Oral Toxicity OECD 408

At Altogen Labs, we adhere to the most rigorous standards for repeated dose 90-day oral toxicological evaluation, implementing the OECD Test Guideline 408 (TG 408) as a foundation for assessing the sub-chronic toxicity of chemical compounds. Altogen Labs study protocol is designed to evaluate the systemic effects of repeated oral exposure to test substances over a 90-day period. The most recent revisions incorporate additional endpoints to enhance the detection of endocrine activity while maintaining the comprehensive assessment of neurological, immunological, and reproductive toxicological effects.

Initial Considerations

The 90-day repeated dose oral toxicity study provides critical data concerning potential adverse effects associated with prolonged chemical exposure. Altogen Labs conducts the study following acute toxicity evaluations or shorter-duration studies, such as the 28-day repeated dose toxicity test, this study further characterizes systemic toxicity and contributes to the identification of target organ specificity, potential for chemical accumulation, and the establishment of a dose-response relationship. The data obtained are instrumental in defining safe exposure levels for human health risk assessments and guiding dose selection for chronic studies.

Principle of the Test

Altogen Labs’ 90-day oral toxicity study is designed to assess the potential toxic effects associated with prolonged exposure to a test chemical. The study is conducted by administering the test compound daily to multiple groups of rodents at graduated dose levels. The primary objectives of Altogen Labs’ assessment are to identify the major toxicological effects of the substance, determine the specific organs or systems affected, evaluate the potential accumulation of the chemical in biological tissues, establish a no-observed-adverse-effect level (NOAEL), and assess endocrine, neurological, reproductive, and immunotoxicity endpoints.

To ensure systematic data collection, Altogen Labs test subjects undergo daily clinical evaluations, weekly functional examinations, and comprehensive necropsy with histopathological assessment at the conclusion of the study. In cases where toxicity is observed, a satellite recovery group is included to evaluate the potential reversibility or persistence of toxic effects following cessation of exposure.

Description of the Method

Altogen Labs’ study design comprises three treatment groups, each receiving a progressively higher dose of the test substance, along with a concurrent control group for comparative analysis. In cases where a limit test is warranted, a single high dose of at least 1000 mg/kg/day is administered to determine the absence of adverse effects.

Rats are the preferred species for this study at Altogen Labs due to their well-documented physiological responses; however, mice are used when scientifically justified. All rodents used in the study at Altogen Labs are selected from standardized laboratory strains to ensure uniformity in physiological responses and minimize confounding variables. The environmental conditions within the testing facility at Altogen Labs remain meticulously controlled, with temperature maintained at 22°C ±3°C, relative humidity kept within the range of 30% to 70%, and a 12-hour light-dark cycle implemented. All test subjects are provided with standardized diets that are free of endocrine-disrupting contaminants such as phytoestrogens, which are restricted to concentrations below 350 μg of genistein equivalents per gram of diet. Drinking water is made available ad libitum throughout the study.

Dosing is conducted via oral gavage, dietary incorporation, or dissolution in drinking water, depending on the physicochemical properties of the test compound. The selected route of administration accurately reflects human exposure conditions to ensure regulatory relevance. Throughout the duration of the study, all animals undergo continuous monitoring for clinical signs of toxicity, and data on body weight, food consumption, and water intake are recorded at weekly intervals.

Procedure

Number and Sex of Animals

At Altogen Labs, each dose group consists of at least 20 animals, evenly distributed between males and females, to allow for a comprehensive evaluation of sex-specific toxicological effects. If interim necropsies are required, additional animals are incorporated into the study design. In cases where the persistence or reversibility of observed toxic effects must be assessed, satellite groups comprising a minimum of five animals per sex per dose group are maintained for an extended post-exposure period.

Dosage Selection and Administration

Doses are selected based on prior toxicological data, ensuring that the highest dose level induces observable toxicity without causing undue suffering or mortality. A descending sequence of dose levels is utilized to establish dose-dependent responses and define a NOAEL. The control group, which serves as a benchmark for evaluating treatment-related effects, receives either no exposure to the test substance or a vehicle-only administration if a carrier substance is used.

Limit Test

If a test at a single dose level of at least 1000 mg/kg/day produces no observable adverse effects and toxicity is not anticipated based on the known properties of structurally related compounds, a full study incorporating multiple dose levels is not required. The limit test provides a rapid and efficient means of assessing the potential toxicity of a test substance under conditions of high exposure. However, if human exposure scenarios suggest the possibility of significant toxicological effects at higher doses, a complete dose-response assessment still is necessary.

Observations

Throughout the study at Altogen Labs, the clinical condition of each test subject is assessed daily for signs of morbidity or mortality. In addition to routine evaluations, weekly examinations are performed to detect potential neurotoxic, immunotoxic, and endocrine-mediated effects. Neurological assessments include sensorimotor reactivity evaluations, grip strength measurements, and motor activity assessments to detect alterations in neuromuscular function. Behavioral analysis encompasses the examination of posture, movement abnormalities, autonomic responses, and grooming behaviors. Ophthalmological assessments are conducted both at baseline and at the conclusion of the study to identify any test-related ocular abnormalities.

Clinical Pathology and Endocrine Testing

Hematology and Serum Biochemistry

At study termination, Altogen Labs ensures blood samples are collected to conduct comprehensive hematological and biochemical analyses. These evaluations include hematocrit measurements, hemoglobin concentration assessments, erythrocyte and leukocyte counts, platelet enumeration, and coagulation parameter assessments. Serum biochemistry analyses involve quantifying sodium, potassium, glucose, total cholesterol, HDL, LDL, urea, creatinine, total protein, albumin, and hepatic enzyme levels, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT).

Endocrine-Specific Biomarkers

Altogen Labs’ study incorporates endocrine-sensitive endpoints to enhance the detection of hormonal perturbations. Thyroid hormone assessments include quantification of thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH). Lipid metabolism parameters, including total cholesterol, HDL, and LDL, provide additional insight into metabolic effects mediated by thyroid hormone activity. If deemed relevant based on the toxicological profile of the test substance, reproductive hormones such as testosterone, estradiol, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) are analyzed. To minimize variability in hormone quantification, blood samples are collected under strictly standardized conditions, accounting for circadian influences, estrous cycle variations, and stress-induced hormonal fluctuations.

Necropsy and Histopathology

At study termination, all Altogen Labs test subjects undergo necropsy to assess macroscopic and microscopic tissue alterations. Organs including the brain, heart, liver, kidneys, adrenal glands, spleen, testes, epididymites, prostate, seminal vesicles, ovaries, uterus, cervix, thyroid gland, and pituitary gland are excised, weighed, and subjected to histopathological examination.

Data Analysis and Statistical Interpretation

All Altogen Labs quantitative data are subjected to rigorous statistical analysis to identify significant treatment-related effects. The selection of statistical methods is determined based on the study design and includes parametric and non-parametric tests such as analysis of variance (ANOVA) for continuous variables, chi-square tests for categorical outcomes, and regression modeling for dose-response analysis. Control group data are compared against historical reference values to ensure data reproducibility and facilitate inter-study comparisons.

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