given to the test animals in their diet, dosing is usually continuous for 7 days a week. If the material is administered by gavage (oral bolus dose), by dermal application, or by inhalation, doses are frequently given 5 days a week, which is acceptable to EPA because of practical considerations (EPA, 1984).

The type of statistical analysis performed on the toxicity data resulting from these studies depends on the type of data under consideration (see, for example, Gad and Weil, 1982, for review). Interpreting the meaning of statistical significance for any particular parameter depends on the dose level at which it was achieved, the biological significance of the finding, and the normal spontaneous occurrence of this finding in the strain and species being tested.

For regulatory purposes, the no-observed-effect level (NOEL) is defined as a dose level at which no effects attributable to the pesticide under test can be found. A no-observed-adverse-effect level (NOAEL) can also be determined for each study; however, EPA does not routinely use the NOAEL to regulate pesticide usage. To establish a NOAEL, the toxicologist must determine what is and what is not adverse effect, which can be defined differently by different scientists. For example, effects such as hair loss can be considered adverse by some and not by others. Plasma and red blood cell cholinesterase inhibition can be viewed as either an adverse effect or simply as a market of exposure to a pesticide.

EPA uses the NOEL to calculate the acceptable daily intake (ADI) of the pesticide under consideration. More recently, the EPA has replaced the ADI with the reference dose, or RfD. Chronic studies, such as reproduction studies and lasting 1 year or longer in the rat or dog are used for this purpose. EPA does not routinely use the NOEL determined from teratology (developmental toxicity) studies for calculating ADIs because the observed effect are not considered chronic; however, these NOELs can be used to support the calculated ADI. EPA does routinely use developmental toxicity NOELs for other types of risk assessments, such as calculating the risk from acute, daily dietary or occupational exposure or from exposure of homeowners to a developmental toxicant.

EPA's toxicity testing requirements for food and nonfood use pesticides have been published in 40 CFR Part 158. In general, for food use chemical with maximum human exposure, the following toxicity tests are required:

• acute oral toxicity

• acute dermal toxicity

• acute inhalation toxicity

• primary eye irritation

• primary dermal irritation

• chronic feeding toxicity

• dermal sensitization

• acute neurotoxicity

• 90-day toxicity

• 21-day dermal toxicity

• 90-day neurotoxicity study

• reproduction study



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