Housing husbandry and welfare provision for animals used in toxicology studies: Results of a UK questionnaire on current practice (1994)

Housing Husbandry and Welfare Provision

A Report by the Toxicology and Welfare Working Group

Editor R Hubrecht
ISBN 0 900767 94 4

Members of the Toxicology and Welfare Working Group
A Wilson (BTS), R Hubrecht (UFAW), WA Bradley (ABPI), D Buist (BLAVA),
D Smith (LASA), R Francis (IAT) and R James (LASA)

Published by Universities Federation for Animal Welfare

© UFAW 1995


Contents

Background
Methods

Summarised Results on this page
Mice
Rats
Guinea Pigs
Rabbits
Dogs
Non-Human Primates
Discussion

Appendix - Detailed Results with data on separate page
Mice
Rats
Guinea Pigs
Rabbits
Dogs
Non-Human Primates


Background

Laboratory animal husbandry standards are governed in the UK by The Animals (Scientific Procedures) Act 1986 and its associated Code of Practice. The Code of Practice specifies high standards of care that are enforced by the Home Office Inspectorate. Nonetheless, it provides only limited advice on enrichment techniques.

The Toxicology and Welfare Working Group was formed on 15 December 1993 to address and promote welfare issues in regulatory toxicology which is concerned with the screening of pharmaceuticals, chemicals, agro-chemicals and other such materials to ensure their safety in use. The Toxicology and Welfare Working Group consists of representatives from the British Toxicology Society (BTS), the Universities Federation for Animal Welfare (UFAW), the British Laboratory Animal Veterinary Association (BLAVA), the Association of British Pharmaceutical Industries (ABPI), the Laboratory Animal Science Association (LASA), the Institute of Animal Technology (IAT) and an observer from the Home Office.

Regulatory Toxicology involves the use of laboratory species in well-established study designs, and one of the objects of the Group is to review housing, husbandry and welfare provisions and to seek ways of improving animal welfare during the studies. To do this the group produced a questionnaire in May 1994 to be circulated to laboratories, either known or thought to be, carrying out toxicological studies. The Group hoped to document current housing and husbandry practice, and to determine the extent to which welfare innovations were being explored or implemented. The Group also wanted to find out whether specific innovations were successes or failures and to discover what improvements are possible under existing regulations.

In this document, data are presented for the species most frequently used in toxicological studies. The Group thanks the respondents and hopes that this will provide an overview of current husbandry techniques in the UK.

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Methods

The Group identified 32 establishments known or thought to be carrying out regulatory toxicology studies; to each of them UFAW sent out questionnaires. Additionally some questionnaires were forwarded through professional bodies, so as to maintain the confidentiality of their mailing lists. The group received 26 replies of which 10 reported that they were not carrying out studies of this sort. Completed forms were received from the 16 remaining establishments. The questionnaire was designed with separate but similar sections for mice, rats, rabbits, guinea-pigs, dogs and primates, and there was provision for other animals to be included. In fact the group received returns for only two other species; one for ferrets, and one for geese.

The questionnaire asked for information on the types of animals used, cage/pen design and structure, the environment, and handling and the animals' response to it. The form also had sections for reports on the animals' behaviour, including incidence of aggressiveness and of specific behaviour categories for each species, which might indicate a poor ability to cope with the laboratory environment. There was also a 'catch all' question asking about any 'other abnormal behaviour'. An open question asked whether any attempts had been made to reduce stress/distress and/or to provide enrichment. The respondents were asked whether they considered these initiatives to be either successes or failures.

The returns were strictly confidential, and there was provision for respondents to remain anonymous, but all respondents provided addresses. The respondents were informed that we would publish the results in an unattributable form.

Return to ContentsSummarised Results

Mice

The 'standard mouse' in toxicity studies is a CD1 bought from a commercial breeder. It is kept in an opaque 'plastic' cage with a solid bottom and mesh top with lighting of about 50lux for 12 hours per day, has an unmeasured noise background and is fed a powdered diet. Bedding is cleaned out twice weekly and the cage is cleaned every other week. The standard mouse is most frequently housed in groups with approximately 150cm2 of cage space per mouse and with males tending to be housed singly in approximately 700cm2 cage space. Handling is dependent on study type, and mice are not normally provided with extra environmental enrichment.

