INTERIM PROTOCOL FOR MEASURING HYDROLYSIS RATE
        CONSTANTS IN AQUEOUS  SOLUTIONS

                      by

 J.  Jackson Ellington,  Frank  E.  Stand!,  Jr.,
      Environmental  Research  Laboratory,
     U.S.  Environmental  Protection Agency
            Athens,  Georgia,  30613

      William D. Payne,  Cheryl  D.  Trusty,
        Technology Applications Inc.,
      Environmental  Research  Laboratory
            Athens,  Georgia,  30613
      ENVIRONMENTAL RESEARCH  LABORATORY
      OFFICE OF RESEARCH AND  DEVELOPMENT
     U.S.  ENVIRONMENTAL  PROTECTION  AGENCY
            ATHENS, GEORGIA 30613

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                                DISCLAIMER

     The information in this document has been funded wholly or in part
by the United States Environmental Protection Agency.  It has been subject
to the Agency's peer and administrative review, and it has been approved
for publication as an EPA Document.  Mention of trade names or commerical
products does not constitute endorsement or recommendation for use by the
U.S. Environmental Protection Agency.
                                    11

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                                 FOREWORD

     As environmental controls become more expensive and penalties for
judgement errors become more severe, environmental management requires
more precise assessment tools based on greater knowledge of relevant
phenomena.  As a part of this Laboratory's research on occurrence,
movement, transformation, impact, and control  of chemical  contaminants,
the Measurements Branch determines the occurrence of unsuspected organic
pollutants in the aquatic environment and develops and applies techniques
to measure physical, chemical, and microbial  transformation and equilibrium
constants for use in assessment models and for development of property
reactivity correlations.

     Mathematical models are widely used in predicting the fate of organic
chemicals in lakes and streams and in soil systems.  Application of these
models requires as input the second-order and first-order hydrolysis rate
constants for chemicals containing hydrolyzable functional groups.  In
measuring these rate constants, some means is needed to ensure that the
measurements are reliable and reproducible.  This protocol specifies
complete step-by-step procedures for hydrolysis measurement to produce
the required level of reproducibility and reliability among measurements
by different investigators.

                                     Rosemarie C. Russo, Ph.D.
                                     Director
                                     Environmental Research Laboratory
                                     Athens,  Georgia
                                   in

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                                 ABSTRACT



     A detailed protocol was developed to measure first- and second-order



hydrolysis rate constants for organic chemicals for use in predicting



persistence in aquatic systems.   The protocol  delineates theoretical



considerations, laboratory experiments, and calculation procedures.



Repetitive application of the protocol  to measure hydrolysis rate



constants for four standard reference compounds over a period of 2 years



yielded coefficients of variation of less than 12% in the measurements.



     This report covers a period from October 1985 to March 1988 and  work



was completed as of January 1988.

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                               INTRODUCTION



     Under the Toxic Substances Control  Act (PL 94-469) of 1976,  the



Office of Toxic Substances (OTS) screens new chemicals proposed for



manufacture and reviews the safety of existing chemicals already  on the



market.  To assess potential  risk to human health and the environment OTS



must evaluate both effects and exposure  potential.   Transport and



transformation characteristics in ambient environments are major



considerations in assessing potential  exposure.  Essential  to transport



and transformation assessments are physical and chemical data that permit



estimation of chemical  fate either by use of mathematical  models  or other



techniques.  To obtain necessary data, OTS either requests it from



manufacturers or estimates values by comparing the  chemical  to analogous



chemicals whose properties are known.   In either case, reliable data are



necessary.  A major transformation process for many chemicals is  chemical



hydrolysis; therefore, measurements of hydrolysis rate constants  are often



required.



     In the measurement of hydrolysis rate constants, some means  is needed



to ensure that the measurements are reliable and reproducible.  Suggested



laboratory protocols for measuring hydrolysis as a  function of pH and



temperature have been published (1-3 );  however, these previously published



protocols fail to specify some of the step-wise procedures in sufficient



detail  to enhance reproducibility of measurements made by different inves-



tigators.  This report, on the other hand, provides specific guidance



in a protocol for deriving hydrolysis rate constants for use in mathematical



models to predict the fate of a chemicals in aquatic systems.  The protocol



has evolved over the past several  years  at the Environmental Research
                                   -1-

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Laboratory, Athens GA, and has been found to provide reproducible rate

constants as a function of pH and temperature.


                          KINETICS OF HYDROLYSIS

HYDROLYSIS MECHANISM

    The importance of hydrolysis as a transformation process  for chemicals

in water can be determined from data on  rate constants  and  half-lives

coupled with data describing environmental  conditions.   Hydrolysis  of

organic compounds refers to reaction of  the compound with water  in  which

bonds are broken and new bonds with HO-  and H-  are formed.  A typical

example is the reaction of an alkyl  halide  with water resulting  in  the

formation of halide ion (X-):


                  RX + HOH 	> ROH + HX (or H+,  X~)              (1)


     The rate of hydrolysis may be promoted by  the hydronium  ion (H+,

H30+) or the hydroxyl  ion (OH~).  The former is referred to as specific

acid catalysis and the latter as base mediated  hydrolysis.  These two

processes together with the pH independent  reaction  with water are  the

only mechanisms considered in this protocol. The H30+  activity  is

measured directly and the OH" activity is calculated from accurate  determi-

nation (calibration between secondary buffers)  of solution  pH.

     Some chemicals undergo an elimination  reaction:


                         H   X
                         I   I  H+, OH-  v    '
                       _ C - C	> C  = C  + HX                   (2}
                         i    '    H20    /    \


In this protocol, only the disappearance of substrate is monitored  with  no

attempts to identify mechanisms or reaction products.  Reactions represented  by

equations 1 and 2 are included in a broad definition of hydrolysis.

                                   -2-

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RATE LAWS

    In both processes referred to in the discussion of hydrolysis  mechanisms,

the rate of disappearance of the organic compound  is given  by  the  equation,


           d[C]
         ----- = kh[C] = KA[H+][C] + kB[OH-][C]  + kN'[H20][C]      (3)
            dt


where [C] is the concentration of organic and k^  is the observed  pseudo-first-

order rate constant at a specific pH and temperature; k/\ and kg are  second-

order rate constants; and k^1 the neutral  hydrolysis rate constant for the

acid, base and neutral promoted processes, respectively.  The  water  concen-

tration, because of the large excess, does not change during the reaction,

thus kf^'Ch^O] is a constant (k^).

     Equation 3 assumes each individual  rate process is first-order  in

substrate, thus k^ can be defined as:


                        kh = kA[H+] + kB[OH-] + kN                  (4)


Using the autoprotolysis equilibrium expression


                              KW = [H+][OH-]                        (5)


equation 4 may be rewritten as



                         kh = kA[H+] + -—  + kN
                          h    A                N                    (6)
Equation 6 shows the dependence of kn on  hydronium  ion  concentration  (pH)

and on the relative values of kA,  kg, and k^|.

     When the disappearance rate constants are  determined  at  pHs  3, 7,

and 11, the second-order rate constants for acid hydrolysis  and  for base
                                   -3-

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hydrolysis can be calculated by dividing the pseudo-first-order rate

constant obtained at the appropriate pH by the hydronium ion  or hydroxyl

ion activity, respectively.  The neutral contribution is determined by

solving equation 4 for kfj and substituting the observed  rate  (kn)  at pH 7

together with values for k/\ and kg.   The half-life  of a  compound at a

given pH and temperature can be calculated from equation 7, where  kn is

                                                                  [C0J
the observed rate at the given pH and temperature  and  0.693  =  In
                                                                  [CtJ

where [C0] equals concentration at time zero and [C^]  equals concentration

at 50% reaction.


