PART 2E RISK ASSESSMENT OF ACTIVITIES INVOLVING GENETICALLY MODIFIED ANIMALS

Transcription

1 PART 2E RISK ASSESSMENT OF ACTIVITIES INVOLVING GENETICALLY MODIFIED ANIMALS Introduction 1. This Part provides guidance on the risk assessment of activities involving genetically modified (GM) animals. The term animal is used on its broadest sense, and includes both vertebrates and invertebrates. The guidance is written in general terms. You will need to take account of the specific species on a case by case basis. Obviously containment measures for mammals are going to be very different to those for, for example, insects or nematodes. 2. This Part does not cover the risk assessment of animals infected with genetically modified micro-organisms (GMMs). For guidance on risk assessment of GMM infected animals you should refer to Parts 2A (bacteria and lower eukaryotes) and 2B (viruses) as appropriate. Where you are assessing activities involving both GM animals and GMMs you will need to consider both the risks from the GMMs and the risks from the GM animals to ensure that all aspects are appropriately controlled. Interpretation of GM in relation to animals 3. GM animals are those where their genetic material has been altered using a method that does not occur naturally, but excluding chemical or physical mutagenesis. Methods which do result in genetic modification include techniques which incorporate recombinant nucleic acid into the animal in a relatively stable form, even if not all cells of the animal contain the modification. Mosaics, with only proportions of their cells carrying the genetic modification, are therefore considered to be GMOs. Similarly the modification does not have to involve modification of the germ-line. 4. Techniques, such as the direct injection of naked DNA to elicit an immune response would not normally be considered to constitute genetic modification. This is because although it could be said to be a transient change to the animal s genome the effect will be very short lived. 5. It should be noted that the contained use legislation covers the breeding on of a genetically modified animal. Even when a GM animal is crossed with a non-gm animal the progeny will be considered to be GMOs. The one exception to this generality is when tests show beyond reasonable doubt that no modified genetic material has been passed to the progeny. 6. In some cases, GM animals may be exempt from control under the Contained Use Regulations. In particular these include GM animals produced by cell fusion (including protoplast fusion) between any eukaryotic species (so long as no recombinant nucleic acid or other GMOs are involved) and self-cloned animals where the GMO is unlikely to cause disease (harm) to humans. Self-cloning is where all of the inserted nucleic acid involved is derived from the same species or one with which it can naturally exchange genetic material by homologous recombination. Non self recombinant vectors / or vector sequences may be used so long as they have an extended history of safe use in the animal. (See the Guide to the Genetically Modified Organisms (Contained Use) Regulations 2000 for further information 1.) 7. The contained use legislation covers activities involving GM animals supplied by others unless the animals have a marketing consent granted under the Deliberate Release Directive (90/220/EEC) or similar product based legislation. (In fact there are no such examples at present.) This means that things such as GM mice are controlled under the contained use legislation even when you have no intention to further genetically modify them. Legislative requirements for risk assessment 1 Guide to the Genetically Modified Organisms (Contained Use) Regulations 2000, ISBN Available from HSE Books, priced

2 8. The requirements for risk assessment are derived from two sets of Regulations, as described in paragraphs of Part 2 of the Compendium. The Genetically Modified Organisms (Contained Use) Regulations 2000 (referred to hereafter as the Contained Use Regulations) and the Genetically Modified Organisms (Risk Assessment) (Records and Exemptions) Regulations 1996 (as amended in 1997) (referred to hereafter as the Records and Exemptions Regulations). Together with Section 108 (1) of the Environmental Protection Act 1990, the Records and Exemptions Regulations require that for all activities involving GM animals a risk assessment is made in respect of environmental protection and that records of that assessment are kept for 10 years. The Contained Use Regulations require that for all activities involving GM animals the risk is assessed in relation to human health and safety. 