The rat is commonly used in toxicology research due to its metabolic and physiological similarities to humans. Key reasons for its use include its small size, short lifespan, docile nature, and low cost. Several rat strains are commonly employed, including Wistar, Sprague-Dawley, and Long-Evans rats. Housing conditions and administration of test compounds require careful consideration to obtain reliable results and prevent disease transmission.

1. Dr.Rahul Vaja
(B.V.Sc&A.H , M.V.Sc)
1

2. The Rat (Rattus Norvegicus)
• The rat, considered to be the first animal to be domesticated for strictly scientific purposes, was first
used experimentally in France in the study of adrenal gland function.
• Many of the rat strains commonly used in toxicology today, including the Wistar, Sprague-Dawley,
and Long Evans. The Fischer 344, another commonly used strain, was developed for use in cancer
research.

3. Choice of the Rat in Toxicology Research
• The rat has become a species of choice because of
• Metabolic similarities,
• Their small size,
• Relatively docile nature,
• Shortlife span,
• Short gestation period.
• Although the rat is a species of choice in toxicology research because of the many physiological
similarities and anatomical characteristics, differences are also present.
• The placenta is considerably more porous in the rat. This difference could increase the chance of fetal
exposure to an administered test material or increase the overall level of fetal exposure to an
administered test material.
• The overall distribution of intestinal microflora is different in the rat, which could lead to differences in
the metabolism of an orally administered test material.

4. 1. Wistar rat
2. Sprague Dawley rat
3. Lewis rat
4. Long-Evans rat
5. Zucker rat
6. Biobreeding rat
7. Hairless rats
8. Royal College of Surgeons (RCS) rats
Strains of rat

5. Wistar rat
• Outbred albino rat.
• Wistar Institute, USA in 1906
• Most popular
• Wide head, long ears, and a tail length is less than its body length.
• The Sprague Dawley rat and Long-Evans rats were developed
from Wistar rats.
• Spontaneously hypertensive rat (SHR) and Lewis rat are
developed from Wistar rats.
• Wistar rats are more active than others

6. Sprague Dawley rat
• Outbred multipurpose breed
• Calm and ease to handle
• The average litter size of the Sprague Dawley rat is 11.0.
• Have increased tail to body length ratio compared with Wistar rats.

7. Lewis rat
• Developed by Dr. Lewis from Wistar stock (1950)
• A docile behavior, and low fertility.
• High incidences of neoplasm: adenomas of the pituitary and adenomas/adenocarcinomas of the
adrenal cortex, mammary gland tumors and endometrial carcinomas in females etc.
• Research: transplantation research, induced arthritis/inflammation, experimental allergic
encephalitis, and STZ-induced diabetes.

8. Long-Evans rat
• Outbred rat developed by Drs. Long and Evans in 1915 by crossing several Wistar females with a wild
gray male.
• Long Evans rats are white with a black hood, or occasionally white with a brown hood.
• Use: behavioral and obesity research.

9. Zucker rat
• Genetic model for research on obesity and hypertension.
• A lean Zucker rat, denoted as the dominant trait (Fa/Fa) or (Fa/fa);
• Obese Zucker rat, which is actually a recessive trait (fa/fa) of the leptin receptor, capable of
weighing up to 1 kilogram
• Obese Zucker rats have high levels of lipids and cholesterol & are resistant to insulin without
being hyperglycemic,
• Obesity due to hyperphagic nature & excessive hunger

11. • Current specifications for temperature and humidity are 18°C to 26°C and 30% to 70% relative humidity.
• Toxicity might increase at temperature extremes, toxicity might increase linearly with temperature, or
toxicity might remain constant with increasing temperature to a threshold, then begin to increase.
• Variations in light intensity should be taken into consideration when arranging animals on cage racks for
toxicology studies.
• Most research facilities operate on a 12-hr light/12-hr dark cycle, but a 14-hr light/10-hr dark cycle is also
acceptable.
• The rat is a social animal and whenever possible should be housed in pairs or groups of three.
• For the purpose of most toxicity studies, this might not be practical, but should be considered.

12. HOUSING
• May be housed in solid bottom shoe-box cages with bedding, generally in groups.
• Solid bottom caging with bedding recommended.
• Provide mice with warmth, security, and nesting material.
• Lids rest on top of the cage with locks or clamps.
• Mouse lid wires placed closer together than rat cages.
• Change bedding no less than twice a week.
• Cage and animal room sanitation are very important.
• Need to follow SOPs per facility
• Examples -
• Solid bottom cages/accessories – 1-3 times per week
• Cage shelving – At least once per month
• Wire bottom cages – At least once every 2 weeks

13. BEDDING
• Should be non-toxic, non-nutritive, unpalatable, non-abrasive, absorbent and inexpensive.
• Processed wood chips
• Corn cob products.
• Rodents generally fed ad libitum – given a continuous supply of food and water.
• Non-pelleted diets available – For use when food intake being measured or when substances are being
added.
• Food consumption – 3-6 grams, or 1.5 grams per 10 grams of body weight, per day

14. Study Design
• The length and design of toxicology studies used to predict human risk are
governed by guidelines issued by regulatory bodies such as FDA, EPA, and their
counterparts worldwide.
Maximum Tolerated Dose Study in Rats

15. • Subchronic and chronic toxicity studies are designed to assess the test compound effects following
prolonged periods of exposure.
• The highest dosage level in each of these studies should produce a toxic effect such that a target organ
can be identified.
• The lowest dosage level should provide a margin of safety that exceeds the human clinical dose and
ideally allows for the definition of a no observable effect level (NOEL).

