Dose-mortality curves

We first examined the resistance of the OCR strain to three GABA antagonist/insecticides, i.e., dieldrin, fipronil, and EBOB. Figure 1 shows the dose-mortality curves for the insecticidal activity of dieldrin and fipronil determined 24 h after topical application to the OCR and WHO/SRS strains without any synergist treatment. en estimated using the 24-h LDjo values, the OCR strain was found to be 1800-fold more resistant to dieldrin than was the WHO/SRS strain (LDjo° = 19.7 pg/fly LDjo ° = 10.9 ng/fly), whereas the former was 32-fold more resistant to fipronil than the latter (LDso° = 103 ng/fly = 3.26 ng/fly). These values approximate the reported... 

Figure 4. Dose response curves representing per cent mortality (within 48 hours) of approximately 20 g mice (CRE CD BR ICR) injected with specified doses of ether soluble acetone filtrate (ESAF), ether soluble acetone precipitate (ESAP), water soluble acetone filtrate (WSAF), and water soluble acetone precipatate (WSAP) from Prorocentrum concavum (SIU 364). Each dose was administered by ip injection into 10 mice. LD50S were determined using probit analysis. A correlation coefficient (R) is provided for each LD5Q.

The lARC has concluded that epidemiological studies have established the relationship between benzene exposure and the development of acute myelogenous leukemia and that there is sufficient evidence that benzene is carcinogenic to humans. Although a benzene-leukemia association has been made, the exact shape of the dose-response curve and/or the existence of a threshold for the response is unknown and has been the source of speculation and controversy. Some risk assessments suggest exponential increases in relative risk (of leukemias) with increasing cumulative exposure to benzene. At low levels of exposure, however, a small increase in leukemia mortality cannot be distinguished from a no-risk situation. In addition to cumulative dose other factors such as multiple solvent exposure, familial connection, and individual sus-... 

Figure 72 A typical dose-responsive curve where the percentage response or mortality is plotted against the log of the dosage.

However, one caveat should be mentioned at this point. If you examine Figure 7.3 closely, you will observe that the lines for lethality and efficacy do not exactly follow the same slope. In cases where the mortality/toxicity dose-response curves follow a shallower slope, the TI will necessarily be lower in the lower dosage range. This is... 

Figure 5.1 Dose-response curve illustrating the log of the dose that causes a of 50 percent mortality in the test population.

Comparison of dose-response curves-2. Plotting the dose-response curve demonstrates that the concentrations that cause mortality to 50% of the population are distinctly different. However, the slopes of the two curves appear to be the same. In many cases this may indicate that the compounds interact similarly at the molecular level. 

Comparison of dose-response curves-3. Cumulative toxicity plots for compounds 1 and 3. Notice that the plots intersect at roughly 50% mortality. 

Occasionally, it is difficult to set up concentrations for the test if the median values for the chronic endpoints is close to the values for a toxicant that induce mortality over the duration of the experiment. Loss of replicates can occur if the mortality rates are high enough. Use of the dose-response curve of the acute data should help in identifying useful boundary conditions for the higher concentrations of xenobiotic. 

Consider the hypothetical data given in Table 18. These data may be plotted in a number of ways. If the percentage mortality is plotted against dose, the curve shown in Figure 18 is obtained. If the percentage mortality is plotted against log dose, the curve shown in Figure 19 is obtained. This conforms closely to a cumulative normal distribution curve. 

However, not all dose-response curves follow Haber s rule. If the dioxin data referred to above are considered again and time is plotted on the x-axis, with dose needed to produce a 10% mortality on the y-axis, then the data are well fitted by an equation ... 

As well as mortality, other types of response can be plotted against dose. Similarly a median effective dose can be determined from these dose-response curves such as the ED50 where a pharmacological,... 

By plotting the dose-response curves for these species after exposure to acephate and comparing the EEC to these curves, we see that the EEC predicted mortalities are 83, 7, and 1% for the oriental fruit fly, melon fly, and Mediterranean fly, respectively (Figure 5.4). 

Survival at a given initial (peak) concentration in the water was defined by a dose-response curve using a logistic model, with mortality occurring immediately after exposure. The parameters of this curve are obtained from the results of a hypothetical mesocosm experiment. The numbers of A. aquaticus collected 1 week after application of the chemical were regressed on the peak concentrations of the chemical occurring immediately after application. 

Figure 4. Assumed hamster dose-response curve This curve exhibits a fundamental assumption about the occurrence of decompression sickness in hamsters that they respond according to a normal dose-response curve and that mortality will go to 100%,...

Figure 6. Generalized hamster dose-response curves If the nitrogen partial pressure is high enough, the mortality will eventually go to 100%. However, with lower partial pressures the mortality rises to some asymptotic value after a constant time period. In this domain one can study the time effects independent of the nitrogen partial pressure.

Figure 6 shows three postulated dose-response curves that could be expected. In the curve marked high P. tissue, the ultimate response is 100% mortality because the inert gas partial pressure was so high that all animals were afflicted. If the depth of the dive is lowered (curves marked low P. tissue), the curve shifts to the right (towards increased exposure time) and flattens at a time In this range of pressures it is... 

Oose levels At least three and preferably four dose levels should be used to produce a range of toxic effects and mortality rates (e.g., a range from 10 to 90% and bracketing the expected LO50). The data should be suf icient to produce a dose response curve and permit an acceptable determination of the LD50. 

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