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Replacing Animals for Acute Systemic Toxicity Testing

ICCVAM, with support from NICEATM, built a U.S. strategy and roadmap to use alternative approaches for required acute systemic toxicity testing. Development and implementation of these approaches will involve four key steps:

  1. Defining testing needs
  2. Identifying available alternatives
  3. Developing integrated approaches to testing and assessment
  4. Addressing both scientific and non-scientific challenges

The ICCVAM Acute Toxicity Workgroup is coordinating activities to achieve these goals. They began by finding existing alternatives and deciding what activities were needed to promote their use. They then used this information to develop an implementation plan for addressing the roadmap goals in the area of acute systemic toxicity testing. Activities supporting this effort include:

NICEATM and ICCVAM activities related to this effort are described below and throughout this website.

NICEATM Evaluation of the Use of Acute Oral Hazard Classification to Predict EPA Acute Dermal Hazard Classification

Acute oral and dermal systemic toxicity test data are used to determine hazard label and protective equipment requirements for pesticide users, workers, and handlers.

NICEATM conducted a retrospective data analysis that was used to support EPA guidance on waiving acute dermal toxicity tests for pesticide formulations. This guidance is expected to greatly reduce laboratory animal use.

This analysis used acute oral toxicity data provided by EPA for active ingredients and similar information for pesticide formulations. NICEATM ensured only high-quality data was used in its evaluation. The analysis was summarized in a poster (Paris et al.) presented at the 2016 SOT annual meeting.

Workshops on Alternatives for Acute Toxicity Testing

Two NICEATM workshops assessed the state of the science for replacements for animal use in acute systemic toxicity testing:

  • Attendees at a 2015 workshop on Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing (summarized in Hamm et al. 2017) developed strategies to advance alternative methods for product safety testing that meet the needs of regulatory agencies (workshop organized by NICEATM, PISC, and PCRM).
  • A 2016 workshop and webinar series (summarized in Clippinger et al. 2018) focused on needs to replace animals for acute inhalation toxicity testing (workshop and webinars organized by NICEATM and PISC).
Use of High-Throughput Screening Data to Reduce Animal Use for Acute Oral Toxicity Testing

NICEATM evaluated the use of high-throughput screening (HTS) data from the interagency Tox21 and the EPA ToxCast programs to reduce animal use for acute oral toxicity testing. The data were analyzed for correlation and model fit to rat oral LD50 data to determine which tests or combinations of tests best characterized rat oral toxicity data. The analysis suggested that, for some substances, combinations of in vitro assays and data from small model organisms such as zebrafish could be used to predict outcomes of rat acute oral toxicity tests. This project was described in a poster presentation (Polk et al.) at the 2015 SOT annual meeting.

Request for Data and Information on Technologies Used to Identify Substances with the Potential to Cause Acute Systemic Toxicity

NICEATM requests available data and information on approaches and/or technologies currently used to identify substances with the potential to cause acute systemic toxicity when:

  • Swallowed
  • Inhaled
  • Absorbed through the skin

Submitted information will be used to assess the state of the science and determine technical needs for non-animal test methods.

Acute systemic toxicity tests are conducted to determine whether a single or short-term dose of a substance can cause illness or death when inhaled (inhalation toxicity testing), swallowed (oral toxicity testing), or absorbed through the skin (dermal toxicity testing). These tests are required by multiple regulatory agencies and can use large numbers of animals. NICEATM supports efforts to develop, validate, and implement alternative approaches for acute systemic toxicity testing that replace, reduce, or refine animal use.

While the Federal Register notice asked that data be submitted by September 2016, NICEATM continues to accept submissions of relevant data. Respondents should provide information on any activities relevant to the development or validation of alternatives to in vivo tests currently required by regulatory agencies that assess acute oral, dermal, or inhalation toxicity. Of specific interest are chemical-specific data from non-animal tests for acute systemic toxicity hazard, as well as available data on the same chemicals from in vivo acute systemic toxicity tests, such as human or animal studies or accidental human exposures.

Respondents should include their name, affiliation (if applicable), mailing address, telephone, email, and sponsoring organization (if any) with their communications.

Responses to this notice are posted on this page, so no proprietary, classified, confidential, or sensitive information should be included in responses.

Responses to Federal Register Notice