In spite of ad lib feeding only two sites reported an incidence of obesity over 5%. There was no indication whether there was a difference between mice given powdered or expanded diets.

The reporting rate for behaviours that may be abnormal or indicate stress was generally low. There was an impression that there might be fewer behavioural problems with the CD1 mouse but other strains were not used sufficiently frequently to be certain of this. Whilst the majority of users did not report any very significant problems, 5 of the 15 sites reported an incidence of one or two behavioural problems greater than 5%; these problems were biting of cages, non-specified stereotypical behaviour, barbering and circling.

However, the assessment of these behaviours may have suffered because it was derived from normal daytime contact (which in dietary studies may be minimal). Mice are nocturnal, and a better assessment would require monitoring during some part of the active period (See Discussion p. 5, point 3).

Few sites made any efforts to improve mouse welfare. Much more effort is needed to investigate the needs of mice so as to suggest practical improvements. Greater effort should be made to monitor the responses of mice to housing and husbandry regimes during their active period.

Detailed Data

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Rats

The typical repeat dose toxicology rat is a Sprague-Dawley CD strain, on a dietary or gavage study. It is housed four or five to a cage (which is likely to be made of clear plastic with a grid bottom and mesh top). Its diet is a low protein, low energy formulation provided ad lib as pellets or expanded diet. If it is on a carcinogenicity study it might have sore hocks and may become obese. It welcomes handling, it is not aggressive and most users report few behavioural abnormalities.

There are obvious difficulties in assessing behaviour of rats - observations are generally made during the day, when rats are inactive. A more precise assessment would require monitoring during some part of the active period.

The small number of establishments using both group and single-housed animals believed the latter to be more aggressive and less contented. Another establishment indicated that they made every attempt to avoid single-housing. That establishment also ensured single animals were handled at least daily, even on dietary studies. Two of the three establishments using single-housing used cages that probably did not allow visual contact with neighbours, and none allowed direct physical and olfactory contact between single-caged rats.

Observations were necessarily subjective and hence there must have been differences in what different establishments considered abnormal or rare or frequent. However, sore hocks was noted sufficiently often to give cause for concern. It was reported in both solid and grid bottomed cages and in both Wistar and CD rats, generally in older and larger animals.

Obesity occurred even with low protein, low energy maintenance diets.

A wide variety of measures was used to improve welfare - but only subjective assessments were available to indicate success or failure. These would suggest that single-housing and bright lighting should be avoided, and that if single housing is unavoidable attempts should be made to provide rats housed in these conditions with some form of social contact.

Detailed Data

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Guinea Pigs

The typical guinea-pig used in regulatory toxicology (mostly for sensitisation studies) is the Dunkin Hartley strain. It is purchased rather than bred in-house, and is usually housed in pairs or groups. The sizes of the animals were not given, which made assessment of the cage sizes difficult. Guinea-pigs normally approximate 300-500g at the start of sensitisation studies and are not usually more than 1000g at the finish. Home Office codes of practice provide recommendations up to 650g. If the animals are kept long term at heavy weights, then the cage sizes are generally on the small side.

The incidence of behavioural abnormalities, which mainly comprised wire biting and self-inflicted trauma, was generally considered to be low, although one site recorded a high incidence of wire biting. There was, however, no indication as to how respondents monitored their animals for these behaviours. Only one of the eleven establishments kept guinea-pigs in large floor pens with environmental enrichment.

Detailed Data

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Rabbits

The typical rabbit is the New Zealand White. It is single-housed in either conventional plastic or solid metal cages. It is fed on pelleted diet which some users supplement with hay. Respondents who provided hay also reported a reduced incidence of inappetance and hairball.

There was a low incidence of sore hocks, which occurred on both grid floors and punched floors, and was exacerbated by increased body weight. Floor pens had been tried by three of the thirteen respondents, but only one used this method for toxicity studies. The environment was rarely monitored for noise and lighting levels, although day length was controlled in all cases.

