Skip to Main Navigation
Skip to Page Content

COVID-19 is an emerging, rapidly evolving situation.

Get the latest public health information from CDC and research information from NIH.

U.S. flag

An official website of the United States government

Dot gov

The .gov means it's official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you're on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Share This:
https://ntp.niehs.nih.gov/go/refchem

Chemical Lists for Test Method Development and Evaluation

Below are lists of chemicals that may be useful for development or evaluation of new test methods. Some lists were developed during studies on new test methods and approaches conducted by NICEATM or compiled by NICEATM for inclusion in the Integrated Chemical Environment (ICE). Others have been recommended by ICCVAM or others for validation of alternative test methods.

  • Reference Chemical Lists (indicated with an "R" below) include chemicals that cause a specified well-characterized biological effect and therefore can be used to assess the performance of an assay designed to measure that effect.
  • Non-reference Chemical Lists have inclusion criteria that are less restrictive than those of reference chemical lists. These lists may include chemicals with uncharacterized or ambiguous biological effects.

Lists are downloadable as both Excel spreadsheets and tab-delimited text files. Lists may also be downloaded from ICE.

Where applicable, the sections below also include links to the ICCVAM Test Method Evaluation Reports or references in the scientific literature in which the lists were originally published. Links are also available to pages on the NICEATM website that have additional information about the context under which some lists were developed. Users of these lists are encouraged to consult these resources to help them decide whether any of these lists might be useful for a specific test method development activity.

Acute Systemic Toxicity

Recommended Reference Substances for Evaluation of In Vitro Basal Cytotoxicity Methods for Predicting the Starting Dose for Rodent Acute Oral Toxicity Tests

Published as Table 3-1 in:
Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). ICCVAM test method evaluation report: in vitro cytotoxicity test methods for estimating starting doses for acute oral systemic toxicity tests. National Institute of Environmental Health Sciences; 2006 Nov. NIH Publication No.: 07-4519.

More information about the NICEATM validation study of in vitro cytotoxicity test methods

Chemicals Evaluated for Carcinogenic Activity

EPA IRIS Carcinogenicity Classifications

This list contains chemicals classified for weight of evidence of carcinogenicity according to the EPA Guidelines for Carcinogen Risk Assessment (2005). Detailed information on these chemicals is available in the EPA IRIS database.

Genotoxicity Classifications

This list  includes chemicals reviewed for Ames test results and genotoxicity classifications by Kirkland et al. 2016. Chemicals are classified as either Ames positive or Ames negative. Chemicals are also classified as “Genotoxic” or “Not genotoxic” based on a combination of Ames test results, in vivo genotoxicity results, in vitro mammalian cell tests, and carcinogenicity findings.

IARC Classifications

This list contains chemicals classified in IARC Monographs 1-125 evaluating carcinogenicity to humans. Agents are classified according to four criteria:

  • Group 1: Carcinogenic to humans
  • Group 2A: Probably carcinogenic to humans
  • Group 2B: Possibly carcinogenic to humans
  • Group 3: Not classifiable as to its carcinogenicity to humans

NTP Cancer Bioassay Chemicals

This list contains environmental and occupational chemicals with data collected from NTP two-year bioassays to assess toxic and/or carcinogenic effects in rodents. NTP describes the strength of the evidence for conclusions regarding each chemical using five categories of carcinogenic activity: Clear Evidence of Carcinogenic Activity (CE), Some Evidence of Carcinogenic Activity (SE), Equivocal Evidence of Carcinogenic Activity (EE), No Evidence of Carcinogenic Activity (NE), and Inadequate Study of Carcinogenic Activity (IS).

RoC Classifications

This list contains chemicals classified for carcinogenic potential according to the 14th Report on Carcinogens. Chemicals are listed as either "Known" carcinogens or "RAHC" (Reasonably Anticipated to Be Human Carcinogens).


Endocrine-active Substances

Androgen Receptor Agonist and Antagonist Chemicals

Published as Table 2 in:
Kleinstreuer NC, et al. Development and validation of a computational model for androgen receptor activity. Chem Res Toxicol. 2016;30(4):946-964. doi: 10.1021/acs.chemrestox.6b00347.

Published as Table 3 in:

Browne P, et al. Development of a curated Hershberger database. Reproductive Toxicol. 2018;81:259-271. doi: 10.1016/j.reprotox.2018.08.016
Please note: the lists above do not include chemicals included in Table 3 of Browne et al. but described as giving conflicting results in multiple in vivo assays.

