# Presentation: 741790

## Nanotechnology In Vivo Characterizations

***Toxicology Discussion: ***
***December 11, 2008***

***Use of Informatics to Expedite and Validate the Application of ***
***Nanotechnology in Biomedicine***

## Nanotechnology In Vivo Characterization Toxicology Meeting Agenda

| In Vivo Characterization Toxicology Meeting |  |
| --- | --- |
| December 11, 2008 2:00-3:00 PM EST |  |
| Agenda Item | Time |
| Introduction | [2:00-2:05 PM] |
| Review of Existing DRAFT Toxicology Wireframes and Model | [2:05-2:15 PM] |
| Discussion on Toxicology Questions
 | [2:15-2:55 PM] |
| Closing and Next Steps | [2:55-3:00 PM] |

## DRAFT Nanotechnology In Vivo Characterization Model and Wireframes

## DRAFT In Vivo Characterization Model

**Notes:**
Pharmacokinetics – The branch of pharmcology dedicated to the determination of the fate of substances adminisitered to a living organism; Explores what a body does to the drug.  Includes the routes and mechanisms of absorption, distribution, metabolism, and excretion.

## DRAFT In Vivo Toxicology

## In Vivo Characterization - Toxicology

## Toxicology - Animal Model

## Toxicology - Treatment

## Slide 9

## DRAFT In Vivo Concepts

## Nanotechnology Toxicology Questions

## Nanotechnology Pharmacokinetics (Toxicology) Questions

- What scientific questions related to nanotechnology toxicology *in vivo* characterizations should we (and can we) focus on addressing?
- What toxicology concepts are important to capture?
- Are there specific files (spreadsheets, images, graphs) related to toxicology characterizations that should be uploaded or parsed for efficient data entry and searching?
- What toxicology concepts are important to capture for interfacing with toxicology modeling and simulation systems or analysis tools in the future?
- Of the identified concepts discussed during the meeting, which concepts should be included in a set of "minimal information" about a nanotechnology *in vivo* characterization?
- Are there any nanotechnology in vivo characterization data sets (or publications) available that we can leverage to validate our design going forward?

## 1. What scientific questions related to nanotechnology toxicology in vivo characterizations should we (an can we) focus on addressing? 

**Focus on the differences related to nanotechology toxicology studies vs. regular toxicology studies**
- Comparison of physical characterizations (size, surface, surface area, mass) vs toxicity
- Nanoparticle material characterizations and properties vs. toxicity
- Measure particle biodegradability
**What happens to a nanoparticle after it performs its function (i.e. Fate of the nanoparticle)? Includes clearance – systemic, body, bio-distribution studies, excretion (Addressed in PK/ADME studies)**
**Sample preparation/handling for nanoparticles important (OECD Guidelines for sample handling)**

## 2. What toxicology concepts are important to capture?  

**DRAFT list of toxicology parameters: **

**Clinical Chemistry**
- BUN, GLUC, ALP, Globulin, Chloride, AST, Creatinine, A/G Ratio, ALT, Total Protein, Total Bilirubin, Sodium, Potassium, Phosphate, Calcium, CGT, Albumin, Amylase, ...

**Organ/Body Weight**
- Organ, Absolute Weight, Per Body Weight, Per Brain Weight

**Hematology**
- Red Blood Cells (Hct, Hb, MCH, MCHC, MCV, RBC, Red Cell Distribution Width), White Blood Cells (Lymphocytes, Macrophate/Monocytes, Granulocytes, Total Leukocytes), Clotting Potential (Platelet Count, Mean Platelet Volume, Platelet Distribution Width)

**Toxicity**
- LD50, EC50, TC50

**Clinical Observation – Animal Observation/Behavioral**
- Description (qualitative)

**Survival**
- Survival Time

**Gross Pathology**
- Organ/Tissue,          Lesion Type

**Histopathology**
- Organ/Tissue,          Lesion Type

- Include: date/age of animal, reproductive, behavior, everything in pharmacology, biochemical parameters, developmental toxicology, dose-related concepts, lowest effect level, no effect level

**Notes:**
BUN: Blood urea nitrogen. A measure primarily of the urea level in blood. Urea is cleared by the kidney and diseases which compromises the function of the kidney will frequently lead to increased blood levels. The blood BUN level can also rise in patients who are dehydrated.

