Isooctyl acrylate

Bioaccumulation: aquatic / sediment

Administrative data

Endpoint:

bioaccumulation: aquatic / sediment

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

June 2, 2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Structurally, the test substance contains an acrylate ester functionality which is outside of the structural domain which the Catalogic software suite uses to predict log BCF and BCF values. However, the baseline BCF estimation provides a maximal possible BCF based on chemical characteristic and then subtracts the contributions of mitigating factors (size, metabolism, water solubility, acidic character, and phenolic character). Acidic and phenolic characters are not mitigating factors in this class of compound. Water solubility and size are estimated through well doumented methods however metabolism is severely underestimated by use of an epoxidation metabolic pathway rather than the alkyl ester biotically mediated pathway. Therefore, this QSAR may only predict a maximum upper bounds for the log BCF (and BCF) values.

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

other: QSAR simulation report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSARs R.6, May/July 2008.

Deviations:

yes

Remarks:

QPRF guidance is specific to single endpoints of clearly defined chemicals.The test material is UVCB & no direct guidance was available.QPRF was followed for the major components & the observed endpoint is expected to fall within that range estimated.

Principles of method if other than guideline:

Catalogic BCF base-line model v1.04

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Isooctyl acrylate

EC Number:

249-707-8

EC Name:

Isooctyl acrylate

Cas Number:

29590-42-9

Molecular formula:

C11H20O2

IUPAC Name:

2-methylheptyl prop-2-enoate

Details on test material:

29590-42-9
isooctyl acrylate (IOA)
CH2CHC(O)O(CnH2n+1) where n=7,8, or 9

Homolog and isomer compositon:
As a UVCB the exact composition is variable but a typical composition is:
Reaction products of propenoic acid with C7 alcohols (branched): >1.25%
Reaction products of propenoic acid with C8 alcohols (branched): >94.00%
Reaction products of propenoic acid with C9 alcohols (branched): >4.00%

SMILES Notation for test materials for Isooctyl Acrylate:
C7_1S: O=C(C=C)OCCCCC(C)C
C7_2S: O=C(C=C)OCCC(C)C(C)C
C7_3S: O=C(C=C)OC(C)C(C)C(C)(C)
C7_Et:: O=C(C=C)OCC(CC)CCC <2-ethyl secondary branched isoheptyl acrylate>
C8_1S: O=C(C=C)OCCCCCC(C)C
C8_2S: O=C(C=C)OCCCC(C)C(C)C
C8_3S: O=C(C=C)OCC(C)C(C)C(C)C
C8_Et:: O=C(C=C)OCC(CC)CCCC <2-ethyl secondary branched isooctyl acrylate>
C9_1S: O=C(C=C)OCCCCCCC(C)(C)
C9_2S: O=C(C=C)OCCCCC(C)C(C)(C)
C9_3S: O=C(C=C)OCCC(C)C(C)C(C)(C)
C9_4S: O=C(C=C)OC(C)C(C)C(C)C(C)(C)
C9_Et:: O=C(C=C)OCC(CC)CCCCC <2-ethyl secondary branched isononyl acrylate>

Radiolabelling:

no

Sampling and analysis

Details on sampling:

tests performed in silico; not applicable

Test solutions

Vehicle:

no

Details on preparation of test solutions, spiked fish food or sediment:

tests performed in silico; not applicable

Test organisms

Test organisms (species):

other: QSAR simulation.

Details on test organisms:

QSAR based on experimental BCF data from MOE (Japan) and proprietary databases, using Cyprinus carpio and salmonids.

Study design

Test type:

other: QSAR

Test conditions

Hardness:

tests performed in silico; not applicable

Test temperature:

tests performed in silico; not applicable

pH:

tests performed in silico; not applicable

Dissolved oxygen:

tests performed in silico; not applicable

TOC:

tests performed in silico; not applicable

Salinity:

tests performed in silico; not applicable

Details on test conditions:

tests performed in silico; not applicable

Nominal and measured concentrations:

tests performed in silico; not applicable

Reference substance (positive control):

yes

Details on estimation of bioconcentration:

Estimated using the BCF base-line model v.01.04 of the Catalogic software suite.

Results and discussion

Bioaccumulation factor

Type:

other: maximum BCF

Value:

120 - 940

Basis:

other: QSAR; relationships derived from proprietary data from a large collection of public and private databases

Remarks on result:

other: Bioaccumulation values are range of simulated results for several different structures representative of IOA

Details on kinetic parameters:

tests performed in silico; not applicable

Results with reference substance (positive control):

A single structural analog was located in the training set. That is 2-ethylhexyl methacrylate (CAS No. 688-84-6) whose metabolic pathway is properly predicted. This particular reference material yeilded an estimated log BCF value of 1.4641±0.1006 (BCF 29.1, range 23.0940 - 36.7029) compared to the experimental log BCF value of 1.570 (BCF = 37.2).

Details on results:

The UVCB (unknown, variable,complex, or biological) nature of this test substances precludes reporting a single value or range of values for a single substance. Therefore, we have performed simulations on 13 compounds ranging from very simple to the most heavily branched to provide a representative cross section of the range BCFs to be expected for this UVCB substance.
This material is partially outside the structural domain of the Catalogic software suite because the acrylate ester moiety is not represented in the training set. A single analogous substance (2-ethylhexyl methacrylate; CAS No. 688-84-6) is the closest structural analog and was properly predicted.
The value reported represents a range of maximum BCF values which do not properly account for metabolic degradation.

