United States      Prevention, Pesticides     EPA712-C-98-059
          Environmental Protection    and Toxic Substances     January 1998
          Agency        (7101)
vvEPA    Fate, Transport and
          Transformation Test
          Guidelines
          OPPTS 835.2130
          Hydrolysis as a Function
          of pH and Temperature

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                           INTRODUCTION
     This guideline is one  of a  series  of test  guidelines that have been
developed by the Office of Prevention, Pesticides and Toxic Substances,
United States Environmental  Protection Agency for use  in the testing of
pesticides and toxic substances, and the  development of test data that must
be submitted to the Agency  for review under Federal regulations.

     The Office of Prevention, Pesticides and Toxic Substances (OPPTS)
has  developed this guideline through  a process of harmonization that
blended the testing  guidance  and requirements that  existed in the Office
of Pollution Prevention and  Toxics  (OPPT) and appeared in Title  40,
Chapter I,  Subchapter R of the Code of Federal Regulations  (CFR),  the
Office of Pesticide Programs (OPP) which appeared in publications of the
National Technical  Information Service (NTIS) and the guidelines pub-
lished by the Organization  for Economic Cooperation and Development
(OECD).

     The purpose of harmonizing these  guidelines  into a single set of
OPPTS  guidelines is to minimize variations among the testing procedures
that must be performed to meet the data  requirements of the U. S. Environ-
mental Protection Agency  under the Toxic  Substances  Control Act  (15
U.S.C. 2601) and the Federal Insecticide, Fungicide and Rodenticide Act
(7U.S.C. I36,etseq.).

     Final  Guideline Release: This guideline  is available from the U.S.
Government Printing Office, Washington, DC 20402 on The Federal Bul-
letin  Board.   By  modem  dial   202-512-1387,  telnet   and   ftp:
fedbbs.access.gpo.gov  (IP 162.140.64.19), or  call 202-512-0132 for disks
or paper copies.  This  guideline is also available electronically in ASCII
and PDF (portable document format) from EPA's World Wide Web  site
(http://www.epa.gov/epahome/research.htm) under the heading "Research-
ers and  Scientists/Test Methods and Guidelines/OPPTS  Harmonized Test
Guidelines."

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OPPTS 835.2130   Hydrolysis as a function  of pH and temperature.
     (a) Scope—(1) Applicability. This guideline  is intended to meet test-
ing  requirements   of  both  the Federal  Insecticide,   Fungicide,  and
Rodenticide Act (FIFRA) (7 U.S.C. 136, et seq.) and the Toxic Substances
Control Act (TSCA) (15 U.S.C. 2601).

     (2) Background.  The source material used  in developing this har-
monized OPPTS test guideline are OPPT 796.3510, OPP 161-1 Hydrolysis
Studies, and OECD 111 Hydrolysis as a Function of pH.

     (b) Introduction—(1) Background and purpose,  (i) The majority
of the earth's surface  is covered by water in the form  of oceans, seas,
rivers, lakes,  streams, or ponds. As a result, chemical substances or mix-
tures  released to the environment are likely to enter aqueous media and
could undergo  transformation via hydrolysis. Hydrolysis represents the
transformation of a chemical substance by reaction with water into new
chemicals different from their precursors.  Certain  classes of these sub-
stances, upon entering aquatic media,  can undergo hydrolysis, which  is
one of the most common chemical  reactions controlling  stability and is,
therefore,  one of the principal chemical transformation pathways of these
substances in the environment.

     (ii)  Since hydrolysis  can  be  such  an important  chemical  trans-
formation pathway for certain classes of chemical substances, it is nec-
essary, in assessing the fate of these chemicals in the environment, to know
whether, at what rate, and under what conditions  a substance will hydro-
lyze. Some of these reactions  can occur so rapidly that there may be great-
er concern for the transformation products than for the parent substance.
In other cases, a chemical substance will be resistant to hydrolysis under
typical environmental conditions, while in other instances, the substance
may have an intermediate stability that can result in the need for an assess-
ment of both the parent substance and  the transformation products. The
importance of abiotic hydrolysis in aqueous media in the environment can
be determined quantitatively  from data on hydrolysis rate constants and
half-lives.

