USEPA Efforts in Harmonization of Acute Toxicity Test Guidelines with OECD

1992 ◽  
Vol 11 (3) ◽  
pp. 285-291 ◽  
Author(s):  
Mary C. Henry
Keyword(s):  
Pollution Prevention ◽  
Screening Methods ◽  
Animal Testing ◽  
Oral Toxicity ◽  
Dermal Irritation ◽  
Structure Activity ◽  
Pain And Suffering ◽  
Development And Validation ◽  
Further Development

The USEPA, as a member of the OECD, is involved in the review of OECD guidelines and OECD's plans for revisions. The guidelines reviewed to date include: acute oral toxicity, eye and dermal irritation/corrosion, and skin sensitization. The revisions to the guidelines have emphasized reductions in animal usage in lab testing, and refinements which reduce/eliminate pain and suffering of animals. Screening methods, such as use of structure-activity relationships and physicochemical properties of test substances, which would eliminate chemicals that did not require animal testing, or sharply reduce the number of animals required for testing, were also recommended for some guidelines. In vitro methods were also examined as screens to eliminate severely toxic chemicals, but most of these methods still require further development and validation. The proposed revisions are discussed in detail in this report. This report has been reviewed by the Environmental Protection Agency's Office of Pollution Prevention and Toxics, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency.

In Vitro Assessment of Skin Irritation Potential of Surfactant-based Formulations by Using a 3-D Skin Reconstructed Tissue Model and Cytokine Response

2016 ◽  
Vol 44 (6) ◽  
pp. 523-532 ◽  
Author(s):  
Russel M. Walters ◽  
Lisa Gandolfi ◽  
M. Catherine Mack ◽  
Michael Fevola ◽  
Katharine Martin ◽  
...  
Keyword(s):  
Raw Materials ◽  
Skin Irritation ◽  
Clinical Testing ◽  
Personal Care ◽  
Animal Testing ◽  
Repeated Testing ◽  
Dermal Irritation ◽  
Testing Programme ◽  
Skin Irritation Test

The personal care industry is focused on developing safe, more efficacious, and increasingly milder products, that are routinely undergoing preclinical and clinical testing before becoming available for consumer use on skin. In vitro systems based on skin reconstructed equivalents are now established for the preclinical assessment of product irritation potential and as alternative testing methods to the classic Draize rabbit skin irritation test. We have used the 3-D EpiDerm™ model system to evaluate tissue viability and primary cytokine interleukin-1α release as a way to evaluate the potential dermal irritation of 224 non-ionic, amphoteric and/or anionic surfactant-containing formulations, or individual raw materials. As part of our testing programme, two representative benchmark materials with known clinical skin irritation potential were qualified through repeated testing, for use as references for the skin irritation evaluation of formulations containing new surfactant ingredients. We have established a correlation between the in vitro screening approach and clinical testing, and are continually expanding our database to enhance this correlation. This testing programme integrates the efforts of global manufacturers of personal care products that focus on the development of increasingly milder formulations to be applied to the skin, without the use of animal testing.

scholarly journals The use of Bayesian methodology in the development and validation of a tiered assessment approach towards prediction of rat acute oral toxicity

2022 ◽  
Author(s):  
James W. Firman ◽  
Mark T. D. Cronin ◽  
Philip H. Rowe ◽  
Elizaveta Semenova ◽  
John E. Doe
Keyword(s):  
In Silico ◽  
Oral Toxicity ◽  
New Approach ◽  
Combining Data ◽  
Assessment Approach ◽  
In Vivo Testing ◽  
Degree Of Confidence ◽  
Development And Validation

AbstractThere exists consensus that the traditional means by which safety of chemicals is assessed—namely through reliance upon apical outcomes obtained following in vivo testing—is increasingly unfit for purpose. Whilst efforts in development of suitable alternatives continue, few have achieved levels of robustness required for regulatory acceptance. An array of “new approach methodologies” (NAM) for determining toxic effect, spanning in vitro and in silico spheres, have by now emerged. It has been suggested, intuitively, that combining data obtained from across these sources might serve to enhance overall confidence in derived judgment. This concept may be formalised in the “tiered assessment” approach, whereby evidence gathered through a sequential NAM testing strategy is exploited so to infer the properties of a compound of interest. Our intention has been to provide an illustration of how such a scheme might be developed and applied within a practical setting—adopting for this purpose the endpoint of rat acute oral lethality. Bayesian statistical inference is drawn upon to enable quantification of degree of confidence that a substance might ultimately belong to one of five LD50-associated toxicity categories. Informing this is evidence acquired both from existing in silico and in vitro resources, alongside a purposely-constructed random forest model and structural alert set. Results indicate that the combination of in silico methodologies provides moderately conservative estimations of hazard, conducive for application in safety assessment, and for which levels of certainty are defined. Accordingly, scope for potential extension of approach to further toxicological endpoints is demonstrated.

