Specific death rate

Mortality associated with acrylonitrile exposure was evaluated as part of a study of 15 643 male workers in a rubber plant in the United States (Akron, Ohio) (Delzell Monson, 1982). Included in the analysis were 327 workers who were employed for at least two years in the plant between 1 January 1940 and 1 July 1971, and who had worked in two departments where acrylonitrile was used, i.e., 81 worked only in the nitrile rubber manufacturing operation where exposures to 1,3-butadiene (see this volume), styrene (lARC, 1994a) and vinylpyridine also occurred and 218 only in the department where the latex was coagulated and dried. [No information on levels of exposure to acrylonitrile was provided ] Mortality among these workers was assessed through 1 July 1978 and compared with age- and calendar-time-specific rates for white men in the United States. SMRs were 0.8 ( = 74 95% CI, 0.7-1.0) for all causes of death, 1.2 ( = 22 95% CI, 0.8-1.9) for all cancers combined, 1.5 ( = 9 95% CI, 0.7-2.9) for lung cancer, 4.0 ( = 2 95% CI, 0.5-14.5) for urinary bladder cancer and 2.3 ( = 4 95% CI, 0.6-5.8) for cancers of the lymphatic and haematopoietic system. SMRs for lung cancer by duration of employment were [1.0] (4 observed, 3.8 expected) [95% CI, 0.3-2.7] for < 5 years, and [3.3] (5 observed, 1.5 expected) [95% CI, 1.1-7.8] for 5-14 years. No case was observed with duration > 15 years. 

The identification of phenomena that explain the behavior of a studied system depends on the analysis of their kinetic data. Normally, this kinetic analysis is performed using characteristic variables calculated from the experimental data. The specific rates and the yield coefficients are the common values used in this task. When cell concentration data are available, cell growth and death rates, as well as cell viability, are the best kinetic variables to characterize the population physiological state. In the absence of this information - as can occur, for example, with immobilized cells - the treatment must be based on substrate consumption or on metabolites production (Miller and Reddy, 1998). 

The specific growth rate can be calculated from cellular concentration data if the cell viability is sufficiently high. When the cell death rate is significant, the value obtained from Equation 4 is in fact an apparent specific rate, since the measured values in the laboratory are determined as a balance between growth and death. The apparent rate is related to the true specific growth rate by the following equation ... 

Similar to what has been shown in Table 8.1 for specific growth rate, many mathematical expressions listed in Table 8.3 employ Monod-type structures for limiting phenomena, and Aiba and Shoda-type structures for inhibitory behavior. Limiting components for cell death are lactate and ammonia, that is, the presence of these byproducts increases the specific cell death rate. On the other hand, substrates, such as glucose and glutamine, inhibit cell death (Equations 48 to 52). 

Table 8.3 Kinetic expressions for specific cell death rate in ani mal cell systems ...

Several of the terms above have been discussed in Sec. 7 rg and r are the specific rates (per broth volume) for cell growth and death, respectively rsm is the specific rate of substrate consumed for cell maintenance, and are the stoichiometric yield coefficient of species i relative to biomass x. The maintenance term in Eq. (19-81) can result... 

Fig. 1.2. Age-specific rates of all events and of incident events for stroke (i.e. not including transient ischemic attack closed circles), myocardial infarction and sudden cardiac death combined (i.e. not including unstable angina open circles), and acute peripheral vascular events (triangles) in men and women in Oxfordshire from 2002 to 2005 (Rothwell et a . 2005).

The specific rate of cellular death, k, is defined as the number of dying cells per unit (e.g. billion) of living cells present in the culture medium per unit time (e.g. hour). 

As a first approximation has often been considered as a constant. Yet more detailed kinetic analyses have shown that the specific rate of cell death is also affected by the chemical composition of the medium and several physicochemical parameters, such as pH, temperature and osmotic pressure. It is often lowest at the start of the culture, and then gradually increases due either to depletion of essential nutrients or accumulation of inhibitory metabolites. 

