FINAL DRAFT
               United States
               Environmental Protection
               Agency
4>EPA       Research  and
               Development
              HEALTH AND ENVIRONMENTAL  EFFECTS DOCUMENT
              FOR ENDOTHALL
              Prepared for
              OFFICE OF SOLID WASTE AND
              EMERGENCY RESPONSE
              Prepared by
              Environmental  Criteria and Assessment Office
              Office of Health and  Environmental Assessment
              U.S. Environmental Protection Agency
              Cincinnati, OH  45268

                         DRAFT: DO NOT CITE OR QUOTE
                                NOTICE

               cument 1s a preliminary draft.  It has not been formally released
                Environmental Protection Agency and should not at this stage be
               o represent Agency policy.  It  1s being circulated for comments
               ilcal accuracy and policy Implications.

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                                  DISCLAIMER

    This report  1s  an external draft  for  review purposes only and  does  not
constitute  Agency  policy.   Mention of  trade names  or  commercial  products
does not constitute endorsement or recommendation for use.
                                      11

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                                    PREFACE
    Health and  Environmental  Effects  Documents (HEEOs) are prepared  for  the
Office of Solid  Waste  and Emergency Response  (OSWER).  This  document series
Is Intended to support listings under  the  Resource  Conservation  and Recovery
Act (RCRA) as  well as to provide health-related limits and  goals  for  emer-
gency and  remedial actions under  the Comprehensive  Environmental  Response,
Compensation  and  Liability  Act  (CERCLA).   Both  published  literature  and
Information obtained for  Agency Program Office  files are evaluated  as  they
pertain to potential human health,  aquatic  life  and environmental  effects of
hazardous waste  constituents.   The  literature searched for In  this document
and  the  dates  searched   are  Included In  "Appendix:  Literature  Searched."
Literature search  material  Is current up  to 8 months previous  to  the  final
draft date  listed  on  the front  cover.   Final  draft document  dates  (front
cover) reflect the date the document Is sent to the Program Officer (OSWER).

    Several  quantitative  estimates  are  presented  provided  sufficient  data
are available.   For systemic  toxicants,  these  Include Reference  doses (RfDs)
for  chronic   and  subchronlc  exposures  for  both  the Inhalation  and  oral
exposures.   The  subchronlc  or  partial  lifetime RfD 1s  an  estimate of  an
exposure  level   that would not  be expected  to  cause adverse  effects  when
exposure occurs  during a  limited  time  Interval  I.e., for an  Interval  that
does  not  constitute a  significant portion  of the  Hfespan.  This  type of
exposure estimate  has  not been extensively used,  or rigorously  defined as
previous risk assessment  efforts  have  focused  primarily on  lifetime exposure
scenarios.   Animal data   used  for  subchronlc  estimates  generally  reflect
exposure  durations of  30-90  days.   The  general  methodology  for  estimating
subchronlc RfDs  1s  the same as  traditionally employed for  chronic  estimates,
except that subchronlc  data are utilized  when available.

    In the case  of suspected  carcinogens,  RfDs are  not estimated.   Instead,
a  carcinogenic  potency   factor,  or   q-j*   (U.S.  EPA,  1980),  Is  provided.
These potency  estimates  are  derived  for  both oral  and Inhalation  exposures
where possible.  In addition, unit  risk  estimates for air  and drinking water
are presented based on  Inhalation and oral  data, respectively.

    Reportable quantities  (RQs)  based on both chronic toxlclty  and carclno-
genldty are derived.  The RQ Is  used  to determine the quantity of a hazard-
ous substance  for  which   notification  Is  required In  the event  of  a release
as  specified  under  the   Comprehensive  Environmental  Response,  Compensation
and Liability  Act  (CERCLA).   These two  RQs  (chronic toxlclty  and carclno-
genldty) represent two of six  scores developed  (the remaining  four reflect
1gn1tab1l1ty,  reactivity, aquatic  toxlclty,  and acute mammalian  toxlclty).
Chemical-specific  RQs reflect the lowest of  these six primary criteria.   The
methodology  for  chronic   toxlclty and  cancer  based  RQs  are  defined  In  U.S.
EPA, 1984 and 1986a, respectively.
                                      111

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                              EXECUTIVE SUMMARY

    Endothall (145-73-3)  1s  a  colorless or white  solid at room  temperature
(Martin and  Worthing,  1979; Worthing  and  Walker,  1983).   It Is soluble  In
common organic  solvents  and  soluble  1n water  (Worthing  and Walker,  1983;
Hartley and  K1dd,  1983).   Pennwalt Corp.  1n  Wyandotte,  MI,   1s  the  only
current domestic  manufacturer  of  this  compound  (SRI,  1987; USITC,  1987).
Its current  U.S.  production volume  1s not available.   Various  formulations
of  endothall  are  used  as  preemergence and  postemergence herbicides,  turf
herbicides,  aquatic  herbicides  and  alglddes,  deslccants for  alfalfa  and
clover, and  cotton  harvest aids  (Worthing and  Walker,  1983;  WSSA,  1983;
Melster,   1988).    Tradenames   Include   Accelerate,  Aquathol  K,   Des-1-cate,
Herbicide 273 and Hydrothol  191  {Melster, 1988).
    If released  to  the  atmosphere,  endothall Is  expected to exist  predomi-
nantly In  aerosol  form  and may  be removed by either wet  or  dry  deposition.
Photolysis Is  not  expected  to  be an  environmentally  relevant  fate  process
(Relnert  and Rodgers, 1984).   If released  to soil  or  water,  endothall  would
be  subject to  rapid  blodegradatlon under appropriate  conditions.  Field  and
laboratory studies Indicate that endothall generally  has  a half-life  of  <1
week  1n  surface waters  under  aerobic conditions  (S1ms1man  et  al.,  1976;
Relnert et al., 1985, 1986, 1988; S1kka and R1ce,  1973;  Relnert  and  Rodgers,
1987;  Holmberg  and Lee,  1976;  Langeland and Warner,  1986).   This  compound
blodegrades  more  slowly  In  water  under   anaerobic   conditions  and  has  a
half-life of ~2  months  (Slmslman et  al., 1976).  Arthrobacter sj>.,  Isolated
from   sediment,  metabolized   14C-endothall   under   aerobic   conditions  and
Incorporated  the 14C  Into  glutamlc,  aspartlc  and  citric adds, and  to  a
lesser extent  alanlne,   phosphate  esters   (not  positively  Identified)  and
                                      1v

