f/EPA
              United States
              Environmental Protection
              Agency
              Environmental Research
              Laboratory
              Duluth MN 55804
EPA-600 3-78-049
May 1978
              Research and Development
A Rapid  Method
for Estimating Log  P
for Organic
Chemicals

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                RESEARCH REPORTING SERIES

Research reports of the Office of Research and Development, U.S. Environmental
Protection Agency, have been grouped into nine series. These nine broad cate-
gories were established to facilitate further development and application of en-
vironmental technology.  Elimination  of  traditional grouping was consciously
planned to foster technology transfer and a maximum interface in  related fields.
The nine series are:

      1   Environmental Health Effects Research
      2.  Environmental Protection Technology
      3.  Ecological Research
      4   Environmental Monitoring
      5.  Socioeconomic Environmental Studies
      6   Scientific and Technical  Assessment Reports (STAR)
      7   Interagency  Energy-Environment Research and Development
      8.  "Special" Reports
      9.  Miscellaneous Reports

This report has been assigned to the ECOLOGICAL RESEARCH series. This series
describes research on  the effects of pollution on humans, plant and animal spe-
cies, and materials. Problems are assessed for their long- and short-term influ-
ences. Investigations include formation, transport, and pathway studies to deter-
mine the fate of pollutants and their effects. This work provides the technical basis
for setting standards to minimize undesirable changes in living organisms in the
aquatic, terrestrial, and atmospheric environments.
This document is available to the public through the National Technical Informa-
tion Service, Springfield, Virginia 22161.

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                                              EPA-600/3-78-049
                                              May 1978
      A RAPID METHOD FOR ESTIMATING LOG P

             FOR ORGANIC CHEMICALS
                       by

                Gilman D. Veith
Environmental Research Laboratory - Duluth, MN  55804

               Richard T. Morris
  University of Wisconsin-Superior,  WI  54880
        ENVIRONMENTAL RESEARCH LABORATORY
       OFFICE OF RESEARCH AND DEVELOPMENT
      U.S. ENVIRONMENTAL PROTECTION AGENCY
            DULUTH, MINNESOTA  55804

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                                  DISCLAIMER

     This report has been reviewed by the Environmental Research Laboratory-
Duluth, U.S. Environmental Protection Agency, and approved for publication.
Mention of trade names or commercial products does not constitute endorsement
or recommendation for use.
                                     ii

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                                   FOREWORD

     Many of the test protocols for screening organic chemicals for potential
harmful effects in the environment rely on correlations of known effects with
physical properties of the chemicals.  The partition coefficient of a chemical
in an n-octanol/water system provides insight into the tendency of chemicals
to accumulate in lipoid tissues, to adsorb onto particulate matter coated with
natural organic material, and to resist biodegradation.  Specific correlations
exist between the partition coefficient (expressed as Log P), the water
solubility, and the bioconcentration factor of organic chemicals in fish.
This report sets forth a rapid, inexpensive method for estimating Log P,
which will greatly enhance screening tests for evaluating the potential
hazards of chemicals in the environment.
                                     iii

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                                   ABSTRACT

     A rapid, inexpensive technique based on reverse-phase high pressure
liquid chromatography has been developed to estimate  the n-octanol/water
partition coefficient of organic chemicals.  The system consists of a
preparative Micro-Pak C-10 Qy reverse-phase column eluted with a 15 percent
water/85 percent methanol solvent flowing at 2 ml/min at room temperature.
The chemicals are detected in the eluant with a standard ultraviolet detector
or a fraction collector system followed by appropriate analysis of the
fractions to determine the retention time of the chemical.  A linear
calibration of the logarithm of retention time with the logarithm of the
partition coefficient (Log P) is attained by using a  mixture of benzene,
bromobenzene, biphenyl, bibenzyl, pp'DDE, and 2,4,5,2',5' pentachlorobiphenyl
as reference standards of known Log P-  Chemicals with Log P of approximately
3 elute in less than 10 min whereas those with Log P  greater than 5 elute
after 20 min.
                                      iv

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                                   CONTENTS

