Alternative Approaches to Validation Modular Approaches

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Alternative Approaches to Validation Modular
Approaches

• Leonard Sauers, PhD, DABT
• The Procter Gamble Company

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• In order to be validated, an alternative testing
  method must go through a rigorous process
  involving scientific review panels, testing
  laboratories, evaluation committees, and eventual
  publication of test data. This is not an easy
  nor simple process.

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Validation Successes

• Alternatives for evaluating skin corrosivity
• Screening assays for embryotoxicity
• Local lymph node assay for skin sensitization
• Screening assay for phototoxicity
• Refinements to the acute oral toxicity test

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Why is this list not longer?

• Questions asked are very difficult.
• Databases are limited.
• The animal model is seen as the standard to which
  the alternative must be compared.

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Overcoming Barriers The Modular Approach

• The aim of the modular approach is to simplify
  the validation process.
• As opposed to seeking broad validation of an
  alternative test, the modular approach seeks to
  validate a test for a specific purpose e.g. a
  specific class of chemicals.

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Application of the Modular Approach
Antimicrobial Cleaning Products

• Antimicrobial cleaning products are considered
  pesticides by the EPA and must be registered
  under FIFRA before marketing can begin.
• Animal testing for skin and eye irritation is
  required for these registrations to determine
  appropriate cautionary labeling.
• Alternative methods exist today for these
  endpoints and are used broadly.
• However these methods have not undergone formal
  review for this purpose and therefore EPA is
  limited in their ability to accept them.

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Application of the Modular Approach
Antimicrobial Cleaning Products, cont.

• Instead of waiting for broad-scale validation of
  alternative methods for evaluating skin and eye
  irritation, why not go forward today and gain
  formal acceptance of these methods specifically
  for antimicrobial cleaning products for which
  sufficient supporting data are available.

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Path Forward

• Determine the scope of the project i.e. define
  antimicrobial cleaning product.
• The major consumer products companies that
  manufacture these products assembled and sent to
  a third party (IIVS) all their animal and
  non-animal data for skin and eye irritation for
  these formulations. Seven companies
  participated.
• IIVS did a complete analysis of the data,
  identified data gaps and is working with the
  various companies to fill those gaps.

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Path Forward, cont.

• Once the database is complete, a comprehensive
  document will be submitted to ICCVAM for
  technical review. This document will outline a
  standardized approach for how alternative methods
  can be used to determine appropriate skin and eye
  labeling of antimicrobial cleaning products. All
  supporting data will be included.

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Can the modular approach be applied to
developmental neurotoxicity?
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What are the barriers to a modular approach to
DNT?

• Complexity of the neural system function based
  on interconnecting systems
• The need for understanding a behavioral response.
• Data generated on this endpoint are relatively
  limited.

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Can a modular approach ever be used?

• There are certain classes of materials, e.g.
  organophosphates, for which a good understanding
  of neurotoxicity is available.

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Path Forward for DNT

• Can alternative methods be used to understand
  relative developmental neurotoxicity?
• Can alternative methods be used to confirm that
  DNT would not be the most sensitive toxicity
  endpoint?