This is an internal DART Committee Meeting
The DART committee provides a forum where scientists from industry, government, and academia can exchange information and initiate activities to advance science related to DART, and to develop consensus on the appropriate use of experimental data for human health risk assessment.
To promote harmonization of anogenital distance (AGD) and nipple/areola retention measurement in male rats, this project aims to publish a review of existing methods and recommend best practices and considerations for these two methods.
In collaboration with the European Teratology Society, the joint working group has collected historical data on thyroid hormone measurement in rodent studies to determine best practices for these measurements.
The goal of this working group is to determine the degree of reliability and human relevance of in vitro rodent markers/assays for puberty timing endpoints by critically evaluating the epidemiological and toxicological literature on both normal development and altered development after exposures. A series of review articles are underway and anticipated to be completed in 2022.
Clinical pathology data from control animals in previously conducted juvenile animal toxicity studies has been gathered. Data analysis is underway, and a manuscript that could be used as a reference across the industry is in development.
A points-to-consider manuscript is in development, outlining initial approaches to inclusion, the role of nonclinical data, and common practices during global drug development plans.
This working group aims to enable better predictive toxicology for DART effects by sharing relevant knowledge of chemical-protein target interactions, pharmacokinetics, and major developmental toxicity study outcomes. To this end, the team has initiated two case studies on the well characterized teratogens, Retinoic Acid and Thalidomide.
This group strives to provide additional information and confidence that fetal skeletal examination using microCT is acceptable for regulatory use in nonclinical fetal evaluation studies. The study design and participants in a multi-site in vivo study comparing microCT and alizarin red staining is being finalized. Experimental work is anticipated to begin in 2022.
This working group, in collaboration with the HESI Immuno-Safety Technical Committee (ITC), convened key stakeholders to discuss both current and novel methodologies in preclinical and translational safety assessment of pregnancy risk associated with immunomodulatory therapy. This group will sunset after the workshop publication is completed.
This project aims to define which preweaning developmental landmarks (PDLs) have value, interpretation, and benchmark responses through both a survey and data collection.
This working group will collect data on a diverse set of compounds to increase the predictive power of a QSAR model for the prediction of placental transfer in rats; outputs from this model can be used as a tool to enhance the exposure based predictions of in vitro assays.
This working group is organizing a series of webinar modules to train federal and international regulators, clinicians, academic investigators, contract research organization scientists, and private sector scientists on the best practices and principles of interpreting DART data in the context of regulatory frameworks and processes.
The goal of the project is to survey labs using HanWister and Sprague Dawley rats in DART studies to understand if reproductive performance in the strain is waning/evolving. Team will publish findings on this analysis.
This scoping group aims to create a new approach methodologies (NAMs) toolbox that will provide for and clarify the context of use for alternative assays that will comply with various regulatory guidelines so that they can ultimately validate for us as a NAM.
This new initiative aims to leverage the HESI DART Committee’s membership and technical work to facilitate career development (with a focus on training and networking) of the next generation of developmental toxicologists. The program(s) will be advertised outside of the traditional and well-established networks to expand our reach to individuals who belong to historically under-represented groups, thereby broadening the pool of trainees.
National Institute of Environmental Health Sciences / National Toxicology Program
This is an internal DART Committee Meeting
The HESI DART Committee 2021 Spring Meeting will take place on April 20-21, 2021 from 9am-1pm EST. The virtual meeting is open to DART Committee participants only.
The goal of this workshop is to convene key stakeholders to discuss both current and novel methodologies in preclinical and translational safety assessment of pregnancy risk associated with immunomodulatory therapy. Through the sharing of case examples, followed by longer in-depth discussion within each session, the goal ...
Save the date! HESI DART Committee and European Teratology Society Workshop on Thyroid Hormone Assessment: Implications for Developmental and Reproductive Toxicology
This satellite workshop to the 45th Annual Meeting of the European Teratology Society is addressed to participants working in industries or regulatory bodies who are involved in testing and assessment of the potential developmental toxicity of chemicals.
This workshop will consider new strategies to identify developmental hazards taking into account the current state of science which may include alternative possibilities or improvements to the current Segment 2 design. These considerations could include the use of new technology to overcome some of the limitations in ...
Increased research to improve preclinical models to inform the development of therapeutics for neonatal diseases is an area of great need. This article reviews five common neonatal diseases – bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, perinatal hypoxic–ischemic ...
The liver represents a major eliminating and detoxifying organ, determining exposure to endogenous compounds, drugs, and other xenobiotics. Drug transporters (DTs) and drug-metabolizing enzymes (DMEs) are key determinants of disposition, efficacy, and toxicity of drugs. Changes in their mRNA and protein expression levels ...
Drug dosing in neonates should be based on integrated knowledge concerning the disease to be treated, the physiological characteristics of the neonate, and the pharmacokinetics (PK) and pharmacodynamics (PD) of a given drug. It is critically important that all sources of information be leveraged to optimize dose selection for ...
This review provides insight in cross-species developmental differences of absorption, distribution, metabolism, and excretion properties in the kidney, which should be considered in neonate/juvenile study interpretation, hypotheses generation, and experimental design.
The HESI Developmental and Reproductive Toxicology (DART) Committee launched a multisector collaborative research effort to increase the knowledge base in the nonclinical neonatal space to better inform decisions made in the clinic.
This review is part of a multisector collaborative research effort coordinated by the HESI Developmental and Reproductive Toxicology (DART) Committee to increase the knowledge base in the nonclinical neonatal space to better inform clinical treatment decisions made for the newborn patient population (De Schaepdrijver et ...