PBT Assessment - REACh

PART R11 – PBT ASSESSMENT
information can be used in a weight of evidence approach to conclude that the substance is not
B/vB (see "conclusions on the endpoint").
LOG KOW
For the PBT and vPvB assessment a screening criterion has been established, which is log Kow
greater than 4.5. The assumption behind this is that the uptake of an organic substance is driven by
its hydrophobicity. For organic substances with a log Kow value below 4.5 it is assumed that the
affinity for the lipids of an organism is insufficient to exceed the B criterion, i.e. a BCF value of
2000 L/kg (based on wet weight of the organism, which refers to fish in most cases).
Care must be taken in case that a substance is known to bioaccumulate by a mechanism other than
passive diffusion driven by hydrophobicity. E.g. specific binding to proteins instead of lipids might
result in an erroneously low BCF value if this value is estimated from log Kow.
For some groups of chemicals, such as metals and surface active compounds, log Kow is not a valid
descriptor for assessing the bioaccumulation potential. Information on bioaccumulation of such
substances should therefore take account of other descriptors or mechanisms than hydrophobicity.
At log Kow values between 4 and 5, log BCF increases linearly with log Kow. This linear relationship
is the basis for the B screening criterion of log Kow > 4.5. However, at very high log Kow (>6), a
decreasing relationship between the two parameters is observed. Apart from experimental errors in
the determination of BCF values for these very hydrophobic chemicals, reduced uptake due to the
increasing molecular size may play a role as well. Moreover, the experimental determination of log
Kow for very hydrophobic chemicals is normally also very uncertain due to experimental
difficulties. The reliability of modelled Kow values > 10 is not known. Ideally the results of several
model predictions should be considered. The aquatic BCF of a substance is probably lower than
2000 L/kg if the calculated log Kow is higher than 10. Given that none of the models have
experimental information in this range, more than one model should be used to estimate the Kow
value and the results evaluated by expert judgement.
OCTANOL SOLUBILITY
Octanol is often used as a surrogate for fish lipids. With a low solubility in octanol, the log Kow and
hence the BCF can be either high or low, depending on the water solubility of the substance.
Therefore, the solubility in n-octanol is not a parameter that is directly related to the BCF value.
However, if the solubility of a substance in octanol is so low that the maximum concentration levels
that can be attained in organisms do not reach levels sufficient to elicit any toxic effects, it can be
reasoned that such accumulation would not be of concern. The concentration of a substance at
which the occurrence of toxic effects normally can be excluded is 0.002 mmol/l in n-octanol. This
indicative trigger value may however not apply to chemicals with specific toxicity (specific mode of
action). Furthermore, octanol solubility is only an indicator for substances accumulating in fatty
tissues. Finally, information on octanol solubility should in particular be accompanied and
complemented by information on mammalian toxicity or toxicokinetics to confirm the absence of
uptake and/or chronic toxicity.
IN VITRO DATA ON AQUATIC BIOACCUMULATION
In vitro methods such as fish liver S9 and primary hepatocyte assays provide information on
metabolism and hence biotransformation in the organism. Because metabolism is considered to be
the dominant mechanism of elimination of hydrophobic substances, such in vitro tests have
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