High-dose studies

We have no proof that lead causes cancer in humans. Kidney tumors have developed in rats and mice given large doses of lead. The animal studies have been criticized because of the very high doses used, among other things. The results of high-dose studies should not be used to predict whether lead may cause cancer in humans. The Department of Health and Human Services (DHHS) has determined that lead acetate and lead phosphate may reasonably be expected to be... 

Of course, many scientists who worked in the laboratory setting were not so sure the results of their work should be taken quite so seriously. They doubted that results from high-dose studies in animals had much relevance to typical human exposures - such experiments would, at best, reveal some of the secrets of the ways carcinogens worked, but were of little use in predicting human risks. 

Effects to be expected at low exposures must be identical with those observed at the high doses studied. 

In the high-dose study of rats, all but 6 percent of the psilocybin was excreted within twenty-four hours. In humans, only 80 to 85 percent of psilocybin and its metabolites is excreted within eight hours, in the urine (about 65 percent), bile and feces (15 to 20 percent). Some 15 to 20 percent lingers on, stored in fatty tissues significant quantities appear in urine up to a week later. A full 25 percent of the originally administered dose enters urine as psilocin. 

Felbamate. Felbamate is an adjuvant anticonvulsant, containing the warning that its use is associated with a marked increase in the incidence of aplastic anemia and that patients being started on the drug should have liver function tests performed before therapy is initiated. Animal studies have revealed a statistically significant increase in hepatic cell adenomas in high dose studies (18). It is postulated that this cancer was induced by toxic by-products urethane and methyl carbamate. Felbamate is not recommended as first-line therapy and is indicated for those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia or liver failure is deemed acceptable in light of the benefits provided by its use. 

Methyl Isobutyl ketone (4-methyl-2-pentanone, hexone [CAS 108-10-1]) Irritating to eyes upon direct contact. Vapors irritating to eyes and resplratoiy tract, Reported systemic symptoms in humans are weakness, dizziness, ataxia, nausea, vomiting, and headache. High-dose studies In animals suggest a potential for liver and kidney injury. 

Tellurium and compounds (as Te) Complaints of sleepiness, nausea, metallic taste, and garlicky odor on breath and perspiration associated with workplace exposures. Neuropathies have been noted in high-dose studies. Hydrogen telluride causes pulmonary irritation and hemolysis however, its ready decomposition reduces likelihood of a toxic exposure. Some tellurium compounds are fetotoxic or teratogenic in test animals. 0.1 mg/m (as Te) 25 mg/m (as Te) Metallic tellurium Is a solid with a sllveiy-whlte or grayish luster. 

A few multiple-dose studies have not found aspirin to alter the antihypertensive effect of beta blockers, even in high doses, but one single-dose high-dose study reported an interaction. Another study suggested that aspirin might attenuate the benefit of carvedilol in heart failure, but the evidence is currently too slim to warrant a change in practice. 

Parameter Effect High dose studies (with undernutrition) Effect Low dose studies (no undernutrition)... 

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