     (iii) This test guideline was developed to  determine hydrolysis rate
constants and half-lives of substances at any environmentally relevant pH
and temperature anywhere in the United States.

     (2) Definitions and units.  The following definitions apply to this
guideline:

    Hydrolysis is  defined as a chemical reaction of an organic chemical
with water such that one or more bonds are broken  and the reaction prod-
ucts incorporate the elements of water (H2O). This type of transformation
often results in the net exchange of the group X, in an organic chemical
substance RX, for  the OH group from water.  This reaction can be written
as:

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Equation 1

                     RX + HOH   	>  ROH + HX

Another result of hydrolysis can be the incorporation of both H and OH
in a single product. An example of this reaction is the hydrolysis of an
epoxide which can be represented by the reaction:
Equation 2
                        0   +   HOH   4
-j-OH

-(-OH
     Elimination reaction means the reaction of an organic chemical sub-
stance RX in water in which the X group (as HX) is lost. These reactions
generally follow the same type of rate  laws that hydrolysis reactions fol-
low, and, therefore, are also covered in this test guideline.

     First-order reaction means a reaction in which the rate of disappear-
ance of the test substance is directly proportional to the concentration of
the test substance  and is not a function of the  concentration of any other
substance present in the reaction mixture.

     Second-order reaction means  a reaction  in which the  rate of dis-
appearance  of a test  substance is directly proportional to the product of
the first power  of the  concentration of the test substance and the first
power of the concentration of another species in the reaction mixture.

     Half-life (ti/i) of a test substance means the time required for the
concentration of the test chemical to be reduced to one-half its initial con-
centration.

     pH of an aqueous  solution means  the negative decadic logarithm of
the activity of the hydronium ion in solution. For practical purposes, the
activity of the hydronium ion is taken  as  the molar concentration of the
hydronium ion [HsO+J.  Thus, pH is defined mathematically as:

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Equation 3

                    pH = -log [H30+]

    Ion product of water (K^} means the product of the activities of the
hydronium and hydroxide ions in solution. For practical purposes, the ac-
tivity of the  hydronium  ion is taken as the molar concentration  of the
hydronium ion [HsO+], while the activity of the hydroxide ion is taken
as the molar concentration of the hydroxide ion [OH ]. Thus:

Equation 4

                    Kw = [H30+][OH ]

    pKw means the negative decadic logarithm of Kw.

Equation 5

                    pKw = -log Kw

    Specific  acid catalyzed rate constant (kn or kA)  means the second-
order rate constant for the hydrolysis of a chemical catalyzed by the hydro-
nium ion (HsO+). The units of kn are in molar^1 time"1.

    Specific  base catalyzed rate constant (kon or ks) means the second-
order rate constant  for the hydrolysis of a chemical substance catalyzed
by the hydroxide ion (OH ). The units of kon are in molar^1 time L

    Neutral  water  rate  constant (kN)  means the  pseudo first-order rate
constant  for the reaction of a chemical substance with water. The units
of kN are in time"1.

    (3) Principle of the test method—(i) Rate of hydrolysis  as a func-
tion of pH at a fixed temperature. (A) At a fixed temperature, the rate
law for the hydrolysis  of a substrate RX can be put in the form:

Equation 6

-(d[RX]/dt)   =   kh[RX]   =   kH[H30+][RX]  +   kOH[OH -][RX]
+ k'N[H20][RX]

where  kn, kon, and k'N  are the second-order rate constants for acid and
base catalyzed and neutral water processes, respectively. In dilute solu-
tions, such as are encountered in this guideline, water is present in great
excess, and its concentration is, therefore, essentially  constant  during the
course of the hydrolysis reaction. At a fixed pH, the reaction becomes
pseudo first-order and the net hydrolysis rate constant kh is given by the
expression:

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Equation 7

                    kh = kH[H30+] + kOH[OH ] + kN

where kN is now the pseudo first-order neutral water rate constant. Since
this is a first-order process, the half-life (ti/i) is  independent  of the con-
centration of a test substance and is given by the expression:

Equation 8

                      ti/2 = 0.693/kh

At a fixed pH and temperature, equation 6 in this paragraph can be inte-
grated to yield the first-order rate expression:

Equation 9

                    In [Q] = - (kh)t + In [Co]

where [Co] and [Ct] represent the molar concentration of RX, the test sub-
stance,  at time zero and  t, In is the Naperian logarithm, and  kh is the
net hydrolysis rate constant.

