Toxicity studies regulatory

The indicator molecule serves to assess the state of health of the cultured cells. The dye neutral red is often used (healthy cells assimilate the dye, dead cells do not). The major drawback to such systems is that they do not reflect the complexities of living animals and, hence, may not accurately reflect likely results of whole-body toxicity studies. Regulatory authorities are (rightly) slow to allow replacement of animal-based test protocols until the replacement system is proven to be reliable and is fully validated. 

AALAC certified laboratory. In-housing testing included acute, subacute, and subchronic oral, dermal and inhalation studies and specialty reproductive, behavioural, haematological and renal function toxicity studies. Preparation of risk assessment, submissions and presentations to regulatory agencies and trade association. 

Regulatory guidelines require that there be maternal toxicity at the highest dosage level in embryo-fetal developmental toxicity studies. It is important to avoid excessive toxicity in these studies since it is known that marked maternal toxicity can cause secondary developmental toxicity (see discussion in Section 8.4.3, Association between Developmental and Maternal Toxicity ). This secondary developmental toxicity is irrelevant to the assessment of the developmental hazard of the test agent and thus simply confounds the interpretation of the data. 

Repeated dose chronic toxicity studies are performed on two species of animals a rodent and nonrodent. The aim is to evaluate the longer-term effects of the drug in animals. Plasma drug concentrations are measured and pharmacokinetics analyses are performed. Vital functions are studied for cardiovascular, respiratory, and nervous systems. Animals are retained at the end of the study to check toxicity recovery. Table 5.2 shows the duration of the animal studies, which depends on the duration of the intended human clinical trial. Appendix 6 summarizes the information to be submitted to regulatory authorities. 

Most regulatory toxicity studies are conducted in animals to identify possible hazards from which an assessment of risk to humans is made by... 

After one or more lead compounds have been selected for further development, more preclinical investigations are needed before it is possible to start studies in humans. The main studies during this phase are toxicity studies in animals. It is important to note that the goal of these studies is not so much to find safe compounds and rejecf unsafe ones, but rather to learn under which conditions a potentially beneficial compound can be harmful, and to find out how it can be used safely in humans, if at all. Details on the type, duration and extent of toxicity studies needed can be found in various regulatory guidelines issued by ICH, FDA and EMEA and are easily accessible via the internet sites of these bodies. Although there are still differences in the requirements... 

The Indian regulatory system requires submission of reproductive toxicity study data in animals in support of Phase II and Phase III clinical trials. Table I provides all preclinical data that are required for the various phases of clinical studies. 

In addition, certain special toxicity studies (Table 2) are mandated by the Indian regulatory system as part of application submission to the DCGI for review and approval of each of the clinical phases. 

Reproductive and developmental toxicity studies in laboratory animals are conducted under regulatory testing guidelines (e.g., (1-3) as part of the process of evaluating the risk of pharmaceuticals and... 

Each candidate compound for entry into development was tested in FETAX. The objective was to give an early alert for developmental toxicity. A standard development plan was followed when FETAX gave negative results. In the case of a positive FETAX result, the mammalian embryo-fetal toxicity studies (preceded by dose-range finding studies) were brought forward (i.e., just after the regulatory repeat-dose toxicity study in rats). 

Key words Pesticides, Prenatal toxicity study, Two-generation study. Regulatory toxicology. Hazard identification, Risk assessment... 

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