Abnormal toxicity tests

The health effects of sorbic acid and sorbates have been reviewed (165—167). The extremely low toxicity of sorbic acid enhances its desirabiHty as a food preservative. The oral LD q for sorbic acid in rats is 7—10 g/kg body weight compared to 5 g/kg for sodium chloride (165—169). In subacute and chronic toxicity tests in rats, 5% sorbic acid in the diet results in no abnormal effects after 90 days or lifetime feeding studies. A level of 10% in rat diets results in a slight enlargement of the Hver, kidneys, and thyroid gland (170). This same dietary level fed to mice also resulted in an increase in Hver and kidney weight... 

Freedom from abnormal toxicity. The purpose of this simple test is to exelude the presence in a final container of a highly toxie contaminant. Five mice of 17-22g and two guinea-pigs of250-350 g are inoculated with one hnman dose or 1.0ml, whichever is less, of the test preparation. All must survive for 7 days without signs of illness. 

As part of the assessment of reproductive toxicity testing there is a regulatory requirement that fetuses from treated dams are examined for developmental and structural abnormalities by soft tissue examination. Current guidelines (1, 2) stipulate that this is performed in two laboratory species, one rodent (rat or mouse) and one non-rodent (routinely rabbit), in order to assess the safety of a test compound before, or in case, humans are exposed. 

Reviews of the results from the reproductive toxicity testing for the approved monoclonal antibody biopharmaceuticals have shown very few incidences of harm to fetuses. The only notable effects that have been observed are hematologic changes in macaque fetuses exposed to natalizumab, skeletal abnormalities in rabbit fetuses exposed to bevacizumab, and immunological deficits in mice exposed to the efalizumab murine surrogate. In each of these examples the effects seen in the fetuses were predicable based on effects seen in the adult animals. 

The majority of toxicity tests (which particularly are subject to ethical criticism) are firmly based on studies in whole animals, because only in them is it possible to approach the complexity of organisation of body systems in humans, to explore any consequences of variable absorption, metabolism and excretion, and to reveal not only direct toxic effects but also those of a secondary or indirect nature due to induced abnormalities in integrative mechanisms, or distant effects of a toxic metabolite produced in one organ that acts on another. ... 

Apart from standardization of potency, which also serves as an identity test, the material must be checked for sterility and for the absence of viable mycobacteria. Because of their slow growth the latter may not be detected by conventional sterility tests and it is usual to perform check tests by guinea-pig inoculation, or by prolonged culture on Lowen-stein-Jensen medium. The product is also checked for absence of reactogenicity in unsensitized guinea-pigs and if required by the regulatory authority, for abnormal toxicity. 

Dasgupta A. Review of abnormal laboratory test results and toxic effects due to use of herbal medicines. Am J Clin Pathol 2003 120 127-37. 

It is undesirable to use in production any agent known to provoke sensitivity reactions in certain individuals, such as penicillin or other 8-lactam antibiotics. Many of the general requirements for the quality control of biological products, such as tests for potency, abnormal toxicity, pyrogenicity, stability and sterility, also apply to products made by rDNA techniques. 

Toxicity test of rats and mice all showed that no death, increase of serum GOT and abnormal symptoms happened, in the animals (3.2g/Kg).(9) After three rabbits had taken ss (5mg/Kg/day) for four weeks, it was found that their appetite reduced, their weight increased slowly and their hematological, liver and Iddney fiinction examinations and vital organ microscopy had no abnormity.(8)... 

ONCB is considered to be moderately toxic to humans upon acute exposure. Regardless of the route of exposure, cyanotic appearance is the predominant symptom observed in toxicity tests. Repeated exposure to sufficient concentrations of ONCB may cause methemoglobinemia [27]. This blood disorder, in which the body produces an abnormal level of methemoglobin and carmot effectively transport oxygen to the cells, may have accounted for the symptoms... 

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