-------
VII. CURRENT REJECTION RATE

     The following bar charts demonstrate the current and
historical rejection rates for each of the environmental fate
guidelines.  The historical rate does not include studies that
were submitted prior to the publication of the Registration
Standards.  None of the results reported in this section have
been tested for statistical significance, and therefore caution
should be exercised in their interpretation.  The purpose here is
not to develop an empirically defensible rejection rate value.
Rather, the intent is to use rejection rates as the best
indicator available of where additional Agency/Registrant
attention and efforts are warranted to improve the quality of the
studies.  Further caution is warranted since not all rejected
studies were required to be repeated.  In some cases, the
submission of additional, supporting data (e.g. soil
characteristics) was sufficient to upgrade the study to
acceptable.

     Figure 1 illustrates the overall rejection rate for
environmental fate guidelines, which is now estimated at
approximately 28 percent.  This is down from the overall rate of
approximately 54 percent prior to 1986.  As indicated in Figure
1, the overall rejection rate for environmental fate guidelines
has decreased by about 25 to 30 percent every two years since
1986.  While the rejection rate from pre-1986 to post-1988 has
been virtually cut in half, the post-1988 rate still remains
high.   (Note:  SRRD has a goal of reducing all rejection rates^to
10% or less.  Consequently, any rejection rate greater than 10%
is considered high.)

     Figure 2 illustrates what EPA believes is the current
rejection rate within each guideline.  The current rate refers to
all post-1988 studies that were reviewed by the EPA.  The
rejection rate  (percentage of rejected studies) is given at the
top of each guideline bar and the number of rejected studies over
the number of studies reviewed are listed inside each bar.  Some
environmental fate guidelines with an insufficient number of
studies were omitted.  These guidelines  include 161-4, 162-3,
162-4, 163-2, 163-3, 164-4, 164-5, 165-2, 165-3, 165-5, 166-1,
201-1, 202-1.

     Figure 3 illustrates the rejection  rates over time for each
guideline.  For each guideline, the rejection rates from three
time frames are listed for comparison.   The time frames include:
 (a) pre-1986  (not including information  received for Registration
Standards);  (b) from 1986 to 1988; and  (c) post 1988.  In this
figure, some guidelines have showed a continuous drop in
rejection  rates over all three time periods - 164-1, 164-2, 161-
2,  161-3  and 163-1.  Others have shown a drop from pre-1986 to
the present but the trend has not been a continuously downward
one -  165-4, 161-1.  Since no clear trend is evident, it is less

                              - 13 -

-------
certain whether these data represent improved performance in
providing acceptable quality studies for those guidelines.  Three
guidelines show rejection rates that appear to have remained
relatively constant over time - 162-1, 162-2 and 165-1.

     Figure 4 portrays the trend in the photodegradation - water
(161-2), photodegradation - soil (161-3) , leaching and
adsorption/desorption (163-1), terrestrial field dissipation
(164-1), and aquatic field dissipation (164-2) guidelines, all of
which have experienced a continuous drop in the rate of rejection
since pre-1986.

     Figure 5 illustrates rejection rates that have remained
relatively constant or increased over time.  The guidelines in
this category are aerobic soil metabolism (162-1), anaerobic soil
metabolism (162-2), and confined rotational crop (165-1) .


Summary

     Key implications that can be drawn from the following graphs
include:

     (1)  overall rejection rates in environmental fate appear to
          have gone down significantly;

     (2)  the photodegradation - water (161-2), photodegradation
          - soil (161-3), leaching (163-1), terrestrial field
          dissipation (164-1) and aquatic field dissipation (164-
          2)  guidelines have shown a continuous and substantial
          decline in their rejection rates;

     (3)  for the aerobic soil metabolism (162-1), anaerobic soil
          metabolism (162-2), confined crop rotation (165-1)  and
          bioaccumulation in fish (165-4)  guidelines, the
          rejection rate trends do not indicate substantial
          improvement;

     (4)  all of the guidelines examined still have high
          rejection rates when compared to the goal of reducing
          all rejection rates to 10% or less;

     (5)  none of the implications discussed above are based on
          statistically significant results,  and therefore
          caution should be exercised in interpreting them.
                              -  14  -

-------












r—
CD
rr*
\~/j
z










^••H
CO
c
CD
E
c
o £
•^ c
* E
LLJ £
T5 '5
^- CT
O 0
03 _C
cc ^
.2 1
« CJ
^^J ^*^^
.£, 0

(T £
i
^f
M£±
CO



hv ^;;\
I ^ i % t i 	 ^ j
O^ ':*'•• '
00 ^' ' *
CM | v^  - ""'-




i i i

00
00
- *"
CO
,
^
CD
1.1
<55 |
CD W
00 .> .2
00 0 "0
- T £§ ^
oo < "o
O) CL »-
._ LLJ 0
2 E
CO D
Q c
"co


CD
CD "2
00 +3
C3) W
~ T "°
0) ®
CD
4—
O
CD
.Q
O O O O O O c
O 00 CD ^ CN §
*~ C
(!U90J9d) 9iey uoiioafay #'

-------

















CM
£
D
OJ
l~

















,-""•"•1

"°
0
CO
cr
^m **».
n 2
.2 £-
"43 iz:
O 0
0 T3
O«^
»J
DC (U
JvT 0
00 JzS
00 CO
O) Li.
• *f*
-M 2
CO C
A "••
O (D
9; £
^•^ fen
C
^~* *™
^•i /—I
C P
0 .±
^ C
-"7 III
O "J


1,
S^
s

| |
O O O
O 00 CO






o

"5

0
c
o
o
,_
(O









V
I*
»s




\
\










•»
c
o
1
3
S
0
m
4).

•

















v^
r^
CM

s,
N


*
f^r




















r-
CN


•^5
CO

IV
1 i








-







go
CO

se s
0)
r"
S

^s
3)
r- ,
S

' h**
l[
\

\





f
*
?n

'



-





C
C

\
c :

s.
\ .. .•

\
:
1
*\ 	 |

<
*
:£



(T
^~
"^,
tr


* :
0)
in :
 i
?

\


' ' \


'X


\


\




~
>•

^ CO
>~ ^~
T—
CO
CO •£•
*" >-
CN
1
"u) tO
>. T~
fj. "*
I . ^"^ CM
^r Jr ^~ o
00 "E 0 CO«N
^ >* t^ 1 *»
CO ^
- T- ^3 ^ O
± ZZ. CO  ^ J5
•Ji T^ CO r~
CM ^ i -
tr co 5 CM tM
> T- > CO CD
T— -— ^ 
_r: CB t ^
™ U- ' v—
1 ^
IO W CO ro
to -^ .9) r- g
^~ > "§ > 5J 'r~>.
— ~~" 4- <-• — LO
CM o OT P tO
^- CM *fc £3 CD ^
J2 CO ^ S o CO
ir T— 5-J -= g •
*>• CD Q- ^^ if)
CM o E ™ tD
—~~ .CD O CD ^
*— '5r tJ "o cvT
' 1- 0 4-1 1
S « ° = S
tO CD w 03 CD
"D *- O *~
w **" io ^
(iuaoj9d)
uojioefay

-------
CD

D
     0)
     CO
    CC
4=  00
O  00
.CD  O
"5T ^"
cc  ^
«%  w
5J  o
CD  O.

    O
     2  
-------
3§
CO
00
O5
r—
03
£L
£$<

00
00
05
I
CO
CO
0)
r—
00
00
O)

10
o
O.
s^

                   £g "o  o ro O

                   7  ?  S't'to


                   | |  Iff

                   CD to  S. 75 "°
                   "D "D  i_ -— T3
                   ro  ro  o ^~ ~^
 TO O)
 CD  CU
T3  XJ

2  5
 O  O

if  f
  CN  CO

          ro
         _
          o
                o
               CN
  r-  r- CO •<* "*
  CO  CO CO CO CO
o
o
                               o
                               oo
                                                                              CNI

                                                                              4
                                                                              CO
                                                                              CD
                                                                                  CD
                                                                                  JQ

                                                                                  E
                                                                              _  D
                                                                              T  z
                                                                              C^O  co
                                                                              CD  -i
                                                                              r—  CD
                                                                                             00
                                                                                               I


                                                                                             CO
                                                                             CM
                                                                               i

                                                                             5
o
CO
                                                       o
                                                       CM
                                                        T3
                                                         0)


                                                        _OJ


                                                         CD


                                                         W
                                                                                     D
                                                                                     +-•
                                                                                     co
                                                                                     o
                                                                                     .0),
                                                                                     'cF

                                                                                     CO
                                                                                     •i-j
                                                                                     CO
                                       (j.uaojad)
                                        uouoafay
-------
LU
      O
                    CO
                    00
                     03
                  o
                  -Q
                          CO
                          00
        CD
        CO
        0)
                     c Q.
                  c S 2
                  1=5°
                  = -Q "7S
   2 §
   CD O
   E 'g
    o .2
.•=  W EC

8£S
.2 •§ E
o  %« ^~
o  * t«-
t.  ro c
CD  c o
< < O

^ 
-------
VIII. REJECTION FACTORS

     Rejected studies, that were submitted to fulfill
Environmental Fate data requirements, were analyzed to determine
the most common reasons for rejection of studies.  To accomplish
this, EFED scientists catalogued the rejection factors, then
explained why each study deficiency was critical, causing the
study to be found unacceptable.  The rejection factors for each
guideline are listed according to the frequency of their
occurrence.

     Specific references to EPA guidance documents addressing
each rejection factor are given.  The guidance documents_were
also analyzed to determine if the registrants had sufficient
available information to avoid the specified deficiency.  A list
of all guidance documents available for environmental fate
studies is provided in the Appendix.

                 GUIDELINE 161-1 HYDROLYSIS STUDY


jU_   Re-iaction Factor;   A material balance was not provided.

     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 44.

          Standard Evaluation Procedure  (SEP) for Hydrolysis
          Studies.  (June  1985), pages 11 & 12.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December  1989), pages C-280.

     The term  "material balance" measures  the quantity  of a
chemical and its degradates in  a defined system based on total
radioactivity  and/or  other recognized analytical methodology.
The  material balance  is a measure  of how completely the applied
radioactivity  was recovered in  the end products.  This  study  is
designed to measure the hydrolysis of a pesticide in water and
the  formation  and decline of the degradates.  This is achieved by
measuring the  test  substance applied at the beginning of the
experiment and then accounting for it at the end of the
experiment.  The purpose  of this measurement is  to verify that
all  degradates formed are isolated and that an accurate rate  of
hydrolysis is  calculated.  A good  material balance  (90-110%)  is  a
prerequisite  for any  valid  laboratory study.

      Industry  Comment

      Industry  agrees  that acceptable mass  balance  is  needed  for  a
 study to  be  considered valid.   If  there  is no  attempt to provide

                              - 20 -
-------
                                                         Hydrolysis (161-1)

a mass balance or if a significant amount of the starting
activity is not accounted for, the study should be rejected.  The
EPA should be flexible on the definition of acceptable mass
balance, however.  For example, an extremely low solubility
compound which is stable under the conditions of the hydrolysis
study, may well show a reduced mass balance over the period of
the study due to adsorption to surfaces of the test vessel which
can be difficult to quantify precisely.  Hence, rejection should
only occur when there is a gross loss of mass balance.

     Industry Recommendation;  The EPA should be flexible on  the
definition of acceptable mass balance.  Rejection should only
occur when there is a gross loss of mass balance without adequate
explanation.

     EPA Response

     The Agency continues to believe that 90-110 % accountability
should be viewed as an ideal target range. However, the Agency
recognizes that in many cases this is not possible and,
therefore, has assessed the material balance within the context
of the entire study, and has not routinely rejected studies
solely on the basis of low material balance.


2_-_   Rejection Factor;   The study was not conducted in the dark.

     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines (1982),
          page 44.

          Standard Evaluation Procedure (SEP)  for Hydrolysis
          Studies. (June 1985), pages 8 & 10.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989),  pages C-280.

     The hydrolysis study is designed to provide the rate of
hydrolysis of the parent compound,  rates of formation and decline
of hydrolysis products,  and the identity of the hydrolysis
products.  Since photolysis of organic compounds can occur under
normal laboratory lighting conditions, the hydrolysis study
should be conducted in darkness.
                              -  21  -
-------
                                                        Hydrolysis (161-1)
     Industry Comment
     Industry agrees that the elimination of photolysis as a
potential source of degradation in the hydrolysis study is a
basic requirement.

     EPA Response

     No comment.
3.   Rejection Factor;
The study duration and number of
sampling  intervals were insufficient to
establish the decline and half-life.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 45.

          Standard Evaluation Procedure  (SEP) for Hydrolysis
          Studies.  (June 1985), pages 8  &  12.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989), pages C-280.

     Data should be collected until the  decline of the  test
substance and the formation and decline  of degradation  products
are clearly  characterized or for  a duration of 30 days, whichever
comes  first.  The purpose of this is to  assess the kinetics of
pesticide degradation and the formation  and degradation of its
metabolites.  This  information is used to  calculate  a half-life
for the pesticide and predict how long the pesticide and  its
metabolites  will persist in the environment.  If the duration of
the study is not long enough and  does not  have sufficient
sampling points, the confidence in the calculated half-lives  will
be greatly diminished as will the certainty that all degradation
products have been  formed and identified.

     Industry comments

     Industry believes  that appropriate  sampling intervals are
not well defined for the hydrolysis  study. We suggest  that the
study  should continue through two half-lives  or 30 days,  which
ever is shorter.   Samples should  be  taken  at  initiation of the
experiment and  at  least 6 other intervals.  If less  than  10%  of
the chemical has hydrolyzed after 30  days, then it should be
considered stable  to hydrolysis and  analysis  of samples from  the
earlier  intervals  should not  be required.
                              - 22 -
-------
                                                         Hydrolysis (161-1)

      Industry Recommendation;   Industry recommends that the
 Agency clarify the sampling intervals required for the hydrolysis
 study.   We suggest that the study should continue through two
 nalf-lives or 30 days,  which ever is shorter.   Samples should be
 taken at initiation of  the experiment and at least 6 other
 intervals.   If less than 10% of the chemical has hydrolyzed after
 30  days,  then it should be considered stable to hydrolysis and
 analysis of samples from the earlier intervals should not be
 required.

      EPA Response

      EPA agrees that if less than 10% of the chemical has
 hydrolyzed after 30 days,  then  it should be  considered stable to
 hydrolysis.   However, the occurrence of a clear single degradate
 would require identification at lower levels.   Higher
 temperatures  could also be used to demonstrate the stability of
 the chemical.   With reference to sampling intervals,  samples
 should  be taken on a schedule defined by the nature of the
 chemistry involved (e.g.,  chemicals with short half lives may
 require that  numerous early samples be taken,  while more  stable
 chemicals may require fewer early samples, but more intense later
 sampling).  Where little or no  degradation of  the chemical
 occurs,  three sampling  points of 0,  15,  and  30 days would be
 sufficient  to determine the stability of the chemical.
4_!_   Rejection Factor;   It was not specified that the buffer
                         solutions were sterile; therefore, it
                         could not be determined if degradation
                         was due to hydrolysis or biotic
                         processes.

     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines (1982),
          page 45.

          Standard Evaluation Procedure (SEP) for Hydrolysis
          Studies. (June 1985), pages 5.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), page C-280.

     The ^ hydro lysis study is conducted to determine the rate, of
hydrolysis of the active ingredient, rates of formation and
decline of hydrolysis products and the identity of the hydrolysis
products.   It is therefore essential to ensure the sterility of
                              -  23  -
-------
                                                        Hydrolysis (161-1)

buffer solutions and glassware so that the results of the study
are not affected by microbial degradation.

     Industry Comments

     Industry agrees that the equipment and solutions used in
this study should be sterilized at the initiation of the study to
prevent competing microbial degradation.  It is impractical to
require demonstration of sterility throughout the study period,
however.  In addition, if screening studies have shown that the
chemical does not degrade microbially, then sterile condxtions
should not be required.

     Industry Recommendation: The Agency should continue to
require sterilization of the equipment and solutions used in this
study but should not require demonstration of sterility
throughout the study.  Also, sterility should not be required
where screening studies have shown that biodegradation does not
to occur under the conditions of the  study.

     EPA Response

     EPA agrees with industry.  A study in which no degradation
was observed should never be rejected solely on the basis of
failure to prove sterile conditions.  However, reasonable efforts
should be made to assure that sterile conditions are maintained
throughout the study.
 5.   Re-iection  Factors;
The test substance was not
characterized.
      EPA Guidance on this  Factor

           Subdivision N: Environmental  Fate Guidelines  (1982),
           page 44.

           Standard Evaluation Procedure (SEP)  for Hydrolysis
           Studies.  (June 1985), pages 5 & 7.

           FIFRA Accelerated Reregistration Phase 3 Technical
           Guidance. (December 1989),  pages C-280 & C-282.

      Characterization of the test substance involves determining
 the identity and the purity of test substance to ensure that the
 right chemical is being tested and that the impurities  in the
 test substance do not affect the  results of the study.
                              - 24 -
-------
                                                         Hydrolysis (161-1)
     Industry Comments
     Industry agrees that adequate characterization of the test
substance should be a requirement for a valid study.  Industry
suggests that a radiopurity of 95% should be acceptable in most
cases and we would like the Agency to confirm this.

     Industry Recommendation:  No study should be initiated with
a test substance which has not been adequately characterized.  In
using this rejection factor however, the Agency should be
specific in delineating what exactly is deficient with respect to
test substance characterization.  Further, the Agency should
specify what is acceptable radiochemical purity.  Industry
recommends that a radiopurity of 95% should be considered
acceptable unless adequate justification for lower purity is
provided by the registrant.

     EPA Response

     For laboratory studies conducted with radiolabeled
chemicals, the use of a test substance with low radiopurity may
unnecessarily complicate the identification of degradation
products since the fate of the parent and its degradates is
followed by monitoring the radioactivity.

     Industry should strive for the highest possible radiopurity
but not less than 95%.  The Agency understands that achieving a
high level of radiopurity may depend on the chemical
characteristics of the specific compound and on the type of
radioisotope used. The Agency further acknowledges that some
chemicals may require extensive preparation in order to achieve
this high level of radiopurity, and has previously concurred with
time extensions for submission of data to allow for such
preparation. The Agency has also previously accepted the use of
lower purity radiochemicals with adequate justification as to why
higher radiochemical purity could not be achieved.
     Renection Factor;
The incubation temperature was not
maintained.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines (1982),
          page 45.

          Standard Evaluation Procedure (SEP) for Hydrolysis
          Studies. (June 1985), pages 7 & 9.
                              -  25  -
-------
                                                        Hydrolysis (161-1)

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), page C-280 & C-282.

     The temperature of the hydrolysis reaction must be precisely
controlled, since one major purpose of the study is to determine
the hydrolytic rate, which may vary unpredictably if the
temperature is uncontrolled.  A variation in the temperature of
as little as 1°C may lead to an error in the measurement of the
hydrolytic rate of as much as 10%.

     Industry Comment

     Industry agrees that the control of temperature in the
hydrolysis study is critical to the validity of the study.  The
incubation temperature should be controlled to ±2-3°C as
specified by the Agency.  However, where there is slow, or no
hydrolysis, this should not be sufficient reason to reject a
study.  In addition, if the decline curve is linear with a
reasonable correlation coefficient  (r2) ,  some minor temperature
deviation should be acceptable.

     Industry Recommendation; The Agency should continue to
require careful temperature control for this study but should be
flexible where deviations are minor and do not affect the
determination of the hydrolysis rate.  Careful temperature
control is also much less important where the hydrolysis rate is
very slow.

     EPA Response

     Industry should strive to maintain a constant temperature of
±1°C.  Minor deviations from this range would not automatically
be a cause for rejection of the study, but would be taken into
account on a case-by-case basis (especially if little or no
hydrolysis occurred).  Since wide variations in temperature would
almost certainly affect the measured rate of hydrolysis, the
Agency continues to believe that this parameter must be well
controlled in order for the study to generate reliable data.
7.   Re-iection Factor;
Insufficient data were presented to
support the reported conclusion.
     This issue does not normally result in the rejection of a
study, and it is usually repairable by the submission of
additional data.
                              - 26 -
-------
                                                         Hydrolysis (161-1)
      Industry Comment
      Industry agrees that conclusions based on scientifically
 sound data should required.

      EPA Response

      No comment.
 JL-.   Re-iection Factor;
Degradation curves and regression
analysis were not provided.
      This  issue  does  not normally result in the rejection of a
 study,  and it  is usually repairable  by the submission of
 additional data.

      Rejection factors  (7 &  8)  relate  to basic  information
 required by the  agency.   The information pertains  to  important
 study parameters that must be reported so that  a technical
 evaluation of  the data  can be made.

      Industry  Comment

      Industry  agrees  that .degradation  curves and regression
 analysis are important  conclusions of  the study and should be
 provided,  except  where  extremely  slow  or no degradation  was
 observed.

     _Industry  Recommendation:   The Agency should continue  to
 require this information  except in cases where  hydrolysis  did not
 reach 10%  within  30 days,  in which case  the compound  should be
 considered hydrolytically stable.

     EPA Response

     EPA agrees that  if less  than 10%  of  the chemical has
hydrolyzed  after  30 days,  then  it should  be considered stable  to
hydrolysis.  However, the  occurrence of  a clear  single degradate
would require  identification  at lower  levels.  Higher
temperatures could also be used to demonstrate the stability of
the chemical.  With reference to sampling intervals, samples
should be taken on a  schedule defined by the nature of the
chemistry  involved (e.g., chemicals with short half lives may
require that numerous early samples be taken, while more stable
chemicals may require fewer early samples, but more intense later
sampling).   Where little or no degradation of the chemical
occurs,  three sampling points of 0, 15, and 30 days would be
sufficient to determine the stability of the chemical.
                             - 27 -
-------
                                                        Hydrolysis (161-1)
     Additional Industry Comments Hydrolysis Studies
     Co-solvent concentrations sufficient to solubilize the test
chemical should be permitted.  Hydrophobia chemicals may not be
sufficiently soluble in water to allow the experiment to be
conducted with <1% co-solvent.

     EPA Response

     The Agency agrees that conducting a Hydrolysis study with
extremely insoluble compounds may not always be feasible.
However, the Agency is concerned that the use of extreme measures
to solubilize the pesticide  (greater than 1% co-solvent) may
result in unreliable data due to pesticide-solvent interactions
which may impact the hydrolysis rate as well as the types of
degradates formed.  Therefore, the use of co-solvents should be
avoided when possible.  Instead, the pesticide concentration
selected for this study should be within the compound's
solubility limit.  In some cases, this will require that more
sensitive analytical methods be developed.
                               -  28  -
-------
                                                 Photodegradation in Water (161-2)


       GUIDELINE 161-2   PHOTODEGRADATION STUDIES IN WATER
1.   Reiaction Factor;
The light source was not adequately
characterized and was not compared to
sunlight.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 48.

          Standard Evaluation Procedure (SEP) for
          Photodegradation in Water Studies. (June 1985), pages
          5, 8, 9, & 10.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), pages C-284 & C-286.

     The light source used for sample irradiation may be either
natural or simulated sunlight.  If natural sunlight is used, a
record of its intensity and wavelength distribution is required
in addition to other major variables which affect incident light
such as the time of exposure, latitude, time of year and
atmospheric cover.  If an artificial light source is used, its
intensity, wavelength distribution and the length of exposure
should be comparable to sunlight, as the rate of photolysis is
dependent on these factors and will vary if the artificial light
source is different from sunlight.  It has been our observation
that, of the currently available artificial light sources, the
xenon arc lamp best simulates natural sunlight in both wavelength
distribution and intensity.  Therefore, the Agency currently
prefers this light source over other artificial lamps.  The
Agency will consider the suitability of any future light sources
as they become available.

     Industry Comment

     Industry agrees that adequate characterization of  any light
source and  its comparison to natural sunlight is critical to
photolysis  studies.  It would be helpful if "natural sunlight"
could be defined more precisely.  We suggest that sunlight be
defined as  the solar irradiance at 40° North Latitude,  as shown
in the EPA  Mean Solar Data Table  (EPA Chemical Fate Test
Guidelines, 1983, Photolysis in Aqueous Solution in Sunlight, CG-
6000, Office of Toxic Substances, Office of Pesticides  and Toxic
Substances, U.S. Environmental Protection Agency).
                              - 29 -
-------
                                                 Photodegradation in Water (161-2)

     Irradiation equivalent to  30 days  exposure to  standard
sunlight should be acceptable.   For  example,  420 hours  of
continuous irradiation  from a source that  simulates sunlight
would be equivalent to  a  30 day exposure to sunlight with  a
photoperiod of 14 hours.

     Industry Recommendation;   We would like  the Agency to define
standard sunlight and we  suggest that sunlight be defined  as  the
solar irradiance at 40° North Latitude.  We also suggest that
continuous irradiation  equivalent to 30 days  exposure to standard
sunlight should be acceptable for the aqueous photolysis study.

     EPA Response

     Historically, guidance suggested that the light source
parallel that in the intended use area, at the anticipated time
of the year when the pesticide  would normally be applied.  As
noted above, this may have led  to inconsistent studies  which
could not be compared one to the other.  This would seem to be in
conflict with our goal  to utilize "standardized" testing which
would allow comparisons between chemicals.

     Using standardized sunlight with solar irradiance  at  40°
North Latitude is an idea which, although not accounting for
variations in season and natural lighting conditions, may
nevertheless prove more consistent in predicting photolytic
effects.  The Agency is considering  whether or not  this should be
implemented.  In addition the Agency is also  considering when
quantum yield calculations may  be used  to allow the  extrapolation
of the laboratory results to other locations  and times  of  year.
Also the suggested continuous irradiation equivalent to 30 days
exposure to natural sunlight or  420  hours of  continuous
irradiation from a source that  simulates sunlight also  appears to
be a workable alternative to current practice.


2.   Rejection Factor;   Degradates were not  identified.

     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 48.

          Standard Evaluation Procedure (SEP)  for
          Photodegradation in Water  Studies.   (June 1985), page 8.

     -    FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989),  pages C-284.
                              -  30  -
-------
                                                 Photodegradation in Water (161-2)

     Identification of residues present at levels greater than or
equal to 0.01 ppm or 10% of applied, whichever is less, is a
critical element of the aqueous photolysis study.  One primary
purpose of this study is to identify the photodegradates formed
after incubation of the active ingredient in water.  Failure to
identify one (or more) significant metabolites limits the
understanding of the aqueous photolysis under actual use
situations; hence the environmental fate of the pesticide is
unclear.

     Industry Comment

     The Agency's comments (above) are not consistent with the
referenced guidance documents.  Failure to identify compounds
present at 10% of applied should be a reason to reject a study
unless the author can present valid reasons as to why this could
not be achieved.  There is NO valid justification for requiring
registrants to identify compounds at greater than 0.01 ppm and
there is no mention of this requirement in any of the guidance
documents.

     The purpose of this study is to identify the major
photoproducts and these have been defined at those produced in
yields of >10% of the applied test material.  There is no
justification for introducing a 0.01 ppm requirement.

     Industry Recommendation:  Photoproducts produced in yields  '.
of >10% of the applied test material should be identified in this
study unless the registrant can present valid reasons as to why
this could not be achieved.

     EPA Response

     The Agency agrees and will require the identification of all
residues equal to or greater than 10% of the dose rate.  The dose
rate is defined as that applied concentration of the test
substance which does not exceed the solubility limit of the
pesticide in water and is <250 ppm.  This level of residue
identification should provide adequate information for most
chemicals.

     The 10% criterion is a general guideline.  The registrant is
expected to identify single degradates present at concentrations
approaching 10% of the dose rate.  In addition, degradates of
known toxicological or ecotoxicological concern must certainly be
identified and quantified even if they are present at <10% of the
dose rate.
                              -  31  -
-------
3.   Rejection Factor;
                        Photodegradation in Water (161-2)

The material balances were incomplete.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 48.

     -    Standard Evaluation Procedure  (SEP) for
          Photodegradation in Water Studies.  (June 1985), pages
          12.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), page C-284.

     This study is designed to measure the photolysis of a
pesticide in water and the formation and decline of the
degradates.  This is achieved by measuring the test substance
applied at the beginning of the experiment and then accounting
for it at the end of the experiment.  The purpose of this test is
to verify that all degradates formed are isolated and that an
accurate rate of photolysis is calculated.  A good material
balance (90-110%) is a prereguisite for any valid laboratory
study.

     Industry Comment

     Industry agrees that acceptable mass balance is needed for a
study to be considered valid.  If there is no attempt to provide
a mass balance or if a significant amount of the starting
activity is not accounted for, the study should be rejected.  The
EPA should be flexible on the definition of acceptable mass
balance, however.  For example, an extremely low solubility
compound which is stable under the conditions of the aqueous
photolysis study, may well show a reduced mass balance over the
period of the study due to adsorption to surfaces of the test
vessel which can be difficult to quantify precisely.  Hence,
rejection should only occur when there is a gross loss of mass
balance.

     Industry Recommendation;  The EPA should be flexible on the
definition of acceptable mass balance.  Rejection should only
occur when there is a gross loss of mass balance without adequate
explanation.

     EPA Response

     The Agency continues to believe that 90-110% accountability
should be viewed as an ideal target range. However, the Agency
recognizes that in many cases this is not possible and,
                              - 32 -
-------
                                                 Photodegradation in Water (161-2)

therefore, has assessed the material balance within the context
of the entire study, and has not routinely rejected studies
solely on the basis of low material balance.
4.   Rejection Factor:
The test solutions were not buffered and
the pH of the water was not reported.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          pages 47 & 48.

          Standard Evaluation Procedure  (SEP) for
          Photodegradation in Water Studies.  (June  1985), pages
          12 & 7.

          FIFRA Accelerated Reregistration Phase 3  Technical
          Guidance.  (December 1989), pages C-284 &  C-286.

     The aqueous photolysis study should be conducted at  a pH of
greatest hydrolytic  stability to minimize hydrolysis of the test
substance.  Therefore, the test solutions should be buffered  and
their pH maintained  throughout the study.

     Industry Comment

     Industry agrees that the pH of the test  solutions  should be
reported.  Buffers should not be required unless needed to
control hydrolytic stability.

     Industry Recommendation;  The pH of the  test solutions  in
the aqueous photolysis study should be reported.  Buffers should
not be required unless needed to control hydrolytic stability.

     EPA Response

     Buffers are normally required to maintain  constant pH  in
order to reduce contributions from hydrolysis in an aqueous
photolysis study; therefore, a non-buffered photolysis  study of a
chemical which is hydrolytically stable  at pH 5, 7, & 9 would
normally not result  in the rejection of  the study.
                              - 33 -
-------
5.   Rejection  Factor;
                        Photodegradation in Water (161-2)

The analytical methodology was
incomplete and no raw data was provided
to support the conclusions.
     EPA Guidance  on  this  Factor

          Standard Evaluation  Procedure  (SEP)  for
          Photodegradation in  Water  Studies.  (June  1985),  pages
          6,  8,  13 &  14.

          FIFRA  Accelerated Reregistration  Phase 3  Technical
          Guidance.  (December  1989), page C-287.

     The guidelines specifically require that  method validation
data, recovery and method  detection  limit,  quality  control
procedures and results should  be provided.  In addition, raw
data, sample  chromatograms and sample calculations  should  be
included to determine how  the  photolysis rates were derived and
how the photolysis products were identified.

     Industry Comment

     Industry agrees  that  the  information specified in the
guidelines should  be  included  in the study  report.  We are not
certain what  is  meant by "raw  data".  It would be helpful  if the
Agency defined the minimum raw data required for inclusion in the
study report.

     Industry Recommendation;  The Agency should define the
minimum raw data required  for  inclusion in  the study report.

     EPA Response

     Raw data usually consist  of laboratory worksheets, records,
memoranda, notes,  or  exact copies thereof,  which are the result
of original observations and activities of  a study  and are
necessary for the  reconstruction and evaluation of  the report of
that study.   The registrant should submit a representative
sampling of the  raw data (particularly chromatograms and
spectra), to  enable the reviewer to confirm the reported results.
The Agency expects to issue further guidance on raw data
requirements  in  the near future.
                              -  34  -
-------
                                                 Photodegradation in Water (161-2)

6^.   Rejection Factor;   The sampling protocol was inadequate.

     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines (1982),
          page 48.

          Standard Evaluation Procedure (SEP) for
          Photodegradation in Water Studies.  (June 1985), page
          12.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), page C-284.

     Data should be collected until the decline of the test
substance and the formation and decline of degradation products
are clearly characterized or for a duration of 30 days, whichever
comes first.  The purpose of this is to assess the kinetics_of
pesticide degradation and the formation and degradation of its
metabolites.  This information is used to calculate a half-life
for the pesticide and predict how long the pesticide and its
metabolites will persist in the environment.

     If the duration of the study is not long enough and does not
have sufficient sampling points, the confidence in the calculated
half^lives will be greatly diminished as will the certainty that
all degradation products have been formed and identified.  Also,
if insufficient sampling occurred early in a  study with a rapid
decline curve, then statistical evaluation of the data might  lead

to the conclusion that  the data are unreliable, and a new study
would be required.                                         •

     Industry Comment

     Industry agrees  that the Agency's guidance on this  factor is
adequate.   Samples must be taken at the initiation of the study
and at four or more sampling time intervals,  with at  least  one
observation made  after  one-half of the test  substance is degraded
or after the equivalent of 3.0 days natural  sunlight  (12  hours of
light per  day), whichever comes first.  If  less than  10% of the
chemical has degraded after the equivalent  of 30 days of
exposure,  then  it should be considered stable to photolysis and
analysis of samples from, the earlier  intervals  should not be
required.

     Industry Recommendation;  There  is no  need for the  Agency to
change the required sampling protocol.  However,  if  less than 10%
of the chemical has degraded after  the equivalent  of  30  days of
                              - 35 -
-------
                                                  Photodegradation in Water (161-2)

 exposure,  then it should be considered stable to photolysis and
 analysis of samples from the earlier intervals should not be
 required.

      EPA Response

      EPA agrees that if less than 10% of a chemical is found to
 photodegrade within 30 days, then the pesticide should be
 considered photolytically stable in water.  However, the
 occurrence of a clear single degradate would require
 identification at lower levels.   The UV-VIS spectrum (290-800)  of
 the test substance and potential degradates in the medium/media
 used in the study should provide guidance as to the potential for
 a  pesticide to undergo direct photolysis (see attached EFGWB
 Policy_Note 1-2 dated 3/9/92).   In accordance with the OECD
 guidelines,  the Agency would consider a waiver request for the
 Photodegradation in Water data requirement if the molar
 absorption (extinction)  coefficient of the pesticide in water was
 less than  10 1 mole'1 cm'1.  With reference  to  sampling  intervals,
 samples should be taken on a schedule defined by the nature of
 the chemistry involved (eg.,  chemicals with short half lives may
 require that numerous early samples be taken, while more stable
 chemicals  may require fewer early samples, but more intense later
 sampling).   Where little or no  degradation of the chemical
 occurs,  three sampling points of  0,  15,  and 30 days would be
 sufficient to determine the stability of the chemical.
7.   Re-iection Factor;
The temperatures of the test solutions
were not reported.
     EPA Guidance on this Factor

          Standard Evaluation Procedure  (SEP)  for
          Photodegradation  in Water Studies.  (June  1985), pages  5
          & 7.

          FIFRA Accelerated Reregistration Phase 3  Technical
          Guidance. (December 1989), page C-284 & C-286.

     This issue does not normally result in the rejection of a
study, and is usually repairable by the submission  of additional
data.  The temperature of aqueous photolysis study  should be
monitored and maintained at 25 ±1 °C to simulate the actual use
conditions and to avoid contributions from thermal  reactions such
as hydrolysis and oxidation.
                              -  36  -
-------
                                                 Photodegradation in Water (161-2)
     Industry Comment
     The temperature of the photolysis study should be reported
but control at 25 ± 1° is not critical unless hydrolysis is also
occurring at a competing rate under the conditions of the study.

     Industry Recommendation;  The EPA should not invalidate
photolysis studies for failure to control temperature unless
hydrolysis is occurring at a competing rate under the conditions
of the study.

     EPA Response

     Industry should strive to maintain a constant temperature
range of ±1°C.  Minor deviations from this range would not
automatically be a cause for the rejection of the study, but
would be taken into account on a case-by-case basis. Although a
1°C rise in temperature does not affect the rate of photolysis,
it may increase the rate of hydrolysis and other thermal
reactions by 10%, thereby increasing contributions from such
processes.  Since wide variations in temperature would almost
certainly increase contributions from thermal processes, the
Agency continues to believe that this parameter must be well
controlled in order for the study to meet one of its major
intended purposes (eg. to follow the photolytic degradation of
the pesticide in water and its correlation with other competitive
degradation processes such as hydrolysis, microbial
degradation...etc.).
8.   Re-jection Factor;
Volatilization was neither measured nor
controlled.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 47. ,

          Standard Evaluation Procedure  (SEP) for
          Photodegradation in Water Studies.  (June 1985), page
          12.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), pages C-284.

     This deficiency is only critical in situations with
demonstrated poor material balances.  It is needed under these
circumstances to demonstrate that no radioactivity was  lost
                              - 37 -
-------
                                                 Photodegradation in Water (161-2)

through volatilization.  Therefore, traps must  be used  to  monitor
production of volatile photolytic products.

     Industry Comment

     Industry agrees that acceptable mass balance is vital to the
validity of a study and where collection and analysis of volatile
materials is needed to achieve this, it should  be required.

     EPA Response

     No comment.
9.   Rejection Factor;


     EPA Guidance on this Factor
A photosensitizer was used as the co-
solvent.
     -    Subdivision N: Environmental Fate Guidelines  (1982),
          page 47.

     -    Standard Evaluation Procedure  (SEP) for
          Photodegradation in Water Studies.  (June 1985), pages 7
          & 12.

     A photolytic process involves transfer of energy directly
from the light to the affected compound.  This energy transfer
can also occur indirectly from the light to another compound,
which then transfers this energy to the affected compound.  This
process is called photosensitized energy transfer and the
compound responsible for this type of energy transfer is called a
photosensitizer.  The co-solvent used to increase the solubility
of the test substance must not be a photosensitizer, because  it
will erroneously increase the rate of photolysis.

     Industry Comment

     Industry agrees that photosensitizers should not be used as
co-solvents in photolysis studies.  It was helpful that the
Agency recommended the use of methanol and acetonitrile in the
Standard Evaluation Procedure for this study.  It would also.be
helpful if the Agency could provide a list of co-solvents which
they have determined are not acceptable for this study.

     Industry Recommendation;  It would be helpful if the Agency
could provide a list of co-solvents which they have determined
are not acceptable for this study.
                              - 38  -
-------
                                                 Photodegradation in Water (161-2)
     EPA Response
     The Agency neither maintains a list nor has the resources to
develop a comprehensive list of all possible solvents and
substances which could conceivably act as photosensitizers.
However, Industry could develop such a list.
10.  Rejection Factor;
It was not specified that the test
solutions were sterile.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 47.

          Standard Evaluation Procedure  (SEP) for
          Photodegradation in Water Studies.  (June  1985), pages  ?


          FIFRA Accelerated Reregistration Phase 3  Technical
          Guidance.  (December 1989), pages C-284.

     The aqueous photolysis study  is conducted to determine the
rate of photolysis of the active ingredient,  rates  of  formation
and decline of the photodegradates and the identity of the
photolysis products.  Photolysis competes in  nature with
biological metabolism.   Therefore, it is important  that the study
is conducted under sterile conditions to eliminate  interference
from biological degradation.

     Industry Comment

     Industry agrees that the equipment  and  solutions  used  in
this study should be sterilized at the initiation of the study to
prevent competing microbial degradation. It is  impractical to
require demonstration of sterility throughout the study period,
however.  In addition,  if  screening  studies  have shown that the
chemical does not degrade microbially, then  sterile conditions
should not be required.

     Industry Recommendation;   The Agency should continue to
require  sterilization  of the  equipment and  solutions used in  this
study  but  should not require  demonstration  of sterility
throughout the  study.   Also,  sterility  should not be required
where  screening studies have  shown that  biodegradation does not
to occur under  the  conditions of the study.
                               -  39  -
-------
                                                  Photodegradation in Water (161-2)
      EPA Response
      EPA's agrees that a study in which no degradation was
 observed should never be rejected solely on the basis of failure
 to prove sterile conditions.  However, reasonable efforts should
 be made to assure that sterile conditions are maintained
 throughout the study.
 .11«   Reiaction Factor;
The study was terminated before the
half-life of the test substance was
established or before 30 days.
      EPA Guidance on this Factor

           Subdivision N:  Environmental Fate Guidelines (1982)
           page 48.                                            '

           Standard Evaluation Procedure (SEP)  for
           Photodegradation in Water Studies.  (June 1985),  pages 7
           & 12.

      Data should be collected until the decline of the test
 substance and the formation and decline of degradation products
 are  clearly characterized or for a duration of 30 days, whichever
 comes first.   The purpose of this is to assess the kinetics of
 pesticide degradation and the formation and degradation of its
 degradates.   This information is used to calculate a  half-life
 for  the pesticide and predict how long the pesticide  and its
 degradates will  persist in the environment.  If the duration of
 the  study is  not long enough and does not  have sufficient
 sampling  points,  the  confidence in the calculated half-lives will
 be greatly diminished as  will the certainty that all  degradation
 products  have been  formed and identified.

      Industry Comment

     ^ndustry agrees  that the study should  be  continued until the
 decline of the test substance and  the  formation  and decline  of
degradation products  are  clearly  characterized or  for  a duration
of 30 days, whichever  comes  first,  as  specified  in  the Agency's
discussion above.

     EPA Response

     No comment.
                             - 40 -
-------
12.  Rejection Factor;
                                 Photodegradation in Water (161-2)

         The coefficients of determination for
         the data used to determine the half-
         lives were very poor.
     EPA Guidance on this Factor

     There is no specific EPA guidance on this rejection factor.
However, it pertains to basic information relating to data
analysis. It appears that the r2 values  were low and the data
points for the regression analysis were highly scattered making
the first order rate constant unreliable.

     Industry Comment

     Industry agrees that a reasonable correlation coefficient
for the calculation of the photolytic half-life is important in
cases where this route of degradation is competing with other
degradation routes to define the overall dissipation rate of the
compound.  One may frequently encounter low r2 values,  however,
where there is very slow or very fast degradation.  In these
cases, even without a precise calculation of the half-life, the
contribution of aqueous photolysis to the dissipation of the test
substance in the environment will have been adequately
characterized.
reject a study.
Low r2  alone  should  not  be  sufficient  reason to
     Industry Recommendation;  There should be no specific
requirement to meet a minimum correlation coefficient.  Decisions
on the validity of the study should be made on the basis of
whether the data produced in the study answer the question of
photolytic stability and allow for a calculation of the rate
where it is needed.

     EPA Response

     With extremely rapid or extremely slow degradation, r2 needs
to be considered on a study basis.  However, for the vast
majority of these studies, the need to accurately define the
reaction kinetics demands that the data have a good fit to the
regression line; hence, the need for an "acceptable" coefficient
of determination.
                              - 41 -
-------
13.  Rejection Factor;


     EPA Guidance on this Factor
                                                  Photodegradation in Water (161-2)

                          The stability of the pesticide under
                          refrigeration was not addressed.
     -     Standard  Evaluation Procedure (SEP)  for
           Photodegradation in Water  Studies.  (June 1985),  page 5.

     -     FIFRA Accelerated Reregistration Phase 3 Technical
           Guidance.  (December 1989),  pages C-284 & C-287.

     Even  under ideal  conditions  chemicals may degrade  during
storage.   Therefore, if  samples are  taken  and  stored  before
analysis,  a storage  stability study  is  required in order to
assess the effects,  if any,  of storage  on  those samples.   In  many
cases, studies rejected  due to storage  stability data problems
may be upgraded by the registrant with  the submission of
additional data/information.

