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Volume 9, Issue 2  

Avon Joins IIVS Science Advisory Panel

Avon logo black  

IIVS is pleased to welcome Dr. Steve Gettings, Vice President, Product Safety & Integrity, Avon Products, Inc. to its Science Advisory Panel. In 1989 Avon was the first major cosmetics company to announce an end to animal testing, and the Avon Foundation for Women has a similar policy against the use of animals in research that is supported with Foundation funds. Since 1989, the company has utilized in vitro methods to help determine the safety of their products and have partnered with other organizations to develop new alternatives. As a member of the SAP, Dr. Gettings will review and comment on proposed programs, suggest areas of focus, and provide information which will be utilized by the Institute in designing future programs.  Click here to learn more about Avon's non-animal testing policy. 


The Cytosensor Microphysiometer:

A Tool for Assessing the Ocular Irritation of Water Soluble Materials  


The Cytosensor assay is an in vitro cellular toxicity test used to evaluate ocular irritancy. A microphysiometer is used to detect and monitor the rate of extracellular changes in pH after exposure of L929 (mouse fibroblast) cells to a test material. This rate of change in the extracellular pH is caused by variations in the cellular metabolic rate; usually a decrease after exposure to a toxicant.


Metabolism in living cells is tightly coupled to cellular ATP usage and extracellular release of acidic byproducts such as protons, lactic acid, and CO2. Events that disturb the metabolism of cells (such as toxic insult by a test material) will result in a change in the rate at which the cell releases these metabolic byproducts. In general, as a cell is injured its metabolism may initially increase (hormetic response), but as it is exposed to higher doses of toxicant its metabolism rapidly declines. Because of this the rate of extracellular acidification also slows, and this can be easily detected by the Cytosensor.


In a microphysiometer, measurement of changes in pH occurs in the sensor chamber. A silicon chip that serves as a light addressable potentiometric sensor (LAPS) makes up the lower surface of the chamber. A small light producing diode (LED) is located in the Cytosensor under the chamber. This LED pulses light on the LAPS chip producing a photocurrent that is detected by the exterior circuit formed by the framework. The Cytosensor monitors the changes in the photocurrent which is directly related to changes in the cells' acidification rate.  For specific assay procedures, please refer to the Cytosensor Step-By-Step section of our web-site. Would you like to learn how the Cytosensor can be incorporated into an in vitro program? Please contact Study Director, Greg Mun, at or (301) 947-6532.  



First Alternative Method Validated for Identification of Non-Irritant Substances


The Cytosensor has been approved by ECVAM and ICCVAM for assessing water-soluble materials in a Top-Down approach to identify ocular corrosives and severe irritants (EU R41, GHS Cat. 1 and EPA Cat. 1) and for surfactants in a Bottom-Up approach to identify non-irritants (GHS: No Category, EPA Cat. IV). Although the Cytosensor is the first in vitro method validated to identify ocular non-irritants without the need for confirmation in an animal, it is not currently recommended as a full replacement method for surfactants since it cannot adequately identify all levels of irritation. 


An updated Protocol (Number 130)  for the Cytosensor Microphysiometer test method has been defined following the validation of the test method by ECVAM and peer review by ESAC. It is available for download in DB-ALM.   

cytosensor microphysiometer schematic
Scott, L., et al. (2010) A proposed eye irritation testing strategy to reduce and replace in vivo studies using Bottom-Up and Top-Down approaches.

Tox In Vitro 24:1 - 9.



IIVS Webinar on the KeratinoSens Assay for Skin Sensitization

28 September, 10:00 am EDT


KeratinoSens webinar banner 

IIVS is pleased to announce a webinar to discuss the KeratinoSens assay; an in vitro method developed by Givaudan for the assessment of skin sensitization. An introduction to the field of in vitro skin sensitization assays and their current status in the validation review process will be given by Dr. David Basketter, Chair of the ECVAM Skin Sensitization Validation Management Group. Dr. Kimberly Norman, IIVS Study Director, will present the technology behind the KeratinoSens assay, results of a recent ring trial and how the data can be incorporated into a testing program. The webinar is expected to last approximately 45 minutes followed by discussion and questions. There is no cost for participation, but prior registration is required. Please click on the image to the left to register for the event.





IIVS Staff visits California EPA 


California EPA logo

In continuation of the IIVS Outreach program for regulatory agencies, Rodger Curren and Hans Raabe traveled to Sacramento, CA to meet with the California Environmental Protection Agency's (Cal/EPA) Pesticide Programs Division. The opportunity to hold this in vitro assay workshop was provided by Dr. Marylou Verder-Carlos, Assistant Director of the Pesticide Programs Division and Kristie Sullivan of Physicians Committee for Responsible Medicine who had discussed the possibility of such a session during their service on the U.S. EPA's Pesticide Program Dialog Committee.


