Semicarbazine in Fish products:
The importance of collecting true
data and their traceability
Dr Popi Kanari
Director
State General Laboratory,
Ministry of Health
Cyprus
EFSA AF MEETING, PARMA, ITALY
8-9 DECEMBER 2016
Semicarbazine (SEM)
•
What is SEM and where does it come from ?
•
SEM belongs to the hydrazine family of chemicals some members of which
are known to possess carcinogenic potential
Information on the potential hazard of SEM itself is incomplete and the
possibility that it is genotoxic cannot be ruled out
•
•
SEM from Nitrofurans usage
•
SEM has been employed as an excellent marker metabolite for the illicit
use of the Nitrofuran – Nitrofurazone, in food producing animals
EFSA AF MEETING, PARMA, ITALY
8-9 DECEMBER 2016
Nitrofurans
Nitrofurans:
• They are synthetic broad spectrum antimicrobial reagents
• Their use in food producing animals is not permitted since 1993 -1995 in
the EU
• They have however been reported to be used mostly in poultry and
aquaculture production in third countries
• Such reports led to large numbers of these products being tested by MS
prior to acceptance of the goods at the port of entry , in food producing
animals
• Are rapidly metabolized as residues in foods of animal origin and
therefore they are found in animal tissues as protein-bound metabolites
• Sampling of food for Nitrofuran testing in foods of animal origin is
undertaken in the context of the National Residue Monitoring plans
Directive 96/23/EC in accordance with Decision 2002/657/EC
According to the above legislation it is required to
report Only the protein Bound metabolites of Nitrofurans to
prove their illicit use in food producing animals
EFSA AF MEETING, PARMA, ITALY
8-9 DECEMBER 2016
Nitrofurans
Parent cpd
Metabolites
Nitrofurazone
semicarbazide (SEM)
Furazolidone
met 3-amino-2-oxazolidinone (AOZ)
Furaltadone
3-amino-5-methylmorpholino-2- oxazolidinone
(AMOZ)
Nitrofurantoin
1-aminohydantoin (AHD)
Nifursol
3,5-dinitrosalicylic acid hydrazide (DNSH)
EFSA AF MEETING, PARMA, ITALY
8-9 DECEMBER 2016
SEM from different origins other
than Nitrofurans
• SEM was detected also in foods of non animal origin and
this triggered research and was found that its presence in
food may be from sources other than use of
Nitrofurazone
• from azodicarbonamide (ADC) ( not authorized for use in
EU as from 2005 )used as blowing agent for plastic
gaskets for metal lids on glass bottles and jars .Processed
food packaged in bottles and jars where these gaskets are
used ,include baby food !
 ADC also used as a flour improver (not authorized in the
EU but permitted in some third countries ) ,
 From treatment of carrageenan gum (an additive from sea
weeds )with hypochlorite for bleaching and
EFSA AF MEETING, PARMA, ITALY
8-9 DECEMBER 2016
Unbound SEM from different sources
other than Nitrofurans
• The breakdown of ADC (from flour improver or from
blowing agent in plastics ) gives rise to the presence
of SEM in a number processed food consumed such
as breaded fish and chicken consumed by children
• So this SEM in the bread will be in the unbound part
• Also in the case of treatment of carrageenan gum with
hypochlorite ,residual chlorine may persist give rise to
SEM also in the unbound part
EFSA AF MEETING, PARMA, ITALY
8-9 DECEMBER 2016
EFSA opinion on Nitrofurans
Nitrofurans:
-
The EC requested EFSA to provide a scientific opinion on the risks of
human health related to the presence of nitrofurans and their metabolites
in food and whether the Reference Point of Action (RPA, 1.0 ug/kg) for the
marker metabolites is adequate to protect public health.
EFSA (CONTAM)Panel (provided in 2015 (EFSA Journal 13(6) a
Scientific Opinion on nitrofurans and their metabolites in food
Data on occurrence of Nitrofuran metabolites were taken from the residue
monitoring plans of the MS from 2002-2013
And also from RASFF Database where 808 notifications events were
reported ,of which 416 were crustaceans and 150 poultry and meat products
EFSA AF MEETING, PARMA, ITALY
8-9 DECEMBER 2016
Limitations
• EFSA concluded that the occurrence data and from
RASFF were too limited to perform a reliable human
dietary exposure assessment
• The exposure assessment estimation was based on
the scenario in which a single nitrofuran marker
metabolite is present at the RPA of 1 microgm/kg in
foods of animal origin (even worst case scenarios
were applied).