Foreword	iii
Abstract	   iv
Figures	   vi
Tables	vii
Acknowledgments  	 viii

     1.  Introduction  	    1
     2.  Conclusions 	    3
     3.  Recommendations 	    4
     4.  Experimental Procedures	; .  .    5
              Liquid chromatography conditions 	    5
              Test solutions	    6
              Calibration mixture  	    6
     5.  Results and Discussion  	    7
              Correlation of Log P and HPLC retention	    7
              Calculation of Log P	   10
              HPLC estimation of Log P	   10

References   	   15
                                      v

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                                LIST OF FIGURES

Number                                                                    Page

  1   Verification of the dependency of the HPLC relative retention
      time on the Log P for 47 organic chemicals	9

  2   Relationship between Log P and HPLC log retention time of the
      calibration mixture  ... 	  12
                                      VI

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                                    TABLES

Number                                                                   Page

  1   Retention data of a variety of chemicals obtained by using
      gradient elution reverse-phase HPLC 	  8
  2   HPLC retention times and partition coefficients for organic
      chemicals used for calibration	»	11

  3   Comparison of estimated Log P values with reported Log P values
      for 18 organic chemicals	 14
                                      VII

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                               ACKNOWLEDGMENTS

     The assistance of Ned Austin in the early development  of  this  technique
is sincerely appreciated and acknowledged.  Also, we  thank  Donald I.  Mount
for his encouragement and support of this work on rapid screening techniques.
                                     viii

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                                   SECTION  1

                                  INTRODUCTION

     The use of  the n-octanol/water partition  coefficients  (expressed  as  Log
P) has become  the cornerstone of  predicting  the biological  effects  of  organic
chemicals from physical properties through the use  of  structure-activity
correlations (1, 2).   The Log P value has  become  a  critical  physical property
for predicting toxicity to aquatic organisms  (3), bioconcentration  factors
for fish (4),  and water solubility (5).  Moreover,  adsorption  of  chemicals
in sewage sludges and  organic particulate  matter  and the biodegradability of
organic chemicals appear to be related  to  the Log P value.

     Several methods can be used  for measuring or estimating P.   The obvious
method is to mix the chemical with n-octanol and water, shake  the biphasic
system to assure equilibrium, and measure  the  concentration  of  the  chemical
in the two phases.  The value of  P is calculated  as the ratio  of  the
concentration  in the octanol and  the concentration  in  the water.  This
method can be  laborious because emulsions  are  formed and analytical methods
are needed for each chemical in at least one of the phases.  The  use of
radiolabeled chemicals simplifies  the analytical  problems, but  it may  greatly
increase the cost of the measurement.   Also, chemicals with  Log P of 4 and
greater (10,000  times  more in the  octanol  than water)  cannot be measured  with
the same precision as  chemicals that distribute more evenly, and  highly lipid
soluble chemicals are  those of great concern in environmental  hazard assessment.
Another drawback to measuring P is that the measurement cannot be done
reliably when  dealing  with mixtures of  chemicals  of unknown  identity,  such as
would be encountered in complex effluents, because  the bulk  of  the  organic
constituents may alter the solvent-system  behavior.

     If the structure  of a chemical is  known, Log P can be  estimated from
substituent constants  as discussed by Hansch and  Fujita (7).   This  is  probably
the best initial step  in determining Log P since  it can be done without
experimentation and is quite reliable for  many common  organic  chemicals.
However, for some functional groups the substituent-constant approach  is
not yet completely reliable (Personal Communication, 1977, A.  Leo,  Pomona
College, Claremouht, Calif.)  Moreover, the structure  of the chemicals must
be known, which precludes this approach from use  in assessing  potential
hazards of complex effluents, landfill  leachates, or other uncharacterized
mixtures of chemicals.

     The objectives of this study were  to  determine if Log P and  the high
pressure liquid chromatography (HPLC) reverse-phase retention  time  are
related by using a wide variety of industrial  chemicals, and,  if  so, to
develop a method for estimating Log P by using HPLC,   The results are

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summarized in this report, and a method of estimating Log P is suggested
which alleviates some of the problems discussed above.  The constraints on
this research were that the method be inexpensive, require less than 1 hr
of laboratory time, and provide an acceptable measure of Log P-

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                               SECTION 2

                              CONCLUSIONS

The logarithm of the retention time  (Log RT) of organic  chemicals  on  a
permanently bonded  (C-18) reverse-phase high pressure  liquid  chromatography
system is linearly  related to the logarithm of the n-octanol/water  partition
coefficient (Log P).  The relationship is  summarized by  the equation  Log
P = 5.106 Log RT -  1.258 with a correlation coefficient  0.975.