Limitations on the Reliability of In Vitro Predictive Toxicity Models to Predict Pulmonary Toxicity in Rodents

2016 ◽  
Author(s):  
Jeremy M. Gernand
Keyword(s):  
Meta Analysis ◽  
Information Value ◽  
Screening Tests ◽  
In Vitro Tests ◽  
Screening Methods ◽  
Toxicity Screening ◽  
Animal Testing ◽  
Risk Models

Given the rapidly proliferating varieties of nanomaterials and ongoing concerns that these novel materials may pose emerging occupational and environmental risks, combined with the possibility that each variety might pose a different unique risk due to the unique combination of material properties, researchers and regulators have been searching for methods to identify hazards and prioritize materials for further testing. While several screening tests and toxic risk models have been proposed, most have relied on cellular-level in vitro data. This foundation enables answers to be developed quickly for any material, but it is yet unclear how this information may translate to more realistic exposure scenarios in people or other more complex animals. A quantitative evaluation of these models or at least the inputs variables to these models in the context of rodent or human health outcomes is necessary before their classifications may be believed for the purposes of risk prioritization. This paper presents the results of a machine learning enabled meta-analysis of animal studies attempting to use significant descriptors from in vitro nanomaterial risk models to predict the relative toxicity of nanomaterials following pulmonary exposures in rodents. A series of highly non-linear random forest models (each made up of an ensemble of 1,000 regression tree models) were created to assess the maximum possible information value of the in vitro risk models and related methods of describing nanomaterial variants and their toxicity in rat and mouse experiments. The variety of chemical descriptors or quantitative chemical property measurements such as bond strength, surface charge, and dissolution potential, while important in describing observed differences with in vitro experiments, proved to provide little indication of the relative magnitude of inflammation in rodents (explained variance amounted to less than 32%). Important factors in predicting rodent pulmonary inflammation such as primary particle size and chemical type demonstrate that there are critical differences between these two toxicity assays that cannot be captured by a series of in vitro tests alone. Predictive models relying primarily on these descriptors alone explained more than 62% of the variance of the short term in vivo toxicity results. This means that existing proposed nanomaterial toxicity screening methods are inadequate as they currently stand, and either the community must be content with the slower and more expensive animal testing to evaluate nanomaterial risks, or further conceptual development of improved alternative in vitro screening methodologies is necessary before manufacturers and regulators can rely on them to promote safer use of nanotechnology.

Antibody Screening Results for Anti-Nucleocapsid Antibodies Towards the Development of a SARS-CoV-2 Nucleocapsid Protein Antigen Detecting Lateral Flow Assay

2021 ◽  
Author(s):  
David Cate ◽  
Helen Hsieh ◽  
Veronika Glukhova ◽  
Joshua D Bishop ◽  
H Gleda Hermansky ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Point Of Care ◽  
Lateral Flow ◽  
Screening Methods ◽  
Antibody Screening ◽  
Liquid Handling ◽  
Large Numbers ◽  
Accurate Performance ◽  
Further Development ◽  
Assay Conditions

<p></p><p>The global COVID-19 pandemic has created an urgent demand for large numbers of inexpensive, accurate, rapid, point-of-care diagnostic tests. Analyte-based assays are suitably inexpensive and can be rapidly mass-produced, but for sufficiently accurate performance they require highly optimized antibodies and assay conditions. We used an automated liquid handling system, customized to handle arrays of lateral flow immunoassay (LFA) tests in a high-throughput screen, to identify anti-nucleocapsid antibodies that will perform optimally in an LFA. We tested 1021 anti-nucleocapsid antibody pairs as LFA capture and detection reagents with the goal of highlighting pairs that have the greatest affinity for unique epitopes of the nucleocapsid protein of SARS-CoV-2 within the LFA format. In contrast to traditional antibody screening methods (e.g., ELISA, bio-layer interferometry), the method described here integrates real-time reaction kinetics with transport in, and immobilization directly onto, nitrocellulose. We have identified several candidate antibody pairs that are suitable for further development of an LFA for SARS-CoV-2.</p><p></p>

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