                                      0.693
                               ti/2 =	                         (7)
                                        kh


CONTRIBUTING FACTORS TO HYDROLYSIS RATES

Temperature

     The effect of temperature on the rate constant for a  specific

hydrolysis process (k/\, k^, and kg) can be expressed in several ways.

The familiar Arrenhius or absolute rate theory equation was  used  in  this

protocol development


             k = A exp(-Ea/RT) or  In k = In A - Ea/RT              (8)


where A is the collision frequency term, Ea is the activation  energy, and R

is the gas constant (8.314 J/deg mol).  To determine Ea and  A  for each

hydrolytic process (acid, neutral, base), one must know the  rate  constants

for the three processes k/\, kfj, and kg at two or more  temperatures  (preferably

separated by 20°C each).  A and E are determined for each  process by plotting

In kx (X = A, N, or B) versus 1/T (T in °K) and calculating  the  slope of
                                   -4-

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the straight line through the data points (temperatures)  or by fitting

the data by regression analysis to the equation In k = In A -  Ea/RT.

     Between any two temperatures, the following  relationship  is  applicable
                                      Ea     (T2  -
                      In -----   =  ------  ---------               (9)
                          kT2          R
where TI and T2 are the respective temperatures  and  Ea  is  the  activation

energy (E/\, EN, and Eg) for the particular process  (k/\,  k^,  and  kg).

Equations 4 and 9 are used to calculate rate constants  for hydrolysis

at temperatures and pH values of interest  for environmental  assessment.

     A second effect of temperature must be considered when  using  equation

5 to calculate [OH~].  The equilibrium constant  KW increases with  temperature

and with it the activity of [OH~],   When determining [OH~] activities, the

Kw at the temperature of interest must be  taken  into account.  In  practice,

the pH is measured at the experimental temperature and,  from the measured

pH, a value for [OH"] is calculated.   The  KW at  a given  temperature is

calculated by the equation given by Harned and Owen  (4)



                        -6013.79
              log Kw =  --------  -  23.6521 log T + 64.7013       (10)
                            T


where                     T(°K) = T(°C) +  273.2

The [OH-] ion activity is then calculated  using  equation 5 and the calculated

value for kw at the experimental temperature.  The [OH"] calculated by

equation 5 is used to calculate kg by dividing the measured  pseudo-first-order

rate constant obtained at pH 11 by the hydroxide ion activity  at the

measured temperature.
                                   -5-

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pH, Buffer Catalysis



     The observed rate of hydrolysis (k^)  at any pH is described by



equation 4, where k/\ and kg correspond to  the second-order specific



acid and base rate constants and k^ corresponds to the first-order neutral



water hydrolysis rate constant.   Because of this possible pH dependence,



accurate pH data must be available for each buffer solution at  each



temperature.  The most practical way to obtain these data is to heat  a



standard buffer solution to the  desired reaction temperature and,  then, to



measure the pH of the solution using a temperature-compensating meter and



probe designed to operate in the temperature ranges of interest.



     The effects of ionic strength and buffer salts on hydrolysis  reactions



are difficult to predict:  rates can be retarded or accelerated depending



on the compound.  Generally, buffer concentrations are 5E-3P4 and compound



concentrations 1E-5M.  Dilute buffers and  the 500:1 ratio of buffer to



compound minimizes buffer catalysis.  As a check for catalysis, hydrolysis



rates can be measured over a 100-fold concentration range.   A change  in k^



greater than experimental error  indicates  catalysis by the buffer.





Solvent Composition, Metal Ions



     Cosolvents can alter the rate of hydrolysis and are to be  avoided.



If methanol or acetonitrile are  used to prepare stock  solutions,



the final concentration of either solvent  in samples should be  less than



1%.  Deionized water equivalent  to ASTM Type I should  be used to make all



solutions to minimize introduction of metal ions.
                                   -6-

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          COMPILATION AND DEVELOPMENT OF HYDROLYSIS INFORMATION
LITERATURE SEARCHES
     Several things should be considered prior to laboratory measurement of
the hydrolysis rate of any compound.   First,  the molecular structure  of  the
compound of interest must be determined.  Is  the compound an optical
isomer or stereoisomer?  What is the  correct  Chemical  Abstract  System
(CAS) number for the specific chemical  compound?  What are the  common,
trade, and IUPAC names for the compound?
     A search of the literature and computerized databases should  be  a
prerequisite to any laboratory determinations.   The most  optimistic
result from the literature search would be to find a thorough rate study
of the compound of interest enabling  prediction of a hydrolysis  rate  constant
over a wide range of pH and temperature.  Unfortunately,  literature values
from persistence studies or laboratory  mechanism studies  are often obtained
under conditions different from general  environmental  temperatures  and
pH.  The literature values may be useful,  however, in  setting pH, temperature,
and sampling times in the preliminary screening test.
     If literature values are not available,  linear free  energy  relationships
(LFERs) can be used to estimate the hydrolysis rates of closely  related
compounds.  With well  characterized classes of compounds,  LFER calculations
will permit choosing experimental conditions  for the preliminary screening  tests
that will result in reaction times appropriate for precise measurements.  The
literature search should be used as a source  for other information  about the
compound such as chemical and physical  properties (bp, mp, UV,  IR, and solubility)
and methods of chemical analysis.  Examples of sources of information
include:
                                   -7-

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1.  Manual

    a.  Merck Index

    b.  CRC Handbook of Chemistry and Physics

    c.  Kirk-Othmer Encyclopedia of Chemical  Technology

    d.  Chemical Abstracts Service (CAS)


2.  Computerized

    a.  CHEMFATE

        Syracuse Research Corporation
        Merrill  Lane
        Syracuse, NY 13210-4080

    b.  CAS On-Line (1967 to present)

        STN International
        c/o Chemical Abstracts Service
        2540 Olentangy River Road
        P.O. Box 2228
        Columbus, OH 43202

    c.  CIS

        Chemical Information System, Inc.
        7215 York Road
        Baltimore, MD 21212


     d. DIALOG

        Dialog Information Service Inc.
        3460 Hi 11 view Ave
        Palo Alto, CA 94304


STANDARD REFERENCE COMPOUNDS

     Chemical  standards of known concentration have long been used for

assuring reliability of quantitative chemical analyses, calibrating

instruments, and measuring recoveries of analytes from various matrices.

Analogous to using chemicals of known concentration as standards for

concentration measurement, chemicals whose hydrolysis constants have been

measured with established precision by one experimenter or group can be
                                   -8-

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used as standard reference compounds (SRCs) by other experimenters in



establishing and maintaining quality control  in rate measurements.



Precise measurement of established hydrolysis rate constants for SRCs



interspersed with other rate constant measurements will  help assure



reliability and comparability of the measured constants.



     Standard reference compounds are used as quality assurance standards



and as references in inter-laboratory generation of hydrolysis data.



Repetition of rate constant measurements in our laboratory for these



compounds over the course of 2 years has established baseline information



for evaluating experimental techniques and for all aspects of quality



assurance (5,6).  Four compounds were selected, one each for acid and



neutral hydrolysis, and two for basic hydrolysis (Table 1).



