This page provides a current summary of the status of ongoing and completed ICCVAM alternative test
method evaluation projects, as well as projects to which NICEATM, ICCVAM,
and agency scientists are contributing.
Acute Oral Systemic Toxicity |
Test Method |
R&D |
Validation Studies |
Evaluation |
Recommendations to U.S. Agencies |
U.S. Acceptance |
International Acceptance |
Up-and-Down Procedure (oral) |
✔ |
✔ |
✔ |
✔ |
2002 |
2002 (OECD TG 425) |
Fixed Dose Procedure (oral) |
✔ |
✔ |
✔ |
✔ |
2002 |
2002 (OECD TG 420) |
Acute Toxic Class Method (oral) |
✔ |
✔ |
✔ |
✔ |
2002 |
2002 (OECD TG 423) |
In Vitro
Cytotoxicity Test Methods: 3T3 Cells |
✔ |
✔ |
✔ |
✔ |
2008 |
2010 (OECD GD 129) |
In Vitro
Cytotoxicity Test Methods: NHK Cells |
✔ |
✔ |
✔ |
✔ |
2008 |
2010 (OECD GD 129) |
Acute Inhalation Toxicity |
Test Method |
R&D |
Validation Studies |
Evaluation |
Recommendations to U.S. Agencies |
U.S. Acceptance |
International Acceptance |
Acute Toxic Class Method (inhalation) |
✔ |
✔ |
✔ |
(Not applicable - adopted via OECD Test Guideline) |
2009 (OECD TG 436) |
Fixed Dose Procedure (inhalation) |
✔ |
✔ |
Anticipated 2013 (OECD) |
(Not applicable - to be adopted via OECD Test Guideline) |
Anticipated 2014 (OECD) |
Acute Dermal Systemic Toxicity |
Test Method |
R&D |
Validation Studies |
Evaluation |
Recommendations to U.S. Agencies |
U.S. Acceptance |
International Acceptance |
Up-and-Down Procedure (dermal) |
✔ |
In progress |
Anticipated 2013 |
Anticipated 2013 |
Anticipated 2014 |
Anticipated 2014 (OECD) |
In Vitro Metabolism and Toxicokinetics |
Test Method |
R&D |
Validation Studies |
Evaluation |
Recommendations to U.S. Agencies |
U.S. Acceptance |
International Acceptance |
Provision of a Standard for Human Hepatic Metabolism and Toxicity by Assessing as an Indicator Biotransformation Enzyme Induction Using HepaRGĀ®
Cells and Cryopreserved Human Hepatocytes |
✔ |
In progress |
Anticipated 2013 (OECD) |
(Not applicable - to be adopted via OECD Test Guideline) |
Anticipated 2014 (OECD) |
Dermal Corrosivity |
Test Method |
R&D |
Validation Studies |
Evaluation |
Recommendations to U.S. Agencies |
U.S. Acceptance |
International Acceptance |
Corrositex® Assay |
✔ |
✔ |
✔ |
✔ |
2000 |
2006 (OECD TG 435) |
EpiDermTM Assay |
✔ |
✔ |
✔ |
✔ |
2004 |
2004 (OECD TG 431) |
EPISKINTM Assay |
✔ |
✔ |
✔ |
✔ |
2004 |
2004 (OECD TG 431) |
Rat Transcutaneal Electrical Resistance Assay |
✔ |
✔ |
✔ |
✔ |
2004 |
2004 (OECD TG 430) |
SkinEthic RHE Assay |
✔ |
✔ |
✔ |
✔ |
2004 |
2004 (OECD TG 431) |
LabCyte EPI-MODEL24 Assay |
✔ |
✔ |
In progress |
|
|
|
Dermal Irritation |
Test Method |
R&D |
Validation Studies |
Evaluation |
Recommendations to U.S. Agencies |
U.S. Acceptance |
International Acceptance |
EpiDermTM Assay |
✔ |
✔ |
✔ |
(Not applicable - adopted via OECD Test Guideline) |
2010 (OECD TG 439) |
EPISKINTM Assay |
✔ |
✔ |
✔ |
(Not applicable - adopted via OECD Test Guideline) |
2010 (OECD TG 439) |
SkinEthic RHE Assay |
✔ |
✔ |
✔ |
(Not applicable - adopted via OECD Test Guideline) |
2010 (OECD TG 439) |
Investigation of in vitro
dermal irritation assays to evaluate false negative corrosives from in vitro corrosivity tests |
✔ |
✔ |
In progress |
|
|
|
LabCyte EPI-MODEL24 Assay |
✔ |
✔ |
In progress |
|
|
|
Ocular Toxicity |
Test Method |
R&D |
Validation Studies |
Evaluation |
Recommendations to U.S. Agencies |
U.S. Acceptance |
International Acceptance |
Bovine Corneal Opacity and Permeability (BCOP) - Ocular Corrosivity/Severe Irritation |
✔ |
✔ |
✔ |