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other  unidentified  compounds  (S1kka  and  Saxena,  1973).   Endothall  1s  not
expected to  degrade  chemically,  volatilize or adsorb significantly In  water
or  soil  (Relnert  and  Rodgers,  1984;  Relnert et  al.,  1988;  S1ms1man  and
Chesters, 1975;  Swann  et al., 1983).   The blodegradatlon half-life of  this
chemical In soil Is <7 days  and  1t  Is  expected to  persist more 1n soils with
high adsorption  capability.   Rapid blodegradatlon  1s  expected to  limit  the
extent of leaching through soil.
    The most common  route  of human exposure to endothall  Is  probably  dermal
contact by  workers  Involved  In  the manufacture,  handling or  application  of
the herbicide (HSDB, 1988).  The general public could potentially be  exposed
by  Ingestlon  of  contaminated   crops.   Monitoring  data  for  endothall  In
environmental media  (air, water,  soil  and food)  were  not  located  1n  the
available literature dted In Appendix A.
    The potassium and sodium salts of  endothall are  the forms least toxic to
both  aquatic vertebrates  and  Invertebrates,  with 96-hour   LC   s  Of  >IQQ
mg/l.   In  contrast, 96-hour  LC5Qs for  the amlne  and   copper  salts  are  <1
mg/i for a  variety of aquatic  organisms.   Water  hardness did  not Influence
the  toxlclty  of dlsodlum  or  dlamlne  salts  to bluegllls  (Inglls  and  Davis,
1973)  and  pH did not affect  the toxlclty  of Aquathol   K  to  bluegllls  (Mayer
and  Ellersleck,  1986).   The  toxlclty  of  Aquathol K   to blueglll  sunflsh
Increased 5-fold when  the test  temperature  Increased  from 7  to  24°C  (Mayer
and Ellersleck, 1986).
    The  14-day  LC5Q of  endothall to  juvenile Chinook  salmon,  Onchorynchus
tshawytscha. was  62.5 ppm (Llgourl  et  al.,  1983).   Surviving  fish  demon-
strated  poor  survival  when  transferred  to  seawater but good  survival  when
transferred  to  freshwater.  The 10-day  growth  EC5Qs for  various  species  of
marine algae exposed to  the  amlne  and  dlpotassium  salts ranged from 225-3000

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ppm  (Walsh,   1972).   No  short- or  long-term  effects  were  observed  among
natural  populations  of  organisms   1n  ponds  or  reservoirs  treated with  <5
mg/i endothall.
    Experimental evidence  suggests  that endothall 1s not  likely  to bloaccu-
mulate  1n  aquatic  organisms.   S1kka  et al.  (1975)  reported  that  bluegllls
took  up <1%  of  the  available  herbicide  from water  over  a  96-hour  period.
Isensee  (1976)  reported bloaccumulatlon  ratios  of  63, 36,  150  and  10  for
algae,  snails,  daphnlds  and  fish.    Serns   (1977)  was  unable  to  detect
endothall residues 1n tissues of bluegllls  from a pond  that had been treated
3  days  earlier with  endothall  to  give a  concentration of 5  mg/i.   Relnert
and Rodgers  (1986) were unable to detect  endothall  residues  In  tissues  of
bluegllls  from a  reservoir  that  had  been  treated  7  days  earlier  with  2
mg/l  endothall.   Relnert   et  al.   (1988)   reported  BCFs  of  3.9,  12.1  and
768.9 for  the dlpotasslum  salt  of  endothall  In  watermllfoll,  but discounted
the highest value because of experimental  errors.
    Data obtained  from  rats  of  both  sexes  treated with  a single oral dose of
14C-endothall  suggest  that  gastrointestinal  absortlon  1s  poor (Soo  et al.,
1967).   Peak  tissue  concentrations  occurred  within  1  hour  In  all  tissues
sampled  except  the Intestine.  The absorbed  radioactivity occurred predomi-
nately  1n  the  stomach  and  Intestine  (-99% of  the administered  radioactiv-
ity).   About  1% of the administered radioactivity occurred  1n the liver  and
kidneys.   Radioactivity was not found In  fat or milk, and  was  essentially
eliminated from all  tissues within 72 hours.  At least 85%  of the adminis-
tered  dose  was excreted 1n  the feces, but  ~20% of  this  was  unchanged com-
pound  and  80% was bound In  some form.  It seems more  likely  that  the bound
form  1s endothall  that Is  adsorbed  onto gastrointestinal  contents  rather
than  an endothall conjugate.   Small   quantities  were  excreted In  the urine
(~6%),  apparently as unchanged compound, and  In the breath as CO- (~3%).
                                       v1

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    Minimal  data  were  located  In  the  available  literature  regarding  the
health  effects  of endothall.   Acute  toxlclty appears  to be  substantially
greater  for  the  add  form than  for  the  dlsodlum salt.  Oral  LD5Q  values
for rats  of  38-57 mg/kg have  been  reported  for  the add form (Worthing  and
Walker, 1983; Galnes and  Under,  1986)  and 182-197 mg/kg have been  reported
for  the  dlsodlum  salt.   Acute   exposure  to   large   doses  Is  extremely
Irritating and causes erosion  and hemorrhage of  the stomach  (Allender,  1983;
Brleger, 1953b).
    Subchronlc  data  suggest that  dogs  may  be more  sensitive  than  rats  to
oral exposure to  endothall.   In a  dietary study, rats  succumbed to dosages
of  the  Ion of  400  mg/kg/day  and  exhibited  liver and  kidney  lesions  at  40
mg/kg/day  (Brleger,  1953a).   Dogs  treated  by  capsule,  however,  died  at  20
mg/kg/day dlsodlum endothall (16 mg/kg/day endothall  1on) and  had congestion
and  edema  of  the  stomach  at  0.8  mg/kg/day  of  endothall  Ion  (Brleger,
1953b).   The  Investigators  suggested   that  the  lesions   In  the  stomach
resulted  from the  administration   of  the undiluted  test substance without
food.
    There are notable discrepancies between  the  subchronlc and chronic  data.
For example,  no  toxic  effects  were reported In  a  2-year  dietary study  where
rats were  exposed to  2500 ppm dlsodlum endothall  (100  mg/kg bw/day  of  endo-
thall 1on) (Brleger, 1953b).   In a  2-year  dietary study using  dogs (4/dose),
elevated  relative and  absolute  stomach   and  small  Intestine  weights  were
Increased with  dlsodlum  endothall  at  300 and  800  ppm  (6  and 16  mg/kg/day of
endothall  1on), but  no  effects were observed  at  100 ppm (2 mg/kg/day  of  the
Ion) (Keller, 1965;  Penwalt Agchem, n.d.).
    Developmental toxldty  studies  using  rats  suggest  that the dams  are  more
susceptible  than  the fetuses  to oral  administration  of endothall  (Science
                                      vll

