Time to death

Laboratory experiments using rodents, or the use of gas analysis, tend to be confused by the dominant variable of fuel—air ratio as well as important effects of burning configuration, heat input, equipment design, and toxicity criteria used, ie, death vs incapacitation, time to death, lethal concentration, etc (154,155). Some comparisons of polyurethane foam combustion toxicity with and without phosphoms flame retardants show no consistent positive or negative effect. Moreover, data from small-scale tests have doubtful relevance to real fine ha2ards. 

When making comparisons of lethal toxicity, it must be remembered that different mechanisms may be iavolved with different materials, and these need to be taken iato account. Also, comparisons of acute toxicity should take note of differences ia time to death, siace marked differences ia times between dosiag and death may influence ha2ard evaluation procedures and thek implications. In a few kistances, it may be possible to calculate two LD q values for mortaUty one based on early death due to one mechanism, and a second based on delayed deaths due to a different mechanism (69). 

Sevigny JJ, Albert SM, McDermott MP, Schifitto G, McArthur JC, Sacktor N, Conant K, Seines OA, Stern Y, McClernon DR, Palumbo D, Kieburtz K, Riggs G, Cohen B, Marder K, Epstein LG (2007) An evaluation of neurocognitive status and markers of immune activation as predictors of time to death in advanced HIV infection. Arch Neurol 64(1) 97-102... 

INPUT SAMPLE TREATMENT AND TIME TO DEATH DATA. data death ... 

The following is an example of a Kaplan-Meier survival estimates plot. In this plot, we are comparing the time to death for three different treatment regimens. The Kaplan-Meier survival estimate is on the Y axis, and time is represented on the X axis. Each step in the graph lines represents an event. 

Let s assume that you are comparing the two treatment groups of Active Drug and Placebo to see if they display different distributions for time to death. You can run this analysis with PROC LIFETEST as follows ... 

Now let s assume that you want to adjust for gender as a covariate in your comparison of time to death. You can use PROC PHREG to put gender into your model like this ... 

Diamond, S.A., M.C. Newman, M. Mulvey, RM. Dixon, and D. Martinson. 1989. Allozyme genotype and time to death of mosquitofish, Gamhusia affinis (Baird and Girard), during acute exposure to inorganic mercury. Environ. Toxicol. Chem. 8 613-622. 

Lee, C.J., M.C. Newman, and M. Mulvey. 1992. Time to death of mosquitofish (Gambusia holbrooki) during acute inorganic mercury exposure population structure effects. Arch. Environ. Contam. Toxicol. 22 284-287. 

Toxic collar, as above. Each coyote tested was known to have fatally attacked at least 3 domestic sheep within a 30-day period Of the 12 coyotes that attacked the neck region of the sheep and punctured the collar, 9 received lethal doses and became immobilized in 1-3 min and died 3-25 min later. The mean time to death was 11.6 min. One of the three sublethally dosed coyotes survived at last three successful attacks in which the collar was punctured, and two survived two attacks. In all cases, contact with NaCN produced shaking of the head, pawing at the mouth, rubbing the snout on the ground, and ataxia 4... 

Found dead, four cases, time to death unknown Maximum cyanide burden in stomach was 230 mg maximum tissue residues, in mg cyanide/kg FW were 3.5 in blood, 6.3 in liver, and 0.5 in brain 8... 

In pen tests, 25 coyotes were offered lambs with collars containing 5 or 10 mg 1080/mL A total of 23 coyotes attacked and 21 died after collars were punctured in their first (n = 17), second (n = 3), or fifth (n = 1) tests. The average time to death was 217 min (range 115-436 min) 20... 

Acute inhalation lethality data for the rat, mouse, and rabbit for exposure times of 10 s to 12 h were located. A single inhalation study with the dog did not give an exposure duration. The data are summarized in Table 5-4. Data from studies with nonlethal concentrations are summarized in Table 5-5. Barcroft (1931) reported LC50 values and times to death for eight species of animals, the times to death at a constant concentration. Due to experimental design constraints, the LC50 values are not reported here, but relevant data are discussed in the section on relative species sensitivity (Section 4.4.1). 

According to Matijak-Schaper and Alarie (1982), the 30-min LC50 of male Swiss-Webster mice inhaling HCN is 166 ppm. Mortality ratio for the mice (four per exposure group) were 0/4, 2/4, 3/4 and 4/4 for exposure to concentrations of HCN at 100, 150, 220, and 330 ppm, respectively. The recovery period was 10 min, during which the surviving mice appreciably recovered. The LC50 was the same for cannulated mice. At exposure concentrations of 500 and 750 ppm, the mean times to death were 12 min and 2 min, respectively. 

FIGURE 11.29 The effect of tannic acid on time to distress ( ) and time to death ( ) in fish. (Data taken from Swain, 1979). 

Figure 1. Dose and time to death relationships for saxitoxins.

This fraction displayed the greatest killing power however, the most interesting features of tjhis toxin(s) were its fast-acting and "all-or-none nature. All mice deaths, regardless of dose, occurred within one hour. In fact, it appeared that there was a critical dose-dependent time to death, after which, surviving mice recovered completely. Although Yasumoto and coworkers (14, 23) also have... 

Fig. 4.1 Event-free survival for death or hospitalization for new or worsening heart failure in the DAVID trial. Time to death or first hospitalization for new or worsening heart failure in the DAVID trial.

Block randomisation therefore forces the required balance in terms of the numbers of patients in the treatment groups, but things can still go wrong. For example, let s suppose in an oncology study with time to death as the primary endpoint that we can measure baseline risk (say in terms of the size of the primary tumour) and classify patients as either high risk (H) or low risk (L) and further suppose that the groups turn out as follows ... 

In many cases an endpoint directly measures time from the point of randomisation to some well-defined event, for example time to death (survival time) in oncology or time to rash healing in Herpes Zoster. The data from such an endpoint invariably has a special feature, known as censoring. For example, suppose the times to death for a group of patients on a particular treatment in a 24 month oncology study are as follows ... 

The special methods we are going to discuss in this section were first developed primarily in the 1970s and applied in the context of analysing time to death and this is why we generally refer to the topic as survival analysis . As time has gone on, however, we have applied these same techniques to a wide range of time-to-event type endpoints. The list below gives some examples ... 

A total of 12 patients (six in each of the two treatment groups) underwent cardiac transplantation during the study. One issue was how to deal with these patients in the analysis as receiving a transplant will impact on the survival prospects for that patient. In the primary analysis these patients were censored at the time of transplantation. As a sensitivity analysis, the eventual time to death (or censoring at the end of follow-up) was included in the analysis the conclusions were essentially unchanged. 

Specie Bliaa-Calculated LCtso, Concentration, mg>min/m3 mg/m) Duration of Expoaure min, Mortality Fraction Time to Death, hb... 

Oberst et al. 3 questioned the reliability of LCt5QS for CA in early reports. They then tested eight species of animals at "high" concentrations (105-168 mg/m3 for 12-120 min) in an exposure chamber, using CA of 90% purity. Table 4-33 shows the concentrations, exposure times, mortality fractions, and times to death, and Table 4-34 summarizes the LCt5QS. 

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