National Toxicology Program

National Toxicology Program
http://ntp.niehs.nih.gov/go/guidances

Regulatory Guidance on Use of Alternative Methods

View a list of regulations and test guidelines on a separate webpage 

This page lists guidances that have been issued or accepted by U.S. and international regulatory authorities, organized by testing category. These documents do not necessarily establish legally enforceable responsibilities but should instead be viewed as recommendations. Appropriate use of these methods and approaches can reduce animal use and improve animal welfare.

Acute Oral Systemic Toxicity

Method ICCVAM or ICCVAM Agency Contributions U.S. Applicable Guidance OECD Adoption EU Endorsement
Acute toxicity in vitro starting dose procedure, 3T3 cells (reduction and refinement of animal use) ICCVAM 2001 workshop report; ICCVAM 2006 peer review and report; recommended in 2008 Accepted by U.S. agencies in 2008 OECD GD 129 (2010) Via OECD
Acute toxicity in vitro starting dose procedure, NHK cells (reduction and refinement of animal use) ICCVAM 2001 workshop report; ICCVAM 2006 peer review and report; recommended in 2008 Accepted by U.S. agencies in 2008 OECD GD 129 (2010) Via OECD
Harmonized guidance for nonclinical safety studies for pharmaceuticals (reduction of animal use) FDA activity Accepted by FDA via ICH Guidance Document M3(R2) in 2010 NA Via ICH
Waiving or bridging of mammalian acute toxicity tests for pesticides and pesticide products (reduction of animal use) EPA activity EPA guidance (2012) provides for authorizing exemptions from standard requirements under 40 CFR 158.500, 40 CFR 161.340, other regulations and notices NA  
In vitro assays for paralytic shellfish toxin detection (replacement of animal use) FDA activity Receptor binding assay listed as approved method in National Shellfish Sanitation Program Guide for Control of Molluscan Shellfish (2013) NA  
Harmonized guidance for preclinical safety evaluation of biotechnology-derived pharmaceuticals (reduction of animal use) FDA activity Accepted by FDA via ICH Guidance Document S6(R1) in 2012 NA Via ICH

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Biologics Testing

Method ICCVAM or ICCVAM Agency Contributions U.S. Applicable Guidance OECD Adoption EU Endorsement
FDA guidance on preclinical safety evaluation of biotechnology-derived pharmaceuticals (reduction of animal use) FDA activity Accepted via International Conference on Harmonisation Guideline S6 NA Via ICH
FDA guidance on preclinical assessment of investigational cellular and gene therapy products (minimization of animal use) FDA activity Applies to products regulated under 42 U.S.C. 262(i) NA  
USDA provision for exemption to requirement for animal safety testing of veterinary biologics (reduction of animal use) USDA activity Applies to 9 CFR 113.4; VS Memo 800.116 (2013) NA VICH GL50 (2014)

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Dermal Corrosivity and Irritation

Method ICCVAM or ICCVAM Agency Contributions U.S. Applicable Guidance OECD Adoption EU Endorsement
Guidance document on an integrated approach for testing and assessment for skin corrosion and irritation (replacement of animal use)   Accepted by U.S. via OECD GD 203 (2014) OECD GD 203 (2014) Via OECD
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Dermal Phototoxicity

Method ICCVAM or ICCVAM Agency Contributions U.S. Applicable Guidance OECD Adoption EU Endorsement
FDA guidance on photosafety evaluation of pharmaceuticals (reduction or replacement of animal use) FDA activity Accepted via International Conference on Harmonisation Guideline S10 (2013) NA Via ICH
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Immunotoxicity: Allergic Contact Dermatitis

Method ICCVAM or ICCVAM Agency Contributions U.S. Applicable Guidance OECD Adoption EU Endorsement
CPSC guidance to clarify the definition of “strong sensitizer” (reduction or replacement of animal use) CPSC activity Guidance (2014) clarifies acceptability of in vitro test data for testing required under 15 U.S.C. 1261–1278 (FHSA) NA  

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Pyrogen Testing

Method ICCVAM or ICCVAM Agency Contributions U.S. Applicable Guidance OECD Adoption EU Endorsement
In vitro monocyte activation type pyrogen test (replacement of animal use) ICCVAM agency initiative FDA guidance (2012) provides for use in place of USP methods NA  

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Guidance Applicable to Multiple Toxicities

Method ICCVAM or ICCVAM Agency Contributions U.S. Applicable Guidance OECD Adoption EU Endorsement
Guidance regarding replacement, reduction, and refinement of animal use for testing done under the Federal Hazardous Substances Act CPSC activity 15 U.S.C. 1261–1278 NA  
Guidance for waiving or bridging of mammalian acute toxicity tests for pesticides and pesticide products (reduction of animal use) EPA activity 40 CFR 158 NA  
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.