When Animal Testing Is DIM Difficult, Impossible, Meaningless

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When Animal Testing Is DIMDifficult,
Impossible, Meaningless

• Chad B. Sandusky, Ph.D.
• Physicians Committee for Responsible Medicine,
  Washington DC, USA

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EPAs High Production Volume(HPV) Program

• High production volume chemicals (gt1,000,000
  pounds per year)

• Assess existing hazard data

• Assess and fill data gaps

• No risk assessment (limited exposure
  considerations)

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Animal Tests Required
TOTAL 750 800 up to 2000 animals hundreds of
thousands of dollars
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Examples of Current Animal Welfare Principles

• Use in vitro genotoxicity versus in vivo unless
  impossible

• No repeat dose/reproductive testing neededfor
  closed system intermediates

• Maximize use of existing data

• Use weight-of-evidence to avoid checklist
  toxicology

• Use SAR to form chemical categories and
  extrapolate between members

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Extended HPV Program

• Original program ended in 2005

• EHPV initiated in 2006

• PCRM has worked with ACC to develop expanded
  Animal Welfare Guidelines

• Based on experience from review of hundreds of
  HPV test plans and in context of goals of a
  hazard screening program

• Specific examples provided below

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Specific Strategy Examples

• 1. Highly Reactive Materials
• Aluminum alkyls

• Highly reactive to air and water

• Supported by physical-chemical properties

• No mammalian nor ecotoxicity feasible

• Testing is Difficult

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Specific Strategy Examples

• 2. Acidic/Corrosive/Irritating Materials
• Benzene and Hydroxybenzene sulfonic acid

• Strong acids

• Completely ionized in aqueous environment

• Expected to cause localized corrosive
• effects in GI tract

• EPA agreed that mammalian testing
• would not yield Meaningful results

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Specific Strategy Examples

• 3. Rapid Hydrolysis
• Triisopropyl borate (TIPB)

• Rapidly hydrolyzes to boric acid and isopropanol
  in aqueous environment

• EPA agreed to accept bench hydrolysis study at
  stomach acid pH 1.2

• Rapid hydrolysis to well studied products could
  be used to meet SIDS

• No additional animal testing required

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Summary of Strategies

• Highly reactive materials
• Acidic/Corrosive/Irritating materials
• Rapid hydrolysis to well characterized materials

• Others include
• Data from analogs
• Weight-of-evidence
• Gases

• 40 chemical-specific examples and counting,
  reducing numbers of animals by the thousands

• Reduced dermal testing using data from in vitro
  percutaneous absorption studies (OECD 428)