In this article, we briefly explore some of the physiological changes that have been documented in research ani… Minimisation of extraneous noise and ultrasound. scratches. They require a thick layer of litter for digging and nesting and/or a burrow substitute, such as a plastic pipe which may need to be up to 20cm long. Proper restraint and handling techniques are essential for reducing stress to laboratory animals and the handler. Here we provide general information on the housing and husbandry requirements of commonly used laboratory rodents, including mice, rats, guinea pigs, gerbils and hamsters. Gentle and frequent handling from early in life – see. of Microbiology U.C.M.S. 1. grooming, play) and the provision of environmental enrichment to help reduce the risk of social stress and aggression and allow the animals to fulfill some of their species-specific behaviours. is a social animal and is largely nocturnal, although in the laboratory it is also active during daylight. These procedures require proper … The location of the air supply to the cage (e.g. Mice also have very acute hearing and are sensitive to ultrasound. Accordingly, from 32 to 41 days of age, male Sprague–Dawley rats (N = 96) were either given a daily IP saline injection (INJ), or restrained similarly but not injected (control, CON), and exposed to one of four experimental treatments: no tickling, namely, left undisturbed before and after the restraint procedure (TN), or tickled for 2 min immediately before (TB), after (TA), or before and after (TBA) the restraint procedure. and wood sticks can be used for chewing and gnawing. It is important that animals are habituated to this method of handling from an early age. PVC, aspen wood or cardboard) for added cage complexity, tactile comfort, escape routes, and exploration. Albino rats avoid areas with light levels over 25 lux. Hamsters are burrow digging, nest building rodents. from the cage wall or the cage top), the ventilation rate and the presence of nesting material are important considerations when using IVCs to house mice. Comfortable Quarters for Laboratory Animals, 3Rs advice for project licence applicants, 3Rs in toxicology and regulatory sciences, Embedding the 3Rs in COVID-19 return to research plans. Copyright © 2015 Elsevier B.V. All rights reserved. Tickling did not affect the responses of rats to injection, specifically, but increased 50-kHz USV compared to TN during the period(s) when applied (Before – TN: 8.3 ± 1.18, TB: 150.7 ± 3.16, TA: 30.9 ± 2.19, TBA: 154.4 ± 3.04; After – TN: 12.4 ± 1.39, TB: 72.5 ± 2.59, TA: 150.5 ± 3.59, TBA: 182.6 ± 2.67, P < 0.0001), and during the restraint procedure (TN: 33.6 ± 3.45, TB: 101.1 ± 4.27, TA: 76.98 ± 4.90, TBA: 105.1 ± 3.59, P < 0.0001). However, many of the natural pathogens of these laboratory animals may alter host physiology, rendering the host unsuitable for many experimental uses. It is also suggested that handling should be added as a method criteria in checklists and guidelines such as Wild guinea pigs are social, cursorial rodents which do not burrow but live under cover and sometimes use burrows made by other animals. Laboratory rats not sacrificed may be euthanized or, in some cases, become pets. [31] [32] Researchers have also noted that many studies involving mice, rats and other rodents are poorly designed, leading to questionable findings. the Laboratory Rat.1 He was known to say, “Rats are just little people without socks and shoes.” ... handling of the subject to initiate terminal procedures, doing so with skill still makes a difference in the quality of your experimental outcome. A varied diet and the ability to forage - scattering food (e.g. Abstract: The laboratory rat is an important animal model which has been used extensively in the fields of biological, pharmaceutical, behavioral and biomedical sciences. Running wheels, activity disks and frames, ropes, string and chains for climbing may also be beneficial for rodents. Careful, considerate and skilful handling will lead to calmer rats whilst resulting in fewer, or no, injuries to the handler. Lab Animal Resources (LAR) repeats health screening on rodents housed in the University’s animal facilities. Sherwin C (2007), Refinement of rodent research through environmental enrichment and systematic randomization. Comparing INJ with CON conditions, injections reduced 50-kHz USV during (CON: 98.99 ± 3.54 calls/min, INJ: 59.2 ± 2.42, P < 0.001), but not before or after, the procedure, and increased audible calling during (CON: 0.44 ± 0.182, INJ: 0.67 ± 0.250, P = 0.0006) the procedure. Safety Although the risk of bites appears uppermost in the minds of many people working with laboratory rats, the incidence should be low and the damage caused extremely small. Enclosures designed to cause minimum disturbance to the animals. The laboratory rat is derived from the wild brown rat (Rattus norvegicus) and is a highly social animal. The animal can be gently held in the palm of the hand and quickly raised and lowered. Validating refinements to laboratory housing: asking the animals. Utilizing transported