The relevance of cryoprotectant "toxicity" to cryobiology.

Cryoprotective agents are essential for the cryopreservation of almost all biological systems. These additives, however, do not usually permit 100% survival after freezing and thawing, though from a theoretical point of view they should be able to fully suppress all known types of freezing injury. In view of the known biological and physicochemical effects of cryoprotectants, it is suggested that the toxicity of these agents is a key limiting factor in cryobiology. Not only does this toxicity prevent the use of fully protective levels of additive, but it may also be manifested in the form of cryoinjury over and beyond the cryoinjury due to classical causes. Evidence for this extra injury ("cryoprotectant-associated freezing injury") is reviewed. It is suggested that better suppression of toxicity is possible and will lead to advances in cryopreservation.