     Industry Comment

     Industry agrees that  when samples  are stored for a
significant period before  analysis their stability under the
conditions of storage  must be proved.   Some reasonable, short
period of  storage, eg, 10  days at 5°C or 30 days frozen, should
be acceptable, however.

     Industry Recommendation;  Storage  stability data should  only
be required beyond 10  days at 5°C or  30 days frozen.

     EPA Response

Note;      The following  discussion is consistent with the
           position of  the  Chemistry Branches in HED on  the
           requirements for storage stability data (Health Effects
           Division memo  dated January 14,  1993).   The registrants
           are referred to  that document for additional  guidance.
           Industry may,  at its option, propose  an alternative
           guidance document  for Agency consideration.

     Chemicals may degrade during storage,  even under ideal
storage conditions.  Therefore, storage stability data  are
essential  in order to  be confident that any degradation measured
in the test system was due solely to  the environment  of that  test
system, and not due to handling and storage.  Storage stability
is chemical specific and a chemical's stability under storage can
vary depending upon the matrix stored (e.g., soil,  water, organic
extract,  plant tissue,  fish tissue, etc.).  The Agency does
however agree that unless  a pesticide/residue of  concern is
                              - 42  -
-------
                                                 Photodegradation in Water (161-2)

otherwise known to be volatile or labile, storage stability data
will not be needed for samples stored frozen for <30 days.

     For frozen storage intervals >30 days, evidence must be
provided confirming that the identity of residues did not change
during the period between collection and final analysis.
Ideally, storage stability data should be obtained concurrently
with the particular environmental fate guideline study, not
independent from it.

     However, concurrent storage stability studies will not be
required in many cases.  Provided that the pesticide residues are
found to be stable in the matrices of interest, a storage
stability study run in a separate freezer at a different time
period will be acceptable if the storage conditions  (particularly
temperature) are the same as those in the corresponding
environmental fate guideline study.  However, for pesticides
whose residues are known or suspected to be unstable or volatile,
concurrent studies may be needed.  In fact, for such pesticides,
it is advisable to run a storage stability study in advance to
determine proper storage conditions and maximum storage times
before treated samples are placed into storage.


Additional Industry Comments on Photodearadation in Water Studies

     Co-solvent concentrations greater than 1% should be
permitted if needed to solubilize the test material.

     Conclusions from natural water photolysis studies are not
necessarily applicable to all bodies of water but may give a
better  indication of the fate of the pesticide in the
environment.  Natural water photolysis studies should continue to
be regarded as supplemental, to be conducted at the discretion of
the registrant, but not required.

     EPA Response

     The Agency agrees that conducting a Photodegradation in
Water study with extremely insoluble compounds may not always be
feasible.  However, the Agency is concerned that the use of
extreme measures to solubilize the pesticide  (greater than 1% co-
solvent) may result in unreliable data due to pesticide-solvent
interactions which may impact the photolysis rate as well as the
types of degradates formed.  Therefore,  the use of co-solvents
should  be avoided when possible.  Instead, the pesticide
concentration selected for this  study should be within the
compound's  solubility  limit.  In some cases, this will require
that more sensitive analytical-methods' be  developed.
                              - 43 -
-------
                                                  Photodegradation in Water (161-2)

     The Agency agrees  with Industry's comments regarding natural
water photolysis  studies.   Currently,  natural water photolysis
studies are not required to satisfy the environmental fate data
requirements; however,  such studies conducted under special
circumstances previously have been found valuable in evaluating
the photolytic behavior of  the pesticide under natural
environmental conditions.
                              -  44  -
-------
                                                  Photodegradation on Soil (161-3)

            GUIDELINE 161-3  PHOTODEGRADATION ON SOIL


1^   Rejection Factor;   The material balance was incomplete?.

     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 51.

          Standard Evaluation Procedure (SEP) for
          Photodegradation on Soil Studies.  (June 1985), pages 11
          & 8.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989), page C-289.

     This study is designed to measure the photolysis of a
pesticide on the soil and the formation and decline of  the
degradates.  This is achieved by measuring the test substance
applied at the beginning of the experiment and then accounting
for it at the end of the experiment.  The purpose of this test is
to verify that all degradates formed are isolated and that an
accurate rate of photolysis is calculated.  A good material
balance (90-110%) is a prerequisite for any valid laboratory
study.

     Industry Comments

     Industry agrees that acceptable mass balance is needed for  a
study to be considered valid.  If there is no attempt to provide
a mass balance or if a significant amount of the starting
activity is not accounted for, the study should be rejected.  The
EPA should be flexible on the definition of  acceptable  mass
balance, however.  Rejection should only occur when there is a
gross loss of mass balance.

     Industry Recommendation;  The EPA should be  flexible on the
definition of acceptable mass balance.  Rejection should  only
occur when there  is  a gross loss of mass balance without  adequate
explanation.

     EPA Response

     The Agency continues to believe that  90-110  % accountability
should be viewed  as  an  ideal target range. However, the Agency
recognizes that  in many  cases this  is not possible and,
therefore, has assessed  the material balance within the context
                              - 45 -
-------
                                                   Photodegradation on Soil (161-3)
 of the entire study, and has not routinely rejected studies
 solely on the basis of low material balance.
 2.    Rejection Factor;
Volatilization was  neither  measured nor
controlled.
      EPA Guidance on this Factor

           Standard Evaluation Procedure (SEP)  for
           Photodegradation on Soil Studies.  (June 1985),  pages 11
           & 7.

           FIFRA Accelerated Reregistration Phase 3 Technical
           Guidance.  (December 1989),  page C-288.

      The study  must demonstrate that  no radioactivity is  lost
through_volatilization.   Therefore, traps must be used to monitor
production of volatile photolysis products.  This issue connects
directly with low material balances,  where unaccounted-for
components need to be identified (even if it is ultimately
determined to consist of  radiolabeled-C02 or Parent pesticide).

      Industry Comment

      Industry agrees that acceptable  mass balance is  vital to the
validity of a study  and where collection and analysis of  volatile
materials is needed  to achieve this,  it should be required.

      EPA Response

      No  comment.
3.   Rejection Factor;
Artificial light source was not similar
to natural sunlight.
     EPA Guidance on this Factor

          Standard Evaluation Procedure  (SEP) for
          Photodegradation on Soil Studies.  (June  1985), pages  12
          & 7.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), page C-288.

     The light source used for sample irradiation may be either
natural or simulated sunlight.  If natural sunlight is used, a
record of its intensity and wavelength distribution is required
                              - 46 -
-------
                                                  Photodegradation on Soil (161-3)

in addition to other major variables which affect incident light
such as the time of exposure, latitude, time of year and
atmospheric cover.  If an artificial light source is used, its
intensity, wavelength distribution and the length of exposure
should be comparable to sunlight, as the rate of photolysis is
dependent on these factors and will vary if the artificial light
source is different from sunlight.  It has been our observation
that, of the currently available artificial light sources, the
xenon arc lamp best simulates natural sunlight in both wavelength
distribution and intensity.  Therefore, the Agency currently
prefers this light source over other artificial lamps.  The
Agency will consider the suitability of any future light sources
as they become available.

     Industry Comment

     Industry agrees that adequate characterization of any light
source and its comparison to natural sunlight is critical to
photolysis studies.  It would be helpful if "natural sunlight"
could be defined more precisely.  We suggest that sunlight be
defined as the solar irradiance at 40° North Latitude, as shown
in the EPA Mean Solar Data Table  (EPA Chemical Fate Test
Guidelines, 1983, Photolysis in Aqueous Solution in Sunlight, CG-
6000, Office of Toxic Substances, Office of Pesticides and Toxic
Substances, U.S. Environmental Protection Agency).

     Irradiation equivalent to 30 days exposure to standard
sunlight should be acceptable.  For example, 420 hours of
continuous irradiation from a source that simulates sunlight
would be equivalent to a 30 day exposure to sunlight with a
photoperiod of 14 hours.

     Industry Recommendation:  We would like the Agency to define
standard sunlight and we suggest that sunlight be defined as the
solar irradiance at 40° North Latitude.  We also suggest that
continuous irradiation equivalent to 30 days exposure to standard
sunlight should be acceptable for the soil photolysis study.

     EPA Response

     Historically, guidance suggested that the light source
parallel that in the intended use area, at the anticipated time
of the year when the pesticide would normally be applied.  As
noted above, this may have led to inconsistent studies which
could not be compared one to the other.  This would seem to be in
conflict with our goal to utilize "standardized" testing which
would allow comparisons between chemicals.
                              - 47 -
-------
                                                  Photodegradation on Soil (161-3)

     Using standardized sunlight with solar irradiance at 40°
North Latitude is an idea which, although not accounting for
variations in season and natural lighting conditions, may
nevertheless prove more consistent in predicting photolytic
effects.  The Agency is considering whether or not this should be
implemented.  In addition the Agency is also considering when
quantum yield calculations may be used to allow the extrapolation
of the laboratory results to other locations and times of year.
Likewise, the suggested continuous irradiation equivalent to 30
days exposure to natural sunlight or 420 hours of continuous
irradiation from a source that simulates sunlight also appears to
be a workable alternative to current practice. The Agency will
consider Industry's suggestions in revising Subdivision N.
     Rejection Factor:
The test substance was not technical
grade or purer.
     EPA Guidance on this Factor

     -    Subdivision N: Environmental Fate Guidelines  (1982),
          page 50.

     -    Standard Evaluation Procedure  (SEP) for
          Photodegradation on Soil Studies.  (June 1985), pages 5
          & 8.

     -    FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), page C-288.

     The purity of the test substance is critical for accurate
study results.  Any impurities in the test substance may
interfere with the results and may lead to erroneous conclusions
about the instability of the test substance or the types of
photoproducts formed.

     Industry Comment

     Industry agrees that the test substance purity should be a
requirement for a valid study.  We suggest that a radiopurity of
95% should be acceptable in most cases and we would like the
Agency to confirm this.

     Industry Recommendation:  No study should be initiated with
a test substance which is not sufficiently pure.  The Agency
should specify what is acceptable radiochemical purity.
recommends that a radiopurity of 95% should be considered
acceptable unless adequate justification for lower purity is
provided by the registrant.
                              - 48  -
-------
                                                  Photodegradation on Soil (161-3)
     EPA Response
     For  laboratory  studies  conducted with  radiolabeled
chemicals, the use of  a  test substance with low radiopurity may
unnecessarily complicate the identification of  degradation
products  since the fate  of the parent and its degradates  is
followed  by monitoring the radioactivity.

     Industry should strive  for the highest possible  radiopurity
but not less than 95%.   The  Agency understands  that achieving a
high level of radiopurity may depend on the chemical
characteristics of the specific compound and on the type  of
radioisotope used.   The  Agency further acknowledges that  some
chemicals may require  extensive preparation in  order  to achieve
this high level of radiopurity, and has previously concurred with
time extensions for  submission of data to allow for such
preparation.  The Agency has also previously accepted the use of
lower purity radiochemicals  with adequate justification as to why
higher radiochemical purity  could not be achieved.


5_._   Rejection Factor;    Raw data were not  provided.

     EPA  Guidance on this Factor

          Standard Evaluation Procedure (SEP) for
          Photodegradation on Soil Studies.  (June 1985),  pages 6
          & 13.

     This issue does not  normally result in the  rejection of a
study, and is usually  repairable by the submission of additional
data.  The guidelines  specifically require  that  raw data,  sample
chromatograms and sample  calculations be provided on how  the
photolysis rates were  derived and how the photolysis products
were identified.

     Industry Comment

     Industry agrees that the information specified in  the
guidelines should be included in the study  report.  We  are not
certain what is meant  by  "raw data".  It would be helpful  if the
Agency defined the minimum raw data required for inclusion in the
study report.

     Industry Recommendation; The Agency should define  the
minimum raw data required for inclusion in  the study report.
                              -  49  -
-------
                                                  Photodegradation on Soil (161-3)
     EPA Response
     Raw data usually consist of laboratory worksheets, records,
memoranda, notes, or exact copies thereof, which are the result
of original observations and activities of a study and are
necessary for the reconstruction and evaluation of the report of
that study.  The registrant should submit a representative
sampling of the raw data (particularly chromatograms and
spectra), to enable the reviewer to confirm the reported results.
The Agency expects to issue further guidance on raw data
requirements in the near future.
     Re-iection Factor;
The incubation temperature was not
provided.
     EPA Guidance on this Factor

     -    Standard Evaluation Procedure  (SEP) for
          Photodegradation on Soil Studies.  (June 1985) , page 5.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989), page C-289 & 291.

     This issue does not normally result in  the rejection of a
study, and is usually repairable by the submission of additional
data.  Soil temperatures in this study are important because soil
surface temperature increases under sunlight and the heating may
accelerate various nonphotochemical reactions such as hydrolysis
and oxidation.  Thus, if the soil is not cooled, thermal
reactions are likely to increase pesticide loss in the  soil.

     Industry Comment

     Industry agrees that the temperature of the test system
should be reported and that cooling should be used in the study
to control the heating caused by exposure to sunlight.  Imperfect
temperature control should not be sufficient reason to  reject a
study alone, especially if plus or minus 1°C is the qualifier.
Exposure to intense light can lead to temporary fluctuations from
the desired range.  Normally, thin layers of soil are used, and
it difficult to monitor and control the temperature in  the test
system.  Temperature control of the irradiated soil should be
within ± 5° C of the dark controls.

     Industry Recommendation;  The temperature of the test system
should be reported and cooling should be used in the study to
control the heating caused by exposure to light.  Temperature
                              - 50 -
-------
                                                  Photodegradation on Soil (161-3)

 control of the irradiated soil should be within ± 5° C of the
 dark controls.

      EPA Response

      Industry should strive to maintain a constant  temperature  of
 ±1°C.   Minor deviations  from this range would not automatically
 be  a cause for the rejection of the study,  but would be taken
 into account on a case-by-case basis.  Although a 1°C rise in
 temperature does not affect the rate of photolysis,  it may
 increase the rate of hydrolysis and other thermal reactions by
 10%,  thereby increasing  contributions  from such processes.  Since
 wide variations in temperature would almost certainly increase
 contributions from thermal processes,  the Agency continues to
 believe that this parameter must be well controlled in order for
 the study to meet one of its major intended purposes (eg.  to
 follow  the photolytic degradation of the pesticide  in water and
 its correlation with other competitive degradation  processes such
 as  hydrolysis,  microbial degradation	etc.).


 Zi.    Rejection  Factor:    Decrradates were not identified.

      EPA Guidance on this Factor

           Subdivision N:  Environmental Fate Guidelines (1982),
           page  51.

           Standard Evaluation Procedure  (SEP)  for
           Photodegradation on Soil  Studies.  (June 1985), pages  12
           &  7.

          •FIFRA Accelerated Reregistration  Phase 3 Technical
           Guidance.  (December 1989), page C-289.

     The  identification  of those residues present at levels
 greater than  or  equal  to ,0.01 ppm or 10%  of applied,  whichever  is
 less, is  a critical  element of  the  soil photolysis study.   One
 primary reason  this  study is  conducted is to identify the
 photodegradates  on  soil.   Failure to identify  one (or more)
 significant degradates'inhibits  a complete  understanding of the
 soil photolysis.  Hence  prediction  of  the environmental fate
 under actual  use  situations becomes much  more  difficult.

     Industry Comment

     The Agency's comments  (above)  are not  consistent with the
referenced guidance  documents.   Failure to  identify  compounds
present at 10% of applied  should  be a  reason to  reject a study
                              -  51  -
-------
                                                  Photodegradation on Soil (161-3)

unless the author can present valid reasons as to why this could
not be achieved.  There is NO valid justification for requiring
registrants to identify compounds at greater than 0.01 ppm and
there is no mention of this requirement in any of the guidance
documents.

     The purpose of this study is to identify the major
photoproducts and these have been defined at those produced in
yields of £10% of the applied test material.  There is no
justification for introducing a 0.01 ppm requirement.

     Industry Recommendation;  Photoproducts produced in yields
of £10% of the applied test material should be identified in this
study unless the registrant can present valid reasons as to why
this could not be achieved.

     EPA Response

     The Agency agrees that the identification of residues
present at 0.01 ppm may not always be feasible, especially for
those products with field application rates exceeding
approximately 1 Ib ai/A.  The Agency will require the
identification of all residues equal to or greater than 10% of
the dose rate.  This level of residue identification should
provide adequate information for most chemicals.  The dose rate
is defined as that concentration of radiolabeled pesticide in
soil equal to the maximum field application rate at a 1 cm depth.
For example, if the maximum field application rate is 5 Ibs ai/A,
the dose rate should approximate 37.5 fj,g ai/g of soil in the test
system.  All residues present at >10% of this dose rate (i.e.,
3.75 jug parent equivalents/g soil) must be identified.

     In the event that the dose rate must exceed the maximum
field application rate for residue identification purposes,
(e.g., for technological, specific activity, or other
limitations), a separate exaggerated dose rate study may be
conducted.  However, this exaggerated dose rate study cannot be
used to provide kinetics information.  The kinetics study must be
conducted with the maximum dose rate as described above.

     The 10% criterion is a general guideline.  The registrant is
expected to identify single degradates present at concentrations
approaching 10% of the dose rate.  In addition, degradates of
known toxicological or ecotoxicological concern must certainly be
identified and quantified even if they are present at <10% of the
dose rate.
                              - 52 -
-------
                                                  Photodegradation on Soil (161-3)

it-.   Rejection Factor;   The  test was not performed  on soil.

     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines (1982),
          page 50.

          Standard Evaluation Procedure  (SEP)  for
          Photodegradation on Soil Studies.  (June 1985), pages  5,
          9, & 11.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), pages C-288 & C-290.

     This study is conducted  to provide data on Photodegradation
of the active ingredient on soil surfaces.  The supporting
documents provide adequate guidance in soil selection  and require
specific information about the description of  soil type, soil
characteristics, and the test soil source including  country and
state of origin.

     Some submitters have expressed an interest in conducting
this study on glass beads instead of on soil.  Glass beads
however cannot mimic the many processes which  take place in the
soil matrix.

     Industry Comment

     Industry agrees that the soil photolysis  study  must be
conducted on soil.  Maintaining conditions suitable  for microbial
growth (i.e., moist),  however, unnecessarily complicates the
study and does not contribute to the overall purpose of providing
data on soil surface-catalyzed photodegradation.

     Industry Recommendation;  The Agency should require that
studies be conducted on well  characterized soil, but it should
not require that conditions suitable for microbial growth be
maintained throughout the study.  The soils should be permitted
to dry.

     EPA Response

     The Agency agrees that maintaining soil moisture level in
the laboratory studies may be difficult;  however,  a reasonable
effort must be made (eg.,  humidification of the ventilation
airstream)  to keep the soil somewhat moist so as to prevent
significant alteration of the soil structure and properties.
                              -  53  -
-------
                                                  Photodegradation on Soil (161-3)

     Re-iection Factor;   The treatment rate was not reported.

     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines (1982),
          page 50.

          Standard Evaluation Procedure (SEP) for
          Photodegradation on Soil Studies.  (June 1985), page 5.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), page C-288 & 291.

     This issue does not normally result in the rejection of a
study, and is usually repairable by the submission of additional
data.  The treatment rate is important in evaluating the soil
photolysis study, because the amount of disappearance of the
parent and the metabolites formed during the process are
dependent on the initial concentration of the test substance
applied to the soil.

     In many experiments, results are reported as a percent
recovered, rather than as percent of applied.  Also, the amount
of active ingredient used usually closely approximates the
anticipated field use rate.

     Industry Comment

     Industry agrees that the treatment rate must be reported.

     EPA Response

     No comment.

Additional Industry Comments on Photodegradation on Soil Studies

     Soil used for the dark controls should  be treated similarly
to the exposed samples.  Dark controls should be used solely to
evaluate degradation  in the soil photolysis  experiment.
Comparison of degradation rates observed in  the dark controls
with rates from the aerobic soil metabolism  study may not be
appropriate.  The rate of microbial degradation on a thin layer
of air-dried soil is  not likely to duplicate the results of the
soil metabolism study.  Comparing the products found in the soil
photolysis study to those of the aerobic soil metabolism study
should provide an adequate basis for determining any differences.
                              - 54 -
-------
                                                  Photodegradation on Soil (161-3)
     EPA Response
     EPA agrees that comparing the products  found in the soil
photolysis study to those of the aerobic  soil metabolism study
should provide an adequate basis for  identification of the actual
photodegradates.  However, the Agency remains concerned with the
manner in which dark controls are maintained.   In a vast majority
of the Photolysis in Soil studies, the dark  controls are wrapped
in aluminum foil and set aside in the dark without making
sufficient efforts to maintain the same conditions as in the
exposed samples (e.g., moisture level, air flow,  temperature).
Ideally, the dark controls should represent  all processes except
photolysis.  Every effort should be made  to  ensure that,  except
for light, the dark controls and irradiated  samples are
maintained under the same environmental conditions.
                             - 55  -
-------
                                                  Photodegradation in Air (161-4)
             GUIDELINE 161-4 PHOTODEGRADATION IN AIR
1.   Re-iection Factor;   The pesticide degradation in the vapor
                         phase could not be distinguished from
                         degradation that occurred in material
                         adsorbed to the sides of the glass
                         container.

     EPA Guidance on this Factor

     -    FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), page C-292 & C-293.

     Appropriate analytical methods are required to clearly
distinguish between vapor phase and liquid phase photoproducts.

     Industry Comment

     There is extreme procedural difficulty in addressing this
problem.  The reference cited in the Subdivision N Guidelines
(Crosby and Moilanen, 1974) employ a rather large vessel of 72
liters in an attempt to maximize volume to surface area ratio and
thus minimize wall effects.  Sampling the vapor phase in this
type of apparatus is complicated by the extremely low
concentrations of chemical present for many agricultural
chemicals due to their low vapor pressures (typically <10"  mm
Hg).  Attempts with even larger vessels have been made  (Teflon
bags, etc.), but these studies suffer from low material balance.

     Industry Recommendation:  Industry needs significantly more
guidance on this study.

     EPA Response

     It appears that the use of a large vapor-phase photoreactor
which permits compensation for wall effects by maximizing volume
to surface area ratio may present significant experimental
difficulties.  However, in the studies which were_rejected, the
experimenters cooled the reaction vessel, condensing all
vapor-phase components with those already in solution or adherent
to the vessel walls.  This approach further confounded  the study.

     The Agency acknowledges that the test procedures for
photodegradation in air could be improved, and welcomes
suggestions on technical and/or procedural enhancements to the
study protocol.
                              - 56 -
-------
2.   Rejection Factor;


     EPA Guidance on this Factor
                         Photodegradation in Air (161-4)

Air samples were never analyzed
separately from nonvaporized pesticide.
          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989), page C-292 & C-293.

     Photodegradation in air is a vapor phase study which  is
significantly different from the photodegradation in water study.
Appropriate analytical methods are required to clearly
distinguish between vapor phase and liquid phase photoproducts.

     Industry Comment

     Achieving this objective is also difficult.  The dish from
which the chemical is vaporized can be analyzed separately
without too much problem, but analysis of the vapor phase  is
fraught with pitfalls as described above (Rejection Factor 1.)

     EPA Response

     See EPA Response to factor #1.
3,   Rejection Factor;   The material balance was low.

     EPA Guidance on this Factor
          Subdivision N: Environmental Fate Guidelines  (1982),
          page 53.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), pages C-292 & C-294.

     This study is designed to measure the photolysis of a
pesticide in the air and the formation and decline of the
degradates.  Therefore, the test substance applied at the
beginning of the experiment must be accounted for at the end  of
the experiment to be certain that all degradates formed are
isolated and an accurate rate of photolysis is calculated.  A
good material balance  (90-110%)  is a prerequisite for any valid
laboratory study.

     Industry Comment

     With the large incubation vessels, used to minimize surface
interactions, difficulties in achieving good sealing can occur.
                              -  57  -
-------
                                                  Photodegradation in Air (161-4)

Flexibility is needed in assessing the acceptability of mass
balance in an air photolysis study.

     EPA Response

     EPA agrees that the Agency should allow some flexibility in
what constitutes an acceptable material balance for those studies
conducted in large reaction vessels.
     Rejection Factor:
High percentages of unidentified
material were reported.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 53.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), pages C-292.

     The identification of those residues present at levels
greater than or equal to 0.01 ppm or 10% of applied, whichever is
less, is a critical element of the photodegradation in  air study.
One primary reason this study is conducted is to identify the
photodegradates in the air.  Failure to identify one (or more)
significant degradates may result in gaps in the data regarding
the photodegradation in the vapor phase.  Hence the understanding
of the environmental fate under actual use situations will be
unclear.

     Industry Comment

     The Agency's comments (above) are not consistent with the
referenced guidance documents.  Failure to identify compounds
present at 10% of applied should be a reason to reject  a study
unless the author can present valid reasons as to why this could
not be achieved.  There is NO valid justification for requiring
registrants to identify compounds at greater than 0.01  ppm and
there is no mention of this requirement in any of the guidance
documents.

     The purpose of this study is to identify the major
photoproducts and these have been defined at those produced in
yields of >10% of the applied test material.  There is  no
justification for introducing a 0.01 ppm requirement.

     Industry Recommendation;  Photoproducts produced in yields
of >10% of the applied test material should be identified in this
                              - 58 -
-------
                                                   Photodegradation in Air (161-4)

 study unless the registrant can present valid reasons as to why
 this could not be achieved.

      EPA Response

      The Agency agrees that the identification of residues
 present at 0.01 ppm may not always be feasible,  especially for
 those products with field application rates exceeding
 approximately 1 Ib ai/A.   The Agency will require the
 identification of all  residues equal to or greater than 10%  of
 the  dose rate.   This level of residue identification should
 provide adequate information for most chemicals.

      In the event that the dose rate must exceed the maximum
 field application rate for residue identification purposes,
 (e.g.,  for technological,  specific activity,  or  other
 limitations),  a separate  exaggerated dose rate study may be
 conducted.   However, this exaggerated dose rate  study cannot be
 used to provide kinetics  information.   The kinetics study must  be
 conducted with the maximum dose rate as described above.

      The 10% criterion is a  general  guideline.   The registrant  is
 expected to identify single  degradates present at concentrations
 approaching 10% of the dose  rate.   In addition,  degradates of
 known toxicological or ecotoxicological concern  must certainly  be
 identified and quantified even if  they are present at <10% of the
 dose rate.
5.   Rejection Factor;
The registrant did not measure the vapor
pressure at the temperature the study
was conducted.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 52.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), page C-293.

     The vapor pressure should be measured at the same
temperature that the study is conducted, as a different
temperature will affect the results of the study.

     Industry Comment

     There is no mention of the measurement of vapor pressure in
either of the references cited.
                              -  59  -
-------
                                                  Photodegradation in Air (161-4)
     EPA Response
     Vapor pressure at the temperature of the experiment needs to
be measured to calculate the amount of the test substance present
in the vapor phase since the concentration of the test substance
varies with the temperature and pressure in the reaction vessel.


0_^   Re-iection Factor;   The analytical method was inadequate.

     EPA Guidance on this Factor

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December  1989), pages C-292 & C-293.

     Photodegradation  in air is a vapor phase study which  is
significantly different from the photodegradation in water study.
Therefore, it requires appropriate  analytical methods which
clearly distinguishes  between  vapor phase and liquid phase
photoproducts.

     Industry Comment

     Industry needs  significantly more guidance  on this  factor.

     EPA Response

     The Agency  acknowledges the need  for  additional  guidance,
and would welcome  Industry's support  in  the  development  of
additional  SEPs  for  the  remaining  guidelines for which no SEP
currently  exists.

     The  identification  and quantification of both parent and
major  degradates requires the  use  of  methods of analysis which
will unequivocally distinguish between vapor phase and liquid
phase  photoproducts.
      Re-iection Factor;
The spectrum of the artificial light
source was not similar to that of
natural sunlight.
      EPA Guidance on this Factor

           Subdivision N: Environmental Fate Guidelines  (1982),
           page 52.

           FIFRA Accelerated Reregistration Phase 3 Technical
           Guidance.  (December 1989), pages C-292 & C-293.
                               - 60 -
-------
                                                  Photodegradation in Air (161-4)

     The light source used for sample irradiation may be either
natural or simulated sunlight.  If natural sunlight is used,  a
record of its intensity and wavelength distribution is required.
In addition, other major variables which affect incident light
must be used such as the time of exposure, latitude, time of  year
and atmospheric cover.  If an artificial light source is used,
its intensity, wavelength distribution and the length of exposure
should be comparable to sunlight, as the rate of photolysis is
dependent on these factors and will vary if the artificial light
source is different from the natural sunlight.

     Industry Comment

     Industry agrees that adequate characterization of any light
source and its comparison to natural sunlight is critical to
photolysis studies.  It would be helpful if "natural sunlight"
could be defined more precisely.  We suggest that sunlight be
defined as the solar irradiance at 40° North Latitude, as shown
in the EPA Mean Solar Data Table (EPA Chemical Fate Test
Guidelines, 1983, Photolysis in Aqueous Solution in Sunlight, CG-
6000, Office of Toxic Substances, Office of Pesticides and Toxic
Substances, U.S. Environmental Protection Agency).

     Irradiation equivalent to 30 days exposure to standard
sunlight should be acceptable.  For example, 420 hours of
continuous irradiation from a source that simulates sunlight
would be equivalent to a 30 day exposure to sunlight with a
photoperiod of 14 hours.

     Industry Recommendation:  Industry would like the Agency to
define standard sunlight, and we suggest that sunlight be defined
as the solar irradiance at 40° North Latitude.  Industry also
suggests that continuous irradiation equivalent to 30 days
exposure to standard sunlight should be acceptable for the air
photolysis study.

     EPA Response

     Historically, guidance suggested that the light source
parallel that in the intended use area,  at the anticipated time
of the year when the pesticide would normally be applied.  As
noted above, this may have led to studies that could not be
compared to one another because of differences in lighting
conditions.  This would seem to be in conflict with our goal  to
utilize "standardized" testing which would allow comparisons
between chemicals.

     Using standardized sunlight with solar irradiance at 40°
North Latitude is an idea which, although not accounting for
                              -  61  -
-------
                                                  Photodegradation in Air (161-4)

variations in season and natural lighting conditions, may_
nevertheless prove more consistent in predicting photolytic
effects.  The Agency is considering whether or not this should be
implemented.  In addition the Agency is also considering when
quantum yield calculations may be used to allow the extrapolation
of the laboratory results to other locations and times of year.
Also the suggested continuous irradiation equivalent to 30 days
exposure to natural sunlight or 420 hours of continuous
irradiation from a source that simulates sunlight also appears to
be a workable alternative to current practice. The Agency will
consider Industry's suggestions in revising Subdivision N.
8.   Rejection Factor;
A photosensitizer was present in the
primary stock solution.
     A photolytic process involves the transfer of energy
directly from the light to the affected compound.  This energy
transfer can also occur indirectly from the light to another
compound which is then transferred to the affected compound.
This process is called photosensitized energy transfer and the
compound responsible for this type of energy transfer is called a
photosensitizer.  A co-solvent used to increase the solubility of
the test substance must not be a photosensitizer because it will
erroneously increase the rate of.photolysis.

     Industry Comment

     Industry agrees that photosensitizers should not be used in
the test solution.

     EPA Response

     No comment.


9.   Rejection Factor;   No raw data was submitted.

     This issue does not normally result in the rejection of a
study, and is usually repairable by the submission of additional
data. The guidelines specifically require that raw data, sample
chromatograms and sample calculations be provided on how the
photolysis rates were derived and how the photolysis products
were identified.

     Industry Comment

     Industry agrees that the information specified in the
guidelines should be included in the study report.  We are not
                              - 62 -
-------
                                                  Photodegradation in Air (161-4)

certain what is meant by "raw data".  It would be helpful if  the
Agency defined the minimum raw data required for inclusion  in the
study report.

     Industry Recommendation;  The Agency should define the
minimum raw data required for inclusion in the study report.

     EPA Response

     Raw data usually consist of laboratory worksheets, records,
memoranda, notes, or exact copies thereof, which are the result
of original observations and activities of a study and are
necessary for the reconstruction and evaluation of the report of
that study.  The registrant should submit a representative
sampling of the raw data (particularly chromatograms and
spectra), to enable the reviewer to confirm the reported results.
The Agency expects to issue further guidance on raw data
requirements in the near future.

Additional Industry Comments on Photodegradation in Air Studies

     Although there was no rejection rate data on this study  in
your report, our internal evaluation of the rejection rate  is
high.  There is insufficient guidance available for this very
difficult study.  Industry recommends that there be a moratorium
on air photolysis studies until additional guidance can be
provided.                                                      ,

     This study is quite difficult to carry out and requires
specialized equipment.  We recommend additional discussions
between academic, EPA, and industry scientists to determine if a
practical laboratory study can indeed determine pesticide
photolysis in air.  Such a study should be focused on qualitative
aspects, as there is no clear use for quantitative rates.   It
should be required only when there is demonstrated volatility in
a laboratory volatility study.

     Industry offers to establish a forum to address the study
design.

     EPA Response

     The Agency agrees that there is insufficient guidance
available for the Photodegradation in Air data requirement; the
study is costly, complex and if not done extremely well generates
results which are difficult to interpret.  These observations
were made by the Agency almost ten years ago, at which time we
decided to dramatically reduce the instances where the
                              - 63  -
-------
                                                   Photodegradation in Air (161-4)

requirement would be imposed.  Based on an  informal poll,  the
requirement has only been imposed a few times each year.

     Additionally, the thrust of the requirement has  changed
dramatically.  When first promulgated, photodegradation  in air
was conducted to define possible exposure of workers  to
potentially toxic photoproducts, under certain  specialty use
situations (eg., greenhouse use sites).  With the  development of
Subdivision K and U emphasis shifted to general atmospheric
contamination and non-target risk (i.e., contribution to
photochemical smog, or toxic fogs). The Agency  continues to
require this study on a very limited case-by-case  basis.

     The Agency would appreciate input from the industry in
addressing the changing needs for air monitoring in general.  The
suggested forum may be an excellent mechanism to achieve this
goal.
                              - 64 -
-------
                                                  Aerobic Soil Metabolism (162-1)

             GUIDELINE 162-1 AEROBIC SOIL METABOLISM


1.   Rejection Factor:   Residue identification was incomplete.
     EPA Guidance on this Factor

     -    Subdivision N: Environmental Fate Guidelines.
          page 55.
(1982),
          Standard Evaluation Procedure  (SEP) for Aerobic Soil
          Metabolism Studies.   (June 1985), pages 9, 15-16.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December  1989), page C-296.

     The identification of residues present at levels greater
than or equal to 0.01 ppm or 10% of applied, whichever is less,
is a critical element of the aerobic soil metabolism study.  One
primary reason this study is conducted is to identify the
degradates that are formed after application of a pesticide to
soil.  The failure to identify  one (or more) significant
degradates leads to an incomplete understanding of the
metabolism, and hence the environmental  fate.  The result is that
the dissipation under actual use situations will be unclear.

     Industry Comment

     Residues occurring at a level of 10% of the applied
radioactivity or greater should be identified when feasible.  The
criteria for identification of  residues  should be consistent with
the 1982 Guidelines as stated in the purpose of the study [§
162-1 (a)] and with § 162-1  (c) (2)(ii).  The Guidelines state at
§ 162-1 (c)(2)(ii) that the concentration of the test substance
should be ". . . sufficient to  permit .  . . identification of
major degradates formed."

     The identification level specified  above is 0.01 ppm or 10%
of applied.  A residue present  at 0.01 ppm may not be a major
degradate, particularly when the normal  field application rate of
a product is greater than 1 Ib./A.  For  a variety of reasons,
e.g., specific activity limitations for  radiolabeled test
substances, technological limitations for detection/quantitation
methodology, dose rates for soil metabolism studies may differ
significantly from the field application rate.  For products with
lower field application rates,  soil metabolism studies must be
conducted at exaggerated rates  to permit metabolite
identification at the required  level.  However, for products with
field application rates exceeding approximately 1 Ib./A, the
                              - 65 -
-------
                                                  Aerobic Soil Metabolism (162-1)

requirement for identification at 0.01 ppm is excessive since
each component at or exceeding 1% of the treatment dose should be
identified.  Identification of degradates which represent 0.01
ppm is not always technically possible nor practical, especially
when considering that the starting materials may not be purer
than 97%.  Thus it may not necessarily be useful to identify
degradates that represent less than 3% of the applied material.

     b)  On page C-296 of the FIFRA Accelerated Reregistration
Phase 3 Technical Guidance, guidance is provided on the extent of
effort desired for extraction to remove residues from soil, i.e.,
11. . .a reasonable attempt was made - perhaps with multiple
solvent systems - to extract metabolites/degradates."  Guidance
documents do not address the current desire to reduce the
nonextractable residues to less than 10% of the dose rate, using
harsh acid/base digestion if required.  Further, guidance
documents do not address the extent of effort desired to identify
components of the bound residue removed by harsh digestion
procedures.  Although it may be feasible to achieve the
identification level for residues extractable by conventional
means, identification of components obtained following harsh
digestion is generally considerably more difficult due to the
large amounts of coextractives.  Since these components may have
been altered by the methods employed, it should be sufficient to
provide only characterization of these components.

     Industry Recommendations;  a)  The Agency should define
^major degradates' as degradates that represent 10% or greater of
the applied radioactivity.  Using this definition, all major
degradates should be identified.

     b)  Identification of degradates should be limited to those
components which are extractable by reasonable means, i.e.,
organic solvents and water, and not applied to components removed
following harsh acid/base digestion procedures.

     EPA Response

     The Agency agrees that the identification of residues
present at 0.01 ppm may not always be feasible, especially for
those products with field application rates exceeding
approximately 1 Ib ai/A.  The Agency will require the
identification of all residues equal to or greater than 10% of
the dose rate.  This level of residue identification should
provide adequate information for most chemicals.

     In the event that the dose rate must exceed the maximum
field application rate for residue identification purposes,
(e.g., for technological, specific activity, or other
                              - 66 -
-------
                                                  Aerobic Soil Metabolism (162-1)

limitations),  a separate exaggerated dose rate study may be
conducted.  However, this exaggerated dose rate study cannot be
used to provide kinetics information.  The kinetics study must be
conducted with the maximum dose rate as described above.

     The 10% criterion is a general guideline.  The registrant is
expected to identify single degradates present at concentrations
approaching 10% of the dose rate.  In addition, degradates of
known toxicological or ecotoxicological concern must  certainly be
identified and quantified even if they are present at <10% of the
dose rate.

     The Agency agrees that identification of degradates should
be limited to those components that are extractable by  reasonable
means  (e.g., organic solvents and water), and not necessarily
include those components removed following harsh, acid/base
extraction procedures.  These "bound" residues are generally not
available for plant or animal uptake, leaching, or run  off.  _
Harsh extraction, which changes the nature of the residues, is
not necessary.


2_«.   Rejection Factor;   The material balance was inadequate.

     EPA Guidance on this Factor

          Standard  Evaluation Procedure  (SEP) for Aerobic Soil
          Metabolism Studies.   (June 1985), page 3,  15.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.   (December  1989), page C-295.

     This is a controlled  laboratory experiment designed to
measure the breakdown  of a pesticide in  the soil and the
formation and decline  of the metabolites.  Therefore,  the test
substance applied at the beginning  of the experiment must be
accounted for at the end of the experiment to. be certain that all
degradates  formed are  isolated  and  that  an accurate  rate of
degradation is calculated.   A  good material  balance (90-110%)  is
a prerequisite for  any valid laboratory  study.
                               -  67  -
-------
                                                   Aerobic Soil Metabolism (162-1)
      Industry Comment
      Guidance is adequate on the necessity to maintain a good
 material balance.   The guidance is interpreted to mean that an
 adequate mass balance maintained during the course of the study
 is  necessary to assure that all significant degradates formed are
 isolated.   A target material balance of 90-110% would be an
 adequate measure of a study's accountability of the applied
 radioactivity.   It is possible that individual sample time points
 and/or sample replicates could fall outside of the stated
 (target)  material  balance range and not adversely effect
 interpretation of  the results.   The most prevalent example is for
 studies with test  substances which rapidly degrade to volatile
 products,  notably  CO2.

      Industry Recommendation;   The Agency should continue to
 assess any material balance deviations  from the desired target
 range (90-110%)  within the context of the entire study and not on
 a single sampling  interval.

      EPA Response

      The Agency agrees  that the material balance should be
 assessed within the context of  the entire study and not on a
 single sampling interval;  the  90-110% accountability should be
 viewed as  an ideal target range.
3.   Renection Factor:
The study was conducted for an
inadequate length of time to establish
the patterns of formation and decline.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines.
          page 55.
                                (1982),
     -    Standard Evaluation Procedure  (SEP) for Aerobic Soil
          Metabolism Studies.   (June 1985), pages 11-12.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December  1989), page C-295.

     Data are to be collected until the decline of the test
substance and the formation and decline of degradation products
are clearly characterized or for one year, whichever comes first.
The reason for this is to ensure that the kinetics of degradation
of the pesticide and of the formation and degradation of its
metabolites are fully understood.  This information is used to
                              -  68  -
-------
                                                  Aerobic Soil Metabolism (162-1)

calculate a half-life for the pesticide and predict how long it
and its metabolites persist in the environment.  If^the duration
of the study is not long enough or there are insufficient
sampling points, confidence in the calculated half-lives will be
greatly diminished as will the certainty that all degradation
products have been formed and identified.

     Industry Comment

     The purpose of the Aerobic Soil Metabolism study is to
determine the nature and extent of degradation of the parent
chemical and not, necessarily, to determine the half-life of the
parent chemical.  An Aerobic Soil Metabolism test system is an
artificial environment which exerts selection pressure  on
microbial populations.  The populations after 12 months cannot be
expected to resemble those in fresh soil.  Six months is a
sufficient time to characterize the metabolism and rate of
degradation for all intended uses of the pesticide.

     Industry Recommendation;  A maximum sampling period of 6
months would be adequate to reliably determine degradation rates.

     EPA Response

     The Agency continues to believe that  a major purpose of  the
Aerobic Soil Metabolism study is the determination of the half-
life of the parent chemical, as indicated  in each of the guidance
documents.  However, the determination  of  the nature and extent
of the formation and decline of degradation products is also
important  in helping us understand the  fate of the chemical and
anticipate the  likelihood that the compound  (or  its degradates)
will persist in the environment, where  it  may become available to
rotational crops, non-target organisms,  ground water and surface
water.

     A  6-month  timeframe may not be  sufficient to characterize
the degradation of chemicals which are  more than moderately
persistent.  However,  for those chemicals  which  are rapidly
degraded,  Subdivision  N  already allows  for flexibility  in
terminating  the study,  (i.e., until  patterns  of  decline of parent
and patterns of formation/decline of degradates  are established
or for  no  more  than  one  year, whichever comes  first).   This >
provides  a timeframe  sufficient to define  the  kinetic behavior  of
the chemical.   Chemicals found not to degrade  significantly  after
 6 months  will  be considered metabolically  stable.

      The  Agency acknowledges the  "artificial"  nature  of the
Aerobic Soil Metabolism test system, but recognizes  that a
 laboratory study is  intended to  provide preliminary  information
                               -  69  -
-------
                                                   Aerobic Soil Metabolism (162-1)

 about a pesticide (and its degradates) under well-controlled
 conditions, prior to the initiation of field studies.  Variables
 such as moisture content and temperature are maintained to ensure
 viable microbial populations in the soil, with the understanding
 that, as in the field, microbial populations will fluctuate over
 time.
 4.    Re-jaction Factor;
Purity of the test substance was not
specified.
      EPA Guidance on this factor

           Subdivision N:  Environmental Fate Guidelines. (1982),
           pages 42,  54.

           Standard Evaluation Procedure (SEP)  for Aerobic Soil
           Metabolism Studies.  (June 1985), pages 2,  8, 9.

           FIFRA Accelerated Reregistration Phase 3 Technical
           Guidance.   (December 1989),  pages C-295, C-297.

      -     Addendum 5 on Data Reporting to Pesticide Assessment
           Guidelines:  Aerobic Soil Metabolism Studies.  (January
           1988),  page 6.