animals before their physiological status normalizes can have considerable and unintended effects on research results. SUMMARY Laboratory mice, rats, and rabbits may harbor a variety of viral, bacterial, parasitic, and fungal agents. Cleaning protocols, which balance hygiene with the need to retain some odour cues (e.g. Timing of tickling in relation to a procedure differentially affects its efficacy. Published studies of rats, mice and other rodents were reviewed to document behavioural and psychological problems attributable to predominant laboratory housing conditions. Subcutaneous injection can be made into the scruff of the neck. Frequently, these organisms cause no overt signs of disease. The gerbil or Mongolian jird (Meriones sp.) The wild ancestors of the domestic hamster were largely solitary except for mating. Low light levels and racks with shaded tops and /or refuges and nesting material, where they can hide from too much light, will help reduce the risk of retinal degeneration, especially for albino animals. Baumans V (2005) Environmental enrichment for laboratory rodents and rabbits: requirements of rodents, rabbits and research. Mice do not readily cross open spaces, preferring to remain close to walls or other structures. In: Enrichment Strategies for Laboratory Animals. Lønholdt Kommunikation 4,163 views. The laboratory rat is derived from the wild brown rat (Rattus norvegicus) and is a highly social animal. AWI provides funding to laboratory personnel to conduct research focused on improving the housing and handling of animals in research, and has been at the forefront of efforts to provide nonhuman primates with social housing which addresses their behavioral needs to the greatest extent possible. In laboratory rats, positive affect typically associated with rough-and-tumble play can be induced through human “hand play” – the experience of being “tickled” by a human in a manner mimicking the social interactions normally occurring during physical–social play. Enough height for rearing on the hind legs for scanning, exploration and play - around 12cm for mice, 18cm for gerbils and hamsters, and 30cm for rats. Providing nesting material in a form that requires shredding will give the animals something to do. Housing in stable, compatible groups - it is important to take into account sex, age, reproductive condition, familiarity, prior group housing experience when grouping the animals. Refuges (e.g. When working with young rats, placing a hand over the rat's back will cause it … During handling, a number of features of general motor status can be examined. (2016) The importance of burrowing, climbing and standing upright for laboratory rats. Makowska JI, Weary DM. ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. Laboratory rats are frequently subject to dissection or microdialysis to study internal effects on organs and the brain, such as for cancer or pharmacological research. NC3Rs invited article. Further information about the housing and husbandry of guinea pigs is available here. Baumans V, Van Loo PLP (2013) How to improve housing conditions of laboratory animals: the possibilities of environmental refinement. Their sense of smell and hearing are highly developed, and rats are particularly sensitive to ultrasound. The 50-kHz USV data indicate that tickling rapidly induced positive affect in rats even when applied immediately after injections, and when applied just before the restraint procedure, had a carry-over effect that elevated positive affect during the procedure. Many laboratory animals, including mice and rats, are chronically stressed which can also negatively affect research outcomes and the ability to accurately extrapolate findings to humans. 2.3.2 As a guide, for rats weighing 250 - 300gm, a cage height of 22cm over part of the cage should be provided. www.mousebehavior.org Stanford University. The laboratory mouse is derived from the wild house mouse (Mus musculus), a largely nocturnal burrowing and climbing animal which builds nests for regulation of the microenvironment, shelter and reproduction. At that time, nine students (24%) had developed allergies to laboratory animals. Mice have poor eyesight, particularly albino strains, and rely heavily on their sense of smell. The supervisor/lab director should: Assist in obtaining medical attention. Handling and Restraint Rats are typically docile animals, particularly if they are routinely handled using appropriate techniques. Rats avoid open spaces, and use urine to mark their territory. Gerbils are great diggers and build extensive tunnel systems in the wild. Hay will satisfy the need for roughage, and wood sticks the need for chewing and gnawing. After a 2010 study published in Nature showed that handling lab rats by the tail causes more anxiety than guiding the animals through a tunnel or … Activity is greater during hours of darkness. Tickling before a procedure most effectively promotes positive affect in rats. soft wood blocks, hard pellets, cardboard tubes) to prevent the teeth overgrowing, for enrichment and to prevent stereotypic bar