scholarly journals Scientific and Regulatory Policy Committee Points to Consider Review

2016 ◽  
Vol 44 (6) ◽  
pp. 789-809 ◽  
Author(s):  
Wendy G. Halpern ◽  
Mehrdad Ameri ◽  
Christopher J. Bowman ◽  
Michael R. Elwell ◽  
Michael L. Mirsky ◽  
...  
Keyword(s):  
Working Group ◽  
Developmental Toxicity ◽  
Regulatory Policy ◽  
Toxicity Testing ◽  
Clinical Pathology ◽  
End Points ◽  
Anatomic Pathology ◽  
Toxicity Studies ◽  
Study Type ◽  
Policy Committee

Standard components of nonclinical toxicity testing for novel pharmaceuticals include clinical and anatomic pathology, as well as separate evaluation of effects on reproduction and development to inform clinical development and labeling. General study designs in regulatory guidances do not specifically mandate use of pathology or reproductive end points across all study types; thus, inclusion and use of these end points are variable. The Scientific and Regulatory Policy Committee of the Society of Toxicologic Pathology (STP) formed a Working Group to assess the current guidelines and practices on the use of reproductive, anatomic pathology, and clinical pathology end points in general, reproductive, and developmental toxicology studies. The Working Group constructed a survey sent to pathologists and reproductive toxicologists, and responses from participating organizations were collected through the STP for evaluation by the Working Group. The regulatory context, relevant survey results, and collective experience of the Working Group are discussed and provide the basis of each assessment by study type. Overall, the current practice of including specific end points on a case-by-case basis is considered appropriate. Points to consider are summarized for inclusion of reproductive end points in general toxicity studies and for the informed use of pathology end points in reproductive and developmental toxicity studies.

scholarly journals Scientific and Regulatory Policy Committee Points to Consider*: Review of Scientific and Regulatory Policy Committee Points to Consider: Review of Current Practices for Ultrastructural Pathology Evaluations in Support of Nonclinical Toxicology Studies

2019 ◽  
Vol 47 (4) ◽  
pp. 461-468
Author(s):  
Natalie D. Keirstead ◽  
Evan B. Janovitz ◽  
James T. Meehan ◽  
Bruce E. LeRoy ◽  
John R. Megill ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Working Group ◽  
Regulatory Policy ◽  
The United States ◽  
Toxicity Studies ◽  
Ultrastructural Pathology ◽  
Transmission Electron ◽  
Policy Committee ◽  
Current Practices

Anatomic pathology and clinical pathology end points are standard components of almost every nonclinical general toxicity study conducted during the risk assessment of novel pharmaceuticals and chemicals. On occasion, an ultrastructural pathology evaluation using transmission electron microscopy (TEM) may be included in nonclinical toxicity studies. Transmission electron microscopy is most commonly used when a light microscopic finding may require further characterization that could inform on the pathogenesis and/or mechanism of action. Regulatory guidance do not address the use of TEM in general study designs nor whether these assessments should be performed in laboratories conducted in compliance with Good Laboratory Practices. The Scientific and Regulatory Policy Committee of the Society of Toxicologic Pathology (STP) formed a Working Group to assess the current practices on the use of TEM in nonclinical toxicity studies. The Working Group constructed a survey sent to members of societies of toxicologic pathology in the United States, Europe, Britain, and Japan, and responses were collected through the STP for evaluation by the Working Group. The survey results and regulatory context are discussed, as are “points to consider” from the collective experience of the Working Group. This survey indicates that TEM remains an essential diagnostic option for complementing toxicologic pathology evaluations. [Box: see text]

scholarly journals Scientific and Regulatory Policy Committee Points to Consider*: The Toxicologic Pathologist’s Role in the 3Rs

