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Ricin Poisoning

  • Defence Science and Technology Laboratory (Dstl)


Ricin is a naturally occurring toxin derived from the beans of the castor oil plant Ricinus communis. It is considered a potential chemical weapon. Ricin binds to cell surface carbohydrates, is internalised then causes cell death by inhibiting protein synthesis. Oral absorption is poor and absorption through intact skin most unlikely; the most hazardous routes of exposure being inhalation and injection. Features of toxicity mainly reflect damage to cells of the reticuloendothelial system, with fluid and protein loss, bleeding, oedema and impaired cellular defence against endogenous toxins. It has been estimated that in man, the lethal dose by inhalation (breathing in solid or liquid particles) and injection (into muscle or vein) is approximately 5-10 micrograms/kg, that is 350-700 micrograms for a 70 kg adult. Death has ensued within hours of deliberate subcutaneous injection. Management is supportive. Prophylactic immunisation against ricin toxicity is a developing research initiative, although presently not a realistic option in a civilian context.
Toxicol Rev 2003; 22 (1): 65-70
Adis Data Information BV 2003. All rights reserved.
Ricin Poisoning
Sally M. Bradberry,
Kirsten J. Dickers,
Paul Rice,
Gareth D. Griffiths
and J. Allister Vale
1 National Poisons Information Service (Birmingham Centre), City Hospital, Birmingham, UK
2 West Midlands Poisons Unit, City Hospital, Birmingham, UK
3 Dstl Porton Down, Salisbury, UK
Abstract ................................................................................................................65
1. The Potential Use of Ricin as a Chemical Weapon .......................................................................66
2. Mechanisms of Toxicity ...............................................................................................66
3. Toxicokinetics ........................................................................................................66
4. Clinical Features .....................................................................................................66
4.1 Ingestion ........................................................................................................66
4.2 Intramuscular and Subcutaneous Administration ....................................................................67
4.3 Intravenous Administration ........................................................................................67
4.4 Inhalation .......................................................................................................68
4.5 Topical .........................................................................................................68
5. Diagnosis ............................................................................................................68
6. Management .......................................................................................................68
6.1 Ingestion ........................................................................................................68
6.2 Parenteral Exposure ..............................................................................................68
6.3 Aerosol Inhalation ................................................................................................68
6.4 Prophylaxis ......................................................................................................69
7. Conclusion ..........................................................................................................69
Ricin is a naturally occurring toxin derived from the beans of the castor oil plant Ricinus communis. It is
considered a potential chemical weapon. Ricin binds to cell surface carbohydrates, is internalised then causes
cell death by inhibiting protein synthesis. Oral absorption is poor and absorption through intact skin most
unlikely; the most hazardous routes of exposure being inhalation and injection. Features of toxicity mainly
reflect damage to cells of the reticuloendothelial system, with fluid and protein loss, bleeding, oedema and
impaired cellular defence against endogenous toxins. It has been estimated that in man, the lethal dose by
inhalation (breathing in solid or liquid particles) and injection (into muscle or vein) is approximately 5–10 µg/kg,
that is 350–700µg for a 70kg adult. Death has ensued within hours of deliberate subcutaneous injection.
Management is supportive. Prophylactic immunisation against ricin toxicity is a developing research initiative,
although presently not a realistic option in a civilian context.
Ricin is a globular glycoprotein, which makes up 1–5% by length. Castor oil is obtained from the beans by cold pressing and
weight of the beans of the castor oil plant Ricinus communis, an is used as a purgative and laxative. Hot pressing of the beans,
annual shrub common in warm climates. The beans are 0.5–2cm in followed by solvent extraction, is used to produce specialist oils
66 Bradberry et al.
and lubricants. The residue is used as a cattle feed or as a induced hepatotoxicity. Kupffer cell destruction impairs the liver’s
after ricin has been destroyed by heating. Ricin, a capacity to detoxify endogenous toxins, which may contribute to
soluble white powder, is stable under ambient conditions, but can further damage.
Mice administered intraperitoneal ricin show
be detoxified by heating for 10 minutes at 80ºC or for 1 hour at evidence of oxidative stress in the liver and kidneys, with accumu-
lation of lipid peroxidation products that may also arise from
damaged Kupffer cells.
