The Emergence of the Dose--Response Concept in Biology and Medicine

Calabrese, Edward J.
December 2016
International Journal of Molecular Sciences;Dec2016, Vol. 17 Issue 12, p2034
Academic Journal
A historical assessment of the origin of the dose-response in modern toxicology and its integration as a central concept in biology and medicine is presented. This article provides an overview of how the threshold, linear and biphasic (i.e., hormetic) dose-response models emerged in the late 19th and early 20th centuries and competed for acceptance and dominance. Particular attention is directed to the hormetic model for which a general description and evaluation is provided, including its historical basis, and how it was marginalized by the medical and pharmacology communities in the early decades of the 20th century.


Related Articles

  • Dose-response relationships in mutagenicity assays including an appropriate positive control group: a multiple testing approach. Hothorn, Ludwig A.; Hayashi, Makoto; Seidel, Dirk // Environmental & Ecological Statistics;Mar2000, Vol. 7 Issue 1, p27 

    The objective of mutagenicity assays in regulatory toxicology is the decision on non-mutagenicity or mutagenicity. An inherent problem of statistical tests is the possibility of false decisions, i.e., a mutagenic substance will be falsely labeled as non-mutagenic or a non-mutagenic substance...

  • Robust trend tests with application to toxicology. Neuhäuser, Markus; Seidel, Dirk; Hothorn, Ludwig A.; Urfer, Wolfgang // Environmental & Ecological Statistics;Mar2000, Vol. 7 Issue 1, p43 

    In most real data situations in the one-way design both the underlying distribution and the shape of the dose-response curve are a priori unknown. The power of a trend test strongly depends on both. However, tests which are routinely used to analyze toxicological assays must be robust. We use...

  • A Method to Evaluate Hormesis in Nanoparticle Dose-Responses. Nascarella, Marc A.; Calabrese, Edward J. // Dose-Response;2012, Vol. 10 Issue 3, p344 

    The term hormesis describes a dose-response relationship that is characterized by a response that is opposite above and below the toxicological or pharmacological threshold. Previous reports have shown that this relationship is ubiquitous in the response of pharmaceuticals, metals, organic...

  • Bioassays of Shortened Duration for Drugs: Statistical Implications. Kodell, Ralph L.; Lin, Karl K.; Thorn, Brett T.; Chen, James J. // Toxicological Sciences;Jun2000, Vol. 55 Issue 2, p415 

    Declining survival rates in rodent carcinogenesis bioassays have raised a concern that continuing the practice of terminating such studies at 24 months could result in too few live animals at termination for adequate pathological evaluation. One option for ensuring sufficient numbers of animals...

  • Medicine's hottest idea.  // Health & Homeopathy;Winter2003/2004, p6 

    Explains the concept of paradoxical pharmacology. Efficacy of drug when given in small doses; Comparison with homeopathy.

  • The rapid detection of cytotoxicity using a modified human sperm survival assay. Iemmolo, Melissa; Simmons, Leigh; Matson, Phillip // Journal of Assisted Reproduction & Genetics;Apr2005, Vol. 22 Issue 4, p177 

    Sperm were cultured at room temperature in seminal plasma, in the presence or absence of a test item or solution. Progressive motility of the sperm was measured using a Sperm Quality Analyser JIB. A progressive decline in motility of sperm was seen under control conditions from o hr to 24 hrs....

  • Effects of piperonyl butoxide on spontaneous behavior in F1-generation mice. Tanaka, Toyohito; Takahashi, Osamu; Oishi, Shinshi; Ogata, Akio // Toxicology & Industrial Health;Aug2009, Vol. 25 Issue 7, p489 

    Piperonyl butoxide was given in the diet to provide levels of 0 (control), 0.02%, 0.06%, and 0.18% from 5 weeks of age of the F0 generation to 12 weeks of age of the F1 generation in mice. Select reproductive and neurobehavioral parameters were then measured. In exploratory behavior in the F0...

  • Quantitative mechanistically based dose-response modeling with endocrine-active compounds. Andersen; Conolly, Melvin E. // Environmental Health Perspectives Supplements;Aug99 Supplement 4, Vol. 107, p631 

    Presents a method for testing toxicity of endocrine-active compounds on human health. Use of a quantitative mechanistically based dose-response (MBDR) model; Description and application of MBDR in risk assessments; Requirements for acceleration of model development and acceptance.

  • Toxicological diversity: making room for the U-shaped dose response. Calabrese, Edward J. // Human & Experimental Toxicology;Sep2003, Vol. 22 Issue 9, p465 

    Focuses on toxicological diversity and the nature of dose-response. Basic concept of the nature of dose-response; Impact of cancer risk estimation on dose response; Role of U shaped dose -responseto an overall assessment.

  • The marginalization of hormesis. Calabrese, E.J.; Baldwin, L.A. // Human & Experimental Toxicology;Jan2000, Vol. 19 Issue 1, p32 

    Despite the substantial development and publication of highly reproducible toxicological data, the concept of hormetic dose-response relationships was never integrated into the mainstream of toxicological thought. Review of the historical foundations of the interpretation of the bioassay and...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics