Reaction mass of divinylbenzene and ethylstyrene

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Remarks:

Well documented prediction using analogues for validation. BCF values are considered reliable for the four constituents of DVB-55.

Justification for type of information:

QSAR prediction. See Any other information on materials and methods incl. tables and Any other information on results incl. tables for additional information.

Principles of method if other than guideline:

The bioconcentration potential (bioconcentration factor, BCF) of the four major constituents in divinylbenzene (DVB-55) have been assessed using a quantitative structure-activity relationship (QSAR) model (BCF baseline model v.02.06) as described by Dimitrov et al (2005) and implemented in OASIS CATALOGIC v 5.11.12.

GLP compliance:

no

Remarks:

not applicable

Type:

BCF

Value:

219 L/kg

Basis:

other: whole fish steady state

Calculation basis:

steady state

Remarks on result:

other: 1,4-DVB

Type:

BCF

Value:

263 L/kg

Basis:

other: whole fish steady state

Calculation basis:

steady state

Remarks on result:

other: 1,3-DVB

Type:

BCF

Value:

302 L/kg

Basis:

other: whole fish

Calculation basis:

steady state

Remarks on result:

other: 1,4-EVB

Type:

BCF

Value:

263 L/kg

Basis:

other: whole fish

Calculation basis:

steady state

Remarks on result:

other: 1,3-DVB

 3.1          Applicability domain (OECD principle 3)

a.     Domains:

                                                             i.     Descriptor domain    

1.     Predicted Log K_ow: -4.05 <log K_ow< 16.07: in domain

2.     Molecular weight (MW):16.04 < MW < 1131.21: in domain

3.     Predicted Water solubility (C_sat): 0<C_sat<1000000 mg/l: in domain (WATERNT v 1.01 – U.S. EPA)

                                                           ii.     Structural fragment domain: Structural domain is represented by the list of atom-centred fragments (accounting for the first neighbours) extracted fromtraining set chemicals which are correctly predicted. A correct prediction was assumed for those chemicals for which the residuals between predicted and observed values were less than or equal to 0.75 log units.

For the unknown assessed, the agreement of atom-centred fragments with the training data is

Table 2: results on Structure domain

Constituent		Coverage of structural domain
1,4-DVB		20%
1,3-DVB		100%
1,4-EVB		30
1,3-EVB		100%

Note: Although the software noted that the 1,4-DVB and 1,4-EVB are only 20% to 30% in the structural domainas defined by first neighbour atom centred fragments, these two constituents are considered to be in the structural domain because their meta-isomers are 100% in the structural domain.

 

                                                         iii.     Mechanistic domain: The model prediction is based on the assumption of a maximal uptake through passive diffusion and mitigating factors in the uptake (size, dissociation) or the elimination (metabolism). The four constituents are all within the mechanistic domain of the model.

In order to verify the relevance of the model assumption for the unknowns, structural analogues were selected from the training set and processed in parallel (see 3.3.b).

                                                         iv.     Metabolic domain, if relevant: Covered by the structural domain.

b.     Structural analogues:

Structural analogues have been identified by searches within the training data for relevant substructures present in the unknown. As relevant substructure for the search the vinyl- and the benzene structure were used. Some hits were removed based on expert judgement , e.g. due to high degree of halogenations or the presence of fused rings.

Table 3: Structural analogues to the unknown as identified in the training set. (examples)

Identification		Smiles
A1		CC(=C)c1ccccc1
A2		CCc1cccc(C=C)c1
A3		C=Cc1cccc(C=C)c1
A4		CC(=C)c1ccc(Cl)cc1
A5		C=C(Br)c1ccccc1
A6		BrC=Cc1ccccc1
A7		CC(=C)c1ccc(O)cc1
A8		CC(C)(CC(=C)c1ccccc1)c1ccccc1

Note: A2 (1,3-EVB) and A3 (1,3-DVB) are in the training set with experimental data.

 

c.      Considerations on structural analogues:

Results for structural analogues are presented in table 4a/b and discussed in the following.

Table 4a: Experimental and predicted Results for structural analogues.

