TOXICOLOGY

IIBAT offers a range of GLP–Compliant General Toxicology, Risk Assessment and Biocompatibility studies with the support of experts in regulatory toxicology.

Expertise in Regulatory Toxicology in choosing appropriate dose calculations and data interpretation based on the recent toxicological approaches that include Weight of Evidence, HESI recommended RISK21 initiatives, Fit-for-purpose safety evaluations and Adverse Outcome Pathway.

Acute Oral Toxicity Studies

Acute oral toxicity studies evaluate the toxic effects of a substance when administered through the mouth in a single or short-term dose. These studies determine the lethal dose (LD50) and assess symptoms like gastrointestinal distress or systemic toxicity. The results guide safe oral exposure limits and risk assessments. There are three different types of acute studies as given below.

Class Method (423): This method is developed based on the biometric evaluations of the test systems on exposure to a test substance with fixed doses, adequately separated to qualify a substance to be classified based on the Globally Harmonised System (GHS) and hazard assessment.

Up-and-down Method (425): The method estimates an LD50 with a confidence interval (CI) and based on the results, the test substance is classified for acute toxicity according to the classification of Globally Harmonised System (GHS) and labelling of chemicals. Globally the LD50 is calculated using the maximum likelihood method.

Fixed Dose Method (420):  The primary premise of this method is that in the main study only moderately toxic doses are tested, and at the same time it is to ensure that the animals are not exposed to doses that are expected to be lethal.

Dermal Irritation Study (OECD Test No. 404)

This is to assess the health hazards likely to arise from exposure to liquid or solid test substances with an irritation potential on the skin after a single exposure. The extent of irritation is evaluated by providing progressive grading in conjunction with the nature and severity of lesions, and the possibility of reversibility of the effects.

Eye Irritation / Corrosion Study (OECD Test No. 405)

This is to assess the health hazards likely to arise from exposure to liquid or solid, or aerosols test substances in the eyes of animals. Commonly conducted on rabbits or using alternative in vitro methods, the study helps evaluate risks to human ocular health and its safety.

Skin Sensitization Study (OECD Test No. 406)

This study provides information on health hazards likely to arise from exposure to test substances via intradermal injection and/or epidermal application, while assessing whether a substance can cause allergic reactions upon repeated exposure to the skin. It involves methods like the Local Lymph Node Assay (LLNA) or Guinea Pig Maximization Test (GPMT) to predict sensitization risks.

Inhalation Toxicity Study (OECD Test No. 403)

Inhalation studies evaluate the toxic effects of airborne substances such as gas, vapour or aerosol / particulates, following exposure via the respiratory system, through head or nose-only exposure. The study determines safe exposure limits and quantitatively assesses irritation or systemic toxicity risks through inhalation route and possibility of gender susceptibility.

Local Lymph Node Assay (OECD Test No. 451)

Through radioactive labelling the LLNA measures the potential of chemicals to cause skin sensitization by examining the proliferation of lymphocytes in the lymph nodes of mice, thereby determining the immune response potential of a test substance. It is a refined alternative to traditional sensitization tests, providing both ethical and scientific benefits to identify skin sensitizers. There are other non-radioactive methods like 442 A and 442 B as well.

Carcinogenicity Studies (OECD Test No. 451)

These long-term studies, covering a major portion of the life span of animals, are aimed to assess whether a substance can cause development of neoplastic lesions during or after exposure to different doses, eventually causing cancer in animals. Typically involving rodents, they identify potential carcinogens and inform regulatory decisions regarding cancer risks among human beings.

Health Monitoring Study

Health monitoring studies are conducted in healthy volunteers to evaluate the safety of household products such as mosquito coils, incense sticks, liquid vaporizers, and mosquito nets. These studies assess any potential health hazard likely to arise from unintended exposures, including respiratory effects, irritation, or allergic reactions, during typical use scenarios.

Risk Assessment - LLIN following Generic Risk Assessment Model (WHO)

This process evaluates the safety of Long-Lasting Insecticidal Nets (LLINs) based on WHO guidelines. WHO brings out generic models for human health risk assessment of vector control products, generally referred to as generic risk assessment models (GRAMs). This includes hazard assessment, exposure assessment and risk characterization. The model assesses risks to humans and the environment during use and disposal, ensuring effective malaria prevention with minimal harm.      

In vitro Skin Corrosion/Irritation Studies (OECD Test No. 431)

These alternative methods assess a chemical's potential to damage or irritate the skin using cell cultures or Reconstructed Human Epidermis (RhE) models. RhE is a stand-alone replacement for in vivo tests as it closely mimics the biochemical and physiological features of the upper layers of the skin of human beings. They reduce the need for animal testing while providing reliable results and help identifying non-corrosive and corrosive test substances and mixtures in accordance with GHS by determining the weight of evidence.

Abnormal Toxicity Study

This study, also known as a safety test, detects unexpected toxic effects in biological products. It ensures batch-to-batch consistency and safety for human use.

Immunotoxicity Studies

Immunotoxicity studies evaluate the adverse effects of substances on the immune system, including suppression, hypersensitivity, or autoimmunity. They are critical for assessing risks of immunological disorders.

Range-finding Toxicity Studies

These preliminary studies determine the appropriate dose levels for subsequent repeated or prolonged toxicity studies. They provide insights into tolerable and toxic dose ranges, facilitating appropriate study design and number of animals.

Sub-chronic Toxicity Studies (OECD Test No. 408)

Sub-chronic studies involve repeated exposure to a substance over a period of 90 days. They evaluate toxic effects on various organs and establish No-Observed-Effect Levels (NOELs), other than identifying the target organ toxicity caused by the test substance.

Chronic Toxicity Studies (OECD Test No. 452)

Chronic toxicity studies assess long-term toxic effects over extended periods, typically six to twelve months of exposure. These studies help identify cumulative toxicity and health risks in a mammalian species due to potential prolonged and repeated exposure. Other OECD test guidelines include Test No. 453: Combined chronic toxicity / carcinogenicity studies.

Developmental and Reproductive Toxicology Studies

These studies examine the effects of substances on reproduction and development, as a result of prenatal and postnatal exposure to test substances as well as evaluating systemic toxicity in pregnant and lactating females and young as well as adult offsprings. The assessment includes fertility, embryo-fetal development, and postnatal growth. They are crucial for evaluating risks to pregnant women and offspring. The OECD test guidelines include Test No. 414, 421, 422 and 443.