IIVS welcomed the opportunity to exchange views on in vitro testing with a regulatory body that is likely to see an increasing number of registration submissions which contain non-animal testing information to substantiate hazard classifications. Accordingly, the presentations focused on the in vitro ocular and dermal irritation and corrosion assays commonly used by industry for classification and labeling purposes. Rodger and Hans presented in detail how each assay is performed (using images of the step-by-step procedures), how assay quality is ensured, and the national and international regulatory acceptance of the assays. In addition, Rodger presented an update on the US EPA's recent pilot program for a non-animal testing approach to EPA labeling for eye irritation of anti-microbial cleaning products. The presentation included a description of the individual tests, the validation process used, and the rationale behind the suggested testing strategy.


Dr. Verder-Carlos chaired the workshop and provided an overview of Cal/EPA's Department of Pesticide Regulation (DPR) and Office of Environmental Health Hazard Assessment (OEHHA) programs. She also introduced Dr. Joseph Frank, Senior Toxicologist, Division of Registration and Health Evaluation, who described the important role that percutaneous penetration data play in the risk assessment process for the DPR. Dr. Jessica Ryman-Rasmussen of the U.S. EPA gave a comprehensive presentation on percutaneous penetration and its use within her agency. A subsequent discussion indicated that an Expert Workshop on in vitro methods to estimate percutaneous penetration might be beneficial to both industry and the regulatory agencies.


IIVS appreciated the opportunity to interact with Cal/EPA on the important aspects of using data from in vitro methods in a regulatory arena. We especially thank Dr. Verder-Carlos for organizing the workshop at Cal/EPA headquarters, and Kristie Sullivan for overseeing the logistics.


News and Upcoming Events
Recent Publications:

Pfuhler S, Fellows M, van Benthem J, Corvi R, Curren R, Dearfield K, Fowler P, Frotschl R, Elhajouji A, Le Hegarat L, Kasamatsu T, Kojima H, Ouedraogo G, Scott A, and Speit G. (2011) In Vitro Genotoxicity Test Approaches with Better Predictivity: Summary of an IWGT Workshop. Mutat. Res. 723:101-107.



Upcoming Events: 


8th World Congress on Alternatives and Animal Use in the Life Sciences 

August 20 - 25, 2011, Montreal, Canada




August 28 - 31, 2011, Paris, France



Predictive In Vitro Models: Developing Better Models to Predict Clinical Outcomes 

September 21 -22, 2011  Boston, MA



Cleaning Products 2011 

October 5-7, 2011, Washington, D.C.



EPAA/ECVAM Toxicokenetics Workshop 

October 13, 2011, JRC Ispra, Italy



Personal Care Products Council Cosmetic Science Symposium 

October 25 - 27, 2011, Newark, NJ




Visit the IIVS booth at the 8th World Congress on Alternatives and Animal Use in the Life Sciences (WC8)

 World Congress Logo


The goal of WC8 is to bridge the distance between science and policy and to identify opportunities for collaborations. Members of the IIVS team will present oral and poster presentations throughout the congress. In addition you can learn more about our services and educational programs by stopping by booth #18 in the exhibit area.

To view the scientific program or register please visit the congress website. 




Support IIVS

Help IIVS continue important Education and Outreach programs such as our interactions with regulatory agencies  

(see article left).  

Contribute Today!

Hand shake 2
Predictive In Vitro Models Meeting
September 21- 22

Boston, MA 


Hans Raabe will give a presentation titled "Developing Predictive and Reliable In Vitro Assays to Achieve Validation." Read more about this meeting and IIVS' participation in additional meetings on the new Upcoming Meetings page of our website.    



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ICCVAM Proposes Procedures to Reduce Animal Use for Eye Safety Testing 



REACH In the News


ECHA has recently published two reports required by REACH Regulations. Find them along with reaction from the animal protection community on the IIVS website. 

American Society for Cellular and

Computational Toxicology


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Upcoming Member Webinar  

Effectopedia: The Online Encyclopedia of Adverse Effect Pathways

 Click here for more information 



Missed the MetaPath Webinar with the EPA's  

Dr. Patricia Schmieder?  

Click here to listen to a recording  




Join us for a session at the World Congress in Montreal:

Comparing the Challenges  of implementing new non-animal methods in the US and Europe