Alternatives in Toxicology

Spotlights
U.S. and International Acceptance of Alternative Methods, 1998-2012

This table presents a chronological list of alternative test methods.
Guidance for Industry – Pyrogen and Endotoxins Testing: Questions and Answers (PDF | 174 KB)

DHHS. Food and Drug Administration.

June 2012- Includes guidance regarding the use of alternatives to the rabbit pyrogen test (RPT) and the bacterial endotoxins test (BET) for detecting pyrogens in pharmaceuticals and other products. Examples of alternative assays cited include the recombinant horseshoe crab Factor C asssay and monocyte activation type pyrogen tests (MATs).
Seurat-1: Towards the replacement of in vivo repeated dose systemic toxicity testing

The first step in a European research initiative to address the long term strategic target of "Safety Evaluation Ultimately Replacing Animal Testing (SEURAT)".
NTP Requests Information on Assays and Approaches for Neurotoxicity Screening (PDF | 197.3 KB)

Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM)

The National Toxicology Program (NTP) requests information on medium- or high-throughput technologies/assay systems, which allow for the batch screening of compounds (e.g., 25-50) in biochemical- or cell-based assays or alternative (non-rodent) animal models, that might be used to prioritize compounds for in vivo neurotoxicity testing.

The deadline for receipt of information is April 30. More information about the request for information was published April 1 in the Federal Register.
ICCVAM Evaluation of the Use of the LLNA for Potency Categorization

Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM)

The murine local lymph node assay (LLNA) is a stand-alone test method for assessing the hazard potential of a test substance to induce allergic contact dermatitis (ACD). ICCVAM evaluated the use of the LLNA for potency categorization of chemicals causing ACD in humans. ICCVAM concluded that the LLNA can be used to categorize substances as strong sensitizers (Globally Harmonized System of Classification and Labelling of Chemicals Subcategory 1A), although it cannot be considered a stand-alone assay to categorize substances as other sensitizers (Globally Harmonized System of Classification and Labelling of Chemicals Subcategory 1B). Strong sensitizers are those substances considered to have a significant potential for causing hypersensitivity.
TSAR: Tracking System for Alternative test methods Review, Validation and Approval in the Context of EU Regulations on Chemicals

European Commission. Joint Research Centre. Institute for Health and Consumer Protection.

A tool to provide information on the status of alternative methods as they progress from scientific protocols to validation for being used in a regulatory context.

Access: free online

ICCVAM Recommendations to Provide for More Humane Eye Safety Testing (PDF | 149KB)

Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM)

Four test method evaluation reports are now available that provide recommendations for performing eye safety testing more humanely and for developing and using non-animal test methods and strategies.
Summary: International Workshop on Alternative Methods for Leptospira Vaccine Potency Testing

Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM)

A summary of the September 2012 "International Workshop on Alternative Methods for Leptospira Vaccine Potency Testing: State of the Science and the Way Forward.” This workshop brought together international scientific experts from government, industry, and academia to review available methods and approaches for Leptospira vaccine potency testing and recent advances in science and technology.
Reduced Murine Local Lymph Node Assay

The National Toxicology Program - Interagency Center for the Evaluation of Alternative Toxicological Methods

The National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), on behalf of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), announces recommendations for the reduced murine Local Lymph Node Assay (LLNA).
Dots part of the logo image for AltTox.org AltTox.org

Humane Society of the United States and Proctor & Gamble.

The goal of this web site is to advance non-animal methods of toxicity testing through online discussion and information exchange.
Final Recommendations on In Vitro Test Methods for Detecting Ocular Corrosives and Severe Irritants

The National Toxicology Program - Interagency Center for the Evaluation of Alternative Toxicological Methods

The National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), on behalf of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), announces the availability of this report that describes and evaluates four ocular toxicity test methods evaluated by ICCVAM.
Guidance Document on Using In Vitro Data to Estimate In Vivo Starting Doses for Acute Toxicity

DHHS. NIH. National Institute of Environmental Health Sciences. National Institutes of Health.

Describes how to use in vitro cytotoxicity tests to estimate starting doses for acute oral lethality assays.
Routine Use of Topical Anesthetics, Systemic Analgesics, and Humane Endpoints to Avoid or Minimize Pain and Distress in Ocular Safety Testing

NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) and the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM).

The recommendations include protocols that describe how to use topical anesthetics and systemic analgesics prior to and after test article administration in order to avoid animal pain and distress. They also identify specific clinical signs and lesions that can be used as humane endpoints to allow the investigator to end a study early in order to alleviate animal pain and distress.
Report of an ISRTP Workshop: Progress and barriers to incorporating alternative toxicological methods in the US (PDF | 290 KB)

International Society of Regulatory Toxicology and Pharmacology.