2019 ◽  
Vol 47 (7) ◽  
pp. 789-798 ◽  
Author(s):  
Renee R. Hukkanen ◽  
Noel Dybdal ◽  
Niraj Tripathi ◽  
Patricia V. Turner ◽  
Sean P. Troth
Keyword(s):  
Working Group ◽  
Safety Assessment ◽  
Regulatory Policy ◽  
Critical Role ◽  
Medical Professionals ◽  
Sample Collection ◽  
Animal Use ◽  
Special Expertise ◽  
Point Determination ◽  
Policy Committee

Pathologists are trained medical professionals with special expertise in diagnostics, research, and pathophysiology. In these roles, pathologists are well qualified and positioned to engage in conversations about animal use replacement, reduction, and refinement (3Rs), thereby championing the guiding principles of the 3Rs. In particular, toxicology or nonclinical safety assessment is an important area where the discipline of toxicologic pathology can have a critical role in adopting 3Rs principles. As such, a working group of the Society of Toxicologic Pathology Scientific and Regulatory Policy Committee was formed to investigate and summarize some of the areas where veterinary pathologists working in the field of toxicology can increase involvement and impact on 3Rs. This “Points to Consider” publication provides an overview of areas within toxicology where the veterinary pathologist’s perspective may maximize animal value, including refinement of study design, optimizing sample collection, the development of 3Rs focused regulatory policy, and humane end point determination.[Box: see text]

scholarly journals Scientific and Regulatory Policy Committee Points to Consider: Data Visualization for Clinical and Anatomic Pathologists

2018 ◽  
Vol 46 (5) ◽  
pp. 476-487 ◽  
Author(s):  
Sean P. Troth ◽  
Nancy E. Everds ◽  
William Siska ◽  
Brian Knight ◽  
Martin Lamb ◽  
...  
Keyword(s):  
Data Visualization ◽  
Working Group ◽  
Regulatory Policy ◽  
Software Tools ◽  
Study Data ◽  
Toxicity Study ◽  
Graphical Displays ◽  
Different Types ◽  
Policy Committee

Assessment and communication of toxicology data are fundamental components of the work performed by veterinary anatomic and clinical pathologists involved in toxicology research. In recent years, there has been an evolution in the number and variety of software tools designed to facilitate the evaluation and presentation of toxicity study data. A working group of the Society of Toxicologic Pathology Scientific and Regulatory Policy Committee reviewed existing and emerging visualization technologies. This Points to Consider article reviews some of the currently available data visualization options, describes the utility of different types of graphical displays, and explores potential areas of controversy and ambiguity encountered with the use of these tools.

scholarly journals REPRODUCTIVE AND DEVELOPMENTAL TOXICITY STUDIES OF PRULIFLOXACIN (NM441) (4) : A Perinatal and Postnatal Study in Rats by Oral Administration

1996 ◽  
Vol 21 (SupplementI) ◽  
pp. 219-230 ◽  
Author(s):  
Tagahiko MORINAGA ◽  
Shigenobu FUJII ◽  
Shigenori FURUKAWA ◽  
Mikito KIKUMORI ◽  
Kimio YASUHIRA ◽  
...  
Keyword(s):  
Oral Administration ◽  
Developmental Toxicity ◽  
Toxicity Studies

Historical control data on developmental toxicity studies in rodents

2014 ◽  
Vol 54 (3) ◽  
pp. 150-161 ◽  
Author(s):  
Makoto Ema ◽  
Katsumi Endoh ◽  
Ryou Fukushima ◽  
Sakiko Fujii ◽  
Hiroaki Hara ◽  
...  
Keyword(s):  
Developmental Toxicity ◽  
Historical Control ◽  
Control Data ◽  
Toxicity Studies ◽  
Historical Control Data

scholarly journals Predicting the in vivo developmental toxicity of benzo[a]pyrene (BaP) in rats by an in vitro–in silico approach

2021 ◽  
Author(s):  
Danlei Wang ◽  
Maartje H. Rietdijk ◽  
Lenny Kamelia ◽  
Peter J. Boogaard ◽  
Ivonne M. C. M. Rietjens
Keyword(s):  
Dose Response ◽  
In Silico ◽  
Response Curve ◽  
Developmental Toxicity ◽  
Toxicity Testing ◽  
Maximal Effect ◽  
Blood Concentrations ◽  
Reverse Dosimetry