By using a calibration mixture, the  Log P  of other organic chemicals
were estimated with a mean accuracy  of 22.8 percent compared  to  Log P
values reported in  the literature.   The technique permits estimation
of Log P in a maximum of 25 min and  does not require a knowledge of
the structure of the chemical for the estimate.

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                                   SECTION 3

                                RECOMMENDATIONS

1.  The correlation between the estimates of Log P from the technique presented
    in this report and the Log P values from direct measurement is presently
    limited by the number of chemicals tested, particularly high lipophilic
    chemicals.  Additional work is needed to expand the correlation and set
    confidence intervals for estimates of Log P by this indirect method.

2.  The relationship between the dissociation constant of organic chemicals
    and the estimation of Log P by this indirect method is needed to evaluate
    the comparatively large discrepancies between estimated and literature
    Log P values for such chemicals.

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                                    SECTION 4

                             EXPERIMENTAL  PROCEDURES

     Reverse-phase  liquid  chromatography  is a separation process in which
chemicals  are  injected  onto  a column of fine  particles  coated  with a
nonpolar  (water-insoluble) oil and  then eluted with  a polar  solvent such as
water  or methanol.   Recent developments in this field have produced a
permanently  bonded  reverse-phase column in which long-chain  hydrocarbon groups
are  chemically bonded  to  the column packing material resulting in a much more
reproducible separation.   The chemicals injected are moved along the column
by partitioning between the  mobile  phase  and  the stationary  hydrocarbon phase.
Provided  the residual  polar  groups  on the packing can be kept  at a minimum,
mixtures of  chemicals  can  be eluted in order  of the  hydrophobicity, with water-
soluble chemicals eluted  first and  the oil-soluble chemicals last in proportion
to their hydrocarbon/water partition coefficient. These experiments were
intended  to  determine  the  relationship of the retention time on this reverse-
phase  column and the n-octanol/water partition coefficient.


LIQUID CHROMATOGRAPHY  CONDITIONS

     The liquid chromatograph was a Varian 4200 instrument equipped with two
5,000-pai. pumps and a  high pressure stopflow,injector.   The  column was  a Varian
Micropak-'C-10 analytical  reverse phase column (250  mm  x 2 mm  I.D.) or  a
Preparative  Micropak—'C-H  column (250 mm  x 8  mm I.D.),   which  consists  of a
stainless  tube filled with 10-y  Lichrosorb to which  octadecylsilane is
permanently  bonded.  The detector was a 254-nm ultraviolet detector with a
8-yl cell  volume and 1-cm path length.  The detector was interfaced with a
Hewlett-Packard computer for retention-time determination.   For  chemicals
that cannot  be detected by the ultraviolet detector,  a  fraction collector
was used to  collect fractions  at 1.0-min  intervals for  analysis  by gas
chromatography,  liquid  scintillation,  or  other suitable techniques.

     The analytical column was operated at 50  C with a constant temperature
bath.  The solvent  was programmed from 22 percent methanol in  water initially
to 75  percent  methanol  in water  at  a rate of  2 percent/min.  The solvent
flow rate  was  maintained at  20 ml/min at  a pressure  of  approximately 2,500 psi.

     The preparative column  was  operated  at ambient  temperature.   The column
was eluted isocratically with  a  mixture of water and  methanol  (15:85, v/v)
which was  pumped through the column at 2.0 ml/min at  a  pressure  of
approximately  1,200  psi.

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TEST SOLUTIONS

     Chemicals to be tested were dissolved  in a mixture  of  acetone and
cyclohexane (3:1, v/v), which was found  to  be suitable for  compounds over a
wide range of water solubility.  Because only the  retention time of the
chemical,' which is independent of concentration in dilute solutions, is
used in this method, the quantity of individual chemicals in the solution
was adjusted to give a chromatographic peak of at  least  25  percent of the
recorder scale.


CALIBRATION MIXTURE

     Six chemicals for which Log P has been reported were used  to calibrate
the elution time in units of Log P-  The calibration mixture includes
benzene, bromobenzene, biphenyl, bibenzyl,  pp'DDE,  and 2,4,5,2',5'
pentachlorobiphenyl.  The Log P values selected from the literature for
these chemicals were 2.13, 2.99, 4.09, 4.81, 5.69,  and 6.11,  respectively.
(References for Log P values are given in Table 1.)

