Wayne Binns

Chemical Compounds of Veratrum calif ornicum Related to Congenital Ovine Cyclopian Malformations Extraction of Active Material.

Summary The teratogenic material from Veratrum californicum has been extracted from dried plant material by an ethanol extraction of the plant residue remaining after an initial benzene extraction in presence of ammonia, A 250-fold purified preparation from this extract also produced the malformations. It is theorized that the teratogenic material may be an alkaloid of the Veratrum series, likely a glycoside or parent alkamine.

SELENIUM TOXICITY IN DOMESTIC ANIMALS

For many years, selenium has been associated with animal intoxications that occur when plants containing certain levels of this element were consumed by livestock. There has been some attempt at differentiation of these intoxications, sometimes complicated with phytotoxins, from those that result from administration of inorganic selenium The presence of phytotoxins has not been the only complicating factor in Se poisoning. Differences in animal species and individual susceptibility exist. There is also some evidence that organically bound selenium may be more biologically active, when given orally to monogastric animals, than inorganic selenium salts: and that there is variation in toxicity of organic selenium analogs: However, these differences may cease to exist when the different compounds are exposed to ruminal digestion because of the changes that occur during that process. A good example of this modification is the reduction of a considerable percentage of some Se salts to relatively biologically inactive elemental Se in the rumen, thus interfering with its metaboli~rn.~,~ Moxon and Rhian’s review of Se poisoning7 notes that certain elements and compounds, including protein, influence the toxicity of the element when both are given orally to rats. Fluorine, molybdenum, chromium, vanadium, cadmium, zinc, cobalt, nickel, and uranium were found to increase the toxicity of Se, while arsenic and tungsten, to a lesser extent, gave some protection against it. More recently, evidence has been presented that certain methyl supplements8 and sulfateg also give some protection to the same species. It has also been shown that certain aromatic compounds such as bromobenzene, benzene, and naphthalene mobilize tissue Se and stimulate its e ~ c r e t i o n . ~ It seems reasonable to assume that other substances, as yet unrecognized, exist that influence Se metabolism and toxicity. Recent recognition of several selenium responsive diseases in domestic animals6Jo-1g which has instituted the use of Se as a therapeutic agent, makes it imperative that those using this “new drug” have pharmacological knowledge of it, and this is especially true in regard to its toxicology. The objective of this paper is not a complete review of the literature, but to make readily accessible some information concerning the toxicity of Se salts and especially some that may be used therapeutically in domestic animals. As previously mentioned, there is considerable literature concerning selenium poisoning resulting from the ingestion of plants of high Se content. Since this may, at times, involve complicating phytotoxins, and it is doubtful that Se from such sources will be used therapeutically, this paper will deal largely with the inorganic salts of the element. The literature concerning Se toxicity for animals based on measurable amounts given as inorganic salts is not particularly abundant. Horses. Miller and WilliamsZ0 reported that the MLD of Se for equines when administered orally as sodium selenite in a single dose to be 2.2 mg./kg. They also gave two horses feeds containing the salt at the rate of 11 ppm Se for two

Teratogenic compounds of Veratrum californicum as a function of plant part, stage, and site of growth☆

Abstract The level of the teratogen cyclopamine in Veratrum californicum varied considerably among plants from various collection sites. The variation was not correlated with differences in soil type, pH, soil nutrients, elevation, drainage, or sunlight. However, marked variation in both total alkaloid and percentage cyclopamine occurred as a function of stage of growth of the plant. The levels of both were highest in early growing season in the leaves, in midgrowing season in the stems and in late growing season in the root/rhizome system.

Teratogenic Compounds of Veratrum californicum (Durand). III Malformations of the Veratramine-Induced Type from Ingestion of Plant Or Roots

Summary Congenital malformations of the type produced by maternal ingestion of the alkaloid veratramine occurred from maternal ingestion of the plant Veratrum californicum. A preliminary identification of veratramine in benzene extracts from the plant by thin layer chromatography was achieved.

Possible Teratogenic Effects of Veratramine

Summary The alkaloid veratramine, a parent alkamine of the steroidal class of veratrum alkaloids, produced congenital abnormalities in lambs. It did not produce the expected cyclopian deformities but rather abnormalities which included slight lateral or medial bowing of the front legs, slight to marked flexure of knee joint, looseness of the hock or stifle joints, or complete lack of skeletal muscular control (inability to rise).