9. The Records and Exemptions Regulations do not stipulate how the risk assessment must be undertaken, nor the factors to consider. However, Schedule 4 of the Contained Use Regulations sets out matters to take into account and steps which must be included in the risk assessment for human health. The guidance that follows is fully compatible with the Schedule 4 requirements. Although the Contained Use Regulations cover only human health and safety in relation to GM animals, this guidance proposes that a similar procedure also be applied to environmental risk assessment. Annex I contains a copy of Schedule 4 modified to cover both human health and environmental protection. The risk assessment procedure 10. A risk assessment must be carried out, and cover both human health and environmental protection issues. Outline Risk Assessment Procedure 11. In outline, the recommended procedure is: - (i) risk assessment for environmental protection (including hazard identification, assessment of likelihood and consequences; determination of risk; assignment of risk management measures to protect the environment); - (ii) risk assessment for human health and safety; - (iii) assignment of the final containment and control requirements (adjusting (i) to take account of (ii)). 12. As part of the consideration under (ii) it is important to determine whether the GM animal is more likely to cause harm to humans than the non modified parental organism. This is so that you can determine whether the activity has to be notified under the Contained Use Regulations 2000 before work can be commenced. (See paragraphs for further guidance.) RISK ASSESSMENT FOR ENVIRONMENTAL PROTECTION 13. It is far more likely that the GM animals may pose a risk of damage to the environment than to human health. The Environmental Protection Act (in the context of contained use) defines damage to the environment very broadly as being caused by the presence in the environment of GMOs which have escaped from containment and are capable of causing harm to any living organisms supported by the environment. It is therefore important to consider risk to the environment very thoroughly in order to ensure that the appropriate level of control is used to prevent harm occurring. 14. The primary focus should be on the genetic modification itself and whether this will increase (or decrease) the risk. However, you will also have to take into account risks resulting from any intrinsic properties of the animal. For example, they may be a non-indigenous species 2 which could affect the ecological balance of the surrounding environment, a plant pest, a vector for animal diseases etc. In some cases these intrinsic hazards may interact with those resulting from the genetic modification. 15. The aim of the environmental risk assessment is to determine the appropriate containment and control measures to prevent harm occurring. The appropriate containment will vary with both the level of risk and the nature of the animal being controlled. For instance, the containment methods for an insect will be very different to those for farm animals such as sheep. In many cases the control will be provided by a mixture of physical (eg cages), biological (eg sterility), chemical (eg oil traps for insects) and procedural measures (eg 2 The introduction of some non-indigenous species is licensed under the Wildlife and Countryside Act.

3 standard work practices designed to maintain high levels of control). Part 3D contains guidance on containment and control methods for GM animals. Guidance for containment of animals infected with GMMs is in Part 3E. 16. In all cases, the recommended procedures to be followed for assessing environmental risk are as set out in Part 2A. These are: - (a) hazard identification; - then if hazards are identified - (b) assessment of the likelihood of identified hazards being manifested; - (c) assessment of the consequence of identified hazards being manifested; - (d) determination of risk of harm (likelihood x consequence); - (e) selection and assignment of appropriate control measures (risk management); - (f) reiteration of steps (c) to (e) to determine if risks have been reduced to low or effectively zero. (a) Hazard identification 17. The hazards that need to be considered will usually be: - (i) capacity to survive, establish, disseminate, compete with and / or displace other animals; - (ii) (direct) adverse effects on animals and plants; - (iii) potential for transfer of genetic material between the GMO and other organisms; - (iv) products of gene expression, particularly if they are toxic or otherwise biologically active; - (v) phenotypic and genetic stability; and - (vi) other negative effects on organisms. 18. Consideration should be given as to whether any, all, or none of these hazards are characteristics of the host organism, the insert, the vector and the final GM animal. The assessment should consider any other species that the gene could be passed on to, and any adverse effects it could have in that animal. Synergistic effects, or cumulative effects should also be considered. Capacity to survive, establish, disseminate, compete with and /or displace other animals; and, adverse effects on animals and plants. 19. The capacity of the GM animal to survive in the environment will be a key factor to consider. If the animal cannot survive outside of containment, it is unlikely to cause environmental harm. For example, GM Tilapia - a fresh water tropical fish commonly used as a research model - is unlikely to survive in UK rivers, as it requires temperatures of above 27 o C, and is effectively under biological control. 