How Dangerous Could be the Receiving of a Ricin-Contaminated Letter?

Authors

1 Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IR Iran

2 Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, IR Iran

Abstract

In recent years, biotechnology has provided the possibility of creating genetically modified (GM) organisms by transferring genes from sources such as viruses, bacteria, animals, and plants into usually unrelated species. This ability to overcome insurmountable physiological barriers by exchanging genetic materials among all living organisms is a double-edged sword. On the one hand, it allows the creation of organisms desired and designed by humans and on the other hand, it provides an opportunity for undesired spread of genetically altered forms of organisms across the planet endangering other life forms. Presently, the GM crops on the global market have been genetically manipulated to express basic traits such as resistance to insects or viruses, tolerance to certain herbicides, and nutritionally enhanced quality (1). More than 148 million hectares of farmland are under cultivation for GM crops throughout the world (2). Although industrial countries (United States and Canada) are the major producers of GM crops, developing countries such as China and Argentina are very active in this field. In the United States, more than 70% of maize, cotton, and soya are biotechnological varieties (3) and in Canada, more than 70% of the processed food products are genetically engineered (4). Reports indicate that GM crop adoption rate is much higher among the developing than industrialized countries (21% and 9%, respectively) and this is due to the hope these countries have to alleviate hunger and poverty. Developing countries currently account for less than 50% of the global farmlands used for the GM crop cultivation but is predicted to increase to more than 200 million hectares of lands and to include 40 countries by 2015 (3). Most of the debates on agricultural biotechnology center around the potential risks of the GM crops to human health. Some of the health risks include antibiotic resistance, allergenicity, nutritional changes, and the formation of toxins (5). The GM crops are alive and can migrate and spread worldwide; therefore, it is best for the agricultural biotechnology industry to proceed with caution to avoid causing unintended harm to the human health and the environment. This is especially true in the developing countries where limited capacities and infrastructure to face health and environmental disasters exist. In recent years, Cartagena protocol has introduced laws and guidelines and has obliged countries and companies to obey them in the areas of production, handling, and consumption of GM materials; however, it is mainly the responsibility of the national governments to enforce the laws within the borders of a country. The National Institute of Genetic Engineering and Biotechnology (NIGEB) in Iran should play an important role in providing the necessary information for the legislators to assist them in passing the laws for regulation of this important area in agricultural biotechnology.

Keywords


Most recently, we read in the news about sending of ricin-exposed letter to some governmental important people. Ricin is a toxalbumin derived from caster bean (Ricinus communis; Euphorbiaceae), whose oil is employed in medicine. Ricin is a potent and highly dangerous protein, where its exposure can cause severe toxicity in different organs and then death. Because there are many possible ways to expose (including skin, mucosal, gastrointestinal and pulmonary routs) and also regarding to its importance, which is abused as a kind of biological killing weapons, and its potential to affect many people via extremely low dosages, the main headlines attributed to its toxicity signs and symptoms, various probable routs of exposure especially via skin and mucosal contacts have been reviewed here. Nevertheless ricin is an easily produced toxin with known application in biological weapons; it is hard to consider it as a quick bio-killing poison to terror someone via exposed letter.

Most recently, we read in the Yahoo news about sending of ricin-exposed letter to some governmental important people (1).

The first point came to our mind was to see whether ricin can be absorbed by touching the letter and how much it can be dangerous. Although there are a number of reviews and reports on diverse aspects of this poison, toxicokinetic of ricin has not been cleared completely. For this reason, remarked points of view around this concern have been reviewed and considered in this article.

Ricin, a well-known toxalbumin isolated from Ricinus communis (Euphorbiaceae), is found as an extremely toxic natural protein (Figure 1). A main source of ricin, R. communis, is a woody bush, growing up to 1-4 m height, and cultivated as an ornamental plant especially in north of Iran due to its attractive inflorescences in purple during vegetation period. Moreover, its leaves are generally alternate and divided with toothed lobes, and also the remarkable capsules are ordinary green-purple ovoid (up to 1.5 cm) with smooth spines (2). Review of traditional documents reveals that R. communis has been used for various purposes such as antidote, cathartic, cyanogenic, emetic, emollient, expectorant, insecticide, poison, purgative, tonic, while castor oil is introduced as an ingredient in folk remedies for abscess, arthritis, asthma and many other illnesses. Additionally, castor oil is well-known for its cathartic activity to induce labor in natural deliveries, where ricinoleic acid, the main active fatty acid in the oil has been employed in contraceptive jellies (3-7).