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Applications, Inc.,  1982).   In a dietary  study  pregnant rats were given  0,
8, 16 or 24  mg  endothall  1 on/kg/day  on  gestation  days  6-19.   Maternal  deaths
occurred at  the  two higher  doses   but  the  fetuses  of  the  surviving  dams
exhibited  no  signs  of  teratogenldty  or  fetotoxldty.    A   NOAEL   of   8
mg/kg/day  was  Identified  from  this  study  for  teratogenldty   based  on
maternal effects.
    In a 3-generat1on reproductive study, no  effects were observed  when rats
were  exposed to dlsodlum endothall  1n  the  diet  that  provided  a  dosage  of
endothall  Ion  at  4  mg/kg/day  (Scientific  Associates,  1965).   In  the  same
3-generat1on study, however, pups 1n  the 12  mg/kg/day  group had  reduced body
weights and pups 1n the 100  mg/kg/day group died within a week of birth.
    Endothall has  not been  adequately tested  for  carclnogenldty.   There was
no  evidence  of  carclnogenldty  1n  rats  fed   diets  containing  dlsodlum
endothall  at  <2500 ppm {100 mg/kg/day  of  the 1on) for  2 years 1n an  early
study  (Brleger,  1953b).    Endothall  Induced  transformation  of  BALB/c 3T3
cells  (LUton  B1onet1cs,   Inc.,  1981).    Endothall  was  not  mutagenlc  In
microorganisms   (Andersen   et  al.,   1972;  Remondelll   et   al.,    1986;
Microbiological  Associates,  1980a;  Sandier  and  Ham1lton-Byrd,  1981)  and  1n
human  lymphocytes   (Vlgfusson,  1981).   Mixed   results  were   obtained  In
Drosophla  (Wilson et al.,  1956; Sandier  and Hamllton-Byrd,  1981).
    The NOEL  for  gastrointestinal effects  1n dogs from  the chronic oral dog
study  (Keller,  1965; Pennwalt Agchem,   n.d.)  was used  as  the  basis   for  a
verified RfD of  0.02 mg/kg/day for endothal.   This  RfD  1s  adopted as  the RfD
for chronic  oral exposure as  well as subchronlc  oral  exposure  to  endothall
for the  purposes of this document.   An RQ  of 1000  was calculated from the
effect  level  for gastrointestinal  effects  In  the same study.   Endothall  1s
assigned to  EPA  Group D because of Insufficient animal  carclnogenldty  data;
therefore, no q,* or cancer-based RQ  can be derived for endothall.

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                             TABLE OF CONTENTS
                                                                       Page
1.  INTRODUCTION	     1

    1.1.   STRUCTURE AND CAS NUMBER .  .	     1
    1.2.   PHYSICAL AND CHEMICAL PROPERTIES 	     1
    1.3.   PRODUCTION DATA	     2
    1.4.   USE DATA	     2
    1.5.   SUMMARY	     2

2.  ENVIRONMENTAL FATE AND TRANSPORT	     4

    2.1.   AIR	     4

           2.1.1.   Chemical Degradation	     4
           2.1.2.   Physical Removal Processes	     4

    2.2.   WATER	     4

           2.2.1.   Chemical Degradation	     4
           2.2.2.   Volatilization	     4
           2.2.3.   Adsorption	     4
           2.2.4.   Persistence 	     5

    2.3.   SOIL	'	• .  .     9

           2.3.1.   Chemical Degradation	     9
           2.3.2.   Volatilization	     9
           2.3.3.   Persistence 	     9
           2.3.4.   Adsorption	    10

    2.4.   SUMMARY	    10

3.  EXPOSURE	    12

4.  ENVIRONMENTAL TOXICOLOGY	    13

    4.1.   AQUATIC TOXICOLOGY 	    13

           4.1.1.   Acute Toxic Effects  on Fauna	    13
           4.1.2.   Chronic Effects on Fauna	    24
           4.1.3.   Effects on Flora	    26
           4.1.4.   Effects on Bacteria  	    28

    4.2.   TERRESTRIAL TOXICOLOGY 	    28

           4.2.1.   Effects on Fauna	    28
           4.2.2.   Effects on Flora	    28

    4.3.   FIELD STUDIES	    28
    4.4.   AQUATIC RISK ASSESSMENT	  .    30
    4.5.   SUMMARY	    31
                                     1x

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                         TABLE  OF  CONTENTS  (cont.)

                                                                       Page
5.  PHARMACOKINETCS	   33

    5.1.   ABSORPTION	   33
    5.2.   DISTRIBUTION	   34
    5.3.   METABOLISM	   35
    5.4.   EXCRETION	   35
    5.5.   SUMMARY	   36

6.  EFFECTS	   37

    6.1.   SYSTEMIC TOXICITY	   37

           6.1.1.   Inhalation Exposure 	   37
           6.1.2.   Oral Exposure	   37
           6.1.3.   Other Relevant Information	   38

    6.2.   CARCINOGENICITY	   39

           6.2.1.   Inhalation	   39
           6.2.2.   Oral	   39
           6.2.3.   Other Relevant Information	   39

    6.3.   MUTAGENICITY	   39
    6.4.   TERATOGENICITY	   39
    6.5.   OTHER REPRODUCTIVE EFFECTS 	   41
    6.6.   SUMMARY	   41

7.  EXISTING GUIDELINES AND STANDARDS 	   44

    7.1.   HUMAN	   44
    7.2.   AQUATIC	   44

8.  RISK ASSESSMENT	   45

    8.1.   CARCINOGENICITY	   45

           8.1.1.   Inhalation	   45
           8.1.2.   Oral	   45
           8.1.3.   Other Routes. . .	   45
           8.1.4.   Weight of Evidence	   45
           8.1.5.   Quantitative Risk Estimates 	   45

    8.2.   SYSTEMIC TOXICITY	   46

           8.2.1.   Inhalation Exposure 	   46
           8.2.2.   Oral Exposure	   46

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                           TABLE  OF  CONTENTS  (cont.)