✔ |
2008 |
2009 (OECD TG 437) |
Isolated Chicken Eye (ICE) - Ocular Corrosivity/Severe Irritation |
✔ |
✔ |
✔ |
✔ |
2008 |
2009 (OECD TG 438) |
Hen's Egg Test/Choriallantoic Membrane (HET-CAM) - Ocular Corrosivity/Severe Irritation |
✔ |
✔ |
✔ |
ICCVAM review in 2007
found that this test method was not sufficiently accurate for regulatory use and recommended
additional studies |
Isolated Rabbit Eye (IRE) - Ocular Corrosivity/Severe Irritation |
✔ |
✔ |
✔ |
ICCVAM review in 2007
found that this test method was not sufficiently accurate for regulatory use and recommended
additional studies |
Integrated Non-animal Testing Strategy for Eye Irritation Potential
of Antimicrobial Cleaning Products |
✔ |
✔ |
✔ |
ICCVAM review in 2009
concluded that data on the testing strategy were not sufficient to
demonstrate its utility for the proposed application
and recommended additional studies |
BCOP - Nonsevere Ocular Irritation |
✔ |
✔ |
✔ |
ICCVAM review in 2009
found that this test method was not sufficiently accurate for the proposed use and recommended
additional studies |
HET-CAM - Nonsevere Ocular Irritation |
✔ |
✔ |
✔ |
ICCVAM review in 2009
found that this test method was not sufficiently accurate for the proposed use and recommended
additional studies |
ICE - Nonsevere Ocular Irritation |
✔ |
✔ |
✔ |
ICCVAM review in 2009
found that this test method was not sufficiently accurate for the proposed use and recommended
additional studies |
IRE - Nonsevere Ocular Irritation |
✔ |
✔ |
✔ |
ICCVAM review in 2009
found that this test method was not sufficiently accurate for the proposed use and recommended
additional studies |
Cytosensor Microphysiometer Test Method |
✔ |
✔ |
✔ |
✔ |
2011 |
Anticipated 2013 (OECD) |
Routine use of topical anesthestics, systemic analgesics, and humane endpoints in in vivo testing |
✔ |
✔ |
✔ |
✔ |
2011 |
2012 (Updated OECD TG 405) |
In vivo low volume eye test |
✔ |
✔ |
✔ |
ICCVAM reviewed the LVET in 2009 and does not recommend its use for prospective ocular safety testing |
Fluorescein leakage test method - ocular corrosivity/severe irritation |
✔ |
✔ |
✔ |
(Not applicable - adopted via OECD Test Guideline) |
2012 (OECD TG 460) |
Neutral red release test method |
✔ |
✔ |
ICCVAM review in 2009
found that this test method was not adequately validated for regulatory use |
Red blood cell haemolysis test method |
✔ |
✔ |
ICCVAM review in 2009
found that this test method was not adequately validated for regulatory use |
Immunotoxicity |
Test Method |
R&D |
Validation Studies |
Evaluation |
Recommendations to U.S. Agencies |
U.S. Acceptance |
International Acceptance |
Murine Local Lymph Node Assay (LLNA) |
✔ |
✔ |
✔ |
✔ |
1999 |
2002 (OECD TG 429) |
Updated LLNA Protocol (20% animal reduction) |
✔ |
✔ |
✔ |
✔ |
2010 |
2010 (Updated OECD TG 429) |
Reduced LLNA Test Method |
✔ |
✔ |
✔ |
✔ |
2010 |
2010 (Updated OECD TG 429) |
Development of LLNA Performance Standards |
✔ |
✔ |
✔ |
✔ |
2010 |
2010 (Updated OECD TG 429) |
Nonradioactive LLNA Method: LLNA:DA |
✔ |
✔ |
✔ |
✔ |
2011 |
2010 (OECD TG 442A) |
Nonradioactive LLNA Method: LLNA:BrdU-ELISA |
✔ |
✔ |
✔ |
✔ |
2011 |
2010 (OECD TG 442B) |
Nonradioactive LLNA Method: LLNA:BrdU-Flow Cytometry |
✔ |
Interlaboratory validation study required |
|
|
|
|
Use of the LLNA for Testing Pesticide Formulations,
Metals, Substances in Aqueous Solutions, and Other Products |
✔ |
✔ |
✔ |
✔ |
2011 |
2010 (Updated OECD TG 429) |
Use of the LLNA for Skin Sensitization Potency Categorization |
✔ |
✔ |