Ricin consists of an A chain and a B chain, linked by disulphide
bonds. The A chain confers ricin’s cellular toxicity, while the B
3. Toxicokinetics
chain gives ricin the properties of a lectin, that is a plant molecule
with a high affinity for glycoproteins on cell surface receptors. The
As a relatively large protein, ricin is unlikely to be extensively
term ‘toxalbumin’ is also sometimes applied to ricin and refers to
absorbed from the gastrointestinal tract. In animal studies, most
those larger lectin molecules that have a molecular weight similar
orally administered ricin was found in the large intestine after 24
to albumin.
hours, with only limited systemic uptake.
Dermal absorption of
ricin through intact skin is most unlikely to occur, unless there are
1. The Potential Use of Ricin as a Chemical Weapon
open cuts. In mice, intravenously administered ricin was distribut-
ed predominantly to the spleen, kidneys, heart and liver.
The use of ricin to cause mass casualties would require either its
administered intramuscularly was found to localise in draining
aerosolisation by means of a dispersal device, or its addition to
lymph nodes.
Ricin was eliminated as degraded proteins, pre-
food and beverages as a contaminant. It should be noted that by the
dominantly in the urine, in other studies in rats.
oral route, ricin is approximately three orders of magnitude less
toxic than by either the inhalation or parenteral routes. Generating
4. Clinical Features
a large-scale aerosol would be best achieved with a dry powder
consisting of very small particles. By inhalation (breathing in solid
Ricin is toxic via all routes, although the features of poisoning
or liquid particles) and injection (into muscle or a vein), the lethal
and severity of toxicity vary markedly with the dose and route of
dose is approximately 5–10 µg/kg bodyweight, that is for an
exposure. The estimated dose of ricin which is lethal to 50% of
average male weighing 70kg, the lethal dose would be 350–700µg.
mice tested (LD
) by intragastric administration was 20 mg/kg
although the frequently cited human fatal oral dose
2. Mechanisms of Toxicity
of 1 mg/kg bodyweight
remains unconfirmed. In mice, the
by intravenous injection was 5 µg/kg bodyweight.
Ricin binds to cell surface carbohydrates; cells of the
fatal dose by injection in humans has been suggested to be in the
reticuloendothelial system are particularly susceptible since they
order of 1–10 µg/kg bodyweight;
however, there are no reliable
are one of a limited number of cell lines to bear mannose receptors
data to support this.
to which ricin can bind avidly. Once internalised, the ricin A chain
attacks ribosomes and so inhibits protein synthesis, leading to cell
4.1 Ingestion
death. These aspects are covered more extensively by Marsden et
al. in the accompanying review.
Many of the features observed Most cases of ingestion involve eating castor beans. The degree
in poisoning can therefore be explained by ricin-induced endothe- of seed mastication is important since beans swallowed whole may
lial cell damage, with fluid and protein leakage and tissue oedema, pass through the gastrointestinal tract intact, whereas the chewing
causing a so-called ‘vascular leak syndrome’. Disseminated in- of seeds facilitates ricin release.
travascular coagulation has been observed in experimental animals
In cases of substantial ingestion of castor beans, the onset of
following intravenous ricin administration and this is also likely to
gastrointestinal features occurred typically within a few hours with
reflect endothelial cell damage.
oropharyngeal irritation,
Hepatocellular and renal damage is at least partly secondary to pain
and diarrhoea.
vascular damage and impaired tissue perfusion, rather than a direct matemesis,
bloody diarrhoea
or melaena
may occur.
effect of the toxin itself. Animal studies have suggested that Subsequent features reflect fluid and electrolyte loss with hypoten-
Kupffer cells (liver macrophages) are the primary targets in ricin- sion,
Adis Data Information BV 2003. All rights reserved. Toxicol Rev 2003; 22 (1)
Ricin Poisoning 67
and peripheral cyanosis.
