Registration Dossier

Administrative data

Endpoint:
bioaccumulation: aquatic / sediment
Type of information:
(Q)SAR
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented QSAR calculation using analogues for validation. QSAR-prediction is within the parametric domain of the model; however, the reaction mass constituent is only within 59.1% of structural domain of QSAR prediction model.
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Principles of method if other than guideline:
Estimation of the bioconcentration factor (BCF) of Paraformaldehyde, oligomeric reaction products with 4-tert-butylphenol, m-phenylenebis(methylamine) using CATABOL BCF baseline model v. 02.05
GLP compliance:
no
Remarks:
Not applicable for QSAR

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
1.5 Structure codes:
a. SMILES: The test material was assessed using the following two SMILES:
Constituent 1) m-phenylenebis(methylamine) (MXDA) 30%: c1(CN)cc(CN)ccc1
Constituent 2) 4-tert-butylphenol (PTBP) 40%: C(C)(C)(C)c1ccc(O)cc1
Constituent 3) Mannich base 20%: C(C)(C)(C)c1cc(CNCc2cc(CN)ccc2)c(O)cc1
b. InChI: Not available
c. Other structural representation: No other structural representation required.
d. Stereochemical features: No stereochemistry considered.

Results and discussion

Bioaccumulation factoropen allclose all
Type:
BCF
Value:
2.4 dimensionless
Basis:
whole body w.w.
Calculation basis:
other: QSAR
Remarks on result:
other: Constituent 1) m-phenylenebis(methylamine) (MXDA) 30%: c1(CN)cc(CN)ccc1
Remarks:
Conc.in environment / dose:Not applicable
Type:
BCF
Value:
2.67
Basis:
whole body w.w.
Calculation basis:
steady state
Remarks on result:
other: Constituent 1) m-phenylenebis(methylamine) (MXDA) experimental value (nihs)
Remarks:
Conc.in environment / dose:not applicable
Type:
BCF
Value:
14
Basis:
whole body w.w.
Calculation basis:
other: QSAR estimate
Remarks on result:
other: Constituent 2) 4-tert-butylphenol (PTBP)
Remarks:
Conc.in environment / dose:not applicable
Type:
BCF
Value:
68
Basis:
whole body w.w.
Calculation basis:
steady state
Remarks on result:
other: Constituent 2) 4-tert-butylphenol (PTBP) experimental value (nihs)
Remarks:
Conc.in environment / dose:not applicable
Type:
BCF
Value:
3.6
Basis:
whole body w.w.
Calculation basis:
other: QSAR estimate
Remarks on result:
other: Constituent 3) Mannich base
Remarks:
Conc.in environment / dose:not applicable

Any other information on results incl. tables

a.     Predicted value (model result):        

Table 1a: Log BCF and BCF prediction for unknowns.

 

Molecule

log BCFcalc

BCF

BCF experimental

Constituent 1) m-phenylenebis(methylamine) (MXDA)

0.38 (0.27–0.5)

2.42 (1.12–3.72)

2.7

Constituent 2) 4-tert-butylphenol (PTBP)

1.15 (0.9–1.4)

1.15 (-0.64–2.94)

68.08

Constituent 3) Mannich base

0.55 (0.47–0.64)

0.55 (-0.66–1.77)

 

Table 1b: Intermediate Results from LogBCF prediction.

 

Log KOW

Log BCFmax

log BCFcalc

mitigating effect of :

Acids

Meta­bolism

Phenols

Size3

Water solubility

1)

0.15

1.02

0.38

0

0.15

0

0.00

0.578

2)

3.42

2.56

1.15

0

1.30

0

0.08

0.143

3)

3.75

2.80

0.55

0

1.78

0

0.00

0.407

The developers of the QSAR present a decision rule for the interpretation of the predicted Log BCF based on the assessment of their training and validation data (See Table 1c). Based on this decision rule the constituents of Bisphenol A diglycidil ether (BADGE) and the product of hydrolysis are not bioaccumulative with high confidence.

Table 1c: Decision rule for the interpretation of predicted Log BCF values.

Calculated BCF

Conclusion

Log BCFclalc≥ 3.699+0.75

Bioaccumulative – high confidence

3.699 < Log BCFclalc< 3.699+0.75

Bioaccumulative – low confidence

3.699 - 0.75< Log BCFclalc< 3.699

Not bioaccumulative – low confidence

Log BCFclalc< 3.699 - 0.75

Not Bioaccumulative – high confidence

 

b.     Predicted value (comments): Metabolism and water solubillity are the most relevant mitigating factor for the two constituents, specifically constituent 2). Bioconcentration is also reduced due to size constraints. 

c.      Input for prediction: SMILES as specified under 1.5a

d.     Descriptor values:    Prediction is based on Kow prediction based on Epiwin(US Environmental Protection Agency and Syracuse Research Corporation (SRC) 2008). Table 1b gives intermediate results used for in the calculation.

Applicant's summary and conclusion

Executive summary:

The bioconcentration potential of the three major constituents in Paraformaldehyde, oligomeric reaction products with 4-tert-butylphenol, m-phenylenebis(methylamine) have been assessed using a QSAR algorithm as described by Dimitrov et al (2005) and implemented in OASIS CATALOGIC. The model estimates steady state whole fish bioconcentration factor (BCF) based on a maximum BCF and mitigating factors that reduce the BCF.

Two constituents are part of the training set. The unknowns are within the parametric domain of the model and within more than 59% of the structural domain as defined by first neighbour atom centred fragments.

Based on the accuracy in the prediction for the two constituents that are part of the training set and which are building blocks of the third constituent, the predicted BCF including the correction for metabolic reactions are considered reliable.

Assuming that the prediction falls within the range of accurate predictions as defined by the developer the following BCF are calculated for the constituents of Paraformaldehyde, oligomeric reaction products with 4-tert-butylphenol, m-phenylenebis(methylamine).

Molecule

log BCFcalc

BCF

BCF experimental

Constituent 1) m-phenylenebis(methylamine) (MXDA)

0.38 (0.27–0.5)

2.42 (1.12–3.72)

2.7

Constituent 2) 4-tert-butylphenol (PTBP)

1.15 (0.9–1.4)

1.15 (-0.64–2.94)

68.08

Constituent 3) Mannich base

0.55 (0.47–0.64)

0.55 (-0.66–1.77)

 

 

Based on a decision rule derived by the developer of the QSAR model, constituents of Paraformaldehyde, oligomeric reaction products with 4-tert-butylphenol, m-phenylenebis(methylamine) are not bioaccumulative with high confidence.