Part 2
Hazards and Risks Associated with Workplace Exposure to TSE Agents
Health and Safety Law
The Health and Safety at Work etc. Act 1974 (HSWA)
2.1 All work except domestic service is subject to regulation under the HSWA. Employers have general duties to ensure, so far as is reasonably practicable, the health, safety and welfare at work of employees, and to conduct their undertakings in such a way as to ensure, so far as is reasonably practicable, that other persons who may be affected by the work are not exposed to risks to their health and safety. Self-employed people have general duties to conduct their undertakings in such a way as to ensure, so far as is reasonably practicable, that they and other persons are not exposed to risks to their health and safety from the work. Employees have a general duty to take reasonable care for the health and safety of themselves and of other persons who may be affected by their work, and to co operate with their employer or any other person to enable them to comply with any health and safety duties.
The Management of Health and Safety at Work Regulations 1992 (MHSWR)
2.2 The MHSWR provide a framework for controlling health and safety at work. As well as calling for risk assessments, they also require employers to have access to competent help in applying the provisions of health and safety law; to establish procedures to be followed by any worker if situations presenting serious and imminent danger were to arise; and for co operation and co ordination where two or more employers or self employed persons share a workplace.
Genetically Modified Organisms (Contained Use) Regulations 1992
2.3 Experimental work involving the genetic modification of the PrP gene and the production of animals transgenic for the PrP gene, is subject to regulatory control under the Genetically Modified Organisms (Contained Use) Regulations 1992 (as amended). The Advisory Committee on Genetic Modification (ACGM) has prepared a Compendium of Guidance relevant to this type of work. Further information is available from the ACGM secretariat1.
The Control of Substances Hazardous to Health Regulations 1994 (COSHH)
2.4 The COSHH Regulations provide a framework of actions designed to control the risk from a range of hazardous substances including biological agents. Schedule 9 of the COSHH Regulations specifically refers to biological agents which include the TSE agents. The essential elements of the COSHH Regulations are:
- risk assessment;
- prevention of exposure or substitution with a less hazardous substance (if the nature of the activity permits);
- selection of control measures;
- maintenance, examination and testing of control measures, e.g. protective equipment such as safety cabinets;
- provision of information, instruction and training for employees;
- monitoring exposure at the workplace (if a suitable procedure is available);
- health surveillance of employees (where appropriate, and if there are valid techniques for detecting indications of disease) when it can lead to action that will be of benefit to the health of employees.
2.5 The results of the assessment will assist in the selection of appropriate control measures. The primary requirement is to prevent exposure to a biological agent or substitute a safer biological agent, if this is practicable. Often these approaches will not be possible, and in such cases the risk of exposure should be minimised by the use of suitable control measures (see below and Parts 3 and 4).
2.6 The COSHH Regulations identify two broad categories of exposure to biological agents at work: (a) exposure which does not arise from the work but is incidental to it (e.g. healthcare, food production, sewage work) and; (b) exposure resulting from a deliberate intention to work with biological agents (e.g. laboratory research). A risk assessment should be made for both categories, but the scope for risk reduction and control may be less in the former category. Part 4 of this document gives guidance for healthcare work, where the exposure to TSE agents is incidental to the work. Information on work involving the slaughter and processing of cattle can be found in the general guidance on BSE (see bibliography).
The Reporting of Incidents, Diseases and Dangerous Occurrences Regulations 1995 (RIDDOR)
2.7 There is a requirement in RIDDOR for employers to report any infection reliably attributable to work with live or dead humans or animals, exposure to blood or body fluids or any potentially infected material derived from any of the above. There is also the need to report any accident or incident which resulted, or could have resulted, in the release or escape of TSE agents (or other biological agents) categorised in Hazard Group 3 or 4 (see paragraph 2.19). See also ‘accident reporting and health surveillance’ below. Further information can be obtained from the Health and Safety Executive.
Local safety policies and codes of practice
2.8 There is a need to ensure that all employees have a clear understanding of any identifiable risks to their health arising from work, and the actions to be taken in dealing with situations in which exposure may occur. Under the COSHH Regulations employers must provide suitable and sufficient information, instruction and training on the risks and precautions to be taken. Under the MHSWR, they must provide comprehensive and relevant information on the risks and preventative and protective measures, together with adequate health and safety training. Local codes of practice may form part of this process of information, but thorough instruction on their day to-day application is needed in order to make them work effectively.
2.9 Specific information on the arrangements for working safely day to day can best be set out in local codes of practice. Employers have a responsibility to make the policy and codes freely accessible, either by putting them on display or by individual issue. All staff, including all newcomers and temporary workers, must be made aware of them.
