HSP Application note #10
Hansen Solubility Parameters (HSP) and Endocrine Disruptor2010.2.22
HSPiP Team Senior Developer, Dr. Hiroshi Yamamoto
Endocrine disruptors are exogenous substances that act like hormones in the endocrine system and disrupt the physiologic function of endogenous hormones. They are sometimes also referred to as hormonally active agents or endocrine disrupting chemicals/compounds (EDC). Studies have linked endocrine disruptors to adverse biological effects in animals, giving rise to concerns that low-level exposure might cause similar effects in human beings. (WikiPedia)
DDT
I compiled Endocrine Disruptor compounds and logBCF(bio concentration factor), logP, logS data.
| name | Code | LogBCF | logP | logS |
| alachlor | 20878 | 1.1206 | 3.52 | -1.62 |
| aldrin | 20487 | 3.7404 | 6.5 | -5.77 |
| atrazine | 10806 | 0.9 | 2.61 | -2.46 |
| benzophenone | 7761 | 1.0792 | 3.18 | -2.12 |
| butyl benzyl phthalate | 6450 | 1.2129 | 4.73 | -3.57 |
| bisphenol A | 7765 | 1.6415 | 3.32 | -1.82 |
| carbaryl | 20504 | 0.9542 | 2.36 | -1.96 |
| trans-, cis-chlordane | 20489 | 4.2911 | 6.16 | -5.25 |
| cypermethrin | 20985 | 2.62 | 6.6 | -6.40 |
| p,p' -DDT | 12873 | 4.2923 | 6.91 | -6.26 |
| p,p'-DDE | 20491 | 4.08 | 6.51 | -5.40 |
| di-n-butyl phthalate | 5449 | 2.2227 | 4.5 | -2.95 |
| 2,4-dichlorophenol | 8867 | 1.5302 | 3.06 | -0.55 |
| dieldrin | 20638 | 3.9516 | 5.4 | -4.71 |
| diethylhexyl phthalate | 5540 | 2.7694 | 7.6 | -4.57 |
| endrin | 20641 | 3.8739 | 5.2 | -4.60 |
| fenvalerate | 20982 | 2.8463 | 6.2 | -5.62 |
| HCB | 9058 | 4.331 | 5.73 | -6.30 |
| hexachlorocyclohexane, BHC | 20741 | 2.57 | -3.10 | |
| heptachlor | 20492 | 3.9428 | 6.1 | -4.74 |
| kelthane | 20683 | 3.7853 | 5.02 | -4.10 |
| malathion | 16548 | 1.5212 | 2.36 | -1.84 |
| 4-nitrotoluene | 7576 | 0.9031 | 2.37 | -1.49 |
| octachlorostyrene | 20919 | 3.9085 | ||
| PCDDs | 20524 | 4.9868 | 6.8 | -7.70 |
| PCDFs | 20981 | 3.608 | 6.53 | -7.16 |
| pentachlorphenol | 9142 | 2.6628 | 5.12 | -2.85 |
| nonylphenol | 7767 | 2.1903 | -3.20 | |
| simazine | 20697 | 0.5647 | 2.18 | -3.21 |
| trifluralin | 20527 | 3.3579 | 5.34 | -4.74 |
Largest logS is -0.55, so all compounds are relatively hydrophobic compounds.
But I can not categorize compounds with logBCF, logP, logS.
If you want to know how to draw molecules, please refer to Power Tools applications. The full version of this estimation routine is implemented into Y-Predict Powert Tools in HSPiP ver. 4.
So, I calculated HSP for each molecules with HSPiP, and start analyze with SOM (Self Organization Map) neural network.
Hansen Solubility Parameters (HSP)Hansen Solubility Parameters(HSP) were developed by Charles M. Hansen as a way of predicting if one material will dissolve in another and form a solution. They are based on the idea that "like dissolves like" where one molecule is defined as being 'like' another if it bonds to itself in a similar way.
