allows access to the feed but prevents nesting in the feed. Rats will generally use their pawsto scoop out the feed and then lick their paws. The feed jar is weighed at intervals based on thesize of the jar, the amount consumed, and the stability of the compound in the feed. This allowsthe calculation of grams of feed eaten per kilogram of animal body weight per time interval (usuallydaily), and therefore quantitates (in milligrams or gram per kilogram body weight per day) theactual amount of test article consumed. Most feed consumption occurs during the dark cycle, sothe rodent is being “dosed” periodically at night. This differs from gavage, where the test materialis generally given as a once-daily bolus dose in the morning.Rabbits will not eat ground food; 33,45 therefore, any ground, feed-based dose formulation mustbe pelleted prior to administration to rabbits. This may be done in-house or by commerciallaboratories. Because most performing laboratories do not have pelleting capabilities, many compoundsthat may be administered to rodents in the feed are given to rabbits by gavage.Before glass feed jars are used for another study, they should be washed. Then, several jarsthat had been used for the high-dose feed should be rinsed, employing a solvent appropriate forthe test compound they had contained. The jar rinse is then analyzed for the presence of the testcompound. If the results of the analysis are negative, the jars are considered suitable for use inanother study. If not, additional washing may be done, or the jars may be soaked with solvent andreanalyzed.3) Dosing via Drinking Water — The major consideration for use of drinking water as a vehiclefor compound administration is the palatability of the test compound in water. If the animals won’tdrink their water because of its smell or taste, you cannot successfully dose them by this route.Water bottles are used for the dosing solution. These may be polypropylene or polycarbonate ifthe test compound is nonreactive with plastic. Glass bottles may be used (either clear or amber),depending on the reactivity of the compound to light. In our experience, plastic bottles are unsuitablefor rabbit studies because rabbits tend to play with the bottles to the extent that measurement ofwater consumption is almost impossible. Glass bottles in sturdy holders seem to be more reliable.Water consumption is determined by weighing the bottle at intervals determined by the stabilityof the compound and the volume of water consumed daily by the animal. Bottle washes shouldalso be done prior to use for another study to verify absence of test compound.4) Injection — Intravenous — The blood vessels used for intravenous (i.v.) injection in therodent are normally the dorsal and ventral tail veins. Rodents are dosed i.v. at between 2.5 and 10ml per kilogram of body weight. To dilate the vein, the rodent is placed in a warming box undera heat lamp for a few seconds, or the tail is placed in a warm water bath at 37°C. The rodent is© 2006 by Taylor & Francis Group, LLC