Validity of Model (OECD 5 principles):
1) Defined endpoint: Bioconcentration factor
2) Unambiguous algorithm: The predicted value of the Bioconcentration factor is calculated through the following equation:

log BCF = log (∏Fi∙((Kow^n)/((a∙Kow +1)^2n) + Fw∙Fws)

where where Fi are individual mitigating factors (water solubility, molecular size, metabolism, acid character , and phenolic character), Kow is the calculated octanol-water partition coefficient, Fw is the water content of the organism, and Fws is the water solubility threshold. The factors “a” and “n” are proprietary weighting factors which have values of 2.24(±1.428)E-07 and 0.746 ± 0.04997, respectively. The predicted log BCF (and errors) and BCFs of the test compounds reported here are expected to be overestimated because mitigating factor of metabolism is incomplete and the predicted mechanism too slow.
3) Applicability domain: the software's training set contains an alkyl ester methacrylate and numerous other esters which are structurally related to the test substances. The model predicts ester hydrolysis for methacrylates but does not make the same prediction for acrylate esters. However, it has been shown that hydrolysis of the ester bond is the most probable pathway for acrylate metabolism. Therefore, this QSAR underestimates the contribution of metabolic degradation. This results in an inflation of predicted log BCF values, which are used here to provide an upper limit to the experimental log BCF values.
4) Statistical characterization: The uncertainties of this QSAR prediction are based on the ‘goodness of fit’ of test data. Statistics of the model:
• R² = 0.923
• False negatives = 0.16
• False positive = 0.01
• Specificity = 0.99
• Sensitivity = 0.84
5) Mechanistic interpretation: The base-line modeling concept is based on the assumption of a maximum bioconcentration factor (log BCFmax) with mitigating factors that reduce BCF. The maximum bioconcentration potential was described by the multi-compartment partitioning model for passive diffusion. Mitigating factors are divided into two groups: chemical dependent factors (log Kow, molecular size, ionization, water solubility) and organism dependent factors (metabolism)

Please see attached QMRF and QPRF for justification of model and applicability.

Reported statistics:

BCF values (incorporating errors) ranged from 120 to 940

Any other information on results incl. tables

Substance (# C’s, branching)	Log BCF (error)	BCF (range)
C7, single branched	2.1171 (±0.2608)	130.9483 (71.8290 - 238.7262)
C7, double branched	2.0892 (±0.2823)	122.8005 (64.1062 - 235.2339)
C7, triple branched	2.0804 (±0.3110)	120.3372 (58.8031 - 246.2635)
C7, 2-ethyl branched	2.3547 (±0.2378)	226.3080 (130.8881 - 391.2911)
C8, single branched	2.4112 (±0.2168)	257.7508 (156.4588 - 424.6196)
C8, double branched	2.3906 (±0.2390)	203.9858 (117.6522 - 353.6714)
C8, triple branched	2.3875 (±0.2831)	244.0619 (127.1745 - 468.3818)
C8, 2-ethyl branched	2.6693 (±0.1897)	466.9818 (301.7172 - 722.7698)
C9, single branched	2.7220 (±0.2161)	527.2299 (320.5531 - 867.1615)
C9, double branched	2.7214 (±0.2216)	526.5020 (316.0822 - 877.0008)
C9, triple branched	2.6958 (±0.2413)	496.3637 (287.8724 - 855.8546)
C9, quadruple branched	2.7054 (±0.2957)	507.4579 (256.8621 - 1002.5361)
C9, 2-ethyl branched	2.9726 (±0.1353)	938.8582 (687.5432 - 1282.0353)

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Remarks:

OECD five principles

Conclusions:

By this QSAR implemented through the BCF base-line model_v.01.04 of Catalogic, the upper limit of the bioconcentration factor (BCF) for isooctyl acrylate is predicted to range from 120 to 940.

Executive summary:

Bioconcentration of the UVCB material isooctyl acrylate was estimated utilizing the BCF base-line model v.01.04 of Catalogic and 13 representative structures. Structurally, the test substances are outside the domain of the training set of the software. However, this software is able to reliably predict an upper limit of the BCF through its baseline BCF estimation methodology where a maximum BCF is predicted and then mitigating factors (size, metabolism, water solubility, acid character, and phenolic character) are applied to reduce the value of this number. The metabolism pathway predicted by Catalogic is epoxidation at a low probability, while the known metabolic pathway is a rapid biologically mediated hydrolysis. Therefore the known metabolism will reduce the amount of IOA available for bioconcentration, while the prediction underestimates the effects of metabolism. Through this logic, the predicted BCFs, as estimated in Catabolic, provide an upper boundary to the expected values.  

The upper limit of the bioconcentration factor (BCF) for IOA is predicted to range from 120 to 940. This indicates IOA is not expected to be bioaccumulative according to the accepted EU threshold of BCF = 2000.  

This study is classified acceptable with restrictions as a key study because it predicts an upper boundary of the BCF value using a validated software suite (OASIS Catalogic) and scientifically sound reasoning. It is pertinent to the fate and transport of isooctyl acrylate in the aquatic compartment.