20. Some animals, even when they cannot survive in the long term, may be able to survive for a short period when conditions are favorable. For example some insects may not be able to over winter, but could survive the summer months reasonably well. In such cases, although the long term effect is unlikely to be significant, there would be a short term possibility of some of the other hazards discussed below being realised and these must be considered. 21. Where a GM animal has an intrinsic ability to survive it is important to consider how they might interact with the environment and whether they present any of the other hazards listed below. 22. GM animals may cause harm simply by their presence in the environment. If they are intrinsically adapted to the climate and environment they may out compete and displace other populations of animals. Predation may be a problem. Effects on plant species should also be considered. Establishment of significant populations of escaped GMOs may lead to overgrazing and serious ecological impacts. Loss of biodiversity in plant species could in turn adversely affect the ability of the environment to support its normal animal populations. Especial care must be taken over non-indigenous species 3. Troublesome escapes by farmed non indigenous non-gm animals such as coypu, mink and zander (fish) are well documented, and may provide a model for some GM animals. Problems have included excessive growth in numbers, over successful competition with native species and physical damage to the environment. Whilst it seems probable that GM animals would be no more likely to cause such problems than non-manipulated species, the possibility of 3 Note that a licence may be required under the Wild Life and Countryside Act - contact the Biotechnology Unit in DETR for further information.

4 problems similar to those outlined here should always be considered. 23. Although in many cases the ability to survive and compete for resources will probably be the same as for non-modified relatives, it is possible that the genetic modification itself gives the GM animal a competitive advantage. For example, GM salmon modified to grow more quickly might out compete their non-modified wild relatives. Similarly, introduced cold tolerance could increase an animal s range, and increased fecundity could also lead to a competitive advantage. Conversely the modification may lead to decreased fitness and weakened ability to compete. Examples might include sterility (such as trisomy in fish) and dependency on a nutrient supplement. 24. Another factor that can affect survival and dissemination in the environment will be whether it is possible to recall escaped animals. For farm animals such as sheep it should be feasible to retrieve escapees. However, fish, insects and small mammals may be extremely difficult, if not impossible, to recall. There is increasing work being undertaken with GM invertebrates. The small size and complex life-cycle of many of these may open up additional pathways for dispersion, and tracking of the animals may be difficult. Potential for transfer of genetic material between the GMO and other organisms 25. In addition to the possibility of harm being caused by the presence of the actual GM animal, consideration should be given to the possibility of the modified genetic material being transferred to wild or domesticated relatives. Factors to consider will include: - presence of sexually compatible species in the environment; - whether the GM animal is sterile; - the sex of the GM animal. If only females escape (and they are recallable) the chances of gene transfer into the wider population will be greatly reduced. 26. The nature of the hazard which might result from gene transfer should also be considered. For example, if the animal had been modified to produce high levels of tumours, would there be an ecological impact of dissemination of such a gene in the environment? The likelihood of selection pressure acting on the modified trait should also be considered as it would affect the likelihood of the gene being spread through the population. Products of gene expression, particularly if they are toxic or otherwise harmful; phenotypic and genetic stability; and, other negative effects on organisms. 27. Although the possibility should (where appropriate) be considered, it is relatively unlikely that animals will be modified to produce toxins per se, or that the modification will have pleotropic effects which lead to an alteration in natural toxin production. It is much more likely that animals will be modified to produce biologically active substances - for example, blood clotting factors produced in sheep s milk. The possible harmful effects of these biologically active substances on other animals should be considered, but are relatively unlikely to pose a serious hazard. 