    (B) In order to determine kh as  a function of pH, at a fixed tempera-
ture Tj,  it is necessary to obtain the values of kH,  kon, and kN in equation
7 under paragraph (b)(3)(i)(A) of this guideline. This can be  accomplished
by measuring kh at three different pH's at a fixed  temperature Tj  and solv-
ing the  three equations for kn, kon, and kN. This has been  carried out
mathematically and the results are summarized below. Equation 7, under
paragraph (b)(3)(i)(A)  of this guideline  can be written in the following
form:

Equation 10

                    kh(l) = kH[H3+]i + koH[OH-]i + kN

where i corresponds to the pH at which the  hydrolysis rate  constant kh
is measured. For the boundary conditions:

Equation 11

                         i =  1, pH = x

                         i = 2, pH = x + y

                         i = 3, pH = x + y + z.

When the lowest pH is 3 and  the increments are  at least 2— (i.e., if x>2,
y « 2, z « 2) then kn, kon, and kN are given  by the following mathe-
matical  expressions:

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Equation 12

                     kH = 10*kh(1) - 10*kh(2)

Equation 13
Equation 14

                     kN = -10ykh(i) + kh(2) - 10-zkh(3).
     (C) The  term pKw that  appears in equation  13  under paragraph
(b)(3)(i)(B) of this guideline can be calculated from equation 5 under para-
graph (b)(2)(viii) of this guideline and the following equation:

Equation 15

              logioKw = -(6014/T)-23.651ogioT  +   64.70

where  T is  the  absolute temperature in K,  T = t + 273.2, and t is the
temperature in degrees centigrade.

     (D) For 25 °C  and x = 3, y = z = 4, the pH  values for i =  1, 2,
and  3  correspond to  3,7, and 11 (using equation  11  under paragraph
(b)(3)(i)(B) of this guideline); pKw = 14.00 (using  equation 5 under para-
graph  (b)(2)(viii)  of  this guideline  and  equation 15  under paragraph
(b)(3)(i)(C) of this guideline).

     (E) To determine kn, kon, and kN  at temperature Tj experimentally,
the three pH's 3,  7,  and 11 have been chosen. It should  be noted that
the pH's need not be  precisely 3,  7, and  11, but must be close to these
pH values (e.g. pH ±0.3). However, the pH must be fixed  and measured
precisely to ±0.03 pH units. Solutions of test substance are prepared at
an initial molar concentration of 10 3 M or less in buffered distilled water
at pH's 3, 7, and 11 [Co]. The  solutions are placed in a constant tempera-
ture  bath controlled to ±0.1  °C at temperature tj(°C),  or Tj(K), and the
concentration of test substance is  measured  at regular time intervals [Ct]
to provide a minimum of 7 time points between 10 and 80 percent hydroly-
sis. Linear regression analysis of these data in equation 9 under paragraph
(b)(3)(i)(A)  of this  guideline  with t  as  the independent variable and
In [Ct]  as the dependent variable gives a slope equal to -kh. From the
exact values of the three pH's in equation  11 under paragraph (b)(3)(i)(B)
of this  guideline,  x, y, z are calculated. Using  the precise values of x,
y, and z and  the  experimental values  of  kh(i> at the three pH's (i  = 1,
2, 3) in equations 12, 13, and 14 under paragraph (b)(3)(i)(B) of this guide-
line, along  with  pKw  (calculated from  equation  5  under paragraph

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(b)(2)(viii) of this guideline and equation 15 under paragraph (b)(3)(i)(C)
of this guideline at temperature Tj), kn,  kon, and kN can be calculated.

     (F) The hydrolysis rate constant at any pH of environmental concern
at temperature  Tj  can be  calculated using  the  values  of kn,  kon, kN,
[HsO+],  and [OH ]  in  equation 7 under paragraph (b)(3)(i)(A)  of this
guideline. Finally, the half-life of the test substance can be calculated by
substituting the value of kh in equation 8 under paragraph (b)(3)(i)(A) of
this guideline.