✔ |
✔ |
✔ |
2009 (UN GHS) |
Dermal Phototoxicity |
Test Method |
R&D |
Validation Studies |
Evaluation |
Recommendations to U.S. Agencies |
U.S. Acceptance |
International Acceptance |
3T3 NRU Phototoxicity Test |
✔ |
✔ |
✔ |
(Not applicable - adopted via OECD Test Guideline) |
2004 (OECD TG 432) |
3T3 NRU Phototoxicity Test: Application to UV Filter Chemicals |
✔ |
✔ |
✔ |
(Not applicable - adopted via OECD Test Guideline) |
2004 (OECD TG 432) |
Dermal Absorption |
Test Method |
R&D |
Validation Studies |
Evaluation |
Recommendations to U.S. Agencies |
U.S. Acceptance |
International Acceptance |
In Vitro Dermal Absorption |
✔ |
✔ |
✔ |
(Not applicable - adopted via OECD Test Guideline) |
2004 (OECD TG 428) |
Genetic Toxicity |
Test Method |
R&D |
Validation Studies |
Evaluation |
Recommendations to U.S. Agencies |
U.S. Acceptance |
International Acceptance |
In Vitro Micronucleus Assay |
✔ |
✔ |
✔ |
(Not applicable - adopted via OECD Test Guideline) |
2010 (OECD TG 487) |
In Vivo Comet Assay |
✔ |
✔ |
In progress (JaCVAM) |
|
|
|
In Vitro Comet Assay |
✔ |
In progress (JaCVAM) |
|
|
|
|
Cell Transformation Assays |
✔ |
✔ |
✔ |
(Not applicable - to be adopted via OECD Test Guideline) |
Anticipated 2013 (OECD) |
BHAS Cell Transformation Assay |
✔ |
✔ |
In progress (JaCVAM) |
|
|
|
Developmental Toxicity |
Test Method |
R&D |
Validation Studies |
Evaluation |
Recommendations to U.S. Agencies |
U.S. Acceptance |
International Acceptance |
Frog Embryo Teratogenesis Assay: Xenopus (FETAX) |
✔ |
✔ |
✔ |
ICCVAM evaluation in 2000
found that FETAX was not sufficiently reliable for regulatory use and provided recommendations
for improving accuracy and reliability |
Endocrine Disruptor |
Test Method |
R&D |
Validation Studies |
Evaluation |
Recommendations to U.S. Agencies |
U.S. Acceptance |
International Acceptance |
In vitro Andogen Receptor (AR) Binding |
✔ |
ICCVAM review in 2004
found validation studies conducted to date to be inadequate - ICCVAM published recommendations on future validation studies |
In vitro AR Transcriptional Activation (TA) |
✔ |
ICCVAM review in 2004
found validation studies conducted to date to be inadequate - ICCVAM published recommendations on future validation studies |
In vitro Estrogen Receptor (ER) Binding |
✔ |
ICCVAM review in 2004
found validation studies conducted to date to be inadequate - ICCVAM published recommendations on future validation studies |
In vitro ER TA |
✔ |
ICCVAM review in 2004
found validation studies conducted to date to be inadequate - ICCVAM published recommendations on future validation studies |
BG1Luc ER TA Assay Evaluation |
✔ |
✔ |
✔ |
✔ |
✔ |
2012 (OECD TG 457) |
MCF-7 Cell Proliferation Assay Evaluation |
✔ |
✔ |
✔ |
Results of NICEATM validation study
indicated that the MCF-7 cell proliferation assay protocol requires further development to support transferability |
Pyrogenicity |
Test Method |
R&D |
Validation Studies |
Evaluation |
Recommendations to U.S. Agencies |
U.S. Acceptance |
International Acceptance |
The Human Whole Blood/IL-1 In Vitro Pyrogen Test |
✔ |
✔ |
✔ |
✔ |
2009 |
2010 (European Pharmacopeia) |
The Human Whole Blood/ IL-1 In Vitro Pyrogen Test Using Cryopreserved Human Whole Blood |
✔ |
✔ |
✔ |
✔ |
2009 |
2010 (European Pharmacopeia) |
The Human Whole Blood/IL-6 In Vitro Pyrogen Test (WB/IL-6) |
✔ |
✔ |
✔ |
✔ |
2009 |
2010 (European Pharmacopeia) |
In Vitro Pyrogen Test Using Human Peripheral Blood Mononuclear Cells (PBMC/IL-6) |
✔ |
✔ |
✔ |
✔ |
2009 |
