Carcinogenicity Mode of Action Evaluations to Change Regulatory Standards

Project Summary

Toxicological analysis increases regulatory cleanup standards by 1,000-fold for manufacturing client.

Our client faced investigation and potential remediation requirements for the pesticide lindane (gamma-hexachlorocyclohexane; HCCH) and related isomers ((alpha-HCCH, beta-HCCH, delta-HCCH) detected in groundwater at a former manufacturing facility in Nevada.

The Nevada Department of Environmental Protection (NDEP) had promulgated risk-based target concentrations (Basic Comparison Levels, or BCLs) for each isomer based on the potential carcinogenicity of alpha-HCCH. These limits relied on a U.S. Environmental Protection Agency (EPA) assessment that classified alpha-HCCH as a direct-acting, DNA-active carcinogen, applying a linear low-dose extrapolation model to calculate cancer slope factors.

Our analysis of the data demonstrated that alpha-HCCH causes toxicity in laboratory animals through a threshold-based mode of action rather than direct DNA interaction. We presented this toxicological analysis to NDEP, which accepted our threshold-based mode of action evaluation.

This scientific assessment resulted in:

• A 1,000-fold increase in the BCL for alpha-HCCH
• Recognition that other isomers should not be considered equally toxic to alpha-HCCH
• Similar increases in BCLs for the related compounds.

These revised values remain in regulatory use today.