Modeling of uncertainty associated with dose-response curves as applied for probabilistic risk assessment in laser safety

2001 ◽  
Author(s):  
Karl Schulmeister ◽  
Gerald Sonneck ◽  
Herbert Hoedlmoser ◽  
Frank Rattay ◽  
John Mellerio ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Dose Response ◽  
Probabilistic Risk Assessment ◽  
Response Curves ◽  
Laser Safety ◽  
Dose Response Curves ◽  
Probabilistic Risk

scholarly journals Application of a Framework for Grouping and Mixtures Toxicity Assessment of PFAS: A Closer Examination of Dose-Additivity Approaches

2020 ◽  
Author(s):  
Philip E Goodrum ◽  
Janet K Anderson ◽  
Anthony L Luz ◽  
Graham K Ansell
Keyword(s):  
Risk Assessment ◽  
Carboxylic Acids ◽  
Dose Response ◽  
Sulfonic Acid ◽  
Hazard Index ◽  
Mixture Toxicity ◽  
Response Curves ◽  
Toxicity Studies ◽  
Data Gaps ◽  
Dose Response Curves

Abstract Environmental occurrence and biomonitoring data for per- and polyfluoroalkyl substances (PFAS) demonstrate that humans are exposed to mixtures of PFAS. This article presents a new and systematic analysis of available PFAS toxicity study data using a tiered mixtures risk assessment framework consistent with United States and international mixtures guidance. The lines of evidence presented herein include a critique of whole mixture toxicity studies and analysis of dose-response models based on data from subchronic oral toxicity studies in rats. Based on available data to-date, concentration addition and relative potency factor methods are found to be inappropriate due to differences among sensitive effects and target organ potencies and noncongruent dose-response curves for the same effect endpoints from studies using the same species and protocols. Perfluorooctanoic acid and perfluorooctane sulfonic acid lack a single mode of action or molecular initiating event and our evaluation herein shows they also have noncongruent dose-response curves. Dose-response curves for long-chain perfluoroalkyl sulfonic acids (PFSAs) also significantly differ in shapes of the curves from short-chain PFSAs and perfluoroalkyl carboxylic acids evaluated, and additional differences are apparent when curves are evaluated based on internal or administered dose. Following well-established guidance, the hazard index method applied to perfluoroalkyl carboxylic acids and PFSAs grouped separately is the most appropriate approach for conducting a screening level risk assessment for nonpolymeric PFAS mixtures, given the current state-of-the science. A clear presentation of assumptions, uncertainties, and data gaps is needed before dose-additivity methods, including hazard index , are used to support risk management decisions. Adverse outcome pathway(s) and mode(s) of action information for perfluorooctanoic acid and perfluorooctane sulfonic acid and for other nonpolymer PFAS are key data gaps precluding more robust mixtures methods. These findings can guide the prioritization of future studies on single chemical and whole mixture toxicity studies.

scholarly journals A critique of the use of hormesis in risk assessment

2005 ◽  
Vol 24 (5) ◽  
pp. 249-253 ◽  
Author(s):  
Kirk T Kitchin ◽  
J Wanzer Drane
Keyword(s):  
Risk Assessment ◽  
Dose Response ◽  
A Priori ◽  
Assessment Process ◽  
Data Sets ◽  
Response Curves ◽  
Dose Response Curves ◽  
Post Hoc ◽  
Public Health Protection ◽  
Default Assumption

There are severe problems and limitations with the use of hormesis as the principal dose-response default assumption in risk assessment. These problems and limitations include: (a) unknown prevalence of hormetic doseresponse curves; (b) random chance occurrence of hormesis and the shortage of data on the repeatability of hormesis; (c) unknown degree of generalizability of hormesis; (d) there are dose-response curves that are not hormetic, therefore hormesis cannot be universally generalized; (e) problems of post hoc rather than a priori hypothesis testing; (f) a possible large problem of ‘false positive’ hormetic data sets which have not been extensively replicated; (g) the ‘mechanism of hormesis’ is not understood at a rigorous scientific level; (h) in some cases hormesis may merely be the overall sum of many different mechanisms and many different dose-response curves - some beneficial and some toxic. For all of these reasons, hormesis should not now be used as the principal dose-response default assumption in risk assessment. At this point, it appears that hormesis is a long way away from common scientific acceptance and wide utility in biomedicine and use as the principal default assumption in a risk assessment process charged with ensuring public health protection.

Dose-response Curves in the Fibrin Plate Assay Fibrinolytic Activity of Proteases

1974 ◽  
Vol 32 (02/03) ◽  
pp. 356-365 ◽  
Author(s):  
F Haverkate ◽  
D. W Traas
Keyword(s):  
Dose Response ◽  
Fibrinolytic Activity ◽  
Enzyme Concentration ◽  
Response Curves ◽  
Agar Gel ◽  
Porcine Tissue ◽  
Plate Assay ◽  
Fibrin Plate ◽  
Different Types ◽  
Dose Response Curves

SummaryIn the fibrin plate assay different types of relationships between the dose of applied proteolytic enzyme and the response have been previously reported. This study was undertaken to determine whether a generally valid relationship might exist.Trypsin, chymotrypsin, papain, the plasminogen activator urokinase and all of the microbial proteases investigated, including brinase gave a linear relationship between the logarithm of the enzyme concentration and the diameter of the circular lysed zone. A similar linearity of dose-response curves has frequently been found by investigators who used enzyme plate assays with substrates different from fibrin incorporated in an agar gel. Consequently, it seems that this linearity of dose-response curves is generally valid for the fibrin plate assay as well as for other enzyme plate bioassays.Both human plasmin and porcine tissue activator of plasminogen showed deviations from linearity of semi-logarithmic dose-response curves in the fibrin plate assay.

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