TOXICITY

Taxus brevifolia is not poisonous. There has been confusion over this issue for two reasons, both of which will be clarified here.
1) The Pacific Northwest of the United States has actually only been 'civilized' and 'settled' for a little over 100 years. Most of the people that 'settled' this country were of European or Asian decent. They recognized the yews when they got here and mistakenly assumed they were poisonous like the yews in their homelands.

European yews (Taxus baccata) and Japanese yews (Taxus cuspidata) are poisonous because they contain toxic amounts of the cardiotoxic alkalodial fraction named 'taxine'.

Taxus brevifolia got a bad rap due to guilt-by-association and that is why many websites, encyclopedias and botanical publications list Taxus brevifolia as poisonous.

There are no documented instances of poisoning in humans or animals with Taxus brevifolia.

"The cardiotoxic alkaloidal fraction 'taxine' is relatively abundant in Taxus baccata (European Yew) and even more so in Taxus cuspidata (Japanese Yew), which are the most frequent causes of stock poisonings by yew, but the taxine fraction is almost absent in Taxus brevifolia, and Pacific Yew is indeed a frequent browse of moose, elk and deer." (Suffness (1995), Taxol Science and Applications, page 8).

"Early chemical studies of the toxicity of yew indicated that the major toxicity was due to 'taxine', which is now known to be a mixture of alkaloids with

taxine A and taxine B as the major constituents. Taxine causes death from asphyxia due to cardiac and respiratory failure." (Suffness (1995), Taxol Science and Applications, chapter 12, The Toxic Constituents of Yew, page 311).

Due to an idiosyncrasy of nature, Taxus brevifolia is lacking in harmful amounts of poisonous alkaloids as documented by V.E.Tyler, Jr. (1960).

"Note On the Occurrence of Taxine in Taxus brevifolia". Journal of the American Pharmaceutical Association Scientific Edition, Vol. 49, No. 10,

pages 683-684.

Taxine yield from fresh needles of Taxus brevifolia, analyzed by Tyler, showed .00077% of fresh weight, and "cyanogenetic glycosides of this type were found to be absent in this alkaloid-poor species."

Acute Oral Toxicity Study in Rats - Limit Test (Summary)

A. Purpose - to provide information on health hazards likely to arise from a short term exposure to Montana YewTip™ Powder (Taxus brevifolia) by the oral route.

B. Procedure - Each animal received 5,000 mg/kg of the test substance, as 25% ww suspension in distilled water by intubation. The animals were observed for mortality, signs of gross toxicity and behavorial changes at least once daily for 14 days. Body weights were recorded prior to initiation and at termination.

C. Results - All animals survived, gained weight and appeared active and healthy. There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behavior.

D. Conclusion - The single dose acute oral LD 50 of Montana YewTip™ Powder

(Taxus brevifolia) is greater than 5,000 mg/kg of body weight.

Test Method Number -P203

Study Number - 7734

Sponsor - Trimedica, Inc, Tempe, AZ

Test Substance - Montana YewTip™ Powder (Taxus brevifolia)

Test Substance Decription - dark green powder

PSL Reference Number - E90601-5D

Dates of Test - June 14-28, 1999

Notebook Number - 99-38, pages 222-227

Product Safety Labs - Chicago, IL.

2) Another confusing issue regarding toxicity of Taxus brevifolia is also a case of 'guilt-by-association'. Adverse effects of chemotherapeutic drugs produced from Taxus brevifolia (Taxol) and Taxus baccata (Paclitaxel) are different than herbal preparations of Taxus brevifolia.

"The ethanol:Cremophor vehicle required to solubilize paclitaxel in Taxol is toxic. Although it has been used to administer other drugs, such as cyclosporine

and teniposide, the amount of Cremophor necessary to deliver the required doses of Taxol is significantly higher than that administered with any other marketed drug. Thus the vehicle has been shown to cause serious or fatal hypersensitivity episodes at nearly every step in the developmental path, in both preclinical and clinical testing. One mediator of the hypersensitivity reaction is endogenous histamine release, and prophylaxis to counteract histaminergic mechanisms reduce the incidence of hypersensitivity reactions."

(Suffness (1995), Taxol Science and Applications, Chapter 9, page 241.)

Cremophor is polyethoxylated castor oil.

"Several other toxic side effects have been attributed to Taxol (Paclitaxel), including cardiotoxicity, neutropenia, peripheral neuropathy, mucositis, gastrointestinal toxicities, alopecia, arthralgias and myalgias.

(Gotaskie and Andreassi, 1994).

(Medical Attributes of Taxus brevifolia by Maria Costello and Kelly Kellmell (1997).

Wilkes University, PA.

Taxol (Paclitaxel) is administered intravenously with pre-treatment with other drugs to counter the adverse effects.