                                                                        Page
 9.  REPORTABLE QUANTITIES 	   48

     9.1.   BASED ON SYSTEMIC TOXICITY 	   48
     9.2.   BASED ON CARCINOGENICITY	   48

10.  REFERENCES	   52

APPENDIX A: LITERATURE SEARCHED	   64
APPENDIX B: SUMMARY TABLE FOR ENDOTHALL	   67
APPENDIX C: DOSE/DURATION RESPONSE GRAPH(S) FOR EXPOSURE TO
            ENDOTHALL	   68
                                      xl

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                               LIST  OF  TABLES
No.                               Title                               Page
4-1     Median Response Concentration  for  F1sh and Amphibians
        Exposed to Endothall	   14
4-2     Median Response Concentration  for  Invertebrates Exposed to
        Endothall	   22
6-1     Mutagen1c1ty and Genotoxldty  Summary Table  for Endothall .  .   40
9-1     Toxldty Summary for  Oral  Exposure to Endothall Using the
        Beagle Dog.	   49
9-2     Composite Scores for  Endothall  Ion Using  the Dog	   50
9-3     Endothall: Minimum Effective Dose  (MED) and  Reportable
        Quantity (RQ)	   51

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                             LIST  OF  ABBREVIATIONS

ADI                     Acceptable dally Intake
ATP                     Adenoslne trlphosphate
BCF                     B1oconcentrat1on factor
BR                      B1oaccumulat1on ratio
BSP                     Bromosulfophthaleln
bw                      Body weight
CAS                     Chemical Abstract Service
DUEL                    Drinking water exposure level
ECso                    Concentration effective to 50% of recipients
                        (and all other subscripted concentration levels)
GSH                     Reduced glutathlone
HA                      Health Advisory
150                     Median Inhibition concentration
Koc                     Soil sorptlon coefficient standardized with respect
                        to organic carbon
Kp                      Sediment-water partition coefficient
LCso                    Concentration lethal to 50% of recipients
                        (and all other subscripted dose levels)
LD5Q                    Dose lethal to 50% of recipients
NOAEL                   No-observed-adverse-effect level
NOEL                    No-observed-effect level
ppm                     Parts per million
RfD                     Reference dose
RQ                      Reportable quantity
RVd                     Dose-rating value
RVe                     Effect-rating value
SGOT                    Serum glutamlc oxaloacetlc transamlnase
SGPT                    Serum glutamlc pyruvlc transamlnase
                                     X111

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                               1.   INTRODUCTION
1.1.   STRUCTURE AND CAS NUMBER
    Endothall Is currently referred  to  by  CAS  as  7-oxab1cyclo[2.2.l]heptane-
2.3-d1carboxyl1c acid  (SANSS, 1987).   Endothall  1s  also  known as  endothal
and  3,6-endo-epoxycyclohexane-1,2-d1carboxyl1c add  (WSSA,  1983).   Trade-
names  Include   Accelerate.   Aquathol   K,   Des-1-cate,  Herbicide   273   and
Hydrothol  191  (Melster, 1988).   Discontinued  names  Include Hydout,  Hydro-
thol,  Hydrothol  47  and  Nlagrathal  (Melster, 1988).   The  structure,   CAS
Registry  number,  empirical  formula  and molecular  weight  for  this  compound
are as follows:
                      H                      0
                       ^CHCOOH
                      9
                  H2C | CHCOOH
                      H
CAS number:  145-73-3
Empirical formula:  CgH1Q05
Molecular weight:  186.16
1.2.   PHYSICAL AND CHEMICAL PROPERTIES
    Endothall,  which 1s  available as  a hydrate,  1s a  white or  colorless
solid at  room temperature (Martin and  Worthing,  1979; Worthing and  Walker,
1983).  It  1s  soluble  1n water, acetone, dloxane, methanol,  Isopropanol  and
ether  (Worthing  and   Walker.   1983;   Hartley  and  Kldd,   1983).    It   1s
noncorroslve  to metals  and  1s nonflammable  (Worthing  and  Walker,  1983).
Selected  physical   and   chemical  properties  are  as   follows  (Worthing  and
Walker. 1983; WSSA, 1983; Relnert and Rodgers, 1984):

              Melting point:                     144°C
              Boiling point:                     not  available

0168d                               -1-                              04/19/89

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              Vapor pressure:                    not available
              Water solubility at 20°C:           100,000 mg/l
              Log Kow:                           1.91
              pKal:                              3.4
              pKa2:                              6.7
              Density at 20°C:                   1.431  g/cm3

The hydrate of  endothall  forms  Its anhydride at 90°C.   It  1s  a  dibasic  acid
and  forms  water  soluble  amlne  and alkali  metal  salts.   It  1s  stable  In
acids.  Of  the  three stereolsomers of  this  chemical,  the  endocls  Isomer  Is
the most effective herbicide (Worthing  and Walker,  1983).
1.3.   PRODUCTION DATA
    Pennwalt Corporation In Wyandotte, MI, 1s  the  only  domestic  manufacturer
of  endothall   (SRI,   1987;  USITC,  1987).   It  1s  made by  the  D1els-Alder
condensation  of  furan  and  malelc anhydride  (Worthing and  Walker,  1983).
Data  pertaining  to the amount  of endothall  produced or used 1n  the  United
States were not located In the available literature.
1.4.   USE DATA
    The sodium,  potassium  and  amlne  salts  of  endothall  are  used  as  pre-
emergence  and postemergence  herbicides,  turf herbicides, aquatic herbicides,
alglddes,  desslcants  for   alfalfa  and  clover,  and  cotton  harvest  aids
(Worthing  and Walker, 1983;  WSSA, 1983;  Melster,  1988).
1.5.   SUMMARY
    Endothall (145-73-3)  1s  a colorless or white  solid at  room temperature
(Martin and  Worthing, 1979;  Worthing  and Walker,  1983).   It 1s  soluble  In
common  organic  solvents and  soluble  1n  water (Worthing  and Walker,  1983;
Hartley and Kldd,  1983).   Pennwalt  Corp.  In Wyandotte.  MI,  1s  the  only
current domestic  manufacturer of  this  compound  (SRI,  1987;  USITC,  1987).