Pre-renal impair- Ricin was allegedly used in the assassination of the Bulgarian
ment secondary to hypovolaemia is common in patients with defector Georgi Markov. Those investigating the case estimated
substantial gastrointestinal fluid loss
and may progress to renal the injected dose of ricin to be some 500µg, although ricin was
In more severe cases, hypovolaemic shock, with never isolated analytically.
There was immediate pain at the site
oliguria or anuria, may ensue.
haema- of injection (the thigh), with fatigue, nausea, vomiting and fever
and hyaline casts on urine microscopy
have also developing over the next 24 hours. At admission, some 36 hours
been reported. after the incident, local necrotic lymphadenopathy was present and
gastrointestinal haemorrhage ensued with hypovolaemic shock
Some degree of transient liver damage is likely in all but the
and renal failure; death occurred on the third day. At autopsy there
mildest cases, with increased hepatic transaminase and lactate
was evidence of pulmonary oedema and haemorrhagic necrosis of
dehydrogenase activities,
and less commonly hyperbilirubi-
the small bowel; haemorrhages were observed in the lymph nodes
Occasionally, liver function tests remain normal until
local to the injection site, in the myocardium, testicles and pancre-
several days after exposure.
Other reported features include disorientation,
A 36-year-old chemist self-administered two intramuscular in-
jections of ricin prepared from a single castor bean.
Although it
intravascular haemolysis,
was calculated that he had injected 150mg ricin, this would be
impossible from a single bean. The maximum amount of ricin that
blurred vision.
is extractable from a single bean is about 10mg, which would
Investigations may show a metabolic acidosis,
equate to a maximum dose of no more than 140 µg/kg bodyweight.
or hypoglycaemia,
Ten hours after the injections, he complained of headache and
and increased creatine kinase activity.
rigors. He developed anorexia and nausea, a sinus tachycardia,
In a series of ten paediatric castor bean ingestions, seven had
erythematous areas around the puncture wounds and local
transient ECG abnormalities, including QT interval prolongation
lymphadenopathy at the sites of injection. Investigation showed
(in five cases), intraventricular conduction disturbance and repo-
mildly increased hepatic transaminase activities. He was dis-
larisation changes. The authors suggested that these changes were
charged well after 10 days.
probably secondary to metabolic disturbances.
It is possible that
A 20-year-old man was admitted to hospital 36 hours after
these abnormalities may have resulted from ricin-induced apopto-
injecting castor bean extract subcutaneously.
He complained of
sis of key elements of the cardiac conduction system. Such an
nausea, weakness, dizziness, chest and abdominal pain and myal-
effect of ricin has been noted in vivo in rats.
gia with paraesthesiae of the extremities. Hypotension, anuria and
In fatal cases, death usually occurs on the third day or later and
a metabolic acidosis were noted on examination and fresh blood
is due to multi-organ failure.
The most common findings at
was present in the rectum, possibly related to the development of a
autopsy are ulceration of the mucosa of the stomach and small
bleeding diathesis. Hepatorenal and cardiorespiratory failure then
intestine, necrosis of mesenteric lymph nodes, hepatic necrosis
developed and the patient died 18 hours after admission following
and nephritis.
an asystolic arrest.
4.2 Intramuscular and Subcutaneous Administration
4.3 Intravenous Administration
When intravenous ricin 18–20 µg/m
(approximately 0.5 µg/kg
Rats administered ricin 5µg (33–50µg/kg bodyweight) intra-
bodyweight) was investigated as a potential chemotherapeutic
muscularly survived a maximum of 35 hours. Post-mortem exam-
agent it caused flu-like symptoms with marked fatigue and myal-
ination of the intestinal tract demonstrated severe haemorrhage
gia, and sometimes nausea and vomiting.
with apoptosis of cells lining the small intestine, particularly the
ileum, which showed marked lymphoid cell and macrophage In studies using ricin A chain linked to a monoclonal antibody
infiltration of villi. The stomach and colon were largely unaffect- for anti-tumour immunotherapy, the principal dose-limiting ad-
verse effect was ‘vascular leak syndrome’. This was characterised
Adis Data Information BV 2003. All rights reserved. Toxicol Rev 2003; 22 (1)
68 Bradberry et al.
by hypoalbuminaemia,
oedema-associated weight gain,
Ricin is severely irritating to the eye. In animal studies, pseudo-
pulmonary function abnormalities including reduced forced vital membranous conjunctivitis occurred following application of ricin
capacity, pleural effusion,
pulmonary oedema,
renal insuffi- solutions in concentrations of 1 : 1000–1 : 10 000.
ciency (with oliguria and impaired creatinine clearance),
5. Diagnosis
ac failure and hypotension,
sometimes in association with a
pericardial effusion.
