Bis(2,4,4-trimethylpentyl)phosphinic acid

Dermal absorption

Administrative data

Endpoint:

dermal absorption

Type of information:

(Q)SAR

Adequacy of study:

key study

Justification for type of information:

QSAR prediction

SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
The Dermal Permeability Coefficient Program (DERMWIN) v2.0 estimates the dermal permeability coefficient (Kp), the dermally absorbed dose per event (DAevent) and Dermal Absorbed Dose (DAD) of organic compounds via water contact. The Kp, DAevent and DAD estimation methodology was taken directly from the US EPA document (and supplemental Excel spreadsheet): USEPA. 2004.  Risk Assessment Guidance for Superfund (RAGS), Volume I: Human Health Evaluation Manual (Part E, Supplemental Guidance for Dermal Risk Assessment) Interim.  Document and spreadsheet available online at:http://www.epa.gov/oswer/riskassessment/ragse/index.htm
The estimation methodology in DERMWIN v2.0 is an update of the method and equations used in previous versions of DERMWIN that were based on the U.S. EPA document "Dermal Exposure Assessment: Principles and Applications" (USEPA, 1992). DERMWIN requires only a chemical structure to estimate Kp.  Structures are entered into DERMAL through SMILES (Simplified Molecular Input Line Entry System) notations.  Several methods are available for entering SMILES notations into DERMWIN (see the SMILES Entry section).  Users unfamiliar with SMILES notations can consult the document "A Brief Description of SMILES Notation".  Chemical Abstract Service (CAS) Registry numbers may be used to enter SMILES notations automatically through use of the SMILECAS database containing SMILES for 103,000+ compounds.
The DERMWIN data entry fields are described in the Data Entry Fields section. The data entry fields have been extended in DERMWIN v2.02 to allow access to the DAD variables (Dermal Absorbed Dose variables).
DERMWIN estimates a log Ko/w for every SMILES notation by using the estimation engine from the EPI Suite v4.10 KOWWIN Program.  DERMWIN also automatically retrieves experimental log Ko/w values from a database containing more than 15000 organic compounds with reliably measured values.  When a SMILES structure matches a database structure (via an exact atom-to-atom connection match), the experimental log Ko/w value is retrieved and used to predict Kp, rather than the estimated value.
- Estimation: The estimation methodology is taken from the following source document and on-line material: USEPA. 2004.  Risk Assessment Guidance for Superfund (RAGS), Volume I: Human Health Evaluation Manual (Part E, Supplemental Guidance for Dermal Risk Assessment) Interim.  Available online at:http://www.epa.gov/oswer/riskassessment/ragse/index.htm. See USEPA (2004) for a complete description.
Estimation Equation for Kp: The Kp estimation equation designated as equation 3.8 in USEPA (2004) is: log Kp (cm/hr)   =   -2.80  +  0.66 log Ko/w  -  0.0056 MW (r2 = 0.66), where Ko/w is the octanol/water partition coefficient and MW is the molecular weight. The associated on-line Excel spreadsheet (http://www.epa.gov/oswer/riskassessment/ragse/index.htm) uses more significant figures. DERMWIN implements the equation from the spreadsheet which is: log Kp (cm/hr)   =   -2.805063  +  0.6645865 log Ko/w  -  0.0056118 MW
Estimation of Kp for Specific Classes: Previous versions of DERMWIN included Kp estimation equations for specific classes of compounds (Alcohols, Phenols, Steroids) based on equations in USEPA (1992). These equations are no longer included in DERWIN v2.00.
The method requires tevent (hr/event) and Cw, the concentration of the chemical in water (mg/cm3).  The DERMWIN entry screen contains entry fields for both variables.  Unless changed by the user, tevent  uses a default value of 0.58 hr/event (taken from the on-line Excel spreadsheet) and Cw uses a default value of 0.0 mg/cm3.  When DERMWIN sees a Cw default of 0.0 mg/cm3, it does not use 0.0 in the prediction equations; instead, it calculates the water solubility of the chemical for Cw from the log Ko/w .  Log Ko/w has been correlated with water solubility in the following equation (Meylan and Howard, 1996; Environ. Toxicol. Chem. 15: 100-6): log S  =  0.796  -  0.854 log Ko/w  -  0.00728 MW  + MW Sum(fi), where  S  is the water solubility in moles/liter, MW is the molecular weight, and  (Sum)fi  is the summation of correction factors for various chemical classes.  This equation was derived by correlating measured log Ko/w  values and measured water solubilities of 1450 compounds;  it has a correlation coefficient (r2) of 0.934,  a standard deviation of 0.585 log units, and an absolute mean error of 0.442 log units.  DERMWIN uses this equation to estimate the water solubility in mg/cm3; Cw is then assigned this value.  If a Cw value other than 0.0 is entered into DERMWIN by a user, DERMWIN uses only the entered value.
Estimation of DAD (Dermal Absorbed Dose).
 Experimental Log Ko/w Database Retrieval

DERMWIN is designed to search a special database of experimental log Ko/w values and use a value if found.  The database, and its index file, are named "EXPKOW.DB" and "EXPKOW.IDX", respectively (they are installed during the EPI Suite installation).  DERMWIN generates a "structure-representation" for each SMILES entry and then searches the database for a matching "structure-representation".  If a match is found, the experimental log Ko/w value is used in Kp calculations (if a value is not entered in the Log Kow entry field). To disable experimental usage, simply delete (or rename) either the database or the index file. A "structure-representation" will produce a database match if there is an exact atom-to-atom connection match.  If more than one match is found, all exact matches are presented in a selection box for user selection. For example, if a SMILES for 1,2-dichloroethylene is entered (CLC=CCL  or  ClC=CCl), the experimental values for the cis- and trans-isomers are shown.  For large or complex structures, it is possible to produce a "structure-representation" match for a compound other than the exact SMILES entry.

Data source

Reference

Reference Type:

other: QSAR model

Title:

DermWin v 2.01

Author:

US Environmental Protection Agency

Year:

2011

Bibliographic source:

EPI Suite

Materials and methods

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

QSAR model

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2,4,4-trimethylpentyl)phosphinic acid

EC Number:

280-445-7

EC Name:

Bis(2,4,4-trimethylpentyl)phosphinic acid

Cas Number:

83411-71-6

Molecular formula:

C16H35O2P

IUPAC Name:

bis(2,4,4-trimethylpentyl)phosphinic acid

Results and discussion

Absorption in different matrices:

Skin penetration constant (Kp) (estimated): 0.000604 cm/hr

Any other information on results incl. tables

Results:

GENERAL Equation:  log Kp = -2.80 + 0.66 log Kow - 0.0056 MW

   Kp (predicted): 6.04e-004 cm/hr

 

Dermally Absorbed Dose per Event for Organic Compounds - Water Contact:

  Water Conc (mg/cm3): 0.38 (estimated by program)

  Fraction Absorbed : 1.0000

 

  DA(event): 1.03e-003 mg/cm2-event (using eqn 3.2 & 3.3)

                  (tau = 4.54 hr, t* = 10.9 hr)

 

Dermally Absorbed Dose (70 kg Adult) - Water Contact:

  DAD: 1.09e-001 mg/kg-day (using eqn 3.1)

Applicant's summary and conclusion

Conclusions:

The dermal permeability of bis(2,4,4 trimethylpentyl)phosphinic acid is predicted to be relatively low.

Executive summary:

The DERMWIN model, part of the US EPA EPIWIN Suite, estimated the skin penetration constant (Kp) to be 0.000604 cm/hr.