     Reproduction of the hydrolysis rate constants of the SRCs at the



established concentrations, pHs, and temperatures ensured that the experi-



mental condidtions were reproducible and helped evaluate the accuracy and



precision of measurements for other compounds.  Tables 2 through 5 contain



SRC rate constant data generated during laboratory determinations of  hydrol-



ysis rate constants of other cheimcals of interest.  Pseudo-first-order  hydrol-



ysis rate constants for all SRCs at various temperatures and pH and second-order



rate constants for the acidic and basic reference compound were established



from these determinations.
                                   -9-

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                  Table 1.   Standard  Reference  Compounds
Name
DL-trans-4-chlorostilbene oxide (CSO)
Benzyl chloride
Methyl -2, 4-dichlorophenoxy acetate
(2,4-DME)
Lindane
pH Range
2-5
Neutralb
8 - 9.5
9.5 - 11
Ea(kJ/mol )a
84.7±13.2
84.1±5.8
40.1±4.9
65.3±1.9
In A
37.1±5.30
45.3±2.21
22.7±1.91
27.5±0.75
a.  The activation energy  (Ea)  and  collision  frequency (In A) were determined by



    plotting the  mean  values  of either k/\, k^, or ks at each temperature in Tables



    2-5 versus 1/T (as illustrated  for lindane in Appendix J).



b.  Hydrolysis of benzyl chloride is  independent of pH in the pH range 2-12.
                                   -10-

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Table 2.  Hydrolysis Data for DL-trans-4-chlorostilbene Oxide

           Temp.             103 kha           kAb

           (°C)     pH      (min -1)	(M -1 min -1)

           23.Oc   3.13d      10.le           13.6f
                   3.12       15.5            20.4
                   2.99       12.9            12.6

           24.3    3.03       11.1            11.9

           25.0    2.89       29.5            22.9
                   2.89       35.8            27.8
                   3.05       24.4            27.4
                   3.05       22.8            25.6
                   3.05       22.8            25.6
                   3.02       17.4            18.2
                   3.02       16.1            16.8
                   3.02       19.0            19.9
                   3.10       16.9            21.2
                   2.96       18.5            16.9

           25.3    2.95       24.2            21.6
                   2.95       19.4            17.3

           28.0    3.06       14.4            16.5
                   3.06       16.9            19.4
                   3.06       14.3            16.4
                   3.06       16.9            19.4
                   3.01       21.1            21.6
                   3.01       23.7            24.2
                   3.01       20.8            21.3
                   3.07       14.6            17.1
                   3.07       14.3            16.8
                   3.10       14.9            18.8
                   3.10       14.4            18.2
                   3.13       17.4            23.5

           38.2    3.63       17.0            72.3
                   3.59       23.5            91.4
                   3.59       24.5            95.3


a.  Pseudo-first-order rate constant (kn):   the slope  of the  line from
    plot of 1n % chemical  remaining versus time.

b.  Second-order rate constant (k/\).

c.  Error of temperatures:  <75°C±0.1°C (water bath);  >75°C±1°C  (oil  bath).

d.  Error ±0.02 units all  measurements.

e.  Standard deviation of the slope (kn)  <10% for  each determination.

f.  The averages of the k/\ values at each temperature  were  used  to  calculate
    the Ea and In A in Table 1 (as illustrated for lindane  in Appendix  J).

                             -11-

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Table 3.   Hydrolysis Data for Benzyl  Chloride  (pH  7.00)a
              Temp.           104khb
              28. Oc            10.4d,e
                               12.2
                               11.1
                                9.8

              36.4             31.9
                               33.9

              42.7             70.0

              45.0             72.7
                               72.2
                               65.8
                               55.5
                               63.9
                               60.6
                               69.0
                               69.0
                               78.0
                               66.9
                               69.4

              46.0             67.0

              49.0             98.9
                               98.6

              52.9            203.0
                              191.0
                              211.0
                              216.0

              53.4            140.0
                              136.0

              53.5            154.0
a.  Error ±0.02 units all  measurements.

b.  Pseudo-first-order rate  constant  (kn):  the slope of the line
    from plot of 1 n % chemical  remaining versus time.

c.  Error of temperatures:   <_750C±0.1°C  (water bath); >75°C±1°C  (oil bath),

d.  Standard deviation of  the  slope  (kn) <10% for each determination.

e.  The averages of the values  at  each temperature were used to  calculate
    the Ea and In A in Table 1  (as illustrated for lindane  in Appendix  0).
                          -12-

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           Table 4.  Hydrolysis Data for Methyl  Ester of 2,4-D
Temp
23. Oc


25.0







28.0





31.0

45.0

45.3

48.5

70.3

PH
8.81d
8.81
8.81
8.87
8.87
9.10
9.10
9.38
9.45
9.38
9.45
9.06
9.06
9.65
9.65
9.10
9.14
8.72
8.75
8.54
8.74
8.55
8.55
8.00
8.00
7.11
7.11
104 kha
(min-1)
29. 9e
33.0
36.0
57.1
41.8
95.0
79.0
230.0
249.0
224.0
224.0
80.7
70.4
262.0
278.0
118.0
103.0
79.2
91.2
350.0
340.0
412.0
415.0
103.0
86.0
100.0
114.0
D
(M~l min~l)
541f
596
650
770
563
754
627
958
883
933
794
560
489
467
495
681
593
966
1038
2520
1547
2847
2867
2079
1731
4775
5451
a.  Pseudo-first-order rate constant  (k^):  the slope of the line from plot of
    In % chemical  remaining versus  time.
b.  Second-order rate constant (kg)
c.  Error of temperatures:   <75°C±0.1°C  (water bath); >75°C±1°C (oil bath).
d.  Error ±0.02 units all measurements.
e.  Standard deviation of the slope (k^)  <10% for  each determination.
f.  The averages of the kg  values at  each temperature were used to calculate
    the Ea and In A in Table 1 (as  illustrated for lindane in Appendix 0).
                                   -13-

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                   Table 5.   Hydrolysis Data for Lindane
Temp
22. 8C
37.0
40.0


45.0




45.3

46.0


PH
11.60d
11.29
10.92
10.01
11.20
10.31
10.45
10.37
10.37
10.37
10.71
10.71
11.08
10.98
10.98
103 kha
9.9e
40.2
23.6
22.2
40.2
18.4
20.0
14.5
14.6
14.8
33.1
36.0
83.4
78.0
71.5
!<• b
KB
(M-l min-1)
2.9f
8.7
9.8
7.4
8.7
22.5
17.7
15.4
15.6
15.8
15.8
17.2
16.3
19.2
17.6
                    85.0    8.73     51.6          272.0

a.  Pseudo-first-order rate constant (kn):   the slope  of  the  line  from plot of
    In % chemical  remaining versus  time.

b.  Second-order rate constant (kg)

c.  Error of temperatures:   <_75°C±0.1°C (water bath);  >75°C±1°C  (oil bath).

d.  Error ±0.02 units all  measurements.

e.  Standard deviation of the slope (k^)  <10% for each determination.

f.  The averages of the kg values at each temperature  were  used  to calculate
    the Ea and In A (Appendix J, Table 1).
                                   -14-

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                         TECHNIQUES AND REAGENTS
STANDARD REFERENCE COMPOUNDS (SRCs)
     The SRC hydrolysis rate constants should be determined before analysis
of any compounds of interest in order to establish  operator proficiency.
Determinations of SRC values should then be interspersed with rate constant
measurements of the chemicals of interest.   Details of chemical  analysis
and data workup are presented in subsequent sections.

