Dosing, defined

Several lipids A have been tested in cancer patients MPLA, SDZ MRL 953, and ONO-4007 were injected i.v. in phase I trials. The maximal tolerated dose found is lower than or close to the optimal dose defined in animals. Humans are more sensitive to lipid A than rodents so it is possible that similarly to the toxic dose, the effective dose is lower in humans than in animals. 

Safety factor approach for chemicals that cause deterministic effects. Traditional toxicologic procedures for chemicals that can induce deterministic effects, which are assumed to have a threshold dose, define RfD for humans or animals as some fraction of NOAEL. This fraction is determined by establishing safety factors to account for weaknesses and uncertainties in the data and in the extrapolation from animals to humans. In the safety factor approach, doses below RfD are assumed not to result in a response because they are below the threshold of toxicity (Dourson and Stara, 1983 Renwick and Lazarus, 1998 Weil, 1972). 

Defined as repeated and prolonged intake of high doses Defined as intake of single (or multiple) very high doses... 

It is essential to establish certain criteria to evaluate the synthesized compounds, in particular their radioprotective effectiveness and their toxicity. For each of the molecules we synthesize, first we evaluate its acute (48 hours) and medium-term (2-30 days) toxicity in male Swiss CD1 mouse. The molecule is injected intraperitonally at different concentrations to determine the LD5o,ox/48h/ defined as the concentration which kills 50% ofthe animals at 48 hours. Then, radioprotective effectiveness is determined in the same animal model. In a preliminary study, the product is administered at the maximum tolerated dose (defined as 1/2 LD5otox/48h) 15 or 90 minutes before radiation exposure at doses LD,ooirr/3od nd LD,ooirr/3od + 2 Gy (LD,ooirr/3od is defined as the irradiation dose which kills 100% of the animals 30 days after exposure). Survival is observed for 30 days. In a second experiment we determine the Dose Reduction Factor (DRF) for the most radioprotective compounds. DRF is the ratio between the LDsoirr/sod of treated mice and that of non treated mice. 

Eossella FV, Lippman SM, Shin DM, et al. Maximum-tolerated dose defined for single-agent gemcitabine A phase 1 dose-escalation study in chemotherapy-naive patients with advanced non-small cell lung cancer. J Clin Oncol 1997 15 310-316. 

Phase I Clinical Evaluation-The first testing of a new compound in human subjects, for the purpose of establishing the tolerance of healthy human subjects at different doses, defining its pharmacologic effects at anticipated therapeutic levels, and studying its absorption, distribution, metabolism, and excretion patterns in humans. 

The units of absorbed dose defined in the previous section are quite adequate for the quantitative assessment of the effects of radiation to inanimate objects, like irradiated transistors or reactor fuel. For protection of people, however, the important thing is not the measurement of energy deposited—i.e., the absorbed dose—but the biological effects due to radiation exposure. Unfortunately, biological effects and absorbed dose do not always have one-to-one correspondence, and for this reason a new unit had to be defined a unit that takes into account the biological effects of radiation. 

The determining parameter in these curves is the oxygen dose, defined as the exposure time multiplied by the partial pressure. Its unit is the Langmuir L. One Langmuir represents one second of exposure to a partial pressure of 133 Pa (1 torr) 1... 

Fig. 17. Variation of RBE with linear energy transfer (LET). RBE represents the limiting RBE at very low doses, defined by the ratio (Xj/ax of the linear coefficients (Redrawn from [72])...

Gray n (Gy) The SI unit of absorbed radiation dose, defined as the absorption of 1 J/kg of body mass, i.e.. 

How is the median dose defined in a population-level toxicity study ... 

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