ENTRIES A–Z
Philip Winn in Dictionary of Biological Psychology, 2003
The graphic representation of the magnitude of a DRUG effect as a function of the dose of the drug. The dose effect curve, also known as the DOSE RESPONSE CURVE, is an essential feature of well-controlled experiments in pharmacology and PSYCHOPHARMACOLOGY. Although data can be represented in varying ways, the basic curve is a plot of the size or magnitude of the effect on the y-axis and the dose (or concentration) of the compound under study on the x-axis. The ideal dose effect curve has at least three doses of the drug plus VEHICLE, and preferably more. The range of the doses should ideally be quite broad. For example, a common strategy is to test drug doses that vary by log concentrations. It is important to show a relationship between dose and effect in order to clearly demonstrate a specific, physiological effect of the drug. The shape of dose effect curves can vary depending on the pharmacological or neurochemical effects of the drug, as well as the behaviour under study. Most dose effect curves show a positive linear relationship between dose and effect; however, in most systems an asymptote is reached in which further increases in dose will not result in a stronger response. Also common in psychopharmacology are inverted U-shaped dose effect curves. In this case, the maximum effect is reached at a certain dose, and then decreases with further increases in dose.
General Surgery
Tjun Tang, Elizabeth O'Riordan, Stewart Walsh in Cracking the Intercollegiate General Surgery FRCS Viva, 2020
How is chemotherapy delivered?Combination: Use different classes for broader coverage of activity and reduce risk of resistant subclonesFor example, in the FEC regime, all have single-agent activity against breast cancer, but when combined the response rate is two to three times higher.High dose Give on steeper part of sigmoid dose–response curve.
Hormesis
T. D. Luckey in Radiation Hormesis, 2020
What is the significance of radiation hormesis? The biopositive nature of low doses of ionizing radiation virtually eliminates the concept that all radiation is harmful.527,530 It may be argued that stimulation is the earliest indication of the presence of minute doses of a harmful agent. A stimulant, even in low doses, is not necessarily beneficial. Nor is it generally considered to be useful to apply stimulants on a chronic basis. A few, such as caffeine or nicotine, are tolerated. Perhaps the data of radiation hormesis are only part of a bigger picture. Several questions arise. What is the shape of the complete dose-response curve? What is the optimal dose? Could ionizing radiation be essential for life? If it were, a deficiency should develop when the daily dose was significantly lowered. Conversely, if no deficiency developed when background exposure was significantly lowered, whole-body exposure to low doses of ionizing radiation could be considered to be an innocuous stimulant. Might it be a useful agent for providing optimum health? These questions indicate the real significance of radiation hormesis.
An overview of current practices for regulatory risk assessment with lessons learnt from cosmetics in the European Union
Published in Critical Reviews in Toxicology, 2021
Emma Arnesdotter, Vera Rogiers, Tamara Vanhaecke, Mathieu Vinken
Hazard characterisation is the second stage in the hazard assessment and is defined as “the qualitative and, wherever possible, quantitative description of the inherent properties of an agent or situation having the potential to cause adverse effects” (WHO/IPCS 2009a). Hazard characterisation should include a dose–response assessment and its associated uncertainties (WHO/IPCS 2009a). The relationship between the dose and the associated adverse health effects is often represented as a dose–response curve. In human health toxicology, the point of departure (POD) is used as a reference point and is defined as the highest external dose on a dose–response curve devoid of adverse health effects, i.e. the NOAEL. The POD is usually derived from (sub)chronic animal studies in the most sensitive and relevant species, typically rodent, rabbit or dog, and based on the critical effect. There are two main approaches used for determination of the POD, namely the NOAEL approach and the bench-mark dose (BMD) approach (Figure 4(A,B)). The strengths and weaknesses of both methods have been discussed in several publications (Travis et al. 2005; Sand et al. 2008; Davis et al. 2011; Haber et al. 2018).
Assessing the impact of different neutron RBEs on the all solid cancer radiation risks obtained from the Japanese A-bomb survivors data
Published in International Journal of Radiation Biology, 2023
Luana Hafner, Linda Walsh, Werner Rühm
It is noted that typically results from the LSS are based on a value of the neutron RBE of 10. The curvature parameter gives evidence on the shape of the dose response curve: the closer the parameter to zero the closer to linearity is the curve. In the present study the shape of the dose response curve as a function of neutron RBE is analyzed using an LSS dataset with a longer follow-up period (1958–1998) than Little and Muirhead (2004) did, based on the DS02 system (Young and Kerr 2005). The LSS dataset with the follow-up period from 1958 to 1998 (Preston et al. 2007) is chosen in this study, because of the availability of the separate neutron and gamma absorbed doses. In the most recent published dataset Grant et al. (2017) with a follow-up until 2009, only the total weighted colon dose including the RBE = 10 weighted neutron dose is considered and no information on separate neutron and gamma absorbed doses are published. Furthermore, the LSS publicly available grouped dataset from Grant et al. (2017) and Preston et al. (2007) cannot be merged, because no unique identification number nor a unique set of matching variables is provided in the datasets, due to their grouped nature.
Thresholds of adversity and their applicability to endocrine disrupting chemicals
Published in Critical Reviews in Toxicology, 2020
Experimental science is not capable of determining the shape of the dose-response at very low doses. Hypotheses regarding where on the dose-response curve the true threshold lies are beyond the ability of science to resolve. So, limitations on our ability to probe all of the scientific considerations involved do not permit the direct observation of true thresholds. But, they surely exist – it is inconceivable that a single molecule of any substance can, of itself, produce significant detrimental consequences in an organism or (for ecotoxicological considerations) a population. Continuing to spend energy and time debating the irresolvable issue of true thresholds is detrimental to a logical and workable comprehensive approach to risk assessment. Thus, the focus of regulatory risk assessment has always been centered around “practical/experimental” thresholds.
Related Knowledge Centers
- Clinical Endpoint
- Drug Development
- Mechanoreceptor
- Sensory Neuron
- Stimulus–Response Model
- Dose
- Stimulus
- Stressor
- The Dose Makes The Poison
- Threshold Dose