Predictive Value of In Vitro Systems for Neurotoxicity Risk Assessment

2004 ◽  
pp. 29-40
Author(s):  
Marion Ehrich ◽  
David C. Dorman
Keyword(s):  
Risk Assessment ◽  
Predictive Value ◽  
In Vitro Systems

scholarly journals Key Challenges and Opportunities Associated with the Use of In Vitro Models to Detect Human DILI: Integrated Risk Assessment and Mitigation Plans

2016 ◽  
Vol 2016 ◽  
pp. 1-20 ◽  
Author(s):  
Franck A. Atienzar ◽  
Eric A. Blomme ◽  
Minjun Chen ◽  
Philip Hewitt ◽  
J. Gerry Kenna ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Data Interpretation ◽  
In Vitro Models ◽  
Drug Induced ◽  
Integrated Risk Assessment ◽  
Integrated Risk ◽  
Challenges And Opportunities ◽  
Black Box Warnings ◽  
In Vitro Systems

Drug-induced liver injury (DILI) is a major cause of late-stage clinical drug attrition, market withdrawal, black-box warnings, and acute liver failure. Consequently, it has been an area of focus for toxicologists and clinicians for several decades. In spite of considerable efforts, limited improvements in DILI prediction have been made and efforts to improve existing preclinical models or develop new test systems remain a high priority. While prediction of intrinsic DILI has improved, identifying compounds with a risk for idiosyncratic DILI (iDILI) remains extremely challenging because of the lack of a clear mechanistic understanding and the multifactorial pathogenesis of idiosyncratic drug reactions. Well-defined clinical diagnostic criteria and risk factors are also missing. This paper summarizes key data interpretation challenges, practical considerations, model limitations, and the need for an integrated risk assessment. As demonstrated through selected initiatives to address other types of toxicities, opportunities exist however for improvement, especially through better concerted efforts at harmonization of current, emerging and novel in vitro systems or through the establishment of strategies for implementation of preclinical DILI models across the pharmaceutical industry. Perspectives on the incorporation of newer technologies and the value of precompetitive consortia to identify useful practices are also discussed.

Dental optical coherence tomography: a comparison of two in vitro systems

1999 ◽  
Vol 29 (2) ◽  
pp. 85-89 ◽  
Author(s):  
L L Otis ◽  
B W Colston ◽  
M J Everett ◽  
H Nathel
Keyword(s):  
Optical Coherence Tomography ◽  
Optical Coherence ◽  
In Vitro Systems

Body Mass Index, Follicle-Stimulating Hormone and their Predictive Value in vitro Fertilization

2018 ◽  
Vol 69 (7) ◽  
pp. 1842-1845
Author(s):  
Lavinia Stelea ◽  
Izabella Petre ◽  
Marius Craina ◽  
Brigitha Vlaicu ◽  
Alina Sisu ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Risk Factor ◽  
In Vitro Fertilization ◽  
Body Mass ◽  
Predictive Value ◽  
Follicle Stimulating Hormone ◽  
Vitro Fertilization ◽  
Weight Problems ◽  
Fertility Disorder

The aim of this study was to determine if body mass can be considered a risk factor for infertility, and if we can find any correlations between the age values and the FSH and estradiol values, and between the BMI values and the FSH and estradiol values. Our whole sample contains 100 patients splinted in two groups (pregnant patients N1=57 subjects, 57%, and not � pregnant patients N1=43 subjects,43%). In the first part we conducted our analysis on the whole group and after that we focused the analysis on the two groups and we made some comparisons between the groups. We obtained a medium, extremely significant correlation in all scenarios between the age and the FSH values. This is the best association from all the cases which we tested. In all twelve cases we have a positive correlation (r ] 0). As well, we obtained that a BMI value higher than 25can be considered a risk factor for obtaining a pregnancy (p[0.05, RR ] 1, OR]1) . Our study shows that women who have weight problems have much less chances of conceiving a baby, even if they ovulate normally. The risk of infertility increases proportionally to the extra pounds. Irregular ovulation in women is the most common fertility disorder due to obesity disease.