0168d                               -2-                              04/19/89

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Its current  U.S.  production volume  Is  not  available.  Various  formulations
of  endothall  are  used  as  preemergence and  postemergence  herbicides, turf
herbicides,  aquatic  herbicides  and  alglddes,  deslccants  for  alfalfa and
clover,  and  cotton  harvest  aids  (Worthing and  Walker,  1983;  WSSA,   1983;
Melster,  1988).    Tradenames   Include   Accelerate,  Aquathol  K,   Des-1-cate,
Herbicide 273 and Hydrothol  191 (Melster,  1988).
0168d                               -3-                             06/22/89

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                2.  ENVIRONMENTAL FATE AND TRANSPORT PROCESSES
2.1.   AIR
2.1.1.   Chemical Degradation.   Endothall  Is  stable  to photolysis  (Relnert
and  Rodgers,  1984).   Pertinent  data  regarding  other  chemical  degradation
processes  1n  the atmosphere  were not  located  In  the  available  literature
cited 1n Appendix A.
2.1.2.   Physical  Removal   Processes.   A  "negligible"   vapor  pressure  for
endothall (Slmslman et  al.,  1976) suggests that  this compound  may not exist
1n  the  vapor  form 1n  the atmosphere  (Elsenrelch  et al.,  1981).   Dry deposi-
tion  of  aerosols  containing endothall may  be an Important  removal  process.
The  relatively  high   water  solubility  of  endothall   suggests  that  this
compound may also be removed from the atmosphere by wet  deposition.
2.2.   WATER
2.2.1.   Chemical Degradation.   Endothall  1s  stable  to oxidation,  hydroly-
sis and photolysis (Relnert and Rodgers,  1984; Relnert et al., 1988).
2.2.2.   Volatilization.   Using  the  method  of  Nine  and  Mookerjee  (1975),
Henry's  Law  constant  for   endothall  has  been  estimated  to  be  ~3xlO~12
atm-m3/mole  at   25°C.   This  value  of  Henry's  Law  constant  suggests  that
volatilization  of  endothall  from water  surfaces  would be  an  Insignificant
fate process.
2.2.3.   Adsorption.  Relnert  and Rodgers  (1984) determined  the  sediment/
water  partition coefficient  (Kp) for  endothall  (dlpotasslum  salt)  1n  two
different sediment/water systems.  Sediment obtained  from Pat Mayse  Lake 1n
northeastern  Texas   was   predominantly   sand  with   0.683%   organic  carbon
content, and  sediment obtained  from Roselawn Cemetery  Pond  In  north central
Texas was  predominantly clay with  1.29% organic carbon  content.   Endothall
was added  to  the systems  at  concentrations that ranged between  2.0  and  6.3


0168d                               -4-                              04/19/89

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mg/l.   After  equilibration  between the  phases was  achieved,  the mean  Kp
value for endothall  was  determined to be 0.937  1n  the  lake  water  system and
1.42  1n  the  pond water  system.   These values corresponded  to  K    values  of
137  and  110,  respectively.   Analysis  of  data obtained   by  S1ms1man  and
Chesters  (1975)  using  sediment/water  samples from  Lake  Tomahawk  1n southern
Michigan  Indicate  that  endothall  had  K    values  ranging  between 2.7  and
6.0.  These  experimental data  Indicate  that adsorption to  suspended  solids
and  sediments  1n water  should  play a relatively minor  role 1n the fate  of
endothall In aquatic systems.
2.2.4.   Persistence.    Blodegradatlon   and   blotransformatlon   are   the
dominant  removal processes  for  endothall  1n  aquatic  systems  (Relnert  and
Rodgers,  1984; S1ms1man  et al.,  1976).   Endothall  (dlpotasslum salt)  at  an
Initial  concentration  of  0.41  mg/l was  applied to  a  recreational area  1n
Pat  Mayse Lake,  an ol1gomesotroph1c  lake  In  northeast Texas.   Subsequent
monitoring  data   Indicated  that  endothall  had  a  half-life   of  0.33  days
(Relnert  et  al., 1988).   Dilution  may  have played an  Important role  In the
reduction of  the herbicide level  1n  the treated area,  since  only  a  portion
of  the  water body  (1.7% of  total  surface  area)  was treated  and  transport
from  treated  to nontreated  areas  was  possible.    S1kka   and  Rice  (1973)
studied  the  persistence  of endothall  (dlpotasslum  salt) 1n  pond water, both
In aquaria and under field  conditions.   In  a pond treated  to give  concentra-
tions  of 2  mg/i  endothall, serial  samples  were taken  and  nondetectable
levels were found 1n the water  and  top 1 Inch of the  hydrosoll (sediment)  36
days  after  treatment.    In  the  aquaria  treated  to  give concentrations  of  2
and  4 mg/l  endothall,  50% loss  1n concentration  was  observed In ~4 days,
with  nondetectable  levels  existing  after 7 days.   In autoclaved pond  water,
no degradation of  endothall had occurred after  9 days;  however, 1  day after
application  6.9% of the radlolabeled endothall  appeared  In  the  sediment.

