Dibromodibenzo[b,def]chrysene-7,14-dione

Partition coefficient

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

partition coefficient

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

supporting study

Study period:

2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

1. SOFTWARE
EpiSuite /KOWWIN

2. MODEL (incl. version number)
EpiSuite 4.1
KOWWIN version 1.68

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS : 1324-11-4
SMILES : O=C1c5c(ccc(c5c2ccc3C(=O)(c6ccccc6c4ccc1c2c34))Br)Br
c62C(=O)c3c(c4c6c1c(C(=O)c5c(c(Br)ccc5)c1cc2)cc4)c(Br)ccc3
c62C(=O)c3c(c4c6c1c(C(=O)c5c(c1cc2)cc(Br)cc5)cc4)ccc(Br)c3

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attachment

5. APPLICABILITY DOMAIN
See attachment

6. ADEQUACY OF THE RESULT
See attachment

Principles of method if other than guideline:

KOWWIN uses a "fragment constant" methodology to predict log P.  In a "fragment constant" method, a structure is divided into fragments (atom or larger functional groups) and coefficient values of each fragment or group are summed together to yield the log P estimate.   KOWWIN’s methodology is known as an Atom/Fragment Contribution (AFC) method.  Coefficients for individual fragments and groups were derived by multiple regression of 2447 reliably measured log P values.  KOWWIN’s "reductionist" fragment constant methodology (i.e. derivation via multiple regression) differs from the "constructionist" fragment constant methodology of Hansch and Leo (1979) that is available in the CLOGP Program (Daylight, 1995).  See the Meylan and Howard (1995) journal article for a more complete description of KOWWIN’s methodology.

To estimate log P, KOWWIN initially separates a molecule into distinct atom/fragments.  In general, each non-hydrogen atom (e.g. carbon, nitrogen, oxygen, sulfur, etc.) in a structure is a "core" for a fragment; the exact fragment is determined by what is connected to the atom.  Several functional groups are treated as core "atoms"; these include carbonyl (C=O), thiocarbonyl (C=S), nitro (-NO2), nitrate (ONO2), cyano (-C/N), and isothiocyanate (-N=C=S).  Connections to each core "atom" are either general or specific; specific connections take precedence over general connections.  For example, aromatic carbon, aromatic oxygen and aromatic sulfur atoms have nothing but general connections; i.e., the fragment is the same no matter what is connected to the atom.  In contrast, there are 5 aromatic nitrogen fragments: (a) in a five-member ring, (b) in a six-member ring, (c) if the nitrogen is an oxide-type {i.e. pyridine oxide}, (d) if the nitrogen has a fused ring location {i.e. indolizine}, and (e) if the nitrogen has a +5 valence {i.e. N-methyl pyridinium iodide}; since the oxide-type is most specific, it takes precedence over the other four.  The aliphatic carbon atom is another example; it does not matter what is connected to -CH3, -CH2-, or -CH< , the  fragment is the same; however, an aliphatic carbon with no hydrogens has two possible fragments: (a) if there are four single bonds with 3 or more carbon connections and (b) any other not meeting the first criteria.

It became apparent, for various types of structures, that log P estimates made from atom/fragment values alone could or needed to be improved by inclusion of  substructures larger or more complex than "atoms"; hence, correction factors were added to the AFC method.  The term "correction factor" is appropriate because their values are derived from the differences between the log P estimates from atoms alone and the measured log P values.  The correction factors have two main groupings: first, factors involving aromatic ring substituent positions and second,  miscellaneous factors.  In general, the correction factors are values for various steric interactions, hydrogen-bondings, and effects from polar functional substructures.  Individual correction factors were selected through a tedious process of correlating the differences (between log P estimates from atom/fragments alone and measured log P values) with common substructures.

Two separate regression analyses were performed.  The first regression related log P to atom/fragments of compounds that do not require correction factors (i.e., compounds estimated adequately by fragments alone).  The general regression equation has the following form:

 log P  = Σ(fini ) +  b     (Equation 1)

where Σ(fini )  is the summation of fi (the coefficient for each atom/fragment) times ni (the number of times the atom/fragment occurs in the structure) and b  is the linear equation constant.  This initial regression used 1120 compounds of the 2447 compounds in the total training dataset.

The correction factors were then derived from a multiple linear regression that correlated differences between the experimental (expl) log P and the log P estimated by Equation 1 above with the correction factor descriptors.  This regression did not utilize an additional equation constant.  The equation for the second regression is:

 lop P (expl)  -  log P (eq 1)  = Σ(cjnj )       (Equation 1)

where Σ(cjnj )  is the summation of cj (the coefficient for each correction factor) times nj  (the number of times the correction factor occurs (or is applied) in the molecule).