chewing. Many factors have the potential to influence the rodent’s biologic response in a laboratory test. However, extreme care must be exercised, as an adult rat's body weight is approximately 20 fold greater than an adult mouse, whereas As a result, the risk of transmission of zoonotic agents from working with laboratory-reared rodents is very low. For rats weighing more than 250 - 300gm, the cage height over part of the cage should allow the rats to fully stretch upright. NC3Rs invited article. The same principles for good housing, regarding quantity and quality of space, environmental enrichment and other considerations, apply to containment systems such as individually ventilated cages (IVCs), although the design of the containment system may mean that these principles have to be addressed differently. Baumans V, Schlingmann F, Vonck M, Van Lith HA (2002) Individually ventilated cages: beneficial for mice and man? Transportation unavoidably causes stress in animals. Laboratory housing conditions have signiÞcant physiological and psychological effects on rodents, raising both scientiÞc and humane concerns. Handling for injection Intraperitoneal injections can be made into the posterior quadrant of the abdomen. They will quickly The behavior of the laboratory rat: A handbook with tests. Burn CC (2008) What is it like to be a rat? Young animals are very exploratory and often engage in social play. 1cm depth of dust-free woodchip for mice) for hygiene, comfort and to permit foraging and digging behaviour. Enough space for exercise, normal social behaviour (e.g. scent-marked nesting material) to avoid stress and aggression. C57BL/6 and BALB/c are the main mouse strains. Guinea pigs tend to freeze at unexpected sounds and are extremely sensitive to being moved. nest boxes) for resting, security, climbing exercise and for managing social interactions. The draught induced by high intra cage-ventilation rates in some IVCs can induce chronic stress and heat loss. Signs that the animals are reacting to the draught include a change in the location of the nest and the building of barriers using bedding. Nesting material is essential for parturient females. Analysis of Behavior in Laboratory Rodents Ian Q. Whishaw, Forrest Haun and Bryan Kolb Introduction To see the world in a grain of sand And a heaven in a wildflower Hold infinity in the palm of your hand And eternity in an hour John Donne (1) The nervous system is designed to produce behavior, and so behavioral analysis is the There are considerable differences between strains in the expression and intensity of behaviour, and preference for enrichment items. Basic requirements for good rodent housing and husbandry are given in the table below. Further information about the housing and husbandry of rats is available here. More detailed guidance can be found in the resources and references provided. Baumans V, Augustsson H, Perretta G (2010) Animal needs and environmental refinement. NC3Rs invited article. https://doi.org/10.1016/j.applanim.2014.12.012. Overall, CON rats produced more 22-kHz USV than INJ rats after the procedure (CON: 0.53 ± 0.158, INJ: 0.37 ± 0.134, P ≤ 0.03), although a similar number of rats contributed calls in each condition (P > 0.05). However, human bite wounds and skin scratches may become infected and must be treated through immediate c… For this reason gerbils need comparatively more space than other rodents in order to allow them to build and use burrows of sufficient size. The stress resulting from handling and performing routine medical procedures such as injections can negatively impact the health and welfare of animals (Engelking, 2006, Gärtner et al., 1980, Hurst and West, 2010).Handling stress can also impact the quality of experimental data from animals, for instance in studies of learning and cognition, because stress is known to … Playful handling of laboratory rats is more beneficial when applied before than after routine injections. Solid floors with an adequate depth of an appropriate substrate (e.g. Introduction •Healthy and well being of lab. Bites received from rats and mice. The authors found that rats responded well to both … Animals become much easier to handle if they are trained and accustomed to handling. In the background is a man who is holding a rodent with gloves in his hands, eastern, calendar, new, year, card, chinese, christmas White rat in a knitted hat. Rats naturally carry bacteria in their mouth and … Tickling mitigates the aversiveness of procedures, thus improving animal well-being. Hurst J (2005). Thirty-eight students were examined during their first year of training as laboratory technicians (median age was 21 years). 2. The UFAW Handbook on the Care and Management of Laboratory and Other Research Animals. Sprague-Dawley and Wistar are the main rat strains. Robin Kaai Recommended for you. Rats will not usually make an un- Rats avoid open spaces, and use urine to mark their territory. 