0168d                               -5-                              04/19/89

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Figures 2-1 and  2-2  show the respective disappearance  patterns  of  endothall
from  the  pond and aquaria.   In other pond  studies  carried out  under  field
conditions, the  half-life for  the disappearance  of endothall  (dlpotasslum
salt) was  found  to range  between 4.1  and  12  days (Relnert and Rodgers,  1987;
Holmberg and  Lee,  1976; Langeland and Warner,  1986).  Both  the dlpotasslum
and  the  dlamlne salts  persisted  <7  days when  used In  Gatan  Lake,  Panama
(Relnert and  Rodgers, 1987).  When static  greenhouse experimental  pools were
treated with  endothall   (dlpotasslum  salt) at  levels  of  0.03,  1.6 and  4.5
mg/i,  the  average  half-life  of  this  compound was  determined  to be  4.01
days  (Relnert  et  al.,  1985).  The  pools  contained  water,  sediment  and
Eurasian watermllfoll.  In a laboratory static  shake  flask study,  Relnert et
al.  (1986) studied  the  blotransformatlon and  blodegradatlon  of  endothall
(dlpotasslum  salt)  at  levels  of  0.5,  2.0  and  4.0 mg/l  In water  samples
obtained from Pat  Mayse Lake  (In  Texas).   Based on  the  evolution  of  radlo-
labeled-CO-,   a  first-order   blotransformatlon  rate  coefficient  of   0.083
days'1 and half-life  for blotransformatlon of 8.45 days  were calculated.
    In  various  field   studies,  endothall  (dlpotasslum salt)  was  found  to
persist  In sediment   between  0  and  7 days,  while  the  amlne salt has  been
shown to persist for >21  days  (Relnert and Rodgers,  1987).  It has also been
shown that a  reduction  of  the  dissolved oxygen  content  of water could  have a
significant effect  on  the degradation  of endothall.   In  a  simulated  lake
Impoundment,   72% of  added endothall  persisted  1n water  for  30  days  because
of  prolonged  anoxlc conditions  following  weedklll.   Rapid  disappearance
occurred only after  restoration of  oxygenated conditions  (S1ms1man et al.,
1976).   Short-term  Incubation  of 14C-endothall  with  an  Arthrobacter  sp_.,
Isolated  from sediment  revealed  that  14C was  Incorporated  Into  glutamlc,
aspartlc and  citric  adds and  to  a   lesser extent alanlne, phosphate  esters
(not    positively    Identified)   and    other    unidentified   compounds.

0168d                               -6-                               04/19/89

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                2.00-
                                                     WATER
                                                     HVDROSOIL
                    Q46
       24   28  32   36   40   44
DAYS AFTER TREATMENT
                                    FIGURE 2-1
   Endothall  Residues 1n Water and the Top 1-Inch of Hydrosoll of a Treated
  Farm Pond,  with Time.  (The bars represent the range  of  duplicate values.)
                          Source:    S1kka  and  R1ce,  1973
0168d
  -7-
04/11/89

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                                           •    • WATER-4ppm
                                           »    * WATER-2 ppm
                                           «..—_« MYDROSOIU- 4 ppm
                                           •——•• MYOfiOSOIL- 2 ppm
                                12   16    20    24   28

                                   0*VS AFTER TREATMENT
                                    FIGURE  2-2

   Endothall Residues In Water  and Hydrosoll  of Aquaria Treated with 2 and  4
  ppm of  the Herbicide.   (The bars represent the range  of duplicate  values.)

                          Source:   S1kka and  R1ce,  1973
0168d
-8-
04/11/89

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I40-glutam1c  acid accounted  for  a  large  proportion  of  the  14C  assimi-
lated  Into  the  cells.   Apparently,  radlolabeled  C was  Incorporated  Into
glutamlc  acid  by  the trlcarboxyllc  add cycle  and an  alternate,  unknown
pathway  following  Initial   splitting  of  the  oxablcyclo  ring  {Slkka  and
Saxena, 1973).
2.3.   SOIL
2.3.1.   Chemical  Degradation.    Chemical  degradation  processes  are   not
expected  to contribute significantly  to  the  loss of this  compound  from soil
(Slmslman et al., 1976).
2.3.2.   Volatilization.     The    relatively   high   water   solubility   and
negligible vapor pressure of endothall suggest  that  volatilization  from soil
surfaces would not be a significant fate  process.
2.3.3.   Persistence.  As In aquatic  environments,  degradation of  endothall
1n soil appears  to be  due primarily  to mlcroblal  activity.   Mlcroblal degra-
dation  rather  than  chemical  degradation  1s evidenced  by the  observations
that   1)  reduction   of  soil   moisture  and  temperature  markedly  reduced
endothall degradation,  2)  treatment  of  soils with  nonlabeled  endothall  and
nutrients  followed   by  labeled   endothall   led  to   Increased  degradation
compared  with samples  not similarly  pretreated, and  3)  addition of  mlcroblal
Inhibitors, such as  pentachlorophenol, to  soil  reduced  degradation  {Slmslman
et  al.,  1976; Tweedy  and  Houseworth,  1976).  Endothall  reportedly persists
2-7  weeks  1n  soil  (Tweedy and  Houseworth, 1976).    Approximately  70%  of
14C-endothall  added   to  an  Ontario  soil  was  evolved  as  14CO?  In  7  days;
the remaining endothall existed 1n a  nonextractable  form,  probably  no longer
as  endothall  (Slmslman et  al.,  1976).   On a  clay loam soil, an  85%  loss of
14C-endothall    was  observed  In  14   days.   Slower   rates were observed  1n
0168d                               -9-                              04/19/89

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sandy soil,  which  may have  had  a higher organic  content  than did the  clay
loam, resulting  1n greater  adsorption and  slower  degradation (Slmslman  et
al., 1976).
2.3.4.   Adsorption.   Experimentally  determined   K     values  of   2.7-137
(see  Section  2.2.3.)  Indicate high  mobility 1n  soil  (Swann et al.,  1983).
However, fairly  rapid degradation 1n  the soil  column  Is  expected to  limit
the extent of leaching.  Nevertheless, some  potential exists  for groundwater
contamination.
2.4.   SUMMARY
    If  released  to  the atmosphere, endothall  1s  expected  to  exist predomi-
nantly  1n  aerosol  form and may  be removed  by either  wet or  dry deposition.
Photolysis 1s  not  expected  to  be an  environmentally  relevant fate  process
(Relnert and  Rodgers,  1984).   If released to soil  or water,  endothall  would
be  subject to rapid blodegradatlon under appropriate conditions.  Field  and
laboratory studies  Indicate  that endothall   generally has  a  half-life of  <1
week  In surface waters  under  aerobic conditions  (Slmslman  et  al.,  1976;
Relnert  et al., 1985, 1986,  1988;  Slkka and  R1ce,  1973;  Relnert and Rodgers,
1987; Holmberg  and  Lee,  1976;  Langeland  and Warner,  1986).   This compound
blodegrades  more slowly  1n  water  under  anaerobic  conditions  and   has  a
half-life of  ~2  months  (Slmslman et  al., 1976).  Arthrobacter  s_£., Isolated
from  sediment,  metabolized   14C-endothall   under  aerobic   conditions   and
Incorporated   the  14C  Into  glutamlc,  aspartlc  and dtrlc  adds,  and  to  a
lesser  extent  alanlne,  phosphate  esters  (not positively  Identified)  and
other unidentified  compounds  (Slkka  and  Saxena,   1973).  Endothall  1s  not
expected to  degrade  chemically,  volatilize  or adsorb significantly 1n  water
or  soil  (Relnert  and Rodgers,   1984;  Relnert  et  al.,  1988;  Slmslman  and
Chesters, 1975;  Swann et  al., 1983).  The  blodegradatlon  half-life  of  this


