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Reference: Fryer, HR and Mclean, AR, (2011). There is no safe dose of prions. PloS one, 6 (8), e23664.Citable link to this page:


There is no safe dose of prions.

Abstract: Understanding the circumstances under which exposure to transmissible spongiform encephalopathies (TSEs) leads to infection is important for managing risks to public health. Based upon ideas in toxicology and radiology, it is plausible that exposure to harmful agents, including TSEs, is completely safe if the dose is low enough. However, the existence of a threshold, below which infection probability is zero has never been demonstrated experimentally. Here we explore this question by combining data and mathematical models that describe scrapie infections in mice following experimental challenge over a broad range of doses. We analyse data from 4338 mice inoculated at doses ranging over ten orders of magnitude. These data are compared to results from a within-host model in which prions accumulate according to a stochastic birth-death process. Crucially, this model assumes no threshold on the dose required for infection. Our data reveal that infection is possible at the very low dose of a 1000 fold dilution of the dose that infects half the challenged animals (ID50). Furthermore, the dose response curve closely matches that predicted by the model. These findings imply that there is no safe dose of prions and that assessments of the risk from low dose exposure are right to assume a linear relationship between dose and probability of infection. We also refine two common perceptions about TSE incubation periods: that their mean values decrease linearly with logarithmic decreases in dose and that they are highly reproducible between hosts. The model and data both show that the linear decrease in incubation period holds only for doses above the ID50. Furthermore, variability in incubation periods is greater than predicted by the model, not smaller. This result poses new questions about the sources of variability in prion incubation periods. It also provides insight into the limitations of the incubation period assay.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's version Funder: Oxford Martin School   Funder: Foods Standards Agency   Notes:Copyright 2011 Fryer, McLean. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Bibliographic Details

Publisher: Public Library of Science

Publisher Website:

Journal: PloS onesee more from them

Publication Website:

Issue Date: 2011

pages:Article: e23664


Urn: uuid:e3674180-2f18-4618-ba1d-edc924cde043

Source identifier: 209556

Eissn: 1932-6203


Issn: 1932-6203 Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: Animals Humans Mice Prion Diseases Scrapie Stochastic Processes Dose-Response Relationship, Drug Prions Algorithms Models, Biological Public Health Tiny URL: pubs:209556


Autor: Fryer, HR - - - Mclean, AR - institutionUniversity of Oxford Oxford, MPLS, Zoology - - - - Bibliographic Details Publisher: Publi



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