GUIDELINES FOR INJECTION VOLUMES, NEEDLE SIZES AND OSMOTIC MINIPUMP SIZE CONSIDERATIONS A.

Maximum Injection Volumes and Needle Sizes A list of recommended maximum injection volumes and needle sizes for a variety of dosing sites in laboratory animals is provided. It is a guideline and should be used with good judgment and prior experience. These guidelines apply to healthy, adult animals. Contact a veterinarian for unhealthy animals, or species or routes not listed. Administration of excessive dose volumes may produce pain, excitement, altered physiological parameters (e.g., serum electrolyte imbalance, increased blood pressure, increased respiratory rate, etc.), and cause abnormal compound absorption. A large IM injection into a small muscle mass may force the dose into fascial planes and SC tissues that may accelerate lymphatic drainage and may also cause pressure necrosis or nerve damage. For parenteral routes of administration (a route other than PO), it may be less irritating to administer the dose halved in two separate locations. For studies requiring repeated parenteral dosing, the same site should not be used for two consecutive administrations. Table 1. Recommended Maximum Dosing Volumes Species Mouse Rat Hamster Swine PO a 20 ml/kg 20 ml/kg (max. 5 ml) 20 ml/kg 10 ml/kg (max 15) IV bolus b 10 ml/kg 5 ml/kg (max. 2.5 ml) 5 ml/kg 2.5 ml/kg IV slow injection c 20 ml/kg 10 ml/kg (max. 2.5 ml) 10 ml/kg 5 ml/kg IP a 20 ml/kg 20 ml/kg (max. 5 ml) 20 ml/kg 1 ml/kg SC a 20 ml/kg 20 ml/kg 20 ml/kg 1 ml/kg (max 2) IM a IN a

0.05 50 l ml/site 2 sites/day 0.1 ml/site 100 l 2 sites/day 0.1 ml/site 100 l 2 sites/day 0.25 ml/kg (max 0.5)

a. IV = intravenous; IP = intraperitoneal; IM = intramuscular; SC = subcutaneous; PO = per os; IN = intranasal drip b. Bolus injections should be carried out at ~ one minute. c. Factors to consider using slow intravenous injections or intravenous infusion include solubility or irritancy of the vehicles and compounds. For slow intravenous injection over the course of 5-10 minutes, a standard needle, a butterfly needle, or an intravenous catheter may be used.

Approved 12/21/05; Revised 3/21/12

Note: Not shown in Table 1 is subplantar injection for mouse/rat: maximum 0.1 ml per foot (normally one foot). Table 2 Recommended Intravenous Infusion Infusion Period Mouse Rat Total Daily Volumes (ml/kg) 4 Hour 24 Hour 4 Hour 24 Hour (-) data not available 96 4 20 60 Rate (ml/kg/h) 5 2.5 1 24 (Dose Volumes/Rates) Swine

Species

IV (bolus)/ slow injection (gauge) <25 <23 <25 <20

Table 3 Recommended Needle Sizes IV IMa IP (gauge) (infusion) (gauge) (gauge)

SC* (gauge)

PO

Mouse Rat Hamster Swine

<25 <23 <25 <20

<23 <21 <21 <20

<23 <21 <21 <20

<20 <20 <20 <20

20 24 gauge gavage cannula 16 20 gauge gavage cannula 18 gauge gavage cannula Drench gun/ gavage tube 6mm <15kg 8mm>15kg

B. Osmotic Minipumps - Animal Considerations Osmotic minipumps can be implanted subcutaneously or intraperitoneally following the animal size guidelines in Table 4. We recommend use of the smallest size pump allowable for the solubility of the agent and experimental duration. If you use the Alzet pumps, additional information is found at: http://www.alzet.com

Approved 12/21/05; Revised 3/21/12

ALZET Pump Model # 1003D 1007D 1002 2001D 2001 2002 2ML1 2ML2 2ML4

Table 4. Pump Models Recommended by Animal Size Mouse (minimum body weight) Rat (minimum body weight) Subcutaneous Intraperitoneal Subcutaneous Intraperitoneal 10g 20g 10g 20g 20g N/A 20g 150g

N/A

N/A

150g

300g

Approved 12/21/05; Revised 3/21/12