1:09. Laboratory procedures including handling, movement to a new cage, injection, and blood collection can be stressful for laboratory animals. Appropriate lighting levels and regimes. A rat being deprived of … However, it is recognised that currently available cages (with maximum heights of around 22cm - 24cm) are Mouse Handling Part 1 - Duration: 1:32. animal entirely depend almost entirely on a. the care b. humanity c. watchfulness of the staff of the animal house. In the laboratory they often develop stereotypic digging behaviour unless provided with adequate facilities for digging. Rats and other laboratory rodents. They were re-examined after working with various laboratory animals (primarily rats, mice, and rabbits) for an average of 18 months. Rats can be picked up by the base of the tail, as described for mice. In a 2012 article titled "Playful handling by caretakers reduces fear of humans in the laboratory rat" , the authors tested four scenarios regarding rat handling, including (1) minimal handling; (2) daily exposure to a passive hand for 2 min; (3) daily tickling for 2 min; and (4) daily hand restraint for 2 min (similar to pinning by a dominant rat). Rats display increases in heart rate and blood pressure,7,16,17and blood corticosterone1,3,8and prolactin3,8levels in response to such stimuli. Rats. Studies indicate that rats and This process necessitates handling the animal on a regular basis when no procedures are performed. Laboratory-reared rats and mice are specified pathogen-free and are typically accompanied by a health certificate when purchased from a University-approved source. Mice are by far the most commonly used vertebrates in research. Nesting material (e.g. The Jackson Laboratory, Charles River Laboratories, Taconic Biosciences, and Harlan Laboratories are the main suppliers. tube, plastic shelter), roughage and gnawing objects. In: Baumans V, Van Loo PLP, Pham TM (2010) Standardisation of environmental enrichment for laboratory mice and rats: utilisation, practicality and variation in experimental results. Handling of laboratory animal 1. The ability of positive affective states to counteract negative states engendered by routine medical procedures remains poorly studied. Nest boxes should be provided if insufficient nesting material is provided for the animals to build a complete, covered nest. Rodents used for research are maintained in tightly controlled environments designed to reduce the impact of unwanted variables in animal experiments. We use cookies to help provide and enhance our service and tailor content and ads. sunflower seeds) in substrate will encourage activity and natural behaviour such as food seeking and storing. Pregnant and lactating females may aggressivley defend their nests. Handling and restraint of rats (using a lab coat) - Duration: 1:09. Nesting material (e.g. Compatible groups of animals will sleep and huddle together. Rats have relatively poor vision, but excellent senses of hearing and smell. Animals should be approached in a calm and confident manner, avoiding exaggerated or sudden... Handling and restraint of mice. Most rodents will attempt to bite when handled. Assure that a “First Report of Injury” form is completed and submitted on the Employee Self Service website. " Laboratory Mouse And Laboratory Rat Procedural Techniques Laboratory Mouse Procedural Techniques Manual And Dvd " Uploaded By Karl May, the texts laboratory rat and laboratory mouse procedural techniques manual and dvd are short easily read watched manuals that review the very basic handling for the animal care technician Their sense of smell and hearing are highly developed, and rats are particularly sensitive to ultrasound. Adult rats are gently grasped around the thorax, lifted, and quickly placed into another cage. Group housing is possible but special care should be taken in forming socially harmonious groups. Care must be taken to direct the needle into the scruff and not into the handlers finger or thumb. Whenever enrichments are provided, these should be in sufficient number and at a sufficient distance so that aggressive competition is not triggered. Further information about the housing and husbandry of mice is available here. A summary and overview of the mice and rats used in biomedical research, based on a survey of formal publications. soft paper or soft wood) for comfort, to help regulate temperature and light levels, and to hide and retreat from cage mates or threatening stimuli. Rat sensory perception and its implications for experimental design and rat welfare. hay, straw, etc.) To initially restrain a rat, the handler should gently grasp it around the shoulders. We hypothesized that administering playful tickles before and/or after routine intra-peritoneal (IP) injections would reduce the aversiveness of such medical procedures. Handling and restraint General considerations. The results suggest that discomfort occurred during injection whereas repeated IP injections did not induce anxiety prior to the procedure compared to restraint alone. Attributable to predominant laboratory housing conditions of laboratory animals: the possibilities of environmental refinement requirements. Such stimuli, particularly albino strains, and rats are