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                                   SECTION  5

                             RESULTS  AND  DISCUSSION


CORRELATION OF LOG P AND  HPLC  RETENTION

     Previous work at  this  laboratory  (6)  has  shown  that  the  reported  values
of Log P  for a wide variety of organic chemicals  are correlated  to  the
retention volume  of the chemical  in  the  reverse-phase HPLC  column.   The data
obtained  by using the  gradient elution with  the analytical  column (2 mm I.D.)
are  summarized in Table 1.   In this  table, the retention  volume,  K,  is
corrected for minor column  variations by using phenol as  an internal standard
and  setting its retention equal to 1.00.   The  log K  values  are presented
relative  to the K value of  phenol.

     The  Log P values  were  taken  from Leo, Hansch, and Elkins (8) except for
those of  the PCB.  Because  thesS  formulations  (the Aroclor's) consist  as
mixtures, the log K values  are presented .as  ranges of values  obtained
for  the major component peaks  observed in  the  HPLC chromatograms.   The Log P
values for PCB's  are those  provided  by Chiou et al.  (5) for PCB's   having
three to  six chlorine  atoms per molecule.  The Log P values used  for the
Aroclor's were:   Aroclor  1016  and Aroclor  1242, 5.58;  Aroclor 1248,  6.11;
and  Aroclor 1254, 6.72 (Table  1).  Although  these values  are  only approximations,
the  possible deviation must be small since the entire range for  these  PCB's
is small.

     The  data in  Table 1  were  analyzed by  a  family regression procedure as
illustrated in Figure  1.  The  data can best  be summarized by  power  function
of Log P  = a(log  K) ,  where a  and b  are  constants with r2 for the correlation
equal to  0.870.   Although this variance  may  seem  somewhat large,  the
correlation includes ketones,  aldehydes, phenols, aromatic  amines,  ethers,
aromatic  hydrocarbons, and  a variety of  chlorinated  hydrocarbons  that  span
over six  orders of magnitude of lipophilic properties.  The relationship
between Log P and log  K is  best approximated with a  power function  because
of the solvent gradient used with the analytical  column to  optimize resolution.
The  solvent gradient increases the methanol  concentration during  the analysis,
and  the retention of highly lipophilic chemicals  is  less  than that  which
would have resulted by using a constant  solvent composition.

     Having demonstrated  a  strong correlation  between Log P and  the  HPLC relative
retention time, the secondary  objectives of  developing a  simple method for cal-
culating Log P from retention  times  and  reducing  the cost of  the  analysis were
pursued.   The use of phenol as an internal standard  was judged too  tedious, and
the non-linear correlation  resulting from  the  gradient elution increased both
the cost and the complexity of the analysis.   The use of  isocratic  elution

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TABLE 1.  RETENTION DATA OF A VARIETY OF CHEMICALS  OBTAINED
     BY USING GRADIENT ELUTION REVERSE-PHASE HPLC