Other common features included weak-
Detection of anti-ricin antibodies could aid the diagnosis in
nausea and vomiting,
myalgia, associated in some cases
those individuals exposed to ricin who survive for 2–3 weeks.
with increased total creatine kinase activity,
joint discomfort,
However, humoral immunoglobulin M responses would likely be
and occasionally ‘allergic reactions’ during
of short duration only. No immunological memory would be
the infusion.
anticipated without boosting. Anti-ricin antibodies would not be
In a study of 56 patients treated with ricin A chain immunotox-
detected in those dying soon after exposure. In these circum-
in, 12 required interruption or termination of treatment due to the
stances, the use of a ribosome inactivation test
would be more
severity of adverse effects, and two patients died as a result of
useful. A sensitive enzyme-linked immunosorbent assay was de-
vascular leak syndrome.
Vascular leak syndrome was more
veloped by Leith et al.
that could detect ricin in selected tissues
common in patients who had received radiotherapy prior to im-
up to 48 hours following its intramuscular administration. Beyond
this timeframe, toxin detection would be unlikely, although it may
well be possible to extend the sensitivity of this assay and hence,
4.4 Inhalation
perhaps, the window for retrospective identification.
Non-human primates exposed to ricin by inhalation, developed
6. Management
necrotising interstitial and alveolar inflammation with oedema and
fibrinopurulent pneumonia. These manifestations typically oc-
6.1 Ingestion
curred after a dose-dependent delay of 8–24 hours.
findings have been observed in rodents.
The benefit of gastric lavage or the administration of activated
An allergic syndrome has been observed in workers occupa-
charcoal is uncertain but may be considered if patients present
tionally exposed to castor bean dust.
Susceptible patients
within the first hour following ingestion of ricin. Gastrointestinal
presented with acute onset conjunctivitis,
fluid losses should be replaced. Cardiopulmonary, hepatic and
ing, urticaria and wheeze,
which responded to conventional
renal function should be monitored. Organ dysfunction should be
measures and removal from exposure. Historically, castor bean
managed conventionally.
dust has been the cause of endemic asthma in the locality of a
castor oil mill.
The allergen identified as being responsible for
6.2 Parenteral Exposure
this effect is now known not to be ricin itself but a separate protein.
Symptomatic and supportive measures are the mainstay of
management of this highly toxic route of exposure. There is some
4.5 Topical
evidence that the intravenous administration of ricin antibody
shortly (within 1–2 hours) after ricin exposure may improve
Both type I and type IV allergic responses have been reported
although this has to be confirmed and probably has no
following dermal exposure to castor bean dust.
A 21-year-old
utility in a civilian population where there would be no near real-
female had an anaphylactic-type response after a castor bean from
time detection of ricin exposure.
her necklace disintegrated in her fingers. She immediately devel-
oped sneezing, rhinitis and periorbital oedema, with facial urticar-
6.3 Aerosol Inhalation
ia and erythema, requiring subcutaneous adrenaline (epineph-
However, as suggested in section 4.4, ricin is only one of Removal from exposure and airway support with adequate
several allergenic proteins in castor beans. ventilation are the priorities. Pulmonary oedema should be treated
Adis Data Information BV 2003. All rights reserved. Toxicol Rev 2003; 22 (1)
Ricin Poisoning 69
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A rapid, sensitive, and specific method for ricinine identification and quantification in plasma has been developed by LC-HRMS. Deuterated ricinine was used as internal standard. From 100 μL of plasma, ricinine is extracted using micro-solid phase elution, which allows a reduced extraction time, by eliminating the evaporation step. Eluate is directly injected in the LC-HRMS system. Chromatographic separation was performed using a reverse phase C18 column with a 4.5-minute gradient elution. The method was validated according to European Medicines Agency (EMA) guidelines. Linearity was verified between 0.25 and 500.0 ng/mL; the maximum precision calculated was 19.9 % for LLOQ and 9.6 % for quality control, and accuracy was within ± 5.6 % of the nominal concentrations. Selectivity, carry-over, matrix effect and stability were also verified according to EMA guidelines. The method allows the rapid and reliable identification of ricin-exposed victims in case of terrorist attacks or poisonings: 3 intoxication cases are reported.
