`
`GOOD PRACTICE GUIDELINES
`
`Administration of Substances
`
`(Rat, Mouse, Guinea Pig, Rabbit)
`
`Members of the working Group.‘
`Dr H B Waynforth (Chairman); Professor P Brain; Mr T Sharpe; Mr D F Stewart,‘
`Mr K A Applebee; Dr P G G Darke (Home Ofiice Observer)
`
`Other articles in the series include.‘
`
`Selection of Animals for Scientific Purposes
`
`Collection of Blood Samples (Rat, Mouse, Guinea Pig, Rabbit)
`
`Polyclonal Antibody Production in Rabbits
`
`Standards of Rodent Surgery
`
`Euthanasia
`
`Handling and Restraint (Rat, Mouse, Guinea Pig, Rabbit)
`
`Record Keeping for the Personal Licence Holder
`
`Laboratory Animal Allergy
`
`Articles were contributed by scientists and technologists established in the field and
`were peer reviewed
`
`Series 1/Issue 1 — October 1998
`
`Laboratory Animal Science Association, PO Box 3993, Tamworth, Staffordshire, B78 3QU
`Telephone: 01827 259 130 Fax: 01827 259 188 — e-mail: lasa@globalnet.co.uk
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`LASA GOOD PRACTICE
`GUIDELINES
`
`ADMINISTRATION OF SUBSTANCES
`
`(RAT, MOUSE, GUINEA PIG, RABBIT)
`
`Introduction
`
`Many research programmes require the administration of substances to laboratory species.
`The effect of this on the animals concerned may be minimal or profound, depending on
`the substance itself, the formulation, the volume, the frequency of dosing and the skill of
`the operator. Practical expertise in a particular method should be gained by guidance from
`an experienced person and carried out under supervision until competence is attained. A
`good skill level then needs to be maintained by regular use of the method.
`
`Substance and formulation
`
`Every effort should be made to flnd out as much as possible about likely toxicity and to
`choose a dose which will avoid unnecessary toxic effects.
`Solubility problems are not uncommon. Therefore information and advice should be
`sought
`in order to ensure that formulations are effective, of minimal
`toxicity and
`compatible with the route of administration required.
`
`Dosing technique
`
`Recommended sites and methods in rats, guinea pigs and rabbits are outlined in the table
`below. General recommendations include:
`
`1.
`2.
`
`3.
`
`4.
`U1
`
`Firm but sympathetic restraint is essential for all methods.
`Always use the smallest needle diameter which will allow reasonably swift
`injection of the substance. Make certain the needle is only long enough to reach
`the intended site of injection.
`Always use the smallest possible volume compatible with the solubility of the
`substance.
`
`Use aseptic technique for injections wherever possible.
`Always observe the animals carefully after dosing for any adverse effects.
`
`Common sites for dosing
`
`sahenous vein
`
`Gavage, or in food
`or water
`Scruff or flank
`
`Rabbit
`Drench (small
`volumes or ava e
`Scruff or flank
`
`‘ Rat
`Oral
`Gavage, or in
`Gavage, or in
`food or water
`food or water
`Scruff or flank
`Scruff or flank
`
`Subcutaneous
`
`Intramuscular Anterior thi h
`Intravenous
`Tail vein
`
`Anterior thi h
`Tail vein
`
`Anterior thi h
`Ear vein or
`
`Anterior thi h
`Ear vein
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`Series 1: Issue 1: Administration of Substances (Rat, Mouse, Guinea Pig, Rabbit)
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`A)
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`Oral dosing
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`LASA GOOD PRACTICE
`GUIDELINES
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`2.
`
`Key points include:
`1.
`Gavage using a flexible catheter attached to a syringe is a practical method in the
`species listed. Inflexible cannulae can be used, but great care is required to avoid
`trauma The gavage catheter is passed via the mouth, which induces swallowing
`movements so that the catheter passes down the oesophagus into the stomach.
