Dose-response relation

In an early study in 1971, Cole22 found an association between coffee drinking and lower urinary tract cancer based on a case-control study of 445 cancer patients (345 men, 100 women) and 451 population controls who were matched for age and sex. The analyses had controlled for cigarette smoking and occupation however, there was no consistent dose response relation, and the summary risks were significant only in women,... 

Buchanan R L, Smith J L and Long W (2000), Microbial risk assessment dose-response relations and risk characterization , International Journal of Food Microbiology, 58, 159-172. 

A dose-response relation was found between dietary PCB concentrations and porphyrins in liver and excreta. PCB concentrations in the 500 mg/kg group were about 900 mg/kg DW liver and 78 mg/kg DW excreta in the 50 mg/kg group, liver had about 150 mg/kg DW... 

These drugs are the most prescribed medicines in the world. For certain NSAIDs, ibuprofen and indomethacin, there has been shown a dose response relation for renal failure risk. For individual NSAIDs, those with longer half lives than 12 hours have proved to be more dangerous. There has not been shown any clear advantages for selective cox-2-inhibition to the more unselective in this aspect. 

With some possible exceptions (to be discussed in Chapter 9), dose-response relations identical or similar to those shown in Figure 3.1 are observed for all expressions of chemical toxicity. Indeed, the absence of such a dose-response relationship is often used as evidence that a chemical has not caused a particular response. Criteria for causation in... 

Figure 9.1 Dose-response relations for essential nutrients.

Dose-response relations in key primary-producer species in service-important ecosystems should be examined under field conditions. 

A dose-related increase in genotoxicity is one of the relevant criteria for identification of positive findings. In practice, this will be most helpful for in vitro tests, but care is needed to check for cytotoxicity or cell cycle delay, which may cause deviations from a dose-response related effect in some experimental systems. 

The application of the principles of dose-response relations to Phase II and III clinical trials focuses on the practical aspect of determining which doses will be selected for these trials and which will be taken forward to registration (see below). Each subject in a clinical trial will have his or her own efficacy and safety dose-response curve for a given drug. The shape and position of these curves will be determined by individual subject characteristics - age, gender, genetically... 

Unlike SSRIs, venlafaxine shows a positive dose-response relation patients with mild depression may respond to lower doses, whereas patients with more severe or recurrent depression may respond better to higher doses. 

Aquatic insect populations were the most sensitive group, especially mayflies, stoneflies, and dipterans. These, and other invertebrates, showed rapid and permanent reductions in biomass and diversity at 1.0 pg/L and higher. Diversity showed an apparent dose-response relation, with no effect at 0.1 pg/L, intermediate reductions at 1 pg/L, and maximal reductions at 10 and 50 pg/L... 

The first of these is the quantitative analysis of dose-dependent drug actions, for example, to infer dose-response relations from clinical correlates of variable compliance (Efron and Feldman, 1991 Urquhart, 1991a). 

Regarding the compositional differences shown for animal products, whether they are important for health depends, as for the plants, on the overall composition of the diet of the people who eat them. The vitamin E content in milk is far too small for relevant differences to affect health (Nielsen ef al. 2004), and too little is known about the dose-response relations of the impact of conjugated linoleic acids on health. However, the increased vitamin E level may still be important to prevent oxidation of the fat, a problem that can be exacerbated by increased levels of polyunsaturated fatty acids (Dhiman ef al. 1999, Nielsen ef al. 2004). However, while oxidised milk is clearly not good for health, its rancid taste and smell allows detection and rejection before consumption and thus prevents harm to health, similar to plant toxicants. Also in line with the plants, while the use of roughage is clearly more extensive in organic farming, some conventional farmers use almost identical feed compositions and are therefore likely to produce the same quality of products in this respect. 

The study of receptors has not featured as prominently in toxicology as in pharmacology. However, with some toxic effects such as the production of liver necrosis caused by paracetamol, for instance, although a dose-response relation can be demonstrated (see chap. 7), it currently seems that there may be no simple toxicant-receptor interaction in the classical sense. It may be that a specific receptor-xenobiotic interaction is not always a prerequisite for a toxic effect. Thus, the pharmacological action of volatile general anesthetics does not seem to involve a receptor, but instead the activity is well correlated with the oil-water partition coefficient. However, future detailed studies of mechanisms of toxicity will, it is hoped, reveal the existence of receptors or other types of specific targets where these are involved in toxic effects. 

Toxicity shows a dose-response relationship and may range from subtle biochemical changes to lethality and may involve receptor interactions. The dose-response relation depends on certain assumptions the toxic response is a function of the concentration at the target site, the concentration at the target site is a function of dose, the toxic response is causally related to the compound. 

Wu, M.-M., Kuo, T.-L., Hwang, Y.-H. and Chen, C.-J. (1989) Dose-response relation between arsenic concentration in well water and mortality from cancers and vascular diseases. American Journal of Epidemiology, 130(6), 1123-32. 

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