Full-text available
Ricin toxin is a disulfide-linked glycoprotein (AB toxin) comprising one enzymatic A chain (RTA) and one cell-binding B chain (RTB) contained in the castor bean, a Ricinus species. Ricin inhibits peptide chain elongation via disruption of the binding between elongation factors and ribosomes, resulting in apoptosis, inflammation, oxidative stress, and DNA damage, in addition to the classically known rRNA damage. Ricin has been used in traditional medicine throughout the world since prehistoric times. Because ricin toxin is highly toxic and can be readily extracted from beans, it could be used as a bioweapon (CDC B-list). Due to its extreme lethality and potential use as a biological weapon, ricin toxin remains a global public health concern requiring specific countermeasures. Currently, no specific treatment for ricin intoxication is available. This review focuses on the drugs under development. In particular, some examples are reviewed to demonstrate the proof of concept of antibody-based therapy. Chemical inhibitors, small proteins, and vaccines can serve as alternatives to antibodies or may be used in combination with antibodies.
Full-text available
Ricin toxin is an agent of biodefense concern and we have been developing countermeasures for ricin threats. In doing so, we sought biomarkers of ricin toxicosis and found that in mice parenteral injection of ricin toxin causes profound hypoglycemia, in the absence of other clinical laboratory abnormalities. We now seek to identify the mechanisms underlying this hypoglycemia. Within the first hours following injection, while still normoglycemic, lymphopenia and pro-inflammatory cytokine secretion were observed, particularly tumor necrosis factor (TNF)-α. The cytokine response evolved over the next day into a complex storm of both pro- and anti-inflammatory cytokines. Evaluation of pancreatic function and histology demonstrated marked islet hypertrophy involving predominantly β-cells, but only mildly elevated levels of insulin secretion, and diminished hepatic insulin signaling. Drops in blood glucose were observed even after destruction of β-cells with streptozotocin. In the liver, we observed a rapid and persistent decrease in the expression of glucose-6-phosphatase (G6Pase) RNA and protein levels, accompanied by a drop in glucose-6-phosphate and increase in glycogen. TNF-α has previously been reported to suppress G6Pase expression. In humans, a genetic deficiency of G6Pase results in glycogen storage disease, type-I (GSD-1), a hallmark of which is potentially fatal hypoglycemia.
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Hypoglycemia may be induced by a variety of physiologic and pathologic stimuli and can result in life-threatening consequences if untreated. However, hypoglycemia may also play a role in the purported health benefits of intermittent fasting and caloric restriction. Previously, we demonstrated that systemic administration of ricin toxin induced fatal hypoglycemia in mice. Here, we examine the metabolic landscape of the hypoglycemic state induced in the liver of mice by two different stimuli: systemic ricin administration and fasting. Each stimulus produced the same decrease in blood glucose and weight loss. The polar metabolome was studied using 1H NMR, quantifying 59 specific metabolites, and untargeted LC-MS on approximately 5000 features. Results were analyzed by multivariate analyses, using both principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), to identify global metabolic patterns, and by univariate analyses (ANOVA) to assess individual metabolites. The results demonstrated that while there were some similarities in the responses to the two stimuli including decreased glucose, ADP, and glutathione, they elicited distinct metabolic states. The metabolite showing the greatest difference was O-phosphocholine, elevated in ricin-treated animals and known to be affected by the pro-inflammatory cytokine TNF-a. Another difference was the alternative fuel source utilized, with fasting-induced hypoglycemia primarily ketotic, while the response to ricin-induced hypoglycemia involves protein and amino acid catabolism.