      This  issue does not  normally result in the rejection of a
study,  and is  usually repairable  by the submission of additional
data.

      A  technical  grade or purer test substance is required.   A
technical  grade test substance is the  active ingredient which
does  not contain  inert ingredients other than  one used for
purification of the  active  ingredient.   A technical grade  or
purer test substance is essential for  this study as one objective
of the  study is to determine the .fate  of the pesticide and its
degradates in  a controlled  laboratory  setting.   Impurities in the
test  material  will likely confound the results.

      Industry  Comment

      Industry  agrees that adequate characterization of the test
substance  should  be  a  requirement  for  a  valid  study.   We suggest
that  a radiopurity of  95% should  be acceptable  in  most cases  and
would like the Agency  to  confirm  this.

      Industry Recommendation:  No  study  should  be  initiated with
a test substance which has not been adequately  characterized.   In
using this rejection factor however, the Agency  should be
                              -  70  -
-------
                                                  Aerobic Soil Metabolism (162-1)

specific in delineating what exactly is deficient with respect to
test substance characterization.  Further, the Agency should
specify what is acceptable radiochemical purity.  Industry
recommends that a radiopurity of 95% should be considered
acceptable unless adequate justification for lower purity is
provided by the registrant.

     EPA Response

     For laboratory studies conducted with radiolabeled
chemicals, the use of a test substance with low radiopurity may
unnecessarily complicate the identification of degradation
products since the fate of the parent and its degradates is
followed by monitoring the radioactivity.

     Industry should strive for the highest possible radiopurity
but not less than 95%.  The Agency understands that achieving a
high level of radiopurity may depend on the chemical
characteristics of the specific compound and on the type of
radioisotope used.  The Agency further acknowledges that some
chemicals may require extensive preparation in order to achieve
this high level of radiopurity, and has previously concurred with
time extensions for submission of data to allow for such
preparation.  The Agency has also previously accepted the use of
lower purity radiochemicals with adequate justification as to why
higher radiochemical purity could not be achieved.
5.   Rejection Factor;
The experimental design was inadequate
to assess the metabolism in soil.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines.
          pages 54-55.
                                (1982),
          Standard Evaluation Procedure (SEP) for Aerobic Soil
          Metabolism Studies.  (June 1985), pages 9-12.

     -    FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989), page C-295.

     This is a general criticism of the methodology employed by
the study author to evaluate the rate of degradation of the
pesticide in the soil and the rate of formation and decline of
the degradation products.  The aerobic soil metabolism study is a
laboratory study conducted under controlled conditions designed
to control as many variables as possible so that the data will
reflect degradation in soil due to microorganisms as well as
                              - 71 -
-------
                                                  Aerobic Soil Metabolism (162-1)

chemical degradation by the soil constituents, including water.
Other degradation processes, such as those caused by photolysis,
are prevented from occurring so that the data will solely reflect
soil metabolism under aerobic conditions and that the data may be
compared to data on other pesticides.  If the design of the
experiment does not follow the general guidance as outlined in
either Subdivision N or the SEP for aerobic soil metabolism, the
data may not be useful for predicting the fate of the chemical
and its degradates in the environment.

     Industry Comment

     Guidance for overall study design is adequate.

     Industry Recommendation; The experimental design should be
flexible; unnecessary requirements should be waived.  For
example, if a chemical has been shown to be photolytically stable
on soil, it should not be a requirement to conduct the study in
the complete absence of light.

     EPA Response

     The Agency agrees that the experimental design must have
some flexibility.  Requirements in Subdivision N pertaining to
experimental design are generic and cannot possibly address the
unique physical/chemical properties and behavior of each
individual pesticide.  In evaluating the experimental design, the
Agency considers whether generally-accepted methods were used,
whether sufficient numbers of measurements were made to achieve
statistical reliability, and whether sufficient controls were
built into all phases of the experiment.  In the example given in
the Recommendation, exclusion of light may still be necessary
because of its effects on microbial behavior and the resulting
impact on degradation.
6.   Rejection Factor;
The incubation temperature was not
reported.
     EPA Guidance on this factor

     -    Subdivision N: Environmental Fate Guidelines.  (1982),
          page 55.

          Standard Evaluation Procedure  (SEP) for Aerobic Soil
          Metabolism Studies.   (June 1985), page 11.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December  1989), pages C-295, C-298.
                              - 72 -
-------
                                                  Aerobic Soil Metabolism (162-1)

          Addendum 5 on Data Reporting to Pesticide Assessment
          Guidelines:  Aerobic Soil Metabolism Studies.  (January
          1988),  pages 6,7.

     This issue does not normally result in the rejection of a
study, and is usually repairable by the submission of additional
data.

     This information is important because temperature will
likely affect the metabolism rate.   Guidance for this study
requires that the study be conducted at a constant temperature
within a specified range.

     Industry Comment

     Guidance is adequate for the reporting of incubation
temperature.  However, a constant temperature of ±1°C is
technically difficult to maintain for a one-year incubation.  A
greater range, ±2-3°C, should be acceptable since it is doubtful
that this wider range would effect either the rate of degradation
or degradation pathway.

     Industry Recommendation:  The Agency should consider a wider
range, ±2-3°C, as the definition of constant temperature.

     EPA Response

     Industry  should strive to maintain a constant temperature of
±1°C.  Minor deviations  from this range would not automatically
be a cause  for rejection of the study, but would be taken into
account on  a case-by-case basis.  Since variations in temperature
will almost certainly affect the measured rate of metabolism, the
Agency continues to  believe that this parameter must be ^well-
controlled  in  order  for  the study to meet one of its major
intended purposes.   Minor fluctuations may be tolerable when the
results of  the study are not adversely impacted and the study
objectives  are met.
 7.   Rejection Factor;
The soil textures could not be confirmed
because the soils were not classified
usincr the USDA Soil Textural
Classification System.
      EPA Guidance on this factor

           Subdivision N:  Environmental Fate Guidelines.   (1982),
           pages 42-43,  55.
                              - 73 -
-------
                                                   Aerobic Soil Metabolism (162-1)

      -    Standard Evaluation Procedure (SEP)  for Aerobic Soil
           Metabolism Studies.   (June 1985),  pages 2,  8,  10.

      -    FIFRA Accelerated Reregistration Phase 3 Technical
           Guidance.   (December 1989)  pages C-295,  C-297.

      -    Addendum 5 on Data Reporting to Pesticide Assessment
           Guidelines:   Aerobic Soil Metabolism Studies.   (January
           1988),  pages  6-7.

      This  issue does not normally result in the rejection of a
study,  and is  usually repairable  by the submission of additional
data.

      Soil  characteristics may  affect the results of this  study.
The USDA Soil  Textural  Classification System is the standard
method by  which soils are classified.   This  classification
provides important information about the soil  which is then  used
in deriving conclusions from the  results of  the study.

      Rejection factors  5-10  relate to basic  information required
to be included in any study  submitted to the EPA.   The
information pertains to important study parameters that must be
reported so that  a technical evaluation of the data can be made.
In most cases,  studies  rejected solely on these reporting
deficiencies are  likely to be  upgraded by the  registrant  by  the
submission of  the additional data/information.

      Industry  Comment

      Guidance  is  adequate for  reporting the  soil textural
classification.   The Agency  needs to  specify any additional
requirements for  reporting soil characteristics.

      Industry  Recommendation;   The  Agency should specify  the soil
characteristics,  i.e.,  percent organic matter,  cation exchange
capacity,  percent content of sand,  silt,  and clay,  bulk density,
and pH, to be  reported  in addition  to  the USDA soil textural
classification.

      EPA Response

      Soil  characteristics are  currently specified  in the  SEP and,
with the exception of bulk density, also  in  the  Phase 3 Technical
Guidance Documents.  Complete  physical,  chemical and
mineralogical  characteristics  are necessary  for  a  reasonable
comparison of  soils.  When soil characteristics  are reported in  a
nonstandard way  (i.e.,  not according to the  well established USDA
                              - 74  -
-------
                                                  Aerobic Soil Metabolism (162-1)

scheme),  comparison of study results with those of other studies
becomes more difficult.
8.   Rejection Factor;
The analytical methodology was
incomplete and no raw data were provided
to support conclusions.
     EPA Guidance on this factor

          Subdivision Ns Environmental Fate Guidelines.  (1982),
          page 55.                                          :

          Standard Evaluation Procedure  (SEP) for Aerobic  Soil
          Metabolism Studies.   (June 1985), pages' 2,  3,  13,  14.

          FIFRA Accelerated Reregistration Phase 3  Technical
          Guidance.   (December  1989), pages C-296,  C-298.

          Addendum 5 on Data Reporting to Pesticide Assessment
          Guidelines:  Aerobic  Soil Metabolism  Studies.   (January
          1988), pages 7-8, 9.

     The analytical method needs  to adequately  identify  all
degradates that are formed after  application  of a pesticide to
soil.  Raw data are frequently  needed in order  for  the reviewer
to validate  the registrant's reported results and conclusions.


     Industry Comment

     Guidance for methodology,  presented in Appendix 3 of the
Standard Evaluation Procedure,  is adequate  in specifying
techniques for identification.  However, the  guidance does not
specify the  number and/or  combinations  of chromatographic
techniques required to  provide  adequate identification by
cochroraatography.

     Guidance documents do not  specify  the  amount of raw data to
 include with the  report.

      Industry Recommendation;   The Agency should specify, for the
general  case, the number of independent chromatographic
techniques  necessary  to adequately support  identity of a
metabolite  by cochromatography.

      The Agency should define what raw data need to be included
 in the final report.
                               - 75  -
-------
                                                   Aerobic Soil Metabolism (162-1)
      EPA Response
      Identification of degradates must be established using two
 different analytical techniques except when unambiguous
 identification is made using a method such as GC/MS or NMR.  In
 general,  the Agency will not consider chromatographic techniques
 utilizing the same stationary phase with two different solvent
 systems (or the same solvent system with two different stationary
 phases),  to be adequate two-method verification of degradate
 identity.

      Raw data usually consist of laboratory worksheets,  records,
 memoranda,  notes, or exact copies thereof,  which are the result
 of original observations and activities of  a study and are
 necessary for the reconstruction and evaluation of the report of
 that study.   The registrant should submit a representative
 sampling  of the raw data (particularly chromatograms and
 spectra),  to enable the reviewer to confirm the reported results.
 The Agency expects to issue further guidance on raw data
 requirements in the near future.
     Re-iection  Factor;
     Industry Comment
The raw data examined did not support
the half-life reported by the
registrant.
     Guidance  is adequate  in  specifying methods  for half-life
determinations.  However,  degradation of pesticides in  soil
seldom follow  first-order  kinetics.

     Industry  Recommendation:  The Agency should allow
first-order and non-first-order determinations of the half-life.
These methods  may include, but are not limited to, DT50
determinations and multi-phasic first-order calculations of
several half-lives.

     EPA Response

     The Agency agrees that the degradation kinetics should be
correctly defined, based on statistical evaluation of the
measured data  using an appropriate degradation model.  Some
degradation patterns do not follow either first-order or multi-
phasic first order kinetics very well.  Therefore, non first-
order determinations of the half-life should be utilized by data
submitters when appropriate, to more reliably predict the
dissipation characteristics of the compound under those
conditions.
                              -  76  -
-------
                                                  Aerobic Soil Metabolism (162-1)
10.  Renaction Factor;
Deqradate characterization data were
presented as percent of recovered rather
than percent of applied.
     EPA Guidance on this factor

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989), page C-298.

     This issue does not normally result in the rejection of a
study, and is usually repairable by the submission of additional
data.

     Results must be reported in terms of percent of applied
radioactivity in order that a material balance may be calculated.
Results reported in terms of percent of recovered radioactivity
can not be used to determine if all the pesticide applied at the
beginning of the study has been accounted for.  It is important
to be certain that all degradates formed are isolated and an
accurate rate of degradation is calculated.

     Industry Comment

     Guidance is adequate for the presentation of data to support
the reported material balance and amounts of degradates.

     Industry Recommendation; If data are expressed as a percent
of the recovered in an effort to resolve material balance
problems, the Agency should review the study according to the
criteria stated in Rejection Factor #2 above.

     EPA Response

     Data presented as "percent of recovered" tend to mask
recovery problems  (i.e., poor material balances).  Interpretation
of such data becomes more difficult, if not impossible.  Such
reporting of data  does not help resolve material balance
problems, but from our experience further confounds them.
                              - 77 -
-------
                                                 Anaerobic Soil Metabolism (162-2)

             GUIDELINE  162-2  ANAEROBIC SOIL METABOLISM


1.   Rejection  Factor;    Residue  identification was  incomplete.

     EPA Guidance  on this Factor

     -     Subdivision  N:  Environmental Fate Guidelines.   (1982),
           page  58-59.

     -     Standard Evaluation  Procedure (SEP)  for  Anaerobic  Soil
           Metabolism Studies.   (August 1988),  pages  9,  17.

     -     FIFRA Accelerated  Reregistration Phase 3 Technical
           Guidance.   (December 1989) ,  page C-300.

     The identification of those  residues  present  at levels
greater than or equal  to  0.01  ppm or  10% of applied,  whichever  is
less, is a critical element  of the anaerobic soil  metabolism
study.  One  primary reason this study is conducted is to  identify
the degradates  that are formed after  application of  a pesticide
to soil.   The failure  to  identify one (or  more)  significant
degradates leads to an incomplete understanding of the
metabolism,  and hence  the environmental fate.   The result is that
the dissipation under  actual use  situations will be  unclear.

     NOTE: The  original Subdivision N guidance for this
requirement  describes  a significantly deficient approach  to
monitoring Anaerobic (terrestrial) Soil metabolism.   As a
consequence  of  later thinking,  we have urged submitters to
utilize the  Anaerobic Aquatic  (sediments)  protocol,  which is much
more useful, using soil instead of sediments.   Studies conducted
under the  original protocol  are likely to  have very  inadequate
sampling and consequently an unreliable degradation  rate  and
metabolite estimation.

     Industry Comments

     a)   The 1982  Guidelines require  analysis,  if  feasible,  of
residues occurring at  0.01 ppm or greater  when plants are treated
at the nominal  field rate.  Industry  recommends  that  individual
compounds  comprising 10%  or greater of  the applied radioactivity
should be  identified, when feasible.   The  criteria for
identification  of  residues should be  consistent  with  the  1982
Guidelines as stated in the purpose of  the study [§  162-2(a)] and
with § 162-2(c)(2)(ii).

     The identification level  specified above  is 0.01 ppm or 10%
of applied.  A  residue present at 0.01  ppm may not be a major
                              - 78  -
-------
                                                 Anaerobic Soil Metabolism (162-2)

degradate, particularly when the normal field application rate of
a product is greater than 1 Ib./A.  For a variety of reasons,
e.g., specific activity limitations for radiolabeled test
substances, technological limitations for detection/quantitation
methodology, dose rates for soil metabolism studies may differ
significantly from the field application rate.  For products with
lower field application rates, soil metabolism studies must be
conducted at exaggerated rates to permit metabolite
identification at the required level.  However, for products with
field application rates exceeding approximately 1 Ib./A, the
requirement for identification at 0.01 ppm is excessive since
each component at or exceeding 1% of the treatment dose should be
identified.  Identification of degradates which represent 0.01
ppm is not always technically possible nor practical, especially
when considering that the starting materials may not be purer
than 97%.  Thus it may not necessarily be useful to identify
degradates that represent less than 3% of the applied material.

     b)  On page C-300 of the FIFRA Accelerated Reregistration
Phase 3 Technical Guidance, guidance is provided on the extent of
effort desired for extraction to remove residues from soil, i.e.,
"...a reasonable attempt was made - perhaps with multiple solvent
systems - to extract metabolites/degradates."  Guidance documents
do not address the current desire to reduce the nonextractable
residues to less than 10% of the dose rate, using harsh acid/base
digestion if required.  Further, guidance documents do not
address the extent of effort desired to identify components of
the bound residue removed by harsh digestion procedures.
Although it may be feasible to achieve the identification level
for residues extractable by conventional means, identification of
components obtained following harsh digestion is generally
considerably more difficult due to the large amounts of
coextractives.  Since these components may have been altered by
the methods employed, it should be sufficient to provide only
characterization of these components.

     c)  The NOTE above is clear in the direction the Agency has
provided on use of the Anaerobic Aquatic (§ 162-3) rather than
the Anaerobic Soil study design (§ 162-2).  However, the Agency's
direction has not been adequately communicated to registrants and
the Agency's mechanism of communication is not known to Industry.
The Anaerobic Aquatic (§ 162-3) study design cannot provide data
to assess item II.A.(b)  of the Standard Evaluation Procedure for
Anaerobic Soil Metabolism Studies (§ 162-2), i.e., to provide
information on "...the rate of formation and degradation of
aerobic degradation products formed during aerobic preincubation;
..."  Accordingly, Anaerobic Aquatic studies  (§ 162-3) should not
be required for terrestrial use products.
                              - 79 -
-------
                                                 Anaerobic Soil Metabolism (162-2)

     Industry Recommendations;  a) The Agency should define
%major degradates' as degradates that represent 10% or greater of
the applied radioactivity.  Using this definition of major
degradates, all major degradates should be identified.

     b)  Identification of degradates should be limited to those
components which are extractable by reasonable means, i.e.,
organic solvent and water, and not applied to components removed
following harsh acid/base digestion procedures.  The Agency
should also allow flexibility in metabolite identification based
upon the efforts involved.  For example, certain polar
metabolites may not be amenable to separation, cleanup, and/or
identification.  In such cases, characterization should be
sufficient, since polar metabolites usually tend to degrade
further.

     c)  Guidance is requested from the Agency concerning the
Agency's position that chemicals should be tested by the
Anaerobic Aquatic study design (§ 162-3) and the use of field
soil rather than sediment when using the Anaerobic Aquatic study
design (§ 162-3) for Anaerobic Soil Metabolism studies  (§ 162-2).

     EPA Response

     The Agency agrees that the identification of residues
present at 0.01 ppm may not always be feasible, especially for
those products with field application rates exceeding
approximately 1 Ib ai/A.  The Agency will require the
identification of all residues equal to or greater than 10% of
the dose rate.  This level of residue identification should
provide adequate information for most chemicals.

     In the event that the dose rate must exceed the maximum
field application rate for residue identification purposes,
(e.g., for technological, specific activity, or other
limitations), a separate exaggerated dose rate study may be
conducted.  However, this exaggerated dose rate study cannot be
used to provide kinetics information.  The kinetics study must be
conducted with the maximum dose rate as described above.

     The 10% criterion is a general guideline.  The registrant is
expected to identify single degradates present at concentrations
approaching 10% of the dose rate.  In addition, degradates of
known toxicological or ecotoxicological concern must certainly be
identified and quantified even if they are present at <10% of the
dose rate.

     The Agency agrees that identification of degradates should
be limited to those components that are extractable by reasonable
                              - 80  -
-------
                                                 Anaerobic Soil Metabolism (162-2)

means (e.g., organic solvents and water), and not necessarily
include those components removed following harsh acid/base
extraction procedures.  These "bound" residues are generally  not
available for plant or animal uptake, leaching, or run off.
Harsh extraction, which changes the nature of the residues, is
not necessary.

     The Agency agrees that a mechanism is needed to communicate
new or changing Branch policies in a more timely fashion, and is
currently developing a mechanism which involves capturing such
changes as "Policy Note" documents; these would then be made
available (via dial-in modem) from EFED's Pesticide Information
Network (PIN) bulletin board system.

     According to Subdivision N (162-2 (b) (2)), "data from an
anaerobic soil metabolism study need not be submitted if data
from the anaerobic aquatic metabolism study described in 162-3 of
this subdivision have been submitted.'1  Because of the inadequacy
of the sampling protocol described in Subdivision N for the
Anaerobic Soil Metabolism study (30 and 60 days of anaerobic
incubation), the Agency is currently recommending that the
Anaerobic Aquatic Metabolism (162-3) study protocol be followed
when an Anaerobic Soil Metabolism (162-2) data requirement has
been triggered.  The Anaerobic Aquatic Metabolism study protocol
provides for adequate sampling intervals to fully describe the
patterns of decline of parent and formation and decline of
degradates under anaerobic conditions.

     The usefulness of the Anaerobic Soil Metabolism study as it
is currently described in Subdivision N and the SEP is an issue
for future guideline revision.


2.   Rejection Factor;   The material balance was inadequate.

     EPA Guidance on this Factor

          Standard Evaluation Procedure (SEP) for Anaerobic Soil
          Metabolism Studies.  (August 1988), pages 4, 16-17.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989), page C-299.

     This is a controlled laboratory experiment designed to
measure the breakdown of a pesticide in the soil and the
formation and decline of the degradates.  This is achieved by
measuring the test substance applied at the beginning of the
experiment and then accounting for it at the end of the
experiment to be certain that all degradates formed are isolated
                              - 81  -
-------
                                                 Anaerobic Soil Metabolism (162-2)

and that an accurate rate of degradation is calculated.  A good
material balance  (90-110%) is a prerequisite for any valid
laboratory study.

     Industry Comment

     Guidance is adequate on the necessity to maintain a good
material balance.  The guidance is interpreted to mean that an
adequate mass balance maintained during the course of the study
is necessary to assure that all significant degradates formed are
isolated.  A target material balance of 90-110% would be an
adequate measure of a study's accountability of the applied
radioactivity.  It is possible that individual sample time points
and/or sample replicates could fall outside of the stated
(target) material balance range and not adversely effect
interpretation of the results.  The most prevalent example is for
studies with test substances which rapidly degrade to volatile
products, notably CO2.  It is also noted that maintaining
material balance can be more difficult with anaerobic than
aerobic studies due to measurement and summing of residue in
water and soil phases versus only soil for aerobic studies.

     Industry Recommendation:  The Agency should continue to
assess any material balance deviations from the desired target
range (90-110%) within the context of the entire study and not on
a single sampling interval.

     EPA Response

     The Agency agrees that the material balance should be
assessed within the context of the entire study and not on a
single sampling interval; the 90-110% accountability should be
viewed as an ideal target range.
                                Q f\
                                O £*
-------
3.   Rejection Factort
                        Anaerobic Soil Metabolism (162-2)

The purity of the test substance was not
specified.
     EPA Guidance on this factor

     -    Subdivision N: Environmental Fate Guidelines.
          page 42, 58.
                                (1982),
          Standard Evaluation Procedure  (SEP) for Anaerobic Soil
          Metabolism Studies.   (August 1988), pages 2, 10.

   .  -    FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December  1989), pages C-299, C-301.

     This issue does not normally result in the rejection of a
study, and is usually repairable'by the submission of additional
data.

     A technical grade or purer test substance is required.  A  ,
technical grade test substance  is the active ingredient which
does not contain inert ingredients other than one used for
purification of the active ingredient.  A technical grade or
purer test substance is essential for this study as one objective
of the study is to determine the fate of the pesticide and its
degradates in a controlled laboratory setting.  Impurities in the
test material will likely confound the results.

     Industry Comment

     Industry agrees that adequate characterization of the test
substance should be a requirement for a valid study.  We suggest
that a radiopurity of 95% should be acceptable in most cases and
would like the Agency to confirm this.

     Industry Recommendation;  No study should be initiated with
a test substance which has not been adequately characterized.  In
using this rejection factor however, the Agency should be
specific in delineating what exactly is deficient with respect to
test substance characterization.  Further, the Agency should
specify what is acceptable radiochemical purity.  Industry
recommends that a radiopurity of 95% should be considered
acceptable unless adequate justification for lower purity is
provided by the registrant.

     EPA Response

     For laboratory studies conducted with radiolabeled
chemicals, the use of a test substance with low radiopurity may
unnecessarily complicate the identification of degradation
                              -  83  -
-------
                                                 Anaerobic Soil Metabolism (162-2)

products since the fate of the parent and its degradates is
followed by monitoring the radioactivity.

     Industry should strive for the highest possible radiopurity
but not less than 95%.  The Agency understands that achieving a
high level of radiopurity may depend on the chemical
characteristics of the specific compound and on the type of
radioisotope used. The Agency further acknowledges that some
chemicals may require extensive preparation in order to achieve
this high level of radiopurity, and has previously concurred with
time extensions for submission of data to allow for such
preparation. The Agency has also previously accepted the use of
lower purity radiochemicals with adequate justification as to why
higher radiochemical purity could not be achieved.
4,   Rejection Factor;
The storage stability data were not
provided, although the raw data indicate
that both soil samples and extracts were
stored prior to analysis.
     EPA Guidance on this factor

          Standard Evaluation Procedure  (SEP) for Anaerobic Soil
          Metabolism Studies.   (August 1988), page 13.

     -    FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December  1989), page C-302.

     Even under ideal conditions, chemicals may degrade during
storage. Therefore, if samples  are taken and stored before
analysis, a storage stability study is required in order to
assess the effects, if any, of  storage on those samples.  In many
cases, studies rejected due to  storage stability data problems
may be upgraded by the registrant by the submission of additional
data/information.

     Industry Comment

     Industry agrees that storage stability data must be provided
(if the samples are stored for  an extended period of time) for
the parent and metabolites in tissue samples.  Since the nature
of the residue is unknown at the start of the study, flexibility
is required on the means of obtaining the data.

     Industry Recommendation;   Industry recommends that EPA
accept a 4- to 6-month grace period for sample storage during
which no storage stability information would be required,
provided that samples have been stored properly.  If samples are
                              - 84 -
-------
                                                 Anaerobic Soil Metabolism (162-2)

stored more than 6 months, the registrant should: a)  Reference
storage stability data already obtained from relevant sample
types and storage conditions in other studies; or b)  Analyze a
representative substrate as soon as practicable  (i.e., within 4
to 6 months of collecting the samples), and then repeat the
analysis at the end of the study.  The chromatographic profiles
may be compared to insure that no gross changes have occurred
during storage.  This is consistent with the policy on plant
metabolism studies currently in force in the Chemistry Branches
of the Health Effects Division (P. Paul conversation with R.
Loranger, 6/23/92) .

     EPA Response


     Chemicals may degrade during storage, even under ideal
storage conditions. Therefore, storage stability data are
essential in order to be confident that any degradation measured
in the test system was due solely to the environment of that test
system, and not due to handling and storage.  Storage stability
is chemical specific and a chemical's stability under storage can
vary depending upon the matrix stored (e.g., soil, water, organic
extract, plant tissue, fish tissue, etc.).  Therefore, the Agency
is concerned that a blanket 4- to 6-month grace period for sample
storage, during which no storage stability information would be
required, may not be appropriate for environmental fate testing.
The Agency does however agree that unless a pesticide/residue of
concern is otherwise known to be volatile or labile, storage
stability data will not be needed for samples stored frozen for
<30 days.

     For frozen storage intervals >30 days, it is recommended
that evidence be provided confirming that the identity of
residues did not change during the period between collection and
final analysis.  The Agency has agreed to let industry develop a
draft storage stability guidance document to address this and
other storage stability issues.  Final Agency judgement on this
issue will be reserved for the Storage Stability follow-up
guidance.

     Ideally, storage stability data should be obtained
concurrently with the particular environmental fate guideline
study, not independent from it.  However, concurrent storage
stability studies will not be required in many cases.  Provided
that the pesticide residues are found to be stable in the
matrices of interest, a storage stability study run in a separate
freezer at a different time period will be acceptable if the
storage conditions (particularly temperature) are the same as
those in the corresponding environmental fate guideline study.
                              -  85  -
-------
                                                 Anaerobic Soil Metabolism (162-2)

However, for pesticides whose residues are known or suspected to
be unstable or volatile, concurrent studies may be needed.  In
fact, for such pesticides, it is advisable to run a storage
stability study in advance to determine proper storage conditions
and maximum storage times before treated samples are placed into
storage.
     Rejection Factor;
Degradates present in small
concentrations were not identified.
     EPA Guidance on this Factor

     -    Subdivision N: Environmental Fate Guidelines.  (1982),
          pages 58-59.

     -    Standard Evaluation Procedure  (SEP) for Anaerobic Soil
          Metabolism Studies.   (August 1988), pages 9, 17.

     -    FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December  1989), page C-300.

     Identifying residues present at levels greater .than or equal
to 0.01 ppm or 10% of applied, whichever is less, is a critical
element of the anaerobic soil metabolism study.  One primary
reason this study is conducted  is to identify the degradates that
are formed after application of a pesticide to soil.

     Industry Comment

     a)  The 1982 Guidelines require analysis, if feasible, of
residues occurring at 0.01 ppm  or greater when plants are treated
at the nominal field rate.  Industry recommends that individual
compounds comprising 10% or greater of the applied radioactivity
should be identified, when feasible.  The criteria for
identification of residues should be consistent with the 1982
Guidelines as stated in the purpose of the study [§ 162-2(a)] and
with § 162-2(c)(2)(ii).

     The identification level specified above is 0.01 ppm or 10%
of applied.  Residues present at 0.01 ppm may not be a major
degradate, particularly when the normal field application rate of
the product is greater than 1 Ib/A.   For a variety of reasons,
e.g., specific activity limitations for radiolabeled test
substances or technological limitations for
detection/quantitation methodology, dose rates for soil
metabolism studies may differ from the field application rate.
For products with lower field application .rates, soil metabolism
studies need to be conducted at exaggerated rates to permit
                              - 86 -
-------
                                                 Anaerobic Soil Metabolism (162-2)

metabolite identification at the required level.  However, for
products with field application rates exceeding approximately 1
Ib./A, the requirement for identification at 0.01 ppm is
excessive since each component at or exceeding 1% of the
treatment dose should be identified.  On the other hand, when the
application rate is low, major degradates or the parent compound
may be present at a concentration less than 0.01 ppm.
Identification of degradates which represent 0.01 ppm is not
always technically possible nor practical.  Especially when
considering that the starting materials may not be purer than 97%
and thus will not necessarily be useful to identify degradates
that represent less than 3% of the applied material.

     b)  On page C-300 of the FIFRA Accelerated Reregistration
Phase 3 Technical Guidance, guidance is provided on the extent of
effort desired for extraction to remove residues from soil, i.e.,
"...a reasonable attempt was made - perhaps with multiple solvent
systems - to extract metabolites/degradates."  Guidance documents
do not address the current desire to reduce the nonextractable
residues to less than 10% of the dose rate, using harsh acid/base
digestion if required.  Further, guidance documents do not
address the extent of effort desired to identify components of
the bound residue removed by harsh digestion procedures.
Although it may be feasible to achieve the identification level
for residues extractable by conventional means, identification of
components obtained following harsh digestion is generally
considerably more difficult due to the large amounts of
coextractives.  Since these components may have been altered by
the methods employed, it should be sufficient to provide only
characterization of these components.

     Industry Recommendations; a)  The Agency should define
*major degradates' as degradates that represent 10% or greater of
the applied radioactivity.  Using this definition of major
degradates, all major degradates should be identified.

     b)  Identification of degradates should be limited to those
components which are extractable by reasonable means, i.e.,
organic solvent and water, and not applied to components removed
following harsh acid/base digestion procedures.

     EPA Response

     The Agency agrees that the identification of residues
present at 0.01 ppm may not always be feasible, especially for
those products with field application rates exceeding
approximately 1 Ib ai/A.  The Agency will require the
identification of all residues equal to or greater than 10% of
                              -  87  -
-------
                                                 Anaerobic Soil Metabolism (162-2)

the dose rate.  This level of residue identification  should
provide adequate information for most chemicals.

     In the event that the dose rate must exceed the  maximum
field application rate for residue identification purposes,
(e.g., for technological, specific activity, or other
limitations), a separate exaggerated dose rate study  may be
conducted.  However, this exaggerated dose rate study cannot  be
used to provide kinetics information.  The kinetics study must be
conducted with the maximum dose rate as described above.

     The 10% criterion is a general guideline.  The registrant is
expected to identify single degradates present at concentrations
approaching 10% of the dose rate.  In addition, degradates of
known toxicological or ecotoxicological concern must  certainly be
identified and quantified even if they are present at <10% of the
dose rate.

     The Agency agrees that identification of degradates should
be limited to those components that are extractable by reasonable
means (e.g., organic solvents and water), and not necessarily
include those components removed following harsh acid/base
extraction procedures.  These "bound" residues are generally  not
available for plant or animal uptake, leaching, or run off.
Harsh extraction, which changes the nature of the residues, is
not necessary.
     Rejection Factor;
The experimental design was inadequate
to accurately assess the degradation
under anaerobic conditions.
     EPA Guidance on this Factor

     -    Subdivision N: Environmental Fate Guidelines.
          pages 58-59.
                                (1982),
          Standard Evaluation Procedure  (SEP) for Anaerobic Soil
          Metabolism Studies.   (August 1988), pages 10-13.

     -    FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December  1989) page C-299.

     This is a general criticism of the methodology employed by
the study author to evaluate the rate of pesticide degradation in
the soil and the rate of formation and decline of the degradation
products.  The anaerobic soil metabolism study is a laboratory
study conducted under controlled conditions designed to account
for as many variables as possible so that the data will reflect
                                88  -
-------
                                                 Anaerobic Soil Metabolism (162-2)

 degradation in soil due to microorganisms as well  as chemical
 degradation by the soil constituents,  including water.   Other
 degradation processes,  such as those caused by photolysis,  are
 prevented from occurring so that the data will solely reflect
 soil  metabolism under anaerobic conditions and so  that  the  data
 may be  compared to data on other pesticides.   If the design of
 the experiment does not follow the general guidance as  outlined
 in either Subdivision N or the SEP for anaerobic soil metabolism,
 the data  may not be useful for predicting the fate of the
 chemical  and its degradates in the environment.

      Industry Comment

      The  anaerobic metabolism  of a chemical with a long aerobic
      life may be suitably characterized by a study which begins
 with  anaerobic conditions.   If the intent is  to  determine the
 fate  of the parent compound, then the  requirement  for aerobic
 incubation is unnecessary.  Since the Anaerobic Aquatic  study may
 be submitted in lieu of an Anaerobic Soil study  [see §
 162-2(b)(2)],  there is  limited justification  for an initial
 aerobic phase in the latter study.

    _Industry Recommendation:   The experimental  design  should be
 flexible;  unnecessary requirements should be  waived.  For
 example,  if a chemical  has  been shown  to  be photolytically  stable
 on soil,  it should not  be a requirement to conduct the  study in
 the complete absence of light.   Industry  requests  the Agency to
 allow the  Anaerobic Soil  Metabolism study to  be  conducted without
 aerobic incubation for  chemicals with  an  aerobic half-life
 greater than 100  days.

     EPA Response

     The Agency  agrees  that the  experimental  design must  have
 some flexibility.   Requirements  in Subdivision N pertaining to
 experimental  design  are generic and  cannot  possibly address  the
unique  physical/chemical  properties  and behavior of each
 individual  pesticide.   In evaluating the  experimental design, the
Agency  considers whether  generally-accepted methods were  used,
whether^sufficient numbers  of measurements were  made to achieve
statistical  reliability,  and whether sufficient  controls  were
built into  all phases of  the experiment.   In the example  given  in
the Recommendation,  exclusion of light may  still be necessary
because of  its effects on microbial behavior and the resulting
impact  on degradation.

    _The Agency agrees that the anaerobic metabolism of a
chemical with a long aerobic half-life may be suitably
characterized by a study which forgoes the aerobic preincubation.
                              -  89  -
-------
                                                 Anaerobic Soil Metabolism (162-2)

The 100 day figure proposed by Industry for allowing the
Anaerobic Soil Metabolism study to be conducted without aerobic
incubation for chemicals seems reasonable, and its implementation
will be considered.  However, the aerobic preincubation would
certainly be indicated for those compounds which degrade somewhat
rapidly under aerobic conditions.
     Re-}ection Factor;
                         The length of frozen storage was not
                         specified.  Frozen storage stability
                         data are required to confirm that the
                         residues were stable.

     EPA Guidance on this factor

          Standard Evaluation Procedure (SEP) for Anaerobic Soil
          Metabolism Studies.  (August 1988), page 13.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989), page C-302.

     Even under ideal conditions, chemicals may degrade during
storage. Therefore, if samples are taken and stored for long
periods of time prior to analysis, a storage stability study is
required in order to assess the effects, if any, of storage on
those samples.  In many cases, studies rejected due to storage
stability data problems may be upgraded by the registrant
submitting additional data/information.

     Industry Comment

     Industry agrees that storage stability data must be provided
(if the samples are stored for an extended period of time) for
the parent and metabolites in tissue samples.  Since the nature
of the residue is unknown at the start of the study, flexibility
is required on the means of obtaining the data.

     Industry Recommendation:  Industry recommends that EPA
accept a 4- to 6-month grace period for sample storage during
which no storage stability information would be required,
provided that samples have been  stored properly.  If samples are
stored more than 6 months, the registrant should: a)  Reference
storage stability data already obtained from relevant sample
types and storage conditions  in  other studies; or b)  Analyze a
representative substrate as  soon as practicable  (i.e., within 4
to 6 months of collecting the samples), and  then repeat the
analysis at the end of the study.  The  chromatographic profiles
may be  compared to insure that no  gross changes have occurred
during  storage.This is consistent  with  the policy on plant
                                 90  -
-------
                                                 Anaerobic Soil Metabolism (162-2)

metabolism studies currently in force in the Chemistry Branches
of the Health Effects Division  (P. Paul conversation with R.
Loranger, 6/23/92).

     EPA Response

     Chemicals may degrade during storage, even under ideal
storage conditions. Therefore, storage stability data are
essential in order to be confident that any degradation measured
in the test system was due solely to the environment of that  test
system, and not due to handling and storage.  Storage stability
is chemical specific and a chemical's stability under storage can
vary depending upon the matrix stored (e.g., soil, water, organic
extract, plant tissue, fish tissue, etc.).  Therefore, the Agency
is concerned that a blanket 4- to 6-month grace period for sample
storage, during which no storage stability information would  be
required, may not be appropriate for environmental fate testing.
The Agency does however agree that unless a pesticide/residue of
concern is otherwise known to be volatile or labile, storage
stability data will not be needed for samples stored frozen for
< 30 days.

     For frozen storage intervals >30 days, it is recommended
that evidence be provided confirming that the identity of
residues did not change during the period between collection  and
final analysis.  The Agency has agreed to let industry develop a
draft storage stability document to address this and other
storage stability issues.  Final Agency judgement on this issue
will be reserved for the Storage Stability follow-up guidance.

     Ideally, storage stability data should be obtained
concurrently with the particular environmental fate guideline
study, not independent from it.  However, concurrent storage
stability studies will not be required in many cases.  Provided
that the pesticide residues are found to be stable in the
matrices of interest, a storage stability.study run in a separate
freezer at a different time period will be acceptable if the
storage conditions (particularly temperature)  are the same as
those in the corresponding environmental fate guideline study.
However, for pesticides whose residues are known or suspected to
be unstable or volatile,  concurrent studies may be needed.  In
fact, for such pesticides, it is advisable to run a storage
stability study in advance to determine proper storage conditions
and maximum storage times before treated samples are placed into
storage.
                              -  91  -
-------
                                                 Anaerobic Soil Metabolism (162-2)
8.   Rejection Factor;
Method detection limits were not
provided.
     EPA Guidance on this Factor

          Standard Evaluation Procedure  (SEP) for Anaerobic Soil
          Metabolism Studies.   (August 1988), pages 3, 14, 15, 17

     -    FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December  1989), page C-299.

     This rejection factor relates to basic  information required
to be included in any study submitted to the EPA.  The
information pertains to an important study parameter that must be
reported so that a technical evaluation of the data can be made.
In most cases, studies rejected solely on this reporting
deficiency are likely to be upgraded by the  registrant by the
submission of the additional data/information.

     Industry Comment

     Guidance is acceptable for the necessity to report method
detection limits for quantitation.

     Industry Recommendation;   Method detection limits for
quantitation will be reported.

     EPA Response

     No comment necessary.
9,   Rejection Factor;
Large discrepancies existed in the data
for duplicate samples collected after
anaerobic conditions were established.
The data, therefore, cannot be used
reliably to calculate the rate of
degradation in soil under anaerobic
conditions.
     EPA Guidance on this Factor

          Standard Evaluation Procedure  (SEP)  for Anaerobic  Soil
          Metabolism Studies.   (August 1988),  pages  3,  12.  •

     In order for the data to be  statistically significant,  the
soil treatments must be replicated.  Replicate treatments  should
                              - 92 -
-------
                                                 Anaerobic Soil Metabolism (162-2)

provide similar, if not the same, results.  If the results are
dissimilar, a standard statistical methodology may then be used
to disqualify the study as unreliable.  Large discrepancies may
be indicative of a major problem in the experimental design
and/or analytical methodology.

     Industry Comment

     In test systems where microbial processes are occurring, it
is not uncommon to observe variations of 10% or more in
degradation rates even with study durations of 60 days or less.
Especially at later sampling intervals when the level of parent
may be minimal and bound residues may be significant, precision
diminishes due to the summing of parent residues in the water and
soil phases.  It is unrealistic to expect that results would  be
'the same'.

     Industry Recommendation;  Industry requests the Agency to be
flexible recognizing the limitations of analyzing minute
quantities of residues.

     EPA Response

     The Agency is aware of the limitations involved  in analyzing
small quantities of residues and strives to take these into
account when interpreting such data.
     Rejection Factor;
The study was conducted for an
inadequate length of time to establish
the patterns of formation and decline of
the pesticide under anaerobic
conditions.  The study should have been
conducted for 60 days.
     EPA Guidance on  this Factor

          Subdivision N: Environmental  Fate  Guidelines.
          page  58.
                                 (1982),
           Standard  Evaluation Procedure  (SEP)  for  Anaerobic Soil
           Metabolism  Studies.   (August 1988),  pages  12,  13

           FIFRA Accelerated  Reregistration  Phase 3 Technical
           Guidance.   (December  1989), page  C-299.

      In  the  case  of a highly persistent  compound,  the time
 required to  meet  the  intent  of  the  guidance may exceed 60 days.
                              - 93 -
-------
                                                 Anaerobic Soil Metabolism (162-2)

 Data should have been collected for at least 60 days after
 anaerobic conditions were established for this particular active
 ingredient.   This is to be certain that the kinetics of pesticide
 degradation and of the formation and degradation of its
 metabolites are fully understood.   The data are used to calculate
 a  half-life for the pesticide and predict how long it and its
 degradates^will persist in the environment.   If the duration of
 the  study is not long enough or there are insufficient  sampling
 points,  the reliability of the calculated half-lives will be
 greatly  diminished as will the certainty that all  degradation
 products have been formed and identified.

      Experimenters may fail to conduct the study for a  sufficient
 length of time because they (inappropriately)  choose to save all
 samples  frozen until the conclusion of the study.   They therefore
 might not be aware of the chemical's persistence.   Ideally,
 samples  should be analyzed soon after collection,  and results
 compared throughout the course of  the study.

      Industry Comment

      As  noted under Rejection Factor 1,  the  Agency recognizes the
 deficiency of guidance documents for Anaerobic Soil Metabolism  in
 specifying a study duration sufficient to  observe  formation  and
 decline  of degradates.   The anaerobic metabolism of a chemical
 with  a long  aerobic half-life may  be suitably characterized  by  a
 study which  begins with anaerobic  conditions.   If  the intent is
 to determine the  fate of the parent compound,  then the
 requirement  for aerobic incubation is unnecessary.  Since  the
 Anaerobic Aquatic study may be submitted in  lieu of an  Anaerobic
 Soil  study [see §  162-2(b) (2)] , there is limited justification
 for an initial aerobic phase in the latter study.