What can perhaps be surprising is that one can assign HSP to so many different things. Gases like carbon dioxide, solids like carbon-60, sugar, and biological materials like human skin, depot fat, DNA, and even some proteins all have HSP. The list can be continued with drugs, polymers, plasticizers, and in fact any organic material and even many inorganic materials like salts. The only requirement for an experimental confirmation is that the material must behave differently in a sufficient number of test solvents upon contact. Pirika JAVA Demo Applet calculate HSP. HSPLight is available here. |
| ID | LogBCF | dD | dP | dH | sqrt(Volume) |
| 20878 | 1.1206 | 18.6 | 8.3 | 5.7 | 15.5 |
| 20487 | 3.7404 | 19.7 | 9.4 | 0.8 | 14.9 |
| 10806 | 0.9 | 18.4 | 8.6 | 12.8 | 13.4 |
| 7761 | 1.0792 | 20.4 | 7.5 | 4.6 | 12.8 |
| 6450 | 1.2129 | 18.5 | 8.2 | 3.9 | 16.7 |
| 7765 | 1.6415 | 19.0 | 5.9 | 12.1 | 14.5 |
| 20504 | 0.9542 | 19.6 | 9.6 | 7.6 | 12.9 |
| 20489 | 4.2911 | 19.4 | 12.7 | 1.4 | 15.4 |
| 20985 | 2.62 | 19.1 | 7.1 | 5.2 | 18.1 |
| 12873 | 4.2923 | 20.1 | 3.9 | 2.9 | 15.8 |
| 20491 | 4.08 | 20.5 | 6.6 | 3.2 | 15.1 |
| 5449 | 2.2227 | 17.3 | 8.1 | 3.7 | 16.3 |
| 8867 | 1.5302 | 19.9 | 8.1 | 12.0 | 10.9 |
| 20638 | 3.9516 | 20.0 | 11.0 | 1.2 | 15.0 |
| 5540 | 2.7694 | 16.8 | 5.6 | 3.4 | 19.9 |
| 20641 | 3.8739 | 20.0 | 11.0 | 1.2 | 15.0 |
| 20982 | 2.8463 | 19.4 | 6.2 | 5.3 | 18.7 |
| 9058 | 4.331 | 21.2 | 4.5 | 3.1 | 12.5 |
| 20741 | 2.57 | 18.3 | 15.9 | 4.1 | 14.1 |
| 20492 | 3.9428 | 19.4 | 11.5 | 1.1 | 14.8 |
| 20683 | 3.7853 | 20.5 | 4.4 | 7.8 | 15.8 |
| 16548 | 1.5212 | 15.2 | 8.6 | 9.3 | 16.4 |
| 7576 | 0.9031 | 19.4 | 7.2 | 4.1 | 11.0 |
| 20919 | 3.9085 | 20.9 | 5.7 | 2.3 | 14.3 |
| 20524 | 4.9868 | 20.7 | 5.1 | 4.9 | 14.1 |
| 20981 | 3.608 | 21.5 | 5.0 | 3.8 | 13.7 |
| 9142 | 2.6628 | 20.8 | 4.9 | 9.4 | 12.1 |
| 7767 | 2.1903 | 17.2 | 3.8 | 6.7 | 15.6 |
| 20697 | 0.5647 | 18.7 | 9.2 | 13.9 | 12.8 |
| 20527 | 3.3579 | 18.0 | 5.8 | 3.3 | 16.2 |
SOM: Self Organization Map Neural Network
|
Input vector for SOM is [dD, dP, dH, sqrt(Volume)].
And SOM arrange similar vectors to near position.
I think there are 6 categories for these compounds.