AbstractDevelopmental toxicity testing is an animal-intensive endpoints in toxicity testing and calls for animal-free alternatives. Previous studies showed the applicability of an in vitro–in silico approach for predicting developmental toxicity of a range of compounds, based on data from the mouse embryonic stem cell test (EST) combined with physiologically based kinetic (PBK) modelling facilitated reverse dosimetry. In the current study, the use of this approach for predicting developmental toxicity of polycyclic aromatic hydrocarbons (PAHs) was evaluated, using benzo[a]pyrene (BaP) as a model compound. A rat PBK model of BaP was developed to simulate the kinetics of its main metabolite 3-hydroxybenzo[a]pyrene (3-OHBaP), shown previously to be responsible for the developmental toxicity of BaP. Comparison to in vivo kinetic data showed that the model adequately predicted BaP and 3-OHBaP blood concentrations in the rat. Using this PBK model and reverse dosimetry, a concentration–response curve for 3-OHBaP obtained in the EST was translated into an in vivo dose–response curve for developmental toxicity of BaP in rats upon single or repeated dose exposure. The predicted half maximal effect doses (ED50) amounted to 67 and 45 mg/kg bw being comparable to the ED50 derived from the in vivo dose–response data reported for BaP in the literature, of 29 mg/kg bw. The present study provides a proof of principle of applying this in vitro–in silico approach for evaluating developmental toxicity of BaP and may provide a promising strategy for predicting the developmental toxicity of related PAHs, without the need for extensive animal testing.

scholarly journals Dietary Route of Exposure for Rabbit Developmental Toxicity Studies

2016 ◽  
Vol 154 (1) ◽  
pp. 90-100
Author(s):  
Bethany R. Hannas ◽  
Robert G. Ellis-Hutchings ◽  
Valerie A. Marshall ◽  
Claire Terry ◽  
Alene A. McCoy ◽  
...  
Keyword(s):  
Developmental Toxicity ◽  
Toxicity Studies ◽  
Route Of Exposure

Critical Values in Anatomic Pathology

2006 ◽  
Vol 130 (5) ◽  
pp. 638-640 ◽  
Author(s):  
Jan F. Silverman ◽  
Telma C. Pereira
Keyword(s):  
Patient Safety ◽  
Improve Patient Safety ◽  
Clinical Pathology ◽  
Critical Values ◽  
Surgical Pathology ◽  
Anatomic Pathology ◽  
Wide Range ◽  
Enhance Patient Safety ◽  
Pathology Reports ◽  
Improve Patient

Abstract Similar to critical values (CVs) in clinical pathology, occasional diagnoses in surgical pathology and cytology could require immediate notification of the physician to rapidly initiate treatment. However, there are no established CV guidelines in anatomic pathology. A retrospective review of surgical pathology reports was recently conducted to study the incidence of CVs in surgical pathology and to survey the perceptions of pathologists and clinicians about CVs in surgical pathology, with a similar analysis of CVs performed in cytology. The results indicated that CVs in surgical pathology and cytology are uncommon but not rare and that there is a wide range of opinion among pathologists and between pathologists and clinicians about the need for an immediate telephone call and about the degree of urgency. It was obvious from the study that there is a lack of consensus in identifying what constitutes surgical pathology and cytology CV cases. Since the Institute of Medicine's report on medical errors, there has been an increasing number of initiatives to improve patient safety. Having guidelines for anatomic pathology CVs could enhance patient safety, in contrast to the current practice in which CV cases are managed based on common sense and on personal experience. Therefore, a discussion involving the pathology community might prove useful in an attempt to establish anatomic pathology CV guidelines that could represent a practice improvement.

Sign in / Sign up

Export Citation Format

Share Document