      Industry Recommendation;   As  recommended  under Rejection
 Factor 1,  guidance should be revised for Anaerobic Soil
 Metabolism to include at a  minimum when  required (if  it is
 currently the Agency's  position that all chemicals should be
 tested by the Anaerobic  Aquatic protocol) and  the  use of  field
 soil  rather  than  sediment when using the Anaerobic Aquatic study
 design.   The experimental design should  be flexible; unnecessary
 requirements  should be waived.  For example,  if  a  chemical has
 been  shown to be photolytically stable,  it should  not be  a
 requirement  to conduct the  study in the  complete absence  of
 light. _Industry requests the  Agency to  allow  the  Anaerobic  Soil
Metabolism study to  be conducted without aerobic incubation  for
 chemicals with an  aerobic half-life  greater than 100 days.
                              ^  94  -
-------
                                                 Anaerobic Soil Metabolism (162-2)
     EPA Response
     According to Subdivision N  (162-2  (b)  (2)), "data from an
anaerobic soil metabolism study need not be submitted if data
from the anaerobic aquatic metabolism study described in 162-3 of
this subdivision have been submitted."  Because of the inadequacy
of the sampling protocol described in Subdivision N for the
Anaerobic Soil Metabolism study  (30 and 60 days of anaerobic
incubation), the Agency is currently recommending that the
Anaerobic Aquatic Metabolism (162-3) study protocol be followed
when an Anaerobic Soil Metabolism (162-2) data requirement has
been triggered.  The Anaerobic Aquatic Metabolism study protocol
provides for adequate sampling intervals to fully describe the
patterns of decline of parent and formation and decline of
degradates under anaerobic conditions.  The test media should
always be sediments collected from areas predominantly under
anaerobic conditions.

     The usefulness of the Anaerobic Soil Metabolism study as it
is currently described in Subdivision N and the SEP is an issue
for future guideline revision.

     The Agency agrees that there needs to be flexibility in
designing this experiment.  Requirements in Subdivision N
pertaining to experimental design are generic and cannot possibly
address the unique physical/chemical properties and behavior of
each individual pesticide.  In evaluating the experimental
design, the Agency considers whether generally-accepted methods
were used, whether sufficient numbers of measurements were made
to achieve statistical reliability,  and whether sufficient
controls were built into all phases of the experiment.


11.  Rejection Factor:   No raw data were provided to support the
                         conclusions.

     EPA Guidance on this factor

     -    Subdivision N: Environmental Fate Guidelines.  (1982),,
          page 59.

     -    Standard Evaluation Procedure (SEP)  for Anaerobic Soil
          Metabolism Studies.  (August 1988),  pages 3, 15.

     This issue does not normally result in the rejection of a
study, and is usually repairable by the submission of additional
data.
                              -  95  -
-------
                                                 Anaerobic Soil Metabolism (162-2)

     Raw data are frequently needed in order for EPA to validate
the registrant's reported results and conclusions.

     Industry Comment

     Industry is not certain what is meant by "raw data."
Guidance documents do not specify the amount of raw data to
include with the report.  It would be helpful if the Agency
defined the minimum raw data required for inclusion in the study
report.

     Industry Recommendation;  The Agency should define the
minimum raw data required for inclusion in the study report.

     EPA Response

     Raw data usually consist of laboratory worksheets, records,
memoranda, notes, or exact copies thereof, which are the result
of original observations and activities of a study and are
necessary for the reconstruction and evaluation of the report of
that study.  The registrant should submit a representative
sampling of the raw data  (particularly chromatograms and
spectra), to enable the reviewer to confirm the reported results.
The Agency expects to issue further guidance on raw data
requirements in the near future.
12,  Rejection Factor;
A complete description of the test
water, including the pH and dissolved
oxygen content, was not provided.
     This  issue  does  not  normally result  in  the  rejection of  a
study, and is usually repairable by  the submission  of  additional
data.

     A description  of the test water is essential for  the purpose
of defining the  conditions under which the study is conducted.

     Industry Comment

     Industry agrees  that a description of the test water is
essential  for the purpose of defining the conditions under which
the  study  is conducted.

     Industry Recommendation;  The Agency should specify that
anaerobicity  (pH and  redox potential) should be  demonstrated  and
reported.
                              - 96 -
-------
                                                 Anaerobic Soil Metabolism (162-2)
     EPA Response
     The Agency agrees that pH and redox potential should be
determined, and both the SEP and the Phase 3 Technical Guidance
documents specify that these measurements are to be reported.
The Agency welcomes additional discussion on a clear definition
of "anaerobic conditions."
13.  Rejection Factor;
The soil was not classified according to
the USDA Soil Textural Classification
System.
     EPA Guidance on this factor

          Subdivision N: Environmental Fate Guidelines.
          pages 42-43, 59.
                                (1982),
     -    Standard Evaluation Procedure  (SEP) for Anaerobic Soil
          Metabolism Studies.   (August 1988), pages 2, 9, 11.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December  1989), pages C-299, C-301.

     This issue does not normally result in the rejection of a
study, and is usually repairable by the submission of additional
data.

     Soil characteristics may affect the results of this study.
The USDA Soil Textural Classification System is the standard
method by which soils are classified.  This classification
provides important information about the soil which is then used
in deriving conclusions from the results of the study.

     Rejection factors 8 to 13 relate to basic information
required to be included in any study submitted to the EPA.  The
information pertains to important study parameters that must be
reported so that a technical evaluation of the data can be made.
In most cases, studies rejected solely on these reporting
deficiencies are likely to be upgraded by the registrant by the
submission of the additional data/information.

     Industry Comment

     Guidance is adequate for reporting the soil textural
classification.  The Agency needs to specify any additional
requirements for reporting soil characteristics.
                              -  97  -
-------
                                                 Anaerobic Soil Metabolism (162-2)

     Industry Recommendation;  The Agency  should specify  the soil
characteristics, i.e., percent organic matter,  cation exchange
capacity, percent content of sand, silt, and  clay,  bulk density,
and pH, to be reported in addition to the  USDA  soil textural
classification.

     EPA Response

     Soil characteristics are currently  specified  in the  SEP and,
with the exception of bulk density,  also in the Phase 3 Technical
Guidance Documents.  Complete physical,  chemical and
mineralogical characteristics are necessary for a  reasonable
comparison of soils.  When soil  characteristics are reported in a
nonstandard way  (i.e., not according to  the well established USDA
scheme), comparison of study results with  those of other  studies
becomes more difficult.
                               -  98  -
-------
                                               Anaerobic Aquatic Metabolism (162-3)


          GUIDELINE  162-3 ANAEROBIC AQUATIC METABOLISM
1.
Rejection Factor;
The sampling protocol was inappropriate
because it contained too few sampling1
intervals and was inadequate to
establish the half-life for the
pesticide.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines.
          page.60.  '    ,      .       • • . . .
                                                     (1982) ,
     - .•..  FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.   (December 1989), page C-303..   .

     Data are to be collected until  the decline of the test
substance and the formation and decline of degradation products
are clearly characterized or for one year, whichever comes first.
This is to be certain that the kinetics of pesticide degradation
and of the formation and degradation of its metabolites are fully
understood.  This information is used to calculate a half-life
for the pesticide and predict how long it and its degradates will
persist in the environment.  If the  duration of the study is not
long enough or there are insufficient sampling points, the
reliability in the calculated half-lives will be greatly
diminished as will the certainty that all degradation products
have been formed and identified.

     Industry Comment

     The purpose of the Anaerobic Aquatic Metabolism study is to
determine the nature and extent of degradation of the parent
chemical and not, necessarily, to determine the half-life of the
parent chemical.  An Anaerobic Aquatic Metabolism test system is
an artificial environment which exerts selection pressure on
microbial populations.  The populations after 12 months  cannot  be
expected to resemble  those in fresh  soil.  Six months is  a
sufficient time to characterize the  metabolism and rate  of
degradation for all intended uses of the pesticide.

      Industry Recommendation;  A maximum sampling period of  6
months would be adequate to reliably determine degradation rates.

      EPA Response

      The Agency continues  to believe that  a major purpose of  the
Anaerobic Aquatic Metabolism study  is rthe  determination  of  the
half-life of the parent  chemical, as indicated  in  each of the
                              - 99  -
-------
                                               Anaerobic Aquatic Metabolism (162-3)

guidance documents.  However, the determination  of  the nature and
extent of the formation and decline  of degradation  products  is
also important in helping us understand  the  fate of the chemical
and anticipate the likelihood that the compound  (or its
degradates) will persist in aquatic  environments, where it may
become available to irrigated crops, non-target  organisms, ground
water and surface water.

     A 6-month timeframe may not be  sufficient to characterize
the degradation of chemicals which are more  than moderately
persistent.  However, for those chemicals which  are rapidly
degraded. Subdivision N already allows for flexibility in
terminating the study  (i.e., until patterns  of decline of parent
and patterns of formation/decline of degradates  are established
or for no more than one year, whichever  comes first).  This
provides a timeframe sufficient to define the kinetic behavior of
the chemical.  Chemicals found not to degrade significantly  after
6 months will be considered metabolically stable.

     The Agency acknowledges the "artificial" nature of the
Anaerobic Aquatic Metabolism test system, but recognizes that a
laboratory study is intended to provide  preliminary information
about a pesticide (and its degradates) under well-controlled
conditions, prior to the initiation  of field studies.  Variables
such as redox potential and temperature  are  maintained to ensure
viable microbial populations in the  sediment, with  the
understanding that,  as in the field, microbial populations will
fluctuate over time.
     Rejection Factor:   The pesticide residues were quantified
                         using a chemically nonspecific
                         analytical method.  No attempt was made
                         to characterize the pesticide residues
                         in soil and water matrices.

     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines.  (1982),
          pages 60-61.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.   (December 1989), page C-303.

     One primary reason this study is conducted is to identify
each and every significant degradate that is formed after
application of a pesticide to the aquatic environment, if
feasible.  An analytical method that is chemically nonspecific
cannot distinguish between different residues, as it can only
                             - 100 -
-------
                                               Anaerobic Aquatic Metabolism (162-3)

measure the total amount of those residues present with no regard
to their individual identities.  The identification of residues
present at levels greater than or equal to 0.01 ppm or 10% of
applied, whichever is less, is a critical element of the
anaerobic aquatic metabolism study.

     Industry Comment

     a)  Although no Standard Evaluation Procedure or Pesticide
Assessment Guideline has been issued for Anaerobic Aquatic
Metabolism, guidance regarding identification of
metabolites/degradates is presented in Subdivision N Guidelines
and Phase 3 Technical Guidance.

     b)  Residues occurring at a level of 10% of the applied
radioactivity or greater should be identified when feasible.  The
criteria for identification of residues should be consistent with
the 1982 Guidelines as stated in the purpose of the study  [§
162-3  (a)] and with § 162-3 (c)(2)(ii).  Guidelines state at  §
162-3  (c)(2)(ii) that .the test substance should be applied at a
rate "... sufficient to permit . . . identification of major
degradates."

     The identification level specified above is 0.01 ppm or  10%
of applied.  A residue present at 0.01 ppm may not be a major
degradate, particularly when the normal field application rate of
a product is greater than 1 Ib./A.  For a variety of reasons,
e.g., specific activity limitations for radiolabeled test
substances, technological limitations for detection/quantitation
methodology, dose rates may differ significantly from the field
application rate.  For products with lower field application
rates, Anaerobic Aquatic Metabolism studies must be conducted at
exaggerated rates to permit metabolite identification at the
required level.  However, for products with field application
rates exceeding approximately 1 Ib./A, the requirement for
identification at 0.01 ppm is excessive since each component at
or exceeding 1% of the treatment dose should be identified.
Identification of degradates which represent 0.01 ppm is not
always technically possible nor practical, especially when
considering that the starting materials may not be purer than
97%.  Thus it may not necessarily be useful to identify
degradates that represent less than 3% of the applied material.

     c)  On page C-303 of the FIFRA Accelerated Reregistration
Phase 3 Technical Guidance, guidance is provided on the extent of
effort desired for extraction to remove residues from soil, i.e.,
"...a reasonable attempt was made  - perhaps with multiple solvent
systems  - to extract metabolites/degradates."  Guidance documents
do not address the current desire to reduce the nonextractable
                              - 101  -
-------
                                               Anaerobic Aquatic Metabolism (162-3)

residues to less than 10% of the dose rate, using harsh acid/base
digestion if required.  Further, guidance documents do not
address the extent of effort desired to identify components of
the bound residue removed by harsh digestion procedures.
Although it may be feasible to achieve the identification level
for residues extractable by conventional means, identification of
components obtained following harsh digestion is generally
considerably more difficult due to the large amounts of
coextractives.  Since these components may have been altered by
the methods employed, it should be sufficient to provide only
characterization of these components.

     Industry Recommendation;  a)  Since the Agency is
recommending the Anaerobic Aquatic protocol, using soil instead
of sediment, for the Anaerobic Soil metabolism study, it is
highly recommended that written guidance be issued, e.g., a
Standard Evaluation Procedure.  To the extent possible, it is
recommended that study design, reporting requirements, etc. be
consistent for the Anaerobic Soil and Anaerobic Aquatic
requirements.  If the Agency desires, Industry is willing to
draft a Standard Evaluation Procedure for EPA.

     b)  The Agency should define 'major .degradates' as
degradates that represent 10% or greater of the applied
radioactivity.  Using this definition of major degradates, all
major degradates should be identified.

     c)  Identification of degradates should be limited to those
components which are extractable by reasonable means, i.e.,
organic solvent and water, and not applied to components removed
following harsh acid/base digestion procedures..

     EPA Response

     The Agency acknowledges the need for additional guidance,
and would welcome Industry's support in the development of
additional SEPs for the remaining guidelines for which no SEP
currently exists.

     The issue of nonspecific analytical methods to quantitate
residues was not addressed in Industry's response.  The
identification and quantification of both parent and major
degradates requires the use of methods of analysis that will
unequivocally distinguish between the various degradates arid/or
metabolites in an extract, as well as between these components
and other substances which might interfere with the analysis. In
some cases, methods used are simply too non-specific  (e.g., One-
Dimensional Thin Layer Chromatography with UV visualization,
                              -  102  -
-------
                                               Anaerobic Aquatic Metabolism (162-3)

total radioactivity),  and cannot possibly distinguish/confirm
components.


3.   Rejection Factor;   Material balances were incomplete.

     EPA Guidance on this Factor

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.   (December 1989), page C-303.

     This is a laboratory experiment designed to measure the
breakdown of a pesticide in the hydrosoil/water medium  and the
formation and decline of the metabolites.  This is achieved by
measuring the test substance at the beginning of the experiment
and then accounting for it at the end of the experiment to ensure
that all degradates formed are isolated and that an accurate rate
of degradation is calculated.  A good material balance  (90-110%)
is a prerequisite for any valid laboratory study.

     Industry Comment

     Guidance is adequate on the necessity to maintain  a good
material balance.  The guidance is interpreted to mean  that an
adequate mass balance maintained during the course of the study
is necessary to assure that all significant degradates  formed are
isolated.  A target material balance of 90-110% would be an
adequate measure of a study's accountability of the applied
radioactivity.  It  is possible that  individual sample time points
and/or sample replicates could fall  outside of the stated
 (target) material balance range and  not adversely effect
interpretation of the results.  The  most prevalent example is for
studies with test substances which rapidly degrade to volatile
products, notably C02.  It is also noted that maintaining
material balance can  be more difficult with anaerobic than^
aerobic studies due to measurement and summing of residue  in
water and soil phases versus only soil for aerobic  studies.

     Industry Recommendation: The Agency  should  continue  to
assess any material balance deviations from the  desired target
range  (90-110%) within the context of the entire  study  and not  on
a single  sampling  interval.

     EPA  Response

     The  Agency agrees that  the material  balance should be
assessed  within the context  of  the entire study  and not on a
 single  sampling interval;  the  90-110% accountability should be
viewed  as an ideal  target  range.
                              - 103 -
-------
                                                Anaerobic Aquatic Metabolism (162-3)

4.1.   Re-jaction Factor;    Degradates were not identified.

      EPA Guidance on this Factor

           Subdivision N:  Environmental Fate Guidelines.   (1982),
           page 61.

           FIFRA Accelerated Reregistration Phase 3 Technical
           Guidance.   (December 1989),  page C-303.

      The  identification of residues present at levels greater
than  or_equal  to 0.01 ppm or 10% of applied,  whichever is less,
is a  critical  element of  the anaerobic aquatic metabolism study.
One primary  reason this study is conducted to identify the
degradates that are  formed after application of a  pesticide to
the aquatic  environment.   Failure to identify one  (or more)
significant  degradates  may result in an unclear understanding of
the metabolism,  and  hence the environmental fate.   Thus  the
understanding  of dissipation under actual use situations  is
uncertain.

      Industry  Comment

      a)  Although no Standard Evaluation Procedure or Pesticide
Assessment Guideline has  been issued for Anaerobic Aquatic
Metabolism,  guidance regarding identification of
metabolites/degradates  is presented in Subdivision N Guidelines
and Phase  3  Technical Guidance.

      b)  Residues occurring at a level of 10% of the applied
radioactivity  or greater  should be identified when feasible.  The
criteria for identification of residues should be  consistent with
the 1982 Guidelines,  as stated in the  purpose of the study [§
162-3(a)], and with  § 162-3(c) (2) (ii).   Guidelines state  at §
162-3(c)(2)(ii)  that the  test substance should be  applied at a
rate  "...  sufficient  to permit .  .  .  identification of  major
degradates."

      The identification level specified above is 0.01 ppm or 10%
of applied.  A residue  present at 0.01 ppm may not be a major
degradate, particularly when the normal field application rate of
a product  is greater than 1  Ib./A.   For a variety  of reasons,
e.g.,  specific  activity limitations  for radiolabeled test
substances,  technological  limitations  for detection/quantitation
methodology,  dose rates may  differ significantly from the field
application  rate.  For  products  with lower field application
rates, Anaerobic  Aquatic Metabolism studies must be  conducted at
exaggerated  rates to permit  metabolite identification at  the
required level.   However,  for products with field  application
                             - 104 -
-------
                                               Anaerobic Aquatic Metabolism (162-3)

rates exceeding approximately 1 Ib./A, the requirement for
identification at 0.01 ppm is excessive since each component at
or exceeding 1% of the treatment dose should be identified.
Identification of degradates which represent 0.01 ppm is not
always technically possible nor practical, especially when
considering that the starting materials may not_be purer than
97%.  Thus it may not necessarily be useful to  identify
degradates that represent less than 3% of the applied material.

     c)  On page C-303 of the FIFRA Accelerated Reregistration
Phase 3 Technical Guidance, guidance is provided on the extent of
effort desired for extraction to remove residues from soil, i.e.,
".  . .a reasonable attempt was made - perhaps  with multiple
solvent systems - to extract metabolites/degradates."  Guidance
documents do not address the current desire to  reduce the
nonextractable residues to less than 10%  of the dose rate, using
harsh acid/base digestion if required.  Further, guidance
documents do not address the extent of effort desired to identify
components of the bound residue removed by harsh digestion
procedures.  Although it may be feasible  to achieve the
identification level for residues extractable by conventional
means, identification of components obtained following  harsh
digestion is generally considerably more  difficult due  to  the
large amounts of coextractives.  Since these components may have
been altered by the methods employed, it  should be sufficient  to
provide only characterization  of these components.

     Industry Recommendation:  a)  Since  the Agency is
recommending the Anaerobic Aquatic protocol, using  soil instead
of  sediment, for the Anaerobic Soil metabolism  study,  it  is
highly recommended  that written guidance  be  issued, e.g.,  a_
Standard Evaluation Procedure.  To the extent possible,  it is
recommended  that study design, reporting  requirements,  etc. be
consistent for  the  Anaerobic  Soil and Anaerobic Aquatic
requirements.   If  the Agency  desires,  Industry  is willing to
draft  a Standard Evaluation  Procedure for EPA.

     b)  The Agency should define major  degradates  as  those that
 represent  10%  or greater of  the  applied  radioactivity.   Using
 this definition of  major degradates,  all  major  degradates should
 be identified.

      c)   Identification of degradates should be limited to those
 components which are  extractable by reasonable  means,  i.e.,
 organic  solvent and water,  and not applied to components removed
 following harsh acid/base digestion procedures.
                              - 105 -
-------
                                                Anaerobic Aquatic Metabolism (162-3)
      EPA Response
      Industry's response does not seem to address the rejection
 factor issue of degradate identification.  The intended purpose
 of these laboratory studies is the clear and unequivocal
 identifxcation and quantification of both parent and major
 degradates.   The submitted study(ies)  were apparently rejected
 because no attempt was made to identify and quantify any of the
 degradates which occurred.   Thus the intended purpose of the
 study could not be met.   Studies such as these might be
 repairable if the submitter had retained frozen samples, which
 could be reanalyzed provided there was adequate storage stability
 data to support the results.
     Rejection Factor?    The test substance was not technical
                          grade oar purer.
     EPA Guidance  on this  Factor

          Subdivision N: Environmental  Fate Guidelines.
          page  60.
(1982) ,
          FIFRA Accelerated  Reregistration Phase  3  Technical
          Guidance.   (December  1989), page C-303.,

     A technical grade or purer test substance  is required.  A
technical grade test  substance  is  the active  ingredient  which
does not contain inert ingredients other  than one used for
purification of the active ingredient.  A technical grade or
purer test substance  is essential  for this study, as one
objective of the study is to determine the fate of  the pesticide
and its degradates in a controlled laboratory setting.
Impurities in the test material  will likely confound the results.

     Industry Comment

     Industry agrees  that adequate characterization of the test
substance should be a requirement  for a valid study.  We suggest
that a radiopurity of 95% should be acceptable  in most cases and
would like the Agency to confirm this.

     Industry Recommendation:  No  study should  be initiated with
a test substance which has not been adequately  characterized.  In
using this rejection  factor  however, the Agency should be
specific in delineating what exactly is deficient with respect to
test_substance characterization.   Further,  the  Agency should
specify what is acceptable radiochemical purity.  Industry
recommends that a radiopurity of 95% should be  considered
                             - 106 -
-------
                                               Anaerobic Aquatic Metabolism (162-3)

acceptable unless adequate justification for lower purity is
provided by the registrant,

     EPA Response               ,

     For laboratory studies conducted with radiolabeled
chemicals, the use of a test substance with low radiopurity may
unnecessarily complicate the identification of degradation
products since the fate of the parent and its degradates is  •   :
followed by monitoring the radioactivity.       ,

     Industry should strive for ,the highest possible radiopurity
but not less than 95%.  The Agency understands that achieving a
high level of radiopurity may depend on the chemical
characteristics of the specific compound and on the type of
radioisotope used.  The Agency further acknowledges that some
chemicals may require extensive, preparation in order to achieve
this high level of radiopurity, and has previously concurred with
time extensions for submission of data to allow for such
preparation.  The Agency has also previously accepted the use of
lower purity radiochemicals with adequate justification as to why
higher radiochemical purity could not be achieved.
6.
Rejection Factor;
The test water was not characterized.
Foreign soils werenot completely
characterized and may not have been
typical of those in the United States,
The soil must be representative of that
found at an intended use site.
     EPA Guidance on These Factors

          Subdivision N: Environmental Fate Guidelines.
          pages 42-43, 61.
                                                     (1982).,.
          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. -  (December 1989), pages C-3Q3, C-305.

     This issue does not normally result in the rejection of a
study, and is usually repairable by .the submission of additional
data.

     Rejection factors 1 to 6 relate to basic information
required to be included, in any study submitted to the EPA.  The
information pertains to important study parameters that must be ;
reported so that a technical evaluation of the data can be made.
In most cases, studies rejected solely on these reporting
                             - 107 -
-------
                                               Anaerobic Aquatic Metabolism (162-3)

deficiencies are likely to be upgraded by the registrant by the
submission of the additional data/information.

     Industry Comment

     a)  Industry agrees that a description of the test water is
essential for the purpose of defining the conditions under which
the study is conducted.

     b)  Guidance is adequate for reporting the soil textural
classification.  The Agency needs to specify any additional
requirements for reporting soil characteristics.

     Industry Recommendation;  a)  The Agency should specify that
anaerobicity (pH and redox potential) should be determined and
reported.

     b)  The Agency should specify the soil characteristics,
i.e., percent organic matter, cation exchange capacity, percent
content of sand, silt, and clay, bulk density, and pH, to be
reported in addition to the USDA soil textural classification.
Guidance is requested from the Agency concerning the Agency's
position that chemicals should be tested by the Anaerobic Aquatic
study design (§ 162-3) and the use of field soil rather than
sediment when using the Anaerobic Aquatic study design  (§ 162-3)
for Anaerobic Soil Metabolism studies  (§ 162-2).

     EPA Response

     The Agency agrees that pH and redox potential should be
determined, and the Phase 3 Technical Guidance document specifies
that these measurements are to be reported.  The Agency welcomes
additional discussion on a clear definition of  "anaerobic
conditions."

     With the exception of bulk density, soil characteristics are
currently specified in the Phase 3 Technical Guidance Documents.
Complete physical, chemical and mineralogical characteristics are
necessary for a reasonable comparison of sediments and soils.
When soil characteristics are reported in a nonstandard way
(i.e., not according to the well established USDA textural
scheme), comparison of study results with those of other studies
becomes more difficult.  Also, data from one or more laboratory
studies may enable better prediction of real-world behavior if
the soil characteristics in the laboratory are  sufficiently
similar to anticipated domestic use sites.

     Because of the inadequacy of the sampling protocol described
in Subdivision N for the Anaerobic Soil Metabolism study  (30 and
                              -  108  -
-------
                                                Anaerobic Aquatic Metabolism (162-3)

60 days of anaerobic incubation),  the Agency is currently
recommending that the Anaerobic  Aquatic Metabolism  (162-3) study
protocol be followed when  an Anaerobic Soil Metabolism  (162-2)
data requirement has been  triggered.   The Anaerobic Aquatic
Metabolism study protocol  provides for adequate sampling
intervals to fully describe the  patterns of decline of parent and
formation and decline of degradates under anaerobic conditions.,
The test media should always be  sediments collected from areas
predominantly under anaerobic  conditions.
                               - 109  -
-------
                                                 Aerobic Aquatic Metabolism (162-4)

            GUIDELINE 162-4 AEROBIC AQUATIC METABOLISM

NOTE:_ The usefulness  of the Aerobic Aquatic, Metabolism study as
described in  Subdivision N,  when an aerobic soil metabolism study
has already been conducted,  and the question of what  additional
information this study provides are issues for further
discussion.

is.   Re-lection  Factor;    The sampling schedule was inadequate.

     EPA Guidance on this Factor

          Subdivision  N:  Environmental Fate Guidelines.   (1982),
          page  63.          „

          FIFRA Accelerated  Reregistration Phase 3 Technical
          Guidance.   (December  1989),  page C-307.

     Data are to be collected until  the decline of the  test
substance and the formation  and decline of degradation  products
are clearly characterized or for ,30  days,  whichever comes  first.
The reason for  this is  to ensure that  the  kinetics of pesticide
degradation and the formation and degradation of its  degradates
are fully understood.   This  information is used to calculate a
half-life for the pesticide  and predict how long it and its
degradates will persist in the  environment.   If the duration of
the study is not long  enough or there ,are  insufficient  sampling
points, the reliability of the  calculated  half-lives  will  be
greatly diminished as will the  certainty that all  degradation
products have been formed and identified.

     Industry Comment     ,

     Guidance for study duration is adequate.

     Industry Recommendation: ,  Industry agrees that data should
be collected until the  decline  of the  test substance  and the
formation and decline of  degradation products are  clearly
characterized,  or for 30  days,  whichever comes first.

     EPA Response

     No comment.
                             - 110 -
-------
                                                Aerobic Aquatic Metabolism (162-4)

2_--   Reiection Factors   Material balances were incomplete.

     EPA Guidance on this Factor

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989), page C-307.

     This is a controlled laboratory experiment designed to
measure the breakdown of a pesticide in the hydrosoil/water
medium and the formation and decline of the degradates.  This is
achieved by measuring the test substance at the beginning of the
experiment and then accounting for it at the end of the
experiment to be certain that all degradates formed are isolated
and an accurate rate of degradation is calculated.  A good
material balance (90-110%) is a prerequisite for any valid
laboratory study.

     Industry Comment

     Guidance is adequate on the necessity to maintain a good
material balance.  The guidance is interpreted to mean that an
adequate mass balance maintained during the course of the study
is necessary to assure that all significant degradates formed are
isolated.  A target material balance of 90-110% would be an
adequate measure of a study's accountability of the applied
radioactivity.  It is possible that individual sample time points
and/or sample replicates could fall outside of the stated
(target) material balance range and not adversely effect
interpretation of the results.  The most prevalent example is for
studies with test substances which rapidly degrade to volatile
products, notably CO2.   It also noted that maintaining material
balance can be more difficult with aerobic aquatic than aerobic
soil studies due to measurement and summing of residue in water
and soil phases versus only soil for aerobic studies.

     Industry Recommendation;  The Agency should continue to
assess any material balance deviations from the desired target
range (90-110%) within the context of the entire study and not on
a single sampling interval.

     EPA Response

     The Agency agrees that the material balance should be
assessed within the context of the entire study and not on a
single sampling interval; the 90-110% accountability should be
viewed as an ideal target range.
                             - Ill -
-------
                                                Aerobic Aquatic Metabolism (162-4)
3.
Re-iection Factor;
Residues were incompletely
characterized.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines.
          page 63.
                                                     (1982) ,
          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.   (December 1989), page C-307.

     Identification of residues present at levels greater than or
equal to 0.01 ppm or  10% of applied, whichever is less, is a
critical element of the aerobic aquatic metabolism study.  One
primary reason this study is conducted is to identify the
degradates that are formed after application of a pesticide to
the aquatic environment.  Failure to identify one  (or more)
significant degradates may leave gaps in the understanding of the
metabolism, and hence the environmental fate.  Thus, the
understanding of dissipation under actual use situations is
unclear.

     Industry Comment

     a)  Although no  Standard Evaluation Procedure or Pesticide
Assessment Guideline  has been issued for Aerobic Aquatic
Metabolism, guidance  regarding identification of
metabolites/degradates is presented in Subdivision N Guidelines
and Phase 3 Technical Guidance.

     b)  Residues occurring at a level of 10% of the applied
radioactivity or greater should be identified when feasible.  The
criteria for identification of residues should be consistent with
the 1982 Guidelines,  as stated in the purpose of the study  [§
162-4(a)], and with  § 162-4(c)(2)(i).

     The identification level specified above is 0.01 ppm or  10%
of applied.  A residue present at 0.01 ppm may not be a major
degradate, particularly when the normal field application rate  of
a product is greater than  1 Ib./A.  For a variety of reasons,
e.g.,  specific activity limitations for radiolabeled test
substances, technological  limitations  for detection/quantitation
methodology, dose rates may differ significantly from the field
application rate.  For products with  lower  field application
rates, Aerobic Aquatic Metabolism studies must be  conducted at
exaggerated rates to permit metabolite  identification at  the
required level.  However,  for products with field  application
rates  exceeding  approximately  1 Ib./A,  the  requirement  for
identification at  0.01 ppm is  excessive  since  each  component  at
                              - 112 -
-------
                                                Aerobic Aquatic Metabolism (162-4)

or exceeding 1% of the treatment dose should be identified.
Identification of degradates which represent 0.01 ppm is not
always technically possible nor practical, especially when
considering that the starting materials may not be purer than
97%.  Thus it may not necessarily be useful to identify
degradates that represent less than 3% of the applied material

     c)  On page C-307 of the FIFRA Accelerated Reregistration
Phase 3 Technical Guidance, guidance is provided on the extent of
effort desired for extraction to remove residues from soil, i.e.,
"...a reasonable attempt was made - perhaps with multiple solvent
systems - to extract metabolites/degradates."  Guidance documents
do not address the current desire to reduce the nonextractable
residues to less than 10% of the dose rate, using harsh acid/base
digestion if required.  Further, guidance documents do not
address the extent of effort desired to identify components of
the bound residue removed by harsh digestion procedures.
Although it may be feasible to achieve the identification level
for residues extractable by conventional means, identification of
components obtained following harsh digestion is generally
considerably more difficult due to the large amounts of
coextractives.  Since these components may have been altered by
the methods employed, it should be sufficient to provide only
characterization of these components.

     Industry Recommendation:  a)  If the Agency desires,
Industry is willing to draft a Standard Evaluation  Procedure for
EPA.

     b)  The Agency should define  lmajor degradates' as
degradates that represent 10% or greater of the applied
radioactivity.  Using this definition of major degradates, all
major  degradates should be identified.

     c)  Identification of degradates should be limited to those
components which are extractable by reasonable means,  i.e.,
organic solvent and water, and not applied to components removed
following harsh acid/base digestion procedures.

     EPA Response

     The Agency acknowledges  the need for additional guidance,
and would welcome  Industry's  support in  the development of
additional SEPs for  the remaining  guidelines  for which no  SEP
currently exists.

     The Agency agrees that  the  identification  of  residues
present at 0.01 ppm  may not  always be feasible, especially for
those  products with  field  application rates exceeding
                              - 113 -
-------
                                                 Aerobic Aquatic Metabolism (162-4)

 approximately 1 Ib ai/A.  The Agency will require the
 identification of all residues equal to or greater than 10% of
 the dose rate.  This level of residue identification should
 provide adequate information for most chemicals.  The dose rate
 is  defined as that concentration of radiolabeled pesticide in the
 dissolved phase equal to the concentration expected when the
 maximum label rate is applied to a 1 hectare pond, 2 meters deep.
 All residues present at alO% of this dose rate must be
 identified.

      In the event that the dose rate must exceed the maximum
 field application rate for residue identification purposes,
 (e.g.,  for technological,  specific activity,  or other
 limitations),  a separate exaggerated dose rate study may be
 conducted.   However,  this  exaggerated dose rate study cannot be

 used to provide kinetic information.   The kinetics study must be
 conducted with the maximum dose rate as described above.

      The 10% criterion is  a general guideline.   The registrant is
 expected to  identify single degradates present at concentrations
 approaching  10% of the dose rate.   In addition,  degradates of
 known^toxicological or ecotoxicological concern must certainly be
 identified and quantified  even if  they are present at <10% of the
 dose  rate.

      The Agency agrees that identification of  degradates should
 be  limited to  those components that are extractable by reasonable
 means  (e.g., organic  solvents  and  water),  and  not necessarily
 include  those  components removed following harsh acid/base
 extraction procedures.   These  "bound"  residues  are generally not
 available for  plant or animal  uptake,  leaching,  or run off.
 Harsh extraction,  which changes  the nature of  the residues  is
 not necessary.          .


4-s-   Rejection Factor;   The test  water was not  characterized.

     EPA Guidance  on  this  Factor

                                                          (1982) ,
Subdivision N: Environmental Fate Guidelines.
page 63.
          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.   (December 1989), pages C-307, C-309.


     A description of the test water is essential for the purpose
of defining the conditions under which the study is conducted.
                             - 114 -
-------
                                                 Aerobic Aquatic Metabolism (162-4)

This rejection factor relates  to basic  information required to  be
included in any study submitted to  the  EPA.   The information
pertains to an important study parameter that must be reported  to
ensure a technical evaluation  of the  data can be made.  In most
cases, studies rejected solely on this  reporting deficiency are
likely to be upgraded by the registrant by the submission of the
additional data/information,   ;

     Industry Comment

     Industry agrees that a description of the test water is
essential for the purpose of defining the conditions  under which
the study is conducted.

     Industry Recommendation:  The Agency should specify  that
aerobicity (Ph and dissolved oxygen concentration)  should be
determined and reported.

     EPA Response

     The Phase 3 Technical Guidance.document  already  specifies
that pH and redox potential should be reported.   Dissolved oxygen
concentration should also be- reported.
                               115
-------
                                             Leaching and Adsorption/Desorption (163-1)

        GUIDELINE 163-1 LEACHING AND ADSORPTION/DESORPTION

1.   Rejection Factor;   Deqradates were not identified.

     EPA Guidance on this Factor

          Subdivision N: Environmental Fate  Guidelines  (1982),
          pages 66-67.

          Addendum 6 on data reporting for Leaching and
          Adsorption/Desorption Studies, page 6.

          Standard Evaluation Procedure  (SEP) for  Soil Column
          Leaching Study.  (June 1985), page  11.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989), page C-311.

     Identification of residues present at levels  greater  than  or
equal to 0.01 ppm or 10% of applied, whichever  is  less,  is a
critical element of the Leaching and Adsorption/Desorption study.
One reason this study is conducted  is to determine the mobility
of parent and its degradates in soil.  Failure  to  identify one
(or more) significant degradates results in  gaps in the
understanding of the mobility of the chemical and  its degradation
products in soil and their leaching potential in ground  water.

     Industry Comment

     The identification of degradates has never been a
requirement for batch equilibrium studies.   The mobility of
"major" degradates has been a testing requirement, however.   The
testing of degradates may be prepared from either  1) aging the
test substance under aerobic conditions for  30  days or one half-
life (whichever is shorter) in one  soil type and performing soil
column leaching or soil TLC studies, or 2) performing batch
equilibrium studies on individual degradates.

     Industry realizes that minor metabolites may  be of  interest.

     Industry Recommendation:  Industry recommends that  a  joint
EPA/Industry work group set criteria for triggering degradate
studies based on physical/chemical  properties  (Kow) . persistence.
application rate of the active ingredient, as well as.  "major"
degradates from soil metabolism studies.   (See  also
recommendations above under Rejection Factor 3).
                              -  116  -
-------
                                             Leaching and Adsorption/Desorption (163-1)
     EPA Response
     Although  the  identification of  degradates is best addressed
 in the degradation (abiotic,  biotic)  studies  and is not a formal
 requirement  for  Leaching  and  Adsorption/Desorption studies,  the
 Agency does  require mobility  information on all residues equal to
 or greater than  10% of  the  dose  rate,  as defined by the
 degradation  and  metabolism  studies.   In addition,  the mobility of
 degradates of  known toxicological or ecotoxicological concern
 must certainly be  defined even if they are  present at <10% of the
 dose rate.

     The Agency  agrees  that the  mobility of degradates of concern
 can be determined  by aging  the test  substance under aerobic
 conditions for 30  days  or one half-life (whichever is shorter)
 and performing soil column  leaching  studies using the aged soil.
 However, soil  TLC  studies using  aged soil are no longer
 acceptable.  At  this time the Agency requests that batch
 equilibrium  studies be  performed using individual  degradates  in
 four soils each  for each  degradate;   however,  the  Agency has
 agreed to further  discussion  with industry  on this topic and  will
 finalize its position at  that time.

     The Agency  and Industry  have agreed to form a joint
 workgroup to discuss and  resolve the  issues regarding the
 appropriate  criteria for  triggering  and conducting mobility  -
 adsorption/desorption  (163-1) studies.   These criteria will be
 incorporated into  any future  revisions  of this  guideline.
2.   Rejection Factor;
The test soils were autoclaved prior to
conducting the study.
     EPA Guidance on this Factor

     EPA does not have any formal guidance on autoclaving of the
test soils.  However, it is well established that autoclaving the
soils significantly changes their physical and chemical
properties, which may affect the adsorption of pesticides by the
soils.

     Industry Comment

     Industry agrees in principle.  However, exceptions should be
allowed for compounds that are rapidly degraded in soil.  Soil
sterilization techniques should be allowable in batch equilibrium
studies for the exception noted above, and should not be allowed
in the_case of aged mobility studies.  Moreover, the use of soil
sterilization techniques has been mentioned in the Phase 3
                             - 117 -
-------
                                             Leaching and Adsoiption/Desorption (163-1)

Technical Guidance for summarizing Leaching  and Adsorption/
Desorptioh studies.

     Industry Recommendation;  An exception  should be allowed for
compounds that are rapidly degraded in soil„

     EPA Response

     For those specific pesticides and/or degradates that degrade
rapidly in soil  (i.e., within hours of application), the Agency
would consider requests for a waiver of the  mobility requirement.
However, the registrant would be required to demonstrate that the
rate of degradation was such that equilibrium  could not be
established.  If the parent compound degrades  rapidly,
information on the mobility of its degradates  will be of primary
importance.

     If the registrant chooses to use sterilized soil to study
the mobility of rapidly degraded compounds,  the batch equilibrium
studies must include reference chemicals of  known mobility.   The
sterilization technique used must avoid, to  the maximum extent
possible, any alteration of the soil matrix  which could distort
the mobility characteristics.


3.   Rejection Factor;   The material balance  was incomplete.


     EPA Guidance on this Factor

          Standard Evaluation Procedure  (SEP)  for Soil Column
          Leaching Study.  (June 1985), page  15.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989), pages C-311, C-314 & C-315.

     This experiment is designed to measure  the adsorption and
desorption of a pesticide.  This is achieved by measuring the
test substance applied at the beginning of the study and then
accounting for it at the end of the experiment to monitor the
disappearance of the parent and formation and  decline of the
degradates.  A good material balance  (90-110%) is a prerequisite
for any valid laboratory study.

     Industry Comment   -     .

     1)  In principle we agree with this concept, obtaining good
material balances makes good analytical sense.  However, in some
instances special analytical techniques are  required for which
                             - 118  -
-------
                                             Leaching and Adsotption/Desorption (163-1)

there is no guarantee  that  a material  balance of 90-110% can be
achieved.  The Agency  should make  allowance  for these special
circumstances  (e.g., hydrophobic compounds),  where additional
efforts have been made endure  a good material balance,  but,  due
to the nature of the test chemical,  material  balance in the  range
of 90-110% is not achievable.

     2)  The study objective is to obtain partition  coefficients/
mobility_information.   The  requirement to measure  the formation
and decline of degradates appears  to be a new requirement and is
beyond the scope of the study  objectives.  Formation and decline
of degradates is addressed  in  soil metabolism studies.

     Industry Recommendation:  Guidelines need to  be revised to
include material balance requirements.   The  issue  of measuring
the formation and decline of degradates has never  been  and should
not be a requirement for leaching  and  adsorption/desorption
studies, given the study objectives.

     The larger issue  of adsorption/desorption studies  of
degradates needs to be addressed.   Industry recommends  that  a
joint EPA/Industry work group  set  criteria for triggering
degradate studies based on  physical /chemical  properties (KOT.) .
persistence, application rate  of the active ingredient,  asWwell.
as, "major" dearadates from soil metabolism studies
additional comments under Rejection Factor 1).

     EPA Response
(See
     Measuring the formation and decline of degradates  is best
addressed in the degradation studies  (abiotic, biotic)  studies
and is not a formal requirement for Leaching and Adsorption/
Desorption studies. . However, in situations where degradation of
the test material occurs during the course of the study, it may
be necessary to characterize and quantify the degradates.   (For
further discussion of which degradates to consider, see Rejection
Factor 1 above).  In these rare cases, an acceptable material
balance should approach 90-110% of the applied test substance in
order to permit defining the mobility characteristics of both
parent and major degradates as clearly as possible.

     The Agency and Industry have agreed to form a joint
workgroup to discuss and resolve the issues regarding the
appropriate criteria for triggering and conducting mobility -
adsorption/desorption (163-1) studies.  These criteria  will be
incorporated into any future revisions of this guideline.
                             - 119 -
-------
4.   Re-lection Factor;
                   Leaching and Adsorption/Desorption (163-1)

Soils and sediments were incompletely
characterized.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 65.

          Standard Evaluation Procedure  (SEP)  for  Soil  Column
          Leaching Studies.  (June  1985), page  9.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989), pages C-311 & C-313  .

     This issue does not normally  result in the rejection of  a
study, and is usually repairable by the submission of additional
data.  Information on the soil  class, texture, pH, and  percent
organic matter is necessary to  verify that the soil is
representative of agricultural  soils.  If foreign  soils are used,
such data on soil class, textural  classification,  and crop use
are needed to indicate  its similarity to U.S.  soils.

     Industry Comment

     Industry agrees that soil/sediment  characteristics should be
provided, including  soil class, texture, pH and percent organic
matter, as representative of agricultural use  or other
appropriate uses.

     Industry Recommendation:   The Agency should specify  the  soil
characteristics  to be reported, in addition to the USDA soil
texture classification.

     EPA Response

     Soil characteristics to be reported are  currently  specified
in the SEP and,  with the exception of bulk density, also  in the
Phase 3 Technical Guidance documents.  Additional  information^
concerning physical, chemical,  and mineralogical  characteristics
may be reported  if this information contributes  to the
understanding of the process(es)  observed  in  the  study.
      Rejection Factor;
Desorption of  a ma-ior decrradate was not
addressed.
      The purpose of leaching and adsorption/desorption study is
 to provide data on the mobility of the pesticide and its
 degradates and to determine their leaching potential in ground
                              - 120 -
-------
                                             Leaching and Adsorption/Desorption (163-1)

water.  Adsorption/desorption coefficients calculated  from batch
equilibrium study are used to determine the  mobility of  the  test
substance in different soil types.  If no data is provided on the
desorption of a major degradate, the information on the  mobility
of the degradate and its leaching potential  in ground  water  is
incomplete.

