OECD TG 408, OECD Test Guidelines for the Testing of Chemicals, Section 4 (Health Effects) as part of the “90-day oral repeated-dose toxicity study in rodents, ” i.e., the 90-day oral toxicity study in rodents following repeated administration. It was first adopted in 1981 and updated in 1998. The test is an in vivo toxicity study designed to evaluate the toxic effects, target organs, and dose-response relationship of a substance following repeated oral administration over a period of 90 days.
The basic principle of the test is as follows:
- The test substance is typically administered daily to rats via gavage or, if necessary, through their food or drinking water for 90 days.
- Typically, three dose groups and a control group are used; the dose levels are determined based on a 28-day preliminary study (TG 407) or existing data. The high dose should produce toxic effects but should not result in a high mortality rate or excessive pain.
- Each group typically consists of at least 20 animals (10 males + 10 females); additional animals may be included for blood and tissue analyses.
- The animals are clinically monitored daily; their body weight and feed and water intake are recorded regularly.
- At the end of the study, hematology, clinical chemistry, and urinalysis tests will be performed.
- The organ weights are measured, and a macroscopic necropsy is performed.
- A histopathological examination of the major organs and tissue samples is performed.
- If necessary, endocrine-sensitive endpoints (thyroid hormones, sperm parameters, estrous cycle) and neurotoxicity indicators can be evaluated.
The key parameters reported in the study are as follows:
- Dosages Used (mg/kg/day) and Route of Administration
- Clinical observations and their onset
- Changes in Body Weight and Feed/Water Intake
- Hematological parameters (complete blood count, white blood cell differential, etc.)
- Clinical chemistry parameters (liver and kidney function tests, electrolytes, glucose, lipids, etc.)
- Urinalysis Results
- Organ weights (absolute and relative)
- Findings from the macroscopic necropsy
- Histopathological findings (target organs and all major tissues)
- NOAEL/LOAEL Values and Dose-Response Relationship
- Data on Measurement Uncertainty and Repeatability
What is the purpose of the study?
OECD TG 408 is being conducted for the following scientific and regulatory purposes:
- Determination of Repeated-Dose Toxicity: Assessment of Systemic Toxic Effects and Target Organs Following 90 Days of Repeated Oral Exposure
- Evaluation of the Dose-Response Relationship: Determination of NOAEL and LOAEL Values
- Assessment of target organ toxicity: Evaluation of histopathological changes, particularly in the liver, kidneys, hematopoietic system, endocrine organs, and reproductive organs
- Provision of preliminary data for chronic studies: As a basis for dose selection in studies on chronic toxicity (TG 452) and carcinogenicity (TG 451, TG 453)
- Support in preparing regulatory submissions: Used in safety assessments under REACH, for biocides, plant protection products, pharmaceuticals, pesticides, and industrial chemicals
- Contribution to Risk Assessment: Provision of Baseline Data for Risk Assessment in Scenarios Involving Repeated Exposure
- Preliminary assessment of endocrine effects: If applicable, screening for endocrine activity based on endpoints such as thyroid hormones, sperm parameters, and the estrous cycle
- Evidence-Based Approach: A Contribution to the Holistic Assessment of the Substance in Conjunction with Other Toxicological, Physicochemical, and Exposure Data
OECD TG 408 does not provide direct information on acute toxicity or carcinogenicity; these effects must be evaluated in separate tests. The results should be interpreted in the context of the substance’s chemical structure, the data from the 28-day study (TG 407), chronic/carcinogenicity studies, and the exposure assessment.
As part of our nano-testing services, we conduct 90-day repeated-dose oral toxicity studies in accordance with OECD TG 408 with scientific rigor, utilizing our accredited laboratory infrastructure and quality management system. Our scope of services includes the following:
- Preparation of a study protocol in accordance with OECD TG 408
- Scientific justification for the dose levels based on the physicochemical properties of the test substance, the TG 407 data, and the available toxicity information
- Selection of a suitable carrier (vehicle) and evaluation of solubility and stability
- Determination of animal species, sex, age, route of administration, and observation period
- Planning the control and treatment groups, the number of animals, and additional analysis groups
- Compliance with Ethical Review and Animal Welfare Requirements
For information on study design, dose determination, histopathological planning, sample collection conditions, testing schedules, and reporting procedures for your 90-day repeated-dose oral toxicity studies in accordance with OECD TG 408, please feel free to contact Nano-Test.