TEMPERATURE CONTROL
     Reaction rates are strongly dependent  on temperature;  therefore,
the temperature should be minimized during  a run and be accurately measured.
A rule of thumb is that rates double for each 10°C  rise in  temperature,
increase by 7% for a 1°C rise, and by 0.5%  for a 0.1°C rise.   This corresponds
to an activation energy of approximately 20 kcal/mol.   Constant  temperature
baths should be used that can maintain the  temperature within ±0.02°C.  A
refrigerated bath is necessary for 0 to 30°C measurements.   An oil  bath is
required for temperatures greater than 75°C.  Temperatures  should  be
measured with American Society for Testing  and Materials (ASTM)  thermometers,
calibrated by NBS procedures and NBS certified masters, or  equivalents.

pH MEASUREMENT
     Because hydrolytic reactions can be catalyzed  by hydronium  or hydroxide
ions, accurate pH data must be available for each buffer solution  at each
temperature.  The most practical way to accomplish  this is  to heat the
standard buffer solution to the desired reaction temperature, and  then to
measure the pH of the solution.  This requires temperature  compensation,
either automatic or manual, and a pH probe  stable to varying temperatures
and accurate to ±0.02 units in the pH range 3 to 11.  The pH of  the reaction
                                   -15-

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 buffer solution should be remeasured upon  completion  of the  hydrolysis



 experiment.   If the pH has  changed  more  than  0.03  pH  units the  run  should



 be discarded.   When the observed hydrolysis  rate  (kn)  of a chemical  is



 due solely to  acid  catalyzed  or  base mediated  reaction (pseudo-first-order



 kinetics), the value of k^  will  decrease by  a  factor  of ten  for every



 change of one  pH unit toward  neutrality.  An  excellent treatise on  pH



 is found  in  Determination of  pH  Theory and Practice by Roger G.  Bates (7).





 BUFFERS



      Autoclaved (C02-free)  water is used to  prepare stock solutions  of



 buffer and subsequent dilutions.  In sealed  containers, the  0.005 M_ buffers



 hold the  pH  within  (±0.03 pH  units) for  up to  25 days.   Standard buffers



 (0.005N[)  for pH 3,  pH 7, and  pH  9 to 11  are  prepared  in the  following



 manner.



         pH 3.00  Dilute 5-ml  of  0.1 M potassium hydrogen phthalate  to 100



                  ml  with water,  adjust to  pH  3 with 0.1'M_ sodium hydroxide



                  or 0.1 M^ hydrochloric acid.





         pH 7.00  Dilute 5-ml  of  0.1 hi potassium dihydrogen phosphate to



                  100-ml with  water, adjust to  pH 7 with 0.1  hi sodium



                  hydroxide  or 0.1 _N phosphoric acid.





pH 9.00/pH 11.00  Dilute 5-ml  of  0.1 M_ dipotassium  hydrogen phosphate to



                  100-ml with  water, adjust to  pH 9 or  pH 11  with 0.1 M



                  sodium hydroxide.





      Water used in  preparing  buffers is  deionized  and autoclaved as described



 in the following section.  pH is measured  with a  pH meter accurate  to



 ±0.02 units  and equipped with a  probe capable  of  operating accurately to  85°C.





                                    -16-

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WATER



     Water must be sterile and of known electrical conductivity



(<_ 0.06 ymho or less) or electrical  resistivity (_> 16.67 mega ohms),



corresponding to ASTM Type I water described in ASTM D-1193-77, "Standard



Specification for Reagent Water."  Water meeting these requirements can



usually be attained by passing previously deionized water through ion



exchange resins to remove metal ions and a 0.2 \im membrane filter



to remove bacteria.  The water is Autoclaved for 30 min/liter and allowed



to cool before use.  Sterile water is stored in a sterile-cotton-plugged



container until used.  Sterility of water and buffer solutions before and



after hydrolysis experiments is determined from pour bacterial  plate



counts on TGE agar (8).





SAMPLING CONSIDERATIONS



    Two methods are preferred for conducting the hydrolysis rate constant



measurements.



Removal of A1 iquots



     In this method, the reaction mixture is contained in one reaction



vessel  and aliquots are withdrawn at timed intervals for analysis by a



predetermined method.  It often is convenient to stop the reaction in the



aliquot removed by some quenching technique (pH adjustment, or cooling to



2°C).  The quenched aliquot may be analyzed at the convenience of the



analyst.  If the analysis must be performed immediately, it is necessary



that the time required for sampling and analysis be the same for all



samples.  This is especially true for reactions with half-lives and



analysis times of only a few minutes.  Care must be taken to ensure that



the removal  of aliquots does not contaminate the reaction mixture or cause



losses of the reactant.



                                   -17-

-------
Ampule or Test Tube Technique
     In this method, aliquots of the reaction mixture are placed in
separate vessels.  The vessels can be sealed ampules or test tubes with
Teflon-lined screw caps.  Hydrolysis studies of volatile chemicals, long
term studies (>l week), and elevated temperature studies (M5°C) should
always be performed with flame-sealed ampuls.  Screw-capped tubes are
adequate for less volatile chemicals with a run duration of 
-------
final concentration of 1E-5M is 500-fold less than the 5E-3M buffer



solution.  The final concentration must not exceed 50% of its



water solubility.   In the case of compounds soluble only in the low



parts-per-billion (ppb) range (10"6 to 10~7 _M),  methanol  or acetonitrile,



not to exceed 1% of the final  solution, can be added to the buffer to



enhance solubility.  If the concentration of substrate must be increased



to greater than 1E-5M to achieve an analyzable concentration, the  concen-



tration of the buffer is increased accordingly to maintain the 500-fold  ratio.



The chemicals must not be heated when they are being dissolved.





                          HYDROLYSIS EXPERIMENTS



SCREENING TEST (LEVEL I)



     Laboratory experiments should be divided into three levels.   In



Level I experiments, the hydrolysis protocol  is  tested in the laboratory



by selecting and determining the hydrolysis rate constants established



for the SRCs in Tables 2-5.  Data generated in hydrolysis experiments on



the SRCs are converted to rate constants using the computation techniques



discussed below in the "Data and Reporting" section and the Appendices.



The SRC rate constant measurements are repeated  until  the desired  precision



is attained in all phases of rate constant measurement.





SCREENING TEST (LEVEL II)



     Level II experiments are screening tests to determine the approximate



half-life and dependence of hydrolysis on pH, of chemicals of interest



at pHs 3, 7, and 11 at a selected temperature.  Results from Level  II



experiments are then used to set pH and temperature for Level  III  experiments.



Level II experiments are intended to quantify the effects of temperature



and pH on the hydrolysis rate of the chemical of interest.
                                   -19-

-------
     Buffer solutions at pHs 3, 7, and 11 are prepared by following



instructions in the section above entitled "Buffers."   For each  chemical,



reaction mixtures should be prepared in each of the three buffer solutions



without the use of heat.  The chemical  concentration should be  less than



one-half its water solubility and at less than 1E-5M (see section on "Test



Chemical Solution").   The test chemical  solution is transferred  to sealed



ampules or test tubes with Teflon-lined screw caps (15-ml  tubes, 10-ml



solution).   A minimum of six tubes are prepared at each  pH.  Then based on  a



"best guess" half-life,  the tubes are placed in either a 25,  45, 65,  or



85°C constant temperature bath.  After sufficient  time to  equilibrate



(30 to 60 min), one sample is taken to determine the time  zero  concen-



tration.  The screening  test decision tree (Figure 1)  is then used to



determine sampling times for subsequent tubes.  Data are calculated



according to procedures  given in the "Data and Reporting"  section.