     (ii) The rate of hydrolysis as a function of pH and temperature.
(A) In order to calculate kh at any temperature of environmental concern,
it is necessary to determine kn, kon, and kN as a function of the tempera-
ture  T [K]. This  can be accomplished by  using the Arrhenius equation
for the three different rate processes:

Equation 16

                    kH = AH exp(-EH/RT)

Equation 17

                    k0H = AOH exp(-EOH/RT)

Equation 18

                    kN = AN exp(-EN/RT)

where  AH, AOH, and AN are constants and EH, EOH, and EN correspond
to the energy of activation for the acid, base, and neutral water processes;
T is the absolute temperature in K; and R is the gas constant, which equals
1.99 x lO-3 kcal/mole or 8.31 x 10 3 kJ/mole. Equations 16, 17,  and 18
in this paragraph are conveniently transformed to the  following  expres-
sions:

Equation 19

                    In kH = In AH - (EH/R)(1/T)

Equation 20

                    In kOH = In AOH - (EOH/R)(1/T)

Equation 21

                    In kN = In AN - (EN/R)(1/T)

     (B) Paragraph (b)(3)(i) of this guideline describes a  procedure for de-
termining kn, koH,  and kN by measuring kh  at pH's  3, 7, and 11 in

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buffered distilled water at temperature Tj. These experiments are repeated
at two other elevated temperatures Tk and TI, each temperature being sepa-
rated by at least  15°C (15 K). These experiments yield kn, kon, and kN
as a function of the temperatures Tj, TK, and TI. Using these data in equa-
tions 19, 20, and 21 under paragraph (b)(3)(ii)(A) of this guideline and
linear regression  analysis, AH, AOH, AN,  EH, EOH, and  EN can be deter-
mined. For  example, for  Equation  19, linear regression analysis  with In
kh as the dependent variable and (1/T) as the independent variable yields
a slope which is equal to -(En/R) and a y-intercept equal to In AH.

     (C) With the appropriate Arrhenius constants  A and E in equations
16, 17,  and 18 under  paragraph (b)(3)(ii)(A) of this guideline, kH, k0H,
and kN, can be calculated at any environmentally relevant temperature Tm
of concern. At a fixed (pH)n of environmental concern,  [HsO+]n and
[OH ]n can be calculated;  and using these results in  equation 7 under para-
graph (b)(3)(i)(A) of this guideline along with kn, kon, and kN, kh can
be calculated for  temperatures Tm and pHn.  Using the same procedure for
other combinations of temperature and pH, kh can be computed as a con-
tinuous  function  of both pH  and  temperature within  the experimental
range. The corresponding  half-life can be calculated by using kh in equa-
tion 8 under paragraph (b)(3)(i)(A) of this guideline.

     (D) The technical support document under paragraph  (e)(2) of this
test guideline gives a complete discussion of the scientific aspects of the
kinetics of hydrolysis.  This document should be carefully reviewed before
carrying out these hydrolysis experiments.

     (4) Applicability  and specificity, (i)  There are several different com-
mon  classes of organic chemical substances  that are  subject to trans-
formation by hydrolysis. These classes of substances include alkyl halides,
epoxides, ethers,  esters, amides, carbamates, phosphoric and phosphonic
esters, lactones, and anhydrides. Processes  other  than  nucleophilic dis-
placement by water can also take place. Among these are elimination reac-
tions that exhibit kinetic behavior similar to hydrolysis and are, therefore,
also covered in this test  guideline. This  test guideline  is not applicable
to the above classes of chemicals which contain functional  groups which
ionize or protonate and are located close to the hydrolytic reaction center.

     (ii) For most test  substances, the hydrolysis experiments should be
carried out at pH's 3,  7, and  11. However,  for a few chemicals,  the rate
of hydrolysis could be  too rapid at pH's  3  and 11  so that measuring the
loss of test substance would be too  difficult. For these substances,  the
hydrolysis experiments should be carried  out at pH's 5  and/or 9 because
the rates are reduced by  approximately a factor of 100 relative to pH's
3 and/or 11. At pH's 5, 7, and 9, equations 12, 13, and 14 under paragraph
(b)(3)(i)(B)  of this guideline are still applicable. If the rates are  still  too
fast  at pH's 5 and/or 9, then the temperature should be adjusted to give
rates that are easily measured in the laboratory.

