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Dietary Supplements: A Framework for Evaluating Safety
alkenylcatechol derivatives capable of producing severe allergic dermatitis (Everist, 1981; Keeler and Tu, 1983). Toxicodendron species (poison ivy, poison oak, and poison sumac) contain these alkenylcatechol allergens, the major constituent of which is urushiol, in all parts of the plant (Cheeke, 1998; Keeler and Tu, 1983). Most adverse reactions reported from this plant family are through dermal contact (Cheeke, 1998), but there is reason to be concerned about ingestion of plants containing urushiol and its analogs. Some cases of severe damage to gastric mucosa and death have been reported in humans ingesting these species (Kingsbury, 1964). Presumably, the severe reactions have occurred in response to internal immune/allergic response. Given that individual susceptibility to dermal reactions in humans varies widely, but most animals are not affected (Cheeke, 1998), it would probably not be prudent to regard lack of adverse effects following animal ingestion of dietary supplement ingredients containing these compounds as an indication of safety in humans.
The Apiaceae contains plants commonly consumed as vegetables or condiments, such as carrots, parsnips, celery, and dill (Anethum, Apium, Daucus, Pastinaca species). The phytochemicals of concern in this family include piperidine alkaloids, polyacetylenes, and coumarins (Cheeke, 1998; Everist, 1981). Conium (piperidine) alkaloids are of concern because they can cause nervousness, nausea, vomiting, ataxia, coma, and death due to respiratory failure in many different animals, including humans (Cheeke, 1998; Colegate and Dorling, 1994). Alkaloid levels vary considerably with plant growth stage and are particularly high in flowers and seeds. Poisoning in humans has resulted from mistaking Conium maculatum (poison hemlock) for parsley or anise seeds (Kingsbury, 1964). The most toxic alkaloid, γ-coniceine, has an LD50 in a mouse bioassay of 2.5 mg/kg (Burrows and Tyrl, 2001).
Some polyacetylenes are acutely toxic, resulting in rapid death due to complete paralysis and respiratory failure. The compounds act on the central nervous system, causing extremely violent convulsions, abdominal pain, and delirium in humans (Cheeke, 1998). Levels of the toxin (cicutoxin) are very high in roots of Cicuta species and a single root is capable of killing a cow (Kingsbury, 1964). There are structurally related compounds in carrot roots, although evidence of toxicity in humans from these compounds is minimal, probably because of extremely low levels (Cheeke, 1998). Simple coumarins can block the vitamin K pathway, thus inhibiting blood coagulation, and also can cause photosensitivity on exposure to sunlight. Photosensitivity, resulting in severe sunburn, has been observed following ingestion of celery soup, and sensitivity also occurs via dermal contact with the vegetable (Boffa et al., 1996; Seligman et al., 1987). Celery oil and celery