There was no real evidence of stereotypic behaviour, although the responses did not indicate to what extent this was monitored by respondents. The incidence of skeletal injury was of the order of 1%. Seven respondents had tried enrichment of some form, which ranged from chews and pipes to shelves and boxes, but apart from the provision of hay only two sites continue to do so for toxicology studies (group housing in one case, vet bed and shelving in the other). Four respondents are continuing to assess the value of such enrichment.

Detailed Data

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Dogs

The typical establishment houses beagles, two or more to a solid-floored pen which is cleaned out daily, and during which time animals are allowed to run in a corridor. Other human contact occurs during study procedures and sometimes during a further period of exercise/socialisation. The provision of toys and/or additional pen furniture, such as boxes, frames, ramps, and a new pen design holding four dogs all seemed to be helpful.

There was a low reported incidence of 'abnormal' behaviour comprising biting the wire of the pen, a very low incidence of self inflicted trauma and circling but this could be because most observations would have been made when the dogs were conscious of the observer's presence. There was a low incidence of aggression and aversion to strangers.

Detailed Data

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Non-Human primates

The typical primate in regulatory toxicology is captive bred, and lives in solid walled cages with a mesh or barred front providing some visibility to animals in neighbouring cages. The most frequently used species are the cynomolgus macaque, an Old World monkey, and the common marmoset, a New World monkey.

Old World primates apparently receive a different quality of housing than marmosets. Old World primates are less likely to be given visual retreats, whilst marmosets are often provided with structures such as nest boxes. Old World primates are much more likely to be single-housed than marmosets, although there is a trend to use or assess group-housing or the use of connecting cages. (Members of the group have reported that since the questionnaire was completed there has been a significant move towards group-housing Old World Primates.) Sites with single-housed Old World primates were more likely to report an incidence of abnormal behaviour, and the only site that housed marmosets singly was also the only one to report behavioural abnormalities.

The feed of primates can broadly be split into three categories: the standard diet (provided daily, and usually readily accessible), supplementary foods (provided as an addition to the daily diet and which may vary from day to day), and forage (primarily provided to occupy the primates over an extended period). Marmosets receive a more varied standard diet than Old World primates and the diet is more likely to be given ad lib. There is not, however, much difference in the provision of supplementary foods, and over 50% of the respondents gave some form of foraging provision.

Old World primates showed a low incidence of biting the wire or shell of the cage, self mutilation, circling and weaving, while marmosets showed no biting of the wire/shell or self mutilation, and a very low incidence of circling and weaving (when weaving did occur it was associated with single housing). A wide variety of procedures was used to improve the welfare of both Old World monkeys and marmosets, and these met with a considerable degree of success.

Primates used in regulatory toxicology are usually not handled for enrichment purposes, and most sites reported that their animals were either cautious of being caught or attempted to avoid capture. Some considered, however, that the response of the animals improved with time and that there was considerable variation between animals. The animals' response to strangers was thought to be wary or curious in Old World monkeys and curious in marmosets. Aggression was an occasional problem.

The importance of good cage design was emphasised by the response to the question on injuries due to the cage. There were substantial differences between different designs, but unfortunately, none of the respondents specified the type of injury, the severity; or whether it was caused by the cage itself or by the type of social housing adopted within the cage.

Detailed Data

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Discussion

Not surprisingly for such a novel initiative, the Group identified a number of limitations of the questionnaire. For example, not all the respondents used the same kinds of measures and some replied using percentages, while others used qualitative language. It is also difficult to attach weight to the given incidences or percentages given in the sections because no details were supplied regarding the number of animals held, or the volume of work undertaken. In retrospect two other significant questions should also have been asked. Although in terms of The Animals (Scientific Procedures) Act 1986 all types of establishment are equal, firstly, the type of toxicology facility (pharmaceutical/agrochemical company, contract house, academic establishment etc), and secondly, the number of animals held in the establishment and number used in a typical year, would have a considerable bearing on the interpretation of the results. Despite these reservations, the Toxicology and Welfare Working Group feel that this questionnaire has been a valuable pioneering exercise.

