Background and Purpose: Potential effects of plastic microparticles (MPs) on human health is of increasing interest to scientists and regulators given their ubiquitous presence in the environment. Some reviews of these data have reported potential developmental and reproductive toxicity (DART) as the “critical effects” (effects exhibiting the lowest NOAEL/BMD) of MPs. Understanding potential hazards and risks associated with MPs is an evolving science; however, the issue of insufficient particle characterization by studies evaluating such has been raised given the importance of physicochemical properties and potential impacts on biological systems. This study applies systematic methods to gather, appraise, and integrate the relevant empirical evidence of potential effects of MPs on DART outcomes in both epidemiological and experimental animal studies. Methods: This assessment was conducted using a stepwise and highly refined systematic approach based on problem formulation exercises that were documented in an a priori protocol. Following an evidence identification stage, a critical appraisal method that combines explicit and transparent determinations of risk of bias (systematic error), test article attributes and characterization information (based on the published Nano- and Microplastic Particle Toxicity Assessment Tool), with internal and construct validity evaluations for DART study conduct and reporting (based on subject matter expertise) was applied. Results: The systematic literature search (first performed on December 17, 2021 and updated on April 4, 2023) resulted in identification of 22 publications that met the inclusion criteria. These 22 publications were then evaluated for internal validity. Key areas of uncertainty included: consistent lack of comprehensive particle characterization, ambiguity in details of test agent administration, and flaws in outcome assessment methodologies. Particle characterization risk of bias was driven by insufficient reporting on critical components such as particle stability within the test medium, specific details regarding the suspension matrix (e.g., additives, components of suspension), and particle concentration in terms of number/volume. Aspects of test material administration that were not well defined by study methodologies include a lack of analytical verification of concentrations, lack of measuring homogeneity and stability of the test substance (especially in drinking water studies), and lack of methods on test material preparation, including basic information such as the vehicle used. Outcome assessments generally lacked reporting of specific methodology for assessment of sperm parameters and histopathological examination/scoring of testis and ovarian tissues. Based on the internal validity evaluation, 6 of the 22 studies achieved sufficient scores to proceed in the evaluation. These studies report effects of exposure to pristine polystyrene MPs in mice (ICR, BALB/C, or C57BL/6 strains) via drinking water or gavage with exposure periods ranging from ~18 days (i.e., gestational exposure) to 90 days. Polymer sizes ranged from 0.5 – 10 µm, with 5 µm particles being the most frequent. Three studies assessed male reproductive toxicity, including sperm parameters, testicular histopathology, and organ weights. Three studies assessed female reproductive toxicity with F1 generation evaluations; one of these studies also included a limited assessment of the F2 generation. None of the identified studies followed published standardized and harmonized OECD/EPA test guidelines. In the final stage of the assessment framework, these 6 studies were evaluated in context of applicability in risk assessment. This evaluation included determining whether key criteria for assessing risk were established in each of the studies (i.e., statistical analysis, dose-response relationship, relevant concentration range, reporting of an effect threshold or adequate data to derive one, and test particle relevance). No study sufficiently met the minimum standards for use as a candidate study in risk assessment and development of reference values. Conclusions: This assessment underscores the need for robust and appropriate study design that consider critical QA/QC criteria, in conjunction with adequate reporting, to increase the confidence and reliability of studies available to inform important scientific policy questions.