Thomas A. Ban: Psychopharmacology. Baltimore: Williams and Wilkins; 1969

Leon S. Morra’s Extracts - 12
Part One, Chapter Two: Animal Pharmacology
B. Toxicity

“The purpose of animal toxicity studies is to uncover the toxic, or hazardous properties of a drug and to establish the circumstances in which they become manifest.”

1.     Toxicity Studies

Animal toxicity studies are carried out in four steps.

a.              “In the acute toxicity studies the new substance is administered in single, increasing doses by various routes to small groups of animals belonging to two or more species”

b.              “In the subacute toxicity studies the compound is administered by several (at least two) routes, over a two to 12 week period, in at least three dosage ranges (one of them has to be large enough to be visibly effective or even lethal) to small groups of animals belonging to two or more species.”

c.              “The only difference between the subacute and chronic toxicity testing is in the duration of the study. This is extended from three months to a maximum of two years… immediately after termination of the drug administration or at any time when toxic effects occur, some of the affected animals are sacrificed for pathological evidence of injury, while some others are taken off the drug and returned for further observation… The various parts of the body described in detail (including miscroscopic examination) are: skin, brain, eye, pituitary, tyroid, thymus, adrenals, tongue, stomach, small intestine, colon, heart, ling, liver, parncreas, spleen, bladder, kidney, gonads, including uterus, and prostate, lymph nodes and bone marrow. Particular attention is paid to the alimentary canal when the drug is given orally and to the site of injection if administered parenterally… No clinical investigation should commence with a potentially psychoactive compound prior to the completion of chronic toxicity testing lasting at least six months.” 

d.              “Special toxicity procedures were devised to detect potential carcinogenicity, to reveal the effect of the new drug on reproduction, to show its possible toxicity in interacting with other drugs and to recognize whether it is dependency producing.”  

July 6, 2017