According to EMA guideline, the PDE ( permitted daily exposure) is calculated by dividing NOAEL/LOAEL value by some safety factors.
My problem is how to identify the NOAEL/LOAEL basing on the data of toxicological studies.
For example, I have some data as in the attachment and the authors provide the information of studies as below:
" Rat: 30 day study, intravenous and subcutaneous All rats given 8.1 g/kg IV and 2 of 12 given 2.7 g/kg died within 10 minutes in convulsive shock and were found to have dilation of proximal and distal convoluted renal tubules. The 8.1 g/kg dose given sc was tolerated by females for the entire 30 day treatment period; males, however, had to be sacrificed after their third dose, and were found to have coagulative necrosis of 50 to 85% of the proximal convoluted tubules, but no other organ pathology. Toxicity in survivors was similar by either route of administration. The following biochemical and morphological changes were observed in survivors during or immediately following the treatment period: decreases in serum transaminases, protein (8.1 g/kg/day dose), alkaline phosphatase, calcium, and triglycerides; increases in serum sodium, potassium, inorganic phosphorus, protein (
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