Phenethylamine

Henry's Law constant

Administrative data

Endpoint:

Henry's law constant

Type of information:

(Q)SAR

Adequacy of study:

key study

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:

Estimation of the Henry’s Law Constant HENRYWIN v3.20 (Bond Contribution Method; EPI Suite v4.11) (QMRF)

HENRYWIN estimates the Henry's Law Constant of organic compounds at 25 °C using the methodology originally described by Hine & Mookerjee (1975). The original methodology was updated and expanded at Syracuse Research Corporation as described in Meylan & Howard (1991). A subsequent update included additional fragment and correction factors.
HENRYWIN estimates Henry's Law Constant (HLC) by two separate methods that yield two separate estimates. The first method is the Bond Contribution Method and the second is the Group Contribution Method. In addition HENRYWIN calculates the HLC based on user-entered or estimated values for vapour pressure and water solubility. The estimation accuracy of the latter method depends strongly on the reliability of the experimental values and hence cannot be specified in this QMRF.
However, an independent evaluation (Altschuh et al., 1999) for a diverse set of organic chemicals found the bond method more accurate than the group method:
- Comparison of 76 reliably measured results with VP/WS and group contribution method
o Bond contribution method with smallest averaged error and fewest number of outliers,
o VP/WS method slightly worse,
o Group contribution method: considerably worse; method failed completely for hexachlorocyclohexanes; some strong outliers from other chemical classes.
- Shortcomings of bond method:
o Missing differentiation of isomers (inherent problem of all fragment methods),
o Bad performance for most of the organochlorine pesticides.
Therefore, the QMRF focuses primarily on the estimation of the HLC using the Bond-Method.

1.0 QSAR identifier
1.1 QSAR identifier (title) HENRYWIN for estimation of the Henry’s Law Constant (HLC)
1.2 Other related models -
1.3 Software coding the model HENRYWIN v3.20 (EPI Suite v4.11)
2.0 General information
2.1 Date of QMRF 10 Oct. 2013
2.2 QMRF author and contact details BASF SE, Department of Product Safety, Ludwigshafen, Germany
2.3 Date of QMRF update(s) -
2.4 QMRF update(s) -
2.5 Model developer(s) and contact details Original model: Hine and Mookerjee (1975); improved by: Meylan and Howard (1991)
2.6 Date of model development and/or publication See 2.5
2.7 References to main scientific papers and/or software package - Hine, J. and Mookerjee, P.K. 1975. The intrinsic hydrophilic character of organic compounds. Correlations in terms of structural contributions. J. Org. Chem. 40: 292-298.
- Meylan W.M. and Howard P.H. (1991). Bond contribution method for estimating Henry's law constants. Environmental Toxicology and Chemistry. 10 (10): 1283–1293, October 1991.
- Altschuh, J.R., Bruggemann, H. Santl, G. Eichinger, and O.G. Piringer. 1999. Henry’s law constants for a diverse set of organic chemicals: experimental determination and comparison of estimation methods. Chemosphere 39: 1871-87.
2.8 Availability of information about the model The model is non-proprietary and can be downloaded freely from US EPA.
Training and validation data sets are available (http://esc.syrres.com/interkow/EpiSuiteData.htm).
2.9 Availability of another QMRF for exactly the same model No (http://qsardb.jrc.it/qmrf/).
3.0 Defining the endpoint
3.1 Species The HLC is estimated for the uncharged molecule.
3.2 Endpoint HLC at 25 °C
3.3 Comment on the endpoint -
3.4 Endpoint units Given as unitless LWAPC as well as HLC in atm*m³/mol, Pa*m³/mol and unitless.
3.5 Dependent variable LWAPC
(LWAPC = log water-to-air partition coefficient; LWAPC is the logarithm of the reciprocal unitless HLC. The unitless HLC is converted to units of atm*m³/mol by multiplying it by the gas constant (8.206x10-5 atm*m³/mole K) and the temperature (298.16 K). To convert units of atmosphere (atm) to Pascals (Pa), atm is multiplied by a factor of 101325)
3.6 Experimental protocol Not available
3.7 Endpoint data quality The HLC is estimated via three methods in HERNYWIN:
1) Bond contribution
2) Group contribution
3) Vapour pressure/water solubility ratio
4.0 Defining the algorithm
4.1 Type of model - Bond and Group contribution method: QSAR
- VP/WS ratio: calculation
4.2 Explicit algorithm HENRYWIN estimates two separate HLC values (one using the group method and one using the bond method). The bond contribution methodology splits a compound into smaller units (one atom to another atom only). The bond method includes individual hydrogen bond values; the group method does not. In addition the HLC is calculated via vapour pressure and water solubility.
1) Bond contribution method: Multi-linear regression with correction factors:
LWAPC = Σ((Bi)(Nj) + (Ci)(Mj))

