Table 1.
Three common models used for interaction testing and interpretation of additivity of insecticidal proteins
| Model | Assumptions/requirements | Model use/interpretation | Experimental | ||
|---|---|---|---|---|---|
| Strengths | Challenges | Strengths | Challenges | ||
| CAa | Proteins have the same MoA Dose–response has same upper threshold and same slope A single relative potency factor applies for comparison of the dose-response of any two agents |
Conservative from an ERA standpoint Can be designed to assess doses in the active range |
MoA may not always be a priori clearly defined/ established Well-established, full dose– response data of a similar shape are prerequisite |
Any uniform ratio of the combined agents could be selected for a given dose–response dataset | Requires full set of dose–responses to generate comparison parameter (e.g., LC50) |
| RAb | Proteins have different MoA Dose–response has same upper threshold Doses selected must have a measurable effect when each agent is presented alone |
The most conservative from an ERA standpoint By default, the design assesses doses in the active range |
MoA may not always be a priori clearly defined/ established Have to avoid testing at a sublethal dose |
Minimal dose requirements (e.g., can work with as few as 1 or 2 selected doses) | Requires parallel testing of individual agents at same selected dose(s) |
| Empiricalc | One (or more) of the agents to be tested has no toxicity to the test organism | No direct relation to MoA interpretations No need to calculate an expected response (e.g., default expectation for one agent is zero activity) |
If the agents act against the same target pest, establishing a nominal sublethal dose to use can be difficult | Minimal dose requirements (e.g., can work with as few as 1 or 2 selected doses) | May require a larger dataset for robust statistical analysis |
aAlso known as dose addition, simple similar action, similar joint action, or Loewe additivity.
bAlso known as independent joint action, independent action, Bliss independence, or effect additivity.
cAlso known as simple empirical or simple statistical test.