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     (c) Test procedures—(1) Test conditions—(i) Special laboratory
equipment. Special laboratory equipment shall include:

     (A) A thermostatic bath that can be controlled to 0.1  °C in the tem-
perature range 10-90 °C.

     (B) A pH meter with an accuracy of ±0.03 pH units or better.

     (C) Stoppered volumetric flasks (no grease), Mininert valves, or glass
ampoules that can be sealed.

     (ii) Purity of water. Reagent-grade water shall be used (e.g. water
meeting ASTM Type IIA standards or an equivalent grade).  ASTM Type
IIA water is described in ASTM D—1193-77 "Standard Specification for
Reagent Water."  Copies may be obtained from the American Society for
Testing and Materials, 1916 Race St., Philadelphia, PA 19103.

     (iii) Sterilization. It is required that all glassware be sterilized. Asep-
tic conditions shall be used in the preparation of all solutions  and in carry-
ing out all hydrolysis experiments to minimize or eliminate biodegradation.
Glassware can be sterilized in an autoclave or by  any other suitable non-
chemical methods.

     (iv) Temperature controls. All hydrolysis experiments  shall be car-
ried out at a temperature controlled to ± 0.1  °C.

     (v) Volatile  chemical substances. If a test substance is volatile,  it
is  extremely important to take special precautions when carrying  out hy-
drolysis experiments, especially at very high temperatures. Thus, the reac-
tion vessels must be  effectively  sealed.  Sealed tubes  or tubes with gas-
tight Mininert valves  are recommended for elevated temperature  studies.
At lower temperatures, volumetric flasks or tubes with Teflon-lined screw
caps can often be used successfully. Volumetric or  other glass-stoppered
flasks  should be used  without grease. In addition, the reaction vessel
should be almost completely filled,  and when conducting the hydrolysis
experiments, especially at elevated temperatures, it is extremely important
to  submerge the reaction vessel completely below the fluid in  the constant-
temperature bath.

     (vi) pH. (A) It is  recommended that all hydrolysis experiments be
performed  at pH's  of approximately 3, 7,  and 11  (or 10, if necessary)
but  fixed  precisely  to  ±0.03  pH  units.  Buffers  listed in  paragraph
(c)(2)(i)(A)  of this  guideline are strongly recommended. Alternatively, a
pH-stat may be used to avoid the use of buffers and thus potential prob-
lems with buffer catalysis.

     (B) In  order to measure the pH accurately,  the pH meter must be
calibrated with NBS primary and secondary standards.  In addition,  some
hydrophobic test substance could adsorb to the surface of the glass elec-
trode in the pH meter  and cause anomalous kinetic results. Hence, for

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these hydrophobic substances, the glass electrode  should  be checked for
contamination.

     (vii)  Concentration of solutions  of test substances. It is required
that the concentration of the test substance be less than one-half its solu-
bility in water and not greater than 10 3  M.

     (viii) Buffers. For  certain test  substances, buffers may catalyze the
hydrolysis reaction. If this is suspected,  then hydrolysis rate determinations
shall be carried out with the appropriate buffers and the same experiments
shall be repeated at buffer  concentrations lowered by at least a factor of
5. If the hydrolysis  reaction produces  a  change of greater than 0.03 pH
units  in the lower  concentration buffers  at the end of the  measurement
time,  then the test substance concentration shall be lowered by at  least
a factor of 5. Alternatively, test  substance concentration and buffer con-
centration may be both lowered simultaneously by a factor of 5. A suffi-
cient criterion for minimization of buffer  catalysis is an observed equality
in the hydrolysis rate constant of two different solutions differing in buffer
or test substance concentration by a factor of 5.

     (ix) Light sensitive test chemicals. The solution absorption spectrum
should be employed to determine whether a particular test  chemical is po-
tentially subject to photolytic transformation upon exposure to light. The
absorption spectrum can be obtained by using  test  guideline OPPTS
830.7050, entitled  "Absorption  in  aqueous  solution:  Ultraviolet/visible
spectra."  under paragraph (e)(3) of this guideline. For substances that ab-
sorb light of wavelengths  greater than 290 nm, it is  recommended that
the experiments  be carried out by wrapping the reaction vessels with alu-
minum foil, by  the  use of amber or red colored glassware, by the use
of amber or red safelights, or any  other suitable  technique which will
eliminate the possibility of photolytic transformation.