     Industry Comment

     See comments and recommendations in this section  for
Rejection Factors 1 and 3,

     EPA Response

     When using batch equilibrium techniques, a separate
adsorption/desorption study must be conducted for the  parent and
for each degradate of concern.  For further  information  on what
constitutes degradates of concern, see the responses in  this
section for Rejection Factors 1 and 3.                           •
6.
Rejection Factor;
Foreign soils were used which may not be
tvpica]. of soils in the United States.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 65.

          Standard Evaluation Procedure  (SEP) for Soil  Column
          Leaching Studies.  (June 1985), page 9.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989), pages C-311 & C-313.

     Information on the soil class, texture, pH, and percent
organic matter is necessary to verify that the soil is
representative of agricultural soils.  If foreign soils are used,
such data on soil class, textural classification, and crop use
are needed to indicate its similarity to U.S. soils, since
mobility of pesticides in such soils may be dramatically
different than in domestic soils  (eg., in a volcanic ash)„

     Industry Comment

     We agree that the information on soil class, texture, pH and
percent organic matter is relevant for mobility considerations«
However, information on crop use is irrelevant and should not be
                              - 121  -
-------
                                             Leaching and Adsotption/Desorption (163-1)

required.  The Agency should specify  the  soil  characteristics  to
be reported in addition to the USDA soil  textural  classification.

     Industry Recommendation;  Information  on  crop use  is
irrelevant and should not be required.  The Agency should  specify
the soil characteristics to be reported in  addition  to  the USDA
soil texture classification.

     EPA Response

     Soil characteristics to be reported  are currently  specified
in the SEP and, with the exception of bulk  density,  also in the
Phase 3 Technical Guidance documents.  Additional  information
concerning physical, chemical, and mineralogical characteristics
may be reported if this information contributes to the
understanding of the process(es) observed in the study.

     EPA strongly prefers that domestic soils  be used in the
mobility studies.  However, the Agency will accept non-
domestic/European soil for two of the four  soils required  if and
only if the soils are characterized according  to the USDA  system.
The soils selected should be representative of and appropriate
for the use patterns being supported.  All  additional studies
using non-domestic soil(s) would be considered supplemental.
7.   Re-lection Factor;
Kd values (values of soil/water
relationships) were not reported.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 66-67.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989), pages C-312 & C-314.

     Adsorption/Desorption coefficients  (Kd) calculated  from
batch equilibrium studies are used to determine the mobility  of
the test substance in different soil types.  If no data  are
provided on the rate of adsorption and desorption, the
information on the mobility of the degradate and its leaching
potential in ground water is incomplete.

     Industry Comment

     Information on Kd values  should be supplied.   However, the
requirement on the "rate" of adsorption and desorption is  beyond
                              - 122  -
-------
                                             Leaching and Adsoiption/Desorption (163-1)

 the  stated scope of these type -of studies, as referenced in the
 Pesticide Assessment Guidelines'.  '    '      •        • .

      Industry Recommendation:   The requirement on the "rate" of
 adsorption and desorptibn is beyond the stated scope of these
 type of  studies,  and should be-stricken as a study requirement.

      EPA Response

      EPA agrees that "rate" is beyond the scope of the current
 guidelines.     '      . .     ,  •     •-':•;.•    ••. .
 8...   Rejection  Factor;
The desorptionphase was done serially.
with incomplete removal of the
supernatant at each step-
     _This rejection  factor relates to basic analytical techniques
required for a  sound scientific study.   In an adsorption/
desorption  (batch  equilibrium)  study,. incomplete removal of
supernatant from the desorption phase would-result in an
erroneous calculation of the'  amount., of.'•. test substance -desorbed
from the soil.  This results,-In1 an inaccurate assessment of the
adsorption/desorption potential of the chemical and hence its
mobility in the soil.

     Industry Comment             ;          ^

     Efforts to remove as  much  supernatant as possible is a
reasonable approach  to this issue'.   Moreover,  serial desorption
is a_well documented method of  performing  this type of study.
Provided the amount  of residual radioactivity in the supernatant
is accounted for,  the resulting partition  coefficient can be
accurately determined.

     Industry Recommendation:   A calculated partition coefficient
that takes into account residual radioactivity associated with
the supernatant should-be  acceptable.         .

     EPA Response

     The Agency agrees that serial  desorption is a well
documented technique  for Batch  Equilibrium studies;  however,  the
problem described here arose because  it was apparent to  the
reviewer that a large portion of the  supernatant was not removed.
This would result in  an underestimation of  the amount of
radioactivity desorbed and the  appearance  that the chemical is
less mobile than it actually is. .The. Agency  continues to believe
that the additional work required  for removal  of the majority of
                             - 123 -
-------
                                             Leaching and Adsorption/Desoiption (163-1)

the supernatant during the desorption phases would yield  a more
accurate estimation of the desorption coefficient.
9,   Rejection Factor;
The soil texture could not be confirmed
because the soil was not classified
using the USDA Soil Textural
Classification System.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 65.

          Standard Evaluation Procedure  (SEP)  for  Soil  Column
          Leaching Studies.  (June  1985), page  9.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989), pages C-311 & C-313.

     This issue does not normally  result in the rejection  of  a
study, and is usually repairable by  the submission of additional
data.  Information on the soil  class, texture, pH,  and  percent
organic matter is necessary to  verify that the soil is
representative of agricultural  soils.  If foreign  soils are used,
such data on soil class, textural  classification,  and crop use
are needed to indicate  its similarity to U.S.  soils.

     Industry Comment

     The soil information mentioned  above in Rejection  Factor 9
should be provided.

     Industry Recommendation;   See Rejection Factor 9 above.

     EPA Response

     Soil characteristics to be reported are currently  specified
in the SEP and, with the exception of bulk density, also in the
Phase 3 Technical Guidance documents.  Additional  information
concerning physical, chemical,  and mineralogical characteristics
may be reported if this information  contributes to the
understanding of the process(es) observed in the study.
                              -  124 -
-------
                                             Leaching and Adsorption/Desolation (163-1)

10.  Re-jaction Factor;   It was not established  that  the  time
                         used allowed sufficient for  the
                         soil;solution slurries  to reach
                         equilibrium.

     EPA Guidance on this Factor

          Subdivision N: Environmental Fate  Guidelines  (1982),
          page 67.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), pages C-312 & C-314.

     Sufficient time must be allotted for the equilibration of
the test substance with the soils so that they achieve  an
equilibrium and the adsorption/desorption coefficients  are
accurately determined.

     Industry Comment

     In principle we agree.  However, exceptions should be
allowed for compounds that rapidly degrade and for classes of
compounds that exhibit very low adsorptive properties.

     Twenty-four  (24)  hours should be maximum equilibration time
required for adsorption and desorption studies.

     Industry Recommendation;  Exceptions should be allowed for
compounds that rapidly degrade and for classes of compounds that
exhibit very low adsorptive properties.

     Twenty-four  (24)  hours should be maximum equilibration time
required for adsorption and desorption studies.

     EPA Response

     The Agency agrees that chemicals which  fall outside  of the
'norm'  (eg., compounds which degrade rapidly or  which exhibit
very low adsorptive properties) should be granted wider latitude.

     The Agency concurs with establishing a  standard  24-hour
maximum equilibration time for all chemicals as  a consistent
experimental parameter.  However, if preliminary studies  indicate
that 24 hours is insufficient for complete equilibration  to
occur, the registrant may chose to equilibrate for a  longer time
to more accurately determine the mobility characteristics.  It
should be noted that failure to allow sufficient time for full
equilibration may underestimate the adsorption coefficient of the
chemical and hence, overestimate mobility.
                             - 125 -
-------
11.  Re-jaction Factor;
                   Leaching and Adsorption/Desoiption (163-1)

The bioassay methods used in the study
were not acceptable analytical
techniques.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982) ,
          pages 64-71.

          Standard Evaluation Procedure  (SEP)  for Soil  Column
          Leaching Studies.  (June 1985), pages  8-17.

     The analysis and identification of  the parent and  degradates
should be carried out by well established analytical  techniques.

     Industry Comment

     If one can draw conclusions on mobility,  then the  use  of
validated bioassay techniques should be  allowed.  Precision of
the analytical method should be sufficient to  allow measurement
of a soil partition coefficient.

     Industry Recommendation;  By whatever analytical method, the
precision of the analytical method should be sufficient to  allow
measurement of a soil partition coefficient.

     EPA Response

     With nearly all chemicals, conventional analytical
techniques  (e.g., TLC, HPLC, etc.) are preferred, although
detection of decreasingly smaller concentrations of compounds may
pose a significant analytical challenge.

     The Agency recognizes that a variety of immunoassay
techniques have been developed over the  years,  with new ones
appearing with increasing frequency.  We agree  that some of these
emerging techniques may be the only ones with  sufficient
sensitivity or specificity to detect parent compounds and/or
degradates of concern.  However, their use should be  discussed
with the Agency early in the registration process, so that  the
merits of the method can be evaluated.

     A joint EPA/Industry work group has been  formed  to discuss
the development of acceptance criteria for bioassay methods used
in association with mobility studies.
                              - 126  -
-------
12.  Relaction Factor;
                   Leaching and Adsorption/Desorption (163-1)

Soil used in the study was not prepared
properly.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 65.

          Addendum 6 on data reporting for Leaching and
          Adsorption/Desorption Studies. page 6.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989), pages C-312 & C-313.

     It appears that the soils used in this study were not aged
to allow for microbial degradation so that the mobility  of the
degradates could be monitored to determine their leaching
potential in ground water.

     Industry Comment

     We are assuming that this rejection refers to "aged" soil
column leaching studies.  For these studies, the testing of
degradates may be determined from either 1) aging the test
substance under aerobic conditions for 30 days or one half-life
(whichever shorter) in one soil type and performing soil column
leaching or soil TLC studies, or 2) performing batch equilibrium
studies on individual degradates.

     Industry Recommendation;  Prepare soils for the "aged"  study
by aging the test substance for 30 days or one half-life
(whichever is shorter) for case 1 above.. Otherwise, perform
batch equilibrium studies on individual degradates.  Further
clarification of how to prepare soil leaching columns is heeded.
EPA should rewrite a separate guidance document for conducting
aged soil column leaching studies to address the following
issues:  1) the number of soils which must be tested, and 2)
preparation of  "aged" soil.  Industry proposes that only one soil
column study should be conducted with sandy loam soil to examine
reasonable worst-case leaching potential.

          EPA Response

     Additional guidance on conducting aged soil column leaching
studies is available in the Standard Evaluation Procedure  (SEP)
for Soil Column Leaching Studies  (June  1985).

     The current  EPA policy requires that  the test substance be
aged under aerobic  conditions  for  30 days  or  one half-life
                              -  127 -
-------
                                             Leaching and Adsorption/Desorption (163-1)

 (whichever is  shorter),  followed by Soil Column Leaching studies
 of  that  aged soil;  soil  TLC studies are no longer  recommended.

     Alternately,  the Batch Equilibrium study can  be conducted
 with each pure degradate (synthesized or purified  from the aged
 soil) which had previously been identified as a degradate of
 concern  in the degradation (abiotic,  biotic)  studies.   For
 further  details, please  see the response to Rejection Factor 1.

     It  is recommended that mobility studies for unaged parent
 use the  Batch  Equilibrium protocol  as the testing  method;
 however,  the batch  equilibrium study using characterized aged
 soil  (instead  of individual degradates)  is inappropriate and may
 lead to  invalid results.   The  Agency continues to  accept aged
 mobility studies using soil columns.

     The Agency does  not  agree with the recommendation that only
 one soil column study be  conducted  with sandy loam soil to
 examine  the worst-case leaching potential.   "Worst-case" leaching
 potential cannot be accurately predicted from the  use  of a single
 soil; a  sandy  loam  soil may not present a "worst case"  for many
 pesticides.  The Agency requires information on the  leaching
 potential of a chemical in scenarios  other than the  worst  case in
 order to fully understand the  leaching characteristics  of  the
 pesticide and  its degradates.   Ideally,  the Agency prefers
 individual  batch equilibrium studies  for the parent  and, where
 feasible,  for  major degradates.   The  registrant may  however elect
 to perform column leaching studies.   After aerobic aging of the
 parent in four soils,  the treated and aged soils are then  placed
 on the appropriate, respective soil  columns,  with  proper care
 having been taken in  the  preparation/packing of the  columns„  The
 study will  then proceed as  described  in the SEP for  column
 leaching studies.
3-3*  Re-jaction Factor;   Test solution was not characterized„

     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 64.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), page C-311.

     The test solutions must be analyzed with an appropriate
analytical methods, to positively identify the parent and its
degradates and to monitor any impurities that might be present in
the test solutions.
                             - 128 -
-------
                                             Leaching and Adsotption/Desorption (163-1)
     Industry Comment
     By whatever analytical method, the precision of the
analytical method should be sufficient to allow measurement  of  a
soil partition coefficient.

     Industry Recommendation;  The analytical method should  be
precise enough to allow measurement of a soil partition
coefficient of the parent compound and/or, degradates, as
appropriate„

     EPA Response
14,
     No comment.
Rejection Factor;
The data were presented on a percentage
basis with no actual concentrations.
     This issue does not normally result in the  rejection  of  a
study, and is usually repairable by the submission of additional
data.  In some cases, studies rejected solely on these  reporting
deficiencies are likely to be upgraded by the registrant by the
submission of the additional data.

     Industry Comment

     More clarification regarding this rejection factor is
needed.

     Industry Recommendation;  Please provide further information
so industry can comment on this rejection factor.

     EPA Response

     This factor relates to the reporting of raw data for  the
calculation of partition coefficients.  It appears that, instead
of reporting the actual data on the concentration of test
substance in each stage of the adsorption/desorption phases,  data
were only presented as percentages; it was not possible to
determine whether these percentages were "percentage of applied"
or "percentage recovered."   Since the reviewer  was unable to
ascertain how much test substance was used, it became extremely
difficult to confirm the registrant's calculations.

     Other Industry Comments/Other Concerns

     The increasing use of computer models for assessing
pesticide mobility requires the generation of a  range of Kd
                              -  129  -
-------
                                             Leaching and Adsorption/Desorption (163-1)

values.  The batch equilibrium  study  is preferred.   Soil  column
leaching studies and soil TLC studies are  suitable for  comparing
the mobility of degradates  to mobility of  the parent.   The
Guidelines should be modified to  show that the  soil  column
leaching study provides supplemental  data  on degradates.  If  the
Agency does not accept soil TLC data  as the primary  measure of
mobility, this study should be  removed from the guideline.

     The triggering of leaching and adsorption/desorption studies
needs to be addressed.  If  the  Kow is  greater that  1000, then  the
compound will be strongly adsorbed and there is no need to
conduct an adsorption/desorption  experiment.  Likewise, the
continued reporting of Freundlich isotherms when other  more
appropriate adsorption models may apply, is unnecessary and
should be deleted as a Guideline  requirement in special cases.
Also, alternative approaches for  providing mobility  information
should be discussed and given latitude in  meeting data
requirements.  For example, consideration  should be  given to  the
use of OECD Adsorption/Desorption Guideline 106.

     In addition industry would like  to see an  entire rewrite of
the guidance for conducting leaching/adsorption/desorption
studies, with separate guidance from  the Agency for  both  batch
equilibrium and aged column leaching  studies.

     EPA Response

     The Agency agrees that the soil  TLC study  should be
eliminated from the guidelines.   In the past, however,  the Agency
has allowed registrants to provide Kd  values calculated from Rf
values using the Hamaker's equation,  provided that there  was  an
adequate database (reference material of known  Kd in  the same
test soils) so that the Hamaker's  equation could be  applied in a
scientifically sound manner.

     The Agency welcomes the opportunity to discuss  the larger
issue of setting criteria for triggering degradate studies based
on physical/chemical properties,  etc. as part of a joint
EPA/Industry work group.  Such  a  dialogue  would also prove
helpful in laying the groundwork  for  future revision of the
guidelines.

     The reporting of Freundlich  isotherms  is required, in part,
for computer-modeling purposes.   However,  the registrants are
encouraged to also apply the data  to  other adsorption models  when
additional information may be gained.

     With respect to the OECD 106  guideline, the Agency has been
aware of on-going revisions of  OECD guidelines  and efforts to
                             - 130 -
-------
                                               Leaching and Adsorption/Desorption (163-1)

define soil  selection  for these studies.   The Agency  is  also
aware of  the current development of environmental  fate guidelines
for pesticides by the  European Community.
                                - 131 -
-------
                                                    Laboratory Volatility (163-2)
               GUIDELINE 163-2 LABORATORY VOLATILITY
      Re-jection Factor;    Analytical methodology was insufficient.

      EPA Guidance on this Factor

           Subdivision N:  Environmental Fate Guidelines (1982),
           page 71-74.

           FIFRA Accelerated Reregistration Phase 3 Technical
           Guidance.  (December 1989),  page C-316 & C-319.

      This rejection  factor pertains to basic information  required
for the  laboratory volatility study.   Appropriate analytical
methods  are  required to monitor the air samples and determine  the
actual rate  of volatilization under controlled conditions.

      Industry  Comment

      The analytical  methodology should be appropriate  to  meet  the
intent of the  study.  The laboratory volatility study  is  an
intermediate step in determining the environmental fate of  the
chemical,  and  the analytical  method need not be overly precise  if
the purpose  of the study  is to confirm the need for field
studies.

      Industry  Recommendation:   The  purpose for conducting the
experiment and the significance of  the results should  be
considered when evaluating the analytical method.   If  the study
demonstrates that volatilization is unlikely to be a significant
mechanism for  environmental dissipation,  then an analytical
method which allows  the determination of 5-10% of the  amount
applied  may  be adequate.

      EPA Response

      The Agency agrees that the analytical methodplogy should be
appropriate  to meet  the intent of the guideline,  which is to
determine the  actual rate or  extent of pesticide volatilization
from  soil, and assumes that the reference to 5-10% of  applied
refers to the  residue level above which identification is
required.  An  analytical  method of  sufficient  sensitivity is
almost always  required to determine the actual  rate or extent of
volatilization from  soil.

     As  a trigger for the volatility  requirement,  the  Agency has
determined that where vapor pressure  exceeds  10"4 mmHg,  these
studies  are  almost always  required.   Where vapor pressure is less
                             - 132 -
-------
                                                    Laboratory Volatility (163-2)

than about 10"6 mmHg, these studies are almost never required.
Between these two limits, the Agency will continue to_require the
volatility studies on a very limited case-by-case basis, usually
dependent on human and ecological toxicity concerns.,

     The Agency is considering other parameters that may be more
appropriate for use in determining the need for the volatility
studies.  The use of the ratio of Henry's Constant to kd as a
trigger factor is a topic for further discussion.
2.   Re-iection Factor;
The study was not carried out over a
long enough period of time to clearly
define a volatility decline curve.
     EPA Guidance on  this  Factor

          Subdivision N: Environmental  Fate  Guidelines (1982),
          page  73.

          FIFRA Accelerated Reregistration Phase 3  Technical
          Guidance.  (December 1989),  page C-316.

     Monitoring of  air  samples should be conducted continuously
 or at  intervals which increase with time until the nature of the
 residue decline curve has  been clearly  established.

     Industry Comment

     The  laboratory volatility study has historically been used
 to assess volatilization only for chemicals  which the EPA
 believed  posed a  significant inhalation hazard to workers.  The
 changing  use of this study, as indicated in the foreword to the
 rejection rate analysis, requires updated guidance on conduct of
 the study.   Studies for assessing environmental fate may need to
 be longer than those for assessing the risk to workers.

     The  changing expectations for the study will require
 clarification of  several requirements,  including determination of
 the nature of the residue decline curve.  Recent work by Jury, et
 al. (1983a, 1983b,  1983c)  has shown that several volatilization
 patterns  can be expected depending on the physical properties of
 the compound.  Demonstrating that volatilization of the pesticide
 follows the expected behavior should be adequate characterization
 of the "residue decline curve".
                               - 133  -
-------
                                                     Laboratory Volatility (163-2)
 References
      Jury,  W.  A.,  W.  F.  Spencer,  and W.  J. Farmer. 1983a.
 Behavior Assessment Model for Trace Organics in Soil: I.
 Description of Model.   J. Environ.  Qual. 13:558-564.

      Jury,  W.  A.,  W.  F.  Spencer,  arid W.  J. Farmer. 1983b.
 Behavior Assessment Model for Trace Organics in Soil: I. Chemical
 Classification and Parameter Sensitivity.   J.  Environ.  Qual
 13:567-572.

      Jury,  W.  A.,  W.  F.  Spencer,  and W.  J. Farmer. 1983c.
 Behavior Assessment Model for Trace Organics in Soil: I,
 Application of Screening Model.   J. • Environ. Qual. 13:573-579.

      Industry  Recommendation:  The  laboratory volatility
 guideline should be revised to reflect its current use  in
 assessing environmental, fate.  The  study should be required only
 when  the vapor pressure  of the active ingredient is greater than
 1 X ID' mm Hg  at 25°C, and other  physical  properties  of  the
 active ingredient  indicate that volatilization will be  a
 significant  mechanism  for dissipation.

      EPA Response

      The  Agency agrees that there may be insufficient guidance
 available for  the  Volatility data requirements,  particularly as
 they^apply  to  the  determination of  the environmental  fate of
pesticides.  The Agency  and Industry have  agreed to form a joint
workgroup to discuss and resolve  issues  regarding the appropriate
 criteria  for triggering  and conducting laboratory and field
volatility  (163-2  and 163-3)  studies.  These criteria will be
 incorporated into  any future revisions of  this  guideline.
3.   Re-jection Factor;
The soil was not analyzed immediately
after treatment. Therefore, the
application rate was not confirmed.
     EPA Guidance on this Factor

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), pages C-316 & C-319.

     Application rate must be known, since the monitoring of the
test_substance (volatilization rate of the pesticide) is based on
the initial concentration of the pesticide used on soil.
                             - 134 -
-------
                                                    Laboratory Volatility (163-2)
     Industry Comment
     The volatilization rate of the pesticide is calculated from
the concentration of the pesticide in air and the surface area of
the soil.  If volatilization is determined by the difference in
soil concentrations with time, the initial concentration must be
known.  It is not necessary to know the initial concentration in
soil if the concentration in air is measured directly. • Analysis
of the soil merely provides confirmation that the pesticide was
applied at the desired rate.  While analysis of the soil may be
desirable, it is not essential, if there is other evidence to
validate the application rate.  Known weights or volumes of
chemical added to the soil and demonstrated stability in the test
solution could be the minimum evidence supporting proper
application rate.

     Industry Recommendation;  Confirmation of application rate
must be provided by soil analyses or by other means such as known
weights or volumes applied to the soil.   .           .

     EPA Response

     The Agency agrees that the analysis of soil provides
confirmation that the pesticide was applied at the1 desired rate.
This  information is necessary because  the application rate should
approximate the highest  recommended rate for a^single
application.  However, according  to current guidelines,
volatilization cannot be determined by the difference in  soil
concentrations with time; decreases, in the concentration .of  a
pesticide-in soil cannot distinguish between a decrease due  to
volatilization and that  due to  soil metabolism of  the test
material.  Therefore, air samples must be  collected  and analyzed
for the active ingredient and/or  major degradates  where any
volatilization has occurred.

     ,Due to  the  carefully controlled  conditions  under which
laboratory volatility studies are conducted,  the Agency agrees
that known weights  or-volumes of  pesticide applied to the soil
can be used  to confirm the  rate of  application,  provided  that  the
known weights  or volumes of pesticide added  to  the soil at the
desired application rate can be verified by  the registrant.
                              - 135 -
-------
 4_._   Re-lection Factors


      EPA Guidance on this Factor
                           Laboratory Volatility (163-2)

No material balance was reported or the
data reported was insufficient.
           FIFRA Accelerated Reregistration Phase 3 Technical
           Guidance.  (December 1989),  page C-316.

      This experiment is designed to measure the volatilization of
 a pesticide under controlled laboratory conditions.  This is
 achieved by measuring the test substance applied at the beginning
 of the study and then accounting for it at the end of the
 experiment.   A good material balance (90-110%)  is a prerequisite
 for any valid laboratory study.

      Industry Comment

      The requirement for a material balance of 90-110% can best
 (frequently only)  be met by use  of radiolabeled test substances
 and Industry agrees  that radiolabeled formulations of many
 products can be simulated in laboratory tests.   However,  when it
 is not possible to use radiolabeled products,  EPA should be
 flexible in its material balance requirement.

      The FIFRA Accelerated Reregistration Phase 3 Technical
 Guidance, page C-316 and the Pesticide  Assessment Guidelines
 163-2  state  that the study is conducted to determine the
 concentration of the active ingredient  in air  following
 application  of a typical end use product to soil.   The
 requirement  for a good material  balance expands the scope of the
 study  to include soil  analyses and degradation  product analyses
 (see rejection factor  5)  which complicate the  study and duplicate
 the requirements of  the aerobic  soil  metabolism study.

     The laboratory  volatility study  complements an aerobic soil
metabolism study and should be viewed in context.   Laboratory
volatility studies should not be required when  the  aerobic  soil
metabolism study has already demonstrated the significance  of
volatilization as a  mechanism of dissipation.

     Industry  Recommendation:  Laboratory volatility studies
should be designed to  determine  volatilization  of active
ingredients when applied as  a typical end use product.
Registrants should not  be  required to conduct aerobic  soil
metabolism studies on  each typical  end  use product.  Registrants
should concentrate on  reporting  accurate  analyses of the  active
ingredient in  air.
                             - 136 -
-------
                                                    Laboratory Volatility (163-2)
     EPA Response
     The Agency agrees that the volatility requirement should not
be imposed if acceptable metabolism studies prove that
volatilization is not a likely route of dissipation of the
pesticide.  However, the identification of volatile compounds
produced during the metabolism studies remains a requirement; the
need for further studies on volatile degradates would depend on
toxicity concerns.

     The Agency is considering other parameters that may be more
appropriate than vapor pressure for use in determining the need
for the volatility studies.  The use of the ratio of Henry's
Constant to kd as  a trigger factor is  a topic  for further
discussion.

     The use of radiolabeled test material continues to be the
best technique for generating acceptable material balances,
including trapping/identification of volatile degradates, and
determination of whether or not any of the test material has
sorbed to the sides of the test vessel.  Identification of
degradates in soil is usually not required if acceptable
metabolism studies are available.  However, the determination of
the concentration(s) of active ingredient and/or major degradates
in air is still needed.
5.
Rejection Factor;
Not all manor formulation categories
were tested.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          pages 71 & 72.

     This issue does not normally result in the rejection of  a
study, and is usually repairable by the submission of additional
data.

     Industry Comment

     If the registrant  can provide information to demonstrate
that there is a worst-case formulation, then only one test should
be required.

     EPA Response

     The Agency would agree to accepting results from one
laboratory volatility study using a "worst-case" formulation  of
the chemical if the registrant is prepared to be regulated under
                              - 137  -
-------
                                                    Laboratory Volatility (163-2)

 "worst-case"  assumptions.   As a point of interest,  if the
 specific%chemical  involved is marketed in two or more
 formulations  (e.g.,  an EC  and a Dust),  the formulated products
 may be  sufficiently  different to trigger additional testing in
 several other guideline areas,  including Field Dissipation (164-
 11 *
ILi.   Re-lection  Factor;    The soil was  autoclaved before the test

     EPA Guidance  on  this Factor

     EPA does not  have  any formal guidance  on autoclaving of the
test soils.  However, autoclaving soils  significantly changes
their physical  and chemical properties,  which may affect the
adsorption of pesticides  by the  soils.   Also,  sterile soil would
not generate metabolites,  some of which  might be volatile.

     Industry Comment

     Studies which attempt to simulate actual conditions should
be conducted on soil  which has not been  autoclaved unless there
are compelling  reasons  to slow the rate  of  degradation by
eliminating microorganisms.

     The FIFRA  Accelerated Reregistration Phase  3  Technical
Guidance, page  C-316  and  the Pesticide Assessment  Guidelines
indicate that the  study is conducted to  determine  the
concentration of the  active ingredient in air following
application of  a typical  end use product to soil.  Neither
document requires  the volatilization of  metabolites to be
determined.

     Industry Recommendation:  EPA should develop  and publish
guidance on use of  sterilized soils.  Volatilization  studies of
metabolites should  not  be  a general requirement.

     EPA Response

     For those  pesticides  that degrade rapidly in  soil  (i.e.,
within hours of application), the Agency would consider requests
for a waiver of the laboratory volatility requirement.  However,
the registrant  would be required to demonstrate  that  the rate of
degradation was such that  equilibrium could not  be established.
If the parent compound  degrades rapidly, information  on the
volatility of its degradates  will be of  primary  importance.

     If the registrant  chooses to use sterilized soil  to study
the volatility  of rapidly  degraded compounds,  the  study must
                             - 138 -
-------
                                                    Laboratory Volatility (163-2)

include reference chemicals of known volatility.  The  .
sterilization technique used must avoid, to the maximum extent
possible, any alteration of the soil matrix which could distort
the mobility characteristics.

     Although the guidelines do not specifically address the
volatility of metabolites, significant volatile degradates must
be identified unless it can be shown that they are not of
toxicological or ecotoxicological concern.
7.
Re-jection Factor;
                         The rate of volatilization was
                         incorrectly calculated and could not be
                         determined with the information
                         provided.

     EPA Guidance on this Factor

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), page C-319.

     This issue is normally not a criterion for rejection of a
study, and is usually repairable by the submission of additional
data.  However, if the intent of the study cannot be met by the
submission of this additional data, then a new study would be
required.

     Industry Comment

     Volatilization rates should be calculated correctly.
Additional guidance from EPA on the correct calculation should be
provided.

     EPA Response

     The Agency acknowledges the need for additional guidance for
this guideline; this point will be considered when the
Subdivision N guidelines are revised.


8.   Rejection Factor;   The experiments were not replicated.

     Rejection factors 7 and 8 relate to basic information
required by the EPA.  The information pertains to important study
parameters that must be reported so that a technical evaluation
of the data can be made.  In some cases, studies rejected solely
on these reporting deficiencies are likely to be upgraded by the
registrant by the submission of the additional data.
                              -  139  -
-------
                                                     Laboratory Volatility (163-2)
      Industry Comment
      In experiments which require analysis of samples taken over
 time,  unusual results are readily apparent.  Replication may not
 be necessary when a clear pattern of volatilization has been
 demonstrated.
      Industry Recommendation:  EPA should explain its
 expectations for replication and the level of statistical
 significance required.

      EPA Response

      The purpose of the study is to provide information on the
 actual  rate or extent of pesticide volatilization from soil under
 controlled conditions;  the "demonstration of a clear pattern" of
 volatilization from soil does not necessarily address the
 question of rate or extent.   The intent is not to replicate the
 experiment,  but,  at a minimum,  to perform duplicate analysis at
 each  sampling interval.   Guideline 160-5 of Subdivision N
 specifies that the  registrant provide a summary of the data  an
 analysis of the data, sufficient data for the Agency to verify
 calculated statistical  values,  and a statement of conclusions to
 be drawn from the analysis.   If only a single data point is
 provided at each sampling interval,  its variability cannot be
 determined.

 ADDITIONAL AGENCY COMMENTS

      If  a chemical  has  the potential to be highly volatile (the
 vapor pressure exceeds  10"4 mm Hg) and  if volatile  components  are
 trapped  in the volatile  traps in the aerobic  metabolism (162-1)
 study,_then it is apparent that volatilization will  be a
 significant  mechanism for dissipation  of  the  active  ingredient
 The Agency would  then consider  accepting  a waiver request  for the
 laboratory volatility data requirement.   However,  the  field
volatility data requirement  (163-3)  would then be  imposed.  A
proposed trigger  for the  field  study is 20% of the dose (either
as parent  or a degradation intermediate,  excluding 14C02) being
volatilized  in the  aerobic metabolism  study.
                             - 140 -
-------
                                                      Field Volatility (163-3)
            GUIDELINE  163-3  FIELD VOLATILITY STUDIES
1.
Relaction Factor;
The soil data, were inadequate to confirm
the application rate.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 75.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance. (December 1989), pages C-320 & C-321.

     Application rate is required to accurately determine the
volatility of the test substance and to ensure that the study
conditions closely resemble actual use conditions.

     Industry Comment

     Confirmation of the application rate by some method is
necessary to ensure that the study conduct meets the intent of
the protocol.  The EPA Guidance assumes that the registrant seeks
to simulate actual use conditions and that the application method
will give a homogeneous distribution in soil.  The registrant may
design the study to maximize the potential for volatilization or
simulate actual use conditions such as by applying the  chemical
to a cropped field.  In either case, soil analyses may  not
provide a satisfactory indication of the application rate due to
inhomogeneity of the application.  Direct application of some
formulation types, such as granules, will not give a homogeneous
distribution of product, and the determination of application
rate by soil analysis may give unsatisfactory results.

     In a volatility study, soil data are used to confirm the
application rate and provide a measure of the amount of chemical
remaining in the field.  The volatilization rate of the chemical
and its concentration in air are determined by air sampling, not
by soil analyses.

     Industry Recommendation:  Generally, soil samples  should be
obtained immediately after application to confirm the application
rate.  When soil analyses are not adequate by virtue of factors
inherent in the study design, alternatives such as known weights
or volumes applied should be acceptable.  Verified calibration of
the application equipment and demonstrated performance  of the
equipment may be acceptable also.
                              -  141  -
-------
                                                        Field Volatility (163-3)
      EPA Response
      The Agency agrees  that  the analysis  of  soil  provides
 SSf1S?n^^bat-t:he Pesticide was applied  at  the  desired rate.
 This information is necessary because  the application  rate should
 approximate the highest recommended rate  for a  single  aSplicatloS
 under field conditions.  However, the  Agency also agrees that
 environmental factors at the time of application  (such L  w?nd
 ?hTla?  C™P CJVSr) Ca? affect the amount  of  Pesticide found in
 2?«S?i    Therefore' soil analysis or other means•such as known
 rffkts or ™lumes of Pesticide applied to the  soil may be used
 to confirm the rate of application, provided that the  calibration
 and performance of the application equipment is verified 1DratlOn
 2U.   Re-jection Factor!
                          Data on soil characteristics was not
                          provided.
      EPA Guidance on this Factor

           Subdivision N:  Environmental Fate Guidelines (1982)
           page 75.                                            '

           FIFRA Accelerated Reregistration Phase 3 Technical
           Guidance.  (December 1989),  pages C-320 & C-321.

 Qt.11,KrThiS,qisSUe does not  normally result in the rejection of a
 study,  and is  usually repairable by the submission of additional
 data    Information on the soil class,  texture,  pH,  and percent
 organic matter is necessary to verify that the  Soil is PSrCent
 representative of agricultural soils.   If foreign soils are used
 S?n£5i,°? ^J.01™:  textural classification,  and crSp use   '
 are needed to  indicate its  similarity to U.S. soils.

     Industry  Comment

     Data  on soil characteristics should be provided  by the
     ??^;  T?S  ^idance on use of foreign soil  conflicts with
     r  ??n^l^ed  Reregistration  Phase 3 Technical Guidance,
 thuSited'staJes indlCateS  that the  stu^ must ^e  conducted in


 .    Industry Recommendat-.inn;  The following soil characteristics
should be provided by  the registrant:   soil  class,  tllture  pH
organic matter content and CEC.   Studies  conducted  on foreign
soils which are similar to U.S.  soils should be acceptable.
                             - 142 -
-------
                                                      Field Volatility (163-3)
     EPA Response
     The Agency has previously allowed field studies to be
conducted outside of the United States; a recent example is a
field dissipation study in an apple orchard in Canada.  This rare
event was permitted due to the high degree of similarity of
climate and soil characteristics to those in apple-producing
regions in the United States.  The Agency will continue to
consider the acceptability of non-domestic field studies on a
case-by-case basis.  Before initiating field studies outside the
United States, the registrant should obtain approval from the
Agency.
3.
Re-lection Factor;
The description of experimental
conditions were insufficient.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines  (1982),
          page 74-77.

          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.  (December 1989), pages C-320-C-322„

     This issue does not normally result in the rejection of  a
study, and is usually repairable by the submission of additional
data.  This rejection factor relates to basic  information
required by the EPA.  The information pertains to important study
parameters that must be reported so that a technical evaluation
of the data can be made.

     Industry Comment

     The experimental conditions should be described in
sufficient detail to allow the determination of volatilization.
Weather conditions such as wind speed and temperature  should  be
provided.  Estimates of evapotranspiration through measurement of
water flux or solar  flux should be provided as necessary.  The
following references provide experimental designs which can be
used to determine volatility and indicate which experimental
conditions are necessary.

     Jury, W. A., W. F. Spencer, and W. J. Farmer.   1983.
Behavior Assessment  Model for Trace Organics  in Soil:  I. Model
Description.  J. Environ. Quality  12(4):558-564.
                              - 143 -
-------
                                                       Field Volatility (163-3)

      Glotflety,  D.  E.,  A.  W.  Taylor,  B.  C.  Turner and W.  H.
 Zoller.  1984.  Volatilization  of Surface-Applied Pesticides from
 Fallow Soils.  J.  Agric.  Food  Chem.  32:638-643.

      Glotflety,  D.  E.  ,  M.  M.  Leech,  J.  Jersey,  and A.  W.  Taylor,
 1989.^Volatilization and Wind Erosion of Soil Surface Applied
 Atrazine,  Simazine,  Alachlor  and Toxaphene.   J.  Aqric.  Food Chem
 37:546-551.

      Majewski, M. S., M. M. McChesney and J.  N.  Seiber.  1991. A
 Field Comparison of Two  Methods for Measuring DCPA Soil
 Evaporation Rates.  Environ. Tox.  Chem.  10:301-311.

      Ross, L.  J., S. Nicosia,  M.  M. McChesney,  K.  L.  Hefner,  D.
 A. Gonzalez, and J.  N.  Seiber.  1990.  Volatilization,  Off-Site

 Deposition and Dissipation  of  DCPA  in the Field.  J.  Environ.
 Qual.  19:715-722.

     _Industry  Recommendation:   EPA  should develop guidance for
 specific experimental details  which must be reported.  The
 guidance should  reflect  several acceptable study designs which
 have  been  reported  in the literature  references.

      EPA Response

      There is  an  international  interest  in the  loading of  organic
 compounds  into the  atmosphere;  in addition, the  Office of  Air
 within EPA is  interested in the transport of  pesticides off  the
 site  of application.  An additional concern in  the  field is  the
 dissipation of the pesticide from both the soil  and  the plant
 surfaces.  The Agency is willing  to discuss any  sampling scheme
 for the field  study which would also  help us  address
 international and Agency concerns.

     The Agency agrees that there may be insufficient guidance
 available  for the Field Volatility data  requirement, particularly
 as it applies to the determination of the environmental fate  of
pesticides.  The Agency and Industry  have agreed  to  form a joint
workgroup to discuss and resolve  the  issues regarding the
appropriate criteria for triggering and  conducting laboratory and
 field volatility  (163-2 and 163-3) studies.   These criteria will
be incorporated into any future revisions of  this guideline.

ADDITIONAL AGENCY COMMENTS

     The registrant may request that  the field volatility  data
requirement be waived if and only if  volatiles are monitored
during the terrestrial field dissipation study  (164-1).  If the
                             - 144 -
-------
                                                        Field Volatility (163-3)

registrant chooses  this  approach,  the registrant should design
into the terrestrial  field dissipation study a component capable
of monitoring the volatiles seen in the lab, whether in the
aerobic soil metabolism  (162-1)  or the laboratory volatility
(163-2) study.
                              - 145 -
-------
                                                 Terrestrial Field Dissipation (164-1)


      GUIDELINE 164-1 TERRESTRIAL FIELD DISSIPATION STUDIES
1.   Re-lection Factor;   The original concentration of  the
                         pesticide was not reported or  the
                         reported application rate was  not
                         confirmed in soil samples taken
                         immediately posttreatment.

     EPA Guidance on this Factor

          Subdivision N - Environmental Fate Guidelines (1982).
          p. 79.

          Environmental Fate - Addendum 2 - Series 164-1  (1986).
          p. 9.

          Environmental Fate and Effects Division Standard
          Evaluation Procedure for the Terrestrial Field
          Dissipation Study  (1989).  p. 19.

          FIFRA Accelerated Reregistration - Phase 3 Technical
          Guidance  (1989).  p. C-323-7.

     Soil samples are taken immediately post-treatment  to
establish the concentration of the pesticide in the soil at  the
beginning of the study. In addition, the actual application  rate
of the pesticide must be known to confirm that the maximum label
rate of the pesticide was used.  Dissipation rates at different
pesticide application rates can vary unpredictably because the
soil microorganisms and plants responsible for the degradation
process may respond differently at different concentrations  of
the pesticide.

     Industry Comment

     Industry concurs with the Agency that it is essential to
measure the concentration of parent and metabolites immediately
post-treatment.

     It is also essential to specify the nominal application rate
by detailed reporting of the preparation of the tank mixture
components  (by weight or volume) and by reporting details of the
calibration of application equipment.  Industry does NOT
recommend the routine analysis of tank mixtures which can often
produce misleading results  (dependent on formulation type and
sampling technique).
                              - 146  -
-------
                                                 Terrestrial Field Dissipation (164-1)

     The EPA's guidance has been  consistent  on  the use  of  the
maximum label rate for a terrestrial  field dissipation  study.
Industry concurs„

     Industry agreed  (May 8, 1991 letter on  "Subpart  N"
revisions) with previous Agency advice that  three replicate
samples (either replicated by sub-plot or by composition from
samples taken across  the entire treated area) should  be taken on
all sampling occasions.  Industry believes that the mean analyte
concentration immediately post treatment should normally be
expected to be below  the nominal application rate.  This is
particularly true for applications where crop interception is
significant, but it also applies to bare soil applications.

     With certain active ingredients  and/or  application
techniques  (e.g. granular formulations or certain very labile or
volatile active ingredients) it is difficult to account for most
of the chemical applied.  Experience  has shown  that the recovery
immediately after application may often be expected to be  between
60 and 80% of the nominal value.  This does  not give  adequate
cause for rejection of a field dissipation study provided  the
registrant submits adequate documentation to confirm  the amount
of chemical applied to the plot by the application equipment.

     Industry is aware of very few, if any,  compounds whose
dissipation rates differ markedly within the normal use rate
range of a pesticide.  Industry believes soil types,  etc.  are
more significant variables determining the dissipation rate of a
chemical.

     Industry Recommendation:  EPA should stress the  importance
of the detailed reporting of proper application equipment
calibration and application mixture preparation in order to
confirm application at the normal rate.

     EPA Response

     The Agency agrees that slightly  reduced or exaggerated
applications would not be expected to markedly  alter  the apparent
dissipation characteristics.  However, in order to have as clear
a picture as possible- of the environmental fate  of a pesticide
under field conditions, the immediate post-application rate
should be as close to nominal as possible.   It may even be
advisable to apply a  slightly exaggerated (i.e., 1.1X) rate to
assure that soil levels approximate the maximum label rate.

     The Agency agrees that detailed  reporting  of the equipment
calibration and mixture preparation are important, but notes that
such information can not be used to confirm'the application rate
                             - 147 -
-------
                                                 Terrestrial Field Dissipation (164-1)

and verify the amount of pesticide that actually reached the
field.  Other methods for confirming the application rate,
besides actual soil sampling, is a topic for further discussion.

     We agree that routine analysis of tank mixtures is not
appropriate for this guideline; the analysis of tank mixtures  is
more pertinent to the Tank Mix  (164-4) data requirement.
     Rejection Factor;
The pattern of formation and decline of
the degradates was not addressed.
     EPA Guidance on this Factor

          Subdivision N - Environmental Fate Guidelines  (1982)„
          p. 79.

