Objective of the study

A 21 or 28 day repeated dose dermal study will provide information on possible health hazards likely to arise from repeated dermal exposure to a test substance for a period of 21/28 days

Such sub-chronic dermal toxicity studies are primarily used to derive regulatory concentrations for assessing operator and worker risk in occupational settings.

Circumstances under which the study is recommended to be required

The 21/28-day dermal toxicity study is recommended if the pesticide is intended for agricultural uses or if repeated human dermal exposure may occur.

The study is not required an acceptable 90-day dermal toxicity study is performed and submitted, or if the pesticide is a severe irritant.

Test organism

The study is normally conducted with the adult rat, rabbit or guinea pig. If another species is used, the applicant should provide a justification for its selection.

Test substance

- Technical grade active ingredient
- End-product testing is recommended if the product, or any component of it, can increase dermal absorption of the active ingredient(s) as determined by testing the TGAI, or can increase toxic or pharmacological effects.

Typical endpoints of the study

The principle of the test is that a substance is applied daily to the skin in graduated doses to several groups of experimental animals, one dose per group, for a period of 21/28 days. During the period of application the animals are observed daily to detect signs of toxicity. Animals which die during the test are necropsied, and at the conclusion of the test the surviving animals are sacrificed and necropsied.

Typical endpoints include mortality, toxic response, haematology, clinical pathology, and histopathology.

Where possible, the No Observed Adverse Effect Level (NOAEL) will be reported.

Test guidelines

The following test guidelines may be used for the short-term 21/28 day dermal toxicity studies:
• OECD Guidelines for the Testing of Chemicals. Test No. 410: Repeated dose dermal toxicity: 21/28-day study.
• US EPA Health Effects Test Guidelines. OPPTS 870.3200. 21/28-day dermal toxicity
• EC Testing Method B.9 Repeated dose (28 days) toxicity (dermal). Council Regulation (EC) No 440/2008.