2010 (European Pharmacopeia) |
An Alternative In Vitro Pyrogen Test Using the Human Monocytoid Cell Line MONO MAC 6 (MM6/IL-6) |
✔ |
✔ |
✔ |
✔ |
2009 |
2010 (European Pharmacopeia) |
Biologics and Vaccines
|
Test Method |
R&D |
Validation Studies |
Evaluation |
Recommendations to U.S. Agencies |
U.S. Acceptance |
International Acceptance |
Use of Humane Endpoints in Animal Testing of Veterinary Products |
✔ |
✔ |
✔ |
✔ |
2002 |
1986 (European Union) |
Use of Humane Endpoints in Animal Testing of Rabies Vaccines |
✔ |
✔ |
✔ |
✔ |
2004 |
2002 (European Pharmacopeia) |
Alternative Methods for Botulinum Toxin Potency Testing |
✔ |
ICCVAM workshop in 2006
assessed the state of the science and concluded that additional development and/or validation of these methods were needed
prior to evaluation by ICCVAM |
Alternative Methods for Vaccine Potency and Safety Testing |
✔ |
ICCVAM workshop in September 2010
assessed the state of the science and identified priorities for research, development, and validation efforts: report
detailing conclusions and recommendations published in 2011 |
Alternative Methods for Rabies Vaccine Potency Testing |
✔ |
ICCVAM workshop in October 2011
reviewed the available methods and approaches to reduce, refine, and replace animals used in rabies vaccine potency testing
and developed an implementation strategy to achieve global acceptance and use of these alternatives;
report detailing conclusions and recommendations published in 2012 |
Alternative Methods for Leptospira Vaccine Potency Testing |
✔ |
An ICCVAM workshop in September 2012 will
reviewed the available methods and approaches to reduce, refine, and replace animals used in Leptospira vaccine potency testing
and developed an implementation strategy to achieve global acceptance and use of these alternatives
Report detailing conclusions and recommendations to be published in 2013 |
Alternatives to the HIST Test for Acellular Pertussis Vaccines |
✔ |
An ICCVAM workshop in November 2012 will
reviewed the available alternatives to the murine histamine sensitization (HIST) test
and considered an implementation strategy to achieve global acceptance and use of these alternatives
Report detailing conclusions and recommendations to be published in 2013 |
Up-And-Down Procedure (oral)
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 (oral)
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 (oral)
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 |
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 |
OECD Guidance Document 129 Published |
July 2010 |
PDF |
Developing and Advancing In Vitro
Alternatives to Acute Chemical Systemic Toxicity Testing
Acute oral systemic toxicity testing identifies substances that are
poisonous when ingested so that they may be appropriately labeled and packaged.
An ICCVAM-sponsored workshop explored ways to reduce, refine, or replace animal use for this purpose. |
Milestone |
Date |
Document Link or More Information |
Workshop Held |
February 2008 |
HTML |
Workshop Report Published |
May 2009 |
HTML |
Acute Toxic Class Method (inhalation)
Acute inhalation systemic toxicity testing identifies substances that are
poisonous when inhaled so that they may be appropriately labeled and packaged.
The Acute Toxic Class Method reduces animal use for this purpose. |
Milestone |
Date |
Document Link or More Information |
Publication of OECD Test Guideline 436 |
September 2009 |
PDF |
Evaluation of CorrositexĀ® 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.
