At least two species, rats and dogs most common.

At least 10 animals/sex for rats and 4 animals/sex for dogs for each dose.

Continuous exposure.

At least three, preferably five, dose levels with the highest level causing significant toxicity and the lowest showing no toxicity.

Controls for diet and carrier when the carrier has not been well characterized.

Daily observations similar to those described for the acute toxicity studies

Hematology to include hematocrit, cell counts, and clotting time

Complete blood chemistry at end of test period to include serum enzymes

Gross necropsy including organ weights.

Non rodents-all gross lesions, heart, ovaries, and spleen. All animals are examined.

Rodents-all gross lesions.

In addition for animals in the control and high dose groups heart, lung, thyroid, parathyroid, stomach, small & large intestine, uterus, brain, lymph node, testes, ovaries, spleen and bone marrow are examined. Other groups are examined if changes or equivocal results are seen.