Poisoning reference dose

An additional consideration is noteworthy when comparing acute and chronic toxicity. All chemicals elicit acute toxicity at a sufficiently high dose, whereas all chemicals do not elicit chronic toxicity. Paracelsus often cited phrase all things are poison. .. the dose determines. .. a poison is clearly in reference to acute toxicity. Even the most benign substances will elicit acute toxicity if administered at a sufficiently high dose. However, raising the dose of a chemical does not ensure that chronic toxicity will ultimately be attained. Since chronic toxicity typically occurs at dosages below those... 

A lowest observable adverse effect level (LOAEL) was estimated to be 1.2-1.6 pg/kg, on the basis of human poisoning in Japan (eight people from three families, aged 10-68). In another stndy from Norway, 38 of 70 adults were affected at levels ranging from 1.0 to 1.5 pg/kg. From these data, a provisional acute reference dose (RfD) of 0.33 pg OA equivalents/kg (based on the LOAEL of 1.0 mg OA/kg and a safety factor of 3) was established (for details, see Reference 15). 

Acute exposure involves a single dose. Toxicologists frequently refer to the immediate adverse consequence of an acute exposure as an acute effect. Such events are also referred to as poisonings. This usage is not incorrect, but, as will be seen in a moment, it can be misleading when similarly applied to chronic exposures. 

Narcotic analgesics Morphine and many of its homologues, when administered in medicinal doses, relieve pain and produce sleep. In poisonous doses, these produce stupor, coma, convulsions and ultimately death. Morphine narcotics are sometimes referred to as opiates, since they are obtained from the opium poppy. 

Charcoal does not bind iron, lithium, or potassium, and it binds alcohols and cyanide only poorly. It does not appear to be useful in poisoning due to corrosive mineral acids and alkali. Recent studies suggest that oral activated charcoal given alone may be just as effective as gut emptying followed by charcoal. Also, other studies have shown that repeated doses of oral activated charcoal may enhance systemic elimination of some drugs (including carbamazepine, dapsone, and theophylline) by a mechanism referred to as "gut dialysis."... 

In fact, all substances are poisonous, and there are none that are safe. The right dose alone differentiates a substance as a remedy or as a poison. In other words, no substance is absolutely safe. Important reference could be made to valuable contributions of Theophra Stus (370-286 B.C.), Hippocrates (400 B.C.), and Ebers Papyrus (1500 B.C.). In fact, the use of hemlock by the Greeks to execute the great philosopher Socrates (470-399 B.C.) is an instance of its own. Recently, Ramazzini (1700) documented preventive measures to control industrial hazards among occupational workers (Fig. 2-1). 

---