7 Regulatory Perspective in Translating Science into Policy. . .
79
regulatory monitoring. The WG decided that the data were insufficient to complete
the risk assessment. The relevant brevetoxins and their metabolites need to be
identified and estimates of their oral potencies are needed before an ARfD can be
established (Toyofuku 2006).
At the pWG, the pWG concurred with the WG’s decision that there was
currently insufficient evidence to complete the risk assessment of brevetoxins.
However, despite the WG’s decision regarding the available evidence for a risk
assessment, the WG recognized the body of knowledge resulting from the existing
history of regulatory programs (e.g. in the US, Mexico and New Zealand) and
the absence of human illness in commercially harvested shellfish, where these
programs are implemented. Finally the WG recommended (Codex 2006b) that the
Codex standard identified an action level for the brevetoxins of 20 Mouse Units or
equivalent (conditional on the equivalence information becoming available). During
the discussion at 28th CCFFP, a request was made to FAO/WHO to re-evaluate
brevetoxins because there was no brevetoxin limit recommended by the WG
(Codex 2006a).
Regarding domoic acid (DA), the results of the first outbreak of amnesic shellfish
poisoning that occurred in 1987 in Canada provide the best basis for developing an
acute reference dose (tolerable single day intake, acute TDI). During this outbreak, a
dose- related increase in the severity of signs and symptoms was observed in patients
consuming between 1 mg/kg bw (the LOAEL) and 5 mg/kg bw. Studies in rodents
and cynomolgous monkeys have generally supported these findings. To cover the
full spectrum of human susceptibility, and account for the fact that 1 mg/kg bw was
a LOAEL, this value was divided by a safety factor of 10, to derive a provisional
ARfD of 0.1 mg/kg bw. This value seems reasonable, as one person who consumed
0.33 mg/kg bw did not become ill. The provisional ARfD of 0.1 mg/kg bw provided
the basis for the establishment of the maximum residue limit (MRL) for DA by
Canadian authorities, which on the basis of an intake of 250 g shellfish and a body
weight of 60 kg, was 24, rounded down to 20 g DA/g shellfish. If instead of 250 g
shellfish, a value of 300 g shellfish was used, the MRL would be exactly 20 g
DA/g shellfish.
Very few animal studies have been conducted on the subchronic and chronic
toxicity of DA, and these limited data suggest that cumulative effects of low doses
of DA are unlikely. In this regard, studies based on subacute mouse studies revealed
no differences in behavioral toxicity scores upon re-exposure to DA compared to
a single dose (i.e., behavioral equivalent of kindling). The available data indicate
that chronic sequelae, such as epilepsy and memory deficit, were observed only in
those patients who had suffered severe acute neurological effects (examined up to
3.5 years post-event) after they had ingested a single high dose of DA. It is therefore
unlikely that people who habitually consume small amounts of DA (exposures less
than 0.1 mg DA/kg bw) would experience any chronic effects. Thus, this ARfD
also may be considered a provisional chronic TDI. As shown in Table 7.1, the
consumption of 100, 250 or 380 g shellfish meat by adults would lead to a derived
guidance level of 60, 24 or 16 mg DA/kg shellfish meat, respectively (Toyofuku
2006). The pWG noted that the action levels derived in the report support the current
79
regulatory monitoring. The WG decided that the data were insufficient to complete
the risk assessment. The relevant brevetoxins and their metabolites need to be
identified and estimates of their oral potencies are needed before an ARfD can be
established (Toyofuku 2006).
At the pWG, the pWG concurred with the WG’s decision that there was
currently insufficient evidence to complete the risk assessment of brevetoxins.
However, despite the WG’s decision regarding the available evidence for a risk
assessment, the WG recognized the body of knowledge resulting from the existing
history of regulatory programs (e.g. in the US, Mexico and New Zealand) and
the absence of human illness in commercially harvested shellfish, where these
programs are implemented. Finally the WG recommended (Codex 2006b) that the
Codex standard identified an action level for the brevetoxins of 20 Mouse Units or
equivalent (conditional on the equivalence information becoming available). During
the discussion at 28th CCFFP, a request was made to FAO/WHO to re-evaluate
brevetoxins because there was no brevetoxin limit recommended by the WG
(Codex 2006a).
Regarding domoic acid (DA), the results of the first outbreak of amnesic shellfish
poisoning that occurred in 1987 in Canada provide the best basis for developing an
acute reference dose (tolerable single day intake, acute TDI). During this outbreak, a
dose- related increase in the severity of signs and symptoms was observed in patients
consuming between 1 mg/kg bw (the LOAEL) and 5 mg/kg bw. Studies in rodents
and cynomolgous monkeys have generally supported these findings. To cover the
full spectrum of human susceptibility, and account for the fact that 1 mg/kg bw was
a LOAEL, this value was divided by a safety factor of 10, to derive a provisional
ARfD of 0.1 mg/kg bw. This value seems reasonable, as one person who consumed
0.33 mg/kg bw did not become ill. The provisional ARfD of 0.1 mg/kg bw provided
the basis for the establishment of the maximum residue limit (MRL) for DA by
Canadian authorities, which on the basis of an intake of 250 g shellfish and a body
weight of 60 kg, was 24, rounded down to 20 g DA/g shellfish. If instead of 250 g
shellfish, a value of 300 g shellfish was used, the MRL would be exactly 20 g
DA/g shellfish.
Very few animal studies have been conducted on the subchronic and chronic
toxicity of DA, and these limited data suggest that cumulative effects of low doses
of DA are unlikely. In this regard, studies based on subacute mouse studies revealed
no differences in behavioral toxicity scores upon re-exposure to DA compared to
a single dose (i.e., behavioral equivalent of kindling). The available data indicate
that chronic sequelae, such as epilepsy and memory deficit, were observed only in
those patients who had suffered severe acute neurological effects (examined up to
3.5 years post-event) after they had ingested a single high dose of DA. It is therefore
unlikely that people who habitually consume small amounts of DA (exposures less
than 0.1 mg DA/kg bw) would experience any chronic effects. Thus, this ARfD
also may be considered a provisional chronic TDI. As shown in Table 7.1, the
consumption of 100, 250 or 380 g shellfish meat by adults would lead to a derived
guidance level of 60, 24 or 16 mg DA/kg shellfish meat, respectively (Toyofuku
2006). The pWG noted that the action levels derived in the report support the current