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EC number: 229-722-6
CAS number: 6683-19-8
Not considered as bioaccumulative, BCF < 2000
Concerning to the bioaccumulative
potential reliable experimental data are not available.
The BCF was predicted with the BCF
base-line model v.02.09 which is implemented in Catalogic v5.11.19.
However, the compound is not within the applicability domain of the
model. Its calculated logKow of 19.6 and molecular weight of 1180 Da are
outside of the respective ranges of the training set. Only the
calculated water solubility is within the training set range. The
substance does not meet the general properties requirements. In regard
to the structural fragment domain, 87.69% of the fragments could be
found in correctly predicted training chemicals, only 12.31% are not
present in the training chemicals. The substance is within the
mechanistic domain of the model, i.e. the expected uptake mechanism is
passive diffusion only. In summary, the substance is not within the
applicability domain and the prediction falls in the extrapolation
space. Although its reliability is low it is still acceptable in a
weight of evidence approach. The logKow of CAS 6683-19-8 is 19.6.
According to ECHA’s Guidance on Information Requirements and Chemical
Safety Assessment, Chapter R.11: PBT/vPvB assessment, paragraph
R.126.96.36.199, the aquatic BCF of a substance is probably lower than 2000
if the calculated logKow is higher than 10. Furthermore, the average
maximum diameter of 25.6 Å is also indicative of a limited
bioaccumulative potential. According to the above-mentioned guidance
document the BCF for compounds with an average maximum diameter larger
than 17 Å is probably less than 5000. Additionally, the molecular weight
of 1180 g/mol is also an indicator that the BCF of the compound is lower
than 2000. Taking these data into account CAS 6683-19-5 cannot be
regarded as bioaccumulative. Its BCF value is assumed to be clearly
This result is supported by the findings
of available toxicity studies with mammals, which clearly demonstrated
absence of systemic toxicity. The substance has not bioaccumulation
potential and rapid excretion via the feces is expected (see also
endpoint summary IUCLID section 7.1 Toxicokinetics, metabolism and
The same conclusion was derived by the
ECB PBT working group assessment. CAS 6683-19-8 is not bioaccumulative
and not very bioaccumulative. Seethe
attached official PBT-Assessment No. 77 for the test substance by the
European Commission Joint Research Centre (IUCLID section 13).
Furthermore, the bioaccumulation
assessment with the same conclusion on the bioaccumulation potential is
included in the examples in the "Guidance on information requirements
and chemical safety assessment" (version 3.0, June 2017), Chapter R.11:
PBT Assessment, Example R. 11-3.
Assessment of the bioaccumulation
potential of the degradation products (identified with QSAR
(Catalogic v5.11.19 BOD 28 days MITI (OECD 301C) v09.13 and identified
in the official PBT-Assessment No. 77 for the test substance by the
European Commission Joint Research Centre):
Metilox acid (CAS
Metilox acid was
identified as the main metabolite in CATALOGIC 301C v.09.13.
Furthermore, the assessment of the ECB PBT working group also identified
metilox acid as one of the main metabolites according to the data on a
potential of metilox acid was assessed by the ECB PBT working group.
Experimental BCF data on a close structural analogue
(3-(3-tert-butyl-4-hydroxy-5-methyl-phenyl)-propionic acid revealed a
BCF of <4.3. Another study performed by the Gakushuin University (1988)
derived a BCF of 94-108 at high exposure concentration and 373-532 at
the lower exposure concentration on metilox acid itself. Details can be
found in the attached assessment of the ECB PBT working group.
In addition to the
experimental data, a BCF was predicted with the BCF base-line model
v.02.09. The corrected BCF was 13.5 L/kg. The compound was within the
general parameter domain (logKow, molecular weight and water solubility)
and the mechanistic domain. Concerning the structural fragment domain
86.67% of the compound’s fragments could be found in correctly predicted
training chemicals. Only 13.33% of its fragments were unknown to the
model. Therefore, the substance must be regarded as outside of the
applicability domain. However, the model is regarded as reliable as the
result clearly fits the experimental data.
In conclusion, all
available data indicate a low bioaccumulative potential. Metilox acid
does therefore not fulfill the B/vB criteria and thus not the PBT/vPvB
was identified by the ECB PBT working group as major metabolite of CAS
6683-19-8. It was also identified by Catalogic 301C, however the
quantity was below 0.1% mol/mol parent as it was predicted to be subject
of further degradation. The
logKow was predicted with Catalogic 301C was -1.77
and does not fulfil the screening criteria for bioaccumulative or very
to Annex XIII of Regulation (EC) No 1907/2006.
According to the
experimental data the compound is not bioaccumulative with an
experimental BCF range of only 0.3-2.1 (cf. assessment of ECB PBT
working group and OECD SIDS in IUCLI chapter 13.). Therefore,
the bioaccumulation potential of pentaerythritol is very low. As
a consequence, pentaerythritol is not further assessed and not
included in the table below.
metabolites identified with CATALOGIC 301C
metabolites and information on BOD, BCF, logKow and DiamMax average can
be found in the table. In general, the identified metabolites consist of
pentaerythritol as a core and 2 to 4 metilox acid groups (in some cases
slightly modified at the tert butyl group or the propane chain) attached
to it. In dependence of the amount of metilox groups the logKow values
range from 7.02 to 18.06.In
the absence of experimental data on the degradability and
bioaccumulation the CATALOGIC 301C v.09.13 and BCF base-line model
v.02.09 were used to predict the BOD and the BCF.
the bioaccumulative potential the BCF of the metabolites was predicted
as <10 in the BCF base-line model v.02.09. Furthermore, the larger
metabolites exhibit very high logKow values >10 which is indicative of a
BCF value <2000. The DiamMax average was also taken into account. It
ranges from 21.4 to 25.1Å which is clearly indicative of a hindered
uptake. According to ECHA’s Guidance on Information Requirements and
Chemical Safety Assessment, Chapter R.11: PBT/vPvB assessment, paragraph
R.188.8.131.52 substances with a Dmax-aver larger than 17Å have BCF values
<5000. The respective metabolites clearly exceed this threshold. In
regard to the applicability domain, the metabolites are within the
mechanistic domain, i.e. they are taken up by passive diffusion only.
The larger metabolites are outside of the parameter ranges due to their
high logKow values and molecular weights. The smaller ones are within
the parameter ranges. Concerning the structural domain, the compounds
share 86 to 89% of correctly predicted fragments of the training set.
Consequently, only 11 to 14% of the fragments were unknown. Despite the
overall outcome that the compounds are outside of the applicability
domain, the predictions of the BCF are regarded as reliable and suitable
in a weight of evidence approach together with data on logKow and
all lines of evidence into account, none of the metabolites can be
regarded as bioaccumulative.
and metabolites at a quantity ≥0.1% (mol/mol parent) and a logKow ≥4.
Quantity [% mol/mol parent](1)
BOD Catalogic [%](1)
DiamMax Average [Å](2)
Parent (CAS 6683-19-8)
Metabolite No 1 (Metilox acid; CAS 20170-32-5)
Metabolite No 2 (triester)
Metabolite No 3
Metabolite No 4 (diester)
Metabolite No 5
Metabolite No 6
Metabolite No 7
Metabolite No 8
Metabolite No 9
v5.11.19, CATALOGIC 301C v.09.13
v5.11.19, BCF base-line model v.02.09
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 substance and
its degradation products (Q)SAR results were used for determination of
the bioaccumulation potential. 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
bioaccumulation are not provided.
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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