PBT Assessment - REACh

CHAPTER R11 – PBT ASSESSMENT
Lipid normalising the chosen CBB of 0.001 mmol/kg ww, and assuming a lipid content of 5%,
gives a lipid normalised CBB of 0.02 mmol/kg lipid or 0.02 × molecular weight mg/l lipid.
However, given the uncertainty involved in deciding on the CBB that should be used, it is suggested
that an application factor of 10, to account for species differences and organ versus body differences
be applied to this solubility in lipid/octanol, giving an octanol solubility (mg/l lipid) of 0.002 ×
molecular weight. This would mean octanol solubilities of 1 and 2 mg/l n-octanol (or lipid),
respectively, for substances with molecular weights of 500 and 1,000.
Conclusion: it is proposed that where a chemical has a solubility of less than (0.002 × molecular
weight) mg/l in octanol it should be assumed that the compound has only a limited potential to
establish high body burdens and to bioaccumulate. If it does bioaccumulate, it would be unlikely to
give rise to levels in biota that would cause significant effects.
When there are fish or mammalian toxicity or toxicokinetic studies available, all showing no
chronic toxicity or poor absorption efficiency, and a substance has, in addition, a low solubility in
octanol, no further bioaccumulation testing would be needed, and the chemical can be assigned as
no B, no vB. In theory, such a substance could elicit toxic effects after prolonged times in aquatic
organisms. However, the chance such a thing would occur would be very low.
When there are no other studies available, and a substance has a low solubility in octanol, it is
probable that other types of information (persistency, molecular size) would need be taken into
account in deciding on bioaccumulation testing. It would also be helpful if testing, of the nature
discussed above, were needed for other regulations, that might be useful in this evaluation, then the
need for bioconcentration testing could be assessed when the new data became available.
Other indicators for further consideration
The two indicators, molecular size and lipid solubility, are the most frequently cited physical
limitations for low bioconcentration. However, there are other indicators that could also be used for
indicating whether the bioconcentration of a chemical is limited or reduced despite having a log Kow
> 4.5. These include:
• Biotransformation - discussed in the TF report, ECETOC, 2005, (de Wolf et al, 1992, 1993;
Dyer et al, 2003) and clearly needing development to improve how such information may be
used;
• Other indicators for low uptake, these could for example include
− lack of observed skin permeability (this alone not without substantiating that it is significant
less than uptake in fish),
− very low uptake in long term mammalian studies and/or
− low chronic systemic toxicity in long term mammalian and/ or ecotoxicity (fish) studies
Both these approaches would benefit from further research and investigation for their potential to
indicate limited or reduced bioconcentration. While it is not recommended, based on the current
level of information, to use such indicators alone to predict low bioconcentration, they can act as
supporting information to other indicators in arriving at this conclusion.
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