Highest nontoxic dose

Observations of pregnant rats fed varying concentrations of valerian on days 1 through 8 of pregnancy indicated that the highest nontoxic dose of valerian was 2.8 g/kg. Doses above 2.8 g/kg resulted in reduced placental weight but not reduced birth weight as compared to control (Yao et al. 2003). 

Dichloroethane is one of the more toxic chlorinated solvents by inhalation (49). The highest nontoxic vapor concentrations in chronic exposure studies with various animals range from 100 to 200 ppm (50,51). 1,2-Dichloroethane exhibits a low single-dose oral toxicity in rats LD q is 680 mg/kg (49). Repeated skin contact should be avoided since the solvent can cause defatting of the skin, severe irritation, and moderate edema. Eye contact may have slight to severe effects. 

No LD50 of feverfew has been reported. The highest nontoxic acute dose in rats was reported at 860 mg/kg (Yao and Brown-Woodman 2001). 

The thallium content in hair from persons without environmental or occupational exposure is 5-15 ng/g hair [9,14]. The thallium content in tissue from unexposed humans is highest in colon, kidney, and myocardium. The reported values, however, for all tissues are less than 10 ppb and often below 1 ppb [9,10,17,18]. Cellular distribution studies using nontoxic doses of Tl demonstrated high levels of thallium in the nucleus and showed that 10% of total intracellular thallium accumulated in the mitochondria [10,19]. 

In an in vitro assay with cultured human fibroblasts, aniline produced only marginal increases in sister chromatid exchanges at the highest dose tested, 10 mM whereas two metabolites of aniline, 2-aminophenol and jV-phenylhydroxylamine, doubled the frequency of sister chromatid exchanges at the highest tested nontoxic concentration, 0.1 mM (Wilmer et al. 1981). 

Both rodent and nonrodent studies have been conducted on the parent CDs. Szejtli and Sebestyen reported the parent CDs to be nontoxic at very high oral doses. Mortality was not observed, even in animals treated with the highest possible oral doses. Therefore, the LD50 in rats is reported to be greater than 12.5, 18.8, and 8g/kg body weight for a-, p-, and y-CD, respectively. 

Transient, nontoxic side effects such as dry mouth and nausea may be experienced by patients when serum lithium concentrations are within the therapeutic range (23). These generally occur within 4 hr of the dose when serum lithium concentrations are at their highest... 

The EPA and PDA state that there is no standard treatment schedule therefore, one, two, or more doses every 24 h is acceptable as long as toxicity has been demonstrated, or that a limit dose has been achieved. In addition, if a large volume of material needs to be administered to the rodents, it may be administered as a divided dose, as long as the doses are not separated by more than a few hours. Doses may be selected from the results of a range finding study, or any preliminary tests done with the rodents after administration via the same route. The highest dose selected for the main assay would produce some bone marrow toxicity, including, in the bone marrow or peripheral blood, a decreased number of immature erythrocytes to total erythrocytes. In the case of a nontoxic test article, the limit dose is defined as 2000 mg kg... 

The most common side effect seen on initiation of therapy is a fine hand tremor which disappears after a few weeks of treatment. Transient, nontoxic side effects such as dry mouth and nausea may be experienced by patients when serum lithium concentrations are within the therapeutic range [58,60]. These generally occur within 4 hr of the dose when serum lithium concentrations are at their highest. The impact of these side effects is minimized by operating within a lower therapeutic range. Prudent and careful users of lithium rarely have side effects which are more than mildly discomforting. 

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