Tolerable absorbed dose

Statistical models. A number of statistical dose-response extrapolation models have been discussed in the literature (Krewski et al., 1989 Moolgavkar et al., 1999). Most of these models are based on the notion that each individual has his or her own tolerance (absorbed dose that produces no response in an individual), while any dose that exceeds the tolerance will result in a positive response. These tolerances are presumed to vary among individuals in the population, and the assumed absence of a threshold in the dose-response relationship is represented by allowing the minimum tolerance to be zero. Specification of a functional form of the distribution of tolerances in a population determines the shape of the dose-response relationship and, thus, defines a particular statistical model. Several mathematical models have been developed to estimate low-dose responses from data observed at high doses (e.g., Weibull, multi-stage, one-hit). The accuracy of the response estimated by extrapolation at the dose of interest is a function of how accurately the mathematical model describes the true, but unmeasurable, relationship between dose and response at low doses. 

Tab. 1.3 Tolerable absorbed doses (TRDs) for metals and metalloids (long-term oral exposure) (Eikmann et al. 2002)...

Exposure assessment involves modelling contaminant intakes via ingestion, inhalation and skin contact routes. Some of the algorithms currently used are complex, and some may be difficult to validate. Allowance may also need to be made for intake of the same contaminants from background, especially dietary, sources. In practice, because data on uptake (absorbed dose) are rarely available, the comparison is often between estimated intake and tolerable daily intake (TDI). This is precautionary because soil contaminants are not usually as bioavailable as the pure and soluble compounds typically used in the animal studies conducted to derive tolerable daily intakes. 

The stabilized, orally absorbable form of NADH (ENADA) is a nutritional supplement available in the U.S. since 1995 and in the E.U. since 1997. Based on the patented formulation of this supplement, a number of clinical trials have been launched to prove scientifically that ENADA is effective. In order to get these studies started, an investigational new drag (IND) application was filed with the Food and Drag Administration (FDA). For FDA approval, it must be documented that ENADA (the stabilized oral form of NADH) is safe. For this reason, the maximum tolerated intravenous dose (MTD) of (3NADH (reduced form of beta-nicotinamide adenine... 

The degree to which radiation exposure affects FEP resins is determined by the energy absorbed, regardless of the type of radiation. Changes in mechanical properties depend on total dosage, but ate independent of dose rate. The radiation tolerance of FEP in the presence or absence of oxygen is higher than that of PTFE by a factor of 10 1. 

Sulfonylurea herbicides are generally applied to crops as an early post-emergent herbicide. Crops that are tolerant to these herbicides quickly metabolize them to innocuous compounds. At maturity, residues of the parent compound in food and feed commodities are nondetectable. Metabolites are not considered to be of concern, and their levels are usually nondetectable also. For this reason, the residue definition only includes the parent compound. Tolerances [or maximum residue limits (MRLs)] are based on the LOQ of the method submitted for enforcement purposes and usually range from 0.01 to 0.05 mg kg (ppm) for food items and up to O.lmgkg" for feed items. There is no practical need for residue methods for animal tissues or animal-derived products such as milk, meat, and eggs. Sulfonylurea herbicides are not found in animal feed items, as mentioned above. Furthermore, sulfonylurea herbicides intentionally dosed to rats and goats are mostly excreted in the urine and feces, and the traces that are absorbed are rapidly metabolized to nontoxic compounds. For this reason, no descriptions of methods for animal-derived matrices are given here. 

There is considerable interest in using injectable bisphosphonates, such as pamidronate and zoledronic acid, in patients unable to tolerate or absorb oral bisphosphonates. Zoledronic acid in particular has a potential advantage of once-yearly dosing. Currently, neither drug has received FDA approval for this indication. Ibandronate has recently been approved for this indication. 

Iron-deficiency anemia in chronic PN patients may be due to underlying clinical conditions and the lack of iron supplementation in PN. Parenteral iron therapy becomes necessary in iron-deficient patients who cannot absorb or tolerate oral iron. Parenteral iron should be used with caution owing to infusion-related adverse effects. A test dose of 25 mg of iron dextran should be administered first, and the patient should be monitored for adverse effects for at least 60 minutes. Intravenous iron dextran then may be added to lipid-free PN at a daily dose of 100 mg until the total iron dose is given. Iron dextran is not compatible with intravenous lipid emulsions at therapeutic doses and can cause oiling out of the emulsion. Other parenteral iron formulations (e.g., iron sucrose and ferric gluconate) have not been evaluated for compounding in PN and should not be added to PN formulations. 

Flucytosine is converted in Candida fungi to 5-fluorouracil by the action of a specific cytosine deaminase. As an antimetabolite, this compound disrupts DNA and RNA synthesis (p. 298), resulting in a fungicidal effect Given orally, flucytosine is rapidly absorbed. It is well tolerated and often combined with amphotericin B to allow dose reduction of the lattet... 

Antacids are basic compounds that neutralise acid in gastric lumen, have no effect on gastric acid secretion. They are quantitatively compared in terms of their acid neutralizing capacity (ANC), which is defined as the quantity of 1 N HCl (in MEq) that can be brought to pH 3.5 in 15 minutes by a unit dose of antacid preparation. An ideal antacid should be potent in neutralizing acid, inexpensive, not absorbed from GIT and contain negligible amounts of sodium, should be sufficiently palatable to be readily tolerated with repeated dosage and should be free of side effects. An ideal antacid is yet to be developed. 

---