Toxicity time dependence

Fig. 7. Toxicity of chlorine to aquatic organisms, (a) Time-dependent mortaUty (50%) of four example species in various levels of total residual chlorine in the laboratory, where for A, A.losa aestivalis and B, Salmogairdnerii r (correlation coefficient of the curve) = —0.96 and for C, P/euroneetesplatessa and D, Salmo trutta r = —0.98. (b) A summary of chlorine toxicity to freshwater species, indicating overall no-effect thresholds for acute and chronic exposures. Numbers indicate where more than one test yielded the same result. A different summary figure appHes to marine organisms because of differences in the...

The drug SC-558 acts by a fourth mechanism, specifically inhibiting COX-2. It is a weak competitive inhibitor of COX-1 but inhibits COX-2 in a slow, time-dependent process. Specific COX-2 inhibitors will likely be the drugs of the future because they selectively block the inflammation mediated by COX-2, without the potential for stomach lesions and renal toxicity that arise from COX-1 inhibition. 

The time dependence of the acute toxicity of oil and dispersants on a sensitive freshwater organism, namely, Daphnia magna, was investigated [1805]. Two different oils were used a crude oil from the southwest of France and a gas oil free from volatile substances after being equilibrated with atmosphere. Two commercial dispersants were used British Petroleum Enersperse 1037 and Dasic Freshwater. 

E. Vindimian, B. Vollat, and J. Garric. Effect of the dispersion of oil in freshwater based on time-dependent daphnia magna toxicity tests. Bull Environ Contamination Toxicol, 48(2) 209-215, February 1992. 

Gavage administration of a single dose causes profound gastric toxicity that includes concentration- and time-dependent mucosal... 

Absorption, Distribution, Metaboiism, and Excretion. There is relatively little quantitative information on the systemic absorption of inhaled carbon tetrachloride in animals and humans, with estimates ranging from 30% to 60% (Lehmann and Schmidt-Kehl 1936 McCollister et al. 1951). In order to confirm the dose absorbed during inhalation exposures to carbon tetrachloride, it would be useful to determine the systemic uptake of carbon tetrachloride in additional animal experiments, with special attention to concentration- and time-dependency of absorption. It may be useful to conduct short-term studies of the relative absorption, disposition, and toxicity of inhaled versus ingested carbon tetrachloride. Such studies can yield information pertinent to route-to-route extrapolation and may be more economical than conducting a 2-year inhalation cancer bioassay of carbon tetrachloride. 

Concentration and time dependence of carbon tetrachloride-induced injury to proximal tubule mechanism of action role of metabolism in renal toxicity of carbon tetrachloride. 

Characterization Robust assessment of dose- and time-dependent effects Able to identify more sensitive measmes of toxicity Expensive, usually low amoimt of replicates... 

Additional studies have examined time-dependent molecular events associated with developmental toxicity in mouse embryos (102-104) and differentiating cardiomyocytes from embryonic stem cells (105). These initial time-response studies show the power and sensitivity of toxicogenomic assessments to characterize the timing of molecular changes that associate with developmental toxicity outcomes. 

Nevertheless, the toxicity of fluoroacetate seems to be only partially due to the inhibition of aconitase. The competitive nature of the inhibition, its Xj value (Xj = 20-60 pM)," and the time-dependent nature (but reversible) of the inhibition of aconitase seem to be poorly compatible with the sharp and irreversible toxicity of fluorocitrate. Thus, it has been suggested that fluorocitrate can covalently bind with the proteins that are involved in citrate transport through the mitochondrial membrane. ... 

Better understanding of mechanism of nanotube interaction with biological objects is required the possible toxicity will depend on dose and exposure time ... 

Rosenblatt, D.E., D.G. Doyle, and A.L. Aronson. 1978. Calcium ethyl-enediaminetetraacetate (Ca EDTA) toxicity Time- and dose-dependent studies on intestinal morphology in the rat. Exp Mol Pathol 28 215. 

In addition to the previously mentioned cases, the toxicity of the inhibitor or inducer, as well as the time dependence of the effect, must also be considered because, as... 

Froehner, K., Meyer, W. and Grimme, L.H. (2002) Time-dependent toxicity in the long-term inhibition assay with Vibrio fischeri, Chemosphere 46 (7), 987-997. 

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