2.10 Employers have a duty to consult employees on health and safety matters. Further information and details of additional guidance can be found in the leaflet “Consulting Employees On Health And Safety: A guide to the law” (HSE 1996).
Accident reporting and health surveillance
Accident reporting and recording
2.11 An official local record should be made of all accidents and occurrences with infectious or potentially infectious material involving the exposure of individuals. This applies whether or not the accident is reportable under RIDDOR.
List of employees exposed to human TSE agents
2.12 If a TSE were to develop as a result of occupational exposure, it may only become apparent decades later. Paragraph 11(1) and 11(3) of Schedule 9 of the COSHH Regulations require employers to keep a list of employees exposed to human TSE agents for 40 years following the last known exposure. Such a list is only necessary when there is a deliberate intention to work with the agent or in cases of incidental exposure if a risk assessment shows that there is a significant risk. For routine clinical care of patients with CJD or a related disorder however, this should not be necessary. It is often sensible to duplicate the relevant information with the individual’s health record (see paragraphs 2.14 and 2.15 below).
Health surveillance
2.13 Where it is appropriate for the protection of the health of employees, both MHSWR and COSHH Regulations require that employees are under suitable health surveillance. Under MHSWR, health surveillance must be provided as appropriate, having regard to the risks identified by the risk assessment. Under COSHH Regulations, health surveillance must be provided where: there is an identifiable disease or adverse health effect that may be related to exposure in the workplace; there is a reasonable likelihood that the disease or effect may occur under the particular conditions of work; and there are valid techniques for detecting indications of the disease or effect.
2.14 In view of the difficulties in detecting the early indications of disease, it should be sufficient to set up and maintain a health record as defined in the Appendix of the COSHH Regulations. This could supplement any list of exposed workers. Further information is in Regulation 11(3), Schedule 9, the COSHH General Approved Code of Practice and The Approved Code of Practice on Biological Agents.
2.15 Although not a legal requirement, individual exposure and health records may be of great value for future epidemiological investigations. It is recommended that the minimum information that should be recorded is the full name (and maiden name for women), date of birth, National Insurance number and dates of (relevant) employment. The information on exposure needs to be linkable to individuals, although not necessarily at individual level (i.e. it may be that an indication of representative work can reasonably be applied to all those working in that area). Records should be kept for 40 years after the last known exposure. Regulation 11(4) requires that the records be offered to HSE if the employer ceases to trade before that time.
Risk Assessment
General principles
2.16 Employers must carry out a suitable and sufficient assessment of risks before any work involving potential risk to workers from a substance that is, or may be, hazardous to health. The assessment of risk required by the COSHH Regulations must be reviewed regularly and revised when conditions change, an incident occurs, a deficiency is noted or if, for any other reason, it is suspected that the assessment is no longer valid.
2.17 The risk assessment must include a review of all working procedures. For example, review of procedural controls, arrangements for the safe disposal of waste, the potential for the dispersal of infectious material in the working environment and the contamination of equipment and apparatus.
2.18 Factors that need to be considered in the risk assessment include:
- whether there is a deliberate intention to work with the agent, or if any exposure would be incidental to the work (see paragraph 2.6 above);
- hazard categorisation of the agent (see Table 1);
- origin of the TSE agent;
- type of tissue handled (as this may indicate the likely level of agents present) (see Annex A);
- knowledge of expression of the agent in any experimental model and whether the work is likely to result in a high titre of infectivity;
- assessment of the type of task (e.g. concentration/purification);
- frequency of contact with the agents or materials likely to contain them;
- potential for inoculation injury in the workplace and other possible routes of exposure.
Hazard categorisation of TSE agents
2.19 The appropriate control measures for laboratory work with biological agents are determined largely by the Hazard Group classification of the agent. The EC Classification of Biological Agents establishes a list of biological agents as part of the Council Directive on the protection of workers from risks related to exposure to biological agents at work (90/679/EEC). Details can be found in the ACDP publication “Categorisation of biological agents according to hazard and categories of containment” and the 1998 supplement.
2.20 The classification is based on the risk of infection to a healthy worker using the well established criteria for four Hazard Groups. In determining the appropriate hazard grouping of a biological agent, note is taken of the pathogenicity (disease producing capability) of the organism to man, the hazard to laboratory workers, the potential for transmission to the community and the seriousness of any illness that might result after taking into account the availability of prophylaxis or effective treatment.
