[M.D. Holloway]

Interesting tibit bit on Oleander...

Nerium oleander has historically been considered a poisonous plant based on a number of its compounds that may exhibit toxicity, especially to animals, when consumed in high amounts. Among these compounds are oleandrin and oleandrigenin, known as "cardiac glycosides" which are known to have a narrow therapeutic index and can be toxic when ingested.

Toxicity studies of animals administered oleander extract concluded that the rodent and avian species were observed to be relatively insensitive to oleander "cardioactive glycosides".[8] Other mammals, however, such as dogs and humans, are relatively sensitive to the effects of cardiac glycosides and the clinical manifestations of "glycoside intoxication".[8][9][10]

However, despite the common "poisonous" designation of this plant, very few toxic events in humans have been reported. According to the Toxic Exposure Surveillance System (TESS) in 2002 there were 847 human exposures to oleander reported to poison centers in the United States.[11] Despite this exposure level, from 1985 through 2005, only three deaths were reported. One cited death was apparently due to the ingestion of oleander leaves by a diabetic man.[12] His blood indicated a total blood concentration of cardiac glycosides of approximately 20 microgm/L which is well above the reported fatal level. Another study reported on the death of a woman who self-administered "an undefined oleander extract" both orally and rectally and her oleandrin tissue levels were 10 to 39 microgm/gm which were in the high range of reported levels at autopsy.[13] And, finally, one study reported the death of a woman who ingested oleander 'tea'.[14] Few other details were provided.

In contrast to consumption of these undefined oleander derived materials, there is no toxicity or deaths reported from topical administration or contact with Nerium oleander or specific products derived from them. In reviewing oleander toxicity Lanford and Boor[15] concluded that, except for children who might be at greater risk, "the human mortality associated with oleander ingestion is generally very low, even in cases of moderate intentional consumption (suicide attempts)."[15]

The safety of parenterally and topically administered Nerium oleander extract and its glycoside constituents, intended for therapeutic application, has been studied in animals and humans. These studies all indicate that administration of Nerium oleander extracts as either a parenteral or topical preparation is safe when doses anticipated for commercial products are applied.[16] Toxicity studies that have been conducted in dogs and rodents administered oleander extracts by intramuscular (IM) injection indicated that on an equivalent weight basis, doses of an oleander extract with glycosides 10-times in excess of those likely to be administered therapeutically to humans are still safe and without any "severe toxicity observed".[17] These pre-clinical studies, which also include oral dosing of oleandrin, were conducted in preparation for an investigational drug submission to the U.S. Food and Drug Administration to allow for administration of the oleander extract to patients with cancer.[18]

A study in which a proprietary, concentrated extract of Nerium oleander (containing oleandrin and other cardiac glycosides) was administered orally to humans for the first time was recently concluded.[19] A concentrated oleander extract (PBI-05204) was formulated for oral consumption was given to 46 cancer patients where doses explored included those from 0.2 mg to 10.2 mg extract/day. These doses were administered daily in cycles consisting of 21 out of every 28 days. The researchers concluded that PBI-05204 was "well tolerated up to the 10.2 mg extract/day dosage" with few significant side effects and with evidence of tumor response.[19]

There does not appear to be any toxicity associated with exposure of a Nerium oleander extract to the skin. Both animal[20] and human[21] studies suggest that dermal application of Nerium oleander extract is safe. In four human studies[21][22][22][23] in which a Nerium oleander extract was applied to the skin of people with different dermal conditions, sensitive mass spectrometry based blood analyses were not able to detect the presence of cardio glycosides such as oleandrin, indicating that these compounds are not readily absorbed through the skin.

...orally and rectally...?