| Code | no | name | dD |
dP |
dH |
sqrt(V) | Cl | LogBCF |
| 5449 | 12 | di-n-butyl phthalate | 17.3 |
8.1 |
3.7 |
16.3 | 0 | 2.22 |
| 20985 | 9 | cypermethrin | 19.1 |
7.1 |
5.2 |
18.1 | 2 | 2.62 |
| 6450 | 5 | butyl benzyl phthalate | 18.5 |
8.2 |
3.9 |
16.7 | 0 | 1.21 |
| 20527 | 30 | trifluralin | 18.0 |
5.8 |
3.3 |
16.2 | 0 | 3.36 |
| 20982 | 17 | fenvalerate | 19.4 |
6.2 |
5.3 |
18.7 | 1 | 2.85 |
| Average | 18.4 |
7.1 |
4.3 |
17.2 | 2.45 | |||
| 20491 | 11 | p,p'-DDE | 20.5 |
6.6 |
3.2 |
15.1 | 4 | 4.08 |
| 20919 | 24 | octachlorostyrene | 20.9 |
5.7 |
2.3 |
14.3 | 8 | 3.91 |
| 20981 | 26 | PCDFs | 21.5 |
5.0 |
3.8 |
13.7 | 4 | 3.61 |
| 9058 | 18 | HCB | 21.2 |
4.5 |
3.1 |
12.5 | 6 | 4.33 |
| 12873 | 10 | p,p' -DDT | 20.1 |
3.9 |
2.9 |
15.8 | 5 | 4.29 |
| Average | 20.8 |
5.2 |
3.0 |
14.3 | 4.04 | |||
| 20487 | 2 | aldrin | 19.7 |
9.4 |
0.8 |
14.9 | 6 | 3.74 |
| 20489 | 8 | trans-, cis-chlordane | 19.4 |
12.7 |
1.4 |
15.4 | 8 | 4.29 |
| 20492 | 20 | heptachlor | 19.4 |
11.5 |
1.1 |
14.8 | 7 | 3.94 |
| 20638 | 14 | dieldrin | 20.0 |
11.0 |
1.2 |
15.0 | 6 | 3.95 |
| 20641 | 16 | endrin | 20.0 |
11.0 |
1.2 |
15.0 | 6 | 3.87 |
| Average | 19.7 |
11.1 |
1.2 |
15.0 | 3.96 | |||
| 20683 | 21 | kelthane | 20.5 |
4.4 |
7.8 |
15.8 | 5 | 3.79 |
| 20524 | 25 | PCDDs | 20.7 |
5.1 |
4.9 |
14.1 | 4 | 4.99 |
| 7767 | 28 | nonylphenol | 17.2 |
3.8 |
6.7 |
15.6 | 0 | 2.19 |
| 20878 | 1 | alachlor | 18.6 |
8.3 |
5.7 |
15.5 | 1 | 1.12 |
| Average | 19.2 |
5.4 |
6.3 |
15.3 | 3.02 | |||
| 7761 | 4 | benzophenone | 20.4 |
7.5 |
4.6 |
12.8 | 0 | 1.08 |
| 20504 | 7 | carbaryl | 19.6 |
9.6 |
7.6 |
12.9 | 0 | 0.95 |
| 7576 | 23 | 4-nitrotoluene | 19.4 |
7.2 |
4.1 |
11.0 | 0 | 0.90 |
| Average | 19.8 |
8.1 |
5.4 |
12.2 | 0.98 | |||
| 7765 | 6 | bisphenol A | 19.0 |
5.9 |
12.1 |
14.5 | 0 | 1.64 |
| 8867 | 13 | 2,4-dichlorophenol | 19.9 |
8.1 |
12.0 |
10.9 | 2 | 1.53 |
| 16548 | 22 | malathion | 15.2 |
8.6 |
9.3 |
16.4 | 0 | 1.52 |
| 10806 | 3 | atrazine | 18.4 |
8.6 |
12.8 |
13.4 | 1 | 0.90 |
| 20697 | 29 | simazine | 18.7 |
9.2 |
13.9 |
12.8 | 1 | 0.56 |
| Average | 18.2 |
8.1 |
12.0 |
13.6 | 1.23 | |||
| 9142 | 27 | pentachlorphenol | 20.8 |
4.9 |
9.4 |
12.1 | 5 | 2.66 |
| 20741 | 19 | hexachlorocyclohexane, BHC | 18.3 |
15.9 |
4.1 |
14.1 | 6 | 2.57 |
| 5540 | 15 | diethylhexyl phthalate | 16.8 |
5.6 |
3.4 |
19.9 | 0 | 2.77 |
Green and yellow compounds are very similar. they have very large dD and small dH. The difference is dP.
Both compounds have a lot of chlorine atoms and logBCF is around 4.
With SOM calculation, I did not input Cl# nor logBCF, but SOM categorize very cleverly.
Blue compounds have very large dH.
Pink compounds’ HSP is very similar to Orange compounds’ HSP, but molecular size is small.
And logBCF is small.
Purple compounds may go other categories.
25 to green.
28 to Orange.
21 and 27 make new category.
1 become exception.
I do not know how Endocrine disruptor works, but if HSP is differ, solubility nature is differ.
