PMID- 34742781
OWN - NLM
STAT- MEDLINE
DCOM- 20211122
LR  - 20211122
IS  - 1879-3150 (Electronic)
IS  - 0041-0101 (Linking)
VI  - 204
DP  - 2021 Dec
TI  - Acute toxicity of decarbamoyl gonyautoxin 1&4 to mice by various routes of 
      administration.
PG  - 56-63
LID - S0041-0101(21)00302-0 [pii]
LID - 10.1016/j.toxicon.2021.11.001 [doi]
AB  - Saxitoxin and its derivatives, the paralytic shellfish toxins (PSTs), are well 
      known to be toxic to humans, and maximum permitted levels in seafood have been 
      established by regulatory authorities in many countries. Monitoring of PSTs is 
      typically performed using chemical methods which quantify the concentration of 
      the individual PST analogues, of which there are many. However, since the 
      toxicities of analogues are different, they do not equally contribute to the 
      overall toxicity of the sample. To account for these differences, toxicity 
      equivalency factors (TEFs) need to be determined for each analogue and applied. 
      Currently there are no established TEFs for decarbamoyl gonyautoxin 1&4 
      (dcGTX1&4), which occurs in some clam species such as Mactra chinensis 
      contaminated with PSTs due to metabolism within the shellfish. In this study the 
      median lethal dose of purified, equilibrated epimeric mixture of dcGTX1&4 has 
      been determined by intraperitoneal injection (i.p.) (4.75 mumol/kg) and by feeding 
      (34.9 mumol/kg). The most relevant route of exposure is orally with feeding being 
      more representative of human consumption and more reliable than gavage. Based on 
      the median lethal dose by feeding, a TEF of 0.1 is recommended for dcGTX1&4. 
      Receptor binding activity and i.p. toxicity results showed dcGTX1&4 to be much 
      less toxic than STX (140-170-fold). However, by feeding a much smaller difference 
      in toxicity was observed with dcGTX1&4 being only 11-fold less toxic than STX. 
      Analysis of the gut contents of mice dosed with dcGTX1&4 showed the presence of 
      decarbamoyl gonyautoxin 2&3, decarbamoyl saxitoxin and decarbamoyl neosaxitoxin, 
      all of which are of greater toxicity. This conversion of dcGTX1&4 within the 
      digestive track to more toxic congeners may explain the high relative toxicity of 
      dcGTX1&4 by feeding compared to that determined by i.p. and by sodium channel 
      activity.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Boundy, Michael J
AU  - Boundy MJ
AD  - Cawthron Institute, Private Bag 2, Nelson, 7042, New Zealand. Electronic address: 
      Michael.Boundy@cawthron.org.nz.
FAU - Harwood, D Tim
AU  - Harwood DT
AD  - Cawthron Institute, Private Bag 2, Nelson, 7042, New Zealand.
FAU - Tommasi, Elena
AU  - Tommasi E
AD  - Cawthron Institute, Private Bag 2, Nelson, 7042, New Zealand.
FAU - Burger, Emillie
AU  - Burger E
AD  - Cawthron Institute, Private Bag 2, Nelson, 7042, New Zealand.
FAU - van Ginkel, Roel
AU  - van Ginkel R
AD  - Cawthron Institute, Private Bag 2, Nelson, 7042, New Zealand.
FAU - Waugh, Craig
AU  - Waugh C
AD  - Cawthron Institute, Private Bag 2, Nelson, 7042, New Zealand.
FAU - Selwood, Andrew I
AU  - Selwood AI
AD  - Cawthron Institute, Private Bag 2, Nelson, 7042, New Zealand.
FAU - Finch, Sarah
AU  - Finch S
AD  - AgResearch Limited, Ruakura Research Centre, Private Bag 3123, Hamilton, 3240, 
      New Zealand.
LA  - eng
PT  - Journal Article
DEP - 20211104
PL  - England
TA  - Toxicon
JT  - Toxicon : official journal of the International Society on Toxinology
JID - 1307333
RN  - 35523-89-8 (Saxitoxin)
RN  - 77462-64-7 (gonyautoxins)
SB  - IM
MH  - Animals
MH  - *Bivalvia
MH  - Mice
MH  - Saxitoxin/analogs & derivatives/toxicity
MH  - Shellfish/analysis
MH  - *Shellfish Poisoning
OTO - NOTNLM
OT  - LD(50)
OT  - Metabolism
OT  - Reference material stability
OT  - Saxitoxin
OT  - Toxicity equivalency factor
EDAT- 2021/11/08 06:00
MHDA- 2021/11/23 06:00
CRDT- 2021/11/07 20:35
PHST- 2021/09/06 00:00 [received]
PHST- 2021/10/08 00:00 [revised]
PHST- 2021/11/02 00:00 [accepted]
PHST- 2021/11/08 06:00 [pubmed]
PHST- 2021/11/23 06:00 [medline]
PHST- 2021/11/07 20:35 [entrez]
AID - S0041-0101(21)00302-0 [pii]
AID - 10.1016/j.toxicon.2021.11.001 [doi]
PST - ppublish
SO  - Toxicon. 2021 Dec;204:56-63. doi: 10.1016/j.toxicon.2021.11.001. Epub 2021 Nov 4.