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. 2018 Mar 28;10(4):141.
doi: 10.3390/toxins10040141.

Dose-Response Modelling of Paralytic Shellfish Poisoning (PSP) in Humans

Nathalie Arnich  1 , Anne Thébault  2
Affiliations

Dose-Response Modelling of Paralytic Shellfish Poisoning (PSP) in Humans

Nathalie Arnich et al. Toxins (Basel). .

Abstract

Paralytic shellfish poisoning (PSP) is caused by a group of marine toxins with saxitoxin (STX) as the reference compound. Symptoms in humans after consumption of contaminated shellfish vary from slight neurological and gastrointestinal effects to fatal respiratory paralysis. A systematic review was conducted to identify reported cases of human poisoning associated with the ingestion of shellfish contaminated with paralytic shellfish toxins (PSTs). Raw data were collected from 143 exposed individuals (113 with symptoms, 30 without symptoms) from 13 studies. Exposure estimates were based on mouse bioassays except in one study. A significant relationship between exposure to PSTs and severity of symptoms was established by ordinal modelling. The critical minimal dose with a probability higher than 10% of showing symptoms is 0.37 µg STX eq./kg b.w. This means that 10% of the individuals exposed to this dose would have symptoms (without considering the severity of the symptoms). This dose is four-fold lower than the lowest-observed-adverse-effect-level (LOAEL) established by the European Food Safety Authority (EFSA, 2009) in the region of 1.5 μg STX eq./kg b.w. This work provides critical doses that could be used as point of departure to update the acute reference dose for STX. This is the first time a dose-symptoms model could be built for marine toxins using epidemiological data.

Keywords: PSP; STX; dose-response; marine biotoxins; ordinal modelling; saxitoxin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Predicted probabilities of specified symptoms for different level of doses with the CLMM model in comparison with the observed data.
Figure 2
Figure 2
Predicted probabilities of specified symptoms for different level of doses with the CLM model in comparison with the observed data.
Figure 3
Figure 3
Predicted probabilities from the ordinal model of showing symptoms in function of the dose of ingested PSTs (log10 scale) with five categories of symptoms.
Figure 4
Figure 4
Predicted probability of symptoms more than a specified level in function of the mean dose of ingested PSTs (log10 scale). Lower critical dose (LCD) (for the lower bound of the confidence interval at 95%) (the black dotted segment, left of the dotted red segment), critical dose (CD) (mean) (the dotted red segment), and upper critical dose (UCD) (the upper bound of the confidence interval at 95%) (the black dotted segment right of the red segment), are represented for a risk of 10%. Category of symptoms: 0 = no symptoms; 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms; 4 = death. CI = Confidence Interval.
Figure 5
Figure 5
Diagram of the literature search of reported cases of human poisoning associated with the ingestion of shellfish contaminated with PSTs.
Figure 6
Figure 6
Relative R2 in function of the excluded publication (n = 15).
Figure 7
Figure 7
Category of symptoms in the key studies in function of exposure (n = 15, left, without Akaeda et al. 1998 [9]; Gessner and Middaugh 1995 [18] n = 13).
Figure 8
Figure 8
Distribution of the symptoms by sex in terms of the function of the mean ingested dose (number of males = 70, number of females = 41).
Figure 9
Figure 9
Distribution of the symptoms by age in class in terms of the function of the mean ingested dose (number of individuals < 10 years old = 5, number of individuals 10–20 = 6, number of individuals 20–50 = 36, number of individuals > 50 = 14).
See this image and copyright information in PMC

References

    1. Food and Agriculture Organization (FAO) World Health Organization (WHO) Technical Paper on Toxicity Equivalency Factors for Marine Biotoxins Associated with Bivalve Molluscs. FAO; Rome, Italy: 2016. [(accessed on 27 March 2018)]. p. 108. Available online: http://www.fao.org/3/a-i5970e.pdf.
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    1. U.S. Regulation (Chapter 6: Natural Toxins) [(accessed on 27 March 2018)]; Available online: https://www.fda.gov/downloads/food/guidanceregulation/ucm252395.pdf.

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