• Milk and dairy products were excluded
EFSA AF MEETING, PARMA, ITALY
8-9 DECEMBER 2016
Findings in the EFSA opinion
• .
• Nitrofurazone and its marker metabolite SEM are
genotoxic in vitro .The in vivo tests showed negative
results with Nitrofurazone but no conclusion can be
drawn for SEM
• Acute toxicity studies in Lab animals showed that
for Nitrofurazone and some others ,the lung is an
important target for toxicity leading to respiratory
failure and death signs of neurotoxicity were also
found .
• There is limited evidence that SEM is carcinogenic in
mice but not in rats .SEM increased the incidence of
malignant lung tumours in female mice. Also ,effects
on bone development were observed .
EFSA AF MEETING, PARMA, ITALY
8-9 DECEMBER 2016
Not conclusive studies on SEM
• Because most of the nitrofurans and their metabolite are
genotoxic, and /or carcinogenic derivation of Health
Based Guidance Values were not possible .Therefore
margin of exposure (MOE ) were used.
• SEM carcinogenicity study cannot be evaluated – The
need of a new study for the SEM action mechanism
and more information for genotoxic/carcinogenic
effects
• For Nitrofurazone no conclusion could be drawn on its
possible carcinogenicity and for SEM the available
information was not suitable to derive Ref.Point for
carcinogenicity effects
EFSA AF MEETING, PARMA, ITALY
8-9 DECEMBER 2016
SEM from different origins other
than Nitrofurans
• SEM is monitored in foods of animal origin to test for
illegal use of Nitrofurazone at RPA level (or MRPL
Decision 2002/657/EC, 1.0 ug/kg ) in the bound form
at import control –Decision 2005/34/EC
• Laboratories wash samples to get rid of unbound
SEM and consequently Report bound SEM
 However People do not DO washing steps and consume
usually the bound and unbound SEM
 Problems persist with e.g. breaded products in fish or
chicken
EFSA AF MEETING, PARMA, ITALY
8-9 DECEMBER 2016
Impelemntation of EU legislation
CCa Decision level ;varies from country to country as it depends on
the method used
RPA Reference point of Action 1 microgramme /kg (MRPL)
In Cyprus: for SEM ,CCa is 0,127 microgramme /kg
From a Cyprus pilot study
SEM was determined in a number of food samples breaded and non
breaded and results are shown below . 4 samples were non compliant
but no action could be taken as they results are below RPA .
IF total SEM (bound and unbound )was reported then there would be 3
samples where action would be taken
Other Samples tested were meat, milk, eggs and fish.
EFSA AF MEETING, PARMA, ITALY
8-9 DECEMBER 2016
SEM in imported fish 2015-2016
(CCa=0,127 μg/kg-RPA 1μg/kg)
Kind of fish
Origin
Concentration
(μg/kg)-bound and
unbound
Concentration after
wash (μg/kg)bound
Pangasius fillet
frozen
Vietnam
3,21
0,968
Pangasius fillet
frozen
Vietnam
1,17
0,547
Pangasius fillet
frozen
Vietnam
0,391
0,144
Pangasius breaded
fillet frozen
Vietnam
1,76
0,271
Cod breaded fillet
frozen
Atlantic Ocean
0,135
0,0842
EFSA AF MEETING, PARMA, ITALY
8-9 DECEMBER 2016
SEM in imported fish 2015-2016
Number of samples
Kind of fish
Non compliant
12
Pangasius fillet frozen
3
4
Breaded Cod fillet
2
3
Frozen Shrimps
0
1
Common sole fillet
0
3
Cod Fish Fillet
0
1
Salmon
0
EFSA AF MEETING, PARMA, ITALY
8-9 DECEMBER 2016
What should be the true data
reported for SEM?
• Laboratories wash samples to get rid of unbound SEM and
consequently Report bound SEM
• People however do not DO washing steps and consume usually
the bound and unbound SEM
• It is important to know the source of SEM , if not in the
bound form , but it is also good to know the total , as this the
quantity that is consumed .
• Consumers and especially children eat
breaded fish or chicken for example Bound and unbound
!
• Is this agreeable to Risk assessors and/or Risk managers ?
EFSA AF MEETING, PARMA, ITALY
8-9 DECEMBER 2016
Since more data are needed for
conclusive opinions ,true data and the
origin of the parameters is essential
especially for SEM
If you are going to have breaded
Turkey or salmon for Christmas have
this in mind
Thank you for your
attention
EFSA AF MEETING, PARMA, ITALY
8-9 DECEMBER 2016