          Environmental Fate  - Addendum 2  - Series 164-1  (1986).
          p. 11.

          Environmental Fate  and Effects Division Standard
          Evaluation Procedure for the Terrestrial Field
          Dissipation Study  (1989).  pp. 4, 15, 20, 21.

          FIFRA Accelerated Reregistration - Phase 3 Technical
          Guidance  (1989).  p. C-324-14.

     A primary purpose of the field dissipation study  is  to
identify and quantify the degradates of a  pesticide when  the
pesticide is applied under typical field conditions.   Although
the aerobic soil metabolism study  (162-1)  provides information  on
the identity and amounts of degradates which occur when the
pesticide is applied to soil  in a laboratory situation, patterns
of formation and decline of degradates under actual use
conditions may be different from those observed in the
laboratory.

     Industry Comment

     Industry disagrees that  one purpose of a  field dissipation
study is to identify degradates formed under field conditions.

     The field dissipation study should provide information on
the formation/decline of parent and/or degradates for  which
satisfactory analytical methods have been  developed.

     Industry does  not believe there is adequate guidance on
which degradates merit analysis in the field dissipation  study
 (see Rejection Factor 4).
                              -  148  -
-------
                                                 Terrestrial Field Dissipation (164-1)

     Industry Recommendation;  Improved guidance on the  selection
of potential degradates for analysis in field dissipation  studies
should be agreed between the Agency and Industry  (see Rejection
factor 4).

     EPA Response

     The Agency does not agree with Industry's  first comment.
While the purpose of the laboratory studies is  to provide
guidance on what degradates to look for in the  field, the  purpose
of the field studies is to provide a comprehensive environmental
fate profile of the chemical and its degradates under actual  use
conditions.  Those degradates identified under  laboratory
conditions must also be analyzed for in the field.

     In response to Industry's second comment,  the Agency  remains
concerned that the degradates of ultra-low  (<50g ai/Ha)
application rate pesticides may be difficult to detect in  the
laboratory, and may be even more difficult to detect under field
conditions, and that the development of newer, more sensitive
methods of analysis may be required.

     The Agency agrees with the Industry recommendation.   All
residues of concern identified in the laboratory studies
(microbial degradation, hydrolysis, and photodegradation)  and
present in those studies at levels greater than or equal to 10%
of the applied dose rate, should be analyzed for.

     The Agency recognizes that analysis of samples from field
studies  (which use non-radiolabeled typical end use products) for
all residues of concern identified in the laboratory studies
(which use radiolabeled material) may not always be feasible.
The Agency will take this into consideration when reviewing the
study.
3.
Re-lection factor;
The sampling was not done to depths
sufficient to define the extent of
leaching.
     EPA Guidance on this Factor

          Subdivision N  - Environmental Fate Guidelines  (1982).
          p. 79.

          Environmental  Fate - Addendum 2  - Series 164-1  (1986)
          p. 11.
                              - 149  -
-------
                                                 Terrestrial Field Dissipation (164-1)

          Environmental Fate and Effects Division Standard
          Evaluation Procedure for the Terrestrial Field
          Dissipation Study  (1989).  p. 4, 21.

          FIFRA Accelerated Reregistration - Phase 3 Technical
          Guidance  (1989).,  p. C-323-12.

     Results from the field dissipation study along with data
from other environmental fate studies are used to determine the
leaching potential of a pesticide and whether ground water
monitoring studies are needed.  If it can not be determined how
far through the soil a pesticide or its degradates have moved by
leaching, the potential for contamination of ground water cannot
be assessed.

     Industry Comment

     Industry previously proposed (May 8, 1991 comments on
Subdivision N revision, page 59) a new guideline requirement
involving studies similar to field dissipation studies, but
requiring soil coring and analysis to 90-120 cm on sites that
favored mobility.   This approach concentrates detailed
investigation of potential pesticide/degradate mobility on the
situations where it is most probable.

     Industry fully agrees that potential soil mobility is a
vital objective of the field dissipation study.

     Industry Recommendation;  Industry recommends that detailed
investigation of potential parent/degradate mobility should be
concentrated on no more than two vulnerable sites from which deep
cores will be taken.

     EPA Response

     The field dissipation data requirement was designed to
define dissipation characteristics of a pesticide when used
according to label directions, which include typical use sites.
The selection of particularly vulnerable sites as the initial
testing sites would therefore only be appropriate where such
sites were typical of the proposed use pattern.  As an example, a
proposed fungicide to be used on citrus could be tested at a
vulnerable site in Florida.

     With reference to this rejection factor, sampling must still
be done to a depth sufficient to define leaching at the typical
use site.  "Sufficient" depth means that cores must be taken to
90 cm divided into, at most, 15 cm segments  (smaller increments
may be required depending upon the limit of quantification), and
                              - 150  -
-------
                                                 Terrestrial Field Dissipation (164-1)

analyzed until one residue-free core  is found.   Thus, a maximum
of two segments would need to be analyzed  for relative immobile
compounds, while as many as six segments may have  to  be analyzed
(usually later in the study) for more mobile compounds  (or
compounds with mobile major degradates)„   The remaining
(unanalyzed) cores should be retained, frozen, at  least until the
study is found acceptable by the Agency, provided  there are
adequate storage stability data to support the maximum duration
of storage.
4.   Rejection Factor;
Characterization of residues was not
provided for all sites or the soil was
not analyzed for the correct residues or
for all residues.
     EPA Guidance on this Factor

          Subdivision N - Environmental Fate Guidelines  (1982).
          p. 79.

          Environmental Fate - Addendum 2 - Series 164-1  (1986).
          p. 11.

          Environmental Fate and Effects Division Standard
          Evaluation Procedure for the Terrestrial Field
          Dissipation Study  (1989).  pp. 4, 15, 20, 25.

          FIFRA Accelerated Reregistration - Phase 3 Technical
          Guidance  (1989).  p. C-324-23.

     Ideally, the parent and major degradates as identified from
the laboratory studies (the soil metabolism studies and possibly
the hydrolysis and photolysis studies) which may be present at
0.01_ppm_or 10% of the applied should be monitored in the field
dissipation study.  However, because the field studies generally
use unlabeled material, the analytical methods used in the
laboratory studies may not be appropriate for analyzing field
samples.  The analytical methods used for the analysis of soil
samples must be capable of identifying and quantifying residues
in field samples in order to determine the dissipation of the
pesticide and its degradates.

     Industry Comment

     Industry believes the term "characterization of residues" is
potentially misleading; it is frequently confused with
"identification".  In the case of a field dissipation study
(unless radio-labelled material is used) neither term is correct,,
                             - 151 -
-------
                                                 Terrestrial Field Dissipation (164-1)

     Industry believes that a field dissipation  study should  only
be expected to confirm the formation/decline of  potentially sig-
nificant metabolites.  Therefore the term  "not analyzed for..all
residues" is misleading.

     Analysis of very labile parent or metabolites may be
discontinued after 2 sampling points have  shown  no detectable
residues.

     In situations where a complex mixture of degradates can
occur via microbial and/or physical processes in or  on the soil,
discussion between the Agency and the registrant must consider

relevant factors to agree on a list of degradates for analysis.
Important factors include:

          1) Longevity of degradate in laboratory studies.

          2) Potential mobility of degradate  (aged leaching
          study).

          3) Is  the compound a "terminal residue"?

          4) Can the metabolite be analyzed as part  of a "catch-
          all" generic analytical method?

          5) Likely concentration in the soil vs. analytical  LOD.

          6) Application rate of the active ingredient  (and hence
          potential maximum metabolite concentration).

          7) Potential human effects and ecotoxicology of
          degradate.

          8) Similarity of the metabolite  to other compounds
          which  can serve as  "marker" analytes.

     Industry Recommendation;  Industry recommends that a  joint
EFGWB/Industry work group determine suitable analytes for  inves-
tigation in field dissipation studies.  Analysis for more  than
two or three "marker" analytes should rarely, if ever, be
necessary.

     Industry recommends that only metabolites present at  levels
greater than 10% of applied should be identified and that
normally only these significant metabolites should be considered
for analysis in  field soil studies.  An exception might be other,
less abundant, metabolites demonstrated to have  the  potential to
leach.
                              -  152 -
-------
                                                 Terrestrial Field Dissipation (164-1)
     EPA Response
     In order to determine  the persistence,  run off  potential  and
leachability of a pesticide and  its degradates  under typical
field use conditions, one must be able  to both  identify and
quantify the pesticide and  its degradates.

     For further guidance on which degradates must be considered,
see the EPA response in Rejection Factor 2 above.

     The Agency would concur with the discontinuation of analyses
after two sampling points have shown no detectable residues, if
and only if the analytical  method used  had an acceptable Limit of
Detection and acceptable recoveries.

     A joint EPA/Industry work group has been formed to discuss
and resolve the issues surrounding terrestrial  field dissipation
studies.  As part of this work group, the criteria used to
determine the selection of  degradates for analysis that may be
found in the field dissipation studies  will  be  addressed.   These
criteria will be incorporated into any  future revisions of  this   •
guideline.
5.   Rejection Factors
Complete soil characteristics and field
test data were not provided.
     EPA Guidance on this Factor

          Environmental Fate - Addendum 2 - Series 164-1  (1986).
          p. 8.

          Environmental Fate and Effects Division Standard
          Evaluation Procedure for the Terrestrial Field
          Dissipation Study  (1989).  pp. 3, 4, 14, 16.

          FIFRA Accelerated Reregistration - Phase 3 Technical
          Guidance  (1989).  p. C-323-9.

     This issue does not normally result in the rejection of a
study, and the study is usually repairable by the submission of
additional data.

     This information must be accurate to evaluate the conditions
under which the field study was conducted.  This is a critical
element in determining the rate of dissipation of the test
substance.  For instance, dissipation data are affected by the
type of soil, the amount of rainfall, the slope of the test site;
etc.  In addition, this information is needed to determine
                             - 153 -
-------
                                                 Terrestrial Field Dissipation (164-1)
whether the study was conducted under suitable conditions,
representative of the intended use pattern.

     Industry Comment

     Industry agrees that proper field data reporting is
essential to understanding field soil dissipation data,

     EPA Response

     No comment.
6.   Re-jection Factor;   The analytical methodology was
                         insufficient to identify  the residues
                         (in one case, the analytical method
                         could not distinguish between the parent
                         and its dearadates).

     EPA Guidance on this Factor

          Environmental Fate - Addendum 2 -  Series 164-1  (1986).
          p. 10.

          Environmental Fate and Effects Division  Standard
          Evaluation Procedure for the Terrestrial Field
          Dissipation Study  (1989).  pp. 4,  20, 24.

          FIFRA Accelerated Reregistration - Phase 3 Technical
          Guidance  (1989).  p. C-324-23.

     A primary purpose of the field dissipation study is  to
identify and quantify the degradates of a pesticide when  the
pesticide is applied under typical field conditions.  Because the
field studies most  commonly use unlabeled material, the
analytical methods  used in the laboratory studies may not be
appropriate for analyzing field samples.  The analytical  methods
used for the analysis of soil samples must be capable of
identifying and quantifying residues in field samples in  order  to
determine the dissipation of the pesticide.  Unless the method  of
analysis used is sufficiently specific, evaluation of the
dissipation of the  pesticide under field conditions becomes
meaningless.

     Industry Comment

     The analytical method is not expected to identify residues,
merely to quantify  them. However, Industry agrees  that a  method
                              -  154  -
-------
                                                  Terrestrial Field Dissipation (164-1)

 must be sufficiently specific so that assignment of a detector
 response to a specific analyte is unambiguous.

      Industry agrees that it is ideal to have specific methods
 tor all analytes.  However, in certain circumstances  (e.q  a
 class of related metabolites)  it is appropriate to have a "catch-
 all'  common-moiety method.

      Because common moiety approaches sum the total of various
 metabolites they may be considered as improving the sensitivitv
 of the overall analyses.                               .        *

      Industry agrees that if a company cannot avoid using a
  common moiety  analytical method,  EFGWB may reasonably assume
 that  a majority of detected chemical is present as the most toxic
 or mobile representative  of the compounds quantified by the
 technique.   Given this  assumption,  meaningful (but "worst case")
 evaluation of the results is possible.

   _.  Industry Recommendation:  EPA should accept "common moiety"
 methods where they are  cost effective and where the registrant is
 prepared to be regulated  under "worst-case"  assumptions.

      EPA Response

     _A "common moiety"  method  of  analysis, which expresses
 pesticide residue concentration in  the  sample as the sum total of
 all the various residues  with  that  particular moiety,  with  no
 regard to the identity  of the  individual  components,  may be
 acceptable  in some  cases.   For those pesticides  and their
 degradates  that have been shown in  the  laboratory to be  of  little
 or no_toxicological/ecotoxicological concern,  relatively
 immobile, and not persistent,  a "common moiety"  method may  be
 appropriate.   However,  if there is  a concern about  the parent  or
 any of  its  degradates,  then the analytical method must be able to
 distinguish between the residues.   The  Agency wishes  to  refrain
 from basing its  exposure  assessment  on  the assumption  that  the
 greatest  exposure is to the  most  toxic  residue,  particularly when
 analytical  methods are available  to  define,  with certainty  the
 identity  of the  residues  of  concern  in  the field.

     Before initiating field studies using a "common moiety"
 analytical method, registrants should request  approval from the
Agency.

     For  those  chemicals  that meet the  criteria  described above
 registrants may  resubmit any studies that were rejected solely on
 the basis of the  "common moiety" analytical  technique.  These
studies will then be reevaluated to determine  if they contribute
                             - 155 -
-------
                                                 Terrestrial Field Dissipation (164-1)


to the understanding of the dissipation of the pesticide and  its
degradates in the environment,,
     Rejection Factor;
The data were too variable to accurately
assess the dissipation of the test
substance.
     EPA Guidance on this Factor

          Subdivision N  - Environmental  Fate  Guidelines  (1982).
          p.  80.

          Environmental  Fate -  Addendum 2  - Series 164-1 (1986).
          p.  11.

          Environmental  Fate and Effects Division Standard
          Evaluation Procedure  for the Terrestrial Field
          Dissipation  Study (1989).   pp. 15,  27.

          FIFRA Accelerated Reregistration -  Phase 3 Technical
          Guidance  (1989).   p.  C-324-14, 19.

      Variability in data from a field dissipation study can arise
 from non-uniform application of the test substance to the test
 plots,  inadequate or improper soil sampling  °***™r enable
 Analytical  mSthod.   The dissipation rate and half-life estimates
 of the test substance are usually estimated using regression
 analysis performed on the data in order to indicate how well the
 dissipation rate is described by a first-order kinetics model
 If the data are highly variable, the estimates of the half-life
 provided by the regression analysis are unreliable.

      Industry Continent

      Industry acknowledges  that data  from field  dissipation
 studies are frequently variable.  Many  of the potential  sources
 of variation are inherent  in the field  use pattern  (e.g.,
 granular banded applications,  seasonal  soil  temperature
 variations, weather, plough back of residues etc.).   Care must Joe
 taken in rieldstudieS  to  reduce and/or understand  variability as
 far as possible  (e.g. Industry's agreement to analyze replicate
 sSpKsPat each sampling interval) .   Efforts to  reduce/explain
 variability  should be clearly  reported.

      Despite this  inherent variability, Industry accepts that it
 is responsible  for controlling variability as  far as possible in
 field soil dissipation  studies
                               - 156 -
-------
                                                Terrestrial Field Dissipation (164-1)

     Industry believes that the inability to calculate a
dissipation half life with a high degree of confidence from field
soil dissipation study data should not be a reason for the
rejection of a study.  Industry strongly disagrees with the
assumption that all field dissipation rates should fit a first-
order model. (Reasons for multi phasic dissipation behavior have
been presented in the literature See References 1-4).

     Industry recommends that registrants seek the best
interpretation of parent/degradate dissipation kinetics possible.
This should be based'on their expert knowledge of the chemical's
properties and related field factors  (e.g., seasonal variations
in temperature and/or soil saturation level).  The basis for
calculating half lives should be clearly explained by the
registrant in reports; risk managers should ensure that half
lives used for computer modelling have been calculated from the
most appropriate subset of the field data.

     Industry strongly discourages the use of a,rejection  factor
such as  "too variable".  The important objectives of the field
dissipation are to  investigate the potential persistence and
mobility of parent/degradates.  Normally, sampling/analytical
variability only influences half-life measurement when the half
life is  relatively  long.  In this circumstance, it  is preferable
to quote a range for the half life for each site since that is
what will be found  in practical agricultural use of  the chemical.
It will  frequently  provide useful model sensitivity information
to use half life ranges in mathematical modelling of run off  or
leaching.  Registrants accept that EPA will initially  use the
"worst case" half life indicated by a study; to negate such a
value, Industry will either have to present well-justified
arguments or conduct further studies.

     Field  dissipation studies are normally conducted on two  or
more sites.  The Agency should consider the agreement between
half life ranges measured at the various  sites before rejecting  a
study  on the basis  of data variability.

     Industry  Recommendation; EPA  should  consider  the half
lives/mobilities measured  in  field soil dissipation studies as
indicative  of  a tendency  of  the  active  ingredient/degradate to
dissipate/move.   Neither  criterion is a  "hard"  number.  A range
of  potential half  lives should  always be  considered when
modelling,  etc.  is  needed.

      Industry  recommends  that  registrants seek the best
 interpretation of parent/degradate dissipation kinetics possible
 rather than assuming that first order kinetics are applicable.
                              - 157 -
-------
                                                 Terrestrial Field Dissipation (164-1)
     EPA Response
     The Agency recognizes  that  some amount  of variability is
inherent in any field study.  However,  excessive variability
brings into question the validity  of the data.  In  essence,  the
data needs to describe a clear pattern  of  dissipation.

     Although the Agency stated  that the dissipation  rate  and
half-life are usually estimated  by a first-order model, we agree
that the use of other models to  estimate field dissipation rates
may sometimes be more appropriate.  We  also  agree that  the basis
for calculating half-lives  should  be clearly explained.  If the
registrant has chosen to use a subset of the field  data to
calculate those half-lives, they must provide a justification  for
doing so.

     Field factors such as  seasonal variations in temperature  and
or soil moisture may affect dissipation kinetics.   Field
dissipation studies are normally conducted on two or  more  sites
representative of the areas where  the pesticide is  expected to be
used.  These areas often differ  markedly in  climate and soil
characteristics; therefore, it would not be  unexpected  to  find
that half-lives will also differ markedly.   However,  the Agency
does not see how a comparison of half-life ranges between
dissimilar sites might be useful in explaining data variability
within a single site.  Each study  should stand on its own.
8.   Rejection Factor;
The freezer storage stability data were
inadequate.
     EPA Guidance on this Factor

          Environmental Fate - Addendum 2 - Series 164-1  (1986)
          p. 10.

          Environmental Fate and Effects Division Standard
          Evaluation Procedure for the Terrestrial Field
          Dissipation Study  (1989).  p. 21.

          FIFRA Accelerated Reregistration - Phase 3 Technical
          Guidance  (1989).  p. C-324-20.

     This issue does not normally result in the rejection of a
study, and the study is usually repairable by the submission of
additional data.
                             - 158 -
-------
                                                 Terrestrial Field Dissipation (164-1)

     Freezer storage stability of soil samples is not usually a
problem in the laboratory studies because the samples can be
frozen immediately after collection and are not  stored for long
periods of time.  However, in field studies, soil samples usually
cannot be refrigerated or frozen immediately after collection.
In addition, over the many weeks (or months) of  the study,  ...
samples can accumulate in a freezer prior to analysis.
Therefore, a contemporaneous "spiking-" study must be conducted,
in which a known amount of active ingredient is  added to portions
of soil from an untreated area of soil at the test site at the  '
same time that soil samples from the treated areas are collected.
The "spiked" samples are then stored under the same conditions as
samples from the test plot, and all samples are  analyzed at the
same time.  This should indicate whether the pesticide in-the
samples from the test plots is degrading in the  soil during .. >
handling and storage, and if so, whether it is possible to
normalize the results to account for the amount  of change during
storage.  If the data cannot be corrected in this way, it is  not,
possible to distinguish between the amount of the dissipation '
occurring during storage and the dissipation occurring under
field conditions, and the study must be repeated.

     Industry Comment

     Industry agrees that adequate freezer storage stability
information on one soil is critical to ensure that a field soil
dissipation program is valid.

  '   Most registrants and contractors currently  routinely cool
samples immediately after sampling and freeze cores within a  few
hours.

     Criteria for "acceptable" storage stability need to be
harmonized with the Residue Chemistry branch requirements,,

     Industry Recommendation;  Industry does not agree that the
use of field spiking procedures is essential to  validate field
dissipation studies; nevertheless,  it can be a valid approach„
Freezer storage stability may also be measured in a carefully
controlled laboratory study designed for that purpose.  Data  from
field-spiked samples or from laboratory samples  may be used at
the registrant's discretion.

     EPA Response

Note:     The following discussion is consistent with the     . .
          position of the Chemistry Branches in  HED on the   .•
          requirements for storage stability data (Health Effects
          Division memo dated January 14, 1993).  The registrants
                             - 159 -
-------
                                                 Terrestrial Field Dissipation (164-1)

          are referred to that document for additional guidance.
          Industry may, at its option, propose an alternative
          guidance document for Agency consideration.

     Chemicals may degrade during storage, even under ideal
storage conditions. Therefore, storage stability data are
essential in order to be confident that any degradation measured
in the test system was due solely to the environment of that  test
system, and not due to handling and storage.  Storage stability
in soil is chemical specific; in addition, a chemical's stability
when stored in different soils can vary unpredictably.

     The stability of the parent compound and its suspected
degradates (as best can be determined prior to conducting the
study) under storage conditions should be determined before the
initiation of the field study to assure proper sample handling,
In any case,  evidence must be provided confirming that the levels
of residues and their relative proportions did not change during
the period between collection and final analysis.

     At this time the Agency believes field spiking is important
for those studies conducted under field conditions to ensure
proper handling of samples in the field and their timely
refrigerated storage; however the Agency has agreed to let
industry develop a draft storage stability guidance document  to
address this and other storage stability issues.  Final Agency
judgement on this issue will be reserved for the Storage
Stability follow-up guidance.
     Rejection Factor;
The maximum label rates were not used,
and the soil incorporation, procedure
recommended on the label was not
followed.
     EPA Guidance on  this Factor

          Subdivision N  - Environmental  Fate Guidelines  (1982).
          p.  79.

          Environmental  Fate  - Addendum  2  - Series  164-1  (1986)
          p.  7.

          Environmental  Fate  and  Effects Division Standard
          Evaluation  Procedure for  the Terrestrial  Field
          Dissipation Study  (1989).   pp. 15-16.

          FIFRA Accelerated Reregistration - Phase  3  Technical
          Guidance  (1989).  p. C-323-7.
                              -  160  -
-------
                                                 Terrestrial Field Dissipation (164-1)

     The field dissipation study is done to evaluate the
dissipation of the pesticide under typical use conditions.
Because dissipation rates at different rates of  application of a
pesticide can vary unpredictably, application at the maximum
label rate is needed to estimate dissipation  when the largest
amount of pesticide permitted by the product label is added to
the soil.  Incorporation techniques  (how the pesticide is mixed
with^the soil after application) can also affect the rate of
dissipation.  If a pesticide is sprayed on the surface of the
soil (where it can be photodegraded), the rate of degradation and
the degradates formed may be completely different than if the
pesticide is incorporated or injected into the soil.

     Industry Comment

     Industry fully agrees that a field soil dissipation study
should employ the maximum label rate and that application
methodology should mimic the "worst case" field  approach required
on the label (in terms of maximizing mobility).

     If a number of application methods/incorporation approaches
are permitted on the label, the registrant should explain why the
selected method is believed to represent the worst case with
respect to chemical mobility.

     Industry recommends that if a new use is proposed for a
compound at a higher rate than those used in the initial soil
dissipation studies, the EPA should carefully consider the weight
of the evidence on half lives before requesting  another soil
dissipation study on the basis of the higher field rate.

     Industry Recommendation:  Where the compound label requires
multiple applications, Industry continues to recommend (See May
8, 1991 letter regarding Subpart N revisions)  that a single
application to a bare plot totalling the annual  loading of the
pesticide will be satisfactory.

     Where a number of application methods or incorporation
approaches are permitted,  the registrant should perform a soil
dissipation study for the use pattern that represents the worst
case with respect to chemical mobility.

     EPA Response

     The Agency continues to prefer that a pesticide be applied
according to label directions,  including acceptable and common
agricultural practices.  For example, if the label calls for
weekly applications all summer, then this is how it should be
applied when tested.  We do not believe that combining all
                             - 161 -
-------
                                                 Terrestrial Field Dissipation (164-1)

applications into a single application would accurately represent
the projected dissipation under field conditions.  Nevertheless,
the Agency will consider variations on this approach, on a case-
by-case basis.

     Requests to amend the label to increase the application  rate
may result in the need for additional field monitoring based  on
the specific use patterns and the magnitude of the increase._
Therefore, the need for additional testing is usually determined
on a case-by-case basis.

     We agree that some latitude should be allowed in the
selection of application/incorporation methods where more than
one method appears on the label.  However, the registrant must
assure the Agency that the method selected represents the worst
case with respect to chemical mobility and/or persistence.
10.  Rejection Factor;
The formulation and method of
application were not specified.
     EPA Guidance  on  this  Factor

           Subdivision N -  Environmental  Fate Guidelines (1982).
           p.  78-79.
           Environmental  Fate
           p.  9.
      Addendum 2 - Series 164-1  (1986)
           Environmental Fate and Effects Division Standard
           Evaluation Procedure for the Terrestrial Field
           Dissipation Study (1989).   pp. 3-4.

           FIFRA Accelerated Reregistration - Phase 3 Technical
           Guidance (1989).   p. C-323-6, 7.

      This issue does not normally result in the rejection of a
 study,  and the study is usually repairable by the submission of
 additional data.

      Rates of dissipation of the active ingredient in a pesticide
 may be affected by formulation of the product.  For example, a
 product formulated as a dust will be affected by degradation
 processes differently than a product formulated as a granule, an
 emulsifiable concentrate, an ultra low volume, or a
 microencapsulated.  Therefore, separate field dissipation studies
 may be needed if the major formulation categories are
 significantly different.  The means of application  (e.g., surface
 spray, incorporation, soil injection) can affect the dissipation
                              - 162 -
-------
                                                 Terrestrial Field Dissipation (164-1)

rate as well; in addition, the means of application must  be known
in order to determine whether a procedure  is  used that is not
recommended on that particular product.

     Industry Comment

     Industry agrees that the product  formulation and application
methodology need to be fully specified in  the study report.

     Industry believes that soil  dissipation  studies should not
be needed to differentiate among  liquid formulations (e.g., EC or
ULV); however, a change  in formulation between granules,
microencapsulated formulations  (or equivalent slow release
formulation) and/or liquid formulations may require a study at
one location to confirm  that the  half-life/mobility has not
varied significantly.

     EPA Response

     No comment.
                              - 163 -
-------
11.  Re-jaction factor;
                       Terrestrial Field Dissipation (164-1)

The plants were harvested after
application and the time of harvest was
not given.
     EPA Guidance on this Factor

          Environmental Fate  - Addendum 2  -  Series  164-1  (1986).
          p. 9.

          Environmental Fate  and Effects Division Standard
          Evaluation Procedure for the Terrestrial  Field
          Dissipation Study  (1989).  pp. 16.

     If plants on the treated plots were harvested  shortly after
application, the majority of  the test substance, intercepted by
plant surfaces, may have been removed from the  test site,
resulting in an insufficient  amount of pesticide reaching the
soil.  In situations where a  dense crop cover exists, a study
using a bare soil plot will be necessary to  determine the half-
life of the parent compound and the patterns of formation and
decline of degradates.  A study where the  pesticide is applied  to
a vegetated plot would provide supplemental  information only.

     Industry Comment

     Industry agrees that if  crops are present  on the test field,
harvest dates should be reported; however, the  EPA  comments are
contradictory.  The first point suggests that conducting a study
in the presence of plants may be OK if the plants are not
harvested shortly after application.  The  second point states
that use of a vegetated plot  is of supplemental value only.  This
discrepancy requires clarification.

     Industry agrees (May 8,  1991 letter page 60) that a bare
soil plot is more likely to give consistent half-life/degradate
behavior information.  If no  mobility is demonstrated in a bare
soil plot study, no further work is needed.   However. if
mobility is observed, the registrant may elect  to conduct an
additional study using a cropped plot.  The presence of a dense
cover of a transpiring crop will totally alter  the  plot hydrology
and thus the behavior of a relatively mobile compound, in
addition to reducing the amount of chemical reaching the soil
surface.

     Turf studies are a special case of this rejection factor.
Because chemical application  across the plot is essentially even,
NO BARE SOIL plots should be  needed.
                             - 164 -
                                                                     _
-------
                                                Terrestrial Field Dissipation (164-1)

     Industry Recommendation;  Industry recommends that a bare
soil plot be used to determine half-lives/degradation rates of a
compound normally used on a dense or variable crop canopy  (e.g.
cotton or vines).  However, a cropped plot study may be necessary
later if compound/degradate mobility becomes a significant issue.

     Industry recommends that no bare soil plots be required for
turf dissipation studies.

     EPA Response

     With reference to Industry's first comment, application to  a
cropped field, with immediate post-application removal of  the
treated crop, would be expected to severely distort the results
of the study.  Levels of pesticide in the soil might be extremely
low, even on the day of application, due to interception of the
material by plant foliage.

     With reference to dissipation from turf, the Agency has
evaluated the dissipation  of many chemicals.  Dissipation
characteristics have varied widely between turfed and bare ground
plots.  Chemicals which were found to be immobile in soil
nevertheless demonstrated  significant run off potential when
applied to turf.  Others which were  highly mobile on bare  ground
demonstrated virtually no  potential  to leach to ground water  on
turfed plots.   Therefore,  both studies are needed to gain  a clear
understanding of  the dissipation of  the pesticide under  field
conditions.

     The Agency recognizes that current guidance does not
adequately address  the  complications associated with determining
the  dissipation of  a pesticide  from a cropped  field with a dense
canopy.  However, bare  ground dissipation  studies alone  can_not
satisfactorily  describe the dissipation  of  a pesticide  applied
to,  for example,  the  foliage in an orchard.  Therefore,  in those
cases where  a dense canopy exists,  both  a  bare ground study and a
cropped study are required.  Where a significant  amount of
pesticide  is not intercepted,  either bare  ground studies or
cropped,studies may be  conducted.

      The Agency acknowledges the  need for additional  guidance for
 this guideline; this point will be considered when the
 Subdivision N guidelines are revised.
                              - 165 -
-------
                                                  Terrestrial Field Dissipation (164-1)

      Rejection factor;   Pretreatment samples were contaminated.

      EPA Guidance on this Factor

           Subdivision N - Environmental Fate Guidelines (1982)
           p. 79.                                      .   .

           Environmental Fate - Addendum 2 - Series 164-1 (1986)
           p. 9.    •

           Environmental Fate and Effects Division Standard
           Evaluation Procedure for the Terrestrial Field
           Dissipation Study (1989).  pp. 15, 18, 20.

           FIFRA Accelerated Reregistration - Phase 3  Technical
           Guidance (1989).   p.  C-323-2.

      Pretreatment samples are needed to determine the presence or
 absence of background residues in the soil.   If background
 residues are detected,  it may be due to prior pesticide
 application or a deficiency in the analytical method.  If
 background residues  were present,  it would not be possible to
 distinguish between  the dissipation of residues already present
 and_the dissipation  of  those added during the study.   In
 addition,  repeated exposures of soil microorganisms to a
 pesticide can often  enhance the dissipation rate of the pesticide
 over  what would be expected from a single application to an
 untreated soil.

      Industry Comment

 •  ^  Industry agrees  that only  in a very rare circumstance  should
 it be_necessary to perform  a field soil  study on a plot •
 containing significant  background residues  of the analyte(s).

      Industry Recommendation:   As  long as  the objectives of the
 study can be  met,  even  the  presence of relatively small amounts
 of residue should not be considered a reason for re-jectinq  a
 study.

      EPA Response

      Field dissipation  studies  in  which  the  soil in the field
plot  contains background residues  are difficult  to review;  it  may
not be possible to distinguish  between the dissipation  of
residues already  present and the dissipation of  those added
during the  study.  Also, previous  treatment  with the  same
chemical may  result in  alteration  of  the soil microbial
populations, which could distort the  rate or  nature of  the
                             - 166 -
-------
                                                 Terrestrial Field Dissipation (164-1)

dissipation.  In either case, previous history of treatment with
the subject pesticide  (or one with similar degradates) would
strongly suggest the need for a replacement study.
13.  Rejection factor;
More than one pesticide was applied to
the crop.
     EPA Guidance on this Factor

          Subdivision N - Environmental Fate Guidelines  (1982).
          p. 78.

          Environmental Fate  - Addendum 2  - Series  164-1  (1986).
          p. 9.

          Environmental Fate  and Effects Division Standard
          Evaluation Procedure for the Terrestrial  Field
          Dissipation Study  (1989).  p. 15.              ,

          FIFRA Accelerated Reregistration - Phase  3  Technical
          Guidance  (1989).  p. C-323-4.

     The presence of additional pesticide(s) may interfere with
the dissipation rate of the pesticide under study,  or may  affect
the dissipation rate of the active ingredient  in unpredictable
ways, either by increasing or decreasing the dissipation rate.

     Industry Comment

     Industry disagrees that  this is a realistic reason for
rejection.  A field soil  dissipation study should be  conducted on
a plot maintained using typical agrochemical practices in  the
region.  If a herbicide would typically be applied.during  the
season to remove weed competition or an .insecticide be used to
kill insect pests then such practices should be performed  in the
study, provided:

          The records detailing additional pesticide  application  .
          are fully comprehensive and explain  why  the compound
          was applied.

          The additional  pesticide  is not  of the same chemical
          class as  the test  chemical.

          There is  no analytical  interference.
                              - 167 -
-------
                                                 Terrestrial Field Dissipation (164-1)

           Industry  is  aware  of  few,  if  any,  instances where the
           use  of  a  second pesticide  (in the  same season)  will
           affect  the behavior of  a test chemical.

     EPA Response

     The dissipation of  the  pesticide under  field conditions is
usually sufficiently complex that the presence  of additional
chemicals  with similar physicochemical  characteristics raises the
question of interference,  either  with the  observed rate/
dissipation pattern, or  with the  subsequent  chemical  analysis.
If^the registrant applies  multiple products,  they must provide
evidence for noninterference between components.   Where several
active ingredients  are customarily applied together,  the  Agency
may require data  to support  the Tank Mix data requirement
(guideline 164-4).
14.  Re-lection factor;
The experiment was conducted at only one
site instead of the two recommended in
the Guidelines.
     EPA Guidance on this Factor

          Subdivision N  - Environmental Fate Guidelines  (1982).
          p. 78-89.

          Environmental  Fate and Effects Division Standard
          Evaluation Procedure for the Terrestrial  Field
          Dissipation Study  (1989).  p. 15-16.

          FIFRA Accelerated Reregistration  - Phase  3 Technical
          Guidance  (1989).  p. C-323-5.

     This factor does not constitute a rejection factor.  Data
from an acceptable study can partially fulfill the  terrestrial
field dissipation data requirement; acceptable data are still
required from one or more additional sites, as well as data  from
bare-ground studies.

     Industry Comment

     Industry agrees that this is not a rejection criterion.

     Industry is concerned about the EPA comment that "data  are
still required from one  or more additional  sites, as well as data
from bare ground studies".  Bare ground data is only required
where dense crop canopies would confuse the picture of
dissipation behavior.
                             - 168 -
-------
                                                 Terrestrial Field Dissipation (164-1)

     Industry agrees that data from two sites with deep coring
are required to define field dissipation behavior.

     If needed, additional information on dissipation half life
ranges may be obtained from laboratory study data, historical
soil studies and/or additional field soil studies conducted with
soil coring to only 45 cm.

     EPA Response

     For the Agency's response to the question of the need for
bare ground studies, please see Rejection Factor 11 above.
15.  Rejection Factor;
The Limit of Detection and recovery
efficiencies were not reported.
     EPA Guidance on this Factor

          Environmental Fate - Addendum 2 - Series 164-1  (1986).
          p. 10.

          Environmental Fate and Effects Division Standard
          Evaluation Procedure for the Terrestrial Field
          Dissipation Study  (1989).  p. 3, 4, 15, 24.

          FIFRA Accelerated Reregistration - Phase 3 Technical
          Guidance  (1989).  p. C-324-22.

     This issue does not normally result in the rejection of a
study, and the study is usually repairable by the submission of
additional data.

     The limits of detection  (LOD) for the parent and degradates
under field conditions may be higher than those observed in the
laboratory studies, but must be reported to allow evaluation of
the study.  If during the field study an analytical method was
used which had a relatively high LOD, observations of "no
residues" or "not detected" may be the result of poor methodology
rather than an absence of residues in the soil.

     Industry Comment

     Industry agrees with the EPA on this comment.

     EPA Response

     No comment.
                             - 169 -
-------
                                                 Terrestrial Field Dissipation (164-1)
Additional Re-lection
Factor;
	                Study reiected because deep strata contained
                    residues immediately post application.

     Industry Comment

     Studies have been rejected when immediate post-application
samples have contained residues in deep strata when pre ap-
plication samples were residue free.  Normally, these detects
occurred before the site received irrigation or rainfall.

     Registrants have been unable to convince EPA that these
detects have been artifacts caused by taking cores through
recently deposited residues.  Soil science and logic dictate that
significant pesticide movement cannot take place without
irrigation or rainfall.

     Normally, samples taken at the next sampling interval show
no contamination since the sprayed application mix has had an
opportunity to dry and are thus less prone to spurious transfer
through the soil profile during coring.

     Industry Recommendation:  Industry recommends that
immediately post application, samples be taken only to a  6" depth
(one faction) in order to avoid misleading contaminated samples.

     EPA Response

     The Agency is aware of several techniques which are  in use
which minimize contamination of deep soil strata.  We continue to
prefer that immediate post-application samples be taken to a
depth of 6 inches below the maximum depth of incorporation.  As
an example, if it were necessary to take samples from depths
deeper than 6 inches, excavation of the surface soil before
sampling the greater depths would prevent contamination.  In
addition, the use of zero-contamination soil sampling tubes
should minimize the amount of contamination.

REFERENCES

1.   Gustafson, D.I., and L.R. Holden. 1990. Nonlinear pesticide
     dissipation in soil: a new model based on spatial
     variability. Environ. Sci. Technol. 24:1032.

2.   Hill, B.D. and G.B. Schaalje. 1985. A two-compartment model
     for the dissipation of detamethrin on soil. J. Agric. Food
     Chem. 33:1001.
                              -  170 -
-------
                                                 Terrestrial Field Dissipation (164-1)

     Scow, K.M. and J.Huston.  1992.  Effect of diffusion and
     sorption on the kinetics  of  biodegradation: theoretical
     considerations. J.  Soil Sci.  Soc.  Am. 56:119.

     Timme, G., H. Frehse,  and W.  Laska.  1986. Statistical
     interpretation and  graphic representation of the
     degradational behaviour of pesticide residues. II.
     Pflanzenschutz-Nachrichten 39:187.
ADDITIONAL AGENCY COMMENTS           ;

     The Agency and  Industry are  currently discussing the issues
surrounding and arising  from the  fairly common observation that
levels at time 0 do  not  confirm the field application rates.
                              -  171  -
-------
                                            Aquatic (Sediment) Field Dissipation (164-2)


  GUIDELINE  164-2  AQUATIC (SEDIMENT)  FIELD DISSIPATION STUDIES
1.   Re-jection Factor;
Complete field test data were not
provided.
     EPA Guidance on this Factor

          Subdivision N - Environmental Fate Guidelines  (1982).
          p. 84.

          FIFRA Accelerated Reregistration  - Phase 3 Technical
          Guidance  (1989).  p. C-327-5, 7.

     This issue does not normally result  in the rejection  of  a
study, and the study is usually repairable  by  the submission  of
additional data.

     The reviewer must have this information in order  to evaluate
the conditions under which the field  study  was conducted,  a
critical element in determining the rate  of dissipation  of the
test substance.  For instance, dissipation  data are affected  by
the type of soil or sediment at the site, the  characteristics of
the water being treated,  the flow rate of the  water through the
treated site, the time of year, the topography of the  test site,
etc.  In addition, this information is needed  to determine
whether the study was conducted under suitable conditions,
representative of the intended use pattern.

     Industry Comment

     Industry agrees that a complete  description of the  test
site, weather data, application details,  etc., should  be provided
to the reviewer to assure him that the study was conducted under
a representative use pattern.

     Industry Recommendation;  Agency guidance specifically  for
aquatic dissipation studies is needed.   Industry would like  to
participate in this process.

     EPA Response

     The Agency acknowledges the need for additional  guidance for
this guideline, and would welcome  Industry's participation in the
development of additional SEPs  for the remaining guidelines  for
which no SEPs currently  exist.
                              - 172 -
-------
2.
Rejection factor;
                   Aquatic (Sediment) Field Dissipation (164-2)

The analytical methodology was
insufficient to determine the residue.
     EPA Guidance on this Factor

          Subdivision N - Environmental Fate Guidelines  (1982).
          p. 84.

          FIFRA Accelerated Reregistration - Phase 3 Technical
          Guidance  (1989).  p. C-328-17.

     A primary purpose of the aquatic field dissipation  study  is
to identify and quantify the degradates of a pesticide when the
pesticide is applied under typical use conditions.  Because the
field studies most commonly use unlabeled material, the
analytical methods used in the laboratory studies may not
appropriate for analyzing field samples.  The analytical methods
used for the analysis of sediment and water samples must be
capable of identifying and quantifying residues in field samples
in order to determine the dissipation of the pesticide.  Unless
the method of analysis used is sufficiently specific, evaluation
of the dissipation of the pesticide under field conditions may be
unclear or unreliable.

     Industry Comment

     Industry agrees that the analytical methods for sediment  and
water should be able to read metabolites found in the laboratory
degradation studies.  Industry disagrees with the need to turn
field dissipation studies into outdoor metabolism studies.
Industry also disagrees with the routine requirement to  •
quantitate individual metabolites in field studies.  Only in
cases where the laboratory studies show the formation of a
compound which  is suspected of being especially toxic or mobile
should metabolite quantitation be required in the field. The  use
of total "common moiety" methods should be the option of the
registrant.

     Dissipation rates of metabolites are often not possible  due
to the limited  number of data points on both the  incline and
decline end of  the  curve.  Some metabolites never reach
concentrations  much above the detection levels or exist  as
erratic hits due to their transient nature.

     Industry Recommendation:  The Agency should  not  require
individual metabolite quantitation in this study  on a  routine
base.  This requirement  should be based on a review of  the
results of  the  laboratory degradation studies and should be
triggered by the formation of toxic, persistent or mobile
                              -  173 -
-------
                                             Aquatic (Sediment) Field Dissipation (164-2)

 degradates..   The use of "common moiety" methods should be the
 option of the registrant.

      EPA Response

      The Agency does not agree with Industry's first comment.
 While the purpose of the laboratory studies is to provide
 guidance_on  what degradates to look for in the field,  the purpose
 of  the field studies is to provide a comprehensive environmental
 fate  profile of the chemical and its degradates under actual use
 conditions.   All residues  of concern identified in the laboratory
 studies (microbial degradation,  hydrolysis,  and photodegradation)
 and present  at levels greater than or equal to 10% of the applied
 dose  rate, should be identified in the field.

      A "common moiety"  method of analysis,  which expresses
 pesticide  residue concentration in the sample  as the sum total of
 all the various residues with that particular  moiety,  with no
 regard to  the identity of  the individual  components,  may be
 acceptable in some cases.   For those pesticides and their
 degradates that have been  shown in the laboratory to be of little
 or no^toxicological/ecotoxicological concern,  relatively
 immobile,  and not persistent,  a "common moiety" method may be
 appropriate.   However,  if  there is a concern about the  parent  or
 any of its degradates,  then the analytical  method must  be able to
 distinguish between the residues.   The Agency  wishes  to refrain
 from  basing  its  exposure assessment on the  assumption that the
 greatest exposure is  to the most toxic residue,  particularly when
 analytical methods  are  available to define,  with certainty,  the
 identity of the  residues of concern in the  field.