28. Given that genetic instability is most likely to result in loss of the introduced trait it will rarely be a source of potential harm. One exception to this is when the genetic modification itself is used as a biological control method. For instance, one of the aspects of control may involve sterility introduced by the genetic modification. If this were to revert, the level of control would be reduced. Similarly there may be an introduced nutrient dependency. If removed through genetic instability there could be an increase in the possibility of dissemination in the environment. 29. Consideration should also be given to the possibility of the GM animals acting as novel animal disease vectors. (b) Assessment of Likelihood 30. The next step is to estimate the likelihood of hazards being manifested. It is suggested that likelihood be expressed as high, medium, low or negligible, since it is not possible to quantify all the risks at present. (See Table 6 of Annex IV, Part 2A.) 31. When estimating the likelihood of harm occurring to the environment one of the key factors is going to be that the GM animals are contained and so their access to the environment will be limited. In order to consider likelihood in a meaningful way it is suggested that you start by assuming the basic standard level of containment that would be applied to the equivalent non-gm

5 animal being used for experimental purposes. This might include fish tanks, insect cages, animal houses, fenced fields, barns etc. (See also Part 3D for further advice on the basic standards of containment expected.) The basic level of containment can then be revised as necessary until all of the risks are reduced to low or effectively zero. 32. Other factors which might influence the likelihood include: - the surrounding environment and climactic conditions. Could they support the short or long term survival, establishment and dissemination of the escaped GM animal? (For example, GM salmon next to coastal waters would have a high probability of establishing novel populations if they escape); - is the natural fauna and flora susceptible to disturbance by the GM animal? For instance, the GM animal may occupy the same ecological niche as another organism and hence have greater potential for competition; - where there are sexually compatible relatives there will be greater potential for gene transfer; - is it possible to recall the escapees? (c) Assessment of consequence 33. As well as assessing the likelihood of a potentially harmful effect (hazard) occurring the severity of the consequence must also be estimated. That is, how bad would the harm be if it were to be realised - in terms of seriousness, extent, and reversibility. 34. It should be emphasised that the degree of severity is estimated with the assumption that the GM animals have entered the environment and that harm will occur (even if it is negligible ). The severity consideration should therefore be independent of the consideration of the proposed containment. 35. Evaluation of the magnitude of potential consequence is difficult and inevitably a degree of judgement will be necessary. There is also no hard and fast scale for the level of harm. It is therefore suggested that the consequences of hazards being manifested be described as being severe, medium, low or negligible. (See Table 6 of Annex IV, Part 2A.) 36. The following descriptions may help when making judgements about the severity of the potential consequence. - Severe consequence: a major change in the numbers of one or more species. The interpretation of major will be dependent on the species affected. For example, harm caused to a single individual of a protected species would be major, whereas quite large changes, in terms of numbers, of a ubiquitous and fecund species (eg certain insects) may be relatively insignificant in terms of harm (especially if the population fluctuation is within natural limits). Severe consequences might also be where there is a major change to the functioning of the ecosystem. Severe consequences would be unlikely to be easily reversible. - Negligible consequence: would be where there was no measurable change in any population (plant, animal or microbial) or in any ecosystem function. (This does not preclude some fluctuation in indigenous populations as long as this is within the range of that which could be expected naturally.) (d) Determination of risk 37. The level of risk posed by each identified hazard should be evaluated. Risk is the product of the likelihood of a harmful event occurring and the severity of the potentially harmful effect. This product may be determined using the matrix outlined in Table 6 of Part 2A, Annex IV. In this table risk is defined as high, medium, low or effectively zero. (e) Assignment of control measures to manage the risk 38. The risk assessment will determine the level of risk for each identified hazard in terms of how likely it is to happen and the seriousness of the consequences. The likelihood will to a great extent be determined by the initial set of control measures and containment envisaged. The aim of this part of the assessment is to ensure that all of the risks are low or effectively zero. If any risk exceeds these levels then additional control measures must be assigned and the assessment rechecked to ensure that all risks are reduced to low or effectively zero.