So, human may have at least these 5 types endocrines that HSP is near to above categories.
| 21488 | ESFENVALERATE | 19.4 | 6.2 | 5.3 | 18.7 | 1 | 18.7 | |
| 20764 | heptachlor epoxide | 19.7 | 13.1 | 1.5 | 14.9 | 7 | 14.9 | |
| 20508 | 2,4-dichlorophenoxyacetic acid | 19.8 | 8.6 | 10.7 | 12.3 | 2 | 12.3 |
If I want to categorize new molecules, I need just to calculate HSP using HSPiP.
And from that results, I know new compounds go where.
logP can do so little for this study.
Where do you think Benzo[a]pyrene goes?
| 11548 | Benzo[a]pyrene | 22.8 | 4.8 | 1.8 | 14.28285686 | 0 | 14.3 |
2011.4.25
Drag=Rotate, Drag+Shift=Larger/Smaller, Drag+Alt or Command(Window key)=Translate. This example, I did not use molecular volume.
If you are using HTML5 enable browser such as Chrome, Safari or FireFox (IE9 is out of support), you will see the Canvas. If you pick solvent, solvent name will appear.
In HSPiP, we have 10000 compounds in database.
So I search the green labeled range compounds.
dD= 20 - 22
dP= 4 - 6
dH= 2 -4
There are 66 compounds in DB.
Most of all are poly chlorine compounds.
But these compounds are also belong to green label range.
Are there EDC??
From the point of REACH Regulation, we’d better set these colored HSP area are grey zone.In reagent maker catalog or in ChenSpider like open database, if they are list HSP values, it will be very convenient for user to think about EDC.
If you have the Smiles structure of molecules, you can easily calculate HSE(Health, Safety, Health) properties with HSPiP.
Smiles(Simplified Molecular Input Line Entry Syntax) SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph. Pirika JAVA Demo Applet getting Smiles. Draw2Smiles is available here. |
I checked perfomance of HSPiP V.3.1.X for these compounds.
Only one compound (HCode=21051) is out of line.
| HCode 21051 logP=3.18 |
HCode 20877 logP=5.94 |
HCode 20927 logP=6.31 |
| HCode 20928 logP=6.23 |
HCode 20929 logP=6.63 |
HCode 20931 logP=6.67 |
But other similar compounds logP is around 6, so maybe database value is not correct.
I don't know the version, other software SciQSAR or ScilogP prediction is not so good.
HSPiP(Hansen Solubility Parameters in Practice)The first edition of HSPiP that appeared in November, 2008, greatly enhanced the usefulness of the Hansen solubility parameters (HSP). The HSP values of over 1200++ chemicals and 500 polymers are provided in convenient electronic format and have been revised and updated using the latest data sources in the second edition (March, 2009). A third edition of the HSPiP appeared in March, 2010. There are now 10,000 compounds in the HSP file which also includes data on density, melting point, boiling point, critical parameters, Antoine constants and much more. The user is able to carry out many different sorts of optimisations of solubility, evaporation, diffusion, adhesion, create their own datasets (automatically if required) and explore the huge range of applications for HSP in coatings, paints, nanoparticles, cosmetics, pharma, organic photovoltaics and much more. The 3rd Edition v3.1 was released on 12 December 2010. Current users can upgrade free (now v3.1.09) by downloading the latest .msi installer from http://hansen-solubility.com The 4th Edition v4.0.x was released on 2 Jan. 2013. The Current users can upgrade with free charge. 2013.1.28 The Visual How to manual of HSPiP. You can understand what HSPiP can do. |
Other topic of Bio Medical
GC data of class 1, class 2 solvents in Q3C:
HSP and Tamiflu Solubility parameter of Tamiflu or other H1N1 antiviral compounds
HSP for Rabbit: How to design eau de Cologne for rabbit. what LD50(skin, rabbit) means.
HSP and logP: logP, logKow, it is just HSP volume.
HSP and Carcinogenicity: SOM(self organization map) analysis of Poly-chlorinated compounds
HSP and Endocrine Disruptor: categorize by SOM.
HSP and AntimicroBial. Sulfa Drugs and other kind of Drugs.
Gall stone solubilizer: How to dissolve Cholesterol base Gall Stone.
Caco-2 cell monolayer apparent Permeability:SOM analysis
