4.1. Overview of the PICS Approach

The PICS approach updates and expands on the long-term strategy described in the Working Approach for Potential Candidates document and integrates information from a variety of sources to better understand publicly available information for these chemical substances. The PICS approach synthesizes information from traditional methods and NAMs in key scientific domains including human health hazard to exposure ratio (incorporating multiple specific toxicities), ecological hazard, carcinogenicity, genotoxicity, exposure to susceptible populations, persistence/bioaccumulation, skin sensitization, and skin/eye irritation. For each scientific domain, a workflow was developed that specifies what information is utilized and the logic of how it is integrated. The methodology underlying the individual workflows are designed to incorporate scientific advances in each discipline and may differ from domain to domain. The domain-specific workflows are described in detail in the subsequent sections. Consistent with the Strategic Plan to Reduce the Use of Vertebrate Animals in Chemical Testing²³, the PICS approach integrates NAMs to fill gaps when traditional testing data are not available. In general, each workflow is based on previously accepted methods for prioritizing chemical substances under TSCA²⁴, with a focus on the use of data from study types for which there is traditionally the most confidence in the regulatory toxicology community (e.g., in vivo), followed by those with decreasing confidence depending on the context for use (e.g., in vitro, in silico). Unless otherwise described, the domain-specific workflows generally utilize conservative assumptions to reduce the potential for false negatives at the initial screening stage. This document also presents potential options for future work to improve the approach, as well as caveats and limitations.

The PICS approach is based on two dimensions allowing visualization and separation of the chemical substances along each dimension (Figure 1). The first dimension reflects the overall degree of potential concern related to human health and the environment and is the integration of the individual results from the domain-specific workflows. In the PICS approach, this dimension is referred to as the Scientific Domain Metric (SDM).

Figure 1

Schematic of the Public Information Curation and Synthesis (PICS) approach. The approach integrates publicly available information from seven scientific domains that represent human health and environmental hazard topics into a Scientific Domain Metric (more...)

The second dimension reflects the relative coverage of potentially relevant human health and ecological toxicity and exposure publicly available information that could inform level of effort and resources that may be needed to evaluate that specific chemical substance. This dimension is referred to as the Information Availability Metric (IAM). The level of effort and resources is typically context specific and informed by expert judgment; however, an expert driven approach is not scalable to apply to the thousands of chemical substances on the TSCA active inventory at the initial screening stage. Therefore, a set of modifying criteria were used to inform the set of potentially relevant human health and ecological toxicity information. The modifying criteria were modeled after considerations used in the TSCA New Chemicals Program and include a combination of functional use considerations, environmental half-life, water solubility, molecular weight, and whether the chemical substance is a TSCA exempt polymer. The existence of an authoritative human health assessment would also contribute to this metric. In the PICS approach, the summary result from this dimension is referred to as the IAM.

The SDM and IAM are combined into a graphical representation of the PICS approach for the chemical substances on the TSCA active inventory. In response to public comments, the PICS approach moved away from the defined ‘bins’ of chemical substances that had been proposed in the Working Approach for Potential Candidates. The PICS approach does not determine what a result for a specific chemical substance represents, rather it provides a synthesis of the public information available for individual chemical substances.

4.2. What the PICS Approach is Intended to Accomplish

The current non-confidential, active TSCA inventory contains over 33,000 chemical substances²⁵ with varying amounts and types of available information. Historical approaches that search, compile, and manually evaluate relevant information are very time and resource intensive and are not be feasible for large number of chemical substances. As part of the development of a long-term strategy to inform selection of candidates for further review, an automated approach was developed that extracts, stores, and integrates publicly available information from traditional toxicology, exposure, and environmental fate-related studies, as well as NAMs. The approach relies on an information management and technology infrastructure to efficiently and transparently perform these functions and is one of possible tools that may inform candidate selection for prioritization of TSCA inventory chemical substances. A representation of the PICS approach within candidate identification is provided in Figure 2. The PICS approach is intended to accomplish the following aims:

• Understand the landscape of publicly available information on the over 33,000 data poor and data rich chemical substances on the TSCA active inventory and aid in identifying candidates for prioritization;
• Provide a transparent and reproducible process for integrating available information and identifying potential information gaps;
• Increase efficiency and manage workload by focusing expert review on chemical substances that may have a greater potential for selection as high- or low priority candidates;
• Create a flexible and sustainable process that can adapt to scientific advances and continual generation of new scientific information; and
• Organize the process into modular workflows that can be readily adapted to address prioritization needs under other mandates.

Figure 2

Schematic of the PICS Approach in Relation to Identifying High- and Low priority Candidate Chemical Substances. The PICS approach is a tool that can be used to inform identification of candidate chemical substances. The PICS approach combines results (more...)

4.3. What the PICS Approach is Not Intended to Accomplish

In order to manage expectations, it is also important to define what lies outside the domain of the PICS approach. The PICS approach is not intended to:

• Replace the formal TSCA prioritization or risk evaluation processes;
• Create a ranked list of chemical substances;
• Signal that the EPA has concerns with particular chemical substances or categories of chemical substances;
• Supplant expert judgment and review;
• Utilize confidential business information (CBI); or
• Incorporate systematic review of information to address study and data quality.