Chemical
Hydroquionone
m- Amino ph eno 1
Resorcinol
Catechol
Phenol
o-Amino phenol
4-Methoxyphenol
Aniline
Benzyl Alcohol
o-Toludine
4-Nitrophenol
o-Anisidine
Benzaldehyde
3-Methylphenol
2 -Ph eny 1 e thano 1
4-Methylphenol
Indole
o-Chloroaniline
Benzene
n-Methylaniline
Acatophenone
Cinnamyl Alcohol
4-Chlorophenol
Anisole
2 s 4-Dimethylphenol
Dimethylphthalate
1-Naphthol
3-Methyl-4-Chlorophenol
2 s 4-Dichlorophenol
Pentachloro phenol
4-Phenylphenol
Diethylphthalate
Naphthalene
2,4, 5-Trichlorophenol
Diphenylamine
Diphenyl ether
Anthracene
n,n-Dibutylphthalate
p,p '-Methoxyclor
Endrin
p,p'-DDD
p,p'-DDT
Hexachlorobenzene
Aroclor 1016
Aroclor 1242
Aroclor 1248
Aroclor 1254
K (phenol=1.00)
0.27
0.36
0.36
0.73
1.00
1.00
1.17
1.18
1.40
1.82
1.83
2.00
2.18
2.25
2.27
2.33
2.45
2.48
2.50
2.90
3.18
3.32
3.73
4.00
4.00
5.42
6.46
7.04
8.73
10.42
11.46
12.45
12.65
14.27
14.36
18.50
22.33
24.45
39.81
39.82
41.70
44.69
52.50
35.50-51.30
25.50-60.29
35.50-60.28
35.50-69.20
Log K
(phenol=0.00)
-0.564
-0.439
-0.439
-0.138
0.000
0.000
0.067
0.073
0.146
0.260
0.263
0.301
0.338
0.352
0.357
0.368
0.390
0.395
0.398
0.464
0.503
0.521
0.571
0.602
0.602
0.734
0.810
0.848
0.941
1.018
1.059
1.095
1.103
1.154
1.157
1.267
1.344
1.388
1.600
1.600
1.620
1.650
1.72
1.55-1.71
1.55-1.78
1.55-1.78
1.55-1.84
Log P
0.59
0.17
0.80
0.95
1.46
0.62
1.34
0.98
1.10
1.32
1.91
0.95
1.48
1.96
1.60
1,94
2.25
1.92
2.13
1.82
1.58
1.95
2.39
2.11
2.36
2.11
2.98
3.10
3.08
5.01
3.37
3.15
3.37
3.72
3.50
4.21
4.45
5.15
4.20
4.56
6.02
6.19
6.18
5.58
5.58
6.11
6.72

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                          Benzene


                    Phenol  ». •
                                                                    Methoxychlor
                                                    Naphthalene
Figure 1.
       -0.5          0.0         0.5          IO          1.5

                Log  K  (PhenohO.OO)-HPLC
Verification of the dpendency of the HPLC relative retention time on the Log P for
47 organic Chemicals.
                                                                            2.0

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resulted in a linear correlation  and  the  development  of  a simple calibration
mixture to replace the internal standard.  Although  the  analysis time increases
when the isocratic elution  is  used, substantial  savings  are possible because
it eliminates the need for  one of the HPLC pumps  and  the electronic solvent
programming module (approximately 50  percent  of  the  instrument costs).  Finally,
preparative scale reverse-phase columns produce  linear  calibration curves with
shorter overall retention times at pressures  of  only  1,200 psi.   This column
offers the additional advantage of a  larger loading  capacity which is needed
for analysis of complex  effluents.


CALCULATION OF LOG P

     The calibration mixture is chromatographed  on  the  preparative column,  and
a calibration curve is prepared daily to  eliminate  small differences due to
flow rate or temperature and to follow  the retention  properties  of the column
during prolonged use.  The  calibration  is made by plotting the Log P versus
the logarithm of the absolute  retention time  (Log RT)-   Figure 2 presents the
data from Table 2 in the form  of  the  calibration curve.   The relationship
between Log P and log RT can be fitted  equally well by  using a linear or a
parabolic function when  these  data are plotted.   However,  the linear regression
is more convenient to use in daily calculations,  and  differences between the
linear and exponential models  appear  only if  Log  P  is estimated  by extrapolating
beyond the range of Log  P values  used in  the  calibration.

     The data in Figure  2 can  be  summarized with  the  equation Log P = 5.106
Log RT - 1.258, with a correlation coefficient of 0.975.   The relative
standard deviations of the  slope,  intercept,  and  correlation coefficient of
seven calibration curves during a 2-week  period  were  approximately 1 percent,
14 percent, and 0.1 percent, respectively.  It must be  emphasized that this
correlation is limited in regard  to being representative of the  organic
chemicals encountered.   The calibration mixture  was selected largely on the
basis of Log P values reported in the literature, and the correlation appears
to be linear over five orders  of  magnitude of this  chemical property.  Although
the accuracy of the estimates  might be more convincing  if several hundred
chemicals were presented in the correlation,  it  would be unmanageable to
prepare such a calibration  mixture and use it daily in  the calibration of
the liquid chromatograph.