CorrositexĀ® 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 |
Updates submitted to OECD Test Guidelines 430 and 431 |
July 2009 |
- |
Evaluation of EpiSkinTM,
EPIDERMTM and the SkinEthic RHE Assay for the
Identification of Substances Potentially Irritating to Human Skin
Dermal irritation testing identifies substances that cause
irritation to the skin so that they may be appropriately labeled and packaged.
Use of these in vitro tests reduces animal use for this purpose. |
Milestone |
Date |
Document Link or More Information |
Submission of ICCVAM Comments on Draft Test Guideline to U.S. OECD National Coordinator |
August 2008 |
HTML |
OECD Expert Meeting |
June 2009 |
- |
Adoption of OECD Test Guideline 439 |
July 2010 |
PDF |
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 437 (BCOP) and 438 (ICE) Submitted to U.S. National Coordinator |
August 2008 |
HTML |
Adoption of OECD Test Guidelines 437 and 438 |
September 2009 |
HTML |
Adoption of Guidance Document Supporting OECD Test Guidelines 437 and 438: Collection of Tissues for Histopathology Evalution
and Data on Nonsevere Irritants |
April 2011 |
PDF |
Routine Use of Topical Anesthestics, Systemic
Analgesics and Humane Endpoints in In Vivo Testing
Ocular toxicity testing identifies substances that may
cause irritation to the eye.
Routine use of topical anesthestics, systemic
analgesics and humane endpoints will refine animal use for this purpose. |
Milestone |
Date |
Document Link or More Information |
Peer Review Panel Meeting |
May 2009 |
HTML |
Peer Review Panel Report Published |
July 2009 |
HTML |
Recommendations Made to U.S. Federal Agencies |
September 2010 |
HTML |
Federal Agency Responses Received |
March 2011 |
HTML |
Updated Test Guideline 405 Adopted by OECD |
October 2012 |
PDF |
In Vitro Test Methods for Detecting Nonsevere Irritants
and Substances Not Requiring Ocular Hazard Labeling
- Bovine Corneal Opacity and Permeability Test Method
- Isolated Chicken Eye Test Method
- Cytosensor Microphysiometer Test Method
- Isolated Rabbit Eye Test Method
- Hen's Egg Test - Chorioallantoic Membrane Test Method
Ocular toxicity testing identifies substances that may
cause irritation to the eye.
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 |
- |
Peer Review Panel Meeting |
May 2009 |
HTML |
Peer Review Panel Report Published |
July 2009 |
HTML |
Recommendations Made to U.S. Federal Agencies |
September 2010 |
HTML |
Federal Agency Responses Received |
March 2011 |
HTML |
In Vitro Test Methods for Detecting Nonsevere Ocular Irritants
and Substances Not Requiring Ocular Hazard Labeling
- Fluorescein Leakage Test Method
- Neutral Red Release Test Method
- Red Blood Cell Haemolysis Test Method
Ocular toxicity testing identifies substances that may
cause irritation to the eye.
Use of these In Vitro Test Methods will reduce and refine animal use for this purpose. |
Milestone |
Date |
Document Link or More Information |
ICCVAM Working Group Comment on Background Review Documents submitted to
the European Committee for the Validation of Alternative Methods |
July 2008 |
- |
Test Guideline 460 for Fluorescein Leakage Test Method Adopted by OECD |
October 2012 |
PDF |
Non-animal Assessment Approach for
Evaluating Eye Irritation Potential of Antimicrobial Cleaning Products
Ocular toxicity testing identifies substances that may
cause irritation to the eye.
Use of this in vitro approach could replace animal use for this purpose
to meet EPA labeling requirements. |
Milestone |
Date |
Document Link or More Information |
Submission by IIVS |
January 2008 |
PDF |
Peer Review Panel Meeting |
May 2009 |
HTML |
Peer Review Panel Report Published |
July 2009 |
HTML |
Recommendations Made to U.S. Federal Agencies |
September 2010 |
HTML |
Federal Agency Responses Received |
March 2011 |
HTML |
The In Vivo Low Volume Eye Test
The low volume eye test is an alternative to the traditional in vivo
rabbit eye test that is also used as a reference method for in vitro methods under evaluation. |
Milestone |
Date |
Document Link or More Information |
Peer Review Panel Meeting |
May 2009 |
HTML |
Peer Review Panel Report Published |
July 2009 |
HTML |
Recommendations Made to U.S. Federal Agencies |
September 2010 |
HTML |
Federal Agency Responses Received |
March 2011 |
HTML |
Murine Local Lymph Node Assay (LLNA)
Skin sensitization 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 |
Adoption of OECD Test Guideline 429 |
April 2002 |
PDF |
Update Submitted to OECD Test Guideline 429 |
July 2009 |
- |
Update to OECD Test Guideline 429 Adopted |
July 2010 |
PDF |
Updated Protocol for the Murine Local
Lymph Node Assay (LLNA)
Skin sensitization testing identifies substances that may
act as sensitizers and cause the development of allergic contact dermatitis.