		Log(KOW)		Log BCFmax		Log BCF^Exp		Log BCF^calccorrected		Δ Log BCF		Structure Domain
A1		3.44		2.58		1.80		2.19		-0.39		100% in domain
A2		3.93		2.94		2.57		2.48		0.09		100% in domain
A3		3.80		2.84		2.55		2.42		0.13		100% in domain
A4		4.09		3.05		2.84		2.77		0.07		100% in domain
A5		3.29		2.47		2.00		2.14		-0.14		100% in domain
A6		3.15		2.37		2.10		1.65		0.45		100% in domain
A7		2.96		2.23		1.30		0.99		0.31		100% in domain
A8		6.51		4.50		3.50		3.65		-0.15		100% in domain

 

The predictions for eight structural analogues are within the range defined by the developer for acceptable prediction with -075 <Δ LogBCF <0.75 whereΔ LogBCF = Log BCF^exp– Log BCF^calc. As a matter of fact,A2 (1,3-EVB) and A3 (1,3-DVB) are in the training set with experimental data, and theΔ LogBCF for these two constituents are 0.09 and 0.13.

 

 

Table 4b: Mitigating factors applied by the system in the BCF prediction for structural analogues.

		Acids		Metabolism		Phenols		Size		Water solubility
A1		0.00		0.30		0.00		0.08		0.0135
A2		0.00		0.34		0.00		0.12		0.0065
A3		0.00		0.30		0.00		0.11		0.0075
A4		0.00		0.15		0.00		0.12		0.0034
A5		0.00		0.24		0.00		0.08		0.0153
A6		0.00		0.60		0.00		0.10		0.0460
A7		0.00		1.13		0.00		0.07		0.1990
A8		0.00		0.61		0.00		0.24		0.0003

 

The major mitigating factor lowering the BCF^calc from BCF_max determined by passive diffusion is metabolism followed by size (see Table 4b). The metabolic reaction considered for these analogues are either the oxidation of the vinyl group to an epoxide or the oxidation of the alkyl group to an alcohol. The epoxides and alcohols are subject to further oxidation. Epoxidation on the aromatic ring is also a relevant metabolic pathway. These metabolic reactions are all relevant for the four constituents in DVB-55. Following this assessment the calculated BCF for the four constituents appear to be sufficiently supported.

Validity criteria fulfilled:

yes

Conclusions:

The predicted BCF for the constituents in the unknown indicate a low potential for bioconcentration due to metabolism in the fish. Based on this finding the uncertainty in the prediction reflected in the overall range (112–437) for the BCF values of the four constituents is acceptable and for risk assessment purposes the upper value of the range can be used in a conservative approach. The constituents of DVB-55 are not bioaccumulative in fish (not B).

Executive summary:

The bioconcentration potential (bioconcentration factor, BCF) of the four major constituents in divinylbenzene (DVB-55) have been assessed using a quantitative structure-activity relationship (QSAR) model (BCF baseline model v.02.06) as described by Dimitrov et al (2005) and implemented in OASIS CATALOGIC v 5.11.12. The model estimates steady state whole fish BCF based on a maximum BCF and mitigating factors that reduce the BCF. The four major constituents in DVB-55 are 1,4-divinylbenzene (1,4-DVB), 1,3-divinylbenzene (1,3-DVB), 1,4-ethylvinylbenzene (1,4-EVB), and 1,3-ethylvinylbenzene (1,3-EVB). Structural analogues identified from the training set have been processed parallel to the unknowns. The unknowns are within the parametric domain of the model and within the structural domain as defined by first neighbour atom centred fragments. To assess the relevance of the metabolism as mitigating factor for the unknowns, a comparison of the metabolic reactions proposed for the analogues and the unknowns is made. The metabolic reaction considered for the analogues are either the oxidation of the vinyl group to an epoxide or the oxidation of the alkyl group to an alcohol. The epoxides and alcohols are subject to further oxidation. Epoxidation on the aromatic ring is also a relevant metabolic pathway. These metabolic reactions are all considered relevant for the four constituents in DVB-55 and the predicted corrected BCF values are considered reliable. The following BCF values are calculated for the four constituents of DVB-55:

 

Constituent	CAS Number	SMILES	log BCF^calc	BCF[(mg/kg w.w.)/(mg/L)]
1,4-DVB	1321-74-0	C=Cc1ccc(C=C)cc1	2.34 ± 0.29	219 (112–427)
1,3-DVB	1321-74-0	C=Cc1cccc(C=C)c1	2.42 ± 0.29	263 (135–513)
1,4-EVB	28016-30-1	CCc1ccc(C=C)cc1	2.42 ± 0.16	302 (209–437)
1,3-EVB	28016-30-1	CCc1cccc(C=C)c1	2.48 ± 0.16	263 (182–380)

 

These predictions fall within the range of accurate predictions as defined by the developer of the model. Based on a decision rule derived by the developer of the QSAR model, constituents inDVB-55 are not bioaccumulative with high confidence. The estimated BCF values are in within 0.09 and 0.13 log unit compared experimental values for 1,3-DVB and 1,3-EVB. The QSAR estimation shows that the four constituents in DVB-55 have a low bioaccumulation potential which is consistent with experimental data.