The objective of this workshop [was] to explore progress to date in implementing new, revised and alternative toxicological test methods across regulatory evaluation frameworks and decision-making programs in the U.S., identify barriers to progress and explore potential bridges to facilitate overcoming such barriers. These barriers may be technical, regulatory, economic or societal. Slides and speakers notes for all presentations are also available.
Graphic depicting a human eye and danger sign Evaluation of the Current Validation Status of In Vitro Test Methods for Identifying Ocular Corrosives and Severe Irritants

The Interagency Coordinating Committee on the Validation of Alternative Methods.

A November 2005 report on the utility of four in vitro ocular toxicity test methods.
Chemicals Testing - Guidelines

Organisation for Economic Co-operation and Development.

Provides internationally agreed testing methods used by government, industry and independent laboratories to characterize potential hazards of new and existing chemical substances.
Murine Local Lymph Node Assay (PDF | 9.18 MB)

Interagency Coordinating Committee on the Validation of Alternative Methods; National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods.

The Murine Local Lymph Node Assay (LLNA) is an alternative test method for assessing the allergic contact dermatitis potential of chemicals.
Progress and Barriers To Incorporating Alternative Toxicological Methods in the U.S.

International Society of Regulatory Toxicology and Pharmacology.

The program and presentation slides from a 2005 workshop that examined progress and barriers to date in implementing new, revised and alternative toxicological test methods across regulatory evaluation frameworks and decision-making programs.
Sens-it-iv Project

An EU-funded research project with the goal of developing alternatives to animal testing when assessing skin or respiratory allergens.
Guinea pig in a PVC environmental enrichment tube Alternative Approaches and Animal Use in the Pharmaceutical Industry (PPT | 3.87 MB)

Europa, Gateway to the European Union.

This presentation offers a view of alternatives and the 3Rs from the research and development perspective of the pharmaceutical industry.
Alternative Methods Publications

Institute for In Vitro Sciences, Inc.

A searchable citation database and links to full-text documents on alternative methods in toxicology.
Refinement, Reduction, and Replacement of Animal Use for Regulatory Testing: Current Best Scientific Practices for the Evaluation of Safety and Potency of Biologicals

ILAR Journal.

This article describes animal testing characteristics and regulatory framework. It also discusses current trends in the development and implementation of alternatives, particularly in the field of biologicals testing (i.e. vaccine development).
Regulatory Testing and Animal Welfare

Institute for Laboratory Animal Research.

This collection of journal articles discusses best practices and animal welfare issue in regards to regulatory testing and toxicology test methods.
Animals in Research

Society of Toxicology.

Provides links to presentations, abstracts, articles, position statements and a downloadable brochure on the importance of animals in the science of toxicology.
CPSC Issues Guidance on Assessment of Sensitizing Substances, Requests Comment on Proposed Update to FHSA
Tuesday, April 23, 2013 - 13:49
Interagency Center for the Evaluation of Alternative Toxicological Methods

In a Federal Register notice published March 12, the U.S. Consumer Product Safety Commission (CPSC) announced new guidance to clarify the definition of “strong sensitizer” as the term applies to substances and products regulated by the CPSC. The CPSC also issued a proposal to update the supplemental definition of “strong sensitizer” under the Federal Hazardous Substances Act (FHSA).

The CPSC guidance document is titled “Strong Sensitizer Guidance.” The CPSC issued the document to assist manufacturers of chemical products in understanding how the CPSC assesses whether such products might be strong sensitizers and thus require cautionary labeling under the FHSA. The document describes the types of data that the CPSC considers in making such a determination and available methods for generating such data. It notes that a determination that a particular product is a strong sensitizer must occur on a case-by-case basis and does not solely depend upon the presence of a strong sensitizer in the product.

The guidance document is available on the CPSC website at http://www.cpsc.gov/Global/Regulations-Laws-and-Standards/Regulated-Prod...

The CPSC proposal to update the definition of “strong sensitizer” under the FHSA would update the definitions for “sensitizer,” “significant potential for causing hypersensitivity,” “normal living tissue,” and “severity of reaction.” The goals of the updated definitions are to “eliminate redundancy, remove certain subjective factors, incorporate new and anticipated technology, rank the criteria for classification of strong sensitizers in order of importance, define criteria for ‘severity of reaction,’ and indicate that a weight-of-evidence approach will be used to determine the strength of the sensitizer.”

CPSC is accepting comments on the proposal through May 28, 2013. Instructions for submitting comments are included in the Federal Register notice announcing the proposal, which is available on the FDSys website at http://www.gpo.gov/fdsys/pkg/FR-2013-03-12/pdf/2013-05577.pdf or http://www.gpo.gov/fdsys/pkg/FR-2013-03-12/html/2013-05577.htm.