Aggregate Exposure

Aggregate exposure to the same substance across routes on an absorbed-dose basis using caller fractions; systemic kinetics and route-specific local toxicity are not equivalent.

Description

Apply route-specific absorption fractions and sum absorbed dose amounts on a common basis.

Aggregate exposure combines contributions from different routes for the same chemical. An administered dose is the amount entering a route-specific exposure calculation; an absorbed dose applies an assumption about the fraction taken into the body. Both the time basis and dose definition must remain consistent.^[1]

This tool multiplies each supplied route dose by its absorption fraction, then sums the absorbed values. Its input and output dose amounts are mg/kg. It has no duration input and does not convert an amount into a daily dose rate.

Provide route contributions for the same chemical, body-mass normalization, and exposure interval. Adding doses from different chemicals would not create a toxicity-weighted mixture metric, and adding overlapping contributions would double count them.

When to use Aggregate Exposure

Use it to reconcile a set of externally estimated route doses or compare how route-specific absorption assumptions change an aggregate absorbed amount.

How to use Aggregate Exposure and interpret its calculation

Enter aligned, nonempty administeredRouteDosesMgPerKg and routeAbsorptionFractions lists.
Use nonnegative dose amounts and absorption fractions between 0 and 1. Confirm that every row represents the same chemical and compatible interval.
Run the tool and read absorbedRouteDosesMgPerKg in input order and aggregateAbsorbedDoseMgPerKg as their sum. Retain route labels alongside the lists outside the tool.

absorbed_i = administered_i × fraction_i; aggregate absorbed = Σ absorbed_i

The calculation preserves mg/kg dose-amount units and performs no time conversion.

The implementation computes a paired product for every list entry, then adds the products. It neither assigns route names nor retrieves absorption values.

json

{
  "input": {
    "administeredRouteDosesMgPerKg": [
      1,
      2,
      3
    ],
    "routeAbsorptionFractions": [
      0.5,
      0.2,
      0.1
    ]
  },
  "output": {
    "absorbedRouteDosesMgPerKg": [
      0.5,
      0.4,
      0.3
    ],
    "aggregateAbsorbedDoseMgPerKg": 1.2
  }
}

A zero dose or zero fraction contributes zero. Fraction one preserves the administered amount. All-zero contributions are accepted and produce a zero total; mismatched lists or fractions outside 0–1 are rejected.

Limitations and assumptions

It does not calculate external route doses, dermal area loading, inhaled volume, bioavailability, first-pass metabolism, local toxicity, or time-dependent disposition. Absorption fractions remain user assumptions.

An aggregate absorbed amount is not a target-tissue concentration or a hazard index. It cannot be compared with a mg/kg/day benchmark without an explicit, appropriate time and dose-basis conversion.

Alternative or Complementary methods

Calculate external route contributions with methods suited to each route before aggregation. For concentration over time, use a separately specified disposition model and supply compatible parameters rather than treating the aggregate amount as an arterial concentration.

References

Risk Assessment Guidance for Superfund, Volume I, Part A — U.S. Environmental Protection Agency

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