Multiple -dose toxicity

RTECS Registry of Toxic Effects of Chemical Substances number is a unique and unchanging number used to cross-reference the RTECS database, which is a compendium of data extracted from the open scientific literature. Six types of toxicity data are included in each file (1) primary irritation, (2) mutagenic effects, (3) reproductive effects, (4) tumorigenic effects, (5) acute toxicity, and (6) other multiple dose toxicity. 

Pivotal safety studies in a single relevant species are usually appropriate for MAbs, as are single-dose pharmacokinetic studies, a multiple-dose toxicity assessment with toxico-kinetic sampling, and immunogenicity studies. 

Acute Toxicity The adverse effect occurring within a short time of (oral) administration of a single dose of a substance or multiple doses given within 24 hours. 

Traditionally, the duration of a toxicity study depends on the intended clinical use and disease duration. The potential immunogenicity of the human protein is a significant issue since antibody binding can partially or completely inhibit the biological activity of that protein, affect its catabolism or alter its distribution and clearance. Any multiple-dose study therefore should include evaluation of the impact of antibody formation, including their neutralizing capacity. However, antibody formation in itself should not be a reason for termination of a toxicity study, particularly if the antibodies are not neutralizing or do not alter the pharmacodynamics of the protein. 

Potential toxicity following single and multiple dosing. 

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