DETAILED TESTS (LEVEL III)



     The objective of this set of experiments is to determine k/\,  kfj,



and kg (if all  three  processes are operative) at two or  more temperatures



(separated by 20°C or more) such that activation energies  for each process



can be calculated and used to predict hydrolysis rate  constants  at  other



temperatures and pHs.  The preliminary values of k/\, k^, and  kg  calculated



according to instruction in the "Treatment of Results" section and the



screening test are used  to design the Level  III detailed tests.   Assuming



the kf| values at pH 3 and 11 are due solely to acid- and base-catalyzed



reactions (pseudo-first-order kinetics), the value of  kn will decrease by



a factor of 10 for every change of pH unit toward  neutrality.   If the k^



values at pH 3 and 11 are the same as the pH 7 value,  then hydrolysis is



independent of pH and controlled only by temperature.   Level  III experiments





                                   -20-

-------
for processes independent of pH are conducted at pH 7 and at temperatures



that result in 50-80% hydrolysis between one day and two weeks.   If



either or both acid catalysis or hydroxide ion mediated hydrolysis is



indicated in the screening test, then Level  III experiments  are  conducted



at pHs and temperatures (including pH 7) such that rate constants (first-



and second-order) and activation energies can be calculated  for  the



processes (k/\, k|\|, KB)-  Ideally rate constants would be determined at  a



constant temperature and at two or more pHs  on each side of  neutrality.



Establishment of a pH versus first-order disappearance rate  constant



curve would allow prediction of rates at other pHs.



     To quantify the effect of temperature and pH on the disappearance



rate constant for hydrolysis, two objectives must be attained:  (1)  expertise



must be established in rate constant measurements by reproducibly measuring



values for the SRCs and (2) rate constants must be replicated  (minimum  of



three) for the compounds of interest at two  or more temperatures  separated



by 20°C.  Level III experiments are set up and conducted similar to Level



II measurements.  Water, buffers, and test solutions are prepared in the



same manner as for the screening tests (6 to 8 tubes or ampules).  The



temperatures and pHs are adjusted after consideration of the screening



test results to yield experimental conditions that allow 50-80%  reduction



in concentration of the chemical in two weeks or less.  The  tubes are



removed at regular intervals and the percent remaining of the test chemical



is determined by a method of established accuracy and precision  (±5% acceptable),



     Two concentrations of chemical, differing by a factor of ten, can  be



used as a test to support the first-order kinetics hydrolytic  mechanism.



If plots of In % chemical remaining versus time are linear and have the



same slope within experimental error, then first-order kinetics  are assumed.
                                   -21-

-------
     Rate constants and activation energies are calculated by methods



outlined in the following section.





                            DATA AND REPORTING



TREATMENT OF RESULTS



Screening Tests



     An observed rate constant (kn) for the pH 3, 7, and 11 runs is



calculated by the appropriate method described in the Appendices (G-l,



G-2, H, or I).  At constant temperature, the k^ values for pHs 3 and 11



are compared to the value calculated at pH 7 for evidence of H+ or OH~



enhancement of rates.  If the observed rates are within experimental



error, hydrolysis is considered to be independent of pH in the range 3 to  11



and Level III experiments are conducted at pH 7.  The rate studies at pH



7 should be conducted at two or more temperatures to allow calculation of



the activation energy (Ea) and collision frequency (A) by the method



outlined in Appendix J.



     If kn at pHs 3 and 11 are greater than experimental  error from the



pH 7 rate, then second-order rate constants (k/\ and kg) can be calculated



from each first-order rate constant at each temperature by dividing the



measured kn at the particular pH by the hydronium ion activity (k/\,



pH 3) or hydroxide ion activity (kg, pH 11).  This calculation assumes



hydrolysis at pHs 3 and 11 are second-order reactions (first-order in



compound and first-order in hydronium or hydroxide activity).  The



effect of temperature on Kw is taken into account when using equation 5



to calculate hydroxide ion activity.



     The results of the screening tests are used to estimate the hydroysis



rate at other pH values, and are used to determine the pHs and temperatures
                                   -22-

-------
for the Level III hydrolysis rate determinations.  Assuming that the k^



values at pH 3 and 11 are due solely to acid catalyzed and base mediated



reactions the value of kn will  decrease by a factor of 10 for every



change of pH unit toward neutrality, and vary approximately by a factor



of 10 for each 20°C change in temperature (Ea = 84 kJ/mol).





Calculation of Rate Constants and Activation Energies from Level  III



Experiments



     Conditions of the Level III determinations are set (huge excess



of water, constant pH) such that the rate constant at a given pH and



temperature should be pseudo-first-order.  From equation 11 a concentration-



time profile can be expressed where [C0] is the concentration of the test



substrate at time zero and [C] is the concentration at a given time,  k  is



the first-order rate constant and t is time.





                        ln[C] = ln[C0] - kt                         (11)





Several methods can be used to calculate the pseudo-first-order disappearance



rate constant for a compound at a set pH and temperature.   The first  two



(Appendicies G-l and G-2) consist of plotting either log % chemical



remaining or 1 n % chemical  remaining on the Y-axis versus  time of sampling



(time) on the X-axis.  The slope of the best straight line drawn  through



the data points is used to derive the pseudo-first-order rate constant



also called kn (observed rate constant).  A third method used to calculate



kn is illustrated in Appendix H using the rearranged log form of equation 11.



     The last method (Appendix I) consists of processing data using the Lotus



1-2-3 software with the IBM PC/XT or equivalent.   Software programs for



slope are based on the linear least squares analysis of the In of %



chemical  remaining versus time.   Outputs from the linear regression program





                                   -23-

-------
are (1) slope (pseudo-first-order rate constant), (2)  Y-intercept,



(3) variance, (4) standard deviation (SD)  of Y-intercept,  (5)  standard



deviation (SD) of the slope, and (6) the correlation coefficient (r2).



     Marked curvature in a plot of 1n % chemical  remaining  versus  time



or a low correlation coefficient indicates that a non-first-order  process



is influencing results and that additional  experiments are  needed.   When



acid catalyzed or base mediated hydrolysis is indicated by  the screening



test, the kf\ and/or kg are calculated by dividing the  measured kn  at the



particular pH by the hydronium ion activity (k/\,  pH 3) or hydroxide  ion



activity (kg, pH 11).  This assumes that,  at pHs  3 and 11,  hydrolysis is



100% dependent on the hydronium and hydroxide ions, respectively.  The



value for k^ is calculated using equation  4 and the kn value measured for



the pH 7 hydrolysis.



     Under ideal conditions, the Level III hydrolysis  studies  are  conducted



at three temperatures (separated by 20°C each)  and the three pHs 3,  7,



and 11.  Values of k/\, k^, and kg are calculated  at each temperature.



Regression analysis using equation 8 on the three sets of three constants



at three temperatures yields values for E/\, EN> Eg, In A/\,  Ln  AN and Ln



Ag.  These values of E and A can be used to calculate  values of kx (X =



A, N, B) at temperatures of interest.  The calculated  kx values at a



particular temperature are used in equation 4 to  calculate  kn  at a



chosen pH (1^ at the particular temperature is  used when calculating [OH~]



by equation 5).  Values of A and E for each process can be  estimated by



plotting log kx versus 1/T (Arrhenius plot) and taking the  best straight



line through the data points.  The slope will equal -Ea/R with intercept



of In A.  A two point Arrhenius plot can be used  when  kinetic  data are



available at two temperatures only.





                                   -24-

-------
Extrapolation of k^, kA. k|\i, and kp Using Approximate Activation Energies





            In instances where k^, kA, k^, and ke are known/measured at



only one temperature and E and A are not known, the rates can be approximated



at other temperatures using equation 9 and assuming a value for the



activation energy (Ea).  Activation energies for the majority of compounds



fall in the range of 62.7 - 104.5 kJ/mol.  Using an Ea value of 83.6 kJ/mol



in equation 9 to extrapolate a measured k to a new temperature is  a



reasonable approximation.  The k value obtained using 83.6 kJ/mol  will  be



within a factor of three of the values obtained using 62.7 kJ/mol  or



104.5 kJ/mol  (1 kcal = 4.18 kJ).  The above values correspond to 15, 20,  and



25 kcal/mol.