      Before initiating  field studies using  a "common moiety"
 analytical method,  registrants  should request  approval  from the
Agency.

      For those  chemicals that meet  the criteria described above,
 registrants may  resubmit any studies that were rejected solely  on
 the basis of  the  "common moiety" analytical  technique.   These
studies will  then be  reevaluated to determine  if  they contribute
to the understanding  of  the  dissipation of  the pesticide and its
degradates in the environment.
                               174 -
-------
                                             Aquatic (Sediment) Field Dissipation (164-2)

3_.-   Reiection  factors   The material balance was  insufficient.

     EPA Guidance on  this Factor

          Subdivision N  - Environmental  Fate Guidelines  (1982)
          p. 81.

     Although an adequate material balances  for this  guideline  is
extremely difficult to obtain, the study must define  the  rate of
degradation of  parent as well as the rate  of formation and
decline of all  major  degradates.  The specified rejection
criterion is probably related to a specific  failure on the part
of the experimenter to account for the modes and extent of
dissipation in  the submitted study.

     Industry Comment

     Industry agrees  that both water and sediment  residues must
be quantitated  at each sampling time interval to account  for  the
distribution of residues between these phases.  However,  a true
material balance in a field study is not possible  and the agency
should not reject a study on this basis.

     The Agency needs to define more clearly what  they mean by an
adequate material balance.

     Industry Recommendation;  EPA needs to  better define what is
meant by material balance in an aquatic  field study.  A SEP or
guidance document is  needed for this study.   Industry would like
to participate  in the development of a guidance document.

     EPA Response

     The Agency agrees that a true material  balance is not
possible for a,field  study; the study was probably rejected
because of a failure  on the part of the  experimenter  to account
for the modes and extent of dissipation  in the submitted  study.
The Agency acknowledges the need for additional guidance  for  this
guideline,  and would welcome Industry's  participation in  the
development of additional SEPs for the remaining guidelines for
which no SEPs currently exist.
                             - 175
-------
                                            Aquatic (Sediment) Field Dissipation (164-2)
     Rejection factors
Data were too variable to assess
dissipation.
     EPA Guidance on this Factor

          Subdivision N - Environmental Fate Guidelines  (1982)„
          p. 41.


          FIFRA Accelerated Reregistration - Phase 3 Technical
          Guidance  (1989).  p. C-328-20.

     Variability in data from an aquatic dissipation study can
arise from non-uniform application of the test substance to the
test plots, inadequate or improper sediment or water sampling, or
an unreliable analytical method.  The dissipation rate and half-
life estimates of the test substance are usually estimated using
regression analysis performed on the data in order to indicate
how well the dissipation rate is described by a first-order
kinetics model.  If the data are highly variable, the estimates
of the half-life provided by the regression analysis are
unreliable.

     Industry Comment

     Due to the way they are conducted, field studies produce
variable data.  Since the EPA guidance  (164-1) is to
preferentially use the label use pattern, some products produce
highly variable data unavoidably, i.e., banded granular
formulations, air blast sprayer applications, applications to
rice paddies.  Further, dissipation rates do not follow 1st order
kinetics over the entire range of dissipation.  Force fitting  1st
order kinetics produces low correlations coefficients.

     In an aquatic dissipation study, variability is introduced
by the flooding of the field following application or by applying
the chemical into a flooded field.  In both cases, residues
partition between soil and water in an inconsistent way depending
on the soil type and water depth in the immediate sampling area.
In addition, as the residues fall to levels near the limit of
detection, the analysis results become even more variable.

     Consequently, the agency should not reject studies solely on
the basis of a low correlation coefficient.

     Industry Recommendation:  EPA needs to define what
variability is acceptable in various use patterns.
                              -  176  -
-------
                                             Aquatic (Sediment) Field Dissipation (164-2)
     EPA Response
     The Agency recognizes that some amount of variability is
inherent in any field study and agrees that studies  should not be
rejected provided the variability is suitably explained.
Variability frequently can be estimated by the analyses  of the
application samples or the interception techniques  (cards,
plates, etc.), which permit a check of the homogeneity of
application.

     The Agency stated that the dissipation rate  and half-life
estimates are usually estimated by a first-order  model.  We agree
that the use of other models to estimate  field dissipation rates
may be more appropriate at times.  We also agree  that the  basis
for calculating half-lives should be clearly explained by  the
registrant.

     The Agency agrees that variability of data from the aquatic
dissipation study can be affected by the  timing of  the
application(s) and the partitioning between the water and  soil
phases.  The Agency acknowledges the need for additional guidance
for this guideline; this point will be considered when the
Subdivision N guidelines are revised.
                              - 177 -
-------
                                                     Forestry Dissipation (164-3)

        GUIDELINE 164-3 FORESTRY FIELD DISSIPATION STUDIES
li   Re-iaction  factor;    The data provided were either
                          insufficient or too variable to
                          accurately establish a pattern of
                          dissipation of a chemical and its
                          primary dearadate in a forest
                          environment.

     EPA Guidance on  this Factor

          Subdivision N  -  Environmental Fate Guidelines (1982)
          p. 41.

          FIFRA Accelerated  Reregistration - Phase 3  Technical
          Guidance  (1989).   p.  C-331,332-9,-10,-11,-12,-13.

     Variability in data  from a forestry dissipation  study can
arise from non-uniform application of  the test substance to the
test plots, inadequate or improper sampling of soil,  sediment,
water, or plant material  due to a weak study protocol,  or an
unreliable analytical method.   The dissipation rate and half-life
estimates of the test substance are usually estimated using
regression analysis performed on the data in order to indicate
how well the dissipation  rate is described by a first-order
kinetics model.  If the data are highly variable,  the estimates
of the half-life provided by the regression analysis  may be
unreliable.

     Industry Comment

     No comment.

     EPA Response

     No comment.
     Re-lection factor;   The sampling protocol was inadequate.

     EPA Guidance on this Factor

          Subdivision N - Environmental Fate Guidelines  (1982)
          p. 86-87.

          FIFRA Accelerated Reregistration - Phase 3 Technical
          Guidance (1989).  p. C-331,332-9,-10,-11.
                             - 178 -
-------
                                                    Forestry Dissipation (164-3)

     In forestry dissipation studies, required samples include
soil, sediment, water, or plant material from the treated forest
area, collected at the approximate recommended sampling intervals
for the type of material sampled, and for the length of time
necessary to establish the patterns of decline of parent, and the
formation and decline of degradates, in each of the materials
sampled.  Deficiencies in any of these components could cause the
study to be rejected.

     Industry Comment

     No comment.

     EPA Response

     No comment.
3.   Re-iection factor;   The application rate was not reported.

     EPA Guidance on this Factor

          Subdivision N - Environmental Fate Guidelines • (1982).
          p. 86.

          FIERA Accelerated Reregistration - Phase 3 Technical
          Guidance  (1989).. p. C-331-3.

     This issue does not normally result in the rejection of a
study, and the study is usually repairable by the submission of
additional data.  Other factors may have contributed to  the EPA's
decision to reject the study.  The forestry dissipation  study is
done to evaluate the dissipation of the pesticide under  typical
use conditions.  Dissipation rates at different rates of
application of a pesticide can vary unpredictably because the
soil microorganisms and plants responsible for the degradation
process may respond differently at different concentrations of
the pesticide.  In addition, the actual application rate of the
pesticide must be known to confirm that the maximum label rate of
the pesticide was used. -   .

     Industry Comment

     No comment.

     EPA Response

     No comment.
                              - 179  -
-------
4.   Rejection Factor;
                           Forestry Dissipation (164-3)

No storage stability data were provided
to confirm that samples did not degrade
prior to analysis.
     EPA Guidance on this Factor

          FIFRA Accelerated Reregistration  - Phase 3 Technical
          Guidance  (1989).  p. C-332-17.

     This issue does not normally result in the rejection of a
study, and the study is usually repairable  by the submission of
additional data.  Freezer storage stability of samples is not
usually a problem in the laboratory studies because the samples
can be frozen immediately after collection  and are not stored for
long periods of time.  However, in forestry studies, soil,
sediment, water, and plant tissue samples usually cannot be
refrigerated or frozen immediately after collection.  In
addition, over the many weeks  (or months) of the study, samples
can accumulate in a freezer prior to analysis.  Therefore, a
contemporaneous "spiking" study must be conducted, in which a
known amount of active ingredient is added  to portions of soil,
sediment, water, or plant material from an  untreated area near
the test site at the same time that samples from the treated
areas are collected.  The "spiked" samples  are then stored under
the same conditions as samples from the test plot, and all
samples are analyzed at the same time.  This should indicate
whether the pesticide in the samples from the test plots is
degrading during handling and storage, and  if so, whether it is
possible to normalize the results to account for the amount of
change during storage.  If the data cannot  be corrected in this
way, it is not possible to distinguish between the amount of the
dissipation occurring during storage and the dissipation
occurring under field conditions, and the study must be repeated.

     Industry Comment

     No comment.

     EPA Response

     No comment.
     Rejection Factor;   Field test data were incomplete.

     EPA Guidance on this Factor
          Subdivision N - Environmental Fate Guidelines  (1982)
          p. 87-88.
                             - 180 -
-------
                                                     Forestry Dissipation (164-3)

          FIFRA Accelerated Reregistration  -  Phase  3 Technical
          Guidance  (1989).  p. C-332-14.

     This information is needed to determine  if  the study was
conducted under conditions representative of  the intended use
patterno  This issue does not normally  result in the rejection  of
a study, and the study is usually repairable  by  the submission  of
additional data.  EPA requires this  information  to  evaluate the
conditions under which the field study  was  conducted to determine
the dissipation rate of the test substance.   For instance,
dissipation data have different effects depending on the time of
year it is applied, the amount of rainfall, the  slope of the test
site, etc.

     Industry Comment

     No comment.

     EPA Response

     No comment.
                              -  181 -
-------
 GUIDELINE  164-4  COMBINATION TANK MIXES  FIELD DISSIPATION STUDIES

     There were no studies screened for this guideline.'  However,
guidance on this topic appears in Subdivision N - Environmental
Fate Guidelines  (pages 89-91)„  There is no SEP for this
guideline.    This guideline is essentially the same as specified
in the SEP for 164-1  (Terrestrial Field Dissipation), with the
only difference being that, in addition to separate field studies
for each active ingredient in a product,  two or more active
ingredients are also tested for their own interactions under
field conditions.
                             -  182  -
-------
 GUIDELINE 164-5 LONG-TERM TERRESTRIAL FIELD DISSIPATION STUDIES

     There were no studies screened for this guideline.  However,
guidance on this topic appears in Subdivision N - Environmental
Fate Guidelines (pages 91-94) and in the Acceptance Criteria and
the Guidance for Summarizing Studies [see pages C-335-338 of the
Phase 3 Guidance].  This guideline is essentially the same as
specified in the SEP for 164-1 (Terrestrial Field Dissipation),
with the only difference being the increased duration of the
study.                                        .
                             - 183 -
-------
                                          Confined Accumulation in Rotational Crops (165-1)

    GUIDELINE 165-1 CONFINED ACCUMULATION IN ROTATIONAL CROPS
                              STUDIES

NOTE:     The  Confined Accumulation in Rotational Crops and Field
          Accumulation in Rotational Crops  data requirements have
          been transferred to the Chemistry Branches (Health
          Effects  Division).   RSCB has accepted responsibility
          for  reviewing these studies and for setting rotational
          crop intervals or tolerances,  as  necessary.
     Re-jaction  factor;
The residues in soil were not
characterized.
     EPA Guidance on  this  Factor

          Subdivision N -  Environmental  Fate Guidelines (1982).
          p. 96.

          Environmental Fate  - Addendum  7  -  Series 165-1 (1988).
          p. 13.

          FIFRA Accelerated Reregistration - Phase 3  Technical
          Guidance  (1989).  p. C-339-14.

          Guidance  on How  to  Conduct  Studies on Rotational  Crops
          (2/23/93).  See  Appendix  C:  "Pesticide Reregistration
          Rejection Rate Analysis Residue  Chemistry/Environmental
          Fate Follow Up Guidance for Conducting Rotational Crop
          Studies".

     The purpose of the confined accumulation study is  to
determine the nature  and amount  of  residue uptake in  rotational
crops.  This process  is assessed by analyzing the level and,  if
necessary, the nature of the  residues  in rotational crops in the
confined accumulation study.

     Industry Comment

     Industry agrees  that, as indicated in the above  EPA
Guidance, the purpose of the  confined  rotational crop study as
"to determine the nature and  amount of residue uptake in
rotational crops."  As  indicated in the Pesticide Assessment
Guidelines "such data are  used to establish  realistic crop
rotation restrictions ...  or  to  provide information for
determining if tolerances  are needed  in rotational crops."
Industry further agrees  that  quantification  of total  radioactive
residues in soil during the study will aid in interpretation of
the results of the  study.  However, the character of  the residues
                             - 184 -
-------
                                         Confined Accumulation in Rotational Crops (165-1)

in the soil has already been determined in the aerobic  soil
metabolism, and as a result, characterization of  residues  in the
confined rotational crop study is not necessary.

     Industry Recommendation;  Industry agrees that
quantification of total radioactive soil residues during the
study will aid in interpretation of the results.   However, the
requirement for characterization of the soil  residues should be
eliminated provided that a suitable aerobic soil  metabolism  study
has been conducted.

     EPA Response

     Since the chief consideration for requiring  confined
rotational crop studies is dietary in nature, the Agency agrees
with Industry that soil analysis is not required  and need  only  be
performed at the Registrant's discretion.  Interested parties are
directed to the guidance paper on conducting  rotational crop
studies referenced above.
2.
Re-iection factor;
The length of freezer storage of the
crops was not reported and no freezer
storage stability data were provided.
     EPA Guidance on this  Factor

           Environmental  Fate -  Addendum 7 -  Series 165-1 (1988)„
           p.  12.

           FIFRA Accelerated Reregistration - Phase 3 Technical
           Guidance (1989).  p.  C-341-6.

           Additional Guidance for Conducting Plant and
           Livestock Metabolism Studies (7/16/92).

           Guidance on Generating Storage Stability Data in
           Support of Pesticide Residue Chemistry Studies
           (1/14/93) .

           Guidance on Submission of Raw Data (1/14/93).

      This issue is important in accepting a confined study. The
 information needed to upgrade the experiment may be available.

      Industry Comment

      Industry agrees that storage stability data needs to be
 provided  (if the samples are stored for an extended period of
                              - 185 -
-------
                                          Confined Accumulation in Rotational Crops (165-1)

 time)  for the parent and metabolites in tissue samples.  Sine the
 nature^of the residue is unknown at the start of the study,
 flexibility is required on how this data is obtained.

      Industry Recommendation:   Industry recommends that EPA
 accept a 4-  to 6-month grace period for sample storage during
 which no storage stability information would be required,
 provided that samples have been stored properly.  If samples are
 stored more  than 6  months,  the registrant should:

      a)   Reference  storage stability data already obtained from
 relevant sample types and storage conditions in other  studies;  or

      b)   Analyze a  representative substrate as  soon as
 practicable  (i.e.,  within 4 to 6 months of collecting  the
 samples),  and then  repeat the  analysis at the end of the study.
 The chromatographic profiles may be compared to insure  that  no
 gross  changes have  occurred during storage.

      This is  consistent  with the policy on plant metabolism
 studies  currently in force  in  the Chemistry Branches of the
 Health Effects  Division  (P.  Paul conversation with R. Loranqer,
 6/23/92).                                                  a

     EPA Response

     Chemicals  may  degrade  during storage,  even under ideal
 storage  conditions.  Therefore,  storage stability data are
 essential  in  order  to be confident that any degradation measured
 in the  test system  was due  solely to the environment of that test
 system,  and not due to handling and storage.  Storage stability
 is chemical specific and a  chemical's stability under storage can
vary depending  upon the  matrix in which it  is stored (e.g.,  soil,
water, organic  extract,  plant  tissue,  fish  tissue,  etc.).  In
light  of  the  difficulty  of  spiking samples before  the identity of
the residue is  known and the length of time  needed for  metabolism
studies,  the  present Agency position is that  storage stability
data should not normally be required for samples analyzed  within
4-6 months of collection, provided evidence  is  given that
attempts were made  to limit  degradation of  residues  by  appropri-
ate storage of  matrices  and extracts  during  the analytical
portion of the  study.  In other words,  as stated in  the SEP  on
animal metabolism,  "The  reviewer should be convinced that  storage
conditions have  not  invalidated the  Registrant's results..."

     Interested parties  are  directed  to three guidance  papers
cited above regarding storage  stability, metabolism  and raw  data
for information on  how the Agency will  handle this question  in
confined rotational  crop  studies.
                             - 186 -
-------
3.
Reiaction factor;
                                         Confined Accumulation in Rotational Crops (165-1)
The study application rate does not
reflect normal or maximum use rates and
the application rate was not confirmed.
     EPA Guidance on this Factor

          Subdivision N - Environmental Fate Guidelines  (1982).
          p. 95.

          Environmental Fate - Addendum 7  - Series  165-1  (1988).
          p. 10.

          FIFRA Accelerated Reregistration - Phase  3 Technical
          Guidance  (1989).  p. C-339-1.

          Guidance on How to Conduct Studies on Rotational  Crops
           (2/23/93).

     Confined accumulation studies determine the  amount.of
biomagnification of an active  ingredient by crops grown  in
treated soil.  The amount of biomagnification  observed at
different pesticide application rates  can  vary unpredictably
because the plants grown  in the treated soil may  respond
differently to different  concentrations of the pesticide.
Therefore, it is not possible  to extrapolate the  amount  of  uptake
conducted at rates other  than  when the maximum label rate is
applied.

     Industry Comment

     Industry agrees that the  application  rate of the  pesticide
does need to be confirmed and  should approximate  the maximum use
rate.  If/since the identity and purity of the applied test
material has been established  prior to application, it is^
necessary only  to determine total radioactivity  in  the soil
immediately  after application.

     Industry Recommendation;   Industry recommends  that  EPA place
strong weight in the proper reporting  of application methods,
preparation  of  doses,  etc., in order  to confirm  the application
rate and not reject studies based on  the time  zero  soil  analysis.


     EPA Response

     The Agency believes that  the maximum  application rate must
be used when confined  rotational  crop studies  are performed.
However, time  zero  soil  analysis  is  not required to confirm the
                              - 187 -
-------
                                          Confined Accumulation in Rotational Crops (165-1)

 application rate. The industry recommendation concerning
 reporting of application methods and dose preparation is
 reasonable.  Again,  interested parties are directed to the
 guidance paper on conducting rotational crop studies referenced
 above.
      Re-iection factor;    Material balances were not provided.

      EPA Guidance on this Factor

           Environmental Fate -  Addendum 7 - Series 165-1 (1988)
           pp.  5,  13.

           FIFRA Accelerated Reregistration - Phase 3 Technical
           Guidance (1989).   p.  C-339-13.

           Guidance on How to Conduct Studies on Rotational Crops
           (2/23/93).

      The Acceptance  Criteria of the Phase 3 Technical Guidance
states^that  this  criterion is considered  supplemental for this
guideline and  may not be required for every study.

      Industry  Comment

      Industry  agrees  that attempts should be made to identify as
much^of  the  radioactive residues in the plant tissues as
possible._ However,  the confined rotational crop study is an open
study subject  to  loss of volatile compound and **CO2  (generated by
degradation),  as  well as movement of the  materials  in the soil.
Therefore, obtaining  a  "material balance" or "recovery of applied
material"  is not  a reasonable objective.

      Industry  Recommendation:   Eliminate  the need for complete
"recovery, of applied  material"  in the confined rotational crop
study.  Require only  analysis of plant residues.

     EPA Response

     The Agency concurs  with elimination  of the need for complete
"recovery  of applied  material"  for all times in the  confined
rotational crop study.  In fact,  since soil  analysis  is no longer
required,  this factor becomes moot.
                             - 188 -
-------
                                          Confined Accumulation in Rotational Crops (165-1)

S-z.   Reiection factor a    The test substance was less than
                          analytical grade.

      EPA Guidance on this Factor

           Subdivision N - Environmental Fate Guidelines (1982)
           p.  95.

           FIFRA Accelerated Reregistration - Phase 3 Technical
           Guidance (1989).   p.  C-339-2.

           Additional Guidance for Conducting Plant and
           Livestock  Metabolism Studies (7/16/92).

           Guidance on How to Conduct Studies on Rotational Crot>s
           (2/23/93).                                           *

      The  purpose  of  the confined accumulation in rotational  crops
study is  to determine the nature and amount of  pesticide residue
uptake in rotational crops.   If the test  substance is  less than
analytical grade  (usually <95%  active ingredient),  the
contaminants  in the  test substance as well as residues  arising
from  the  parent may  accumulate  in the test crops and confuse the
evaluation of  the study.

      Industry  Comment

      Industry  agrees  that the radiolabeled material used in  the
study needs to have  a purity of at least  95%.   See also Industry
comments  and recommendation  under Guideline 162-3,  Rejection
Factor 6.

      EPA  Response

    _For  laboratory  studies  conducted with radiolabeled
chemicals, the use of a test  substance with low radiopurity  may
unnecessarily  complicate  the  identification of  degradation
products  since the fate of the  parent and its degradates is
followed by monitoring  the radioactivity.

      Industry  should  strive  for a radiopurity of  s97%.   A lower
radiopurity may be acceptable with adequate justification.   The
Agency understands that achieving a high  level  of  radiopurity may
depend on the  chemical  characteristics of the specific  compound
and on the type of radioisotope used.  The Agency further
acknowledges that some  chemicals  may require extensive
preparation in order  to achieve this high level of  radiopurity,
and has previously concurred  with time extensions  for submission
of data to allow  for  such preparation.  The Agency has also
                             - 189 -
-------
                                          Confined Accumulation in Rotational Crops (165-1)
previously accepted the use of lower purity  radiochemicals  with
adequate justification as to why higher  radiochemical  purity
could not be achieved.
     Re-Section factor:
The supporting raw data were not
provided.
     EPA Guidance on  this  Factor

          Environmental  Fate  - Addendum 7 -  Series 165-1 (1988).
          p. 9, 14.

          FIFRA Accelerated Reregistration - Phase 3 Technical
          Guidance  (1989).  p. C-323-7.

          Guidance  on Submission  of Raw Data (1/14/93).

     This factor alone is  not sufficient to reject a study,  as
the registrant has  the option to  provide reprints of methods,
other studies, raw  data,  relevant letters/memos and material
which will help support the registrant's conclusions.  However,
if the raw data were  necessary to confirm some conclusion or
calculation proposed  by the registrant,  this information must be
provided.


     Industry Comment

     Industry agrees  that "data  ... necessary to confirm some
conclusion or calculation proposed by the registrant ... must be
provided.  However, representative data should be sufficient
instead  of all of  the raw data.   In addition, Industry requests
that the EPA define "raw data".

     Industry Recommendation:  Industry agrees that
representative data must be provided to support conclusions and
calculations.  However, Industry requests that EPA define "raw
data".

     EPA Response

     The Agency has provided additional information about raw
data in  the  1/14/93 document  cited above.
                              - 190 -
-------
                                         Confined Accumulation in Rotational Crops (165-1)
Additional Rejection
Factor No. 1;       Characterization/identification of residt

     Industry Comment

     It is noteworthy that a primary objective of the study,
i.e., to determine the nature of the residues in rotational  crops
was not cited as a key reason for rejection of this study  type.
This issue is of concern to registrants.  Since Residue  Chemistry
Branch have committed to producing a guidance document on
characterization/identification of residues in plant metabolism
studies, Industry requests that the requirements for the confined
rotational crop studies be harmonized with this document,
wherever possible.  Requirements for rotational crops should not
exceed those for plant metabolism and indeed cross-referencing to
the plant metabolism should eliminate the need for detailed
structural confirmation in many cases.

     Industry Recommendation;  Harmonize guidelines for
characterization/identification of rotational crop residues  with
those for plant metabolism.

     EPA Response

      As noted in the 2/23/93 document  on rotational crops,  the
Agency will be applying the same criteria to plant metabolism and
confined rotational crop studies. The Registrant is referred to
the document entitled  "Additional Guidance  for Conducting  Plant
and Livestock Metabolism Studies"  (7/16/92).
Additional  Reiection
Factor No.  2;
Tiered Approach to Confined Accumulation
in Rotational Crops.
      Industry Comment

      The confined rotational crop study is an extremely difficult
 and time consuming study to perform.  It is the equivalent of
 performing several plant metabolism studies with additional
 complicating factors such as:  extremely low residue levels;
 uptake of more than one moiety from the soil; exposure to
 residues over the whole plant growth cycle.  These factors yield
 complex metabolic profiles.  To add to this complexity_the
 present guideline also requires duplication of work being
 performed in the areas of soil metabolism, terrestrial field soil
 dissipation, etc.  In its May 8, 1991 comments on the
                              - 191
-------
                                          Confined Accumulation in Rotational Crops (165-1)

reevaluation/update of PAG, Subdivision N,  Industry proposed a
tiered approach to rotational  crop  issues which would concentrate
on the primary aims of the study, i.e., defining the nature  and
amount of residues in rotational  crop.

     Industry Recommendation:   Industry requests that EPA
urgently review their proposal  and  adopt  a  tiered approach to
rotational crop issues.

     EPA Response

     The Confined Accumulation  in Rotational  Crops data
requirement has been extensively  "refined"  over the past  few
years. _The Agency has reviewed Industry's  comments in its 5/8/91
submission and acknowledges the need to consider revision of the
Confined Accumulation in Rotational Crops data  requirement.   The
Agency believes that the approach discussed in  the document
entitled "Guidance on How to Conduct Studies  on Rotational Crops"
(2/23/93) reflects a tiered approach.
Additional Reiection
Factor No. 3:

     Industry Comment
Time Line of Two Years Too Short.
     A time line of two years for this study  is unreasonably
short.  The study generally requires a new preparation  of
radiochemical because of the large amounts required, has an in-
life phase of at least eighteen months  (often with a seasonally
dependent start date) followed by the identification of complex
metabolic pathways.

     Industry Recommendation:  Amend the time line for  this study
type to four years.  Alternatively, under the proposed  tiered
approach allocate 2.5 years for Tier 1.

     EPA Response

     The Agency is amenable to reevaluating the time lines to be
certain that adequate time is given to the registrant to conduct
the study. However, due to the time restraints of reregistration,
a time line in excess of 2.5 years would not  be acceptable for
the confined study.
                             - 192 -
-------
                                           Field Accumulation in Rotational Crops (165-2)


  GUIDELINE 165-2  FIELD ACCUMULATION IN ROTATIONAL CROPS STUDIES
1.   Rejection factor;
The source of pesticide residues in
control samples of both crops and soils
were not verified.
     EPA Guidance on this Factor

          FIFRA Accelerated Reregistration  -  Phase  3  Technical
          Guidance  (1989).  p. C-342-10.

          Guidance on How to Conduct Studies  on  Rotational  Crops
          (2/23/93) .

     As some control  (untreated) crops and  soils contain
pesticide residues, it should be verified that the  same  (or
similar) pesticide(s) were not previously applied to  the test
area.  If background residues are detected, it may  be due to
prior pesticide application or a deficiency in the  analytical
method.  If background residues of  the test pesticide were
present, it would not be possible to distinguish between the
bioaccumulation of residues already present and  the
bioaccumulation of those added during the study.

     Industry Comment

     Industry agrees that pesticide residues  in  the control
samples may create confusion in interpreting  the results.  Some
explanation should be given, when possible.   Analysis of the
control soil before application will indicate whether there are
any residues present in the soil at the  time  of  application.

     Industry Recommendation:  Provided  it  does  not compromise
the results of the study, contamination  of  the control samples
should not be considered a reason for rejection  of  a  study.
                                193  -
-------
                                           Field Accumulation in Rotational Crops (165-2)
     EPA Response
     The methods employed to analyze the rotational crops should
be specific for all pesticide residues of concern in the subject
commodities. If the analytical procedure determines interfering
compounds it would be considered to be deficient and this would
be a cause for rejection of the studies. It would also be
desirable to employ sites on which the test pesticide had not
been previously applied. If residues are found  in control crop
samples, the Agency will not automatically reject the field
studies. The total study will be examined and consideration  given
to factors such as the relative levels of residues in treated and
control samples. Again, analysis of the soil is not required.
     Rejection factor;
There was a large degree of variability
in the data with no explanation
provided.
     EPA Guidance on this Factor

          Subdivision N  - Environmental Fate Guidelines  (1982).
          p. 100.

          FIFRA Accelerated Reregistration  - Phase  3 Technical
          Guidance  (1989).  p. C-343-19.

          Guidance.on How to Conduct Studies on Rotational  Crops
           (2/23/93).

          Subdivision 0  - Residue Chemistry Guidelines  (1982).

     Variability in data from a field accumulation  study can
arise from non-uniform application of the test substance to the
test plots, inadequate or improper plant sampling,  or an
unreliable analytical method.  If the data  are highly variable,
the extent of uptake of  residues of concern under field
conditions cannot be clearly demonstrated.

     Industry Comment

     Industry agrees that some explanation  should be given  when
there is a large degree  of variability.

     Industry Recommendation:  Since this study type is  likely to
produce considerable variation in results this should not result
in rejection providing adequate explanation is given.
                              -  194  -
-------
                                           Field Accumulation in Rotational Crops (165-2)
     EPA Response
     The Agency agrees that this study can produce  considerable
variation in results  (e.g., field factors such as seasonal
variations in temperature and soil saturation level may affect
dissipation/accumulation kinetics), and should not  be  rejected
provided the variability is suitably explained.

      The Chemistry Branches of HED have taken over
responsibility for the review of these studies and, under the
tiered approach discussed in the 2/23/93 document cited above,
variability is not an important problem. If detectable residues
of concern are observed at the maximum practical plant back
interval (12 months) or a shorter desired plant back interval,
then tolerances for rotational crops are required and  a complete
battery of field trials are required as discussed in Subdivision
O also cited above. The larger number of trials needed for
establishment of tolerances would cover any variation  of the
levels of residues in rotational crops.
3.   Rejection factor;   Residues in soil were not analyzed.

     EPA Guidance on this Factor

          Subdivision N - Environmental Fate Guidelines  (1982).
          p. 100.

          Environmental Fate - Addendum 1 - Series 165-2  (1986).
          p. 4.

          FIFRA Accelerated Reregistration - Phase 3 Technical
          Guidance  (1989).  p. C-343-16.

          Guidance on How to Conduct Studies on Rotational Crops
          (2/23/93).


      The Chemistry Branches of HED have taken over
responsibility for the review of these studies and, as discussed
in the 2/23/93 document cited above, soil analysis is no  longer
required. Therefore this will no longer be a rejection factor.

     Industry Comment

     Industry agrees that soil residues analysis is necessary in
this study.
                             - 195 -
-------
                                           Field Accumulation in Rotational Crops (165-2)

     Industry Recommendation:  Residues in soil should be
analyzed at times of treatment, at time of planting of the
rotational crops to define root zone concentration, and at the
time of rotational crop harvest for the crop  with  the longest
maturation period.  Soil samples from at least the 0- to 15-cm
and 15- to 30-cm depths should be analyzed to determine root-zone
concentrations.  However, if the study is carried  out at the  same
time as the terrestrial field soil dissipation study  (164-1),
then soil analysis from those samples will suffice.

     EPA Response

      See discussion above.
4,   Re-jaction Factor:
                    Planting to harvest intervals were not
                    provided.
EPA Guidance on this Factor
          Subdivision N  -  Environmental  Fate Guidelines (1982).
          p. 100.

          Environmental  Fate  -  Addendum  1 -  Series 165-2 (1986).
          p. 1.

          FIFRA Accelerated Reregistration - Phase 3 Technical
          Guidance  (1989).  p.  C-345-2.

          Guidance  on How to  Conduct Studies on Rotational Crops
           (2/23/93).

          Subdivision 0  -  Residue Chemistry Guidelines  (1982)„

      This issue does not normally result in the rejection of a
 study,  and  the study is  usually upgradable by the submission of
 additional  information.   The  extent of uptake of pesticide
 residues must  be  determined at the growth stages appropriate for
 the various rotational  crops, since rotational crops can be
 harvested either  at maturity  (food crops) or when immature
 (forage for domestic animals; some vegetable crops).  The
 planting to harvest intervals provide the age of crop  (and an
 estimate of its growth  stage) at time of sampling.  In addition,
 this  information  is needed to determine  whether the crops were
 harvested under suitable conditions representative of the
 intended use pattern.
                              - 196 -
-------
                                           Field Accumulation in Rotational Crops (165-2)
     Industry Comment
     Industry agrees that information on the planting to harvest
intervals should be provided.

     EPA Response

     See discussion above.


5_..   Re-iection Factor;   The field test data were  incomplete.

     EPA Guidance on this Factor

          Subdivision N - Environmental Fate Guidelines  (1982).
          p. 99-100.
          Environmental Fate - Addendum 1  - Series 165-2  (1986).
          pp. 2-3.

          FIFRA Accelerated Reregistration - Phase 3  Technical
          Guidance  (1989).  p. C-342-11.

          Guidance  on Submission  of  Raw Data  (1/14/93).

     This issue does not normally result  in the rejection of a
study, and  the study is usually upgradable by  the  submission of
additional  information.  The Agency  must  have  this information to
accurately  evaluate the conditions under  which the field study
was  conducted, which is a  critical element in  determining the
extent of accumulation of  the  test substance.   Field test data
include: the  identity of  the crop planted on  the treated soil; a
description of how  and when  the  crop was  planted;  how and when
the  subject pesticide was  applied; the weather (temperature,
rainfall, wind speed and  direction)  and  condition of the field at
time of  application; the  formulation of  the pesticide applied;
the  application  rate and  the application technique; and
irrigation  (when applied  and how much).  This  information is also
required to determine whether  the study  was conducted under
suitable, representative,  and  appropriate conditions,
representative of the  intended use pattern. Also,  see the 1/14/93
document on raw  data  cited above.

      Industry Comment

      Industry agrees  that field test data should be provided.

      EPA Response

      See comments above.
                              - 197 -
-------
                                            Field Accumulation in Rotational Crops (165-2)
JL-.   Re-lection Factor;    The test substance was not
                          characterized.
     EPA Guidance on  this Factor

          Subdivision N - Environmental  Fate Guidelines (1982).
          p. 98.

          Environmental Fate -  Addendum  1 - Series 165-2 (1986).
          p. 2.

          FIFRA Accelerated  Reregistration - Phase 3 Technical
          Guidance  (1989).   p.  C-342-2.

          Guidance  on How to Conduct Studies on Rotational Crops
          (2/23/93).

          Subdivision 0 - Residue Chemistry Guidelines (1982).

     This issue does  not normally result in the rejection of a
study, and the study  is usually upgradeable by the submission of
additional information.  In the  field accumulation study,  the test
substance can be applied as  a typical end-use product; if so,  the
composition of the  product to be used must be given to determine
if it reflects the  actual formulations to be registered and
applied in the real world (Also,  see Subdivision 0 - Residue
Chemistry Guidelines).

     Industry Comment

     Industry agrees  that the test material should be
characterized.

     EPA Response

     See comments above.
                              - 198  -
-------
     GUIDELINE 165-3 ACCUMULATION IN IRRIGATED CROPS STUDIES

     There were no studies screened for this guideline.  However,
guidance on this topic appears in Subdivision N - Environmental
Fate Guidelines (pages 101-103)  and in the Acceptance Criteria
and the Guidance for Summarizing Studies [see pages C-346-349 of
the Phase 3 Guidance].

     Industry Comment

     Many of the comments made on the field rotational crop
studies apply to this type of study.  Notably, these studies are
very complex to run in the field and large variability is to be
expected.
                              -  199  -
-------
                                                    Accumulation in Fish (165-4)
               GUIDELINE 165-4 ACCUMULATION IN FISH
1.   Rejection Factor;
The analytical methodology was
insufficient to detect the residue.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines.
          page 105.
                                 (1982),
          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.   (December 1989), page C-350

     The identification of those extractable residues present at
levels greater than or equal to 0.05 ppm is a critical element of
the fish accumulation study.  One of the primary reasons this
study is conducted is to identify the residues that accumulate in
fish after exposure to a constant level of a pesticide.
Therefore, the analytical method used to analyze for residues in
the fish tissue and surrounding water must be sensitive enough to
the detect and distinguish between those residues.

     Industry Comment

     No argument if comments in factor #2 below are considered.

     EPA Response

     See comments in factor #2.
2.   Rejection Factor;
Some deorradates present in small
concentrations in edible and non-edible
fish tissues were not identified and/or
quantified.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines.
          page 105.
                                 (1982),
          FIFRA Accelerated Reregistration Phase 3 Technical
          Guidance.   (December 1989), page C-350.

     The identification of those extractable residues present at
levels greater than or equal to 0.05 ppm is a critical element of
the fish accumulation study.  A primary reasons this study is
                             - 200 -
-------
                                                   Accumulation in Fish (165-4)

conducted is to identify the residues that are accumulated in
fish after constant exposure to a pesticide.


     Industry Comment

     Industry agrees that identification of residues in the_fish
is an important part of the study.  According to the Pesticide
Assessment Guidelines, Subdivision N, the purpose of the  fish
accumulation study is  "to determine if pesticide residues  _
accumulate in fish used as human  food sources and to determine
the extent of pesticide residues  in edible portions of such
fish "  Identification of individual analytes that account  for
10% of the residues or 0.05 ppm  (whichever  is greater) _in the
various fish fractions is sufficient for characterization of
residues.

     Industry Recommendation:  Require  identification  of
individual analytes in the  fish  that account  for a minimum  of  10-s
the total residues or  0.05  ppm (whichever  is  greater), along with
the determination of BCFs for  the fish.

     EPA Response

     The Agency has agreed  to  further  discussion with industry on
this topic  and will  finalize  its position at  that  time.
 3_._   Rejection Factor;
The study on the effects of storage on
the analytical results of samples was
not completed.
      EPA Guidance on this Factor

           Addendum 8 on Data Reporting to Pesticide_Assessment
           Guidelines:  Laboratory Studies of Pesticide
           Accumulation in Fish.   (March 1988), page 9.

           FIFRA Accelerated Reregistration Phase 3 Technical
           Guidance.   (December 1989), page C-352.

      Even under ideal conditions, chemicals may degrade during
 storage. Therefore,  if samples are taken and stored before
 analysis, a storage  stability study  is required in  order  to
 assess the effects,  if any, of storage on those samples.  Inmany
 cases, studies rejected due to storage stability_data problems
 may be upgraded by the registrant by the submission of additional
 data/information.
                               -  201 -
-------
                                                     Accumulation in Fish (165-4)
      Industry Comment
      Industry agrees that storage stability data need  (if the
      e?.Jre'.in *act' stored) to be provided for the parent and
 metabolites in tissues samples.  This data may be obtained from
 sources other than the present test samples as long as the data
 are relevant d-e.f similar type samples and similar storage
 conditions and lengths.                                   y

      Industry Recommendation:  Industry recommends that EPA
 accept a 4- to 6 -month grace period for sample storage during
 which no storage stability information would be required
 provided that samples have been stored properly.   If samples are
 stored more than 6 months, the registrant should:

      a)   Reference storage stability data already obtained from
 relevant sample types and storage conditions in other studies;  or

      b)   Analyze a representative substrate as soon as
 practicable (i.e.,  within 4 to 6 months of collecting the
 samples) ,  and then repeat the analysis at the end of the study
 The chromatographic profiles may be compared to insure that  no
 gross changes have occurred during storage.

      This  is  consistent with the policy on plant metabolism
 studies  currently in force in the Chemistry Branches of the
       ?       Division (P.  Paul conversation with R.  Loranger,
     EPA Response

     Chemicals may degrade during storage, even under  ideal
storage conditions. Therefore, storage stability data  are
essential in order to be confident that any degradation measured
in the test system was due solely to the environment of that test
system, _ and not due to handling and storage.  Storage  stability
is chemical specific and a chemical's stability under  storage can
vary depending upon the matrix stored  (e.g., soil, water, organic
extract,  plant tissue, fish tissue, etc.).  Therefore, the Agency
is concerned that a blanket 4- to 6 -month grace period for sample
storage,  during which no storage stability information would be
required,  may not be appropriate for environmental fate testing
The Agency does however agree that unless a pesticide/residue of
concern is otherwise known to be volatile or labile, storage
stability data will not be needed for samples stored frozen for
    days .
     For frozen storage intervals >30 days, it is recommended
that evidence be provided confirming that the identity of
                             - 202 -
-------
                                                   Accumulation in Fish (165-4)

residues did not change during the period between collection and
final analysis.  The Agency has agreed to let industry develop a
draft storage stability guidance document to address this and^
other storage stability issues.  Final Agency judgement on this
issue will be reserved for the Storage Stability follow-up
guidance.

     Ideally, storage stability data should be obtained
concurrently with the particular environmental.fate guideline
study, not independent from it.  However, concurrent storage
stability studies will not be required in many cases.  Provided
that the pesticide residues are found to be stable in the
matrices of interest, a storage stability study run in_a separate
freezer at a different time period will be acceptable if the
storage conditions  (particularly temperature) are the same as
those in the corresponding environmental fate guideline study.
However, for pesticides whose residues are known or suspected  to
be unstable or volatile, concurrent studies may be needed.  In
fact, for such pesticides, it is advisable to run a storage_
stability study  in advance to determine proper storage conditions
and maximum storage  times before treated samples are placed into
storage.
 4_._   Rejection  Factor:
Data on the concentration of the parent
and its dearadates in the exposure water
were not submitted.
      EPA Guidance on this Factor

           Subdivision N:  Environmental Fate Guidelines.  (1982),
         •  pages 105, 106.

           Addendum 8 on Data Reporting to Pesticide Assessment
           Guidelines:  Laboratory Studies of Pesticide
           Accumulation in Fish.   (March 1988), page 9.

           FIFRA Accelerated Reregistration Phase 3 Technical
           Guidance.  (December 1989), pages C-350, C-352.

      The concentration of the test substance must be high .enough
 to facilitate chemical identification of residues in fish.
 However, it must not exceed 1/10 the 96 hr LC50 of the test
 species in order to avoid any toxic effects which- could stress
 the fish and affect their bioaccumulation of the pesticide.  The
 exposure water must also be free of degradates which could stress
 the fish.  Finally, in order to calculate a bioconcentration
 factor  (BCF), which gives an indication of the potential for the
 pesticide to be accumulated in fish tissues, the  concentration of
                              - 203 -
-------
                                                    Accumulation in Fish (165-4)

 the pesticide in the test water must be known and must remain
 constant.

      Industry Comment

      Industry agrees that data on the total concentration of
 pesticide  and key degradates in the test exposure water should be
 provided.   In the case or rapidly metabolized compounds it is not
 possible to maintain a constant nominal concentration of the

 parent pesticide.   This is not a problem,  since similar
 degradation will occur in natural water.

      Industry Recommendation:   EPA should flexibly interpret the
 need to maintain a constant concentration in low-solubility,
 Ixpophilic,  readily degradable compounds.

      EPA Response

      The Agency  agrees that some degree of flexibility in the
 experimental design is warranted,  however significant deviations
 from^the guidance of Subdivision N must be adequately justified.
 Studies should be designed and conducted to meet the  objectives
 of  165-4.  A relatively stable steady state concentration of the
 parent can be achieved using a flow-through system.   For rapidly
 metabolized  compounds,  the number of  turnovers  may need to be
 increased.
5.   Re-lection Factor;
Mortality and growth/weight patterns of
fish throughout the study were not
provided.
     EPA Guidance on this Factor

          Subdivision N: Environmental Fate Guidelines.
          page 105.
                                (1982),
          Addendum 8 on Data Reporting to Pesticide Assessment
          Guidelines:  Laboratory Studies of Pesticide
          Accumulation in Fish.   (March 1988), pages 7, 8, 9.