Uncertainties Associated with Assessing the Risk of an Endocrine Active Substance in the Canadian Environment

2001 ◽  
Vol 36 (2) ◽  
pp. 319-330 ◽  
Author(s):  
Mark Servos ◽  
Don Bennie ◽  
Kent Burnison ◽  
Philippa Cureton ◽  
Nicol Davidson ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Endocrine Disruption ◽  
Endocrine System ◽  
Problem Formulation ◽  
Normal Function ◽  
Weight Of Evidence ◽  
Biological Responses ◽  
Low Concentrations ◽  
Multigenerational Effects

Abstract A number of biological responses and multigenerational effects, mediated through the disruption of endocrine systems, have been observed in biota exposed to relatively low concentrations of environmental contaminants. These types of responses need to be considered within a weight of evidence approach in our risk assessment and risk management frameworks. However, including endocrine responses in an environmental risk assessment introduces a number of uncertainties that must be considered. A risk assessment of nonylphenol and nonylphenol polyethoxylates (NP/NPE) is used as a case study to demonstrate the sources and magnitude of some of the uncertainties associated with using endocrine disruption as an assessment endpoint. Even with this relatively well studied group of substances, there are substantial knowledge gaps which contribute to the overall uncertainties, limiting the interpretation within the risk assessment. The uncertainty of extrapolating from in vitro or biochemical responses to higher levels of organization or across species is not well understood. The endocrine system is very complex and chemicals can interact or interfere with the normal function of endocrine systems in a number of ways (e.g., receptors, hormones) which may or may not result in an adverse responses in the whole organism. Using endocrine responses can lead to different conclusions than traditional endpoints due to a variety of factors, such as differences in relative potencies of chemicals for specific endpoints (e.g., receptor binding versus chronic toxicity). The uncertainties can also be considerably larger and the desirability of using endocrine endpoints should be carefully evaluated. Endocrine disruption is a mode of action and not a functional endpoint and this needs to be considered carefully in the problem formulation stage and the interpretation of the weight of evidence.

In Vitro Toxicology Methods in Risk Assessment

1996 ◽  
Vol 24 (3) ◽  
pp. 325-331
Author(s):  
Iain F. H. Purchase
Keyword(s):  
Risk Assessment ◽  
Hazard Assessment ◽  
Human Health Risk ◽  
In Vitro Test ◽  
In Vitro Methods ◽  
New Concepts ◽  
Vitro Test

The title of this paper is challenging, because the question of how in vitro methods and results contribute to human health risk assessment is rarely considered. The process of risk assessment usually begins with hazard assessment, which provides a description of the inherent toxicological properties of the chemical. The next step is to assess the relevance of this to humans, i.e. the human hazard assessment. Finally, information on exposure is examined, and risk can then be assessed. In vitro methods have a limited, but important, role to play in risk assessment. The results can be used for classification and labelling; these are methods of controlling exposure, analogous to risk assessment, but without considering exposure. The Ames Salmonella test is the only in vitro method which is incorporated into regulations and used widely. Data from this test can, at best, lead to classification of a chemical with regard to genotoxicity, but cannot be used for classification and labelling on their own. Several in vitro test systems which assess the topical irritancy and corrosivity of chemicals have been reasonably well validated, and the results from these tests can be used for classification. The future development of in vitro methods is likely to be slow, as it depends on the development of new concepts and ideas. The in vivo methods which currently have reasonably developed in vitro alternatives will be the easiest to replace. The remaining in vivo methods, which provide toxicological information from repeated chronic dosing, with varied endpoints and by mechanisms which are not understood, will be more difficult to replace.

Use of Toxicokinetics in Risk Assessment Based on In Vitro Data

1993 ◽  
Vol 21 (2) ◽  
pp. 173-180
Author(s):  
Gunnar Johanson
Keyword(s):  
Risk Assessment ◽  
Whole Body ◽  
External Exposure ◽  
Target Dose ◽  
Toxic Response ◽  
Route Of Exposure ◽  
Vitro Data ◽  
In Vitro Data

This presentation addresses some aspects of the methodology, advantages and problems associated with toxicokinetic modelling based on in vitro data. By using toxicokinetic models, particularly physiologically-based ones, it is possible, in principle, to describe whole body toxicokinetics, target doses and toxic effects from in vitro data. Modelling can be divided into three major steps: 1) to relate external exposure (applied dose) of xenobiotic to target dose; 2) to establish the relationship between target dose and effect (in vitro data, e.g. metabolism in microsomes, partitioning in tissue homogenates, and toxicity in cell cultures, are useful in both steps); and 3) to relate external exposure to toxic effect by combining the first two steps. Extrapolations from in vitro to in vivo, between animal and man, and between high and low doses, can easily be carried out by toxicokinetic simulations. In addition, several factors that may affect the toxic response by changing the target dose, such as route of exposure and physical activity, can be studied. New insights concerning the processes involved in toxicity often emerge during the design, refinement and validation of the model. The modelling approach is illustrated by two examples: 1) the carcinogenicity of 1,3-butadiene; and 2) the haematotoxicity of 2-butoxyethanol. Toxicokinetic modelling is an important tool in toxicological risk assessment based on in vitro data. Many factors, some of which can, and should be, studied in vitro, are involved in the expression of toxicity. Successful modelling depends on the identification and quantification of these factors.

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