0168d                               -10-                             04/19/89

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chemical 1n soil 1s <7 days and  H  Is  expected to persist more In soils with
high adsorption  capability.   Rapid blodegradatlon  1s  expected to  limit  the
extent of leaching through soil.
0168d                               -11-                             04/19/89

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                                 3.  EXPOSURE

    The most common  route  of  human exposure to endothall  1s  probably dermal
contact by  workers  Involved In  the  manufacture,  handling or  application  of
the herbicide (HSDB, 1988).  The general public could  potentially  be exposed
by  Ingestlon  of  contaminated   crops.   Monitoring  data  for  endothall  In
environmental media  (air,  water,  soil  and food)  were not  located  In  the
available literature cited 1n  Appendix A.
0168d                               -12-                             04/11/89

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                          4.  ENVIRONMENTAL TOXICOLOGY
4.1.   AQUATIC TOXICOLOGY
4.1.1.   Acute Toxic Effects  on  Fauna.   The acute  toxlclty  of  a variety  of
endothall  products  to fish  and  one  amphibian are presented  In Table  4-1.
These data  reveal  that the  potassium and  sodium salts of endothall  are  the
forms least  toxic  to  aquatic  vertebrates.   Typical  96-hour  LC5Qs for  fish
exposed  to the dlsodlum  salt were  102 mg/l  for  blueglll sunflsh,  Lepomls
macrochlrus  {Inglls  and  Davis,  1973),   105  mg/l   for   redslded   shiner,
Notropls  umbratnis,  and 125  mg/i for  redear  sunflsh, Lepomls  mlcrolophus
(Folmar,  1977).   Typical  96-hour  LC5Qs for  fish   exposed  to  the  potassium
salt  were 440 mg/l  for   blueglll  sunflsh   (Mayer  and Ellersleck, 1986)  and
372  mg/B. for  goldfish,  Carraslus  auratus  (Berry, 1984).  Amlne and  copper
salts generated 96-hour LC5Qs of  <1 mg/l.
    Inglls and Davis  (1973)  reported that  water  hardness  did not  Influence
the toxldty of the dlsodlum or  dlamlne salt  to  blueglll  sunflsh.  Mayer  and
Ellersleck  (1986)   demonstrated  that  pH  was not a factor  affecting  the
toxlclty of Aquathol K to blueglll sunflsh, but  that  an Increase In  the test
temperature from 7  to  24°C  Increased the toxlclty  of Aquathol K 5-fold.   In
the only  study In which the  toxlclty  of an  endothall  product  to  an amphibian
was  assessed,  Mayer and  Ellersleck  (1986)  reported  a static  acute  96-hour
LC5Q  of  1.2  mg/i   for  Fowler's  toad,  Bufo woodhousel  fowlerl. exposed  to
Hydrothol 191.
    The  acute  toxlclty   of   a   variety of  endothall  products   to  aquatic
Invertebrates  1s  presented  1n  Table 4-2.   The  potassium  and   sodium  salts
were  less  toxic to  aquatic Invertebrates than  other endothall  salts,  as they
were  to  aquatic vertebrates.  Mayer and Ellerselck (1986)  reported  a  96-hour
LC50  ^or scud» Gammarus  fasdatus,  exposed  to  the  potassium salt  of 313 mg/l,
0168d                               -13-                             04/19/89

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                                                                                TABLE 4-1


                                               Median Response Concentrations for Fish and Anphtblans Exposed to Endothall
CO
0.
Species
Blueglll sunflsh
Lepomls macrochlrus

Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
.[_, Lepomls macrochlrus
1 Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
o Lepomls nacrochlrus
^ Blueglll sunflsh
^ Lepomls macrochlrus
Median Response Concentration*
Chemical
dlsodlum salt
(liquid formulation)
dlsodlum salt
(granular formulation)
dlamlne salt
dlamlne salt
dlsodlum salt
(19. 2X liquid formulation)
dlsodlum salt
(19. 2X liquid formulation)
dlsodlum salt
(19. 2X liquid formulation)
dlamlne salt
dlamlne salt
dlamlne salt
dlamlne salt
dlamlne salt
dlamlne salt
dlamlne salt
Test
Method
static.
unmeasured
static.
unmeasured
static.
unmeasured
static.
unmeasured
static,
unmeasured
static.
unmeasured
static.
unmeasured
static.
unmeasured
static,
unmeasured
static,
unmeasured
static,
unmeasured
static.
unmeasured
static.
unmeasured
static.
unmeasured
24-Hour
450 ppm a.e.
650 ppm a.e.
1.12 ng/t
(1.06-1.19)
0.90 ng/t
(0.85-0.95)
277 ng/t
(234-328)
249 ng/t
(222-279)
280 ng/t
(242-324)
0.91 ng/t
(0.79-1.05)
0.84 ng/t
(0.76-0.92)
0.78 ng/t
(0.72-0.84)
0.88 ng/t
(0.81-0.96)
1.02 ng/t
(0.95-1.10)
0.87 ng/t
(0.79-0.95)
1.49 ng/t
(1.21-1.83)
48 -Hour
280 ppm a.e.
280 ppm a.e.
1.03 ng/t
(0.95-1.11)
0.90 ng/t
(0.85-0.95)
219 ng/t
(198-242)
181 ng/t
(166-197)
196 ng/t
(178-215)
0.63 ng/t
(0.56-0.71)
0.78 ng/t
(0.72-0.87)
0.68 mg/t
(0.62-0.75)
0.84 mg/t
(0.77-0.91)
0.80 mg/t
(0.72-0.88)
0.87 mg/t
(0.78-0.96)
1.34 mg/t
(1.17-1.53)
96 -Hour
NR
NR
NR
NR
140 ng/t
(126-156)
105 ng/t
(88-125)
102 ng/t
(84-124)
NR
NR
NR
NR
NR
NR
NR
Comments
hardness = 29 mg/t
hardness <= 29 ng/t
temperature = 24'C
hardness = 368.4 mg/t
temperature = 24*C
hardness = 368.4 ng/t
temperature = 24*C
hardness = 52.2 mg/t
temperature = 24*C
hardness = 208.7 mg/t
temperature = 24'C
hardness = 365.2 mg/t
temperature = 24'C
hardness = 52.5 mg/t
temperature = 24*C
hardness =52.5 ng/t
temperature = 24°C
hardness =210 mg/t
temperature = 24'C
hardness = 210 ng/t
temperature <= 24'C
hardness = 368.4 mg/t
temperature = 24'C
hardness = 368.4 mg/t
temperature = 24'C
hardness = 52.5 mg/t
Reference
Hughes and .
Davis. 1965