The ICCVAM-recommended updated protocol will reduce the number of animals used by 20% when
the LLNA is used for this purpose. |
Milestone |
Date |
Document Link or More Information |
Peer Review Panel Meeting |
March 2008 |
HTML |
Peer Review Panel Report Published |
May 2008 |
PDF |
Update to OECD Test Guideline 429 Submitted |
July 2009 |
- |
Recommendations on ICCVAM-recommended Performance Standards Transmitted to U.S. Federal Agencies;
Revised Protocol is Appendix A of Performance Standards |
September 2009 |
HTML |
Recommmendations to U.S. Federal Agencies Accepted |
March 2010 |
HTML |
Update to OECD Test Guideline 429 Adopted |
July 2010 |
PDF |
Development of Performance Standards for the Murine Local
Lymph Node Assay (LLNA)
Skin sensitization testing identifies substances that may
act as sensitizers and cause the development of allergic contact dermatitis.
Accepted performance standards will enable the development of new versions of the LLNA for this purpose. |
Milestone |
Date |
Document Link or More Information |
Draft Performance Standards Published |
September 2007 |
PDF |
Peer Review Panel Meeting |
March 2008 |
HTML |
Peer Review Panel Report Published |
May 2008 |
PDF |
Update to OECD Test Guideline 429 Submitted |
July 2009 |
- |
Recommendations on ICCVAM-recommended Performance Standards Transmitted to U.S. Federal Agencies |
September 2009 |
HTML |
Recommmendations to U.S. Federal Agencies Accepted |
March 2010 |
HTML |
Update to OECD Test Guideline 429 Adopted |
July 2010 |
PDF |
Reduced Murine Local Lymph Node Assay (rLLNA)
Skin sensitization testing identifies substances that may
act as sensitizers and cause the development of allergic contact dermatitis.
The reduced LLNA will reduce animal use for this purpose. |
Milestone |
Date |
Document Link or More Information |
CPSC Nomination |
January 2007 |
PDF |
Peer Review Panel Meeting |
March 2008 |
HTML |
Peer Review Panel Report Published |
May 2008 |
PDF |
Update to OECD Test Guideline 429 Submitted (containing rLLNA procedure) |
July 2009 |
- |
ICCVAM Recommendations on rLLNA Transmitted to U.S. Federal Agencies |
September 2009 |
HTML |
Recommmendations to U.S. Federal Agencies Accepted |
March 2010 |
HTML |
Update to OECD Test Guideline 429 Adopted |
July 2010 |
PDF |
Nonradioactive Murine Local Lymph Node Assay (LLNA)
- LLNA:DA
- LLNA:BrdU-ELISA
- LLNA:BrdU-Flow Cytometry
Skin sensitization testing identifies substances that may
act as sensitizers and cause the development of allergic contact dermatitis.
Nonradioactive version of the LLNA will refine and reduce animal use for this purpose
by enabling more widespread use of the LLNA. |
Milestone |
Date |
Document Link or More Information |
CPSC Nomination |
January 2007 |
PDF |
Peer Review Panel Meeting |
March 2008 |
HTML |
Peer Review Panel Report Published |
May 2008 |
PDF |
Revised Background Review Documents and ICCVAM Recommendations Published |
March 2009 |
HTML |
Second Peer Review Panel Meeting |
April 2009 |
HTML |
Second Peer Review Panel Report Published |
June 2009 |
PDF |
ICCVAM Recommendations on Nonradioactive LLNA: DA and LLNA: BrdU-ELISA Methods Transmitted to U.S. Federal Agencies |
June 2010 |
- |
New OECD Test Guidelines for the LLNA: DA and LLNA: BrdU-ELISA Methods Adopted |
July 2010 |
PDF: OECD TG 442A (DA)
PDF: OECD TG 442B (ELISA) |
Federal Agency Responses Received |
February 2011 |
HTML |
Use of the Murine Local Lymph Node Assay (LLNA)
for Testing Pesticide Formulations, Metals, Substances in Aqueous Solutions, and Other Products
Skin sensitization testing identifies substances that may
act as sensitizers and cause the development of allergic contact dermatitis.
