National Toxicology Program

National Toxicology Program
https://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.

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  
Process for evaluating and implementing alternative approaches to traditional in vivo acute toxicity studies for FIFRA regulatory use (replacement and reduction of animal use) EPA activity 40 CFR 158 NA  
Guidance document on developing and assessing adverse outcome pathways   Accepted by U.S. via OECD Guidance Document 184 (2013) OECD GD 184 (2013) Via OECD
Guidance document on the reporting of defined approaches to be used within integrated approaches to testing and assessment NICEATM and ICCVAM contributed to development of the guidance document Accepted by U.S. via OECD Guidance Document 255 (2016) OECD GD 255 Via OECD
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
Acute Dermal Systemic Toxicity
Method ICCVAM or ICCVAM Agency Contributions U.S. Applicable Guidance OECD Adoption EU Endorsement
Guidance for waiving acute dermal toxicity tests for pesticide formulations and supporting retrospective analysis (reduction of animal use) EPA activity; NICEATM contributed to data analysis EPA guidance (2016) provides for authorizing waivers of required dermal toxicity testing for formulated pesticide products from standard requirements under 40 CFR 158 NA  
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)
USDA guidance for obtaining an exemption from in vivo testing of Leptospira bacterins USDA activity Applies to 9 CFR 113.101-104; VS Memo 800.102 (2013) NA  
USDA Guidelines for Validation of In Vitro Potency Assays USDA activity Applies to 9 CFR 102.3, 113.8; VS Memo 800.112 (2015) NA  
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
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 (2015) NA Via ICH
Immunotoxicity: Allergic Contact Dermatitis
Method ICCVAM or ICCVAM Agency Contributions U.S. Applicable Guidance OECD Adoption EU Endorsement

Adverse outcome pathway for skin sensitization initiated by covalent binding to proteins
(Part 1) (Part 2)

  Accepted by U.S. via OECD GD 168 (2012) OECD GD 168 (2012) Via OECD
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  
Guidance document on the reporting of defined approaches and individual information sources to be used within integrated approaches to testing and assessment (IATA) for skin sensitisation NICEATM and ICCVAM submitted a case study included in the guidance document Accepted by U.S. via OECD GD 256 (2016) OECD GD 256 (2016) Via OECD
Ocular Corrosivity and Irritation
Method ICCVAM or ICCVAM Agency Contributions U.S. Applicable Guidance OECD Adoption EU Endorsement
Histopathological evaluation and collection of data for identification of nonsevere irritants using in vitro methods   Accepted by U.S. via OECD Guidance Document 160 (2011) OECD GD 160 (2011) Via OECD
Non-animal testing scheme for assessing eye irritation potential of antimicrobial cleaning products EPA activity Guidance (2013, updated 2015) describes a non-animal testing scheme to satisfy the in vivo data requirement for eye irritation in 40 CFR 158 for antimicrobial cleaning products NA, but utilizes TG 437 for the BCOP assay  
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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