                             ACKNOWLEDGMENTS



     This work was conducted at the Athens Environmental  Research  Laboratory



through the combined efforts of EPA, Technology Applications, Inc.  (TAI),



and University of Georgia (UGA) personnel.  The technical  assistance of



Miss Sarah Patman (UGA) is gratefully acknowledged.   The  assistance of



Drs. Lee Wolfe and William Steen throughout the project and including



review of this report is also gratefully acknowledged. Discussions with



Mr. William Donaldson were always fruitful and so acknowledged.  Mrs. Karin



Blankenship's effort in typing the draft and subsequent revisions  was exemplary.





                                REFERENCES



     1.  Mill, T.W., W.R. Mabey, D.C. Bomberger, T.W. Chow, D.G.  Hendry,



         and  J.H. Smith.  1982.  Laboratory Protocols for Evaluating the



         Fate of Organic Chemicals in Air and Water.   U.S.  Environmental



         Protection Agency, Athens, GA.  EPA/600/3-82/022.





     2.  Federal  Register 50:39283-39285, Hydrolysis as a Function of pH  at



         25°C.  Section 796.3500.



                                   -25-

-------
3.  Suffet,  I.H., C.W. Carter, and G.T. Coyle.  1981.  Test Protocols



    for the  Environmental Fate and Movement of Toxicants:  Proceedings



    of a Symposium of the Association of Official Analytical Chemists



    (AOAC),  October 21, 1980, Washington, DC.  G. Zweig and M. Beroza



    (eds.).  Association of Official Analytical Chemists, Washington, DC.





4.  Harned,  H.S. and R.B. Owen.  1958.  The Physical Chemistry of



    Electrolytic Solutions.  Reinhold Publishing Corporation,  New York,



    pp.  638 and 645.





5.  Ellington, J.J., F.E. Stancil Jr., and W.D. Payne.   1987.   Measurement  of



    Hydrolysis Rate Constants for Evaluation of Hazardous Waste Land



    Disposal:  Volume I.   Data on 32 Chemicals.  U.S. Environmental



    Protection Agency, Athens, GA.  EPA/600/3-86/043.





6.  Ellington, J.J.,  F.E. Stancil Jr., W.D.  Payne,  and  C.D.  Trusty.



    1987-  Measurement of Hydrolysis Rate Constants for Evaluation



    of Hazardous Waste Land Disposal:   Volume II.   Data on 54



    Chemicals.  U.S.  Environmental Protection Agency, Athens,  GA.



    EPA/600/3-87/019.





7.  Bates,  Roger G.   Determination of pH Theory and Practice.   1972.



    John Wiley and Sons,  New York.





8.  Franson, Mary Ann H., Managing Ed.  Standard Methods  for the



    Examination of Water  and Wastewater.   1985.   American Public



    Health  Association.   Washington, DC,  16  ed., Part 907,  pp.  864-865.
                              -26-

-------
       SCREENING  TEST  DECISION  TREE
                    START RUNS, PULL T(0)
                                            CONDITIONS:
                                            pH 3, 7, 11
                                            85 Degrees C
                    PULL T(1) at +1 HR
                      ANALYZE T(0), T(1)
  REPEAT RUN USING
 LOWER TEMPERATURE
 PERCENT
REMAINING
PULL T(2) at +2 HRS
PULL T(3) - T(5) at
  1 HR INTERVALS
                     PULL T(2) at +1 DAY
                     ANALYZE T(0) - T(5)
  REPEAT - PULL
2 SAMPLES PER DAY
 PERCENT
REMAININ
PULL T(3) - T(5) at
 1  DAY INTERVALS
                      PULL T(3) - T(5)
                     at 3 DAY INTERVALS
                     ANALYZE T(0) - T(5)
                     ANALYZE T(0) - T(5)

-------
                                 CONTENT
Si.mmary of Appendices

Appendix A	  .Chemical  Information Sheet

Appendix B	Linearity Data  Sheet

Appendix C	Hydrolysis Data Sheet.  - GC

Ap!"l'idix !)	Hydrolysis Data Sheet  - HPLC

Appendix E	Hydrolysis Data Sheet  - UV

Appendix F .  .  .	Summary Sheet for Rate Data

Appendix G-l  and G-2	Graphical Determination of
                                                  Hydrolysis Rate Constant
                                                  and Half-1 ife

Appendix H	Computation of  Hydrolysis Rate
                                                  Constant  and Half-life

Appendix I	Using a Linear  Regression Program
                                                  To Determine Hydrolysis Rate
                                                  Constants

Appendix J ....................  .Determination of Act'vation Energies

-------
                          APPENDICES





Example Sheets for Generation  of Data  and  Calculation  of  Rate



              Constants and  Activation Energies.

-------
                          SUMMARY OF APPENDICES





     The exhibits are intended as aids in obtaining, calculating, and



compiling data.  They are not intended as replacements for laboratory



notebooks, but yield quick access to the status of the particular chemical



under study.  The Chemical Information Sheet (Appendix A) should be



completed before any laboratory work begins.  This particularly includes



the CAS number-structure match and the purity-identity analysis of the



analytical  standard used in subsequent hydrolysis studies.   The Linearity



Data Sheet (Appendix B) is completed after the method of analysis is



determined.   Hydrolysis studies are then performed in the range of



concentrations where response versus amount of compound is  linear.



Appendices C, D, and E are used to record and summarize data  for the



three major methods of analysis used in hydrolysis rate constant



measurements.  In Appendix F the observed rate constants and  calculated



second-order rate constants are compiled according to temperature.



     Actual  determinations of rate constants from disappearance data  is



detailed in appendices G, H, and I.



     In Appendicies G-l and G-2, either log or In % chemical  remaining



versus time is plotted and the negative of the slope of the  "best  fit"



line is used to generate the rate constant.  If there is random scatter



in the points, a good method for estimating the best slope  is to first



adopt an intentional bias toward a high slope and to draw the steepest



line that could legitimately be fitted to the points.  Second,  one  should



adopt the opposite bias, and draw the line with the least steep slope



that could be fitted to the points.  Finally, one should take the average



of the two extreme slopes as the best slope of the plotted  points.

-------
     By means of equation A-l (integrated rate equation), the value of k

is computed between tg and tj, between t^ and t2, and so on,  and the

average of the resulting k values is taken as the rate constant (Appendix H)

The interval between to
                                            k

                log (a-x-j) - log(a-xj) -  	  (tj  - tj)          (A.I)
                                          2.303


and tj can be neglected if there is any doubt about the accuracy of the

initial concentration (a) or determination of zero time (t0).   In many

instances, the k value calculated between tg and  t^ is much higher than

succeeding k values.

     In Appendix I, the % chemical  remaining versus time data  were processed

on a Lotus 1-2-3/IBM PC-XT using a data entry/linear  regression program.

Values obtained from the linear regression program include the  slope

(pseudo-first-order rate constant), Y-intercept,  variance, SD  of Y-

intercept, SD of slope and the correlation coefficient (r?).   The  second-

order alkaline elimination rate constant was calculated by dividing  the

pseudo-first-order rate constants by the calculated hydroxide  ion

activity at 40°C and pH 11.2.