CJD and related diseases
2.21 CJD (including nvCJD), GSS, FFI and kuru cause disease in man which, once clinical signs appear, is invariably fatal and there is no effective prophylaxis or treatment available. However, apart from the rare examples of iatrogenic transmission, there is no evidence that CJD, or a related disorder, has been or can be spread from person to person by close contact, or has occurred in workers through occupational exposure. Furthermore, currently there is no evidence that nvCJD patients acquire their disease from occupational exposure. (A significant excess of CJD cases has been found among workers on dairy farms and on farms with a confirmed case of BSE. However, these cases have all been the classical type and not the nvCJD type. Strain typing of the agent causing CJD in farmers whose herds had confirmed cases of BSE showed that they were indistinguishable from classical CJD and distinct from nvCJD and BSE. The incidence of classical CJD in UK farm workers is no higher than in farm workers in other European countries which have not suffered from the BSE epidemic; the significance of this observation is unclear at present.)
2.22 The human TSE agents are classified in Hazard Group 3 because of the severity of infection. However, as it is recognised that the TSEs are unlikely to be transmitted by the aerosol route, derogation from full Containment Level 3 is allowed. This means that, subject to local risk assessment, certain containment measures may be dispensed with.
BSE and related diseases
2.23 BSE, and diseases in other species caused by the BSE agent (spongiform encephalopathy in felines and in captive exotic ungulates), are invariably fatal, once clinical signs have appeared, in the animals they affect. A link between BSE in animals and nvCJD in man has also been established, although there remain uncertainties about, for example, possible routes of exposure. BSE and related agents are now classified in the same Hazard Group as the agent responsible for CJD, i.e. Hazard Group 3 with derogation. Table 1 summarises the current position.
Scrapie and related diseases
2.24 Other animal TSEs (e.g. scrapie) are invariably fatal in the animals they infect, again once clinical signs have appeared. In view of the novel features of all TSE agents, and the uncertainty about infectivity in man, it is recommended that prudent precautions are taken when working with tissues or preparations from infected animals. However, as there is no evidence of transmission of scrapie to humans it is not formally classified as a biological agent or placed in a Hazard Group. Nonetheless, the recent amendment to Directive 90/679/EEC does include a footnote about animal TSEs, which recommends that Containment Level 2 is sufficient for laboratory work with identified scrapie agents. It includes also a precautionary recommendation for Containment Level 3, with derogation applying, for work with TME and CWD. As none of these agents exhibit other hazards specified in the definition of a biological agent, such as allergenicity or toxicity, they are not covered by the COSHH Regulations. However, the MHSWR will apply, and a risk assessment is required by these regulations.
Origin of the TSE agent
2.25 It is usually more difficult, and sometimes impossible, to transmit a TSE agent to a different species at primary passage than to another member of the same species (assuming it is of the same prion protein (PrP) genotype). This is the ‘species barrier’ effect, and is recognised by a shortening of the incubation period following a second passage in the new species. The transmission properties of the TSE agent are dependent on the host from which it is derived and on the passage history. For example, serial sub passage of scrapie agent in mice of different genetic make-up may select ‘strains’ of agent with differences in incubation periods, infectivity and resistance to decontamination. Strain properties of cloned agents sometimes, but not always, alter following serial passage in a new species and re-isolation in the original species. Risk assessment needs to consider the species of origin as well as the species into which the TSE source has been passaged.
2.26 It is particularly important to consider carefully the risks from a TSE agent isolated from any species but which is subsequently passaged in non human primates or any genetically modified species expressing human or primate PrP (e.g. transgenic mice). Tissues from such animals should be treated as if they contained a TSE agent of human origin.
Distribution of TSE infectivity in tissues
2.27 Knowledge of which organs or systems are known to harbour the agent in natural disease is key to performing an adequate risk assessment; and subsequently in deriving suitable control measures to prevent or reduce the risk of occupational exposure to the agents, especially for laboratory work as this may involve contact with high titres of infectivity. However, data on tissue distribution of TSE infectivity are incomplete, and although studies are underway which will provide some additional information, there are likely to be significant remaining gaps in knowledge. The risk assessment needs to take into consideration these uncertainties. A summary of current information is given in Annex A, which will be particularly useful for risk assessments of experimental laboratory work. However, it is important that as further research results emerge these are incorporated into the risk assessment.
