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EC number: 247-952-5
CAS number: 26741-53-7
A significant accumulation in organisms is not expected.
In Article 13 of Regulation (EC) No
1907/2006, it is laid down that information on intrinsic properties of
substances may be generated by means other than tests, provided that the
conditions set out in Annex XI (of the same Regulation) are met.
Furthermore, according to Article 25 of the same Regulation testing on
vertebrate animals shall be undertaken only as a last resort.
According to Annex XI of Regulation
(EC) No 1907/2006 (Q)SAR results can be used if (1) the scientific
validity of the (Q)SAR model has been established, (2) the substance
falls within the applicability domain of the (Q)SAR model, (3) the
results are adequate for the purpose of classification and labeling
and/or risk assessment and (4) adequate and reliable documentation of
the applied method is provided.
For the assessment of the test
substance (Q)SAR results were used for aquatic bioaccumulation.
The criteria listed in Annex XI of
Regulation (EC) No 1907/2006 are considered to be adequately fulfilled
and therefore the endpoint(s) sufficiently covered and suitable for risk
Therefore, and for reasons of animal
welfare, further experimental studies on aquatic bioaccumulation are not
Experimental data on the
bioaccumulation behavior of the test substance are not available.
However, the bioaccumulation potential of the test item is evaluated in
a weight of evidence:
A low potential of bioaccumulation
can be assumed since the calculated logKow of the test item is 10.9 and
the molecular weight is above 500 g/mol (604.694 g/mol). According to
the guidance on information requirements and chemical safety assessment
Chapter R.11 - PBT Assessment - the aquatic BCF of a substance is
probably lower than 2000 L/kg if the calculated log Kow is higher than
10. Furthermore, the maximum diameter of the molecule was calculated
using CATALOGIC v5.11.19. It resulted in an average maximum diameter of
2.02 nm. According to the guidance on information requirements and
chemical safety assessment Chapter R.11 another parameter that directly
reflects the molecular size of a substance is the average maximum
diameter (Dmaxaver). Very bulky molecules will less easily pass the cell
membranes. This results in a reduced BCF of the substance. From a
diverse set of chemicals it appeared that for compounds with a Dmaxaver
larger than 1.7 nm the BCF value was less than 5000 L/kg. It can be
assumed combining the high logKow, the maximum diameter of above 1.7 nm
and the high molecular size of the test item that the test item will not
easily pass the cell membranes, the uptake is reduced and
bioaccumulation will not occur.
These findings are supported using
four scientifically acceptable calculation models:
(1) Catalogic v5.11.19, BCF
base-line model v02.09
(2) US EPA EPISuite v4.11, BCFBAF
(3) US EPA T.E.S.T. v4.2.1
(4) Vega v1.1.3 including CAESAR
v2.1.14, Meylan v1.0.3 and Read-across/KNN v1.1.0
In regards to the reliability of the
QSAR predictions the results from the models included in the Vega model
were not taken into account for the general prediction because the
substance was not within the applicability domain of all Vega models.
The domain of the BCF base-line
model implemented in Catalogic is divided in three sub-domains. (1) The
parameter domain which compares the logKow, water solubility and
molecular size of the substance to the specific ranges of the training
set, (2) the structural fragment domain which compares the atom-centered
fragments of the substance to the ones from the training set and (3) the
mechanistic domain which evaluates the general uptake mechanism of the
compound as only such chemicals which are taken up by passive diffusion
can be predicted. The current substance was within the parameter and the
mechanistic domain of the model. In regards to the structural domain,
48.39 % of the fragments of the substance could be found in correctly
predicted training chemicals. 25.81% of the fragments were not present
in the training chemicals and 25.81% of the fragments were found in
non-correctly predicted training chemicals. Principally, the substance
is not completely within the domain of the model as not all
atom-centered fragments could be found in correctly predicted training
chemicals, however, the result is regarded as reliable and adequate for
the use in a weight of evidence approach and support the overall
conclusion. The predicted BCF value was determined to be 7.76 L/kg.
Metabolism, size and to a minor extent water solubility were the most
important mitigating factors decreasing the BCF value.
The US EPA’s EPISuite includes a
regression-based BCF prediction and a prediction taking the
biotransformation rate into account. Concerning the regression based
prediction the compound was within the molecular weight and logKow
ranges of the model. Furthermore, the maximum number of fragments was
not exceeded. Therefore, the result of the regression-based estimation
is reliable and is regarded as adequate in the weight of evidence
approach. The model predicted the BCF with 164 L/kg.The second model
takes the biotransformation of the compound into account. However, the
test substance was not completely within the applicability domain of the
model. The molecular weight was within the range of the training set,
but exceeded 600 g/mol. Furthermore, the logKow was outside the range of
the training set. Therefore, the estimate may be less accurate. A BCF of
10.36 L/kg (upper trophic level) was estimated. Even though the result
may be less accurate, it supports the overall conclusion in this weight
of evidence approach and is regarded as acceptable.
US EPA’s T.E.S.T. model combines 5
methods in the consensus approach. The model only delivers results if
the substance is in the applicability domain of the respective model. No
results were calculated for the hierarchical clustering, the single
model and the group contribution. The FDA method determined a BCF of
170.74 and the nearest neighbor method resulted in a BCF of 29.98.
Therefore, the consensus method gave a BCF of 71.55. However, the
confidence of the results is low due to the mean absolute error of the
single results. Nevertheless, the results are regarded as reliable in a
weight of evidence approach since the similarity coefficient is close to
the limit values.
In conclusion, in the weight of
evidence approach using all available data, it can be concluded that the
test substance does not significantly accumulate in organisms.
Since it can be expected that the
test substance undergoes a very slow process of hydrolysis and formation
of hydrolysis products cannot be excluded, the bioaccumulation potential
of the hydrolysis products is also considered:
The hydrolysis products would be
2,4-di-tert-butylphenol, pentaerythritol and phosphorous acid that will
be oxidized to phosphoric acid.
2,4-di-tert-butylphenol was already
evaluated by the PBT Working Group in 2008 (ECB Summary Fact Sheet; PBT
List No. 12). The PBT working group concluded that
2,4-di-tert-butylphenol has a moderate bioaccumulation potential with a
BCF of 128 – 436 and does not meet the B criterion.
2,4-di-tert-butylphenol was evaluated in 2015 (PACT). It was also
concluded, that 2,4-di-tert-butylphenol does not fulfil the B criterion.
Both experimental and predicted BCF-values are well below the cut-off
value for bioaccumulation for aquatic organisms as given in Annex XIII
of REACH. This conclusion applies for the parent compound and it is
reasonable to expect that also the transformation products do not meet
the definitive B-criteria.
does not significantly accumulate in organisms.
Pentaerythritol was evaluated in an
OECD SIDS dossier in 1998 (SIDS Initial Assessment Report for 8th SIAM).
It was concluded that the bioaccumulation potential is very low (BCF 0.3
– 2.1; logKow < 0.3). Therefore, pentaerythritol does not meet the
B-criteria and does not significantly accumulate in organisms.
Concerning phosphoric acid an OECD
SIDS dossier exists also (SIDS Initial Assessment Report for SIAM 28,
2009). The bioaccumulation potential seems to be low based on a BCF
value of 3.162 estimated with BCFWIN (from the US EPA EPI Suite).
Furthermore, bioaccumulation is not anticipated for inorganic compounds
that are miscible with water such as phosphoric acid.
in overall conclusion, the potential hydrolysis products do not
significantly accumulate in organisms and the B criterion is not met.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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