Ricin periodate

As in the case of MBS, discussed previously, SMPB was found to be more effective than aliphatic crosslinkers in producing immunotoxin conjugates with ricin that have high yields of cytotoxicity (Myers et al., 1989). This was attributed to the reagent s aromatic ring structure. A comparison with SPDP produced immunotoxin conjugates concluded that SMPB formed more stable complexes that survive in serum for longer periods (Martin and Papahadjopoulos, 1982). 

FIGURE 25.8. (a) Ricin (10 g/ml) various concentrations of the potential chemoprotectant V-hromoacetyl-P-D-galactopyr-anosylamine (NB DG) and ricin added simultaneously with NBPDG were added to different cultures. The LDH activities were determined in culture media after a 48 h incuhation period. Values are the mean SD from at least four cultures. Values with nonidentical superscripts are significantly different (p > 0.05). (b) Ricin (10 g/ml), various concentrations of the potential chemoprotectant V-bromoacety 1- P-D-galactopyranosylamine... 

NBPDG) and ricin added simultaneously with NB DG were added to different cultures. The AST activities were determined in culture media after a 48 h incubation period. Values are the mean SD from at least four cultures. Values with nonidentical superscripts are significantly different (p > 0.05). 

DOT CLASSIFICATION 9 Label None SAFETY PROFILE Deadly poison by ingestion in humans. The seeds contain the deadly poison ricin, a plant lectin (toxalbumin) which inhibits protein synthesis in the intestinal wall. Ingestion of the seeds can cause after a delay period of several hours nausea, vomiting, diarrhea, and intestinal dysfunction. There may be massive fluid and electrolyte loss. Ingestion of as few as 2 seeds could be fatal. A potent allergen. When heated to decomposition it emits toxic fumes of NOx. See also RICIN. 

One sc formulation is capable of releasing sufficient amounts of ricin A-chain (RAC) to elicit IgG formation at protective levels over a period of 4-6 weeks. 

Toxic effects of ricin have latent periods ranging from 2 to 24 h. Symptoms include delayed gastroenteritis, which may be severe and hemorrhagic, followed by delirium, seizures, coma, and death. Toxic effects include intestinal hemorrhage, diffuse nephritis, hepatic necrosis, and on a cellular level pyknosis of the nuclei and karyorrhexis. Patients may experience hypoglycemia, severe dehydration, and shock. Severe exposures may also result in the development of pulmonary edema, respiratory failure, and death within 36-72 h. If death has not occurred in 3-5 days, the victim usually recovers. 

Ricin and related type 2 RIP plant toxins are comparably lethal to laboratory mice under controlled conditions (Table 17.3). Variations in the LD50 values for a single toxin reported by different laboratories are comparable with variations among different toxins. Few controlled animal studies are available for several of these toxins, and comparisons among laboratories are limited by differences in toxin preparations, animal strains, and methodologies employed. The postexposure observation period is a particularly important variable for example, the literature values for the acute toxicity of abrin vary by 80-fold depending on whether intoxicated animals are observed for 24 or 48 h after exposure (Dickers et al., 2003). 

Documented cases of human poisoning by ricin aerosol exposure are unknown. Cautious inferences may be drawn from observations of NHP exposed to ricin under controlled laboratory settings. Human toxicity from ricin inhalation would be expected to occur after a latency period of 24—72 h that may be characterized by loss of appetite and listlessness. Based on extrapolation from NHP studies, other signs and symptoms expected in humans after ricin inhalation may include listlessness, high fever, dyspnea, and coughing or bloody sputum that is delayed for 4—8 h after exposure, as well as bilateral abnormalities on chest radiographs, arterial hypoxemia, neutrophilic leukocytosis, and elevated protein levels in bronchial aspirates (Balint, 1974 Wilhelmsen and Pitt, 1996 Franz and Jaax, 1997). 

Ricin is not inactivated significantly by freezing, chilling, or storage at ambient temperature. Ricin stored at 4°C in the liquid state with a suitable preservative (e.g., sodium azide) retains significant potency for years. Isolated RTA is less stable in solution at 4°C than is the holotoxin, but either can be stored below —20°C for long periods in 10% glycerol. 

After ricin binds to the cell surface, there is always a significant lag period before a decrease in the rate of cellular protein synthesis is observed [93]. This lag period represents the time taken for A chains to move from the cell surface to the cytosol. During the early stages of this lag period, both anti-A-chain and anti-B-chain antibodies are able to protect the cells against the toxin [68]. For the greater part of the lag period, however, the antibodies do not have any... 

Ricin is more toxic by inhalation than by ingestion. The symptoms from inhaling aerosolized ricin are weakness, fever, cough and pulmonary edema. Such effects may onset after a latent period of 8 hours. Death can result in 36 to 72 hours from severe respiratory distress. The toxin binds... 

Medical personnel must consider the varying latent periods before onset of clinical signs. For patients exposed to toxins by aerosol, the latent period varies from minutes (saxitoxin, microcystin) to hours (the staphylococcal enterotoxins), even to days (ricin, the botulinum toxins). 

By definition, chemical warfare agents are volatile in liquid form. Some obvious exceptions are the solid toxics like Adamsite or ricin. Generally, the danger is that the CWM is in a container (glass bottle, cylinder, drum, or shell) and if that is breached, a hazardous concentration is achievable. Some CWM, like mustard, can polymerize in the soil. This can present dangerous conditions for long-term exposure to low levels. The body detoxifies mustard so slowly that even minute levels can produce illness over a long period of time. 

The incubation period for ricin is dependent on the route of transmission. If the toxin is inhaled, the incubation is about 8 h. The incubation period for ingestimi is a few hours to days. If ricin is injected under the skin, the incubation period could be immediate to several hours, depending on the location of injection and the dose of toxin injected. 

Phytohaemagglutinins.—Abrin, ricin, and their isolated A and B chains have been subjected to various chemical treatments and the effect of these on the biological activity of the lectins assessed. Reductive methylation, periodate oxidation, or succinylation of abrin or ricin reduced the toxicity and haemagglutinating ability of the former but not the latter. Treatment with A-acetylimidazole or A-bromosuccinimide resulted in strongly reduced toxicity of abrin and ricin, while 2-hydroxy-5-nitrobenzyl bromide had much less effect. 

Variable toxicity is seen in cases of oral ingestion. Seeds that are chewed are much more likely to cause clinical signs. Seeds swallowed whole may not cause any problems at all (Kinamore et al., 1980). The amoimt of toxalbumins in the seeds will vary by size, weight, moisture content, region, season, and the period of plant growth at the time of harvesting. The ricin content of castor beans can vary from 1% to 10% (Balint, 1974). The... 

---