Att7_Sample Research Outlines.pdf

Sample Research Outlines

I. Research Outline (RO) I: Toxicology Study Conducted by a Contract Research Organization

A. Chronic Study for Audit of Pathology Tables

DTT conducted GLP compliant toxicology studies at a Contract Research Organization (CRO) according to the DTT Specifications (https://doi.org/10.22427/NIEHS-00).

Assume the study being assessed was a chronic (2-year) inhalation study in male and female rats. The core cohort of animals included 50 rats/sex/group in 3 exposure groups and a control. For all animals, the following endpoints were assessed: body weight, clinical observations, and histopathology of all tissues listed in Chapter 8 of the DTT Specifications.

After the final study report is signed the pathology materials are submitted to the NTP Archives. All in-life and histopathology data are entered into a DTT laboratory information management system (currently Provantis).

The histopathology data are peer reviewed by a second pathologist and treatment-related findings are reviewed by a Pathology Working Group (PWG). Following peer review and PWG the individual animal pathology data are updated to reflect final/consensus diagnoses. Final DTT Tables with individual animal data and summarized by group will be available.

Describe the technical approach (including proposed staffing) for conducting assessments of the pathology tables following pathology peer review.

B. 28-day Gavage Study for Audit of Laboratory Report and NTP Toxicity Report

DTT conducted GLP compliant toxicology studies at a Contract Research Organization (CRO) according to the DTT Specifications (https://doi.org/10.22427/NIEHS-00).

Assume the study being assessed below was a 28-day oral gavage study in male and female rats. The core cohort of animals included 10 rats/sex/group in 5 dose groups and a control. For all animals, the following endpoints were assessed: body weight, clinical observations, food consumption, sperm motility and counts and vaginal cytology (SMCVC), clinical chemistry, hematology, thyroid hormones (TSH, free T4, total T3 and total T4), and histopathology of all tissues listed in Chapter 8 of the DTT Specifications.

After the final study report is signed and accepted, the laboratory report, and study records are submitted to the NTP Archives. All in-life, SMCVC, clinical pathology, and histopathology data are entered into a DTT laboratory information management system (currently Provantis).

Finally, these studies will be published in an NTP Toxicity Report.

https://doi.org/10.22427/NIEHS-00 https://doi.org/10.22427/NIEHS-00

Describe the technical approach (including proposed staffing) for conducting assessments of the laboratory reports and NTP report.

II. Research Outline (RO) II: Studies Conducted for Manuscript Publication A. DTT conducted a GLP compliant study at a CRO according to the DTT Specifications referenced above. The study was an in vivo inhalation exposure in rats and mice that evaluated survival, body weight, adverse clinical observations, and diffuse nasalolfactory epithelium degeneration (rats) or necrosis (mice) which resulted in the following publication.

• Huang MC et al. 2021. Whole-body inhalation exposure to 2-ethyltoluene for two weeks produced nasal lesions in rats and mice. Inhalation Toxicology, Vol. 33, Nos. 9–14, 334–346. https://doi.org/10.1080/08958378.2021.2002480.

Describe the technical approach (including proposed staffing) for conducting assessments of a study conducted at a CRO which requires verification of internal consistency and review of original records that are stored at NTP Archives against study data which is housed in the Chemical Effects of Biological Systems (CEBS) database.

B. DTT conducted an internal study of in vitro exposure of primary human hepatocytes which includes key endpoints such as cell viability, cell imaging, and transcriptomics which resulted in the following publication.

• Crizer DM et al. 2021. Benchmark Concentrations for Untargeted Metabolomics Versus Transcriptomics for Liver Injury Compounds in In Vitro Liver Models.

Toxicol Sci. 2021 Jun; 181(2): 175–186. doi: 10.1093/toxsci/kfab036.

Describe the technical approach (including proposed staffing) for conducting assessments of internal studies which require verification of internal consistency.

III. Research Outline (RO) III: Literature-Based Evaluation Assessment DTT conducted a cancer hazard evaluation of antimony trioxide for possible listing in the Report on Carcinogens (RoC). The results of the evaluation are published in the RoC Monograph on Antimony Trioxide (https://ntp.niehs.nih.gov/publications/roc/rocmgraph13)

During the assessment of this publication, information in the monograph shall be reviewed for internal consistency. In addition, all data presented throughout the monograph from citations in Section 8: Evidence Integration and Listing Recommendation should be verified against the original data as presented in the original publication.

https://ntp.niehs.nih.gov/publications/roc/rocmgraph13

III. Research Outline (RO) III: Literature-Based Evaluation Assessment