16. • In addition to the subchronic and chronic toxicity studies, reproductive safety studies might also be required.
Reproductive toxicity studies are typically required for test compounds intended to be administered to women
of childbearing age or that might affect male reproduction.
• These studies include an assessment of the potential effects of the test compound on:
• general fertility and reproductive performance (Segment I),
• developmental toxicity (Segment II),
• or perinatal and postnatal development (Segment III).
• Typically 18 months to 2 years in duration, study is designed to assess the potential of the test compound to
induce neoplastic lesions.
• The highest dosage in a carcinogenicity study should cause minimal toxicity when administered via the
intended route for clinical use.

17. • Rodents have several unique characteristics to be considered regarding the oral administration of test
compounds.
• One of the most important characteristics is the lack of an emetic response.
• The lack of this response allows for a higher dose of a potential emetic compound to be administered
and evaluated.
• Many compounds and excipients can cause emesis in dogs or other large animal species and could lead
to a low level of exposure and erratic blood levels.

18. • Techniques for oral administration of test compounds include mixing in the diet, via gavage or stomach
tube, via capsule, or in drinking water.
• The most widely used methods of oral administration are the dietary and gavage techniques.

19. • The gavage method can be used when the test compound is not stable in the diet
or might not be palatable to the animals.
• The gavage method is also preferable when evaluating toxicokinetics or
pharmacokinetics.
• Methods for solution or suspension might be easier to develop than those
required for dietary mixtures.

20. • With the gavage method of dosing, a more precise amount of the test compound
can be delivered, and this might reduce the amount of test compound required to
complete the study.
• A disadvantage of the gavage method is that it involves handling of the rat for
each dosing.
• Handling of the rat has been shown to increase corticosterone levels and could
affect study results.
• Additionally, daily intubation might lead to death due to esophageal puncture or
inhalation pneumonia.

21. Gavage dosing with infant feeding tube

22. • One of the most common methods of administration of test
compound is via intravenous (IV) injection or infusion.
• The IV route is often the route of choice for compounds that have
poor bioavailability via the oral route or have a short half-life.
Tail vein injection

23. • The tail veins are currently the most widely used for IV injections in the rat.
• The veins are easily visible, especially in young animals, and one person can
perform injections without the use of anesthesia.
• Injection of 2 ml/100 g body weight can be performed without stress to the rat.

24. • Test compounds injected into the peritoneal cavity will be absorbed into the
portal circulation and transported to the liver.
• Based on the level of blood flow and circulatory surface area in the peritoneal
cavity, compounds injected intraperitoneally will be absorbed quickly.
Intraperitoneal injection technique

25. • Intramuscular injection of compounds will result in rapid absorption into general
circulation due to the abundant supply of blood vessels.
• However, the speed of absorption will not be as fast as with an intraperitoneal injection.
• A slow injection with a minimal volume will help to minimize pain. Approximately 1 ml/kg
of solution can be injected per site. If larger volumes are required, multiple injection sites
should be used.

26. • Absorption following subcutaneous injection is typically slower than following
intramuscular injection.
• This could be advantageous if a relatively sustained period of absorption is
desired.
• Another advantage of the subcutaneous route versus the intramuscular route is a
much larger volume of test compound can be administered.
• The rat has not traditionally been used as a model in skin irritation or
sensitization studies.
• The rectal route is not a routinely used method of administration in toxicology.

27. Lateral tail vein
Inferior vena cavaSaphenous (lateral tarsal)
vein
Cardiac puncture,
Jugular vein
Retro-orbital sinus
Blood Collection sites

28. Rat Dissection

30. COMMON DISEASE OF RAT
• Hantavirus Pulmonary Syndrom
• Leptospirosis
• Rat-bite Fever
• Plague
• Colorado Tick Fever
• Cutaneous Leishmaniasis:

31. How to Prevent Infections from Rats????
• Stop rats and mice infesting your home or garden.
• Wear gloves when carrying out pest control against rodents or working in areas where there are
signs rats or mice a have been active. Wash hands after handling anything that rats or mice may
have urinated on. Rodents continually dribble urine where ever they travel.
• In roof voids and other enclosed spaces where rodents have been it is sensible to wear a mask as
dust may carry disease organisms.
• Clean up rodent droppings where ever they are found and disinfect surfaces where rodents could
have travelled.
• Dispose of any food that have been eaten or may have been contaminated by rodents.
• If bitten or scratched by rodents always clean and disinfect wounds and seek medical attention
immediately.