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Alternative Test Method Project Milestones: Methods Endorsed by U.S. Agencies
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This page provides a current summary of the status of ongoing and completed NICEATM-ICCVAM alternative test method evaluation projects for which U.S. regulatory agency endorsement has been received or is pending, as well as projects to which NICEATM, ICCVAM, and agency scientists are contributing.

View summary of status of all ongoing and completed NICEATM-ICCVAM test method evaluations

Alternative test methods:

  • Reduce the number of animals used to the minimum number required to obtain scientifically valid data
  • Refine procedures to lessen or eliminate animal pain and distress
  • Replace animals with non-animal systems or one animal species with a less highly developed one (for example, replacing a mouse with a fish).
More information about the ICCVAM Test Method Evaluation Process

View status of test method evaluation projects grouped by project area

Acute Oral Systemic Toxicity Endocrine Disruptor
Biologics Genetic Toxicity
Dermal Corrosivity Immunotoxicity
Dermal Irritation Ocular Toxicity
Developmental Toxicity Pyrogenicity

Select project name in summary table to jump down the page to details and links

Acute Oral Systemic Toxicity Projects
Test Method R&D Validation Studies Evaluation Recommendations
for U.S. Agencies		 U.S.
Acceptance		 International
Acceptance		 Additional Activities
Up-and-Down Procedure check mark check mark check mark check mark 2002 2002 .
Fixed Dose Procedure check mark check mark check mark check mark 2002 2002 .
Acute Toxic Class Method check mark check mark check mark check mark 2002 2002 .
In Vitro Cytotoxicity Test Methods: 3T3 Cells check mark check mark check mark check mark 2008 In progress .
In Vitro Cytotoxicity Test Methods: NHK Cells check mark check mark check mark check mark 2008 In progress .
Biologics Projects
Test Method R&D Validation Studies Evaluation Recommendations
for U.S. Agencies		 U.S.
Acceptance		 International
Acceptance		 Additional Activities
Use of Humane Endpoints in Animal Testing of Veterinary Products check mark check mark check mark check mark 2004 . .
Use of Humane Endpoints in Animal Testing of Rabies Vaccines check mark check mark check mark check mark 2004 . .
Dermal Corrosivity Projects
Test Method R&D Validation Studies Evaluation Recommendations
for U.S. Agencies		 U.S.
Acceptance		 International
Acceptance		 Additional Activities
Corrositex® Assay check mark check mark check mark check mark 2000 2006 .
EpiDermTM Assay check mark check mark check mark check mark 2004 2004 .
EPISKINTM Assay check mark check mark check mark check mark 2004 2004 .
Rat Transcutaneal Electrical Resistance Assay check mark check mark check mark check mark 2004 2004 .
SkinEthic RHE Assay check mark check mark check mark check mark 2004 2004 .
Immunotoxicity Projects
Test Method R&D Validation Studies Evaluation Recommendations
for U.S. Agencies		 U.S.
Acceptance		 International
Acceptance		 Additional Activities
Murine Local Lymph Node Assay (LLNA) check mark check mark check mark check mark 1999 2002 .
Ocular Toxicity Projects
Test Method R&D Validation Studies Evaluation Recommendations
for U.S. Agencies		 U.S.
Acceptance		 International
Acceptance		 Additional Activities
Bovine Corneal Opacity and Permeability (BCOP) - Ocular Corrosivity check mark check mark check mark check mark 2008 In progress .
Isolated Chicken Eye (ICE) - Ocular Corrosivity check mark check mark check mark check mark 2008 In progress .
Pyrogenicity Projects
Test Method R&D Validation Studies Evaluation Recommendations
for U.S. Agencies		 U.S.
Acceptance		 International
Acceptance		 Additional Activities
The Human Whole Blood/IL-1 In Vitro Pyrogen Test chck mark check mark check mark check mark In progress . .
The Human Whole Blood/ IL-1 In Vitro Pyrogen Test Using Cryopreserved Human Whole Blood check mark check mark check mark check mark In progress . .
The Human Whole Blood/IL-6 In Vitro Pyrogen Test (WB/IL-6) check mark check mark check mark check mark In progress . .
In Vitro Pyrogen Test Using Human Peripheral Blood Mononuclear Cells (PBMC/IL-6) check mark check mark check mark check mark In progress . .
An Alternative In Vitro Pyrogen Test Using the Human Monocytoid Cell Line MONO MAC 6 (MM6/IL-6) check mark check mark check mark check mark In progress . .

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Acute Oral Systemic Toxicity

Up-And-Down Procedure

Acute oral systemic toxicity testing identifies substances that are poisonous when ingested so that they may be appropriately labeled and packaged. The Up-And-Down Procedure reduces animal use for this purpose by up to 70%.
Milestone Date Document Link or
More Information
Publication of OECD Test Guideline 425 1998 PDF
Nomination by the U.S. Environmental Protection Agency (EPA) August 1999 -
Peer Review Panel Meeting July 2000 HTML
Peer Review Panel Follow-up Teleconference August 2001 HTML
Test Method Evaluation Report Published November 2001 Vol 1 - Vol 2
Recommendations Made to Federal Agencies March 2003 HTML
Federal Agency Responses Received December 2003 HTML

Fixed Dose Procedure

Acute oral systemic toxicity testing identifies substances that are poisonous when ingested so that they may be appropriately labeled and packaged. The Fixed Dose Procedure reduces animal use for this purpose by up to 70%.
Milestone Date Document Link or
More Information
Publication of OECD Test Guideline 420 1998 PDF

Acute Toxic Class Method

Acute oral systemic toxicity testing identifies substances that are poisonous when ingested so that they may be appropriately labeled and packaged. The Acute Toxic Class Method reduces animal use for this purpose by up to 70%.
Milestone Date Document Link or
More Information
Publication of OECD Test Guideline 423 1998 PDF

