Leveraging the new predictive toxicology paradigm: alternative testing strategies in regulatory decision-making

2016 ◽  
Vol 3 (6) ◽  
pp. 1380-1395 ◽  
Author(s):  
Timothy Malloy ◽  
Elizabeth Beryt
Keyword(s):  
Safety Data ◽  
Health And Safety ◽  
Risk Prevention ◽  
Toxicity Data ◽  
Predictive Toxicology ◽  
Regulatory Decision ◽  
Testing Strategies ◽  
Comprehensive Health ◽  
Alternative Testing ◽  
Alternative Testing Strategies

Although toxicity data is critical to effective risk prevention and management, comprehensive health and safety data is not available for the vast majority of chemicals in use today.

scholarly journals The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

2020 ◽  
Vol 21 (7) ◽  
pp. 2387 ◽  
Author(s):  
Rong-Jane Chen ◽  
Yu-Ying Chen ◽  
Mei-Yi Liao ◽  
Yu-Hsuan Lee ◽  
Zi-Yu Chen ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Health And Safety ◽  
Adverse Outcomes ◽  
Testing Strategy ◽  
C Elegans ◽  
Testing Strategies ◽  
Alternative Testing ◽  
Alternative Testing Strategies

Nanotechnology has rapidly promoted the development of a new generation of industrial and commercial products; however, it has also raised some concerns about human health and safety. To evaluate the toxicity of the great diversity of nanomaterials (NMs) in the traditional manner, a tremendous number of safety assessments and a very large number of animals would be required. For this reason, it is necessary to consider the use of alternative testing strategies or methods that reduce, refine, or replace (3Rs) the use of animals for assessing the toxicity of NMs. Autophagy is considered an early indicator of NM interactions with cells and has been recently recognized as an important form of cell death in nanoparticle-induced toxicity. Impairment of autophagy is related to the accelerated pathogenesis of diseases. By using mechanism-based high-throughput screening in vitro, we can predict the NMs that may lead to the generation of disease outcomes in vivo. Thus, a tiered testing strategy is suggested that includes a set of standardized assays in relevant human cell lines followed by critical validation studies carried out in animals or whole organism models such as C. elegans (Caenorhabditis elegans), zebrafish (Danio rerio), and Drosophila (Drosophila melanogaster)for improved screening of NM safety. A thorough understanding of the mechanisms by which NMs perturb biological systems, including autophagy induction, is critical for a more comprehensive elucidation of nanotoxicity. A more profound understanding of toxicity mechanisms will also facilitate the development of prevention and intervention policies against adverse outcomes induced by NMs. The development of a tiered testing strategy for NM hazard assessment not only promotes a more widespread adoption of non-rodent or 3R principles but also makes nanotoxicology testing more ethical, relevant, and cost- and time-efficient.

Effects of Population Structure and Admixture on Exact Tests for Association Between Loci

Genetics ◽  
2003 ◽  
Vol 164 (1) ◽  
pp. 381-387
Author(s):  
B Law ◽  
J S Buckleton ◽  
C M Triggs ◽  
B S Weir
Keyword(s):  
Population Subdivision ◽  
Data Sets ◽  
Multilocus Genotype ◽  
Test Statistic ◽  
Exact Test ◽  
Testing Strategies ◽  
Different Populations ◽  
Alternative Testing ◽  
Sparse Data Sets ◽  
Alternative Testing Strategies

Abstract The probability of multilocus genotype counts conditional on allelic counts and on allelic independence provides a test statistic for independence within and between loci. As the number of loci increases and each sampled genotype becomes unique, the conditional probability becomes a function of total heterozygosity. In that case, it does not address between-locus dependence directly but only indirectly through detection of the Wahlund effect. Moreover, the test will reject the hypothesis of allelic independence only for small values of heterozygosity. Low heterozygosity is expected for population subdivision but not for population admixture. The test may therefore be inappropriate for admixed populations. If individuals with parents in two different populations are always considered to belong to one of the populations, then heterozygosity is increased in that population and the exact test should not be used for sparse data sets from that population. If such a case is suspected, then alternative testing strategies are suggested.

scholarly journals The role of alternative testing strategies in environmental risk assessment of engineered nanomaterials

2017 ◽  
Vol 4 (2) ◽  
pp. 292-301 ◽  
Author(s):  
Rune Hjorth ◽  
Patricia A. Holden ◽  
Steffen Foss Hansen ◽  
Benjamin P. Colman ◽  
Khara Grieger ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Environmental Risk ◽  
Environmental Risk Assessment ◽  
Engineered Nanomaterials ◽  
Animal Testing ◽  
Test Systems ◽  
Testing Strategies ◽  
Alternative Testing ◽  
Alternative Testing Strategies

Within toxicology there is a pressure to find new test systems to replace, reduce and refine animal testing. In nanoecotoxicology this raises a number of questions.

Rational Deterrence Theory Revisited: A Progress Report

1995 ◽  
Vol 28 (3) ◽  
pp. 403-436 ◽  
Author(s):  
Frank P. Harvey
Keyword(s):  
Decision Makers ◽  
Testing Strategy ◽  
Testing Strategies ◽  
Wide Range ◽  
Tremendous Amount ◽  
Alternative Testing ◽  
Cumulative Knowledge ◽  
Historical Accounts ◽  
Time And Energy ◽  
Alternative Testing Strategies

AbstractProgress in the debate over rational deterrence has always depended on the ability of scholars to identify a body of evidence that would be appropriate for testing a wide range of propositions derived from the theory. Notwithstanding the tremendous amount of time and energy spent on producing a suitable list of cases, and several noteworthy surveys of the literature, cumulative knowledge about deterrence, both as a theory and as a strategy, remains elusive. It still is unclear whether decision makers have acted according to the logic derived from standard applications of the theory. Moreover, the most prominent testing strategy, originally designed by Paul Huth and Bruce Russett, and later criticized and revised by Richard Ned Lebow and Janice Gross Stein, continues to be plagued by ongoing disputes over methods and case listings. Although debates over the accuracy of historical accounts are constructive, lingering divisions over coding of deterrence successes and failures have become counterproductive, primarily because each side has produced evidence to support their interpretation of events. Very little effort, by comparison, has been directed towards (a) developing alternative testing strategies that lie outside the success/failure framework, or (b) looking at a wider range of propositions derived from the theory. This analysis attempts the task, analyzing in the aggregate 28 cases of superpower rivalry.

scholarly journals The effect of alternative testing strategies and bio-exclusion practices on Johne’s disease risk in test-negative herds

2013 ◽  
Vol 96 (3) ◽  
pp. 1581-1590 ◽  
Author(s):  
S.J. More ◽  
E.S.G. Sergeant ◽  
S. Strain ◽  
W. Cashman ◽  
Kevin Kenny ◽  
...  
Keyword(s):  
Disease Risk ◽  
Johne's Disease ◽  
Johne’S Disease ◽  
Testing Strategies ◽  
Alternative Testing ◽  
Alternative Testing Strategies
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