Acute Toxicity Studies

What is Acute Toxicity Studies?

Acute toxicity studies examine the adverse effects arising from administration of a single dose of a substance or multiple doses given within 24 hours. The substance is usually administered by the oral, dermal and inhalation routes.

The degree of hazard presented by pesticides depends on many complex factors. Although no single factor is completely reliable, the acute toxicity of a chemical probably gives the most useful immediate indication of the potential acute hazards to human users and bystanders and probably also to domestic animals.

Classification of pesticides under the Indian National Regulation is primarily based on acute toxic and irritancy effects and therefore demands, amongst other things, data on acute oral, dermal and inhalation toxicities. Additional specialised studies are used to assess the skin and eye irritancy and skin sensitisation potential of the substance.

To permit assessment of the acute toxicology of a pesticide to exposed humans, studies in animals should examine the most likely routes and forms of exposure. They should be performed with both the active constituent and the products to be marketed.

Acute oral/dermal/inhalation toxicity studies should be performed in at least one mammalian species. The rat is the preferred rodent species for oral studies. LD50 and LC50 values are normally required for hazard classification purposes. Reports should include details of the observed toxic signs, reasons for death and other data which will enable assessment of acute toxic potential.

For skin and eye irritation studies, the rabbit is an acceptable species but properly validated alternatives to the usual in vivo test would be suitable. Eye irritation tests may be unnecessary in the case of substances or formulations where chemical or physical properties suggest this form of toxicity is likely, e.g pH above 11.5 or below 2.

A skin sensitization study is also required to test for possible hypersensitivity reactions to the chemical. Guinea pigs are normally used for sensitization studies. Internationally validated in- vitro alternative methods, such as the murine local lymph node assay (LLNA in vivo), are also acceptable.

What are the Type of Acute Toxicity Studies test?

1. Acute Oral

2. Acute Dermal

3. Acute Inhalation

4. Primary Skin Irritation

5. In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method

6. Acute Eye Irritation Skin Sensitization

General Guidance For Toxicity Testing

• All toxicity studies must be conducted in accordance with the Guidelines for the Testing of Pesticides prescribed in this report.

• The studies must be conducted in Good Laboratory Practice (GLP) certified laboratory. The study reports should be accompanied with the GLP certification from the Study Director and Quality Assurance (QA) certificate from QA unit of the laboratory.Non-GLP or non- Guideline compliant studies will be considered on their scientific merit as additional information/study.

• Studies should use testing regimes which cover the most likely routes/modes of human exposure.

• Studies must be conducted using active constituents or formulations containing an impurity level comparable to that present in the commercial product. All toxicity studies must include details on the composition of the material used in the study, including solvents and vehicles. For chiral compounds the enantiomer ratio used in all toxicity studies must be clearly indicated.

• Each study must clearly identify the name and address of the laboratory which performed the study, the names of the responsible scientists, the report number, the dates when the study was performed and the report was written.

• Studies should be designed to assist in the establishment of No-Observed-Adverse-Effect Levels (NOAELs) in repeated exposure studies and to provide evidence of potential short- and long term hazards, from which an estimate of the pesticide’s relative safety can be deduced.

• The observation period, observational methods utilized and description of pre-mortem and non-lethal effects, their appearance, time course and reversibility.

• The number of animals died or killed for humane reasons, time of death and reasons for humane killing.

• A detailed methodology/procedure and individual animal data should be given. 12. When indicated, as in delayed deaths, the inclusion of gross pathology and possibly histopathology.

• The LD50/ LD50 Cut Off Value/Category as per the Insecticides Rules, 1971 should be given in consonance with the methodology adopted.

• Statistical methodology (Name with reference), if adopted, also need to be given.

• Statement regarding the time period of retention of raw data/test article/specimen to be given.