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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Reference
Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
N/A
Reliability:
2 (reliable with restrictions)
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
Justification for type of information:
1. SOFTWARE
EpiSuite v4.11, US EPA, 2012

2. MODEL (incl. version number)
BCFBAF v3.01

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
see attached information ("BCF_QSAR justification.pdf")

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: BCF
- Unambiguous algorithm:
The BCFBAF method classifies a compound as either ionic or non-ionic. Ionic compounds include carboxylic acids, sulfonic acids and salts of sulfonic acids, and charged nitrogen compounds (nitrogen with a +5 valence such as quaternary ammonium compounds). All other compounds are classified as non-ionic.

Training Dataset Included:
466 Non-Ionic Compounds
61 Ionic Compounds (carboxylic acids, sulfonic acids, quats)

Methodology for Non-Ionic was to separate compounds into three divisions by Log Kow value as follows:
Log Kow < 1.0
Log Kow 1.0 to 7.0
Log Kow > 7.0

For Log Kow 1.0 to 7.0 the derived QSAR estimation equation is:

Log BCF = 0.6598 Log Kow - 0.333 + Σ correction factors
(n = 396, r2 = 0.792, Q2 = 0.78, std dev = 0.511, avg dev = 0.395)

The previous BCFWIN equation:
Log BCF = 0.77 Log Kow - 0.70 + Σ correction factors

For Log Kow > 7.0 the derived QSAR estimation equation is:

Log BCF = -0.49 Log Kow + 7.554 + Σ correction factors
(n = 35, r2 = 0.634, Q2 = 0.57, std dev = 0.538, avg dev = 0.396)

For Log Kow < 1.0 the derived QSAR estimation equation is: All compounds with a log Kow of less than 1.0 are assigned an estimated log BCF of 0.50

- Defined domain of applicability:
Currently there is no universally accepted definition of model domain. However, users may wish to consider the possibility that bioconcentration factor estimates are less accurate for compounds outside the MW and logKow ranges of the training set compounds, and/or that have more instances of a given correction factor than the maximum for all training set compounds. It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no fragment coefficient was developed; and that a compound has none of the fragments in the model’s fragment library. In the latter case, predictions are based on molecular weight alone. These points should be taken into consideration when interpreting model results.

Training Set (527 Compounds):

Molecular Weight:
Minimum MW: 68.08 (Furan)
Maximum MW: 991.80 Ionic: (2,7-Naphthalenedisulfonic acid, 4-amino-5-hydroxy-3,6-
bis[[4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt)
Maximum MW: 959.17 Non-Ionic: (Benzene, 1,1 -oxybis[2,3,4,5,6-pentabromo-)
Average MW: 244.00

Log Kow:
Minimum LogKow: -6.50 Ionic: (2,7-Naphthalenedisulfonic acid, 4-amino-5-hydroxy-3,6-bis[[4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt)
Minimum LogKow: -1.37 Non-Ionic: (1,3,5-Triazine-2,4,6-triamine)
Maximum LogKow: 11.26 (Benzenamine, ar-octyl-N-(octylphenyl)-)

- Appropriate measures of goodness-of-fit and robustness and predictivity:
Accuracy of the Training Set:
n=527
r²=0.833
SD=0.502
Average deviation=0.382

Accuracy of the Validation Set:
n=158
r²=0.82
SD=0.59
Average deviation=0.46


5. APPLICABILITY DOMAIN
- Descriptor domain: The components of the substance are within the molecular weight range of the training set compounds, and all fragments are represented in the training set. Thus, it is concluded, that the substance is within the applicability domain.
- Similarity with analogues in the training set: several linear and branched alkanes and alkenes, which are considered to be similar, are present in the training set.

6. ADEQUACY OF THE RESULT
The QSAR prediction is valid and of good reliability. Thus, the result is adequate for chemical safety assessment.
Principles of method if other than guideline:
Estimation of the bioaccumulation of the components by QSAR (EpiSuite v4.11, US EPA, 2012; BCFBAF v3.01)
GLP compliance:
no
Remarks:
not applicable for in silico study
Type:
BCF
Value:
>= 27.8 - <= 1 220 L/kg
Basis:
whole body w.w.
Remarks on result:
other: calculated seperately for all constituents
Type:
BCF
Value:
326.5 L/kg
Basis:
whole body w.w.
Remarks on result:
other: weighted mean

for details on result see attached file

Conclusions:
The estimation of the bioaccumulation of the components by QSAR (EpiSuite v4.11, US EPA, 2012; BCFBAF v3.01) resulted in values ranging from 27.8 to 1220 L/kg for the single components and a weighted mean of 326.5 L/kg.
The composition of Oxooil LS9 as provided in Iuclid section 1.2 has been taken into consideration. Therefore, this prediction is considered adequate and relevant to adapt the standard information requirement of REACh Regulation Annex IX, Section 9.3.2 

Description of key information

The estimation of the bioaccumulation of the constituents of the substance by QSAR (EpiSuite v4.11, US EPA, 2012; BCFBAF v3.01) resulted in values ranging from 27.8 to 1220 L/kg for the single constituents and a weighted mean of 326.5 L/kg.

Key value for chemical safety assessment

BCF (aquatic species):
326.5 L/kg ww

Additional information

The bioaccumulation potential of Oxooil LS9 was esimated by QSAR (EpiSuite v4.11, US EPA, 2012; BCFBAF v3.01). This method addressing all single constituents of the UVCB substance was considered more suitable than experimental testing, since the physicochemical properties (i.e. water solubility, log Kow, vapour pressure) are spread over a wide range and therefore, make experimental testing and analytics very difficult.

The estimation of the bioaccumulation of the constituents of Oxoil LS9 by QSAR (EpiSuite v4.11, US EPA, 2012; BCFBAF v3.01) resulted in values ranging from 27.8 to 1220 L/kg for the single constituents and a weighted mean of 326.5 L/kg. The highest BCF value of 1220 L/kg was obtained for n-octane (typical concentration 7% in substance) – all other constituents have BCF values lower than 300 L/kg. Other relevant distribution data on n-octane should be taken into consideration as well, especially the short half-life in air of 1.3 days as well as the high Henry’s Law constant of 3.25E+005 Pa-m³/mole (based on measured date taken from the EpiSuite database) resulting in a half-life in river water of ca 1.1 h, and a half-life in lake of 101.5 d.

Although based on the results, there is some potential for bioaccumulation, the physico-chemical and environmental fate properties indicate, that there would be limited environmental exposure because of volatility, photodegradation and limited solubility.