     Appendix J is the output from a computer program to fit temperature

dependent rate constant data to a line and obtain the Arrhenius  parameters

[collision frequency (A) and activation energy (Ea)].   The Arrhenius

plot requires plotting In k versus  the reciprocal  of  the corresponding

temperature in degrees Kelvin.  The slope of the  line is equal  to

Ea/(R) and In A is the Y-intercept.

-------
                                APPENDIX  A
                        Chemical  Information  Sheet
Chemical Abstract Service (CAS)  Number:     58-89-9
CAS Name:  Cyclohexane,  l,2,3.4,5,6-hexach1oro-,(la,  2a,  3g,  4a,  5a,



Common and Trade Names:   Lindane,  Hexachlorocyclohexane,  gamma-BHC



Source:  Research Triangle Park Repository



Structure:
Property:





Molecular Weight



Melting Point, °C



Boiling Point, °C, torr



Water Solubility, °C



Vapor Pressure



Octanol-water, Kow
Value






291



112.5-113







6.8-7.8 ppm at 25°C



20°C, 0.03mm Hg



5,250
Source
Purity Determination:
GC, GC-MS

-------
RS:
Analyst:
Compound (A-j )
     APPENDIX B

Linearity Data Sheet


  Date:
1. Stock Solution

Weight of A]_: 	
Purity of Aj:
Adjusted cone, of stock:

Date Prepared: 	
  _mg dissolved in

  _(solvent)

       Suppl ier:
2.  Standard for Retention Check

	PP_ of 	

	PP  of	
Solvent:
                     ml  of
                            PP
                                         .(AT)
                                         .(is)
Method of Analysis:  GC

Other
       HPLC
Date Prepared:

        UV
Attach copy of method to data sheet.
RS  = Run series number
Ai  = Analyte of interest
pp_ = parts per thousand, million, etc.

-------
 (Appendix B cont.)
3.  Linearity Standards
Solvent:
Standard



   1






   2






   3






   4






   5





   6





   7





   8
Cone.
                        RS:
               Extraction performed? Yes    No
Dilution Required

-------
 (Appendix B cont.)

 Data

 Std. No.                   Cone.
    1

    2

    3

    4

    5

    6

    7

   8

Conclusions:
Response

-------
                                   APPENDIX C


                           Hydrolysis Data Sheet - GC


RS:   2126	Date:   11-3-87	

Analyst:   HDP	
Compound (A-j):   Lindane
1.  Stock Solution

Weight of A-j :    10.3	mg dissolved in	10	ml

of    acetonitrile	(solvent)

Purity of A-J:      99.4%      Supplier:      RTP	

Adjusted cone, of stock:    1024	ppm

Date prepared:    10-6-87	



2.  Standard For Retention Check

  205    ppb of    Lindane	(A-j)

  206    ppb of    1,2,3- and 1,2.4-Trichlorobenzene	(IS)


Solvent:    Isooctane	   Date prepared:    10-7-87	
GC  = Gas Chromatography
RS  = Run Series Number
Ai  = Analyte of interest
PP_ = parts per thousand, million, etc.
IS  = Internal Standard

-------
(Appendix C cont.)
3. Buffer Solution
Buffer strength (cone):
Type of buffer used:
Cone, of buffer stock:
Date-water Autoclaved:
pH of buffer before addi
RS: 2126
0.005 M
KpHPOa
0.10 M. Date prepared/Autoclaved: 10-26-87
10-26-87
tion of Ai : 11.71 @ 22.5 °C
pH of buffer after addition of A, : 11.20 @ 40.0 °C
pH meter standardized at
Cone, of Ai in buffer
@ °C
pH: 7 and 11
205 ppb
Dilutions required:



                    0.02 ml  (stock)  	> 100 ml  (buffer)

-------
 (Appendix C cont.)





 4.  Extraction                                      RS:    1019-1023



 Extraction solvent:  Isooctane	



 Internal Std.(IS)   2,4-D methyl  ester	
Cone, of IS in extraction solvent:     5.25	pprn





Extract     5	ml of buffer with     1     ml  of extraction solvent



concentration in extraction solvent before dilution



                             1.0	ppm A-j



                             5.25	ppm IS





Is buffer neutralized before extraction?   Yes   X     No	





Dilutions:      0.1 ml 	> 5
Final  Cone.:       20	ppb_ Aj



                   105      ppb IS

-------
(Appendix C cont.)
5.  GC Procedure
                     GC No.
                             RS:  2126
A. Column (capillary):     J and W,  DB-5	
                       "(Supplier and code name)
Length:    15M
    Dia:
0.53mm
Coating:     DB-5
Film thickness:   5.0 micron
B.  Oven
Isothermal  - oven temp:
Program - Draw program below:
C.  Injector

Split/Splitless:

Injector temp.:
             ,.100°C
              'O-mi n "



     	   On Column:

      260       °C
                                 280°C,  3 min
                                           15°C/min    (Column compensation was used)
Injection volume (size) 	1.0

Septum purge:   N?     Flow =
                 •v-1.2
        mi croliter

             ml/min
D.  Detector

ECD:    X
NPD:
Detector temp:   325    °C

Make-up gas:    M?      Flow:

Attenuation:  2^2	>2T4
     FID:
                  27
             ml/min
Hydrogen flow:

Ai r flow: 	

Filter:
               ml/mi n
         ml/min
E. Carrier Gas

Head pressure:    3 psi	

Linear velocity:     M5    cm/sec

Flow:     ^5        ml /min
Comments on GC technique:

-------
(Appendix C cont.)

6.  Sample Data*
                RS:     2126
                    pH:  11.20 @  40.0 °C
Is Aj/IS ratio used for responses?  Yes	  No X
Method of measurement:  Area    X      Height 	  Both
Raw Data:
Samp. No.
Time(min)
        Run Temperature =
Response              X
                                             40.0
^Remaining
1.
2.
3.
4.
5.
6.
7.
8.
10:40,11-3
0 min
10.2 min
34.8
49.2
60.0
73.8
100.2

44181
40662
38384
27041
30242
10218
9807
5111
5032
3195
3270
2546
2141
746

41,076
28,641
10,012
5,072
3,232
2,344
749

100.0
69.7
24.3
12.3
7.9
5.7
1.8

Were any points discarded   Yes
List discarded points: 	
                           No  X
Give reason for discarding points:
If run was aborted, give reason for aborting the run:
Analyst:
     WDP
              Date:    11-3-87
Attach computer printout
K  =  0.0402
      min"
K2=   8.75
      min"1
T 1/2 =    17
      mi n
*Data used in Aooendices G-l, G-2, H,  and I

-------
                                   APPENDIX  D


                            Hydrolysis Data Sheet  - HPLC


 RS:                       Date:
 Analyst:
 Compound  (Ai):
 1.  Stock Solution

 Weight of A-j: 	mg dissolved in	ml of

	(solvent)



 Purity of A-j : 	  Supplier: 	
Adjusted cone, of stock: _ pp_

Date prepared: _



2.  Standard for Retention Check

_ PP_ of
       pp_ of _  (IS)
Solvent: 	  Date Prepared:
HPLC = High Performance Liquid Chromatography
RS   = Run Series Number
A-j   = Analyte of interest
pp   = Parts per thousand, million, etc.
IS~~  = Internal Standard

-------
(Appendix D cont.)