Ricin is one of the most toxic proteins known, which has been listed as both chemical and biological warfare agent due to its unique properties. Rapid and sensitive method capable of detecting and distinguishing activity of the whole ricin has very important realistic significance in view of national security and defense. This study reports a reliable surface‐enhanced Raman scattering (SERS)‐based sandwich immunoassay for the detection and differentiation of active ricin from other homologous toxins. In the immunoassay design, magnetic bead conjugated with a monoclonal antibody (mAb) MIL50 which can recognize the ricin in its holotoxin form was used as a capture probe to separate ricin from complex matrix, while both Raman reporter molecule Nile blue A (NBA) and ricin‐specific mAb 14C12 were modified on gold nanoparticles (AuNPs) to form SERS‐nanoprobes. In the presence of ricin, SERS‐nanoprobes bound to the antigen‐captured magnetic beads and formed a sandwich immunocomplex to produce specific hot spots and then generated highly sensitive signals. As a result, the whole ricin could be detected as low as 1 ng/mL and 5 ng/mL in PBS and in plasma, respectively. Not only active and inactive ricin can be discriminated distinctly, but also ricin from other type II ribosome‐inactivating proteins and their agglutinins. Furthermore, the proposed method made an application to practical samples from OPCW biotoxin exercise test, proving this SERS‐based sandwich immunoassay a promising assay for timely response of ricin related risk assessment in terrorist event and human intoxication.
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Aging is a very complex process that is accompanied by a degenerative impairment in many of the major functions of the human body over time. This inevitable process is influenced by hereditary factors, lifestyle, and environmental influences such as xenobiotic pollution, infectious agents, UV radiation, diet-borne toxins, and so on. Many external and internal signs and symptoms are related with the aging process and senescence, including skin dryness and wrinkles, atherosclerosis, diabetes, neurodegenerative disorders, cancer, etc. Oxidative stress, a consequence of the imbalance between pro-and antioxidants, is one of the main provoking factors causing aging-related damages and concerns, due to the generation of highly reactive byproducts such as reactive oxygen and nitrogen species during the metabolism, which result in cellular damage and apoptosis. Antioxidants can prevent these processes and extend healthy longevity due to the ability to inhibit the formation of free radicals or interrupt their propagation, thereby lowering the level of oxidative stress. This review focuses on supporting the antioxidant system of the organism by balancing the diet through the consumption of the necessary amount of natural ingredients, including vitamins, minerals, polyunsaturated fatty acids (PUFA), essential amino acids, probiotics, plants' fibers, nutritional supplements, polyphenols, some phytoextracts, and drinking water.
Food poisoning caused by eating contaminated food remains a threat to global public health. Making the situation even worse is the aggravated global environmental pollution, which poses a major threat to the safety of agricultural resources. Food adulteration has been rampant owing to negligent national food safety regulations. The speed at which contaminated food is detected and disposed of determines the extent to which consumers’ lives are safeguarded and agricultural economic losses are prevented. Micro/nanomotors offer a high-speed mobile loading platform that substantially increases the chemical reaction rates and, accordingly, exhibit great potential as alternatives to conventional detection and degradation techniques. This review summarizes the propulsion modes applicable to micro/nanomotors in food systems and the advantages of using micro/nanomotors, highlighting examples of their potential use in recent years for the detection and removal of food contaminants. Micro/nanomotors are an emerging technology for food applications that is moving toward mass production, simple preparation, and important functions.
Abrin is a plant cytotoxin that poses a high threat to public safety and therefore requires highly sensitive and efficient detection methods. Affibody molecules are artificial affinity proteins that have been widely studied in bioimaging and medical treatment but rarely used in bioassays. In this work, an electrochemiluminescence (ECL) biosensor for abrin was established with biotin and Ru(bpy)3²⁺ dual-labeled phage display affibodies as molecular recognition and signal element. On this basis, dual-labeled polystyrene nanospheres (nano-PSs) were chosen to link with phages and further achieve ultra-sensitive detection. This assay has a triple signal amplification. First, capsid proteins of M13 phages have connected numerous signal molecules. Second, the nano-PSs bound to the surface of the phages also contained quite a few signal molecules. Third, with the theoretically infinitely repeatable “biotin - streptavidin (SA) - biotin” composite unit as the “mortise and tenon structure”, the dual-labeled nano-PSs further formed highly stacked nano-aggregates, ultimately achieving significant signal amplification. Besides, the detection platform of this assay is a portable electrochemiluminescence sensor based on the screen-printed electrode, which is small and easy to operate. Limit of detection (LOD) for abrin of the ECL biosensor was 9.3 fg/mL and the linear detection range was observed from 10 fg/mL to 100 pg/mL. This new biosensing system has also demonstrated good reproducibility, specificity, practicability and has great potential for highly sensitive detection of contaminants, toxins and biomarkers in environmental monitoring and clinical application.