Ricin, a toxic protein in the seeds acts as a blood coagulant. Interestingly, too small amount of this peptide is able to kill a man when exposes via injection or inhalation (LD50 = 22 µgKg -1), while oral exposure to ricin is less toxic (LD50= 20-30 mgKg -1) (5). Actually, ricin is a globular (with around 60-65 kDA) heterodimer peptide in its tertiary structure and found as glycosylated. Two diverse chains of ricin including A and B chains showed very similar molecular weights about 32 and 34 (kDA), respectively (3, 8). Ricin is stable in solid powder or liquid form even at high temperatures while it dissolves in aqueous and weak acids. Although caster bean is the main source for accumulation of ricin, it can be stored in whole parts of the plants.

Toxicity may occur when castor beans are swallowed or chewed by accident especially in children, thus gastrointestinal (GI) intake is a common exposure pathway (9). Other exposure routs of ricin are highly unlikely such as inhalation, skin or mucosal penetration and intravenous injection, which may be used in terroristic attacks. Symptoms of ricin inhalation may be observed as early as 4 hours after exposure including cough related to hard breathing, which is developed quickly by fluid accumulation inside the lungs followed by respiratory collapse and probably death during 36-72 hours after exposure. Although ricin is less toxic via ingestion, the common symptom is diarrhea which can lead to dehydration, circulatory collapse and death in severe situations. The known mechanism of toxicity is interfering with protein synthesis followed by cell death (9, 10).

Regarding data obtained from literature, ricin usually falls in the category of biological weapons of mass destruction and is not transmitted person-to-person but the main concern rises as “Does touching the ricin letter result in serious toxicity and death as a biological killing toxin?” It seems that ricin is unlikely absorbed through normal skin but may result in eye contact or ingestion from hand finally. Furthermore, there is possibility of lacrimation, conjunctivitis, redness, bleeding from membrane in the rear (retinal hemorrhage), impaired vision even blindness, when eye exposure happens. Systemic toxicity might occur after eye exposure. However, injured skin and mucosa are of important routs of exposure, where absorption of ricin through mucous membranes may create serious irritation and inflammation. In case of skin absorption, there is a potential for allergic reactions such as erythema and blistering. Another exposure rout is inhalation of ricin powder. Inhalation can cause a number of signs including fever, cough, storage of liquids in the lungs or edema, respiratory distress, and finally death due to airways obstruction. It is difficult to think that ricin may reach to blood to cause systemic toxicity. However, this way is dangerous rout by itself because of the high risk of severe dyspnea, difficult breathing as well as highly risk of death.

Taking together, ricin may penetrate through irritated or injured skin and also through normal skin if mixed with a solvent carrier but in solid powder form (Figure 2). Anyhow, it is possible to inhale the fine powders of ricin dispersed in the air by breathing, so that inhalation toxicity might occur when a person open an envelope consisted of ricin in solid powder form. Chronic toxicity may be correlated to cytotoxic activity of this peptide on the liver, central nervous system (CNS), kidneys, and adrenal glands (11). There is a little information on carcinogenicity, developmental toxicity, or reproductive toxicity via repeated exposure to ricin.

There is not antidote available for ricin. Although some vaccines have been introduced, their efficacy and safety is under debate. Immediate removing the victim from the source of exposure is the first and important aid and management for ricin toxicity. In case of eye exposure, washing the eyes with large amounts of water for at least 15 min is essential. Also decontamination procedure is acquired for skin exposure. Regarding the emergency of the matter, getting advise from a local poison information center (PIC) is highly recommended. They can triage the patients to skilled divisions within the hospitals for rapid management. The PIC system presently operating in Iran and the US both are comparably helpful (12).

Nevertheless ricin is an easily produced toxin with known application in biological weapons; it is hard to consider it as a quick bio-killing poison to terror someone via exposed letter. Regarding the potential of ricin to be replicated by Escherichia coli bacteria to which the ricin gene has been transferred, ricin became of interest as a chemical weapon agent. According to Organisation for Prohibition of Chemical Weapons (OPCW), in 1978, ricin was used in the "umbrella murder" in London where a ricin-treated bullet was used to shoot a Bulgarian defector who died within a day. Then ricin was included in Schedule 1 of the Chemical Weapons Convention and it is now under control (13).

Authors’ Contribution:

Authors have participated equally in manuscript preparation.

Financial Disclosure:

There is no financial disclosure.

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