Memorandum submitted by the Food Standards
Agency (M15)
EXECUTIVE SUMMARY
1. Marine biotoxins accumulate in the tissues
of filter feeding shellfish and can cause symptoms in humans,
ranging from diarrhoea to serious, and sometimes fatal, neurological
illness. Measures for the monitoring and control of marine biotoxins
are laid down in EU legislation, for which the Food Standards
Agency is the competent authority. The mouse bioassay (MBA) is
the reference test method for the toxins that cause both paralytic
and diarrhetic shellfish poisoning (PSP and DSP).
2. Since summer 2001, unexplained (atypical)
responses have been observed in the MBA when some shellfish, principally
cockles, were tested for DSP. These are positive DSP results within
the terms of EU law. Reasons for the atypical response have been
investigated but it has not so far been possible to identify the
cause. Over recent years, a number of new biotoxins have been
described, so the presence of a new biotoxin is not an unreasonable
proposition and can not be ruled out at this time. A study is
currently being carried out to investigate more comprehensively
the potential toxicity of the shellfish. Until results from that
study are available for consideration by scientific experts, the
Agency will continue, as precautionary measure to protect public
health, to recommend the temporary closure of beds when shellfish
produce the atypical response in the MBA. The Agency has sought
to mitigate the impact on the shellfish industry and allow as
much fishing as possible, consistent with its role of protecting
public health, by the zoning of harvesting areas.
FSA ROLE AND
REMIT
3. The Food Standards Agency (FSA) was set
up in April 2000 to protect public health and restore public confidence
in the way that food safety decisions are made. The FSA is a non-ministerial
government department governed by a Board appointed to act in
the public interest. It is a UK body, accountable to the Westminster
Parliament and to the devolved administrations through the relevant
Health Ministers.
4. The Agency's core values are to:
— Put the consumer first;
— Be open and accessible; and
— Act as an independent voice.
5. Our sphere of interest spans the entire
food chain. We aim to provide clear advice based on the best possible
information, including surveillance data and evidence-based research.
We consult widely, including international expertise, commission
independent research and, wherever possible, seek views from stakeholders
before reaching conclusions. We publish the evidence supporting
our actions, and this is generally accessible via our website
http://www.food.gov.uk/
SHELLFISH BIOTOXINS
AND EU LAW
6. Marine biotoxins are usually produced
by microscopic organisms known as algae or phytoplankton. They
can accumulate in the tissues of filter feeding shellfish and,
if consumed by humans, can cause symptoms, ranging from diarrhoea
to serious, and potentially fatal, neurological illness. There
are three main groups of toxins; those causing:
— Paralytic Shellfish Poisoning (PSP);
— Diarrhetic Shellfish Poisoning (DSP);
and
— Amnesic Shellfish Poisoning (ASP).
7. The symptoms from shellfish biotoxins
are often acute, but chronic (long term) effects cannot be discounted.
For example, an outbreak in Canada 1987 which led to the discovery
of ASP was associated with the death of 3/107 patients, whilst
evidence of neurological dysfunction was still present in some
survivors two years after the incident.
8. In recent years, a number of new shellfish
toxins have been described from many areas of the World. For example,
in 1995, toxins in Irish shellfish exported to other countries
caused human illness. It took four years of investigations before
the Irish authorities identified azaspiracid as the cause, and
a further two years to complete the assessment of risks to public
health. This shellfish toxin is now controlled under EU legislation.
9. EU Directive 91/492 requires Member States
(MS) to operate a shellfish monitoring programme to protect public
health in relation to marine biotoxins, including PSP, DSP and
ASP. Chapter VI, section 2(c) requires Member States to close
production areas where monitoring test results show that placing
the product on the market may constitute a hazard to human health.
In addition, EU Decision 2002/225 (Annex) establishes death of
2 of 3 mice within 24 hours of inoculation as the determining
factor of a positive result in the DSP MBA. The atypical responses
do lead to mouse deaths within that period, and thus are positive
results under EU law.
THE UK MONITORING
PROGRAMME
10. The programme involves the monitoring
of:
— harvesting waters to detect algal
species known to produce shellfish biotoxins; and
— shellfish flesh for biotoxins.
11. EU legislation establishes the mouse
bioassay (MBA), as developed by Professor Yasumoto of Japan, a
leading international expert in shellfish toxins, as the EU reference
method for DSP, and it is this method that is in use routinely
in the UK monitoring programme. The method involves the extraction
of toxins from shellfish flesh and injection of the extract into
mice.