HPLC ESTIMATION OF LOG P

     To determine the accuracy of the calibrated  liquid  chroma tographic method
of estimating Log P by comparison with data reported  in  the literature, the
retention times of 18 chemicals,  including the standards,  were determined,  and
the Log P values'were calculated  from, the regression  equation.   Table 3 presents
the results of these estimates.   The  data show that Log  P  can be estimated with
a mean -accuracy of .22.5+20.1 percent,  of the values reported in the literature.
obtained by using other  methods.   The percent error in Table 3 was calculated
assuming that the literature value is the correct value  for Log  P.  The mean
absolute error in Log P  for this  set  of chemicals was 0.64.   This error is
approximately twice the  error  that can be expected by calculation with the
                                      10

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        TABLE 2.  HPLC RETENTION TIMES AND PARTITION COEFFICIENTS
               FOR ORGANIC CHEMICALS USED FOR CALIBRATION

Chemical
Benzene
Bromobenzene
Biphenyl
Bibenzyl
pp'DDE
2,4,5,2' ,5' penta-
chlorobiphenyl
Retention
time (min)
4.12
7.09
8.85
15.87
21.98
31.58

Log RT
0.615
0.851
0.947
1.201
1.342
1.499

Log P (ref.)
2.13
2.99
3.76a
4.813
5.69
6.11

(7)
(5)
(7)
(7)
(5)
(5)

Mean of Log P values reported.
                                   11

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substituent constants approach  (Leo, personal communication); However,  the
structure of the chemical need  not be known to estimate  the lipophilic
properties with the HPLC method.

     Table 3 also shows that some of the greatest relative errors are observed
with polar chemicals which dissociate in water.  The data indicate  that  the
dissociation of ionizable polar groups is more significant than adsorption
interactions since chemicals such as m-chlorobenzoic acid, 2,4,5-trichlorophenol,
and diphenylomine elute more rapidly than would be expected from their  respective
Log P values.  One explanation  of this observation is that these chemicals
are dissociated in the unbuffered solvent and behave, in part, as ions  in the
elution.  This may be corrected by selecting a series of buffer solvents for
organic acids and bases which assure that the chemical would be in  the
un-ionized form.  However, considerable research is required before a
rationale involving buffer systems can be evaluated with a broad range of
chemicals.
                                      13

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  TABLE 3.  COMPARISON OF ESTIMATED LOG P VALUES




WITH REPORTED LOG P VALUES FOR 18 ORGANIC CHEMICALS

Chemical Reported Log
o-Toluidine
Benzaldehyde
Nitrobenzene
p-Nitrophenol
Dime thy Iphthalate
Benzene
Indole
m-Chlorobenzoic acid
Bromobenzene
Methoxychlor
Naphthalene
Diphenylamine
2,4, 5-Tr ichlorophenol
Biphenyl
Anthracene
p , p ' -DDE
2, 4, 5, 2', 5' PCB
Hexachlorobenzene
1.32
1.48
1.86
1.91
2.11
2.13
2.25
2.68
2.99
4.20
3.41
3.50
3.72
3.76
4.45
5.69
6.11
6.18
Estimated Absolute
P Log P deviation
1.63
2.33
1.82
1.35
3.40
2.39
1.66
0.89
2.92
3.82
3.17
2.37
2.39
3.75
3.45
5.83
6.44
7.42
Mean Standard Deviation
0.31
0.85
0.04
0.56
1.29
0.26
0.59
1.79
0.07
0.42
0.24
1.13
1.33
0.01
1.00
0.14
0.33
1.24
0.64+0.54
Percentage
deviation
23.5
47.7
2.2
29.3
61.1
12.2
26.2
66.8
2.3
10.0
7.0
30.4
35.6
0.3
22.5
2.5
5.4
20.1
22.5+20.1
                        14

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                                  REFERENCES

1.  Gould, R. F., editor.  1972.  Biological Correlations - The Hansch Approach.
    Adv. Chem. Ser. #114.  American Chemical Society, Washington, D.C.

2.  Veith, G. D., and D. E. Konasewich.  1975.  Structure-Activity Correlations
    in Studies of Toxicity and Bioconcentration with Aquatic Organisms.
    International Joint Commission Publication, Windsor, Ont.  347 p.

3.  Carlson, R. M., H. L. Kopperman, and R. E. Carlson.  Structure Activity
    Relationships Applied.  See Reference 2.  p. 57-72.

