Threshold hypothesis

This model tends to approach a zero probability rapidly at low doses (although it never reaches zero) and thus is compatible with the threshold hypothesis. Mantel and Bryan, in applying the model, recommend setting the slope parameter b equal to 1, since this appears to yield conservative results for most substances. Nevertheless, the slope of the fitted curve is extremely steep compared to other extrapolation methods, and it will generally yield lower risk estimates than any of the polynomial models as the dose approaches zero. 

Threshold hypothesis A radiation-dose-consequence hypothesis that holds that biological radiation effects will occur only above some minimum dose. 

So when this approach is used for carcinogens, it takes into account the no-threshold hypothesis (it predicts a risk at all exposures greater than zero), but there should be no pretense that we have arrived at an accurate prediction of risk. The LNT is the default used for carcinogens for low-dose extrapolation. 

Well, it was nothing more than a crude expression of the nothreshold hypothesis, as described in earlier chapters. Under this hypothesis, any exposure to a carcinogen increases the probability that cancer will occur. As we have emphasized several times, it does not mean that any exposure to a carcinogen will cause cancer. If the exponents of the no safe level view meant that an absolutely safe level of exposure could not be identified, then they were correct, assuming the no-threshold hypothesis is correct. (Even assuming the threshold hypothesis is correct, as we have noted earlier, does not establish that we can ever be certain we have identified the completely safe threshold dose for any agent.)... 

The multifaceted function of cuticular hydrocarbons necessitates further theoretical as well as empirical clarification. For example, their use as both fertility signals and nest-mate recognition pheromones may seem contradictory, since the first function requires within-nest idiosyncrasy, i.e., for discriminating fertile from sterile individuals, while the second function requires within-colony odor uniformity. The response threshold hypothesis (Le Conte and Hefetz, 2008) attempts to resolve this apparent conflict in function, as well as to provide a suitable framework for future experiments to test specific parts of the hypothesis. 

Peperzak L, Colijn F, Gieskes WWC, Peeters JCH (1998) Development of the diatom-Phaeocystis spring bloom in the Dutch coastal zone of the North Sea the silicon depletion versus the daily irradiance threshold hypothesis. J Plankton Res 20 517-537 Petterson K, Sahlsten E (1990) Diet patterns of combined nitrogen uptake and intracellular storage of nitrate by phytoplankton in the open Skagerrak. J Exp Mar Biol Ecol 138 167-182... 

If the dose-response curves for the two sample carcinogens are reexamined, it can be seen that response axes represent the fraction of animals that developed extra tumors at particular sites - the bladder in the case of saccharin, and the liver in that of aflatoxin - over their lifetimes of exposure. Another term for this fraction is lifetime risk — the lifetime probability that the specific tumors develop. Each animal in a treatment group was at a certain risk of developing tumors because of the chemical exposure the size of that risk is represented by the measured tumor rate (ignoring the variability inherent in all experimental studies). At some point, below lifetime risks of about 5-10% (1 in 20 to 1 in 10), the experiments lost capacity to detect excess tumor responses. But under the no-threshold hypothesis risks continue to exist at all doses, even if they can not be detected in animal experiments, and disappear completely only when the dose goes to zero. 

For those forms of toxicity for which the threshold hypothesis may not hold - the important case being carcinogenicity - the problem of high-to-low dose extrapolation is more bewitching. Recall that in typical animal cancer studies, and in epidemiology investigations as well, excess lifetime cancer risks lower than about 10% (1/10) are undetectable. What dose-response relationship holds below the region of direct observation And why should we care ... 

For some carcinogens, those that act through genotoxic mechanisms and perhaps some others, there may be some risk at all doses greater than zero (no-threshold hypothesis). 

A significant segment of the community of toxicologists holds that at least certain carcinogens do not act through mechanisms that are consistent with a no-threshold hypothesis, and therefore do not create cancer risks until a threshold dose is passed. (See the discussion of promoters, Chapter 8.)... 

In the discussion of thresholds presented earlier we pointed out that many scientists adopt the no-threshold hypothesis, if not for all, then for at least those carcinogens that act through genotoxic mechanisms. Some biological basis exists for such an assumption, but it is also... 

It is, first of all, obvious that cancer is not our only public health problem Because of the application of the no-threshold hypothesis to chemical carcinogens, this form of toxicity almost always overrides... 

Hummel, P., Vaidehi, N., Floriano, W.B., Hall, S.E., and Goddard, WA. III. (2005) Test of the binding threshold hypothesis for olfactory receptors Explanation of the differential binding of ketones to the mouse and human orthologs of olfactory receptor 912-93. Protein Sci. 14, 703-710. 

C Hopenhayn-Rich, AH Smith, HM Goeden. Human studies do not support the methylation threshold hypothesis for the toxicity of inorganic arsenic. Environ Res 60 161-177, 1993. 

What are the economic and health implications of the linear no-threshold hypothesis for toxins compared to the threshold hypothesis ... 

Roelofs, W. Threshold Hypothesis for Pheromone Perception. J. Chem. Ecol. 4, 685-699 (1978). 

Roelofs, W. L. (1978) The threshold hypothesis for pheromone perception. J. Chem, EcoL, 4, 685-99. 

In relation to the threshold hypothesis discussed above. Mass (1992) has proposed an interesting hypothesis for the role of methylation in the toxicity and carcinogenicity of As which incorporates elements related to the dietary... 

Hirata M, Tanaka A, Hisanaga A, Ishinishi N (1990) Effects of glutathione depletion on the acute nephrotoxic potential of arsenite and on arsenic metabolism in hamsters. Toxicol Appl Pharmacol 106 469-481 Hoffman JL (1980) The rate of transmethylation in mouse liver as measured by trapping S-adenosylhomocysteine. Arch Biochem Biophys 205 132-135 Hopenhayn-Rich C, Smith AH, Goeden HM (1993) Human studies do not support the methylation threshold hypothesis for the toxicity of inorganic arsenic. Environ Res 60 161-177... 

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