12. The laboratories that carry out statutory
biotoxin monitoring on behalf of the Agency are:
— Centre for Environmental, Fisheries
and Aquaculture Science (CEFAS), for England and Wales;
— Department for Agriculture and Rural
Development (DARD), for Northern Ireland; and
— Fisheries Research Services (FRS),
for Scotland
13. The UK National Reference Laboratory
(UK NRL) for shellfish biotoxins is responsible under EU law for
co-ordinating the activities of the monitoring laboratories across
the UK. Although it is based at FRS, it is managed, and operates
separately from the shellfish monitoring functions carried out
there.
14. Temporary Prohibition Orders (TPOs)
are used to close shellfish harvesting areas. TPOs are imposed
by local (food) authorities on the recommendation of the Food
Standards Agency based on the results from the monitoring programme.
Areas remain closed until subsequent sampling has provided satisfactory
toxin testing results. Affected areas remain closed until two
consecutive negative test results, taken a week apart, are observed.
This is considered to be the minimum time necessary for toxin
levels in shellfish to be diluted to within regulatory limits.
Testing at shorter intervals would be unproductive and impracticable,
and would incur disproportionate costs associated with additional
sampling and testing. The costs associated with this work are
paid by the FSA.
DSP TEST METHOD
AND ANIMAL
WELFARE CONSIDERATIONS
15. Commission Decision 2002/225/EEC specifies
the use of biological methods, such as the MBA, to test for the
regulated toxins. It also makes provision for the use of alternative
methods, provided they can detect the required toxins, are no
less effective than the biological methods, and their implementation
provides at least equivalent public health protection. Article
5 stipulates that when the results of the analyses performed demonstrate
discrepancies between different methods, the MBA should be considered
the reference method.
16. The MBA also provides early warning
of new toxins which may have implications for human health. These
would go undetected by chemical methods, which by definition can
only detect known toxins. In correspondence with the FSA, the
European Commission (the Commission) confirmed that it continues
to regard the mouse bioassay as the best method available because
it detects all known toxins. However, it should be noted that
there is no agreed Standard Operating Procedure (SOP) for the
test at the EU level. The Agency has pressed the Commission and
the Community Reference Laboratory for biotoxins (CRL) for urgent
action at the EU level to address this issue. In recognition of
the need for a harmonised DSP MBA method, a CRL Working Group
(which will involve the UK) has been set up to develop a robust
and scientifically validated EU MBA method. This working group
is scheduled to meet several times during 2004.
17. Animal testing in Great Britain has
to be licensed by the Home Office under the Animals (Scientific
Procedures) Act 1986, which implements European Directive 86/609/EEC
(in Northern Ireland the licensing authority is the Department
of Health, Social Services and Public Safety). Under this legislation
such testing can only be licensed when there is no non-animal
alternative, and then only if the number of animals used and their
suffering is minimised, consistent with satisfactorily achieving
the scientific purpose—this is known as application of the
3Rs (replacement, reduction and refinement). The Home Office and
their Northern Ireland counterparts regularly discuss with the
FSA and the test laboratories ways of improving implementation
of the 3Rs in the UK shellfish testing programme. The shared aim
is to move towards non-animal means of testing as soon as practicable—and
to refine animal tests as far as possible in the interim—without
jeopardising continued protection of public health.
ALTERNATIVE METHODS
18. The Agency has commissioned work to
develop alternative chemical tests for specific toxins that could
be used routinely in the monitoring programme, backed up with
a lower level of testing using the MBA to check for new or emerging
toxins. In order for such methods to be suitable for use in this
way, they must be able to detect the full range of known toxins.
This requires preparations of all the regulated toxins to be available
to use as reference standards in the tests, which is not currently
the case. Additionally, the use of such methods needs to be considered
at EU level and the necessary approval procedures have to be followed.
At the present time no chemical alternative methods for detecting
DSP toxins have been approved at EU level.
19. Partly as a result of Agency pressure,
a CRL Working Group is scheduled to undertake work during 2004
to develop a validated EU wide method based on a physico-chemical
analytical technique known as Liquid Chromatography—Mass
Spectrometry (LC-MS), which appears to be the most promising alternative
method for shellfish toxins. The UK is represented on this working
group and will contribute to this important work.
