Total toxic equivalent dose

From this equation, it is apparent that the Total MOE is a dose (BMD(l)) with known toxicological characteristics divided by the total toxic equivalent dose (Total TED). Thus, despite the non-transparent form of the usual equation for... 

Probabilistic risk assessment methods are described herein for determining a popnlation s distribution of the dose from exposure and the combination of that exposnre characterization with appropriate toxicological information to form aggregate and cumulative risk assessments. An individual s dose from exposure is characterized as a set of chemical- and route-specific dose profiles over time. Toxic equivalence factors (TEFs) that reflect the toxic endpoint and exposure duration of concern are used to scale chemical- and route-specific doses to toxic equivalent doses (TEDs). The latter are combined in a temporally consistent manner to form a profile over time of the Total TED. For each individual, a Total MOE is calculated by dividing a toxicologically relevant benchmark dose (e.g. an EDio) by the individual s Total TED. The distribution of the Total MOE in a popnlation provides important information for risk management decisions. 

TCDD is 1. The concentration or dose of each active component in a mixture of concern is multiplied by its TEF to arrive at a TEQ, and the TEQs are added to give the total toxic equivalency of... 

The procedure involves converting oxon to thion toxicity equivalents by multiplying the oxon value by its relative toxicity (ED of thion r ED,.q of oxon) in Table I. The ED. value is the aermal dose in ug/cnr of total body surface which produces 50% inhibition of red cell ChE activity 72 hours after application. The total thion and oxon level is then divided by the thion toxicity equivalents and the factor is multiplied by the safe level established for thion in Table I. This procedure was conducted for the dislodgeable residues of parathion-paraoxon, methidathion-methidathion oxon, and azinphosmethyl-azinphosmethyl oxon. The safe levels for the total disloggeable residues were determined to be 0.06, 0.2 and 1.6 ug/cm, respectively, for... 

Additivity and no interactions. Additivity concepts that explain a shared adverse effect across chemicals include dose or concentration addition, which assumes chemicals share a common toxic MOA, and RA, which assumes chemicals act by toxicologically (and thus also statistically) independent MOA. There is also a body of research on the use of statistical dose-response modeling of empirical data to examine the joint toxic action of defined mixtures where the claim is that MOA assumptions are not necessary (Gennings et al. 2005). Dose addition methods scale the component doses for relative toxicity and estimate risk using the total summed dose, for example, using relative potency factors (RPFs), toxicity equivalency factors (TEFs), or a hazard index (HI). In contrast, RA (also named independent action ) is... 

When the Total MOE approach is used and toxic equivalent factors and doses computed, the BMDs should be comparable. Comparability is increased if all of the BMDs are for the same endpoint (or endpoints related to the common mechanism of action and of comparable severity). Comparability is also increased if the BMDs are all ED s (with the same ) as opposed to all NOAELs or all Lowest Observed Adverse Effect Levels (LOAELs), because the NOAELs and LOAELs are influenced by differences in experimental designs. Comparability is also increased if the BMDs all refer to the same species. 

As an example of what 10-6 would mean in terms of the U.S. population, a total of 20 cases of cancer would result if 10 of the population was exposed at a dose level equivalent to a 10-6 risk for 70 years. That would be one-third of a cancer case per year as an upper limit in the U.S. population compared with the approximately 500,000 annual cancer deaths that occur. The actual number of cases attributable to that particular substance would probably be less, and perhaps none at all would occur unless some additive or synergistic interaction with other substances resulted in enhanced toxicity. 

By the use of radioactively labelled precursor chemicals, the cell s ability to synthesize macromolecules such as DNA, RNA, and proteins, after treatment with the drug, can be measured. A typical result is shown in Fig. 5, for exposure of the cells to the equivalent level of drug found in tumor tissue of a treated animal. The synthesis of new total DNA is selectively and persistently inhibited. Total RNA and protein syntheses are not markedly affected until much higher drug-dose levels, which are frankly toxic to... 

In a randomized, prospective, cost-effectiveness study both teicoplanin and vancomycin were assessed as second-line therapy in 66 neutropenic patients after the failure of empirical treatment with a combination of piperacillin -I- tazobactam and amikacin (10). The primary success of second-line therapy was equivalent, and the direct total costs were similar. Acquisition costs per dose were in favor of vancomycin, but costs derived from administering vancomycin and serum concentration monitoring led to similar costs for both regimens. With the exception of the red man syndrome, which occurred in 10% of vancomycin-treated patients but none of the tei-coplanin-treated patients, toxicity (renal, liver, and ear toxicity, diarrhea, phlebitis) was also similar. 

In contrast to retinoids, carotenoids were considered non-toxic, even when taken chronically in large amounts, until recently, when it was found that ethanol interacts with carotenoids, interfering with their conversion to retinol. In baboons, the consumption of ethanol together with beta-carotene resulted in more striking hepatic injury than consumption of either compound alone (98). This interaction occurred at a total dose of 7.2-10.8 mg of beta-carotene per Joule of diet. This dose is common in people who take supplements and is the same order of magnitude used in the Beta-Carotene and Retinol Efficacy Trial (CARET) (30 mg/day) (99) and in another study (20 mg/day for 12 weeks) (100). The amount of alcohol given to the baboons was equivalent to that taken by an average alcohohc. The well-known toxicity... 

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