Information provided for informational purposes only

Note: This information is provided for reference purposes only. Although the information provided here was accurate and current when first created, it is now outdated.

TRAC 5/27/98


APPENDIX 1

OVERVIEW OF HUMAN HEALTH TOXICITY DATA REQUIRED
FOR THE REGISTRATION OF PESTICIDE CHEMICALS

PLEASE NOTE: The full unabridged data requirements may be found at 40 CFR 158.340. The material provided in this document is merely intended to provide a 'plain-english' guide to the human health toxicity requirements.

Human health toxicity data are used by the Agency to assess the potential hazard a particular pesticide will have on humans, and in turn, for establishing quantitative dose-response relationships between the dose and effect (e.g., reference dose, q1*).

Provided in the following tables (i.e., 'The Basic Data Set' and 'Additional Studies Required....') are the actual nuts&bolts data that registrants are generally required to submit to the Agency for pesticides that have food uses. The difference between these two tables is that the 'Basic Data Set' lists the studies that under most cases are always required for food uses; the next table provides the additional studies that must be provided if a certain condition is met.

The Basic Data Set

DATA REQUIREMENTS

(Test And Guideline #)

WHAT DO THE DATA TELL US?

ACUTE TESTING (the "6-pack")

Acute Oral Toxicity - Rat (81-1) Data from acute toxicity studies provide the Agency with information on the potential for health hazards that may arise as a result of short-term exposure.

Acute toxicity data are used in pesticide labeling for determinations of: precautionary label statements; restricted use classification; child resistant packaging; protective clothing for applicators, and farmworker reentry intervals.

Acute Dermal Toxicity (81-2)
Acute Inhalation Toxicity-

Rat (81-3)

Primary Eye Irritation -

Rabbit (81-4)

Primary Dermal Irritation (81-5)
Dermal Sensitization (81-6)
Acute Neurotoxicity - Rat (81-8)

SUBCHRONIC TESTING

90-Day Oral - Rodent and Nonrodent (82-1) Data from subchronic studies provide the Agency with information on health hazards that may result from repeated exposures to a pesticide over a limited period of time. Depending on the most likely route(s) of exposure, the studies may utilize oral, dermal, and/or inhalation routes of administration for study durations of up to 90 days. Two species are used because of differences in sensitivities among species.

Please note that for food-use evaluations, subchronic testing will be done by the oral route of administration. However, under some circumstances (e.g., the pesticide is deliberately applied to skin, is in Toxicity Category I or II, etc.), subchronic dermal data will also be required (even though dermal is not the intended route of exposure). Also, dermal toxicity data is often available for food-use evaluations because it had been required on account of occupational or residential exposure.

In subchronic toxicity testing, EPA looks at: mortality rates, body-weight changes, diet consumption, and effects in target organs (e.g., enlarged liver). Also, the data are used to establish dose-response relationships (e.g., RfD).

21- or 90-Day Dermal (82-2

or 82-3)

CHRONIC TESTING

Chronic Feeding -Rodent and

Nonrodent (83-1)

Information derived from chronic studies is used to assess potential hazards resulting from prolonged and repeated exposures to a pesticide over a significant portion of the human life span. These studies, which are usually conducted by feeding the test material to several mammalian species for periods or 12 to 24 months or longer, are intended to detect toxic effects which may occur after long-term exposure.

Parameters examined are similar to those from the subchronic testing.

Carcinogenicity - Rat and

Mouse (83-2)

In a cancer study, EPA is looking for evidence of carcinogenic effects (e.g., tumors) after a near lifetime of exposure.

DEVELOPMENTAL TOXICITY AND REPRODUCTION

Developmental Toxicity (Teratogenicity) - Rat and Rabbit (83-3) Developmental toxicity studies are designed to assess the potential of the test substance to induce developmental effects in offspring as the result of exposure of the mother during pregnancy. These developmental effects include: death of the developing organism, structural abnormalities, altered growth, and functional deficiencies.
Reproduction (83-4) Multigeneration reproduction studies are designed to provide information concerning the general effects of a test substance on overall reproductive capability including those effects on gonadal function, estrous cycles, sperm parameters, mating behavior, conception, parturition (giving birth), lactation, weaning, and growth and development of offspring. This study may also provide information about the effects of the test substance on neonatal morbidity and mortality, and preliminary data on developmental toxicity.

MUTAGENICITY

Salmonella Typhimurium Reverse Mutation Assay (84-2) A battery of mutagenicity tests is required for each test substance to assess the potential of the test chemical to affect genetic material (e.g., DNA).
Mammalian Cells in Culture

(84-2)

In vivo Cytogenetics (84-2)

SPECIAL TESTING

General Metabolism (85-1) Metabolism testing provides the Agency with data on how the pesticide is broken down in the body.

Additional Studies Required If Certain Triggers Are Hit

TRIGGER DATA REQUIREMENT

(Test and Guideline #)

WHAT DOES IT TELL US?

SUBCHRONIC TESTING

Pesticide Is a Gas at Room Temperature; or Repeated Inhalation Exposure, at Concentrations Likely to Be Toxic, Is Expected 90-Day Inhalation - Rat

(82-4)

The toxicity of the pesticide via the inhalation route of exposure.

NEUROTOXICITY

Pesticide is an OP (or "OP-like") Delayed Neurotoxicity (Acute) - Hen (81-7) Behavioral effects and physiological effects on the nervous system in adults.
Effects were seen in the Acute Delayed Neurotoxicity Hen (81-7) 28-Day Delayed Neuro-toxicity- Hen (82-6)
Pesticide is an OP or a Carbamate 90-Day Neurotoxicity -Rat (82-5)
If EPA believes that more in-depth developmental toxicity data are indicated

(e.g., developmental testing shows CNS Malformations; Neurotoxicity; Neuropathology; Endocrine Disruptor, etc.)

Developmental Neurotoxicity (83-6)

Behavioral effects and physiological effects on the nervous system in the offspring.

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updated May 17, 1998