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Evaluation of In Vitro Cytotoxicity Test Methods

Acute oral systemic toxicity testing identifies substances that are poisonous when ingested so that they may be appropriately labeled and packaged. In Vitro Cytotoxicity Test Methods replace animal use for initial dose setting for these tests.
Milestone Date Document Link or
More Information
EPA Nomination August 1999 -
Workshop Held October 2000 HTML
Guidance Document Published August 2001 PDF
Workshop Report Published August 2001 PDF
Recommendations Made to Federal Agencies March 2003 HTML
Federal Agency Responses Received December 2003 HTML

Validation Study of In Vitro Cytotoxicity Test Methods

Acute oral systemic toxicity testing identifies substances that are poisonous when ingested so that they may be appropriately labeled and packaged. Neutral Red Uptake Test Methods replace animal use for initial dose setting for these tests.
Milestone Date Document Link or
More Information
Peer Review Panel Meeting May 2006 HTML
Peer Review Panel Report Published June 2006 PDF
Background Review Document Published November 2006 Vol 1 - Vol 2
Test Method Evaluation Report Published November 2006 HTML
Recommendations Made to Federal Agencies March 2008 HTML
Federal Agency Responses Received September 2008 HTML

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Biologics

Use of Humane Endpoints in Animal Testing of Veterinary Products and Rabies Vaccines

Animal testing of biological products and rabies vaccines is performed to ensure that each lot of these products is safe and effective. A USDA directive refines animal use for this purpose.
Milestone Date Document Link or
More Information
USDA Directive Published April 2004 PDF

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Dermal Corrosivity

Evaluation of Corrositex® for the Identification of Substances Potentially Corrosive to Human Skin

Dermal corrosivity testing identifies substances that cause chemical burns to the skin so that they may be appropriately labeled and packaged. Corrositex® reduces and refines animal use for this purpose.
Milestone Date Document Link or
More Information
Corrositex® Submission May 1998 -
Peer Review Panel Meeting January 1999 HTML
Peer Review Panel Report Published June 1999 PDF
Recommendations Made to Federal Agencies June 1999 -
Federal Agency Responses Received October 1999 HTML
Publication of OECD Test Guideline 435 July 2006 PDF


Evaluation of EpiSkinTM, EPIDERMTM and the Rat Skin Transcutaneous Electrical Resistance Assay (TER) for the Identification of Substances Potentially Corrosive to Human Skin

Dermal corrosivity testing identifies substances that cause chemical burns to the skin so that they may be appropriately labeled and packaged. Use of these in vitro tests reduces and refines animal use for this purpose.
Milestone Date Document Link or
More Information
Background Review Document Published August 2001 PDF
Test Method Evaluation Report Published June 2002 HTML
Recommended Performance Standards Published May 2004 PDF
Publication of OECD Test Guidelines 430 and 431 July 2006 TG 430 - PDF
TG 431 - PDF

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Immunotoxicity

Murine Local Lymph Node Assay (LLNA)

Immunotoxicity testing identifies substances that may act as sensitizers and cause the development of allergic contact dermatitis. Use of the LLNA reduces and refines animal use for this purpose.
Milestone Date Document Link or
More Information
Nomination by Sponsors January 1998 -
Peer Review Panel Meeting September 1998 HTML
Peer Review Panel Report February 1999 PDF
Recommendations Made to Federal Agencies February 1999 HTML
Publication of OECD Test Guideline 429 July 2006 PDF

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Ocular Toxicity

In Vitro Test Methods for Detecting Ocular Corrosives and Severe Irritants

  • Bovine Corneal Opacity and Permeability Test Method
  • Isolated Chicken Eye Test Method
  • Isolated Rabbit Eye Test Method
  • Hen's Egg Test - Chorioallantoic Membrane Test Method

Ocular toxicity testing identifies substances that may cause permanent or temporary blindness. Use of these in vitro test methods will reduce and refine animal use for this purpose.
Milestone Date Document Link or
More Information
EPA Nomination October 2003 -
Expert Panel Meeting January 2005 HTML
Expert Panel Report March 2005 PDF
Expert Panel Teleconference September 2005 HTML
Expert Panel Report Addendum November 2005 PDF
Background Review Documents Published October 2007 HTML
Test Method Evaluation Report Published October 2007 HTML
Recommendations Made to Federal Agencies October 2007 HTML
Federal Agency Responses Received May 2008 HTML
Draft OECD Test Guidelines Submitted to U.S. National Coordinator August 2008 HTML

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Pyrogenicity

In Vitro Pyrogen Test Methods

  • The Human Whole Blood/IL-1 In Vitro Pyrogen Test
  • The Human Whole Blood/ IL-1 In Vitro Pyrogen Test Using Cryopreserved Human Whole Blood
  • The Human Whole Blood/IL-6 In Vitro Pyrogen Test (WB/IL-6)
  • In Vitro Pyrogen Test Using Human Peripheral Blood Mononuclear Cells (PBMC/IL-6)
  • An Alternative In Vitro Pyrogen Test Using the Human Monocytoid Cell Line MONO MAC 6 (MM6/IL-6)

Pyrogenicity testing is performed on products to be administered by injection to ensure that each lot of these products is free of substances that could induce a dangerous fever reaction. Use of these in vitro tests could replace animal use for this purpose.
Milestone Date Document Link or
More Information
Submission by ECVAM June 2005 PDF
Peer Review Panel Meeting February 2007 HTML
Peer Review Panel Report Published April 2007 PDF
Background Review Document Published October 2008 HTML
Test Method Evaluation Report Published October 2008 HTML
Recommendations to Federal Agencies November 2008 HTML


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