Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 947-899-4
CAS number: -
The potential for bioaccumulation of fatty acids C18-C22 (even
numbered), tetraesters with pentaerythritol is assumed to be low based
on available data.
Experimental data on bioaccumulation of fatty acids C18-C22 (even
numbered), tetraesters with pentaerythritol is not available. The
evaluation of the bioaccumulation potential of the substance is
therefore based on a Weight of Evidence (WoE), combining all available
related data. This is in accordance to the REACh Regulation (EC) No
1907/2006, Annex XI General rules for adaptation of the standard testing
regime set out in Annexes VII to X, 1.2, to cover the data requirements
of Regulation (EC) No. 1907/2007 Annex IX and X (Guidance on information
requirements and chemical safety assessment Chapter R.7c: Endpoint
specific guidance (ECHA, 2017).
Due to the high potential for adsorption, the substance can be
effectively removed in conventional sewage treatment plants (STPs) by
sorption to biomass. The low water solubility (< 0.518 mg/L at 20 °C,
OECD 105) and high estimated log Kow (> 10, QSAR, VEGA 1.1.3) indicate
that the substance is highly lipophilic. If released into the aquatic
environment, the substance undergoes extensive sorption to organic
matter. Thus, the bioavailability in the water column is highly reduced.
The relevant route of uptake of the substance in aquatic organisms is
expected to be predominantly by ingestion of particle bound substance.
If the substance is taken up by ingestion, absorption is expected
to be low based on the molecular weight, size and structural complexity
of the substance. Large and complex structures like fatty acids C18-C22
(even numbered), tetraesters with pentaerythritol assume a high degree
of conformational flexibility. Dimitrov et al. (2002) revealed a
tendency of decreasing log BCF with an increase in conformational
flexibility of molecules. They suggest that this effect is related to
the enhancement of the entropy factor on membrane permeability of
chemicals. This concludes a high probability that the substance may
encounter the membrane in a conformation which does not enable the
substance to permeate. Furthermore, the substance has a high molecular
weight of 1370.31 – 1426.42 g/mol. Thus, it is unlikely that it is
readily absorbed, due to the steric hindrance of crossing biological
membranes. Following the ‘rule of 5’ (Lipinski et al., 2001), developed
to identify drug candidates with poor oral absorption based on criteria
regarding partitioning (log Kow > 5) and molecular weight (> 500 g/mol),
the substance is considered to be poorly absorbed after oral uptake
(Hsieh & Perkins, 1976).
This interaction between lipophilicity, bioavailability and
membrane permeability is considered to be the main reasons why the
relationship between the bioaccumulation potential of a substance and
its hydrophobicity is commonly described by a relatively steep Gaussian
curve with the bioaccumulation peak approximately at log Kow of 6-7
(e.g., see Dimitrov et al., 2002; Nendza & Müller, 2007; Arnot and Gobas
2003). Substances with log Kow values above 10, which has been
calculated for the test substance, are considered to have a low
bioaccumulation potential (e.g. Nendza & Müller, 2007; 2010).
Furthermore, for those substances with a log Kow value > 10 it is
unlikely that they reach the pass level of being bioaccumulative
according to OECD criteria for the PBT assessment (BCF > 2000; ECHA,
2017). In addition, in a 90-day oral feeding toxicity study with an
analogue substance no treatment-related and no toxicologically relevant
effects for mammals were observed in the study.
This assumption is supported by QSAR calculations using BCFBAF
v3.01 performed for the main components of fatty acids C18-C22 (even
numbered), tetraesters with pentaerythritol. BCF/BAF values of 3.16 L/kg
(regression based) and 0.89 L/kg (Arnot-Gobas estimate, including
biotransformation, upper trophic) were obtained, respectively. Even
though fatty acids C18-C22 (even numbered), tetraesters with
pentaerythritol is outside the applicability domain of the model, the
estimation can be used as supporting indication of low bioaccumulation
potential. The model training set is only consisting of substances with
log Kow values of -1.37 – 11.26 (regression based) and 0.31 - 8.70
(Arnot-Gobas). But it supports the tendency that substances with high
log Kow values (> 10) have a lower potential for bioconcentration and
accumulation as summarized in the ECHA Guidance R.11 and they are not
expected to meet the B/vB criterion (ECHA, 2017).
Based on the physico/chemical properties such as low water
solubility and high potential for adsorption a reduced availability in
water is expected. The high molecular weight of the substance
significantly reduces the absorption due to sterical hindrance to cross
biological membranes. In addition, no toxicologically relevant effects
in mammals were observed in a 90-day oral feeding toxicity study. It can
be concluded that the bioaccumulation potential of fatty acids C18-C22
(even numbered), tetraesters with pentaerythritol is negligible. BCF/BAF
values estimated by QSAR (BCFBAF v3.01) also support this assumption
(BCF values all well below 2000 L/kg).
Taking all these information into account, it can be concluded
that bioaccumulation of fatty acids C18-C22 (even numbered), tetraesters
with pentaerythritol is unlikely to occur.
Dimitrov et al. (2002): Predicting bioconcentration factors of
highly hydrophobic chemicals. Effects of molecular size. Pure Appl.
Chem., Vol. 74(10). 1823-1830
ECHA (2017): Guidance on information requirements and chemical
safety assessment. Chapter R.11: PBT Assessment. European Chemicals
Hsieh, A. and Perkins, E. G. (1976). Nutrition and Metabolic
Studies of Methyl Ester of Dimer Fatty Acids in the Rat. Lipids,
Lipinski et al. (2001). Experimental and computational approaches
to estimate solubility and permeability in drug discovery and
development settings. Adv. Drug Del. Rev. 46: 3-26.
Nendza, M. & Müller, M. (2010). Screening for low bioaccumulation
(1): Lipinski's 'Rule of 5' and molecular size. SAR and QSAR in
Environmental Research, 21(5-6), 495-512. Report date: 2010-04-26.
Nendza, M. and Müller, M. (2007).Literature Study: Effects of
Molecular Size and Lipid Solubility on Bioaccumulation Potential.
Testing laboratory: Fraunhofer Institute for Molecular Biology and
Applied Ecology, Schmallenberg, Germany and Analytisches Laboratorium
für Umweltuntersuchungen und Auftragsforschung, Luhnstedt, Germany.
Report no.: FKZ 360 01 043. Owner company: Umweltbundesamt, Dessau,
Germany. Report date: 2007-02-15.
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.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again