2) Group contribution method: Multi-linear regression:
summation of group contribution values

3) HLC = vapour pressure [Pa] * molecular weight [g/mol] / water solubility [mg/L]
4.3 Descriptors in the model SMILES: structure of the compound as SMILES notation; The chemical structure (as SMILES) is the only required descriptor for estimating the water solubility. All other descriptors can be derived from the chemical structure.
MW: molecular weight
VP: vapour pressure
WS: water solubility
Bond contribution values: Each compound is split into a summation of the individual bonds which comprise the compound. The summation is set equal to the compound's known LWAPC.
Group contribution values: Each compound is split into a summation of the individual groups which comprise the compound.
Correction factors (bond contribution): correction factors are simply mean values of the deviations between known and estimated LWACPs
[Bi = bond contribution value of each bond; Nj =number of instances of each bond; Ci = correction factor value of each factor; Mj = number of instances of each correction factor]
4.4 Descriptor selection Bond contribution values, used to estimate Henry's law constant (HLC)(air-to-water partition coefficient) from chemical structure, have been determined for 59 chemical bonds by a least-square analysis of HLCs for 345 organic compounds.
Hine & Mookerjee (1975) used a total of 212 compounds to derive their group contribution values. The 212 compounds were a subset of the 263 compounds they used to derive bond contribution values.
4.5 Algorithm and descriptor generation SMILES: user entered (required for estimation)
Bond/Group contribution values: List with available bonds/groups
Correction factors: List with factors
MW: molecular weight as derived from chemical structure, only required for VP/WS ratio
VP: user-entered data (if available), otherwise estimated value (MPBPVP v1.43)
WS: user-entered data (if available), other wise use of estimated value (WSKOWWIN v1.42)
4.6 Software name and version for descriptor generation See above
4.7 Descriptor/Chemicals ratio Training dataset:
1) Bond contribution: 442 compounds (On-Line HENRYWIN User’s Guide, Appendix G)
2) Group contribution: 212 compounds (On-Line HENRYWIN User’s Guide, Appendix J)

Descriptors:
1) Bond contribution: bond contribution values and correction factors
2) Group contribution: group contribution values
3) VP/WS: MW, VP, WS
5.0 Defining the applicability domain
5.1 Description of the applicability domain of the model 1) Bond contribution method:
a. Range of MW
b. Range of HLC
c. Maximum number of instances of a bond or correction factor in any of the training set compounds
d. Missing fragments (yields “incomplete” estimate)

2) Group contribution method:
a. Range of MW
b. Maximum number of instances of a group in any of the training set compounds.
c. Missing fragments (yields “incomplete” estimate)

3) VP/WS ratio: Water solubility (< 1.0 mol/L)
5.2 Method used to assess the applicability domain The applicability is assessed by comparing the molecular weight, the log Kow (as used by WSKOW v1.42) and the estimated water solubility of the compound with the corresponding values of the training set.
5.3 Software name and version for applicability domain assessment -
5.4 Limits of applicability Ranges for the 442 compound dataset for regressing the bond method coefficients (On-Line HENRYWIN User’s Guide, Appendix G):
Molecular Weights:
- Minimum = 26.04 (Ethyne)
- Maximum = 451.74 (Flucythrinate, CAS 70124-77-5)
Henry’s Law Constant:
- Minimum = 5.65E-14 atm*m³/mol (LWAPC = 11.636; Karbutilate, CAS 4849-32-5)
- Maximum = 2.03E01 atm*m³/mol (LWAPC = -2.919; Hexafluorethane)
6.0 Defining goodness-of-fit and robustness
6.1 Availability of the training set The complete dataset used to derive bond contribution values and correction factors is listed in the help file of the HENRYWIN program (On-Line HENRYWIN User’s Guide, Appendix G) or can be downloaded from http://esc.syrres.com/interkow/EpiSuiteData.htm.
The dataset used to develop the group contribution method is contained in the publication by Hine & Mookerjee (1975).
6.2 Available information for the training set - CAS number
- Chemical name
- Experimental LWAPC
- Bond estimated LWAPC
- Estimation error
- Regression
a. Original dataset (development of method)
b. Enhanced dataset (update of method)
6.3 Data for each descriptor variable for the training set -
6.4 Data for the dependent variable (response) for the training set LWAPC (experimental):
- computed from experimental data for VP and WS
- measured HLCs
- Sources: USDA, SRC EFDB, pesticide handbooks
6.5 Other information about the training set -
6.6 Pre-processing of data before modelling -
6.7 Statistics for goodness-of-fit Bond estimation method (On-Line HENRYWIN User’s Guide, Ch. 7.3 Estimation Accuracy):
- n = 442
- Correlation coefficient (r2) = 0.977
- Standard deviation = 0.400
- Absolute mean error = 0.249
7.0 Defining predictivity
7.1 Availability of the external validation set Bond contribution method:
- Appendix I of Help file for HENRYWIN: 74 compounds
7.2 Available information for the external validation set - Chemical name
- Experimental LWAPC
- Bond estimated LWAPC
- Estimation error
7.3 Data for each descriptor variable for external validation set -
7.4 Data for the dependent variable for the external validation set -
7.5 Other information about the external validation set -
7.6 Experimental design of test set -
7.7 Predictivity – Statistics obtained by external validation Bond estimation method:
1) Original validation dataset (On-Line HENRYWIN User’s Guide, Appendix I)
- n = 74
- Correlation coefficient (r2) = 0.965
- Standard deviation = 0.475
- Absolute mean error = 0.31