Phase 2 is from 40 to 140 h, where all the specific rates progressively decrease except the cellular death rate, which continues to rise. This reduction in the specific rates of growth and metabolism is mainly due to glutamine limitation. However, the accumulation of lactate and ammonia may also have a kinetic... 

Glutamine depletion as well as lactate and ammonia accumulation are also responsible for the observed increase in the specific rate of cell death. Again a three-term rate expression is selected ... 

The kinetic expression for the specific rate of cellular death (Equation 4.3.18) contains three terms that each express a possible increase of the specific death rate and can be evaluated as follows ... 

However, it is important to note that the specific growth rate is only equal to the dilution rate when all cells in the population are viable. Below 100% viability, the precise relationship between x and D is more complex than the simple model described above, and a number of studies have shown that the actual specific growth rate deviates from D, particularly at low dilution rates. This results from an increase in the proportion of dead cells in the population, which in turn can be related to an increase in the specific rate of cell death (p ) at low D. The specific death rate at a particular dilution rate is related to the proportion of viable (x ) and non-viable cells (x ), where ... 

The SMR is the ratio of the number of deaths observed in a study group divided by the number expected (based on age- or sex-specific rates in the general population) and multiplied by 100. An SMR greater than 100 indicates that the death rate was higher than would be expected. 

In a mortality study of steelworkers employed in a coke oven plant in 1953, increased mortality from respiratory neoplasms (monitored from 1953 to 1961) was observed in coke oven workers compared to expected mortality rates (Lloyd 1971). Specifically, 20 deaths from respiratory neoplasms were observed, compared to the expected 7.5 deaths. The increase in mortality was linked to an increase in mortality from respiratory neoplasms in nonwhite oven workers who had been employed for 5 years. 

Cause-specific mortality rate Deaths from a specific cause per population... 

The corresponding concentration of the substrate in the effluent from the CSTBR can be determined by recognizing that (1) at steady state, equation (13.2.59) is again applicable, and (2) in the absence of cell death and cell maintenance effects, the biochemical reaction obeys a biomass-specific rate law of the Monod form ... 

The expected numbers of death were calculated from the age- and sex-specific rates of the total Belgian population. 

A Monod rate model is used to demonstrate the rate of biomass generation. We neglect the cell death rate. Let us denote the ratio of biomass rate of generation to biomass concentration, rJX, that is the specific growth rate /a also denotes the dilution rate D is defined as number of tank volumes passed through per unit time, FIV. After substitution of D and /a into (6.8.1), the following equation is obtained ... 

The Monod rate model is valid for a CSTR bioreactor with maximum specific growth rate of 0.5 li 1 and K, 2 g-1. What would be a suitable dilution rate at steady-state condition, where there is no cell death if initial substrate concentration is 50g-l-1 and yield of biomass on substrate is 100%. 

The dose of TCDD given to the male rats used in this study, 50 />tg/kg, was approximately twice the LD50, 23 /xg/kg. This large dose was necessary because of the low specific activity of the TCDD- C used. In this study rats lost weight, and their physical condition was poor, which typifies the insidious response to TCDD (J). Survival of the rats for 21 days was not totally unexpected because in previous studies on the lethality of TCDD deaths frequently occurred 20 or more days following a single oral dose of similar magnitude (I). With doses that do not induce untoward effects, the compound may be excreted at a different rate. 

Fatal reactions to Hymenoptera stings are rare they range from 0.09 to 0.48 per million inhabitants and year [31, 32]. However, the true number may be underestimated in one study, specific IgE antibodies to Hymenoptera venoms were detected in 23% of postmortem serum samples from patients who died outdoors from unknown reasons [33]. Between 1961 and 2004, 140 fatal Hymenoptera sting reactions were registered by the federal administration for statistics in Switzerland with about 7.5 million inhabitants, resulting in an average annual fatality rate of 3.18. If these data are extrapolated to Europe with a population of around 500 million, the annual death rate in Europe would amount to about 200. 

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