Toxicity test designs pathology

Since phosphate is also involved in calcium homeostasis via its effects on the renal 25-OHD-la-hydroxylase (and not involving PTH), an imbalance of calcium and phosphate in the diet, or impairment of absorption, can lead to derangement of the control mechanism. It is of interest in relation to food safety evaluation that, in rats, calcium deposition in the kidney (nephrocalcinosis) has been observed in a number of studies on modified starches and microbial biomass . In the latter case, rats fed Candida utilis biomass rich in phosphorus and low in calcium developed nephrocalcinosis, but when the Ca/P ratio was adjusted to unity, renal changes were minimal. There is a clear lesson to be learned here if dietary imbalance per se can cause, or increase the severity of, pathological lesions, particular caution has to be exercised in the design and interpretation of toxicity tests where the test material is included in the diet at high concentrations. 

Shortly before exposure to the test chemical, the animals are weighed and exposed to different test chemical concentrations in the designated chamber for 4 hours. The temperature at which the test is performed should be maintained at 22 °C ( 2°C). Ideally, the relative humidity should be maintained between 30% and 70%, but in certain cases (e.g., aerosols), even this may not be practicable. Food should be withheld during exposure. Water also may be withheld in certain cases. The observation period for acute inhalation toxicity in animals should be at least 14 days. For clinical examination and pathology, the parameters listed for acute oral toxicity may be followed. The following conditions should be monitored during the experiment using a standard inhalation chamber. 

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