Use of the LLNA will refine and reduce animal use for this purpose. |
Milestone |
Date |
Document Link or More Information |
CPSC Nomination |
January 2007 |
PDF |
Peer Review Panel Meeting |
March 2008 |
HTML |
Peer Review Panel Report Published |
May 2008 |
PDF |
Revised Background Review Documents and ICCVAM Recommendations Published |
March 2009 |
HTML |
Second Peer Review Panel Meeting |
April 2009 |
HTML |
Second Peer Review Panel Report Published |
June 2009 |
PDF |
ICCVAM Recommendations on the LLNA Applicability Domain Transmitted to U.S. Federal Agencies |
June 2010 |
- |
Update to OECD Test Guideline 429 Adopted |
July 2010 |
PDF |
Federal Agency Responses Received |
February 2011 |
HTML |
Use of the Murine Local Lymph Node Assay (LLNA)
for Skin Sensitization Potency Categorization
Skin sensitization testing identifies substances that may
act as sensitizers and cause the development of allergic contact dermatitis.
Use of the LLNA will refine and reduce animal use for this purpose. |
Milestone |
Date |
Document Link or More Information |
CPSC Nomination |
January 2007 |
PDF |
Peer Review Panel Meeting |
March 2008 |
HTML |
Peer Review Panel Report Published |
May 2008 |
PDF |
ICCVAM Recommendations on the Use of the LLNA for Skin Sensitization Potency Categorization Transmitted to U.S. Federal Agencies |
June 2011 |
View recommendations |
Federal Agency Responses Received |
February 2012 |
View agency responses |
Use of the In Vitro 3T3 NRU Phototoxicity Test
Dermal phototoxicity testing identifies substances that may
increase skin sensitivity to light so that they may be appropriately labeled and packaged.
Use of the in vitro 3T3 NRU phototoxicity test will refine and reduce animal use for this purpose. |
Milestone |
Date |
Document Link or More Information |
OECD Test Guideline 432 Issued |
April 2004 |
PDF |
In Vitro Method for Measuring Skin Absorption
Dermal toxicity testing identifies substances that may
be poisonous when absorbed through the skin so that they may be appropriately labeled and packaged.
Use of this test method may reduce animal use for this purpose. |
Milestone |
Date |
Document Link or More Information |
OECD Test Guideline 428 Issued |
April 2004 |
PDF |
Draft Test Guideline for the In Vitro Mammalian Cell Micronucleus Test
Genetic toxicity testing identifies substances that may
cause DNA damage and increase risk of cancer or birth defects.
Use of the In Vitro Mammalian Cell Micronucleus Test could reduce animal use for this purpose. |
Milestone |
Date |
Document Link or More Information |
Submission of ICCVAM Comments on Draft Test Guideline to U.S. OECD National Coordinator |
February 2007 |
HTML |
Test Guideline 487 Adopted by OECD |
July 2010 |
PDF |
Frog Embryo Teratogenesis Assay:
Xenopus (FETAX)
Developmental toxicity testing identifies substances that may cause
birth defects so that they may be appropriately labeled.
Use of FETAX could reduce or replace animal use for this purpose. |
Milestone |
Date |
Document Link or More Information |
EPA Nomination |
May 1998 |
- |
Background Review Document Published |
March 2000 |
HTML |
Expert Panel Meeting |
May 2000 |
PDF |
Evaluation of In Vitro ER and AR Binding and TA Assays
Endocrine disruptor testing identifies substances that may
interfere with normal human and animal development.
