Alternatives in Toxicology

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.


Leptospira workshop poster Proceedings: Workshop on Alternative Methods for Leptospira Vaccine Potency Testing

National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM).


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.


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.


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


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.


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.


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.


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.


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.


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.


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).


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.


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.


A New Vision and Direction for ICCVAM: Comments Requested on Draft Document
Thursday, March 13, 2014 - 09:24
Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM)

The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) work together to promote the development, validation, and regulatory acceptance of new and revised regulatory test methods. In a February 2013 editorial in the journal Environmental Health Perspectives, National Institute of Environmental Health Sciences and NTP Director Linda Birnbaum announced upcoming significant changes to the focus and priorities of both ICCVAM and NICEATM.

A draft document now available on the NTP website, titled “A New Vision and Direction for ICCVAM,” describes the initial steps towards a new strategic direction for ICCVAM. Specifically, this document discusses (1) ICCVAM priority setting and areas for scientific focus for immediate resource investment; (2) plans to improve communications with stakeholders and the public; and (3) exploration of new paradigms for the validation and utilization of alternative toxicological methods.

NICEATM invites public comments on “A New Vision and Direction for ICCVAM.” The document will be discussed at the Sept. 24 meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM).

Links to “A New Vision and Direction for ICCVAM,” the Environmental Health Perspectives editorial, and the ICCVAM response to the editorial are available on the SACATM Background Materials page http://ntp.niehs.nih.gov/go/40529, under the heading “New ICCVAM Vision and Procedures.” To submit a comment on “A New Vision and Direction for ICCVAM,” go to http://ntp.niehs.nih.gov/go/opensolicitations and select the “Submit Comment” link beside the SACATM meeting announcement. Written comments submitted by September 10 will be considered during the discussion of the draft document at the SACATM meeting.

For more information about the SACATM meeting, go to http://ntp.niehs.nih.gov/go/32822. This page includes links to the Background Materials page, a preliminary meeting agenda, a registration form to attend the meeting, and a webcast that will be available on the day of the meeting.


Monday, March 31, 2014 - 15:14
Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM)

The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) work together to promote the development, validation, and regulatory acceptance of new and revised regulatory test methods. In a February 2013 editorial in the journal Environmental Health Perspectives, National Institute of Environmental Health Sciences and NTP Director Linda Birnbaum announced upcoming significant changes to the focus and priorities of both ICCVAM and NICEATM.

A draft document now available on the NTP website, titled “A New Vision and Direction for ICCVAM,” describes the initial steps towards a new strategic direction for ICCVAM. Specifically, this document discusses (1) ICCVAM priority setting and areas for scientific focus for immediate resource investment; (2) plans to improve communications with stakeholders and the public; and (3) exploration of new paradigms for the validation and utilization of alternative toxicological methods.

NICEATM invites public comments on “A New Vision and Direction for ICCVAM.” The document will be discussed at the Sept. 24 meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM).

Links to “A New Vision and Direction for ICCVAM,” the Environmental Health Perspectives editorial, and the ICCVAM response to the editorial are available on the SACATM Background Materials page http://ntp.niehs.nih.gov/go/40529, under the heading “New ICCVAM Vision and Procedures.” To submit a comment on “A New Vision and Direction for ICCVAM,” go to http://ntp.niehs.nih.gov/go/opensolicitations and select the “Submit Comment” link beside the SACATM meeting announcement. Written comments submitted by September 10 will be considered during the discussion of the draft document at the SACATM meeting.

For more information about the SACATM meeting, go to http://ntp.niehs.nih.gov/go/32822. This page includes links to the Background Materials page, a preliminary meeting agenda, a registration form to attend the meeting, and a webcast that will be available on the day of the meeting.


Monday, January 6, 2014 - 09:48
Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM)

The European Union Reference Laboratory for alternatives to animal testing (EURL ECVAM) is accepting public comments on draft recommendations for two non-animal test methods. The direct
peptide reactivity assay is recommended as a screening test to identify substances with the potential to cause allergic contact dermatitis. The Bhas 42 cell transformation assay is recommended
as a screening test to identify potential carcinogens.

The draft recommendations are available on the European Union Institute for Health and Consumer Protection website . EURL ECVAM is accepting comments on both draft recommendations through September 13. Comments may be submitted by email to JRC-ECVAM-CONTACT@ec.europa.eu.

This announcement was originally distributed via the ICCVAM-all email list.
Subscribing to the ICCVAM-all email list will enable you to be notified directly of NICEATM and ICCVAM activities. Subscribers receive email notification of publication of NICEATM Federal Register notices, availability of ICCVAM reports, notices of upcoming meetings, requests for public comments or data, and other events of interest to our stakeholders.


Monday, March 31, 2014 - 15:07
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-Products-Rules/strongsensitizerguidance.pdf

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.