Aggregate risk assessments allow for the evaluation of potential adverse health effects that could occur as a result of exposure to a single chemical from all routes (oral, dermal, inhalation) and sources (dietary, water, residential) of exposure combined.
Any appropriate benchmark of toxicity (Point of Departure) selected by the risk assessor such as the no observed effect level (NOEL), the no observed adverse effect level (NOAEL), or the effective dose needed to produce a 10% response (ED₁₀) can be used in CARES NG®.
Aggregate risk can be calculated using three approaches described by the EPA’s Office of Pesticide Programs (OPP) in their 2001 Guidance document.

These approaches are:

• the Total Margin of Exposure (MOE) approach (traditionally EPA/OPP has used the MOE approach when aggregating risk from residential exposures and food and water exposures),
• the Aggregate Risk Index (ARI) approach, and
• the Hazard Index (HI) approach.

The Total MOE approach is the preferred method for aggregating risk when the uncertainty factors for the different routes of exposure (oral, dermal or inhalation) are identical. The Aggregate Risk Index (ARI) is used when multiple MOEs must be aggregated, but different uncertainty factors have been applied to each individual MOE. The HI approach is an alternative that can be used. All of these aggregate calculations are implemented in CARES NG®.

If the assessment is dietary only, then percentage Population Adjusted Dose (PAD) is outputted at each reported percentile. If the assessment is residential only, then MOE is the default output.
The three methods are described below and must be applied in such a way to preserve the demographic, spatial and temporal consistency of the exposure process.

Margin of exposure

where POD_{oral,dermal,inhalation} represents the toxicological Point of Departure of the chemical, and the Dose is the estimated dose (mg/kg/day) from the model for the specified route.

The Aggregate MOE is calculated as per the following formula:

Aggregate Risk Index

The ARI was designed to incorporate into a single index each route’s potency when route-specific Points of Departure are used. The following equation (United States Environmental Protection Agency, 2001) is a simplified way of calculating a chemical’s ARI in a single step:

Hazard Index

The Hazard Index (HI) is a percentage of the Reference Dose (RfD) and is calculated first by determining a Hazard Quotient (HQ) for each route or pathway (oral, dermal or inhalation) of exposure from each source (food, water or residential) of exposure.

The RfD is calculated with the following formula:

The Point of Departure (mg/kg) is a relevant measure of the toxicology endpoint describing the common mechanism of effect. The UF is the Uncertainty Factor.
The Pathway Specific Hazard Index is calculated with the following formula:

United States Environmental Protection Agency (2001). General Principles For Performing Aggregate Exposure And Risk Assessments. Environmental Protection Agency – Office of Pesticide Programs