 

Regression Results

Results of the two successive multiple regressions (first for atom/fragments and second for correction factors) yield the following general equation for estimating log P of any organic compound:

log P  = Σ(fini ) + Σ(cjnj ) + 0.229     (Equation 3)

(num = 2447,   r2 = 0.982,  std dev = 0.217,  mean error = 0.159)

GLP compliance:

no

Type of method:

calculation method (fragments)

Partition coefficient type:

octanol-water

Key result

Type:

log Pow

Partition coefficient:

8.06

Temp.:

25 °C

pH:

7.4

Remarks on result:

other: assumed values for modelling

Conclusions:

The partition coefficient of Vat Orange 1 was calculated with KOWWIN included in EpiSuite 4.1. to be log Kow: 8.06

Executive summary:

Log Kow (version 1.68 estimate): 8.06

Reference 2

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 04, 2018 - January 23, 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 105 flask method

Deviations:

no

Principles of method if other than guideline:

OECD 105 flask method

GLP compliance:

no

Type of method:

flask method

Partition coefficient type:

octanol-water

Analytical method:

other: gravimetric analysis

Key result

Type:

log Pow

Partition coefficient:

1.9

Temp.:

20 °C

Remarks on result:

other: pH not determined

Preliminary visual estimation of the n-octanol solubility

A defined amount of the test item was stirred with n-octanol at room temperature and visually checked for any undissolved parts.

Table1: Results of the preliminary visual estimation of the n-octanol solubility

Amount of test item / mg	Added volume of n-octanol / mL	Total volume of n-octanol / mL	Stirring time / h	Appearance of mixture
3.4	10	10	2.5	not dissolved

According to this preliminary test the solubility of the test item in n-octanol was below 0.34 g/L (without correction for the purity).

Calculation of the partition coefficient log P_OW from the preliminary test

The partition coefficient P_OW may be estimated from the saturation concentrations in n-octanol and water. The estimated partition coefficient was calculated with the water solubility data determined in project 20170176-3 (c_S = 2.6 mg/L) and the data obtained above. It was calculated to be: log P_OW < 2.1. Also the program KOWWIN (part of EPI Suite) was used for calculating the log P_OW of the test item. The calculated value was 8.1. The shake flask method and the HPLC method were not applicable due to the very low solubility of the test item inaqueous and organic solvents. Therefore the partition coefficient was estimated based on the ratio of the solubilities in water and octanol.

Determination of the solubility in n-octanol: Flask method

The individual saturation solubility of the test item in n-octanol was performed within this study according to the flask method. Because of the low solubility of the test item in n-octanol, determined in the preliminary visual estimation (see above) more than the five-fold amount of the preliminary test was used for the flask method. The flask method was performed as described above and subsequently the partition coefficient was estimated based on the ratio of the test item solubility in n-octanol and water. The data for the evaluation are given in Table2.The n-octanol solubility was calculated from the measured and unrounded concentration values and not from the rounded values given in Table2.

Table2: n-Octanol solubility experiments of the test item

Experiment	24 h experiment	48 h experiment	72 h experiment	blank experiment (72 h)
Amount of test item / g	1.50	1.52	1.50	--
Amount of octanol / mL	150	150	150	150
Stirring time at 30 °C / h	24	48	72	72
Weight of filtered filtrate / g	81.21	81.66	82.30	81.49
Calculated volume^1)/ mL	99.4	100.0	100.7	99.7
Residue after evaporation / mg	19.7	21.7	20.1	0.8
n-Octanol solubility / mg/L	198	217	200	8

Remark: 1) calculated with a density of 0.817 kg/L for n-octanol.

With regard to the blank value, the n-octanol solubility of the test item at 20 °C was determined to be c_S = 197mg/L (± 10 mg/L) (without correction of the purity).

Calculation of the partition coefficient log P_OW from the individual solubilities

In the project 20170176-3 the water solubility of the test item at 20 °C was determined to be c_S = 2.6 mg/L.Within this project the n-octanol solubility of the test item at 20 °C was determined to be c_S = 197mg/L. The partition coefficient P_OW was estimated from the individual solubility in n-octanol and water. The partition coefficient P_OW of the test item was determined to be: 

log P_OW = 1.9

All determinations and calculations were carried out without any correction of the purity of the test item. It cannot be excludes that the determined partition coefficient log P_OW originates from octanol soluble impurities of the test item.

Executive summary:

The partition coefficient (n-octanol/water) of the test item was estimated based on the ratio of the individual solubilities of the test item in water and n-octanol. The solubilities were determined according to the flask method.The shake flask method and the HPLC method were not applicable due to the low solubility of the test item inn-octanol and water.

It was found to be:

 

log P_OW = 1.9

Description of key information

The partition coefficient (n-octanol/water) of the test item was estimated based on the ratio of the individual solubilities of the test item in water and n-octanol.

As the test item is insoluble in water and organic solvents, no feasible quantification method for the dye itself is available. Therefore, the dissolved total organic carbon was measured.

The solubilities were determined according to the flask method.

It was found to be: log P_OW= 1.9

As the results of the TOC determination contains not only the test item, but all impurities containing carbon, the partition coefficient of the test item was calculated with KOWWIN v1.68 included in EpiSuite 4.1.

The partition coefficient of Vat Orange 1 was calculated to be log Kow: 8.06

Key value for chemical safety assessment

Log Kow (Log Pow):

8.06

at the temperature of:

25 °C