The Piperonyl Butoxide Task Force II, a group of companies that produces or markets PBO-containing products, has conducted all 11 EDSP Tier 1 screens and has submitted all required documentation and study reports. The US EPA intends to use a weight of evidence (WoE) approach for assessing EDSP Tier 1 results. While the agency issued WOE guidelines, no actual WOE assessments have yet been conducted and released to the registrants. The PBTFII has conducted a WoE analysis for PBO that is consistent with EPA’s guidelines. The WoE analysis for PBO examines each EDSP Tier 1 assay conducted for PBO. It discusses the purpose of the assay, and summarizes the study design and results and provides an overall conclusion for each assay. All 11 individual assays are then considered together to arrive at an overall conclusion for the outcome of the Tier 1 battery. For some assays, other scientifically relevant information is also considered as part of the assessment. The purpose of the WoE analysis is to determine whether PBO has the potential to interact with the endocrine system, as determined by EDSP Tier 1 assays, the Tier 1 battery as a whole and OSRI. A determination that a chemical has the potential to interact with the endocrine system would trigger a need for EDSP Tier 2 testing. The EPA is planning to issue their WOE assessment in late 2014 or early 2015. Subchronic and chronic/carcinogenicity studies Subchronic and chronic studies examine the toxicity of longer-term, repeated exposure to chemicals. They may range from 90 days for subchronic studies, to 12–24 months for full lifetime chronic studies, designed to determine potential for carcinogenesis. They are also intended to identify any noncancer effects, as well as a clear no observable adverse effect level (NOAEL) that is used for risk assessment. Studies conducted on PBO include: 90-day inhalation toxicology study 18-month chronic toxicity/carcinogenicity study in mice 24-month chronic toxicity/carcinogenicity study in rats NOAELs were derived for PBO from both subchronic and chronic studies. These NOAELs are used by the EPA to conduct risk assessments for all individual uses of PBO to ensure that all registered products with PBO pose a reasonable certainty of no harm used according to the label directions. PBO caused an increase in liver tumors in mice that ingested high levels of PBO in the diet for their entire lifetimes. The scientific identification and analysis of the key events leading