Respondents have for the first time been asked to assess their housing and husbandry with particular reference to welfare. As a result, we consider that there are a number of specific points that can be drawn from the results of this questionnaire as follows:

  1. It is clear that many efforts were being made to improve husbandry, although some species were much more likely than others to be the subject of attempts to improve husbandry.

    For example, a range of measures to improve husbandry were being tried with rats, dogs, primates and rabbits. On the other hand, relatively few attempts had been made to improve the welfare of mice and guinea-pigs which were often not provided with bedding. It would seem that there is potential for more effort to be made with these species. Rats were much more likely to be handled by staff than were mice. This was probably not because of any difference in the animals' needs but because it improves the ease with which they can be handled in the future. Marmosets were more likely than macaques to be housed socially and with varied enrichment items. However, there is no reason to assume that macaques are more tolerant of a restricted environment than marmosets.

    Most species were group-housed but some establishments housed their animals singly. The survey showed that rabbits in particular are usually housed singly, and that pen-housing was not common. Perhaps because of this, most of the establishments with rabbits had tried some form of enrichment but unfortunately only one respondent was continuing to provide enrichment during studies. Single-housing is sometimes necessary for experimental or husbandry reasons, but we hope that users will reassess their procedures and husbandry to ensure that single-housing for any species is used only when essential.

    Most laboratory animals (mice, dogs, etc) were normally given a standard diet while primates received a much more varied diet. As far as we know, there is no scientific evidence to suggest that omnivorous non-primates require a less varied diet than primates.
  2. Injury rates varied from species to species. Mice, guinea-pigs and dogs seemed to have relatively few problems. On the other hand rats and rabbits can be vulnerable to sore hocks. Rabbits can suffer broken limbs, possibly due to their large size and limited opportunities for locomotion. Poor cage design can lead to injuries in primates, possibly because they manipulate objects through the mesh or bars of their cages.
  3.  Most respondents considered that their behavioural abnormality rates were low.

    This is to some extent reassuring, but it is necessary to raise the question as to how the animals were monitored. 'Behavioural abnormalities' are important indicators of welfare but may occupy only a relatively small proportion of the animal's time. Moreover, many behavioural abnormalities are not seen when animals are aware of the presence of staff, and in the case of crepuscular or nocturnal animals may not be obvious during the day. Hence the results reported here should be assessed as an indication of behaviours that can occur rather than their prevalence. Moreover, the questionnaire only asked respondents for an incidence rate, and we have no data on the time spent in abnormal behaviours by individual animals. The questionnaire did not ask how behaviour was assessed, but it may be indicative that no one mentioned specific monitoring techniques. An obvious technique for nocturnal animals is to adjust the light cycle so that there is some overlap of the animals' active period with the working day of the staff, and to monitor the animals while they are under red light. In some species such as dogs and primates, it may be necessary to monitor the animals from hides or through television monitors.

    We encourage users to develop more structured methods of sampling and checking their animals for behaviours that may indicate housing or husbandry problems, or the solution to such problems.
  4.  In the open section of the questionnaire, we asked whether any attempts had been made to reduce stress and/or to provide enrichment. Some respondents described procedures to improve welfare that would normally be considered good general practice (gentle but confident handling, never rushing procedures, minimising noise, appropriate caging of animals in view of each other, monitoring the environment to ensure adequacy/lack of problems). These were not reported in the detailed results section. Others had tried more specific improvements. While it was encouraging that such provisions to improve welfare were being considered, the assessment of these provisions suffered the same problems of observation as did the detection of behavioural abnormalities. None of the respondents mentioned any formalised studies or results. It is, therefore, possible that some improvements may have been incorrectly dismissed as of little value and vice versa. We would encourage users to develop more structured assessment techniques and to liaise where possible with scientists carrying out welfare research.

In conclusion, we consider that this document provides a useful overview of current husbandry provisions in regulatory toxicology in the UK. It serves as a suitable base point for comparisons with other countries and to assess future changes. We hope that persons involved in the care and use of animals in regulatory toxicology will exploit this document as a means of assessing their husbandry practices and techniques. We also hope that they will be encouraged to adopt any refinements that have been successfully tried at other establishments, and to initiate studies with the object of validating existing welfare measures and discovering new ones.

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