## 3. Are there specific files (spreadsheets, images, graphs) related to toxicology characterizations that should be uploaded or parsed for efficient data entry and searching? 

**Example Files: **
- Clinical Chemistry
- Hematology
- Organ and Body Weight
- Gross Pathology
- Histopathology
**Pathology Images – Visualize where nanoparticles are in tissues of interest.  Includes standard pathology images and images enabling visualization at the cellular level (TIFF, JPEG Formats)**
**Need to explore whether there is an existing HL7 message for transmitting toxicology data**

## Clinical Chemistry

## Hematology

## Organ Weight

## Body Weight

## Gross Pathology

## Histopathology

## 4. What toxicology concepts are important to capture for interfacing with toxicology modeling and simulation systems or analysis tools in the future?

**Common used programs**
- _[acslXtreme](http://www.acslxtreme.com/)_ – Models distribution and exposure; model kinetics of exposure and tissue distribution and relates to toxicology
- SAS
- Excel Stats
- Limited distribution programs

**Example PK/Toxicology Software:  **_[http://](http://www.boomer.org/pkin/soft.html)__[www.boomer.org/pkin/soft.html](http://www.boomer.org/pkin/soft.html)_

## 5. Of the identified concepts discussed, which concepts should be included in a set of "minimal information" about a nanotechnology in vivo characterization?

**All important to capture**

## 6. Are there any nanotechnology in vivo characterization data sets (or publications) available that we can leverage to validate our design going forward?

**NCL Acute Toxicology Reports**
**UC Toxicology of Quantum Dot – specific to heavy metal particle**
**National Toxicology Program (NTP) NIEHS – Testing of nanomaterials; Review past reports; Includes nano-silver, tio2, au, and carbon nanotube particle types**
**Academic Labs/Industry – e.g. Rice, etc.**

## Closing and Next Steps

## Monthly Topics

| Meeting Date | Agenda Topic |
| --- | --- |
| November 12, 2008 | PK Model, Concepts, and Wireframes |
| December 11, 2008
2:00-3:00 PM EST | Toxicology Model, Concepts, and Wireframes
 |
| January 8, 2009
2:00-3:00 PM EST | Efficacy Model, Concepts, and Wireframes
 |
| February 12, 2009
2:00-3:00 PM EST | Animal Models and Imaging (I/F to caMOD and NCIA)
 |
| March 12, 2009
2:00-3:00 PM EST | Review Model, Concepts, and Wireframes |
| March 31, 2009
2:00-3:00 PM EST | Complete Model, Concepts, and Wireframes |

- Discussion Forum
- _[nano-invivo-char-l@list.nih.gov](mailto:nano-invivo-char-l@list.nih.gov)_

**Thanks for Attending!**

## Reference Links

** ****NCL caNanoLab: **_**[http://](http://cananolab.abcc.ncifcrf.gov/caNanoLab/)**__**[cananolab.abcc.ncifcrf.gov/caNanoLab](http://cananolab.abcc.ncifcrf.gov/caNanoLab/)**__**[/](http://cananolab.abcc.ncifcrf.gov/caNanoLab/)**_
** ****caNanoLab Wiki site: **_**[https://](https://wiki.nci.nih.gov/display/ICR/caNanoLab)**__**[wiki.nci.nih.gov/display/ICR/caNanoLab](https://wiki.nci.nih.gov/display/ICR/caNanoLab)**_
** ****caNanoLab Project site: **_**[http://gforge.nci.nih.gov/projects/calab](http://gforge.nci.nih.gov/projects/calab)**_** **
** ****caNanoLab User’s Group:    **_**[CANANOLAB-USERS-L@LIST.NIH.GOV](mailto:CANANOLAB-USERS-L@LIST.NIH.GOV)**_
** ****caBIGTM ICR Nano Working Group: **_**[http://](http://gforge.nci.nih.gov/projects/nano/)**__**[gforge.nci.nih.gov/projects/nano](http://gforge.nci.nih.gov/projects/nano/)**__**[/](http://gforge.nci.nih.gov/projects/nano/)**_
** ****DRAFT *****In Vivo***** Characterization Materials: **
**https://gforge.nci.nih.gov/docman/index.php?group_id=69&selected_doc_group_id=3982&language_id=1**