`Proper restraint of the animal is critical.
`It is essential that the catheter does not pass into the trachea, as "lung dosing" is
`likely to be fatal. Pre-measure the length of catheter required to reach the stomach,
`on the outside of the animal. There should be no resistance to passing the catheter
`and any encountered may indicate that it
`is in the trachea - withdraw it and
`reintroduce the catheter no more than once or twice only.
`Administration via the food or water is less stressful than by gavage, but many
`substances are not palatable and there is also less certainty about the amount of
`substance which is received by the individual animal.
`
`3.
`
`B)
`
`Subcutaneous dosing
`
`Key points include:
`Use sites where the skin is loose and mobile.
`
`1.
`
`Keep the angle of the injection needle shallow to avoid damage to underlying
`tissues.
`
`C)
`
`Intramuscular dosing
`
`Intramuscular injection in small laboratory species can be difficult because of the
`lack of big muscles.
`It is a route which is not recommended unless there are good
`scientific reasons for using it.
`Key points include:
`Use very small volumes in small laboratory species (see table).
`Make certain the substance is not irritant.
`
`Be certain about the local anatomy: avoid veins, arteries and nerves.
`
`1.
`
`3.
`
`D)
`
`Intravenous dosing
`
`1.
`2.
`
`3.
`
`4.
`
`Key points include:
`Aseptic technique is essential.
`Dilate the vein to aid visualisation and needle entry. Avoid the use of xylene for
`this purpose.
`Penetrate the vessel with a hypodermic needle and check for evidence of blood at
`the hub of the needle before injecting.
`Apply haemostasis after removing the needle and ensure bleeding has stopped
`before returning the animal to its housing.
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`Series 1: Issue 1: Administration of Substances (Rat, Mouse, Guinea Pig, Rabbit)
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`LASA GOOD PRACTICE
`GUIDELINES
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`E)
`
`Intraperitoneal dosing
`
`Key points include:
`Use short needles to avoid damaging abdominal organs.
`Aim to make the injection into one of the posterior quadrants of the abdomen.
`Aspirate on the syringe to ensure that the gut has not been penetrated
`
`1.
`.
`3.
`
`Recommended maximum volumes for dosing
`
`‘ Rat
`20 ml/k
`20 ml/k
`20 ml/k
`5 ml/k
`
`Subcutaneous
`
`20 ml/k
`5 ml/k
`
`Rabbit
`10 ml/k *
`1 ml/k
`
`0.25 ml/k/site
`
`2 ml/k
`
`4 ml/k
`
`Intramuscular
`
`0.05 ml total
`
`0.1 ml total
`
`0.1 ml total
`
`Intravenous **
`
`10 ml/k
`
`Intra n eritoneal
`
`20 ml/k
`
`5 ml/k
`
`10 ml/k
`
`5 ml/k
`
`10 ml/k
`
`* for doses by gavage.
`** limits quoted are for bolus injection carried out over a relatively short period of time
`(less than 1 minute).
`The limits described are for once daily dosing on a routine basis. Exceptions are
`certainly possible, but may need special care and supervision.
`
`References
`
`In: Laboratory Animal
`Bivin WS, Smith GD (1984) Techniques of Experimentation .
`Medicine, (Fox JG, Cohen BJ, Lowe FM, eds). Orlando: Academic Press.
`
`Hull RM (1995) Guideline limit volumes for dosing animals in the preclinical stage of
`safety evaluation. Human and Experimental Toxicology 14, 305-307.
`
`Waynforth HB, Flecknell PA (1992) Experimental and Surgical Technique in the Rat,
`2nd ed. London: Academic Press.
`
`Wolfensohn S, Lloyd M (1998) Handbook of Laboratory Animal Management and
`Welfare. 2nd ed, Oxford: Oxford University Press.
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`Series 1: Issue 1: Administration of Substances (Rat, Mouse, Guinea Pig, Rabbit)
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