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Relative toxicity of dinophysistoxin-2 (DTX-2) compared with okadaic acid, based on acute intraperitoneal toxicity in
Tore Aune1, Stig Larsen, John A B Aasen
1Norwegian School of Veterinary Science, P. O. Box 8146 Dep., 0033 Oslo, Norway. tore.aune@veths.no
Abstract:
When substituting the mouse bioassay for lipophilic marine algal toxins in shellfish with analytical methods, science based factors of relative toxicity for all analogues that contribute to health risk to consumers are necessary. The aim of this paper is to establish the relative intraperitoneal toxicity of dinophysistoxin-2 (DTX-2) compared with okadaic acid (OA). The study was performed as an open, randomised parallel group trial with a four level response surface design within each of the two parallels. In accordance with the response surface design model, the LD50 for DTX-2 and OA was 338 and 206 microg/kg, respectively. By use of common regression analysis, the LD50 of DTX-2 and OA were estimated to 352 microg/kg and 204 microg/kg, respectively. The deviations between the LD50 estimates by the two methods was 4% for DTX-2 and less than 1% for OA. Taken together, these results indicate that the relative toxicity of DTX-2 is about 0.6, compared to OA. Results from the PP2A assay correspond very well with the results obtained by the mouse bioassay. The IC50 concentrations for DTX-2 and OA were 5.94 and 2.81 ng/mL, respectively. This indicates that OA is about twice as toxic as DTX-2. Since inhibition of PP2A is acknowledged as the main mechanism of toxicity of the OA group toxins, this supports the establishment of a relative toxicity factor of DTX-2 of 0.6 compared with OA.
Insights
Determining the relative toxicity of marine algal toxins like dinophysistoxin-2 (DTX-2) and okadaic acid (OA) is crucial for consumer safety. This study found DTX-2 has about 0.6 times the toxicity of OA.
Area of Science:
- Marine toxicology
- Food safety analysis
- Analytical chemistry
Background:
- Mouse bioassays for lipophilic marine algal toxins in shellfish are being replaced by analytical methods.
- Science-based relative toxicity factors are needed for analogues to assess consumer health risks.
Purpose of the Study:
- To determine the relative intraperitoneal toxicity of dinophysistoxin-2 (DTX-2) compared to okadaic acid (OA).
- To establish a relative toxicity factor for DTX-2 against OA.
Main Methods:
- An open, randomized parallel group trial with a four-level response surface design was employed.
- LD50 values for DTX-2 and OA were determined using both response surface design and common regression analysis.
- Protein phosphatase 2A (PP2A) inhibition assays were conducted.
Main Results:
- The LD50 for DTX-2 was estimated at 338-352 µg/kg, and for OA at 204-206 µg/kg.
- The relative toxicity of DTX-2 compared to OA was found to be approximately 0.6.
- PP2A inhibition assays showed OA (IC50: 2.81 ng/mL) is about twice as toxic as DTX-2 (IC50: 5.94 ng/mL).
Conclusions:
- The relative toxicity factor of DTX-2 is established as 0.6 compared to OA.
- Results from the PP2A assay strongly correlate with the mouse bioassay findings.
- Inhibition of PP2A is confirmed as the primary mechanism for OA-group toxin toxicity, supporting the established relative toxicity factor.
