National Toxicology Program

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%.

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%.

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%.

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.

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.

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.

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.

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.

Alternative Methods for Animal Vaccine Potency and Safety Testing

Animal testing of animal vaccines is performed to ensure that each lot of these products is safe and effective. An ICCVAM-sponsored workshop will explore ways to reduce, refine, or replace animal use for this purpose.

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.

Evaluation of EpiSkin^TM, EPIDERM^TM 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.

Evaluation of EpiSkin^TM, EPIDERM^TM 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.

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.

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).

Xenobiotic Detection Systems, Inc. LUMICELL® ER Assay Validation Study

Endocrine disruptor testing identifies substances that may interfere with normal human and animal development. Use of the LUMICELL® ER Assay could reduce animal use for this purpose in the EPA EDSP.

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.

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.

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.

Development of Performance Standards for the Murine Local Lymph Node Assay (LLNA)

Immunotoxicity 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.

Reduced Murine Local Lymph Node Assay (LLNA)

Immunotoxicity 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.

Nonradioactive Murine Local Lymph Node Assay (LLNA)

Immunotoxicity 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.

Use of the Murine Local Lymph Node Assay (LLNA) for Skin Sensitization Potency Categorization

Immunotoxicity 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.

Use of the Murine Local Lymph Node Assay (LLNA) for Testing Mixtures, Metals, and Aqueous Solutions

Immunotoxicity 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.

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.

In Vitro Test Methods for Detecting Nonsevere Ocular 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 irritation to the eye. Use of these In Vitro Test Methods will reduce and refine animal use for this purpose.

In Vitro Test Methods for Detecting Nonsevere Ocular Irritants

• Cytosensor Microphysiometer Test Method
• 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.

Nonanimal 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.

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.