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Snakebite being a quick progressing serious situation needs immediate and aggressive therapy. Snake venom antiserum is the only approved and effective treatment available, but for selected snake species only. The requirement of trained staff for administration and serum reactions make the therapy complicated. In tropical countries where snakebite incidence is high and healthcare facilities are limited, mortality and morbidities associated with snake envenomation are proportionately high. Traditional compilations of medical practitioners’ personal journals have wealth of plant-based snake venom antidotes. Relatively, very few plants or their extractives have been scientifically investigated for neutralization of snake venom or its components. None of these investigations presents enough evidence to initiate clinical testing of the agents. This review focuses on curating Indian traditional snake envenomation therapies, identifying plants involved and finding relevant evidence across modern literature to neutralize snake venom components. Traditional formulations, their method of preparation and dosing have been discussed along with the investigational approach in modern research and their possible outcomes. A safe and easily administrable small molecule of plant origin that would protect or limit the spread of venom and provide valuable time for the victim to reach the healthcare centre would be a great lifesaver.
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The inhalation toxicology of ricin (supplied by Sigma) from the seed variety “Hale Queen” and abrin was examined following head-only exposure of rats to a range of concentrations of each toxin generated as an aerosol from solution using a constant-output nebulizer. The inhalation toxicity of an in-house preparation of ricin from a different seed type, Ricinus communis var. zanzibariensis (R. zanzibariensis), was also assessed for comparison. The approximate LCt50 values determined were very similar for the Sigma ricin and abrin (4.54–5.96 and 4.54 mg min m-3, respectively). However, the LCt50 of ricin toxin prepared in-house from seeds of the R. zanzibariensis variety was assessed to be 12.7 mg min m-3. Ricin prepared from this seed variety was therefore less toxic than Sigma ricin by a factor of almost threefold. Given that both ricin preparations were pure by silver-stained, sodium dodecyl sulfate polyacrylamide electrophoresis gels, the data must reflect differences in specific toxicity between seed varieties. The histopathology was studied in a separate group of experimental animals exposed to approximate LCt30 levels of each in-house toxin preparation and was found to be entirely restricted to the lung. The overall pattern and time course of damage observed were similar for ricin and abrin and were characterized by rapidly progressive and overwhelming pulmonary edema accompanied by acute destructive alveolitis and necrosis/apoptosis of the lower respiratory tract epithelium; severe intraalveolar edema and resulting hypoxia accounted for the majority of deaths in the decedent population. The resolution phase of the pulmonary damage in those animals destined to survive was heralded by a gradual disappearance of edema fluid accompanied by generalized, focally florid, hyperplasia of type II pneumocytes and striking transitory consolidation of the lung parenchyma by chronic inflammatory cells. Despite many similarities in histopathology between abrin and ricin there were some differences. Although by systemic administration abrin is several times more toxic than ricin, when delivered by inhalation there was no significant difference in potency between abrin and the commercial preparation of ricin (Sigma).
