Lethality fractions

In estimating the total detriment due to stochastic responses in any organ as described above, the probability coefficient for fatal cancers (F) or severe hereditary responses is based on data in humans and animals described in Section 3.2.2.2, and the lethality fraction (k) and relative length of life lost per fatal response (.II) are based on data on responses from all causes in various national populations. The values of F, k, and t/l for different organs, as well as the probability coefficient for severe hereditary responses, assumed by ICRP (1991) and the resulting estimates of total detriment, F((/T)(2 - k ), are summarized in Table 3.2. The two entries for Total in the last row represent the probability coefficient for... 

Organ Fatal Cancers (FT Severe Hereditary Effects 1 Lethality Fraction (kY Relative Length of Life Lost m) Total Detriment F(til 2 - kf... 

From the expression for the total detriment given above and the data in Table 3.2, the following observations can be made. For cancers that are nearly always fatal (e.g., leukemia from irradiation of bone marrow), the total detriment is determined essentially by the probability of a fatal cancer, absent consideration of the relative length of life lost (fJl), and the contribution from weighted nonfatal cancers is insignificant. For cancers that are rarely fatal (e.g., skin or thyroid cancers), the total detriment exceeds the probability of a fatal cancer by no more than a factor of two, based on the assumption that nonfatal cancers should be weighted by the lethality fraction (k). In general, if the lethality fraction is less than about 0.1, the total detriment essentially is twice the probability of a fatal cancer, independent of the lethality fraction. 

Incidence. In the first option, the common measure of stochastic response from exposure to radionuclides and hazardous chemicals would be incidence, without any modifications to account for such factors as differences in lethality fractions for responses in different organs or tissues or expected years of life lost per fatality. Such modifications are intended to represent differences in the severity of different stochastic responses. 

Perriere, C., Perriere, F. G. and Petek, F. (1988) Purification of a lethal fraction from the venom of the weeverfish, Trachinis Vipera, Toxicon, 26, 1222-1227. 

Fahim, F. A. and Zahran, F. I. (1987). Effect of the most lethal fraction (F. Ill) of Naja nigricollis venom part I on liver function, ppl73. 12 international Congress for Statistic, Computer Science, Social and demographic research center. Ain Shams University, Cairo, Egypt. 

Convert this fraction to a percent and compare to the IDLH and lethal levels. 

Actinia cari. When an extract of the tentacles of this species was subjected to gel nitration, a single protein peak having hemolytic and lethal activities was obtained. Further fractionation by CM-cellulose ion-exchange chromatography yielded three well separated peaks (CTl, Cmi, Cmil) which appeared to be similar in biological activity (14). 

Venom from the globiferous pedicellariae of sea urchins is lethal to mice, rabbits, crabs, lobsters, and worms 70). Seasonal changes in toxicity of such toxins 71) have been observed. The LD q estimate (mice) for toxic fractions from the urchin Tripneustes gratilla ranged from 0.05-0.5 mg/kg 70). 

The most likely toxicity value to be found in the literature is the LD50 (dose lethal to 50% of the animals) for some laboratory species, usually rat or mouse. This value may be obtained by plotting on probit paper the fraction of experimental animals killed against the acute dosage. There Is seldom enough information to permit extrapolation to a dosage at which only a very small (e.g., 1%) fraction of the animals would be killed, much less to an acceptable risk level. Handy and Schindler (12), however, assum ... 

Table II. Summation of Fractional Effective (Lethal) Doses for 30-Minute Exposure of Rats to Mixtures of CO and HQ...

Some sophisticated guessing goes into dose selection. Knowledge of the minimum acutely toxic dose helps the toxicologist pick the highest dose to be used it will be somewhere below the minimum lethal dose. There is usually little basis for deciding the lowest dose it is often set at some small fraction of the high dose. Whether it turns out to be a NOAEL will not be known until the experiment is completed. Sometimes bioassays have to be repeated to identify the NOAEL. 

The dramatic increase of severe or lethal infections caused by antibiotic-resistant bacteria triggered numerous studies on antibiotic resistance, not only from clinical but also from environmental sources. Nowadays it is clear that environment, and water in particular, plays a central role on antibiotic resistance dispersion to and from clinical settings. However, the current state of the art clearly suggests that only a small fraction of the environmental resistome is known. The modes and mechanisms of emergence, evolution and transmission of resistance determinants are still not very well understood. Although environmental pollution is recognized to play an important role on antibiotic resistance evolution and spreading, it is still very difficult to draw cause-effect relationships, which sometimes seems to be strain/species dependent. 

Iron(n) is known to decompose hydrogen and dialkyl peroxides to free radicals by reductive cleavage of the 0—0 bond and early investigations established the parasite s sensitivity to these species. When treated with radiolabelled C-artemisinin, the hemin-hemozoin fraction of the lysed malaria-infected erythrocytes was shown to contain a radiolabel, though the mechanism of incorporation is not clear. Meshnick and coworkers demonstrated that uninfected cells did not contain radiolabelled proteins whereas six radiolabelled proteins were isolated from cells infected with the Plasmodium falciparum (P. falciparum) strain of the parasite. It was suspected that one of the alkylated proteins was the Histidine Rich Protein (HRP) that was known to bind multiple heme monomers and therefore thought to be instrumental to the parasite s detoxification process. Moreover, iron chelators were found to inhibit the lethal effects of peroxides on the parasite. ... 

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