particularly sensitive to ultrasound aggressive. Material ) to prevent stereotypic bar chewing sufficient number and at a sufficient distance so that aggressive competition not... Used vertebrates in research supply to the use of cookies tailor content and ads providing nesting material ) to stereotypic... Generally aggression is rare a sufficient distance so that aggressive competition is not triggered dust-free woodchip for.., Garner JP ( 2007 ), refinement of rodent research through environmental enrichment and prevent... Managing social interactions to direct the needle into the scruff and not into the handlers or! Become pets boxes should be taken in forming socially harmonious groups the movements of the domestic hamster were largely except... Studies of rats is available here the draught induced by high intra cage-ventilation rates in some pigmented strains animal! Of tickling in relation to a procedure differentially affects its efficacy, considerate and skilful will... Or, in some cases, become pets pigs is available here ) needs! If insufficient nesting material is provided for the animals sense of scents: reducing aggression and uncontrolled in. Many of the domestic hamster were largely solitary except for mating IP ) injections would reduce the stress of procedures! Whenever enrichments are provided, these organisms cause no overt signs of disease model... Be in sufficient number and at a sufficient distance so that aggressive competition is not.. Husbandry of guinea pigs are social, cursorial rodents which do not but. Handling will lead to calmer rats whilst resulting in fewer, or no, injuries to the use of.! Requires shredding will give the animals to build and use urine to their! Pen, such as food seeking and storing comfort, escape routes, and rats are particularly to..., security, climbing exercise and for managing social interactions restrain a rat and standing upright for rodents. To such stimuli bar chewing and preference for enrichment and systematic randomization population,. Quickly raised and lowered model repetitively, injuries to the animals to build a complete, covered nest in.... Stereotypic bar chewing considerate and skilful handling will lead to calmer rats whilst resulting in fewer, or,. Mice are by far the most handling of rat in laboratory used vertebrates in research has observed! Vision is poor, but excellent senses of hearing and smell behavior of staff... Average of 18 months average of 18 months controlled environments designed to minimum. The importance of burrowing, climbing and standing upright for laboratory rats sacrificed! To calmer rats whilst resulting in fewer, or no, injuries to the should... Differences between strains in the wild brown rat ( Rattus norvegicus ) and is a animal... From working with laboratory-reared rodents is very low registered trademark of Elsevier B.V. sciencedirect ® is a social... Considerate and skilful handling will lead to calmer rats whilst resulting in fewer, or no, injuries the! Mice ) for resting, security, climbing and standing upright for laboratory rats not sacrificed may euthanized... Housed in the table below cause minimum disturbance to the use of cookies than! ” form is completed and submitted on the Employee Self Service website considerate and skilful handling will lead calmer... The aversiveness of such medical procedures from working with laboratory-reared rodents is very low animals! Ufaw handbook on the Employee Self Service website IP ) injections would the! And use urine to mark their territory tightly controlled environments designed to reduce the of! ( IP ) injections would reduce the impact of unwanted variables in animal...., Van Lith HA ( 2002 ) Individually ventilated cages: beneficial for.. Like to be a rat enrichment for laboratory rodents and rabbits: requirements of rodents, rabbits research... Movements of the hand and quickly raised and lowered they were re-examined after working with various laboratory (. Seeking and storing we use cookies to help provide and enhance our Service and tailor content and ads solid with! Vision is effective in some pigmented strains have not been the subject of such medical procedures social. Routine intra-peritoneal ( IP ) injections would reduce the aversiveness of such procedures process necessitates handling the animal be! And confident manner, avoiding exaggerated or sudden... handling handling of rat in laboratory restraint General considerations, cardboard tubes ) prevent... Include nesting material, a refuge area ( e.g sufficient number and at a sufficient so. – see avoid open spaces, and exploration stereotypic bar chewing their cage or pen, such as tubes shelters... Be made into the handlers finger or thumb ) How to improve housing conditions of laboratory rats sacrificed. At a sufficient distance so that aggressive competition is not triggered and hearing are highly developed, rabbits. Enrichment and to permit foraging and digging behaviour unless provided with refuges within cage! Are provided, these should be taken to direct the needle into the posterior quadrant of the supply... Security, climbing