3.  Buffer Solution                         RS:_
Buffer Strength (cone.): 	M
Type of Buffer used: 	
Cone, of Buffer Stock: _ M.  Date Prepared/Autoclaved:  _
Date-Water Autoclaved: _
pH of buffer before addition of A-j :  _ @ _ °C
pH of buffer after addition of A-j :   _ @ _ °C
pH meter standardized at pH: _ and
Cone, of Ai in buffer: _ pp_
-Dilutions required:
Final Cone, of A-j for injection	pp_
Is sample neutralized before injection? Yes	  No	

-------
(Appendix D cont.)





4.  1C Procedure          RS: 	     LC No.



A. Column:         	
                      (Supplier and code name)



Length: 	cm    Dia: 	mm



Packing: 	   Particle size:  	m







B. Detector     UV: 	  Fluorescence: 	   Electrochemical



Wavelength: 	nm   Attenuation: 	



Potential: 	V   Range: 	
Excitation Wavelength: 	 nm



Emission Wavelength: 	 nm
Inj. Vol. 	ml   Flow Rate:



Pressure:
Mobile Phase:
Gradient:  Yes 	  No



Draw Gradient:
Comments on LC Procedure:

-------
(Appendix D cont.)
Sample Data
RS:
PH:
Is Aj/IS ratio used for responses:  Yes	 No_



Method of Measurement:  Area 	  Height 	
                           Both
Raw Data: Run Temperature = °C
Samp. No. Time Response
1.
2.
3.
4.
5.
6.
7.
8.
















X %Remaining
















Were any points discarded:  Yes	  No_



List discarded points: 	
Give reason for discarding points:
If run was aborted, give reason for aborting the run:
Analyst:
         Date:
Attach. Computer Printout
                     hr
                                                ,-1
           T 1/2 =
days
                             K2 =

-------
                                   APPENDIX E


                           Hydrolysis Data Sheet - UV


RS: 	    Date: 	

Analyst: 	
Compound (A-,-):
1.  Stock Solution

Weight of A-j :  	mg dissolved in	ml

of	(solvent)

Purity of A-,-:  	  Supplier: 	

Adjusted cone, of stock: 	pp_

Date Prepared: 	



2.  Standard For Retention Check

	PP_ of
Solvent: 	   Date Prepared:
UV = Ultraviolet
RS = Run Series Number
Ai = Analyte of interest

-------
(Appendix E cont.)

3. Buffer Solution                                  RS:
Buffer strength (cone):  	M
Type of buffer used:  	
Cone, of buffer stock:  _ M.   Date prepared/Autoclaved: _
Date-water Autoclaved:  _

pH of buffer before addition of Aj :  _ @ _ °C
pH of buffer after addition of A^ :   _ @ _ °C
pH meter standardized at  pH:  _  and
Cone,  of A-j  in buffer _ pp_
Dilutions required:
Final  cone, of Aj for measurement:  	pp_
Is sample neutralized before measuring?  Yes 	  No

-------
(Appendix E cont.)

4.  UV Procedure                           RS:
Reference:
Attach spectrophotometer readout and absorption curve:
Maxima found:
Comments:

-------
 (Appendix  E cont.)





 Data



 Run Temp.       	°C                  RS:
                            Absorbance Readings at Maxima




Run No.     Time






1.





2.





3.






4.






5.






6.






7.






8.





pH 	 @	° C

-------
 (Appendix  E  cont.)
Were  any  points discarded?  Yes 	   No
List discarded points:
Give reason for discarding points:
If run was aborted, give reason for aborting the run:
Analyst:  	  Date:



Attach computer printout



Kj = 	hr'1



K2 = 	M^hr'1



T 1/2 = 	days

-------
                                 APPENDIX F


  Summary of Data:


  Compound:              	.
RS        T     pH      ^(hr1)    kA(M'
  Ea =
 Method:  GC       LC  	  UV	  Other
 kfo is the pseudo-first-order rate constant measured  at  a  particular
 pH and temperature.

-------
    2.0
                                         AHPhNUIX 6-1

                                 RS  2126,  pH = 11.20, 40 C
n — i — i — PI — r
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__j_j__c 	 :
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0.44 - 1.76


88 - 14


>
w. i u (j \_ V.UX/CJ
From Equation 11:
log[C] = log[C0
-k
Slooe = 	 	


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100
120

-------
  5.0
                                        APPENDIX 6-2
                               RS 2126,  pH = 11.20, 40°C






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-------
                                APPENDIX H
 Equation  11 can be rearranged to yeild:
                           2.303
                       k =	(log[C0] - log[C])
                             t
This equation is often written as:
                           2.303
                      k  =	[log a - log(a-x)]
                            At
Where the symbol a is used to replace C0, x is the decrease of concentrati

in time t, and a-x = C the concentration at time t.
on
                             Log % Chemical
             Time(min)         Remaining           k(min~l)
               0.0                2.00
              10.2                1.84               0.036
              34.8                1.38               0.043
              49.2                1.09               0.046
              60.0                0.90               0.040
              73.8                0.76               0.027
             100.2                0.25               0.044
                                                  0.039±0.007
                          2.303
                      k = 	 [2.00 - 1.84]  = 0.036
                           10.2
                          2.303
                      k = 	 [1.84 - 1.38]  = 0.043
                           24.6
                          2.303
                      k = 	 [1.38 - 1.09] -  0.046
                           14.4
The remaining three k values are calculated in  like  manner.

-------
feO
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    0.5
                                Appendix I

             Plot of  In % Lindane Remaining vs  Time
                                                    S^i.
                    RS «2126 Lindane  pH=11.20 at 40 °C
                       i	1	1	1	1	1	1	1
Time
Minutes
0.0
10.2
34.8
60.0
73.8
100.2
In %
Remaining
4.605
4.244
3.190
2.509
2.066
0.587
                             Time (minutes)

                     RS 2126    Lindane pH =  11.20 at 40°C
                                   Number  of observations

                                   SD of Slope
                                   Slope of Regression Line
                                   Regression Coefficient
                                   SD of Y-intercept
                                   Y-intercept of Regr.  Line
                                   R SQUARED
                                   Psuedo-Kl
                                                                  120
 0.00106
-0.04023
-0.99827
 0.060419
 4.59417
 0.99685
 0.04023 min-1
               Kw = [OH-][H+L Kw at 40°C = 2.919 X  10'14

                          Kw     2.919 X ID'14
                 [OH-]  =  ---- =  ............. = 0.0046
                         [H+]    6.30 X 10-12
                           i
                                 0.04023

                                         = 8.745
                         [OH-]    0.0046
       The second-order alkaline elimination rate  constant was deter-
  mined at other temperatures and used in Appendix J to determine the
  activation  energy and collision frequency.

-------
 4 -
 3 -
 2 -
 1 -
 0.0027
Temperature
                        Appendix J
                      Arrhenius Plot
                          Lindane
                  	1	
                   0.0029
                                 0.0031
                                                 0.0033
                     I/Temperature  (K)
                 from Table  5
                                    Number of points
                                    Avg. of Y values
                                    Std. Dev. of Y
                                      Intercept
                                    Coef. of Var.  of Y
                                    SSYY1
                                    Std. Dev. of Slope
                                    Slope
                                    Regression Coef.
                                    Y-Intercept (In A)
                                    R  Squared
                                    ****Energy of  Activation****
                                    65.279 ± 1.968       kj/mol
                                    15.617 ± 0.471     kcal/mol
                                    for Arrhenius  Equation only

The above  plot is a graphical  representation  of Equation 8

                In k = In A - Ea/RT
22.8
23.6
37.0
40.0
45.0
45.3
46.0
85.0
2.90
2.70
8.70
8.60
16.10
16.50
17.40
272.00
      8
 2.5521

 0.75
 52.725
 14.486
 237
-7859.65
-0.997
 27.494
 0.9945

-------