A systematic review is defined as a high-level review of the available, relevant information in order to extract and analyze all data to address a specific research question. Systematic reviews are becoming an integral part of risk assessments since key steps of the process include using explicit, reproducible methods to identify, select and critically evaluate all quality research in order to minimize bias and provide reliable findings (Cochrane Collaboration 2011). This document provides guidance on how to conduct a systematic literature review and integrate evidence when developing chemical-specific reference values (ReVs) and unit risk factors (URFs). However, this process can also be modified or expanded to address other questions that would benefit from systematic review practices. These guidelines supplement the Texas Commission on Environmental Quality (TCEQ) Regulatory Guidance-442 (RG-442), TCEQ Guidelines to Develop Toxicity Factors (TCEQ 2015). Since the TCEQ published RG-442, systematic review guidelines were needed, which include explicit criteria for determining study quality prior to identifying a key study (e.g., study inclusion and exclusion criteria). Since data are collected from diverse evidence streams (e.g., human clinical data, epidemiological data, animal toxicological studies, mechanistic data), there is a need to evaluate and integrate information from multiple streams to improve the decisionmaking process, increase transparency, minimize bias, and improve consistency between different risk assessments. The systematic review and evidence integration framework can improve regulatory decision-making processes, increase transparency, minimize bias, improve consistency between different risk assessments, and further improve confidence in toxicity factor development. This document is not intended to be an explicit instruction manual, but rather a guide to use for any chemical evaluation.