20. The Commission and the CRL have also
recently agreed to progress the development of reference standards
for the full range of toxins covered by EU law with the EU Joint
Research Centre.
ATYPICAL DSP TEST
RESULTS
21. Since the summer of 2001, atypical responses
have been observed in the DSP MBA for some shellfish samples from
England, Wales and Northern Ireland tested under the statutory
programme. The atypical response involves mice dying more quickly
than they do as a result of known DSP toxins. The species mainly
affected has been cockles, although some atypical responses have
been seen from mussel extracts.
22. Scientific advisers to the industry
have suggested that the response may be an artefact of the way
in which the test is carried out, on the basis that it was only
observed after the transfer of the monitoring programme for England
and Wales to CEFAS. The Agency has carefully considered this suggestion
and, in the course of the programme of work to investigate the
phenomenon, has included studies to address this issue. Nevertheless,
it should be noted that the atypical response has been observed
by DARD as well as CEFAS.
AGENCY FUNDED
WORK
23. The Agency has invested significant
resources in a programme of investigative work and studies to
determine the cause of the atypical response and its implications
for public health. It has sought advice on the most appropriate
lines of enquiry to pursue from a wide range of independent and
Government experts, both at home and abroad. Consultants appointed
by the Shellfish Association of Great Britain also forwarded proposals
on how the matter could be tackled. All suggestions were considered
and, where appropriate, built into the Agency's work programme
or reflected in the reports of work carried out.
24. In October 2001, CEFAS notified the
Agency that atypical results were being observed in the DSP MBA
and identified some work to investigate the issue. Formal proposals
were sought and studies were commissioned in 2002. At the Agency's
request, the UK NRL organised a UK Inter laboratory ring trial
of the DSP method. The Agency subsequently commissioned the UK
NRL to review the testing methods used at the three UK monitoring
laboratories, recognising that there was no agreed Standard Operating
Procedure (SOP) for the test, either in the UK or the EU. Differences
in the ratio of solvent to flesh used in the extraction, as well
as the particle and solvent removal stages of the tests were identified.
Work was carried out to see if any of these differences or environmental
contaminants might account for the atypical response. These studies
eliminated a number of suggested causes of the atypical response.
Further details can be found in a report to the FSA Board in December
2002 (http://www.food.gov.uk/aboutus/ourboard/boardmeetings/boardmeet2002/boardmeeting120202/boardmeet121202)
and are referred to in the Agency's October 2003 report on solvent
investigations.
25. During 2003, an extensive programme
of work was commissioned to standardise the DSP testing procedures.
Hugh Makin, Professor of Analytical Biochemistry at St. Bartholomew's
& the Royal London School of Medicine & Dentistry, was
appointed to assist with this work and independently audit the
DSP testing procedures at the monitoring laboratories. This involved
observing the way in which the test was carried out in practice
at CEFAS, FRS and DARD against the documented interim SOP held
at each of these laboratories and recording any deviations. He
was also asked to report any issues which may otherwise have been
overlooked and which in his opinion could be considered to affect
the test results.
26. A series of studies was also undertaken
to assess whether solvent carried over following extraction may
have been implicated in the atypical response. These studies do
not suggest that there is a direct causal relationship between
ether and/or acetone levels in the extract injected into the mouse
and the atypical responses recorded. The reports of this work,
the Agency's action plan in response to this work and progress
to-date have been published, and can be downloaded from the Agency's
website.
http://www.food.gov.uk/multimedia/pdfs/shellaudittable.pdf
http://www.food.gov.uk/multimedia/pdfs/shellmakinreport.pdf
http://www.food.gov.uk/multimedia/pdfs/shelletherpaper.pdf
http://www.food.gov.uk/science/researh/microsafety/b16programme/shellfish—toxins
27. In addition, the Laboratory of the Government
Chemist (LGC) was funded to carry out a study to assess whether
LC-MS could be used to detect, and possibly identify, the unknown
substance(s) responsible for the atypical responses. The report
of this work is expected to be published on our website by the
end of January 2004.
28. In November 2003 the Home Office approved
proposals for a toxicology study to further investigate the atypical
response. This study will inform the Agency's consideration of
the associated public health implications. So far the study has
confirmed that stored cockle extract is still potent, and is suitable
for use in the investigations. Extracts will be administered to
mice by intraperitoneal injection (ip) and by mouth. The clinical
signs and post mortem findings will be compared. This work is
expected to take place in January, with initial results available
for consideration by the Committee on Toxicity (COT) in early
February. The Committee will be asked to advise on what further
work should be undertaken. The findings from this programme of
work will be used by the Agency to review policy on the closure
of shellfish production areas that generate atypical results in
the MBA.