2) Extended validation dataset (http://esc.syrres.com/interkow/EpiSuiteData.htm)
- n = 1376
- Correlation coefficient (r2) = 0.79
- Standard deviation = 1.54
- Absolute mean error = 1.00
7.8 Predictivity - Assessment of the external validation set A major part of the statistical inaccuracy of the extended compound dataset occurs when the LWAPC exceeds 5. An LWAPC of 5.0 equals a Henry's law constant of 2.48E-2 Pa*m³/mol at 25 °C. Any organic compound with a HLC less than 3.04E-2 Pa-m³/mol is considered essentially non-volatile from water (Thomas, 1990). The estimation accuracy can be improved using a reduced data set with a cut-off of 1.0E-3 Pa*m³/mol. The accuracy for the remaining validation compounds (1077 compounds) has a standard deviation of 1.31 and average deviation of 0.83.
8.0 Providing a mechanistic interpretation
8.1 Mechanistic basis of the model The Henry's Law constant (HLC) can be defined as the ratio of the concentration of a compound in the gas-phase to the concentration of the compound in a dilute aqueous solution at equilibrium.
9.0 Miscellaneous information
9.1 Comments -
9.2 Bibliography - Altschuh, J.R., Bruggemann, H. Santl, G. Eichinger, and O.G. Piringer. 1999. Henry’s law constants for a diverse set of organic chemicals: experimental determination and comparison of estimation methods. Chemosphere 39: 1871-87.
- HENRYWIN Data files used in training & validation: http://esc.syrres.com/interkow/EpiSuiteData.htm.
- Hine, J. and Mookerjee, P.K. 1975. The intrinsic hydrophilic character of organic compounds. Correlations in terms of structural contributions. J. Org. Chem. 40: 292-298.
- Meylan W.M. and Howard P.H. (1991). Bond contribution method for estimating Henry's law constants. Environmental Toxicology and Chemistry. 10 (10): 1283–1293, October 1991.
- Thomas, R. 1990. Volatilization from water. In: Handbook of Chemical Property Estimation Methods. Environmental Behavior of Organic Chemicals. Lyman, W.J, Reehl, W.F., and Rosenblatt, D.H. (editors). Washington DC: Amer Chem Soc pp. 15-1 to 15-30.
- User Guide Help. On-Line HENRYWIN™ User's Guide. HENRYWIN v3.20.
 

Data source

Reference

Reference 1

Reference Type:

other: EPIWIN calculation

Title:

Unnamed

Year:

2016

Report date:

2016

Reference 2

Reference Type:

other: Estimation software

Title:

Estimation Programs Interface Suite for Microsoft Windows, v4.11

Author:

US-EPA

Year:

2012

Bibliographic source:

United States Environmental Protection Agency, Washington, DC, USA; November 2012

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Calculation of Henry's Law Constant. Software used: SRC HENRYWIN v3.20: Bond estimation method

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Phenethylamine

EC Number:

200-574-4

EC Name:

Phenethylamine

Cas Number:

64-04-0

Molecular formula:

C8H11N

IUPAC Name:

2-phenylethanamine

Results and discussion

Henry's Law constant H

Key result

H:

0.082 Pa m³/mol

Temp.:

25 °C

Remarks on result:

other: The substance is within the applicability domain of the model.

Any other information on results incl. tables

Result table for Bond Contribution method from HENRYWIN v3.20

Class		Bond contribution Description	Comment	Value
Hydrogen	4	Hydrogen to Carbon (aliphatic) Bonds		-0.4787
Hydrogen	5	Hydrogen to Carbon (aromatic) Bonds		-0.7715
Hydrogen	2	Hydrogen to Nitrogen Bonds		2.5670
Fragment	1	C-C		0.1163
Fragment	1	C-Car		0.1619
Fragment	1	C-N		1.3010
Fragment	6	Car-Car		1.5828
Result		Bond Estimation Method For LWAPC Value	Total	4.479
		Henrys Law Constant at 25 °C		= 8.12E-007 atm-m3/mole
				= 3.32E-005 unitless
				= 8.23E-002 Pa-m3/mole