Reference 2

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP guideline study, translated from Japanese

Qualifier:

according to guideline

Guideline:

OECD Guideline 305 C (Bioaccumulation: Test for the Degree of Bioconcentration in Fish)

Deviations:

no

Principles of method if other than guideline:

MITI (I) method (1974)

GLP compliance:

yes

Radiolabelling:

no

Details on sampling:

No data

Vehicle:

yes

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

Vehicle/Solvent and Concentrations: HCO-40 were used as solvents in the tests. The concentration of HCO-40 in stock solution was 200 mg/L.
Stock Solutions Preparations and Stability: The test substance and HCO-40 were dissolved in dilution water. The concentration of test substance and HCO-40 were 10 mg/L and 200 mg/L, respectively.

Test organisms (species):

Cyprinus carpio

Details on test organisms:

Test Organisms:
a) Size (length and weight): 9.3 cm (avg.) in length; 22.1 g (avg.) in weight
b) Age: Not described
c) Any pre-treatment: Acclimated for over 7 days before testing, any fishes showing a disease were not used for testing.
d) Supplier/Source: Commercial fish firm, SUGISHIMA YOUGYOJO(KUMAMOTO, JAPAN)

Route of exposure:

aqueous

Test type:

flow-through

Water / sediment media type:

natural water: freshwater

Total exposure / uptake duration:

42 d

Hardness:

No data

Test temperature:

23-27°C

pH:

No data

Dissolved oxygen:

5.6-7.0 mg/L

TOC:

No data

Salinity:

No data

Details on test conditions:

Test Conditions:
a) Type of Test: flow-through
b) Flow-through Rate: 1155 L/day
c) Dilution Water Source: well water
d) Water Temperature: 23 - 27°C
e) DO: 5.6-7.0 mg/L
c) Exposure Vessel Type: 100L Glass Beaker
f) Nominal Concentrations (as µg/L): 2.5 and 25
g) Vehicle/Solvent and Concentrations: HCO-40 were used as solvents in the tests. The concentration of HCO-40 in stock solution was 200 mg/L.
h) Stock Solutions Preparations and Stability: The test substance and HCO-40 were dissolved in dilution water. The concentration of test substance and HCO-40 were 10 mg/L and 200 mg/L, respectively.
i) Number of Replicates: 2
j) Fish per Replicates: 12
k) Feeding: 2% of fish weight in assorted feed daily

Nominal and measured concentrations:

Nominal Concentrations (as µg/L): 2.5 and 25

Reference substance (positive control):

not specified

Key result

Temp.:

23 - 27 °C

Type:

BCF

Value:

> 206 - < 433 dimensionless

Basis:

not specified

Metabolites:

No data

Details on results:

Bioconcentration factor: 229-433 (2.5 µg/L), 206-415 (25 µg/L)

Validity criteria fulfilled:

yes

Conclusions:

Based on the available transalation of the study, the bioconcentration factor addresses all components of the reaction mass. The BCF is: 229-433 (2.5 µg/L), 206-415 (25 µg/L).

Executive summary:

The study was conducted according to OECD 305C (1981). The bioconcentration factor in Cyprinus carpio was 229-433 and 206-415 at 2.5 and 25 µg/L, respectively.

Description of key information

A GLP MITI study assessing the bioaccumulation in Cyprinus carpio and a well-documented Catabol QSAR prediction of the BCF for all isomers using analogues for validation is available.

Key value for chemical safety assessment

BCF (aquatic species):

320 L/kg ww

Additional information

The bioconcentration factor in Cyprinus carpio was 229-433 and 206-415 at 2.5 and 25 µg/L, respectively. The mid-point of these measured values (320 L/kg wet wt.) is used to represent BCF of the substance components in the chemical safety assessment.

 

The bioconcentration potential (bioconcentration factor, BCF) of the four major constituents in divinylbenzene (DVB-55) have been assessed using a quantitative structure-activity relationship (QSAR) model (BCF baseline model v.02.06) as described by Dimitrov et al (2005) and implemented in OASIS CATALOGIC v 5.11.12. Constituents of DVB-55 are not bioaccumulative, as BCF values range from 219 and 302 L/kg.

 

The QSAR predictions are within the same range, as measured in Carp, which is chosen as a key value for the chemical safety assessment.