29. In line with its policy on openness,
Agency activities to resolve the matter, as well as the data generated
by them, have been made publicly available on the website. The
Agency's Board and the public have been informed of developments
through regular reports at open Board meetings.
The Precautionary Approach
30. On the basis that something is being
detected in the MBA which is killing mice more quickly than DSP,
the Agency recommends closure of affected shellfish beds, as a
precautionary measure to protect consumer health. To do otherwise
would be to ignore the conclusions of the Phillips Inquiry into
BSE on the handling of potential threats to health arising from
the food chain. The Phillips report lays great stress on the need
to take precautionary action when the risk is uncertain; to openly
and honestly communicate policy decisions and the basis for them
to the general public, and to ensure that action is implemented
and enforced effectively. This has always been our policy and
we shall continue to apply it.
31. As discussed above, the Agency has yet
to identify the cause of the atypical responses and assess the
human health implications. Until the results of the current work
programme are known later this year, the Agency will continue
to recommend that Temporary Prohibition Orders be placed on beds
where samples generate atypical results.
32. At a meeting hosted by the Agency in
May 2003, Professor Yasumoto indicated that the atypical responses
he observed when he visited CEFAS in May 2003 were likely to be
due to a novel toxin, and he pointed out that the effects of ingested
shellfish toxins on humans are simply not known. He underscored
the need for caution, particularly in respect of vulnerable consumers
(the elderly, the young, those with other illnesses), and reported
that he had seen mice, apparently healthy when alive, exhibit
internal muscle, liver and heart damage on post mortem examination
following oral administration of shellfish toxins. This indicated
that toxic effects might be chronic and insidious, rather than
acute.
33. In view of the potential risks identified
and the associated uncertainty surrounding the issue, the action
taken is considered by the Agency to be proportionate.
INDUSTRY CONSIDERATIONS
34. The FSA has endeavoured to ensure that
any effects of temporary shellfish harvesting restrictions on
industry are kept to a minimum, consistent with the protection
of public health.
35. Following discussions with stakeholders,
the Agency introduced zoning arrangements for the shellfish harvesting
areas most affected by the atypical response problem. The purpose
was to minimise disruption for, and impact on, fishermen, and
allow them to continue fishing wherever practicable.
36. Data from the Local Authorities and
Sea Fisheries Committees for the main fishing areas indicate that,
despite the closures, quota uptake in the Thames Estuary and Wash
fisheries was at least 91% in all areas in 2001 and 2002, and
approaching 100% in most. Comparable data on fishing against quota
for the Burry Inlet, which has been the area most affected by
closures caused by the atypical response, are not readily available.
However, in August 2002 zoning arrangements were put in place,
and since then the whole of the Burry Inlet has only been closed
for 2 weeks in 2002, and 3 weeks in 2003.
TAKING FORWARD
FINDINGS FROM
INVESTIGATIONS
37. Work carried out so far does not suggest
that the atypical response is caused by solvent carry over following
the extraction procedure.
38. Nevertheless, since 17 November 2003
the monitoring laboratories have operated the UK NRL SOP, which
includes steps to ensure no detectable solvent is present in the
extracts injected into mice. Laboratory technicians undertook
training beforehand, so the SOP would be applied consistently.
39. This SOP has been the subject of a further
study to check that it is operating effectively and being applied
consistently. This includes measurement of residual solvent levels.
Results thus far indicate that solvent carry-over at all three
monitoring laboratories is very low, and the method is detecting
recognised DSP toxins. The report of this study is also expected
to be published in January. The Commission and CRL are being kept
informed of developments and are following progress closely.
CONCLUSIONS
The shellfish biotoxin monitoring programme
exists to protect public health. The Agency's role is to ensure
that it is carried out effectively and proportionately. On occasions
it is necessary to restrict harvesting on the basis of test results,
as required by EU legislation. The Agency has taken action to
minimise the impact of the closures resulting from the atypical
response on the industry, where this is consistent with public
health protection, and is committed to resolving the atypical
issue. The FSA is actively pursing improved testing arrangements
and a move away from reliance on the MBA at the EU level.
9 January 2004
| 
