Opportunity:
- Design a study to assess the mode of action (MOA) that leads to tumor development in rodents exposed to acrylamide.
- Publish data in the peer-reviewed literature.
- Provide data for use by international regulatory agencies as part of risk assessments.
Challenges:
- Design an experiment identifying exposure levels, time points and endpoints that would satisfy scientific and regulatory reviewers and minimize criticism.
- Respond to skepticism about the scientific merit of data.
- Gain acceptance from scientific reviewers for a novel MOA for acrylamide.
- Effectively manage regulatory scrutiny related to the safety of acrylamide.
Outcomes:
- Designed study with collaborators to gain acceptance of exposure levels and time points for a robust study design to meet goals: MOA of acrylamide exposure in tumor target tissues.
- Analyzed data using state-of-the-art techniques; developed risk assessment for novel genomic data sets compared against traditional risk assessment.
- Used toxicogenomics-based study design to enable innovative next-generation sequencing (NGS) analysis of gene expression, quantitative PCR to validate NGS data, and development of a risk assessment.
- Identified novel pathways that could lead to tumors, contrary to accepted assumptions: demonstrated a nongenotoxic MOA while review of literature would indicate a genotoxic MOA for acrylamide.
- Supported client’s long-held hypothesis about the MOA of acrylamide.
