Notice of Change to RFA-ES-15-016 "NIEHS SBIR Phase IIB Awards for Validation and Commercialization of Approaches to Reduce Animal Use in Toxicology Testing (U44)"

Notice Number: NOT-ES-16-010

Key Dates
Release Date:  August 29, 2016

Related Announcements
RFA-ES-15-016   

Issued by
National Institute of Environmental Health Sciences (NIEHS)

Purpose

This Notice is to inform potential applicants of changes to RFA-ES-15-016 "NIEHS SBIR Phase IIB Awards for Validation and Commercialization of Approaches to Reduce Animal Use in Toxicology Testing (U44).

Part 2. Section I. Funding Opportunity Description

Purpose

Currently reads:

  • Applicants are encouraged to contact staff at US federal agencies to ensure that their validation plan and objectives follow the relevant requirements or guidance of that authority. Applicants can find appropriate contacts at US federal agencies through ICCVAM by contacting shaughn1@niehs.nih.gov

Modified to read:

  • Applicants are encouraged to contact ICCVAM (iccvam@niehs.nih.gov) to ensure that their validation plan and objectives are relevant to the federal regulatory community. NIEHS program staff will communicate responses from ICCVAM to the applicants.

Part 2. Section I. Funding Opportunity Description

Specific Objectives for SBIR Phase IIB Award Applications

Currently reads:

The NICEATM program priority areas for alternative test method development and validation include, but are not limited to:

  • Ocular Toxicity Testing: Alternative testing approaches (using in vitro or ex vivo assays) to determine eye irritation and corrosion potential remain a high priority. Specifically, tests that are able to differentiate among EPA’s four eye irritation hazard categories (I – IV) are highly desirable. In developing ocular toxicity tests, weight-of-evidence approaches that consider, for example, in vivo testing, structure-activity relationships, and read-across for results on similar test materials, or a decision tree approach, to support a classification are acceptable. Developed Ocular Toxicity Testing schemes for the EPA should be predictive of a range of chemistries such as alkaline and acidic chemistries, surfactant and solvent-based chemistries, and oxidizing chemistries (such as hypochlorite, peroxide, percarbonate, oxygen, bleaches). Testing Regulations and Guidelines for eye irritation/corrosion tests may be found at http://ntp.niehs.nih.gov/pubhealth/evalatm/regs-guidelines/.
  • Reproductive and Developmental Toxicity Testing, to include testing for Endocrine Disruptors: Reproductive and developmental toxicity testing are among the most animal use intensive areas in regulatory toxicology. Therefore, alternative approaches to assess reproductive and developmental toxicity, including endocrine disruption effects, are highly desirable. Alternative approaches may include new in vitro assays, combinations of assays in an integrated strategy designed to cover mechanisms of action and adverse outcomes, as well as computational methods to predict toxicity. The use of phylogenetically lower organisms may also be appropriate.  Testing Regulations and Guidelines from federal agencies for reproductive and developmental toxicity testing, including endocrine disruption, may be found at http://ntp.niehs.nih.gov/pubhealth/evalatm/regs-guidelines/
  • Carcinogenicity Testing: Carcinogenesis is a complex process, often involving multiple organ systems; as such, it is unlikely that a single, predictive alternative method will be appropriate for carcinogenicity testing. In vitro and in vivo genotoxicity tests may contribute to the assessment of genotoxic carcinogens; however, few tests for non-genotoxic assessments exist. Examples of non-animal alternative methods include cell transformation assays (CTA) to detect carcinogenic changes and the gap junction intercellular communication (GJIC) method to detect nongenotoxic carcinogens or tumor promotors. Alternative approaches may include new in vitro assays, qualitative structure-activity relationship and computational methods to predict toxicity, or combinations of assays in an integrated strategy designed to cover mechanisms of action and adverse outcomes. Mutagenicity and genotoxicity assays may also inform the carcinogenesis process. Testing Regulations and Guidelines from federal agencies for genotoxicity and carcinogenicity may be found at http://ntp.niehs.nih.gov/pubhealth/evalatm/regs-guidelines/
  • Acute Toxicity Testing: Current in vivo acute systemic toxicity testing involves an assessment of the general toxic effects of a single dose or multiple doses of a chemical or product, by a particular route (oral, dermal, inhalation), and that occur during a subsequent observation period. Acute toxicity data are common requirements under many regulatory frameworks to provide classification and labelling warning or the possible consequence of exposure to a chemical.  Substances that require classification and labeling include industrial chemicals, biocides, and pesticides.  While a number of acute toxicity testing approaches have been developed and adopted by OECD, additional validated methods are needed. Alternative test methods for oral and acute inhalation toxicity testing are a high priority area for this FOA. Testing Regulations and Guidelines from federal agencies Acute Toxicity Testing may be found at http://ntp.niehs.nih.gov/pubhealth/evalatm/regs-guidelines/