Use of in vitro tests could reduce animal use for this purpose in the EPA Endocrine Disruptor Screening Program (EDSP). |
Milestone |
Date |
Document Link or More Information |
EPA Nomination |
April 2000 |
- |
Expert Panel Meeting |
May 2002 |
HTML |
Expert Panel Report |
September 2002 |
PDF |
Background Review Documents Published |
October 2002 |
HTML |
Test Method Evaluation Report Published |
May 2003 |
HTML |
Addendum to Test Method Evaluation Report Published |
September 2006 |
PDF |
BG1Luc ER TA Test Method Validation Study
Endocrine disruptor testing identifies substances that may
interfere with normal human and animal development.
Use of the BG1Luc ER TA test method could reduce animal use for this purpose in the EPA EDSP. |
Milestone |
Date |
Document Link or More Information |
BG1Luc ER TA Test Method Nomination |
January 2004 |
PDF |
Draft Pre-Screen Evaluation Released |
August 2004 |
PDF |
Submission of the Standard Project Submission Form
to the OECD Test Guidelines Program:
Stably Transfected Transcriptional Activation Assay
for the Detection of Estrogen Receptor Agonists and Antagonists |
September 2007 |
PDF |
Validation Study Initiated |
November 2007 |
HTML |
Peer Review Panel Meeting |
March 2011 |
HTML |
ICCVAM Recommendations on the Use of the BG1Luc ER TA Test Method Transmitted to U.S. Federal Agencies |
February 2012 |
View recommendations |
ICCVAM Recommendations on the Use of the BG1Luc ER TA Test Method Accepted by U.S. Federal Agencies |
August 2012 |
View recommendations and agency responses |
Test Guideline 457 Adopted by OECD |
October 2012 |
PDF |
CertiChem Inc. MCF-7 Cell Proliferation Assay Evaluation
Endocrine disruptor testing identifies substances that may
interfere with normal human and animal development.
Use of the MCF-7 Cell Proliferation Assay could reduce animal use for this purpose in the EPA EDSP. |
Milestone |
Date |
Document Link or More Information |
MCF-7 Cell Proliferation Assay Nomination |
June 2004 |
PDF |
Pre-Screen Evaluation Released |
October 2006 |
PDF |
Validation Study Initiated |
June 2010 |
HTML |
Validation Study Completed |
2011 |
- |
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 |
Acceptance of Test Methods by European Pharmacopeia |
March 2009 |
- |
Acceptance by Federal Agencies |
May 2009 |
HTML |
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 |
Alternative Methods for Botulinum Toxin Potency Testing
Animal testing of botulinum toxin is performed
to ensure that each lot of this product is safe and effective.
An ICCVAM-sponsored workshop explored ways to reduce, refine, or replace animal use for this purpose. |
Milestone |
Date |
Document Link or More Information |
Nomination by the Humane Society of the United States |
October 2005 |
PDF |
Workshop Held |
November 2006 |
HTML |
Workshop Report Published |
February 2008 |
PDF |
Alternative Methods for Vaccine Potency and Safety Testing
Animal testing of vaccines is performed
to ensure that each lot of these products is safe and effective.
An ICCVAM-sponsored workshop explored ways to reduce, refine, or replace animal use for this purpose. |
Milestone |
Date |
Document Link or More Information |
Workshop Held |
September 2010 |
HTML |
Workshop Proceedings Published |
December 2011 |
Workshop Report |
Alternative Methods for Rabies Vaccine Potency Testing
Animal testing of rabies vaccines is performed
to ensure that each lot of these products is effective for its intended use.
An ICCVAM-sponsored workshop will explore ways to reduce, refine, or replace animal use for this purpose. |
Milestone |
Date |
Document Link or More Information |
Workshop Held |
October 2011 |
View webpage |
Workshop Report Published |
September 2012 |
Workshop Report |
Alternative Methods for Leptospira Vaccine Potency Testing
Animal testing of Leptospira vaccines is performed
to ensure that each lot of these products is effective for its intended use.
An ICCVAM-sponsored workshop will explore ways to reduce, refine, or replace animal use for this purpose. |
Milestone |
Date |
Document Link or More Information |
Workshop Held |
September 2012 |
View webpage |
Alternatives to the HIST Test for Acellular Pertussis Vaccines
Animal testing of acellular pertussis vaccines is performed
to ensure that each lot of these products is safe for use.
An ICCVAM-sponsored workshop will explore ways to reduce, refine, or replace animal use for this purpose. |
Milestone |
Date |
Document Link or More Information |
Workshop Held |
November 2012 |
View webpage |