     (x) Substances susceptible  to  oxidation. If a test substance  is sus-
pected of being susceptible to oxidation  with air,  the  following  experi-
ments should be performed. At a fixed pH and temperature, the  rate of
hydrolysis should be determined  with  and without  purging  the reaction
solutions with purified argon or nitrogen gas. If the rate constant kh meas-
ured in the unpurged solution is faster than the rate constant in the  purged
solution, then air oxidation may be occurring and all reaction solutions
should be purged before all hydrolysis rate measurements are performed.
For volatile test substances,  the buffer solution must be purged before add-
ing the test substance.

     (xi) Chemical analysis of solutions of test substance. In determining
the concentration of the test substance in solution, the most applicable ana-
lytical method may be employed.  Chromatographic  methods are rec-
ommended because of their compound  specificity in analyzing the parent
chemical without interferences from impurities. Whenever  practicable, the

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chosen method should have a precision within ±5 percent. The test guide-
line requires  that the specific analytical technique utilized be completely
described.

    (2) Preparations—(i) Reagents and solutions—(A)  Buffer solu-
tions. (7) Prepare buffer solutions using reagent-grade chemicals and rea-
gent-grade water as follows:

    (/)  pH  3:  Use  500 mL of 0.100 M potassium hydrogen phthalate
KH(C8H4O4)  and 223  mL of 0.100 M hydrochloric  acid, diluted  to
1.000 L with water.

    (//) pH  5: Use  250 mL of  0.100 M potassium hydrogen phthalate
and 113 mL of 0.100 M sodium hydroxide, diluted to 500 mL with water.

    (///) pH  7: Use  500 mL of 0.100 M potassium dihydrogen phosphate
(KH2PO4)  and  291  mL  of  0.100  M  sodium  hydroxide,  diluted  to
1.000 L with water.

    (/v) pH  9: Use  250 mL of 0.0250 M borax (Na2B4O7) and 23 mL
of 0.100 M hydrochloric acid, diluted to 500 mL with water.

    (v) pH  11: Use  500 mL of 0.0500 M sodium bicarbonate (NaHCO3)
and 227 mL of 0.100 M NaOH,  diluted to 1.000 L with water.

    (2) Recommended buffers at other pH's are  listed  in test guideline
OPPTS  835.2110, under paragraph (e)(4) of this guideline.

    (B) Adjustment of buffer concentrations. (7) The concentrations of
all the buffer solutions  are the  maximum concentrations to be employed
in carrying out hydrolysis experiments. If the initial concentration of the
test substance is less than 10 3 M, it is extremely important that the buffer
concentrations be lowered  by a corresponding amount, e.g. if the initial
concentration of the test substance is 10 4 M, then reduce the concentration
of the buffers by a factor of 10. In addition,  for those reactions in which
an acid or  base is not  a reaction product, then use the  minimum buffer
concentration necessary for maintaining the pH within + 0.03 units.

    (2) Check the pH of all buffer solutions  with a pH meter at tempera-
ture Tj,  and adjust the pH  to the proper  value with acid or base, if nec-
essary.

    (C) Preparation of test substance solution. (7) If the test substance
is  readily soluble in water, prepare an aqueous solution  of the test sub-
stance in the appropriate buffer  and  determine  the concentration of the
test substance (Co). Alternatively,  a solution of the substance in pure water
may be  prepared and added to an  appropriate  buffer solution, and the con-
centration of the test substance may then be determined. In the latter case,
it is important that the  aliquot be small enough so that the  concentration
of the buffer  in the final solution and the pH of the solution remain essen-

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tially unchanged. Do not employ heat in dissolving the test substance. The
final concentration of the test substance shall be no greater than one-half
its solubility in water and not greater than 10 3 M.

     (2) If the test substance is too insoluble in pure water to permit rea-
sonable handling and reliable analysis, it  is recommended that the  sub-
stance  be dissolved in reagent-grade acetonitrile (or  reagent-grade ethanol
if the hydrolysis experiments are carried out at temperatures above 80 °C),
and buffer solution is then added to an aliquot of the acetonitrile (or etha-
nol)  solution. Do not employ heat to dissolve the substance in acetonitrile
(or ethanol).  The final concentration of the test substance  shall not be
greater than one-half its solubility in water and not greater than 10 3 M.
In addition, it is extremely important that the final concentration of aceto-
nitrile (or ethanol) be 1 volume percent or less.

