(1961) Safety testing of carcinogenic agents.
(1974) Carcinogenicity study of commercial saccharin in the rat.
Eye effects. Injury to the eye ranges from reddening of the outer layer (swimming-pool redness) to cataract formation of the cornea to damage to the iris (coloured part of the eye). Eye irritation tests are conducted when it is believed serious injury will not occur. Many of the mechanisms causing skin corrosion can also cause injury to the eyes. Materials corrosive to the skin, like strong acids (pH less than 2) and alkali (pH greater than 11.5), are not tested in the eyes of animals because most will cause corrosion and blindness due to a mechanism similar to that which causes skin corrosion. In addition, surface active agents like detergents and surfactants can cause eye injury ranging from irritation to corrosion. A group of materials that requires caution is the positively charged (cationic) surfactants, which can cause burns, permanent opacity of the cornea and vascularization (formation of blood vessels). Another chemical, dinitrophenol, has a specific effect of cataract formation. This appears to be related to concentration of this chemical in the eye, which is an example of pharmacokinetic distributional specificity.
(1957) The gastric secretion of drugs -- a pH partition hypothesis.
It has been noted, for example, that if a toxic effect occurs in only 1% of the test animals, the effect will be entirely missed 37% of the time if only 100 animals are used in each test (Friedman, 1969).