Dose-effect relationships

Hasenfratz, M., Battig, K., Acute dose-effect relationships of caffeine and mental performance, EEG, cardiovascular and subjective parameters. Psychopharmacology 114(2), 281-287, 1994. 

Biological monitoring of exposure to coumarin derivatives can be performed by determination of the unchanged compound and/or its metabolites in blood and urine (Table 6). Analytical complexity and the lack of knowledge about the dose-effect relationship in exposed subjects are the primary limitations of this method. 

The database for lead is unusual in that it contains a great deal of data concerning dose-effect relationships in humans. These data come primarily from studies of occupationally exposed groups and the general population. However, the dose data for humans are generally expressed in terms of absorbed... 

Ferguson and Bowman 1990 Gilbert and Rice 1987 Hopper et al. 1986 Krasovskii et al. 1979 Levin et al. 1988 Massaro and Massaro 1987 Overmann 1977 Rice 1985a). It appears that animals are affected at roughly the same blood lead levels as humans. Measured neurotoxic effects in animals include significantly delayed motor function and reflexes, decreased performance on learning tasks, and impaired spatial discrimination. Additional animal studies are needed to investigate the neurotoxic effects of subchronic inhalation exposures to establish external dose-effect relationships. 

Chisolm JJ Jr. 1981. Dose-effect relationships for lead in young children Evidence in children for interactions among lead, zinc, and iron. In Lynam DR, Piantanida LG, Cole JF, eds. Environmental Lead Proceedings on the Second International Symposium on Environmental Lead Research, December, 1978, Cincinnati, Ohio. New York, NY Academic Press, 1-7. 

Epidemiology. Using the epidemiological approach the following preconditions have to be met in order to establish a dose-effect relationship ... 

Pohl-Ruling, J. and P. Fischer, The Dose Effect Relationship of Chromosome Aberrations to Alpha and Gamma Irradiation in a Population Subjected to an Increased Burden of Natural Radioactivity, Radiation Research 80 61-81 (1979)... 

Commission of the European Communities, Directorate General Scientific and Technical Information and Information Management, Luxenbourg. Criteria (Dose/Effect Relationships) for Cadmium Pergammon Press Elmsford, NY, 1978. 

Cantoni, L., M. Salmons, and M. Rizzardini. 1981. Porphyrogenic effect of chronic treatment with 2,3,7,8-tetrach Iorod i ben z.o-p-d io x i n in female rats. Dose-effect relationship following urinary excretion of porphyrins. Toxicol. Appl. Pharmacol. 57 156-163. 

Toxic effects of expositions are calculated for a variety of exposures and effect combinations, assuming a probabilistic dose-effect relationship. Lethal and incapacitating responses (e.g. respiratory effects, topical skin effects or incapacitating eye effects) of varying degrees of severity are addressed. The model also distinguishes between effects resulting from vapour exposure and from exposures to liquid droplets. These primary effect probabilities are subsequently combined to afford overall casualty probabilities for lethality, severe incapacitation and incapacitation due to topical eye effects. 

The toxic effects model translates the exposure profiles into casualty probabilities for the personnel, assuming a probabilistic dose-effect relationship. The casualty levels and spectra can be obtained for various type of health effects, e.g. eye effects, inhalation, percutane, subdivided in two levels (incapacitating and lethal), and various protection levels, e.g. no protection, suit only, mask only, mask and suit, and collective protection. Table 1 gives a typical result for one scenario. In case no protection is used, 63% of the population dies due to inhalation of sarin and 25% dies due to percutaneous exposure. Clearly, when both mask and suit are worn, the casualty levels are dropping drastically. 

Subsequent clinical studies provided additional evidence that GTN exerts antiplatelet activity in vivo and offered insight into the nature of GTN s anti-aggregatory pharmacology. A dose-effect relationship between intravenous GTN and inhibition of platelet aggregation was uncovered in healthy male subjects, in whom plasma... 

Evaluation of the data is not purely a statistical exercise. A number of important factors should be considered (1) dose-effect relationship (2) a shift towards more anaplastic tumors in organs where tumors are common (3) earlier appearance of tumors, and (4) presence of preneoplastic lesions. 

The basic model for ascertaining dose-effect relationships is derived from the sigmoidal effect model, which correlates maximal response (E ), placebo (Eg), and the dose producing 50% of effect (EDjq) ... 

Fox et al., proceed, however, to describe a dose-effect relationship, in spite of the fact that the dust levels available to these authors were not prospective. They use levels of dustiness measured at the time of the survey. It should be stressed that the effect related by this curve does not Include chronic or irreversible disorder, since the plot is based exclusively on reversible effects. Furthermore, the suggestion of a cumulative effect, which would appear supported by a frequency somehow proportioned to duration of employment (i.e., seniority), may not be justified. 

The effect of a substance depends on the amount administered, i.e., the dose. If the dose chosen is below the critical threshold (subliminal dosing), an effect will be absent. Depending on the nature of the effect to be measured, ascending doses may cause the effect to increase in intensity. Thus, the effect of an antipyretic or hypotensive drug can be quantified in a graded fashion, in that the extent of fall in body temperature or blood pressure is being measured. A dose-effect relationship is then encountered, as discussed on p. 54. 

The dose-effect relationship may vary depending on the sensitivity of the individual person receiving the drug, i.e for the same effect, different doses may be required in different individuals. 

The evaluation of a dose-effect relationship within a group of human subjects is compounded by interindividual differences in sensitivity. To account for the biological variation, measurements have to be carried out on a representative sample and the results averaged. Thus, recommended therapeutic doses will be appropriate for the majority of patients, but not necessarily for each individual. 

Related terms Dose—Effect Relationship, Effect Assessment, Concentration—Effect Relationship. 

Combination of analysis and inference of possible consequences of the exposure to a particular agent based on knowledge of the dose-effect relationship associated with that agent in a specific target organism, system, or (sub)population. 

In poisoning cases, the exposure concentration or dose is often unknown and thus, a dose-effect relationship is difficult to evaluate. Therefore, information from poisoning cases generally has a limited use in the hazard assessment. An exception is identification of acute toxic effects. Furthermore, poisoning cases can also indicate whether a substance can become systemically available ... 

Advantages of animal studies include standardized test conditions, the possibility to detect far more effects through invasive measurements and postmortem examinations, the possibihty to investigate modes and mechanisms of action, and to investigate dose-effect relationships for single chemical substances. 

Other terms often used indiscriminately for the dose-response relationship include concentration-effect relationship and dose-effect relationship. According to the joint OECD/IPCS project (OECD 2003 a), which has developed internationally harmonized generic and technical terms used in chemical hazard and risk assessment, the following definitions have been provided although consensus was not achieved ... 

Dose-effect relationship is the Relationship between the total amount of an agent administered to, taken up or absorbed by an organism, system or (sub) population and the magnimde of a continuously-graded effect to that organism, system or (sub) population. ... 

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