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Note for Guidance for Food Contact Materials
Page 67 of 126
Annex 4 to Chapter III

ACCUMULATION IN MAN


This chapter focuses on accumulation in man and not on bioaccumulation in general. Many
experts are familiar with the term `bioaccumulation' as it relates to the fate of a chemical in the
environment. It covers e.g. the behaviour in aquatic organisms and potential for accumulation
through the food web.

In the case of food contact materials the interest centers on the potential for direct accumulation in
mammalian tissues and not on biomagnification through the food chain. However, normally a log
ko/w value below 3 would be considered sufficient evidence for the lack of accumulative potential
in the mammalian body, unless special considerations, e.g. chemical structure, give cause for
concern. On the other hand, a log ko/w of 3 and higher will not by itself be proof of accumulation
as a substance may not be absorbed or be metabolised to substances with no accumulation
potential. In these circumstances other evidence for the absence of accumulative potential is
needed.

It is not possible to give definitive guidance as to the methods to be used, as different approaches
must be followed for different substances according to their chemical structures and physical
properties. If it can be shown by appropriate kinetic studies (absorption distribution, metabolism,
excretion (ADME)) after oral exposure that the biological half-life excludes accumulation, this
would be considered sufficient evidence. Furthermore, the use of appropriately radioactively
labelled substances and autoradiography can demonstrate the existence/absence of an
accumulative potential of a substance.

Guidelines describing in detail the procedures for such studies do not appear to exist, but some
relevant information may be found in existing EU guidelines on veterinary drugs, additives in
animal nutrition, and human drugs. Also IPCS (EHC70 and EHC57) as well as the FDA Red
Book II could be useful sources on possible methodology.

In principle, accumulation is undesirable but not automatically associated with any toxic effects.
In cases where accumulation potential has been demonstrated or its lack not demonstrated, it
remains the responsibility of the applicant to provide evidence that any accumulation found will
not be associated with toxic effects even after long-term exposure.