4.  Neely, W. G., D. R. Branson, and G. E. Blau.  1974.  The Use of the
    Partition Coefficient to Measure the Bioconcentration Potential of
    Organic Chemicals in Fish.  Environ. Sci. Technol. j^, 1113-1115.

5.  Chiou, C. T., V. H. Freed, D. W. Schmedding, and R. L. Kohnert.  1977.
    Partition Coefficient and Bioaccumulation of Selected Organic Chemicals.
    Environ. Science & Technol.  11(5): 475-478.

6.  Veith, G. D., and N. Austin.  1976.  Detection and Isolation of Bioaccumulable
    Chemicals in Complex Effluents.  In p. 297-302.  Identification and
    Analysis of Organic Pollutants in Water (L. H. Keith, [eidtor]) Ann
    Arbor Science Publishers, Inc., Ann Arbor, Michigan.

7.  Hansch, C., and T. Fujita.  1964.  A Method for the Correlation of Biological
    Activity and Chemical Structure.  J. Am. Chem. Soc.  86: 1616-1626.

8.  Leo, A., C. Hansch, and D. Elkins.  1976.  Partition Coefficients and
    Their Uses.  Chem. Rev.  71: 525-616.
                                      15

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                                    TECHNICAL REPORT DATA
                            (Please read Instructions on the reverse before completing)
  REPORT NO.
  EPA-600/3-78-049
                                                            3. RECIPIENT'S ACCESSION NO.
4. TITLE AND SUBTITLE
    A Rapid Method for Estimating Log P for
    Organic Chemicals
             5. REPORT DATE
               May 1978  issuing date
             6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
    Oilman  D.  Veith
    Richard T.  Morris*
                                                            8. PERFORMING ORGANIZATION REPORT NO,
9. PERFORMING ORGANIZATION NAME AND ADDRESS
              10. PROGRAM ELEMENT NO.
                  IBA608
                                                             11. CONTRACT/GRANT NO.
 12. SPONSORING AGENCY NAME AND ADDRESS
 ENVIRONMENTAL RESEARCH LABORATORY-DULUTH MN
 OFFICE  OF RESEARCH AND DEVELOPMENT
 U.S.  ENVIRONMENTAL PROTECTION AGENCY
 DULUTH,  MINNESOTA  55804
55804
13. TYPE OF REPORT AND PERIOD COVE RED
    In House
             14. SPONSORING AGENCY CODE
               EPA/600/03
 15. SUPPLEMENTARY NOTES
 *University of Wisconsin-Superior, WI  54880
 16. ABSTRACT
           A rapid, inexpensive  technique based on  reverse-phase high  pressure
    liquid chromatography has been developed to  estimate the n-octanol/water
    partition coefficient of organic chemicals.  The  system consists  of a
    preparative Micro-Pak C-10    reverse-phase column eluted with a 15  percent
    water/85 percent methanol solvent flowing at 2 ml/min at room temperature.
    The  chemicals are detected  in the eluant with  a standard ultraviolet detector
    or a fraction collector system followed by appropriate analysis of  the
    fractions to determine the  retention time of the  chemical.  A linear
    calibration of the logarithm of retention time with the logarithm of the
    partition coefficient (Log  P)  is attained by using a mixture of benzene,
    bromobenzene, biphenyl, bibenzyl, pp'DDE, and  2,4,5,2',5' pentachlorobiphenyl
    as reference standards of known Log P.  Chemicals with Log P of approximately
    3 elute in less than 10 min whereas those with Log P greater than 5 elute
    after  20 min.
17.
                                KEY WORDS AND DOCUMENT ANALYSIS
                  DESCRIPTORS
                                               b.lDENTIFIERS/OPEN ENDED TERMS  C.  COSATI Field/Group
  Chromatography
  Chemical Detection
 partition coefficients
 hazard evaluation
 n-octanol/water
 Log  P
 lipid  solubility
                99A
                68D
18. DISTRIBUTION STATEMENT

    Release  to  Public
19. SECURITY CLASS (This Report)
  Unclassified
              21. NO. OF PAGES
                       24
                                               20. SECURITY CLASS (This page)
                                                 Unclassified
                           22. PRICE
EPA Form 2220-1 (Rev. 4-77)   PREVIOUS EDITION is OBSOLETE
                                                                 U.S. GOVERNMENT PRINTING OFFICE: 1978-767-140/1306

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