6 RISK ASSESSMENT FOR HUMAN HEALTH AND SAFETY 39. The Contained Use Regulations 2000 require an assessment of risks to human health. It is recognised that for the majority of GM animals currently being used the modified animal poses no additional risk to workers over those that would be expected from the parental (unmodified) animal. These intrinsic hazards will include such things as scratches, bites, allergenicity and zoonoses 4 (especially the possibility of persistent or latent infection). 40. All of these aspects must be considered in any risk assessment so that appropriate containment and control measures can be assigned. However, these potential hazards are, of course, common to all animals, whether GM or not. The risk assessment under the Contained Use Regulations should focus more on the possible additional hazards to human health which result from the genetic modification itself. For example, if an animal line was produced which was modified to contain a receptor for a human virus, these animals may act as a novel reservoir for human disease. Although the possibility of such additional hazards to humans must always be considered, it is recognised that in most cases the activities will not pose any extra hazards to humans. 41. If any additional risks to humans might result from the genetic modification itself, such hazards might include: - novel or increased allergenicity; - possible toxic effects (from the production of toxins or other biologically active proteins); - adverse effects from a change in behaviour or in physical nature. This might include increased aggression; - changes in the ability of the animal to act as a human disease reservoir (eg the insertion of a novel viral receptor). 42. For each hazard identified, you should consider the likelihood of the hazard being realised (given the containment assigned to protect the environment) and the severity of the potential harmful effect. An approach similar to that for assessment of environmental risks is recommended. It might be necessary to adjust the proposed containment if any of the risks to humans are not controlled by the containment assigned to protect the environment. ASSIGNMENT OF FINAL CONTAINMENT AND CONTROL REQUIREMENTS 43. The final containment and control measures assigned must be sufficient to reduce all risks to both humans and the environment to low or effectively zero and prevent harm from occurring. 44. Guidance on containment and control strategies fro GM animals can be found in Part 3D. Trigger for notification ********************** 45. The Contained Use Regulations 2000 require that all activities involving GM animals, where the animal poses a greater risk of harm to human health and safety than the non-modified equivalent are notified to HSE. (Note that the trigger is in relation to human health and safety only. There is no equivalent notification trigger in respect of the environment.) 46. As discussed above the hazards to humans from GM animals are most likely to be those also associated with the non-modified equivalent animal. It will be relatively rare that a significant hazard will result from the genetic modification itself. However, the sorts of possible hazard are discussed at paragraph 41 and should be considered. Of course, in some cases there may be very minor increases in possible risk. For instance, a sheep producing human biologically active protein in its milk could be said to be very slightly more hazardous to humans than a non modified sheep. However, the consequence of the hazard is likely to be low or negligible and it is unlikely that any harm would occur. Such minor 4 In relation to zoonoses we recommend that you refer to the ACDP publication, Working safely with research animals. Management of infection risks, ISBN

7 elevations in risk would not trigger the need for a notification. 47. By analogy, hazards resulting from the genetic modification which could give risk to medium or even severe consequences for human health would trigger a notification requirement, as the risk would be truly greater than that posed by the non-modified animal. For example, a GM animal line might be produced which is susceptible to a human virus through insertion of a viral receptor. The animal might act as a novel reservoir for the human disease and if this were to happen the consequence would probably be medium to severe, depending on the seriousness of the disease in question. Animals (Scientific Procedures) Act 1986 and other Animal Welfare Legislation 48. The Home Office is responsible for regulating the use of protected animals (all vertebrate animals and Octopus vulgaris) for experimental or other scientific purposes, including the production and use of genetically modified animals. Regulation is by certificates and licences issued under the Animals (Scientific Procedures) Act The Home Office maintains an active inspection programme of licensed work. 49. Further animal welfare legislation covers domestic species, farm animal welfare on agricultural land and the movement of animals. MAFF (and the devolved agricultural Departments in Wales and Scotland) have published Codes of Practice for the welfare of most species of farm animal. 50. Further details of the legislative requirements in respect of animal welfare are given in Annex II. Consumption of GM animals 51. It is recommended that the secretariat to the Advisory Committee on Novel Foods and Processes (ACNFP) 5 be consulted at an early stage if it is intended to work on any GM animals which might be used for food. Similarly the Animal Feeds Committee of MAFF should be consulted about the potential use of any GM animals in feed. 5 ACNFP will be under the Food Standards Agency from April 2000.