     (3) Performance  of the test, (i) Prepare the test substance solution
as described in paragraph (c)(2)(i)(C) of this guideline at pH's of approxi-
mately 3,7, and  11. Measure the pH of each solution to + 0.03 pH units
at temperature Tj, where Tj corresponds to  the temperature of the constant
temperature bath where the  hydrolysis experiments will be carried out.
Record the exact values of the three pH's  and the temperature,  Tj, of the
constant temperature bath to 0.1  °C (0.1 K) or less. For each kinetic exper-
iment at  each pH: Measure the  initial concentration of the test  substance
(Co) in triplicate; measure the concentration of test substance in triplicate
at regular time intervals (Ct) to provide a minimum  of 7 time points  with
the extent of hydrolysis between 10 and 80 percent; and repeat each rate
measurement once.  Five of the  seven time points should  be between 20
and  70 percent  hydrolysis.  Rates should  be rapid enough so that 70 to
80 percent of the test substance hydrolyzes within 1 week.

     (ii)  If the  pH at  the  end of the concentration measurements  has
changed  by more than  0.03 units from the initial pH,  repeat the experi-
ments using a solution having a test substance concentration lowered suffi-
ciently to keep the pH variation within 0.03 pH units.

     (iii) Repeat the above experiments at two elevated temperatures, Tk
and TI each temperature separated by at least 15 K (15 °C) and separated
from Tj by at least 15 K (15 °C).

     (4) Analytical methodology. Select an analytical method that is most
applicable to  the analysis of the test substance (paragraph  (c)(l)(xi) of
this guideline).

     (d) Data and reporting—(1) Treatment of results—(i) Rate of hy-
drolysis  as a function  of pH at  a fixed temperature. The objective of
this  set of experiments  is to determine kn, kon, and kN of  the test  sub-
stance  at a fixed temperature Tj, from the  rates  of hydrolysis at the three
pH's (3,  7,  and  11).  This can be accomplished by the following steps.

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     (A) Hydrolysis  experiments shall be carried  out  at three pH's at a
fixed temperature Tj,  and the molar concentration of test substance is
measured in triplicate  as  a function of the time. These data are used to
determine kh at the three pH's (i.e., pH's  3,  7,  and 11 corresponding
to i =  1, 2,  3), and  using  these  data in  equation 9 under paragraph
(b)(3)(i)(A) of this  guideline  and linear regression analysis with  In [Ct]
as the dependent variable and t as the independent variable, the slope of
the best straight line is obtained. The slope of this line is -
     (B) From equation 1 1 under paragraph (b)(3)(i)(B) of this guideline
and the exact values of the pH's (measured precisely to 2 decimal places),
calculate the values x, y, and z.

     (C) Calculate the value of pKw at Tj from the value of log Kw from
equation  15  under  paragraph  (b)(3)(i)(C)   of  this   guideline   and
pKw = -log Kw.

     (D) Using 12, 13, and 14 under paragraph (b)(3)(i)(B) of this guide-
line  and the values of kh(i>,  kh(2), kh(3>, x, y, z, and pKw,  calculate kH,
k0H, and kN.

     (ii) Rate  of hydrolysis as a function of pH  and temperature.  The
objective of this set of experiments is to determine the rate  of hydrolysis
and half-life of the test substance at any pH and temperature of environ-
mental concern.

     (A) The rate constants kH, k0H, and kN as a function of temperature.
Hydrolysis experiments shall be carried out at three pH's at three different
temperatures  Tj, Tk, and TI  and kn, kon, and  kN are  calculated as de-
scribed in paragraph (d)(l)(i) of this guideline.  Using these  data in equa-
tions  19, 20, and  21 under paragraph  (b)(3)(ii)(A) of this guideline  and
linear regression analysis,  AH, AOH, AN, EH, EOH, and EN can be  cal-
culated. For example, consider the experimental data for kn at Tj, Tk, and
TI. Using linear regression analysis of these data in equation 19 with In
kn as the  dependent variable and (1/T) as the independent variable (with
T  in K), the  slope and y-intercept can be calculated. From equation 19,
the slope is equal to -(EH/R); EH can be  calculated using the value of  R
=  8.3 x 10 3  kJ/mole. From equation 19, the y-intercept is equal to In
AH; hence, AH can be calculated.