Modified to read:

The NICEATM/ICCVAM program priority areas for alternative test method development and validation include, but are not limited to:

  • Ocular Toxicity Testing: Alternative testing approaches (using in vitro or ex vivo assays) to determine eye irritation and corrosion potential remain a high priority. Specifically, tests that are able to differentiate among EPA’s four eye irritation hazard categories (I – IV) are highly desirable. In developing ocular toxicity tests, weight-of-evidence approaches that consider, for example, existing in vivo testing, structure-activity relationships, and read-across for results on similar test materials, or a decision tree approach, to support a classification are acceptable. Developed Ocular Toxicity Testing schemes for the EPA should be predictive of a range of chemistries such as alkaline and acidic chemistries, surfactant and solvent-based chemistries, and oxidizing chemistries (such as hypochlorite, peroxide, percarbonate, oxygen, bleaches). Testing Regulations and Guidelines for eye irritation/corrosion tests may be found at http://ntp.niehs.nih.gov/pubhealth/evalatm/regs-guidelines/
  • Developmental and Reproductive Toxicity Testing: Developmental and reproductive toxicity testing are among the most animal-use intensive areas in regulatory toxicology. Therefore, alternative approaches to assess developmental and reproductive toxicity are highly desirable. Alternative approaches may include new in vitro assays, combinations of assays in an integrated strategy designed to cover mechanisms of action and adverse outcomes, as well as computational methods to predict toxicity. The use of phylogenetically lower organisms may also be appropriate. Testing Regulations and Guidelines from federal agencies for reproductive and developmental toxicity testing, including endocrine disruption, may be found at http://ntp.niehs.nih.gov/pubhealth/evalatm/test-method-evaluations/dev-tox/nonanimal/index.html
  • Carcinogenicity Testing: Carcinogenesis is a complex process, often involving multiple organ systems; as such, it is unlikely that a single, predictive alternative method will be appropriate for carcinogenicity testing. In vitro and in vivo genotoxicity tests may contribute to the assessment of genotoxic carcinogens; however, few tests for non-genotoxic assessments exist. Examples of non-animal alternative methods include cell transformation assays (CTA) to detect carcinogenic changes and the gap junction intercellular communication (GJIC) method to detect nongenotoxic carcinogens or tumor promotors. Alternative approaches may include new in vitro assays, qualitative structure-activity relationship and computational methods to predict toxicity, or combinations of assays in an integrated strategy designed to cover mechanisms of action and adverse outcomes. Mutagenicity and genotoxicity assays may also inform the carcinogenesis process. Testing Regulations and Guidelines from federal agencies for genotoxicity and carcinogenicity may be found at http://ntp.niehs.nih.gov/pubhealth/evalatm/regs-guidelines/
  • Acute Toxicity Testing: Current in vivo acute systemic toxicity testing involves an assessment of the general toxic effects of a single dose or multiple doses of a chemical or product, by a particular route (oral, dermal, inhalation), during a subsequent observation period. Acute toxicity data are common requirements under many regulatory frameworks to provide classification and labelling warning of the possible consequence of exposure to a chemical. Substances that require classification and labeling include industrial chemicals, biocides, and pesticides. While a number of acute toxicity testing approaches have been developed and adopted by OECD, additional validated methods are needed. Alternative test methods for acute oral and inhalation toxicity testing, including the validation of 3D organotypic models for toxicant screening, are a high priority area for this FOA. Testing Regulations and Guidelines from federal agencies for Acute Toxicity Testing may be found at http://ntp.niehs.nih.gov/pubhealth/evalatm/regs-guidelines/

All other aspects of the FOA remain the same.

Inquiries

Please direct all inquiries to:

Daniel Shaughnessy, PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: (919) 541-2506
Email: Shaughn1@niehs.nih.gov