Ricin toxoid was prepared by dialyzing ricin against 3.7% formalin for 72 h at 42 to 47°C. The product had greater than 1000-fold reduction in toxicity when tested in two cultured cell assays, and elicited high titer antibodies in mice, as determined by ELISA and in vitro neutralization. A dose-response study established 2.5 μg (125 μg/kg) as a two times threshold immunizing dose. Separate groups of mice were vaccinated by two different routes and three different schedules. All animals were challenged by lethal ricin inhalation. Animals that received an immunization and two boosts subcutaneously or intramuscularly were completely protected from death when challenged 3 weeks after the final boost with 1 or 10 lethal doses of inhaled ricin. At 16 weeks, only 66% of the mice exposed to 10 lethal doses of inhaled ricin survived, but all animals survived a 1 lethal dose exposure. One subcutaneous vaccination gave 56% protection. A serum ELISA titer of ≥1:10,000 or a neutralization titer of ≥1:300 accurately predicted survival from a lethal inhaled dose of ricin. These studies establish a suitable toxoid preparation method and dose necessary to elicit a protective immune response in mice challenged with inhaled ricin, and validate surrogate markers to predict survival.
To the Editor:— The castor bean, the seed of Ricinus communis, is one of the most potent of the antigens that cause anaphylactic type of hypersensitivity in man.1 Usually patients encounter the antigen at their work2,3 or by living in the vicinity of castor bean processing plants,4-6 but this patient's contact with the bean was in an exotic way. The source of the allergic symptoms went unrecognized until she had an acute, severe reaction.Report of a Case: A 21-year-old woman student was admitted to the University Hospitals because facial itching and swelling of her eyelids suddenly developed. Approximately one half hour before the patient arrived at the emergency room she had itching of her eyes and tearing immediately after one of the seed beads of a necklace she was wearing crumbled in her fingers. After attempting to remove the powder of the bead from her fingers
For many years it has been known to Toledo physicians that an "asthma colony" existed in a certain district of East Toledo. Suspicion had long pointed to a linseed oil mill as being the cause of the trouble, for many of these asthmatic patients asserted that their attacks coincided with the odor of linseed oil from the mill when the wind was in the right direction. Complaints had been made at various times to the city health department, but nothing incriminating the oil mill could be found. The state department of health also made an investigation, but did not learn anything of value con
Verfasser berichten ber die Ricinussamen-Vergiftung von 10 Schulkindern. Die Vergiftung verlief bei 4 Kindern mittelschwer, bei 6 war sie leicht. Symptomatische Behandlung fhrte bei smtlichen Fllen zur Heilung. Bei 7 Kindern zeigte das EKG Vernderungen. Toxikologie, Klinikum, Behandlung und Prognose werden besprochen.
Ricin is one of a group of structurally related plant lectins and is extracted from the seeds of the Castor Oil plant, Ricinus communis. Groups of rats were exposed to ricin aerosol by inhalation, total LCt1-11.21 mg.min.m-3 (an approximate LCt30 exposure) and examined, using transmission electron microscopy, at intervals up to 48 h after exposure. The first signs of change in ultrastructure were seen at between 6 and 12 h post exposure in alveolar macrophages and took the form of apoptotic changes primarily in the nucleus. These included heterochromatin condensation at the nuclear periphery and crenulation of the nuclear membrane. There then followed a sequence of changes in the cells of the alveolar wall and blood/air barrier culminating in intra-alveolar oedema at 12 and 15 h after exposure. Damage was first observed in the capillary endothelium and type I epithelial cell changes were evident from 12 h post exposure onward. These changes appeared to be necrotic rather than apoptotic in nature and suggest that mechanisms other than a direct effect of ricin may be involved. Associated with these changes were mixed inflammatory cell infiltrates in the interstitium, isolated type II pneumocyte necrosis and evidence of microvascular microthrombosis. By 48 h after exposure, the intra-alveolar oedema appeared less marked with prominent hyperplasia of type II pneumocytes. The identification that apoptosis of alveolar macrophages plays a significant part in the mechanism of toxicity following exposure to ricin raises the possibility of developing new therapeutic strategies against poisoning by ricin.
A comprehensive review of the literature on allergy due to castor bean is given as it occurs by inhalation of dust particles in the environment of milk working with castor bean. Furthermore it may occur by handling of castor bean and of its expressed residuals after oil production. A case report is presented about a respiratory allergy caused by castor bean meal containing fertilizer used in culturing grass plats. Symptomes of increased dyspnoe following repeated exposures and a strongly positive skin test to an extract of castor bean have been observed. There is strong evidence that the castor bean has a high allergenic potency, requiring attention in allergy tests.