     (B) Rate of hydrolysis  and the half-life  in  the environment.  The
calculation of the rate of hydrolysis and the half-life of the test substance
at  any temperature Tm and (pH)n of the environmental concern can be
accomplished by the following steps.

     (7) Using equations 16,  17, and 18 under paragraph (b)(3)(ii)(A) of
this guideline and the values of AH, AOH,  AN, EH, EOH, and EN determined
above, calculate  kn, kon, and kN at any temperature Tm of environmental
concern.

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     (2) Calculate the ion product of water, Kw at Tm using equation 15
under paragraph (b)(3)(i)(C) of this guideline.

     (3) At a given (pH)n  of environmental  concern, (pH)n is equal to
-log [H3O+]n and [OH ]n  is equal to Kw/[H3O+]n. From the value of
(pH)n,  calculate  [H3O+]n, and from the value of Kw calculated from step
(2) and [H3O^ ]n, calculate [OH ]n.
     (4) Calculate kh using the values of [H3O+]n, [OH ]n, kH, k0H, and
kN in equation 7 under paragraph (b)(3)(i)(A) of this guideline.

     (5) Calculate the half-life, ti/2, by substituting the value of kh in equa-
tion 8 under paragraph (b)(3)(i)(A) of this guideline.

     (2) Test data report — (i) Test conditions. Report the following:

     (A) The name, structure, purity of the test substance, and whether
the substance absorbs light at wavelengths «290 nm.

     (B) If the test chemical absorbs light at wavelengths « 290 nm, indi-
cate the method used to eliminate photolysis.

     (C) The type of reaction vessels used.

     (D) The exact pH's and temperature used for each experiment.

     (E) The type of solvent, if used, to solubilize the test  substance and
the percent by volume.

     (F) the  initial and final pH for each experiment.

     (G) A  description of the buffers used if they are not listed in this
test guideline.

     (H) If buffer effects were observed,  described how they were mini-
mized or eliminated.

     (ii) Specific analytical and recovery procedures.  (A) Provide a de-
tailed description or reference for the analytical procedures, including the
calibration data and precision; and

     (B) If extraction methods were used to separate the solute from the
aqueous solution, provide a description of the extraction method as  well
as the recovery data.

     (iii) Test data report. Report the following:

     (A) The initial molar concentration  [C0] of test substance  for each
replicate and the  mean value for each hydrolysis experiment (i.e., at pH's
corresponding to i = 1, 2, 3, and at temperatures Tj, Tk, TI).

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     (B)  The three separate  values  of the molar concentration (Ct) and
the mean value  for each time point for each hydrolysis experiment (i.e.,
at pH's corresponding to i = 1, 2, 3, and temperatures Tj, Tk, TI).

     (C)  The value of kh(i> and the correlation coefficient for each set of
experiments at temperatures Tj, Tk, TI.

     (D)  The calculated values of kn, kon,  and kN at Tj, Tk, TI (in K)
in tabular form.

     (E)  Using the appropriate data from paragraph (d)(2)(iii)(E) of this
guideline, report the values of A and E and the correlation coefficient for
each process (e.g. AH, EH, and the correlation coefficient, etc.).

     (F)  If the compound was susceptible  to oxidation, report the  data
under paragraph (d)(2)(iii)(A) through  (F) of this guideline for the purged
solutions.

     (e) References. The following references should be consulted for ad-
ditional background information on this test guideline:

     (1) American Society for Testing  and Materials, 1973,  1983, Annual
Book of Standards, Part 31. Standard specification for water, Philadelphia,
PA.

     (2) U.S. Environmental  Protection Agency,  1993,  OPPTS 835.2130.
Technical Support Document, "Hydrolysis as a function of pH and tem-
perature."

     (3)   U.S.   Environmental  Protection   Agency.   (1993a).  OPPTS
830.7050—Absorption in aqueous solution: Ultraviolet/visible spectra.
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