Low-dose effect

Winters WD, Kott KS Continuum of sedation, activation and hypnosis or hallucinosis a comparison of low dose effects of pentobarbital, diazepam or gamma-hydroxy-butyrate in the cat. Neuropharmacology 18 877—884, 1979... 

C Low dose effects usually not measurable directly In human or animal observations Need to extrapolate observed high dose effects to low or zero dose range by theoretical dose-response models ... 

Whether subthreshold doses in animals can produce any animal neurobehavioral component of the loosening of inhibition and inner-directed attention sought for by some clinicians in using less potent drugs for a kind of psychosynthesis is uncertain. Sensitization and habituation studies implicate raphe function but not in any simple way (32), and pavlovian studies show very low dose effects on sensory processing (39,43). 

Precautionary action to reduce the exposure of humans and wildlife to the oestrogenic plastics intermediate bisphenol A looks closer following an EC technical meeting in March. Member States rejected risk assessments put forward by the UK which set aside evidence of low-dose effects on fish and laboratory animals. Bisphenol A is an important plastics intermediate used in polycarbonates and epoxy resins. Global manufacturing capacity stands at two million tonnes per year. 

Data on the toxicokinetics of a substance can be very useful in the interpretation of toxicological findings, and may replace the use of some default extrapolation factors used in route-to-route (Section 5.5) or interspecies extrapolations (Section 5.3). In addition, interindividual differences in sensitivity to toxicants may be identified on the basis of toxicokinetic data, thereby making it possible to make the risk assessment more comprehensive by including sensitive subpopulations (Section 5.4). In conjunction with information on the relationship between concentration-dose at the target site and the toxic effect, toxicokinetic information may be an important tool for extrapolation from high to low dose effects. 

In conjunction with information on the relationship between concentration/dose at the target site and the toxic effect, toxicokinetic information may be an important tool for extrapolation from high to low dose effects. 

Hormesis is the term used for the phenomenon of stimulatory effects at low-level exposure, and inhibition at high-level exposure. The term derives from the Greek word Hormo which means excite or set in motion, and which is also the root of the word hormone. The concept of hormesis dates back to the 1920s. A substance showing hormesis has the opposite effect in small doses compared to effects at large doses. The definition of hormesis does not imply that low-dose effects are necessarily beneficial, only that they are opposite to high-dose effects. 

Van Mansfeld. J.D. and Amons, F. 1975. Inquiry into the limits of biological effects of chemical compounds in tissue culture 1 Low dose effects of mercuric oxide. Zeitschrift fur Naturforschung 30 643-649. 

Figure 11.4 Nonconventional dose-response relationship involving low-dose effects and compensation. (I) True initiation of the response followed by a compensatory response that returns the effects to the 0% level. (II) A negative response due to overcompensation (hormesis) followed by recovery to the 0% effect level. (Ill) The standard sigmoidal dose-response relationship.

Several mathematical models have been proposed for calculating from high-dose experiment data to predicted low-dose effects.72 82 l10 124 271+ 303 395 when only high-dose data are available, it is usually possible to fit several different plausible curves to the data, and these may lead to different predictions of effects of exposure at low doses. 

However, depending on the shape of the dose-response curve, the low-dose effect may be very small. 

FIGURE 6-1 A possible dose-response curve. A singledose experiment at dose Dj would yield approximately the correct prediction of the low-dose effect, whereas an experiment at dose D2 would lead to an underestimate. 

Vom Saal, F.S., Huges, C. An extensive new literature concerning low-dose effects of bisphenol A shows the need for a new risk assessment. Environ. Health Perspect. 113, 926-933 (2005)... 

In the review by Papirmeister et al. (1991), it was noted that sulfur mustard-induced cytotoxicity is dose dependent and that DNA appeared to be more sensitive to mustard-induced alkylation than are other cellular constituents. The low-dose effects of sulfur mustard are characterized by gen-otoxicity and inhibition of mitosis. The loss of cellular reproduction may be due to bifunctional alkylation that ultimately prevents normal DNA replication. It was hypothesized that monofunctional DNA damage might be responsible for low-dose mutagenic and possibly carcinogenic effects. 

High doses of OPs cause similar toxic effects independent of the identity of the OPs. However, low-dose effects are not identieal for all OPs (Moser, 1995). For example, a low dose of fenthion decreased motor aetivity in rats by 86% but did not alter the tail-pinch response, whereas a low dose of parathion did not affect motor activity but did decrease the... 

There is some controversy over the possibility of low dose effects of BPA. Researchers who have published results suggesting that there is a low dose effect of BPA assert that the dose-response relationship is nonmonotonic , which means that health effects may only be observed at low doses while much higher doses result in no effects. However, these studies are weakened by lack of reproducibility and statistical robustness. Furthermore, there is considerable... 

Kaiser J (2000) Endocrine disrupters. Panel cautiously confirms low-dose effects. Science 290(5492) 695-697. 

The current mode of extrapolating high-dose to low-dose effects is erroneous for both chemicals and radiation. Safe levels of exposure exist. The public has been needlessly frightened and deceived, and hundreds of billion of dollars wasted (2). 

Extrapolation from measured high-dose effects to determine low-dose effects. 

More recently, issues of low-dose effects on hormonal systems, particularly reproductive and genetic end-points, have brought into question the adequacy of current toxicity test procedures. These issues have significant implications for chemicals legislation that will have an impact on the chemicals industry and on society. 

Smirnova L, Sittka A, Luch A (2012) On the role of low-dose effects and epigenetics in toxicology. EXS 101 499-550... 

Grawe, I., Abramsson-Zetterba-g, L., and Zetterberg, G. (1998). Low dose effects of chemicals as assessed by the flow cytometric in vivo micronucleus assay. Mutat Res 405, 199-208. 

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