Dose-dependent uptake

Baker TS, Rickert DE. 1981. Dose-dependent uptake, distribution, and elimination of inhaled -hexane in the Fischer-344 rat. Toxicol Appl Pharmacol 61 (3) 414-422. 

Production of Mucosal Damage 2.3.1.2.1 Cell culture Stimulated neutrophils are known to be cytotoxic to cells in vitro (Dull et al., 1987 Dallegri et al., 1990 Grisham et al., 1990b). Several in vitro systems have been used to demonstrate oxidative damage to intestinal cells. Xanthine/XO increased Cr release and decreased [ H]thymidine uptake by IEC-18 small intestinal epithelial cell monolayers in a dose-dependent manner (Ma et al., 1991). Rat enterocytes show decreased trypan blue exclusion and increased protein release when incubated with neutrophils stimulated... 

Bioaccumulation factors for fenvalerate by representative freshwater and estuarine organisms during exposure for 28 to 30 days to various sublethal doses ranged from 40 to 570 for fish, 356 to 4700 for invertebrates, and 477 to 933 for algae (Smith and Stratton 1986). Because of its unusually high lipophilicity, fenvalerate is accumulated at only 30% efficiency by aquatic fauna, and uptake is not dose dependent (Coats et al. 1989). Contamination of algal food of daphnids with fenvalerate does not seem to contribute to an increase in whole-body burdens, although reduced filtration rates... 

Most congeners that accumulated in pup tissues were concentrated in the dam s milk when compared to the feed. PCB uptake by pups was greater during lactation than during gestation. Congeners that accounted for46% of the brain PCB content and also accumulated in a dose-dependent manner were PCBs 105, 138, 141, 153, 168, 178, 179, and 186... 

GULF TOADFISH, Opsanus tau Isolated hepatocytes acclimatized to 18 or 28°C, then exposed to BaP at 18, 23, or 28°C for about 2 h Isolated gill cells acclimatized to either 18 or 28°C for 3 weeks and exposed for 8 h to 1-100 mg BaP/L at incubation temperatures of 18, 23, and 28°C Dose-dependent increase in metabolite production. 23 Rapid metabolism of BaP independent of temperature Accumulation followed a dose-concentration gradient 24 uptake rate was higher for cells acclimatized to 18°C than those acclimatized to 28°C at all incubation temperatures. When cells were exposed to BaP at the respective acclimatization temperatures, uptake rates were similar... 

Ex vivo studies have revealed that trichothecenes can both inhibit and stimulate leukocyte function.12 For example, trichothecenes are toxic to alveolar macrophages,13 but drive differentiation of human myeloid leukemic cells.14 Dose-dependent decreases or increases in B- and T-cell mitogen responses are observable in lymphocytes from animals exposed to T-2 toxin, DON, or various macrocyclic trichothecenes these toxins similarly impair or enhance mitogen-induced lymphocyte proliferation in vitro.12 Rank order of inhibitor potency in rodent and human lymphocyte proliferation assays is Type D > Type A group > Type B group and is dependent on degree of acylation as well as of uptake and metabolism. 

In gas-uptake experiments, Gearhart et al. (1993) demonstrated a dose-dependent decrease in core body temperature with increased inhaled concentrations of chloroform. The decrease in body temperature could account for decreased in vivo chloroform metabolism, partition coefficients, pulmonary ventilation, and cardiac output rates in mice. 

Leander et al. described ready-to-use liposomes that were effective and well tolerated in humans [61]. The iodinated contrast agent was the non-ionic dimer, iodixanol. The particle size of the liposomes was 350 nm with an iodine concentration of 70-80 mg mL encapsulated. They injected doses of 30, 70 or 100 mgl kg intravenously and found maximal enhancement values of 45 HU in the liver and 240 HU in the spleen. The uptake into these organs was not linealy correlated with the injected dose. No serious or unexpected adverse reactions were reported. Dose-dependent changes in leukocyte counts and body temperature were seen. 

A study on the bio distribution of ITG in rats showed a dose-dependent behaviour. At doses of 12.5 and 25 mgl kg large portions of the dose could be recovered in the liver and spleen, whereas at 105 mgl kg , uptake into the liver was prolonged following an extended period of retention in the blood volume. The maximum CT liver enhancement, however, remained proportional to the injected dose. When the mean particle size was increased to 1.5 pm, the selectivity for liver uptake was lost. 

An exposure assessment is the quantitative or qualitative evaluation of the amount of a substance that humans come into contact with and includes consideration of the intensity, frequency and duration of contact, the route of exposure (e.g., dermal, oral, or respiratory), rates (chemical intake or uptake rates), the resulting amount that actually crosses the boundary (a dose), and the amount absorbed (internal dose). Depending on the purpose of an exposure assessment, the numerical output may be an estimate of the intensity, rate, duration, and frequency of contact exposure or dose (the resulting amount that actually crosses the boundary). For risk assessments of chemical substances based on dose-response relationships, the output usually includes an estimate of dose (WHO/IPCS 1999). 

At 2.5 ppt salinity, whole body nickel concentrations increased from 19 to 232 mg/kg DW in a dose-dependent manner (vs. control of 12.5 mg/kg DW) at 15 ppt salinity, nickel increased from 20 to 113 mg/kg DW in combination with copper salts, nickel uptake increased at intermediate salinities... 

In contrast to the SSRIs, venlafaxine has an ascending dose-response curve consistent with its sequential, concentration (and hence dose) dependent effects on serotonin and NE uptake pumps (Table 7-9). At 225 mg per day, the magnitude of the antidepressant effect is 50% higher than that seen with the SSRIs. Also consistent with its dual mechanism of action at higher concentrations, venlafaxine at a dose of 225 mg per day produced an antidepressant response in hospitalized patients with melancholia superior to both placebo and fluoxetine (114, US, 116, H7, H8, H9, 120, 121, 122, 123, 124,125, 126,127, 128,129, 130,131, 132,... 

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