Androgen Steroidogenesis

Published as Table 2 in:

Pinto CL, et al. Identification of candidate reference chemicals for in vitro steroidogenesis assays. Toxicology In Vitro 2018;47:103-119. doi:10.1016/j.tiv.2017.11.003

Estrogen Receptor Agonist and Antagonist Chemicals

Published as Tables 2 and 3 in:
Browne P, et al. Screening chemicals for estrogen receptor bioactivity using a computational model. Environ Sci Technol. 2015 Jul 21;49(14):8804-8814. doi: 10.1021/acs.est.5b02641.

Published as Table 1 in:
OECD. Test no. 455: performance-based test guideline for stably transfected transactivation in vitro assays to detect estrogen receptor agonists and antagonists. In: OECD guidelines for the testing of chemicals. Section 4. Paris: OECD Publishing; 2016. doi: 10.1787/9789264265295-en.

Curated Database of Rodent Uterotrophic Bioactivity

NICEATM compiled data from the peer-reviewed literature for in vivo uterotrophic assays that met six minimum criteria specified by accepted test guidelines. These data have potential utility for:

  • Developing adverse outcome pathways or models of estrogenic activity.
  • Prioritizing chemicals for further testing.
  • Evaluating species-specific responses to chemicals.

NICEATM Guideline-like Uterotrophic Database
More information about the Uterotrophic Database

Estrogen Steroidogenesis

Published as Table 3 in:

Pinto CL, et al. Identification of candidate reference chemicals for in vitro steroidogenesis assays. Toxicol In Vitro 2018;47:103-119. doi:10.1016/j.tiv.2017.11.003

Thyroid Activity

Published as supplemental data in:

Wegner S, et al. Identifying reference chemicals for thyroid bioactivity screening. Reproductive Toxicol  2016;65:402-413. doi:10.1016/j.reprotox.2016.08.016
Please note: only chemicals having a definitive classification of “active” or “inactive” are included.

EPA Chemical Lists

EPA IRIS Carcinogenicity Classifications

This list contains chemicals classified for weight of evidence of carcinogenicity according to the EPA Guidelines for Carcinogen Risk Assessment (2005). Detailed information on these chemicals is available in the EPA IRIS database.

EPA Pesticide Active Ingredients

This list contains chemicals identified as pesticide active ingredients, defined by EPA as the chemicals in a pesticide product that act to control the pests. This list was downloaded from the EPA Chemistry Dashboard on May 27, 2020.

EPA Pesticide Inert Ingredients, Food and Nonfood Use

This list contains chemicals defined by EPA as pesticide inert ingredients, food and nonfood use. The chemicals on this list are inert ingredients used in pesticide products applied to food that have either tolerances or tolerance exemptions in the Code of Federal Regulations (CFR), 40 CFR part 180, or where no residues are found in food. This list was downloaded from the EPA Chemistry Dashboard on May 27, 2020.

Eye Corrosion and Irritation

Recommended Substances for Optimization or Validation of In Vitro Ocular Toxicity Test Methods

Published as Appendix H in:
Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). ICCVAM test method evaluation report: in vitro ocular toxicity test methods for identifying severe irritants and corrosives. National Institute of Environmental Health Sciences; 2006 Nov. NIH Publication No.: 07-4517.

More information about ICCVAM evaluations of in vitro ocular toxicity test methods

Skin Corrosion and Irritation

Recommended Chemicals for Validation of New In Vitro Skin Corrosivity Test Methods

Published in:
Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). Recommended performance standards for in vitro test methods for skin corrosion. National Institute of Environmental Health Sciences; 2004 May. NIH Publication No.: 04-4510.

More about development of the performance standards

Skin Sensitization

Recommended Reference Substances for the Murine Local Lymph Node Assay (LLNA)

Published as Appendix F in:
Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). Recommended performance standards: murine local lymph node assay. National Institute of Environmental Health Sciences; 2010. NIH Publication No.: 09-7357.

NICEATM LLNA Database

Data from analyses of the LLNA conducted on behalf of ICCVAM by NICEATM are available to interested stakeholders as a reference for developing and evaluating alternative approaches to testing and assessment that replace, reduce, or refine the use of animals for identification of potential skin sensitizers.

Tox21 Chemicals

This list includes the 9000+ chemicals tested in the Tox21 Program. Chemicals are from the EPA's invitrodb v3.2 (March 2020).