     As discussed above, it is imperative that the fish are not
stressed during this study which determines the accumulation
potential of a pesticide and the nature of the accumulated
residues.  Two ways in which this can be confirmed include
tracking fish mortality and growth.  Unacceptably high mortality
or unusual growth patterns may signify a problem that could
invalidate the study.  This rejection factor relates to basic
                             - 204 -
-------
                                                    Accumulation in Fish (165-4)

information that must be reported so that a technical evaluation
of the data can be made.  In most cases, studies rejected solely
on this reporting deficiency are likely to be upgraded by the
registrant by the submission of the additional data/information.

     Industry Comment

     Industry agrees that gross observation of the  mortality and
growth patterns of fish throughout the study should be provided.
However, detailed weights of the fish should not be necessary
since there are generally an insufficient number taken  to allow
statistical analysis of biological development.

     industry Recommendation:  Require only gross  observations
and not measurement of actual weights of the fish.

     EPA Response

     As supplementary  information, we agree that  only gross
observations should be  required.   The study should also report
the 96-hr  LC50.
                               -  205  -
-------
 GUIDELINE 165-5 FIELD ACCUMULATION STUDIES OF AQUATIC NON-TARGET
                             ORGANISMS

      There were no studies screened for this guideline.   However,
 guidance on this topic appears in Subdivision N -  Environmental
 Pate Guidelines (pages 107-108)  and in the Acceptance Criteria
 and the  Guidance for Summarizing Studies [see pages  C-354-357  of
 the Phase 3 Guidance].   There is no SEP for this guideline.


    GUIDELINES 166-1, -2, -3  - GROUND WATER MONITORING STUDIES

      There were no studies  screened for these guidelines.
 Guidance on this topic  is  currently being  developed  by the Ground
 Water Section  of EFGWB.  There are no SEPs for these guidelines.


       GUIDELINES 167-1, -2 - SURFACE WATER/RUN OFF STUDIES

      There were no studies  screened for these guidelines.
 Guidance on this topic  is  currently being  developed  by the
 Surface  Water  Section of EFGWB.   There  are no SEPs for these
 guidelines.

               GUIDELINE 201-1 DROPLET SIZE SPECTRUM

      There were  no studies  screened for this  guideline.  However,
 guidance  on this  topic appears  in Subdivision R - Pesticide Spray
 Drift Evaluation,  the Standard  Evaluation  Procedure-  Pesticide
 Spray Drift Evaluation:  Droplet  Size Spectrum Test  and Drift
 Field Evaluation  Test, and  in the  Acceptance  Criteria  and the
 Guidance  for Summarizing Studies  [see pages C-402-403  of the
 Phase 3 Guidance].

             GUIDELINE 202-1 DRIFT FIELD EVALUATION

     There  were no  studies  screened  for  this  guideline.  However,
 guidance  on this  topic appears in  Subdivision R - Pesticide Spray
Drift Evaluation,  the Standard Evaluation Procedure-  Pesticide
 Spray Drift  Evaluation:  Droplet Size Spectrum Test and Drift
 Field Evaluation Test, and  in the Acceptance  Criteria and the
Guidance  for Summarizing Studies  [see pages C-404-406 of the
Phase 3 Guidance].
                             - 206 -
-------
IX.      SUMMARY  TABLE  OF  REJECTION   FACTORS


161-1      HYDROLYSIS STUDY

1)         A material balance was not provided
2)         The study was not conducted in the dark.
3)         The study duration and number of sampling intervals were insufficient to establish the decline and half-life.
4)         It was not specified that the buffer solutions were sterile; before, it could not be determined if degradation was due to hydrolysis or biotic processes.
5)         The test substance was not characterized.
6)         The incubation temperature was not maintained.
7)         Insufficient data were presented to supportthe reported conclusion.
8)         Degradation curves and  regression analysis were not provided.


161-2      PHOTODEGRADATION STUDIES IN WATER

1)         The light source was not adequately characterized and was not compared to sunlight.
2)         Degradates were not identified.
3)         The material balances were incomplete.
4)         The test solutions were not buffered and 1he pH of the water was not reported.
5)         The analytical methodology was incomplete and no raw data was provided to support the conclusions.
6)         The sampling protocol was inadequate.
7)         The temperatures of the test solutions were not reported.
8)         Volatilization was neither measured nor controlled.
9)         A photosensitizerwas used as the co-solvent.
 10)       It was not specified that the test solutions were sterile.
 11)       The study was terminated before the half-life of the test substance was established or before 30 days.
 12)       The coefficients of determination for the data used to determine the half-lives were very poor.
 13)       The stability of the pesticide under refrigeration was not addressed.


 161-3     PHOTODEGRADATION ON SOIL

 1)        The material balance was incomplete.
 2)        Volatilization was neither measured nor controlled.
 3)        Artificial light source was not similar to natural sunlight.
 4)        The test substance was not technical grade or pure.
 5)         Raw data were not provided.
 6)         Theincubationtemperaturewasnotprovided.
 7)         Degradates were not identified.
 8)         The test was not performed on soil.
 9)         The treatment rate was not reported.


  161-4     PHOTODEGRADATION IN AIR

  1)        The pesticide degradation in the vapor phase could not be distinguished from degradation that occurred in material adsorbed to the sides of the glass
            container.
  2)        Air samples were never analyzed separately from nonvaporizedpesticide.
  3)        The material balance was low.
  4)        High percentages of unidentified material were reported.
  5)        The registrant did not measure the vaporpressure at the temperature the study was conducted.
  6)         The analytical method was inadequate.
  7)         The spectrum of the artificial light source was not similar to that of natural sunlight.
  8)         A photosensitizerwas present in the primary stock solution.
  9)         No raw data was submitted.
  162-1      AEROBIC SOIL METABOLISM

  1)         Residue identification was incomplete.
  2)         The material balance was inadequate.
  3)         The study was conducted for an inadequate length of time to establish the patterns of formation and decline.
  4)         Purity of the test substance was not specified.
  5)         The experimental design was inadequate to assess the metabolism in soil.
  6)         The incubation temperature was not reported.


                                                                 -  207   -
-------
 7)         The soil textures could not be confirmed because the soils were not classified using the USDA Soil Textural Classification System.
 8)         The analytical methodology was incomplete and no raw data were provided to supportconclusions.
 9)         The raw data examined did not support the half-life reported by the registrant.
 10)        Dcgradate characterization data were presented as percent of recovered rather than percent of applied.


 162-2      ANAEROBIC SOIL METABOLISM

 1)         Residue identification was incomplete.
 2)         The material balance was inadequate.
 3)         The purity of the test substance was not specified.
 4)         The storage stability data were not provided, although the raw data indicate that both soil samples and extracts were stored prior to analysis.
 5)         Dcgradntcs present in small concentrations were not identified.
 6)         The experimental design was inadequate to accurately assess the degradation under anaerobic conditions.
 7)         The length of frozen storage was not specified.  Frozen storage stability data are required to confirm that the residues were stable.
 8)         Method detection limits were not provided.
 9)         Large discrepancies existed in the data for duplicate samples collected after anaerobic conditions were established.  The data, therefore, cannot be
            used reliably to calculate the rate of degradation in soil under anaerobic conditions.
 10)        The study was conducted for an inadequate length of time to establish the patterns of formation and decline of the pesticide under anaerobic
            conditions. The study should have been conducted for 60 days.
 11)        No raw data were provided to support the conclusions.
 12)        A complete description of the test water, including the pH and dissolved oxygen content, was not provided.
 13)        The soil was not classified according to the USDA Soil Textural Classification System.


 162-3      ANAEROBIC AQUATIC METABOLISM

 1)         The sampling protocol was inappropriatebecause it contained too few sampling intervals and was inadequate to establish the half-life for the
            pesticide.
 2)         The pesticide residues were quantified using a chemically nonspecific analytical method. No attempt was made to characterize the pesticide residues
            in soil and water matrices.
 3)         Material balances were incomplete.
 4)         Dcgradntcs were not identified.
 5)         The test substance was not technical grade or purer.
 6)         The test water was not characterized. Foreign soils were not completely characterized and may not have been typical of those in the United States.
            The soil must be representative of that found at an intended use site.


 162-4      AEROBIC AQUATIC METABOLISM

 1)        The sampling schedule was inadequate.
 2)        Material balances were incomplete.
 3)        Residues were incompletely characterized.
 4)        The test water was not characterized.


 163-1      LEACHING/ADSORPTION/DESORPTION

 1)         Dcgradates were not identified.
 2)         The test soils wore autoclaved prior to conducting the study.
 3)         The material balance was incomplete.
 4)         Soils and sediments were incompletely characterized.
 5)         Dcsorption of a major degradate was not addressed.
 6)         Foreign soils were used which may not be typical of soils in  the United States.
 7)         Kd values (values of soil/water relationships) were not reported.
 8)         The desorptionphase was done serially, with incomplete removal of the supernatant at each step.
 9)         The soil texture could not be confirmed because the soil was  not classified using the USDA Soil Textural Classification System.
 10)        It was not established that the equilibrium time used was sufficient for the soihsolutionslurries to reach equilibrium.
 11)        The bioassay methods used in the study were not acceptable analytical techniques.
 12)        Soil used in the study was not prepared properly.
 13)        Test solution was not characterized.
 14)        The data were presented on a percentage basis with no actual concentrations.


 163-2      LABORATORY VOLATILITY

 1)         Analytical methodology was insufficient.
2)         The study was not carried out over a long enough period of time to clearly define a volatility decline curve.
3)         The soil was not analyzed immediately after treatment. Therefore, the application rate was not confirmed.
                                                              -   208   -
-------
4)         No material balance was reported or the data reported was insufficient.
5)         Not all major formulation categories were tested.
6)         The soil was autoclaved before the test.
7)         The rate of volatilization was incorrectly calculated and could not be determined with the information provided.
8)         The experiments were not replicated.
163-3
           FIELD VOLATILITY
1)         The soil data were inadequate  to confirm the application rate.
2)         Data on soil samples was not provided.
3)         The description of experimental conditions were insufficient.


164-1 TERRESTRIAL FIELD DISSIPATION

1)         The original concentration of the pesticide was not reported or the reported application rate was not confirmed in soil samples taken immediately
           post-treatment.
2)         The pattern of formation and decline of the degradates was not addressed.
3)         The sampling was not done to depths sufficient to define the extent of leaching.
4)         Characterization of residues was not provided for all sites or the soil was not analyzed for the correct residues or for all residues.
5)         Complete soil characteristics and field test data were not provided.
6)         The analytical methodology was insufficient to identify the residues (in one case, the analytical method could not distinguish between the parent and
           its degradates).
7)         The data were too variable to accurately assess the dissipation of the test substance.
8)         The freezer storage stability data were inadequate.
9)         The maximum label rates were not used, and the soil incorporation procedure recommended on the label was not followed.
10)        The formulation and method of application were not specified.
11)        The plants were harvested after application and the time of harvest was not given.
12)        Pretreatment samples were contaminated.
13)        More than one pesticide was applied to the crop.
14)        The experiment was conducted at only one site instead of the two recommended in the Guidelines.
15)        The method of detection limit and recovery efficiencies were not reported.


164-2      AQUATIC FIELD DISSIPATION

1)         Complete field test data were not provided.
2)         The analytical methodology was insufficient to determine the residue.
3)         The material balance was insufficient.
4)         Data were too variable to assess dissipation.


164-3      FORESTRY FIELD DISSIPATION

1)         The data provided were either  insufficient or too variable to accurately establish a pattern of dissipation of a chemical and its primary degradate in a
           forest environment.
2)         The sampling protocol was inadequate.
3)         The application rate was not reported.
4)         No storage stability data were provided to confirm that samples did not degrade prior to analysis.
5)         Field test data were incomplete.
165-1
           CONFINED ACCUMULATION IN ROTATIONAL CROPS
1)         The residues in soil were not characterized.
2)         The length of freezer storage of the crops was not reported and no freezer storage stability data were provided.
3)         The study application rate does not reflect normal or maximum use rates and the application rate was not confirmed.
4)         The test substance was less than analytical grade.
5)         The supporting raw data were not provided.

165-2      FIELD ACCUMULATION IN ROTATIONAL CROPS

1)         The source of pesticide residues in  control samples of bom crops and soils were not verified.
2)         There was a large degree of variability in the data with no explanation provided.
3)         Residues in soil were not analyzed.
4)         Planting to harvest intervals were not provided.
5)         The field test data were incomplete.                                    '
6)         The test substance was not characterized.
                                                                 -   209   -
-------
IfiS-4      ACCUMULATION IN EtSH

I)         The analytical methodology was insufficient to detect the residue.
2)         Some dcgradatcs present in small concentrations in edible and non-edible fish tissues were not identified and/or quantified.
3)         Tho study on the effects of storage on the analytical results of samples was not completed.
4)         Data on the concentration of the parent and its degradates in the exposure water were not submitted.
5)         Mortality and growth/weightpattems of fish throughoutthe study were not provided.
                                                                -  210   -
-------
X.  CONCLUSIONS

     Overall, the rejection rates for environmental fate have
shown improvement.  The pre-1986 aggregate rejection rate for
environmental fate was 54 percent, and the post-1988 rejection
rate is 28 percent.  The photodegradation - water  (161-2),
photodegradation - soil  (161-3), leaching ((163-1), terrestrial
field dissipation  (164-1) and aquatic field dissipation  (164-2)
guidelines have shown a continuous and substantial downward trend
in their rejection rates.  The rejection rate for
photodegradation - water has dropped from 53 percent to  19
percent; for photodegradation - soil from 53 percent to  18
percent; for leaching from 57 percent to 19 percent, for
terrestrial field dissipation from 52 percent to 27 percent, and
for aquatic field dissipation from 95 percent to 21 percent.
While the improvement has been substantial, their  current
rejection rates are still high, in light of OPP's  goal of 10%.

     Four guidelines have not shown improvement.   The pre-1986
rejection rate for aerobic soil metabolism  (162-1) was 25 percent
and the post-1988 rate is 32 percent; for anaerobic soil
metabolism  (162-2), the pre-1986 rejection rate was 33 percent
and the post-1988 is 53 percent; for confined crop rotation  (165-
1), the average rejection rate is 55 percent; and  for
bioaccumulation in fish  (165-4), the average rejection rate is 39
percent.

     The rejection rates associated with those studies that are
part of the sequencing and triggering of the ground water
monitoring studies appear to pose the greatest risk to delaying
REDs.  This is based on  the amount of time it takes  (12  years) to
complete the two sequences that could in turn result in  two more
levels of higher tier studies being triggered.  High rejection
rates at the first level are likely to cascade into the  second
level  (see Chart 1) contributing to high rejection rates there as
well.  This will result  in substantial delays in satisfying the
data requirements  for guidelines in these two levels as  well as
postpone the determination of whether a ground water monitoring
study should be required.  The  terrestrial field dissipation
study is a  critical study, given its role of characterizing
dissipation under  actual field  conditions as well  as triggering
the higher  tier ground water monitoring requirements.

     The three most frequently  cited factors that  have led to  the
rejection of studies  include:  (1) inadequate materials balance;
 (2) degradates/residues  not adequately identified; and  (3)
failure to  adequately establish half-life.

     Industry provided substantial  insight  into:  (1) where
further Agency guidance  would be most useful; and  (2) why certain
rejection factors  occur.   Some  of the rejection factors  reflect
very difficult technical problems.   For example,  revaporization

                              -  211  -
-------
from the walls of test containers make an accurate derivation of
the formation and decline of the parent and degradates in the
photodegradation in air  (161-4) study extremely problematic.

     The tight time frames imposed by FIFRA '88 force industry to
start studies before results from other pertinent studies have
been reviewed and approved by the Agency.  Consequently,
rejection factors in the earlier studies can cascade down into
the subsequent sequence of studies causing them to be rejected as
well.  Industry also pointed out that the time lines for certain
studies were too short.

     Industry asserted that the single most important factor that
has contributed to the high rejection rates in environmental fate
is the many changes the Agency has made in guideline
requirements, which have been retroactively imposed on studies
that had already been initiated.

         The Chemistry Branches of Health Effects Division  (HED)
have taken over the responsibility for review of studies which
determine whether pesticide residues of concern are observed in
rotational crops as a result of uptake from soil of previously
treated fields (Guideline Nos. 165-1 and 165-2). This transfer
was performed because the concern over residues in these
situations is chiefly dietary. While the Branches were not in
attendance at the meeting held with the industry, the 2/23/93
document entitled "Guidance on How to Conduct Studies on
Rotational Crops" has altered some of the data requirements for
rotational crop studies making certain of the previous rejection
factors moot, especially those dealing with analyses of residues
in soil. This paper along with the metabolism,  storage stability
and raw data documents prepared earlier in response to the
Residue Chemistry section of the rejection rate project have
provided additional guidance which addresses the remainder of the
industry's concerns over rejection factors for rotational crop
studies.
                             - 212 -
-------
XI.  RECOMMENDATIONS

     As a result of the rejection rate analysis and the ensuing
discussions with Industry, both EPA and Industry realize the need
for additional guidance on various environmental fate
requirements.  EPA and industry intend to develop and issue the
following documents:
     Storage Stability Guidance proposal
     Raw Data Guidance Proposal
     Interim Protocol Proposal for 161-4
     SEP Proposal  for  162-4
     Guidance  on  Conducting
     Studies on Rotational Crops
Delivered draft
7/27/93

Delivered draft
7/27/93

Delivered draft
7/27/93

Delivered draft
7/23/93

Delivered on
2/23/93  (EPA)
      Industry has  also agreed to provide position papers
 regarding cut off  points  for 161-1 and 161-2.   The development of
 these documents  should further reduce rejection rates for
 environmental fate.

      Consistent  with EPA's Definition of Reregistration,  the
 Agency shall review and evaluate all studies according to
 criteria that (1)  were in place at the time of the Phase  III
 Guidance or (2)  were agreed to by EPA and the registrant  in
 specific protocols prior to the initiation of the study,
 whichever comes  later.  The use of new criteria is not a  valid
 reason for rejecting a study submitted to satisfy reregistration
 data requirements.

      The Agency intends to distribute all relevant environmental
 fate policy notes to NACA, CSMA and CMA for distribution to their
 members.

      The Agency and Industry have also agreed to discuss and
 resolve the issues regarding the appropriate criteria for
 triggering and conducting:

      a)   the photodegradation  in air  (161-4) study;
      b)   mobility - adsorption/desorption  (163-1) studies;
      c)   laboratory volatility (163-2) and field volatility
            (163-3) studies;
      d)   conducting  field dissipation  (164 series)  studies.
                               - 213  -
-------
^         the technical problems identified in the analysis with
the photodegradation in air  (161-4) study, in the interim the
Agency wxll reevaluate the need for this study where it has
already been required.

     Finally, SRRD intends to continue tracking rejection rates
for environmental fate guideline studies.  If significant
reductions in the rejection, rates for these studies are not
realized, further regulatory action may be required
                            - 214 -
-------
XII.  APPENDIX A - EPA GUIDANCE DOCUMENTS

     EPA distributed the following guidance documents to guide
registrants on the correct procedures for conducting
environmental fate studies.  Specific references to these
materials are made under each of the rejection factors listed.

          Subdivision N, Chemistry?  Environmental Fate
          Guidelines - Series 160 through 165-5  (EPA Number
          540/09-82-021, October 1982).

          Subdivision R, Pesticide Spray Drift Evaluation  (EPA
          Number 540/9-84-002, April 1984).

          Subdivision O - Residue Chemistry Guidelines  (1982).


          FIFRA Accelerated Reregistration - Phase 3 Technical
          Guidance  (EPA Number 540/09-90-078, December 1989).

          Data Reporting Guidelines:

               Environmental Fate  - Addendum 1 - Series 165-2
                (EPA Number 540/09-86-149), June 1986.

               Environmental Fate  - Addendum 2 - Series 164-1
                (EPA Number 540/09-87-200), December 1986.

               Environmental Fate  - Addendum 5 - Series 162-1
                (EPA Number 540/9-82-021), January 1988.

               Environmental Fate  - Addendum 6 - Series 163-1
                (EPA Number 540/09-88-026), January 1988

               Environmental Fate  - Addendum 7 - Series 165-1
                (EPA Number 540/09-88-050), 1988.

               Environmental Fate  - Addendum 8 - Series 165-4
                (EPA Number 540/09-88-051), March 1988.

           Standard Evaluation  Procedures:

               Hydrolysis  Studies  (EPA Number  540/9-85-013),  June
                1985.

               Aqueous  Photolysis  Studies  (EPA Number 540/9-85-
                014),  June  1985.

                Soil  Photolysis Studies (EPA Number  540/9-85-016),
                June 1985.
                              - 215 -
-------
      Aerobic Soil Metabolism Studies   (EPA Number
      540/9-85-015), June 1985.

      Anaerobic Soil Metabolism Studies  (EPA Number
      540/09-88-104), August 1988.

      Soil Column Leaching Studies (EPA Number 540/9-85-
      017), June 1985«

      Terrestrial Field Dissipation Studies  (EPA Number
      540/09-90-073), December 1989.

      Pesticide Spray Drift Evaluation: Droplet Size
      Spectrum Test and Drift Field Evaluation Test (EPA
      Number 540/9-86-131), June 1986.

Other Guidance Prepared By Health Effects Division

 Additional Guidance for Conducting Plant and
 Livestock Metabolism Studies (7/16/92).

 Guidance on Generating Storage Stability Data in
 Support of Pesticide Residue Chemistry Studies
 (1/14/93).

 Guidance on Submission of Raw Data (1/14/93).

 Guidance on How to Conduct Studies on Rotational
 Crops (2/23/93).
                    -  216 -
-------
APPENDIX B - Environmental Fate Guidelines

161-1: Hydrolysis
161-2: Photodegradation - water
161-3: Photodegradation - soil
161-4: Photodegradation - air
162-1: Aerobic soil metabolism
162-2: Anaerobic soil metabolism
162-3: Anaerobic aquatic metabolism
162-4: Aerobic aquatic metabolism
163-1: Leach/adsorption/desorption
163-2: Volatility - lab
163-3: Volatility - field
164-1: Terrestrial field dissipation
164-2: Aquatic field dissipation
164-3: Forest field dissipation
164-5: Long term soil dissipation
165-1: Confined rotational crop  (Now Responsibility of Chemistry
                                Branches/HED)
165-2: Field rotational crop  (Now responsibility of Chemistry  '
                             B ranche s/HED)
165-3: Accumulation - irrigation crop
165-4: Bioaccumulation in fish
165-5: Bioaccumulation - aquatic non-target
166-1: Ground water - small prospective
166-2: Ground water - small retrospective
201-1: Droplet size spectrum
202-1: Drift field evaluation
                              - 217 -
-------
-------
             UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                        WASHINGTON, D.C. 20460
                            FEB  231993
                                                OFFICE OF
                                           PREVENTION, PESTICIDES AND
                                              TOXIC SUBSTANCES
MEMORANDUM
SUBJECT:  Guidance on How to Conduct Studies  on Rotational Crops,

FROM:     Ed  Zager,  Chief            ^AA3P***
          Chemistry Branch II: Reregistration SuJ
          Health Effects Division  (H7509C)

                      and

          Debra Edwards, Ph.D., Chief
          Chemistry Branch I: Tolerance  Support
          Health Effects Division  (H7509C)
TO:
Peter Caulkins, Acting Director
Special Review and Reregistration Division  (H7508W)

                and

Lawrence Culleen,  Acting Director
Registration  Division (H7505C)
 THRU
Penelope A. F
Health Effect
               W^Crisp, Ph.D. .
                Division (H7509C)
                                              Director
 Earlier  this  year  the  Chemistry  Branches  of  HED  took  over
 responsibility for the review of data generated on rotational crops
 (Guideline No.'s 165-1 and 165-2). The attached paper  was prepared
 by a team consisting of Dr. R.  Perfetti,  Dr.  R.  Loranger,  Dr.  W.
 Hazel,  F.  Suhre,  M.  Rodriguez and  R.  Quick  in order to provide
 guidance to Registrants and Chemistry Branch  personnel  on how to
 conduct and review these studies. This document will be utilized by
 the  Chemistry  Branches  in  future  reviews  of  rotational  crop
 studies.

 We recommend that this paper be provided to all interested parties.

 cc (With Attachment):  L.  Rossi, S. Irene, RBP, RF,  Petition
 Review Aids File  and Rotational Crops File
                                                       Recycled/Recyclable
                                                       Printed with Soy/Canola Ink on paper that
                                                       contain* at l««st 50% recycled fiber
-------
GUIDANCE ON HOW TO CONDUCT STUDIES ON ROTATIONAL CROPS
-------
INTRODUCTION

The Chemistry Branches of Health Effects Division (HED) have taken
over  the  responsibility  for  review  of  studies which  determine
whether pesticide residues of concern result in rotational crops as
a  result  of  uptake  from  soil  of  previously  treated  fields
(Guideline  Nos.  165-1  and  165-2).  This  transfer was  performed
because the concern  over residues in  these situations is chiefly
dietary. The  following paper  is  intended to provide additional
guidance to HED personnel and  other  interested  parties  as to the
requirements and procedure for review of submitted studies.

HISTORICAL

Studies on "Confined  Rotational Crops" (Guideline Number 165-1) and
"Field Rotational Crops10  (165-2)  are conditionally required under
40 CFR  158  for uses  of pesticides on terrestrial  food  crops and
aquatic food crops. As stated in Subdivision N,  a rotational crop
use is any field-vegetable crop use, aquatic crop use or any other
site use on which it is reasonably foreseeable that  any food or
feed crop may  be produced after application  of a  pesticide. The
purpose of these studies is to determine the nature and amount of
pesticide residue uptake into rotational crops. The confined study
uses  radioactive  material  applied  to   a   small  plot  (often
laboratory/greenhouse). Results of these "hot" studies are used to
determine whether field studies (using non-radioactive pesticide)
are needed  to measure  residues  in  rotational crops  grown under
actual  field  conditions.  Based  on  these data appropriate  crop
rotation  restrictions  (time   from  application  to  planting  of
rotational crop) may  be established and the need for tolerances on
the rotated crops determined.

Review  of these studies has been conducted by  the Environmental
Fate and Ground Water Branch  (EFGWB) in the Environmental Fate and
Effects Division  (or its predecessors in earlier organizations of
OPP) .    Presumably this  assignment was based on  the importance of
soil residues  as a  factor in  determining levels of  residues in
rotational crops.

Traditionally  the confined  study  has  served  as  a  worst-case
indicator of whether  residues could occur in rotational crops.  The
study is often conducted indoors  using  potted plants, conditions
which would tend to reduce the  dissipation of  the pesticide in the
soil.  Until recently, if detectable residues of concern were found
in the crop  during the confined study after the proposed rotational
crop  interval,  the  field trials would  normally  be  required to
assess  whether residues occur  in  rotational  crops  under actual
growing conditions.  In some cases registrants have volunteered to
perform field  studies to refute  results  of  the  confined study,
especially  if  the  registrant  did  not  want a rotational  crop
-------
interval  on  the  label.   If detectable residues were found in the
field  studies  for crops having a 12 month plantback interval (or
after  a shorter interval the registrant desired on the  label), the
registrant would be directed to seek a tolerance under  the FFD&CA.
In this case, a tolerance petition was submitted and responsibility
for review shifted to the  Chemistry Branch in HED.

Recently, EFGWB has been using the results of the  confined studies
alone  to  determine whether tolerances are required for rotational
crops.    Under  this  revised  process,   EFGWB has  deferred  to
Toxicology Branch when radioactive residues of  the parent compound
or closely related metabolites were found in the  crops during the
hot study.   In other words, the field trials have been eliminated
as  an early step in  determining the  need  for  rotational crop
tolerances.  Under  that procedure,  if  Toxicology  Branch   (TOX)
concluded that the residues identified in the confined study were
not toxicologically  significant or,  if they were toxicologically
significant,  but  the  levels  present  were  not  toxicologically
significant,  then no tolerance was  required.    However,  if TOX
concluded the  opposite,  the  registrant was referred  to  the
Chemistry Branches in HED.

Scientific Considerations

Confined  Rotational Crop Studies; 165-1

The protocol for performing the three  required confined rotational
crop  studies  (small  grain, 'leafy  vegetable  and root crop)  is
provided  in  Pesticide Assessment  Guidelines  Subdivision  N.
Acceptance  Criteria  were  discussed  in the   Agency's  Phase  3
Technical Guidance Document. Confined rotational  crop studies are
essentially metabolism  studies; therefore, it is recommended that
the publication entitled "Additional Guidance for  Conducting Plant
and Livestock  Metabolism  Studies"  (7/16/92) be consulted before
conducting a confined rotational  crop study.  (It  should be noted
that,  in the case  of confined  rotational   crop   studies,  the
application rate is IX,  not an exaggerated rate.) . This paper will
refer frequently to that document when discussing various phases of
the subject  experiments.  A flow diagram  describing  the approach
discussed in this paper is  provided in Figure 1  at the  end of this
document.

The following should be considered when a confined rotational crop
study  is  to  be conducted.  The  test material should.be  the pure
active ingredient radiolabeled (PAIRA) with   C  in  a  non-labile
position  (e.g.,  in a ring).  The  parent compound only should be
applied to the appropriate  soil type (usually a  sandy loam) at the
maximum  label  rate  (IX)   and  the  required  three rotated  crops
(small grain, leafy vegetable and root crop)  should be planted at
appropriate  soil aging intervals  (e.g,  1,  4,  7 or  9,  and  12
months).   Sampling of the  soil  is  not required and  need  only be
performed at the  Registrant's  discretion.  The crops should  be
-------
harvested and the appropriate plant parts (see Pesticide Assessment
Guidelines Subdivision O/ Table II) should be sampled and combusted
to determine the total  radioactive residue (TRR).  At this point, if
each of the  three crops demonstrate  a  TRR of  <0.01  ppm in edible
portions at one of the plantback  or soil aging intervals then  the
Chemistry  Branches  will  conclude that  no further  work and  no
tolerances are needed. An appropriate rotational crop restriction
can be set at the shortest interval where no TRR is    >0.01 ppm,
provided that the Registrant is willing to place this interval on
the label. If the TRR  is <0.01 ppm in  all three  crops at the one
month interval,  then no plantback restriction will be needed on the
label. If,  however, in the  three confined studies,  the minimum
intervals at which the  TRR is <0.01 ppm  differ, then the rotational
crop restrictions will be set at the interval appropriate to each
tested crop  group with the longest interval being applied to all
other  (untested)  rotated  crops.  The following example  should be
considered:

     The TRR for leafy vegetables is  <0.01 ppm at the  1  month
     plantback interval, the root  crop TRR is <0.01  ppm at the 4
     month interval and the grain  crop TRR is <0.01  ppm at the 9
     month interval. The rotational  crop  restrictions would be 1
     month for  leafy  vegetables,  4  months for  root  crops  and 9
     months for small grains and all other rotated crops.

It is the Registrant's prerogative to perform additional confined
rotational  crop  studies  on  other  crops  to   establish  less
restrictive intervals based on levels of radioactivity.

In rare cases, TOX  may have  concerns regarding the  presence of a
pesticide or metabolite at levels <0.01 ppm. Determination of the
presence (or absence)  of specific metabolites of concern at levels
0.01  ppm must  be
determined.  The  Registrant is referred  to the  7/16/92  guidance
document  discussed  above  (see  also the  comment regarding  the
application  rate for  confined  rotational crop  studies)  for  a
description  of   the procedures  which  need  to   be  followed  to
accomplish this  determination.  If any one  of the three crops shows
<0.01 ppm at a given interval but the Registrant desires a shorter
interval on  the  label  for  that crop where  the TRR  is >0.01 ppm,
then the  composition  of  the TRR  in that  rotated  crop  (at  the
desired interval) should be determined as described above for the
crop parts where the trigger value (i.e.,  0.01 ppm)  was exceeded.
If  several samples  of the  crop  are  available  at  the  desired
interval, the sample having the highest TRR should be utilized. In
either of the above  cases, this information is needed in order that
-------
the Agency can make  a  conclusion  as to whether the residue is an
inadvertent residue of no concern  or whether cold field trials are
needed to make that determination.

If the metabolism in rotated crops  appears to be  different than
that in  the  primary crop, that is,  if different  metabolites are
observed in rotated  crops than  in primary crops,  the Agency will
make a determination as  to whether the different  rotational crop
metabolites are  of  concern at the levels observed. If necessary,
the HED  Metabolism Committee will be  consulted to expedite this
decision.

The following are examples of the situations' described above;

The primary  (target)  crop  metabolism studies  indicate  that the
parent and metabolites A, B, C,  D and E are present in the plant.
The Agency decides that only the parent and metabolite B need to be
regulated  in  the  tolerance  expression.  The  following  three
scenarios might be encountered regarding rotational crops:

1) The confined  rotational  crop studies indicate  that the TRR is
>0.01 ppm  and  that parent  and  metabolites  A, B,  C and  D are
present. Limited rotational crop  field trials will  normally be
required with analysis  for  parent and  metabolite  B  if  it  is
determined that these residues  -could  be present  at detectable
levels.  If, however, metabolites  A, C and D  are  present at much
higher levels in the rotational crops than in the primary crop, the
HED Metabolism Committee may be consulted as to whether the other
metabolites need to be quantitated.

2) The confined rotational crop  studies show that the  TRR is >0.01
ppm and  that the radioactive residue consists of  no parent and
metabolites  D and  E.  In this case  the  Agency   would  normally
conclude  that  this is   an  inadvertent  residue   of  no  concern
situation and no field trials would be required. A rotational crop
restriction may  be  necessary. As  above however, if metabolites D
and E are  present at much higher  levels  in the rotational crops
than in  the primary crop, the HED Metabolism Committee  may be
consulted as to whether these metabolites need to be quantitated.

3) The confined  rotational crop studies indicate  that the TRR is
>0.01 ppm and that  there is no  parent present but that the major
portion  of  the  TRR consists of  a  new  metabolite F. This will
require a decision, as to whether  there is toxicological concern
over the new metabolite.  At this point the HED Metabolism Committee
may be consulted for an expedited decision. If  it is concluded that
the metabolite  is  of concern at the levels likely to be present,
then F should be analyzed for in the limited rotational crop field
trials.  If  it is decided that F  is of no concern  then,  as in 2
above, this is an inadvertent residue of no concern situation and
no  field  trials    are  necessary.  However,   a rotational  crop
restriction may be necessary.
-------
It  is  recommended that the confined  studies  be submitted to the
Agency as soon after completion as possible, so that the Agency can
make a conclusion as to whether there is a potential  inadvertent
residue of concern (i.e.,  will limited field trials be needed ?) as
expediently as possible.  This  will allow the Registrant to design
the field trials  in  a more efficient  manner (i.e., what compounds
require analysis  in  the field  trials).

Field Rotational  Crop Studies  (Limited and/or Extensive); 165-2

If  the level  of  the total  radioactive  residue  in  the confined
rotational  crops  exceeds 0.01  ppm  at  the  desired rotational
interval or at 12  months,  and  once the nature of the residue in the
rotational crops is understood, then the Registrant should consider
the Agency's position regarding the residue to be  regulated in the
primary crop  (see discussion  above)  to  decide  whether the first
tier  of  field trials  should be  initiated.  That  is,  if  the
composition  of the TRR  in  the  rotational  crops is  such  that
residues which are regulated  in the primary crop are observed at
levels >0.01 ppm in the rotational crop (following the criteria set
forth  in  the 7/16/92 document with  the  exception of exaggerated
application  rates),  then field  trials should  be performed.  For
further guidance on the protocols for carrying out these trials see
Pesticide Assessment Guidelines Subdivisions N and O as well as the
following comments.

The limited field trials  should be conducted on a representative
crop (as defined  in 40  CFR  180.34  (f))  at two sites per crop for
the following 3   crop groups:  root and tuber vegetables  ,  leafy
vegetables and cereal grains for a total  of 6  trials.  The 6 trials
should be conducted on  a  specific  crop in each of the three crop
groups which the Registrant intends to have as a rotational crop on
the label. The soil should be treated at the maximum label rate and
the maximum number of applications and the appropriate crops should
be planted after  the minimum aging interval.  The crops should be
harvested and all of the  plant parts  prescribed in Subdivision 0,
Table II should be analyzed for the residues of concern observed in
primary crops as well as any other  residues of concern specific to
rotational  crops   which  fulfill the  criteria  set forth  in  the
Confined Rotational  Crop  section of this paper. Detection limits
for rotational crops should  be comparable to  those for primary
crops.

If  no  detectable  residue  are  observed  in  raw   agricultural
commodities in the limited field trials, then no tolerances will be
needed. However   plantback restrictions  will normally be needed
unless confined or field studies show no detectable residues of
concern at a  30 day  plantback  interval.

If  the  limited   field  studies  above  indicate  that detectable
residues  will occur,  then  rotational  crop  tolerances will  be
required. The requirement for number of trials would be the same as
-------
that to establish primary tolerances  on all crops (or crop groups)
which the Registrant  intends to have as rotational  crops  on the
label. If the Registrant desires to allow the "universe" of crops
to be rotated, then magnitude  of  the residue data  is required on
representative crops  (see 40 CFR  180.34  (f))  for all crop groups
which could be planted  in a typical  crop rotation sequence. With
respect to treatment,  these  trials should be conducted in the same
manner as discussed above for the limited trials.  If the Registrant
believes that a lesser number of crops would be rotated because of
the nature  of the pesticide or due  to  the way  it  is  used, then
guidance should be obtained  from the Agency regarding  specific data
requirements in that case.  If tolerances exist on the crops to be
rotated as a result of a primary use,  then rotational  data on these
crops would be required only if  residues  in rotated  crops are
significant in comparison to those in the primary crop.

Recmlatorv Considerations

It  is  the  Agency's  position  that  data  waivers or  agreements
concerning  rotational  crop requirements  granted previously  by
EFGWB/EFED should continue to be effective under  this new guidance
and  therefore  HED  will not  reactivate  rotational  crop  data
requirements in these cases.

In  the  future,  under  revised  Guidelines,  the  limited  field
rotational  crop  requirement may be  altered  so  that an increased
number of limited  field  trials will  be required. This requirement
will not be applied retroactively.
-------
       S
       CO
       CC
I
13
 (0
 Q.
S

I
 Q.
                                              2"
                                              a
                                                     ts
                                                       CO
                                                     •s-
                                                     S
                                                      :%
                                                                     S
fi
                   |Q- c £•
                     llfii
                     i CO « O.O
                                   £   CD
                                   •5   c
                                   O-   CD
                                   CD Q.A
                                     O >.
                                   S &*
                                   1«£

                                   2§i

                                   Isl^
                                   S§£
                                   o = 52
                                   Z< £
                                                        21

                                                        8-f
                                                        N-.®
                                                        o-Q

                                                        •1
                                                        3 *
                                                        S
                                                       EC'S
-------
-------
Physical/Chemical Properties
(submitted  with product
chemistry data)
                          Solubility
                           171-2
                                                              Degradation Studies
                                                              (Defines abiotic and bic
                                                              rates of breakdown)
Lab Studies


Hydrolysis
161-1

R




-•
3hotodegradation -
water
161-2
R
1 YR




3hotodegradation -
soil
161-3
R
1 YR




Aerobic soil
metabolism
162-1

1 YR
21
                                                      Data generated:
                                                      1. Material balance
                                                      2. 1/2 life - parent & degradates
                                                      3. Graph of formation & decline
                                                        of parent & degradates
Preliminary environmental fate assessment
(based on lab studies; gives
potential routes of breakdown,
routes of offcsite movement,
uptake in non-target organisms,
and bioaccumulation; data used
in screening models)
Data generated:
1. 1/2 life-parent & degradates
2. Decline-parent & degradates
3. Vertical leaching movement -
  parent & degradates
Terrestrial
  field
dissipation
  164-1
-------
                                   ENVIRONMENTAL
                                       Terrestrial Field An
Vapor
Pressure
171-2

R
                                           I
                                           I
                                     VP > 10 ^(normally)     >v
                                     10'4> VP > 106 (case by casej
                                     VP < 1(T6(rarely)      J
Itlc routes and
       Anaerobic sol!
        metabolism
         162-2
Xl. Pc-isistent &\
mobile, or \ MO
2.Othor monitoring \ ^
data, and 1
3. Toxiloglcal 1
concerns/risk /
Char, of
field
dissipat-
ion
Volatility- I
  163-2
-------
  "E AND GROUND WATER
  lartf
 Id Vegetable Crop Use
                          . Aerial or mist application
                         2. Detrimental to non-target organism)
                           fl.0. herbicides)           ~"
   nsoort Studies
   efines offsite movement of
  arent & degradates)
 Nab
  CR
                   Yes
          ;umu6
       (Defines!
       parent af
  YR

  Degenerated:
  1. Volatility
  2. Air concentration
  3. Vapor pressure
  4. Temp and relative
    humidity
  1YR
Data generated:
  Mobil ty classification
  1 .5
2. Soil binding property
                    1 YR
                                                                 Confined rotational
                                                                      crop
                                                                      165-1
 J

!«••
 1
"Vs
 1
                                                             •-•.,•... ^
                                                               •.
                                                             \
                                                       2YR
Data generated:!
1. Residues foul
  crops from pi
  metabolites! I
                                     2YR
In?
                                              Rotational Crop Stt
                                                  165-1 AND 165-

                                             are no longer part of the Enviroi
                                             discipline. These two studies hj (
                                             transferred to Residue Chemist'
                                            	         I i
-------
                                I
                                I
                                I
                              JL
                        1.Kow> 1000, and
                        2. Half-life > 4 days, and
                        3. Reaches water
I atton Studies
I non-target uptake of
 id degradates)
  Yes

|nd In rotational
     , degradatas &
 t different Intervals
   1 YR

  Data generated:
I 1. Residue concentrations in water, whole
     body edible portions of fish at various
•    sampling times during 28 day exposure
                                     and 14 day depuration
 pmonlal Fate
                          Yes
                                                  No
-------
 Field Studies
                                         Yes
 I
 I
 \
1
                                                                4YR
                                               L  -
Environmental fate assessment
( based on lab and field data;
gives field dissipation rates,
potential to leach, runoff,
volatilize, or bioaccumulate
under typical field conditions
for pesticide and breakdown
products. The environmental
fate assessment may include
modeling estimates)
-------
=- • 1
•
I
I
1
I
I
•
1
1
1
1
1
I
I
I
1
T
Groundwater-
small prospective (Most vulnerable
166-1 site)
CR
I 4YR
1
I
*
T,
Volatility -
field
163-3
"*1

1 '
1 cnar. 01
volatiliza
tlon as a
dissipati !







•            Data generated:
            1. Concentrations of residues
            (parent & degredates) in
       1    ground water
 1. Significant
   hits in ground
   water, or
 2. Other monitoring
   data, and
 3. Toxlloglcal
   Concerns
      No
1.  Characterization of leaching as
   a route of dissipation
              Yes
I Groundwater-
     small
  prospective
     166-1  CR
(typical site)
       •4YR

       1  Data generated:
          1. Concentrations of
I       X resldues(parent &
I       W degredates) In ground water
bUTCOME>
    tai restriction
15t>i
-------
1. Label restrictions
                                        s v.v. •.   X-

                                     " , JA*-
                                              * "V-
                                                         3YR
                                                        sv*- \»*?\^ ^
                                                       ••         ,„''?*'•. •.
                                                      Xx,   ,   ^^*^-

                                                      1. Crop rotation 'nti J
                                                      2. Need for.toler.im f
                                                         (HEP)
-------

\ N
Jprvil restrictions
!• on rotational crop
               Char, of bio-
               concantratlon
               as a route of
               dissipation
                                 1. Establish label
                                   restrictions
                                 2. Set action levels
                                          = Guideline study
                                          ; Information sent to Environmental
                                           Effects Branch for risk assessment
                                         = Regulatory outcome



                                         = Condition statement


                                         = Sequence

                                         = Trigger

                                                                         03/18/93
-------