Chemical warfare agents: estimating oral reference doses

Area of Science:

• Environmental Toxicology
• Chemical Warfare Agents
• Risk Assessment

Background:

• Health risk assessments for sites contaminated with chemical warfare agents (CWAs) necessitate comparing potential exposure levels with the toxic potency of each chemical.
• Toxic potency for noncancer health effects is quantified using Reference Doses (RfDs), representing daily exposure levels unlikely to cause adverse health effects in the human population, including sensitive subgroups.

Purpose of the Study:

• To establish a Reference Dose (RfD) for Agent HD (Sulfur Mustard) to inform health risk assessments.
• To characterize the toxic potency of sulfur mustard for noncancer health effects.

Main Methods:

• RfD derivation involved identifying a no-observed-adverse-effect level (NOAEL) or lowest-observed-adverse-effect level (LOAEL) from toxicity data.
• A two-generation reproductive toxicity study in rats identified the LOAEL for sulfur mustard.
• Uncertainty Factors (UF) were applied for sensitive subpopulations (10), animal-to-human extrapolation (10), LOAEL-to-NOAEL extrapolation (3), and subchronic-to-chronic exposure (10), totaling 3000. A modified UF of 3 was used for LOAEL-to-NOAEL due to mild critical effects (stomach lesions).

Main Results:

• The established Reference Dose (RfDe) for Agent HD (Sulfur Mustard) is 7 x 10(-6) mg/kg/day.
• The critical study identified stomach lesions consistent with sulfur mustard's vesicant properties.

Conclusions:

• The derived RfD for sulfur mustard provides a crucial benchmark for evaluating health risks associated with exposure.
• The methodology ensures protection of the general population and sensitive subpopulations from noncancer health effects.