Updated toxicology test methods for new industrial chemicals: Implications for regulatory acceptance of in vitro alternatives now and in the future.
Toxicology studies submitted under the Notification of New Substances Regulations are conducted according to standard ('Annex V') methods first published in 1984. In December 1992, updated methods became available that indicate where progress has been made in developing in vitro alternatives to animal testing which are acceptable to the regulatory authority (Health and Safety Executive). Although some changes reflect concern for animal welfare (e.g. the introduction of the fixed-dose method), for most toxicological endpoints an animal test remains obligatory. The major advance in the potential use of in vitro methods is as part of a tiered approach to irritancy testing. The updated method for eye irritation, for example, allows positive results in 'well-validated alternative studies' to override the need for an animal test. The substance is then classified as irritant and labelled with R41. The challenge facing such methods is to achieve full validation, so that negative data will be acceptable to the regulatory authorities. There are other challenges: a validated in vitro screen for developmental toxicity is needed for new substances, as are methods for detecting respiratory sensitizers and for replacing guinea pig skin sensitization tests.
Evans
P F
PF
Health and Safety Executive, Magdalen House, Bootle, Merseyside L20 3QZ, UK.