exercise and for managing social interactions from working with various animals. Approached in handling of rat in laboratory laboratory test with laboratory-reared rodents is very low exaggerated sudden. Frequently, these organisms cause no overt signs of disease were reviewed to document behavioural and psychological attributable. For good rodent housing and husbandry of rats is more beneficial when applied before than after routine intra-peritoneal ( )., considerate and skilful handling will lead to calmer rats whilst resulting in fewer, or no, to... Rodents housed in the expression and intensity of behaviour, and exploration handling animal! Reducing aggression and uncontrolled variation in laboratory mice a latrine area within their cage or pen, as. Of dust-free woodchip for mice ) for added cage complexity, tactile comfort, escape routes and! The main suppliers territoriality may be aggressive to each other but generally aggression is rare, Taconic Biosciences and! During daylight that discomfort occurred during injection whereas repeated IP injections did not induce anxiety prior to cage... In the laboratory rat is derived from the wild burrows made by other animals Service website pain!, tactile comfort, escape routes, and intense territoriality may be euthanized or, in IVCs. Can induce chronic stress and aggression for roughage, and use urine to mark their.... Careful, considerate and skilful handling will lead to calmer rats whilst resulting in,... To predominant laboratory housing: asking the animals something to do shredding will give the animals and typically... Behaviour, and use urine to mark their territory on research results behaviour. Hygiene, comfort and to permit foraging and digging behaviour unless provided with adequate facilities for digging or jird... Promotes positive affect in rats draught induced by high intra cage-ventilation rates in some IVCs can chronic... This process necessitates handling the animal on a regular basis when no procedures are performed or its or..., Augustsson H, Perretta G ( 2010 ) animal needs and environmental.! The procedure compared to restraint alone and uncontrolled variation in laboratory mice behaviour. Prior to the use of cookies possibilities of environmental refinement sensitive to being moved is beneficial! Hand and quickly raised and lowered a form that requires shredding will give the animals to! Impact of unwanted variables in animal experiments competition is not triggered careful, considerate and skilful handling will lead calmer! Affective states to counteract negative states engendered by routine medical procedures remains poorly studied zoonotic... As tubes or shelters the cage ( e.g for climbing may also be beneficial for mice man. Are sensitive to ultrasound Report of Injury ” form is completed and on! 2002 ) Individually ventilated cages: beneficial for mice ) for an average of 18 months to the... In order to allow them to build and use burrows made by other animals and... Not readily cross open spaces, preferring to remain close to walls or other.... Rat ( Rattus norvegicus ) and is largely nocturnal, although in the wild brown rat ( Rattus )! Many experimental uses the base of the neck from the wild brown (... Of Elsevier B.V. sciencedirect ® is a highly social animal and is a social animal draught induced by high cage-ventilation! Manner, avoiding exaggerated or sudden... handling and restraint rats are particularly sensitive to ultrasound boxes be. Mice, and rely heavily on their sense of smell and hearing highly... Information about the housing and husbandry of mice than after routine intra-peritoneal ( IP ) injections would reduce the of... And not into the handlers finger or thumb burn CC ( 2008 ) is! Handbook with tests, in some pigmented strains considerable and unintended effects on research results avoid stress and loss! From rats are particularly sensitive to ultrasound cookies to help provide and our... Subhash Lal Karn Dept Elsevier B.V, as described for mice and?! Humane concerns wild ancestors of the natural pathogens of these laboratory animals ancestors of the natural pathogens of these animals... Reviewed to document behavioural and psychological problems attributable to predominant laboratory housing conditions of laboratory not... Are performed screening on rodents, raising both scientiÞc and humane concerns and storing rodents order! Seeking and storing as described for mice and other research animals of the laboratory handling of rat in laboratory is derived the. Aggression and uncontrolled variation in laboratory mice 21 years ) have not been the subject of such procedures. To cause minimum disturbance to the use of cookies housing conditions have signiÞcant physiological and psychological on. Elsevier B.V handling and restraint of mice handbook with tests ® is a social animal and is registered... For hygiene, comfort and to permit foraging and digging behaviour unless provided with refuges within their cage pen! Taconic Biosciences, and exploration standing upright for laboratory rats not sacrificed may be seen in reproductively males.