Toxicology (consultants)
Toxicology assays are laboratory tests used to evaluate the toxic effects of substances on living organisms or biological systems. They are crucial in environmental science, pharmacology, public health, and regulatory assessments to determine the safety and risk of exposure to various substances. Common types of toxicology assays include in vitro assays, which use cultured cells or tissues to test toxicity without using live animals, invivo assays, which involve administering substances to live animals, and ecotoxicological assays, which assess environmental toxicity in water and soil ecosystems. Key parameters assessed include LC50/LD50, NOAEL/LOAEL, IC50, and biomarkers like oxidative stress enzymes, DNA damage, and hormone levels.
In vivo Toxicology
- MTD & DRF
- Acute / Sub chronic/Chronic Toxicity
- Repeated dose toxicity
- Skin irritation
- Eye irritation
Geno toxicity
- Bacterial Reverse Mutation Test (AMES)
- In-vitro Chromosomal Aberration Test
- In-vivo Bone marrow Chromosomal Aberration Test
- In-vitro Mammalian Cell Micronucleus Test
In vivo Toxicology
MTD (Maximum Tolerated Dose) and DRF (Dose Range Finding) studies.
MTD is the highest dose of a substance that can be administered without severe toxicity or death, but may cause reversible signs. It is used to identify a safe upper limit for dosing and support dose selection for longer-term toxicity studies. DRF studies determine a suitable range of doses for longer-term toxicity or efficacy studies. They are short duration, small number of animals, multiple dose levels, and observation of clinical signs.
Acute / Sub chronic/Chronic Toxicity
Acute toxicity refers to toxic effects after a single dose or short-term exposure, typically seen within 24 hours. It is common in accidents and chemical spills, with test subjects typically rodents. Sub-chronic toxicity occurs from repeated exposure over a short-to-medium term, identifying target organs and early signs of toxicity. Chronic toxicity evaluates carcinogenicity, organ damage, and cumulative effects, important for regulatory decisions and long-term safety.
Repeated dose toxicity
Repeated dose toxicity is the harmful effects of a substance when administered repeatedly over a period, determining potential health risks. It is used in drug development, chemical safety assessments, and environmental risk evaluations. Types include subacute (14-28 days), subchronic (90 days), and chronic (3-6 months to 2 years). OECD guidelines for testing include 28-day oral toxicity in rodents, 90-day oral toxicity in rodents, and chronic toxicity studies. Key considerations include administration route, dose selection, animal welfare, and control groups.
Skin irritation
Skin irritation is a crucial inflammatory response in dermal toxicity studies and regulatory safety assessments. The Draize Skin Irritation Test is widely used, but ethical considerations have led to in vitro, ex vivo, and computational models.
Eye irritation
In vivo toxicology studies evaluate the potential of substances to cause eye irritation, often involving the Draize Eye Test. This test, developed by FDA toxicologist John Draize, involves injecting a small amount into rabbits’ eyes, with the results evaluated over up to 21 days. The test scores each eye part, with higher scores indicating greater irritation. Substances are classified as non-irritant, mild, moderate, or severe.
Geno toxicity
Bacterial Reverse Mutation Test (AMES)
The Bacterial Reverse Mutation Test (Ames test) is an in vitro assay used to determine the mutagenic potential of chemical compounds. It assesses if a substance can cause genetic mutations in bacteria’s DNA. The test uses mutant strains of Salmonella typhimurium or E. coli that cannot synthesize histidine due to a specific mutation. If the compound is mutagenic, it causes reverse mutations, allowing bacteria to grow and form colonies. The test uses common Salmonella strains and an S9 mix to simulate mammalian metabolism. It is quick, cost-effective, and useful as a preliminary screen.
In-vitro Chromosomal Aberration Test
The In-vitro Chromosomal Aberration Test is a genotoxicity assay used to detect structural chromosomal damage in cultured mammalian cells, assessing the potential of chemicals, pharmaceuticals, or environmental agents to cause genetic mutations or chromosomal aberrations.
In-vivo Bone marrow Chromosomal Aberration Test
The In-vivo Bone Marrow Chromosomal Aberration Test is a standard genotoxicity test used in toxicology and regulatory toxicology studies. It detects chromosomal damage in rodent bone marrow cells, indicating genotoxic potential through structural aberrations, mitotic index, polyploidy, and endoreduplication.
In-vitro Mammalian Cell Micronucleus Test
The In-vitro Mammalian Cell Micronucleus Test (MNvit) is a method to assess the genotoxic potential of chemical substances by detecting micronuclei in interphase cells, detecting clastogenic and aneugenic effects, and indicating dose-response and cytotoxicity levels.