Sheep and goats
2.28 Bioassays in laboratory rodents have been used to investigate the tissue distribution of TSE infectivity in naturally occurring disease in sheep and goats. Present knowledge of this is given in Annex A, which presents data derived from studies on sheep and goats naturally infected with clinical scrapie. For simplicity, the data on sheep and goats have been combined. However, where minor differences between the sheep and goat data occur, the tissue concerned was placed in the highest category, e.g. pituitary gland would have been placed in the low infectivity category if based on the sheep data alone.
Cattle
2.29 The distribution of infectivity in bovine tissue is being studied in an on-going series of experiments. While early experiments concentrated on naturally infected, clinically affected field cases of BSE, subsequent studies have also addressed the distribution of infectivity in the pre-clinical stage using experimentally infected animals. The majority of studies have used parenteral inoculation of mice to determine whether infectivity was present in a range of tissues. While studies on naturally infected cases are complete, those on cattle that were experimentally exposed by mouth are still on-going. Interim results have been published in 1994 and 1998. In summary, it has so far been shown that:
- from naturally infected field cases the BSE agent has been detected only in brain, spinal cord and retina;
- a wide range of other tissues from naturally infected cattle has shown no detectable infectivity even though donor animals were clinically affected at the time of sampling;
- in cattle experimentally challenged with 100g of infected brain by mouth, infectivity was detected in the distal ileum from 6 months after challenge, becoming undetectable at 22 and 26 months post-challenge but then subsequently re-appearing. From shortly before clinical onset, which was at approximately 35 months post-challenge, infectivity became detectable in the brain, spinal cord, dorsal root ganglia (mid-cervical and mid-thoracic) and, at the time of writing, at one time point in the experiment in bone marrow. This was again in clinically affected animals.
2.30 Mice have been challenged orally also, but with a more restricted range of bovine tissues from confirmed cases of BSE. In these studies, only brain tissue has proved infectious to mice.
Humans
2.31 Limited information is available on the distribution of infectivity in human TSEs. Cases of accidental human to human (iatrogenic) transmission have been associated with the clinical use of human dura mater, cornea and hormones derived from human pituitary glands.
2.32 Lymphoid tissue (tonsils) in nvCJD cases has been found to contain the disease associated form of prion protein. However, the significance of this finding is not yet clear. It is possible that the distribution of infectivity of nvCJD is different from that of other forms of CJD, e.g. in the former there may be more involvement of lymphoreticular tissues possibly involving circulating lymphocytes. The assessment of risks from nvCJD should reflect this uncertainty, and will need to be revised as further research findings emerge about the pathogenesis of nvCJD.
2.33 Advice about clinical interventions on patients known or suspected to have CJD or related diseases and those at risk from CJD is given in Part 4.
Table 1
Summary of categorisation of the agents of TSEs1 |
|---|
|
| Agents associated with: | Hazard Group2 | Comments / Notations |
|
| Creutzfeldt-Jakob disease (CJD) including new variant CJD (nvCJD) | 3 | DE |
| Gerstmann-Sträussler-Scheinker syndrome (GSS) | 3 | DE |
| Kuru | 3 | DE |
| Fatal familial insomnia (FFI) | 3 | DE |
| Bovine spongiform encephalopathy (BSE) and other related animal TSEs3 | 3 | DE |
| Scrapie and other TSEs known not to be linked to BSE |
- |
These agents are not formally categorised4. See Part 3 for recommended laboratory precautions |
|
| 1. | This summarises the 1998 edition of the Approved List of Biological Agents which comes into force on 1 May 1998. |
| 2. | There is an exemption certification concerning the required containment measures for these agents. Full Containment Level 3 may not be necessary for all work with these agents. Further advice can be found in Part 3 of this guidance. |
| 3. | For the purposes of the hazard categorisation ‘related animal TSEs’ include: Feline spongiform encephalopathy (FSE); spongiform encephalopathy (SE) in captive exotic ungulates; transmissible mink encephalopathy (TME); and chronic wasting disease (CWD). This category also includes BSE experimentally transmitted to other species. |
| 4. | The European Directive 97/65/EC on the adaptation of the European classification of biological agents includes the following footnote: |
| “There is no evidence in humans of infections caused by the agents responsible for other animal TSEs. Nevertheless, the containment measures for agents categorised in risk group 3(**) are recommended as a precaution for laboratory work, except for laboratory work relating to an identified agent of scrapie, where Containment Level 2 is sufficient.” |
| D: | A list of workers exposed to these agents should be kept for 40 years following the last known exposure risk. |
| E: | eye protection should be used for laboratory work. |
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1Secretary to the Advisory Committee on Genetic Modification, Health and Safety Executive, Rose Court, 2 Southwark Bridge. London SE1 9HS.
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