Inglls and
Davis. 1973
Inglls and
Davis, 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Inglls and
Davis, 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
00
10

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TABLE 4-1 (cont.)
o
—1
00
CL





1
I





O
CO
Median Response Concentration*
Species
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunftsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomts macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Chemical
dlamlne salt
dlamlne salt
dlamlne salt
dlpotasslum salt
cocoamlne salt
cocoamlne salt
dlsodlum salt
(liquid formulation)
dlsodlum salt
dlsodlum salt
dlsodlum salt
(liquid formulation)
dlsodlum salt
dlsodlum salt
(granular formulation)
dlsodlum salt
(granular formulation)
copper salt
(25X wet table powder)
Test
Method
static.
unmeasured
static,
unmeasured
static.
unmeasured
static
static
static
static
static
static
static
static
static
static
static
24-Hour
1.09 mg/t
(1.01-1.18)
1.02 mg/t
(0.94-1.10)
1.02 mg/t
(0.94-1.11)
428 mg/t
0.8 mg/t
0.3 mg/t
NR
NR
NR
NR
NR
NR
NR
6.70 mg/t
(5.33-8.46)
48-Hour
1.02 mg/t
(0.96-1.09)
0.94 mg/t
(0.90-0.98)
1.00 mg/t
(0.92-1.08)
268 mg/t
0.8 mg/t
0.3 mg/t
NR
NR
NR
450 mg/t
NR
NR
650 mg/t
NR
96-Hour
NR
NR
NR
NR
NR
NR
NR
180 mg/t
NR
280 mg/t
125-150 mg/t
NR
280 mg/t
3.33 mg/t
(2.51-4.4)
Comments
temperature •= 24*C
hardness = 52.5 mg/t
temperature 24°C
hardness = 210 mg/t
temperature 24*C
hardness =210 mg/t
NC
NC
NC
no observed effect at
50 mg/t after 72 hours
or at 100 mg/t after
12 days
soft water
6-hour LCso = 160
mg/t In hard water
NC
NC
no observed effect at
100 mg/t after 21 days
NC
temperature = 18*C
hardness =135 mg/t
Reference
Inglls and
Davis, 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Folraar. 1977
Folmar. 1977
Folmar. 1977
Folmar. 1977
Folmar. 1977
Folmar. 1977
Folmar. 1977
Folmar. 1977
Folmar. 1977
Folmar, 1977
Mayer and
Filers leek. 1986

-------
TABLE 4-1 (cont.)
Median Response Concentration*
Species
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Leporols macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunftsh
Lepomls macrochlrus
Blueglll sunflsh
Leporols macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomls macrochlrus
Blueglll sunflsh
Lepomts roacrochlrus
Blueflll sunflsh
Leporols macrochlrus
Chemical
Endothall Herbicide 282
(67. 9X liquid concentrate)
Hydrothol 191
(53X liquid concentrate)
potassium salt
(40. 3X liquid concentrate)
Endothall
(17. 5X granular formulation)
Aquathol K
(40. 3X liquid
Aquathol K
(40. W liquid
Aquathol K
(40. 3X liquid
Aquathol K
(40. 3X liquid
Aquathol K
(40. 3X liquid
Aquathol K
(40. 3X liquid
Aquathol K
(40. 3X liquid
Aquathol K
(40. 3X liquid
Aquathol K
(40. 3X liquid
concentrate)
concentrate)
concentrate)
concentrate)
concentrate)
concentrate)
concentrate)
concentrate)
concentrate)
Test
Method
static
static
static
static
static
static
static
static
static
static
static
static
static
24-Hour
1.25 mg/t
1.15 mg/t
>580 mg/t
>10 mg/t
>1000
>1000
>1000
>1000
>1000
>2000
>1000
>2000
mg/t
mg/t
mg/l
mg/t
mg/t
mg/t
mg/t
mg/l
1830 mg/t
(1560-2150)
48-Hour
NR
NR
NR
NR
NR
(867-1320)
NR
(1010-2550)
NR
NR
NR
NR
NR
NR
NR
96-Hour
1.20 mg/t
0.94 mg/t
440 mg/t
NR
1070 mg/t
1600 mg/t
1050 mg/t
(798-1380)
1030 mg/t
(845-1260)
975 mg/t
(773-1230)
1740 mg/t
(1410-2150)
1600 mg/t
(1010-2550)
970 mg/t
(840-1120)
343 mg/t
(308-383)
Comments
temperature =
hardness = 44
temperature =
hardness = 44
temperature =
hardness = 44
temperature =
hardness = 40
temperature =
hardness = 44
pH = 6.5
temperature =
hardness = 44
pH = 7.5
temperature •=
hardness = 44
pH = 8.0
temperature =
hardness = 44
pH <= 8.5
temperature =
hardness = 44
pH = 9.5
temperature =
hardness = 44
temperature =
hardness = 44
temperature =
hardness = 44
temperature =
hardness = 44
24°C
mg/t
24"C
mg/t
24°C
mg/t
22BC
mg/t
12«C
mg/l
12°C
mg/t
12°C
mg/t
12«C
mg/l
12«C
mg/l
7*C
mg/l
12°C
mg/l
17°C
mg/l
22°C
rog/l
Reference
Mayer and
Ellersleck.
Mayer and
Ellersleck.
Mayer and
Ellersleck.
Mayer and
Ellersleck.
Mayer and
Ellersleck,
Mayer and
Ellersleck,
Mayer and
Ellersleck,
Mayer and
Ellersleck,
Mayer and
Ellersleck.
Mayer and
Ellersleck.
Mayer and
Ellersleck.
Mayer and
Ellersleck,
Mayer and
Ellersleck,
1986
1986
1986
1986
1986
1986
1986
1986
1986
1986
1986
1986
1986

-------
TABLE 4-1 (cont.)
0
03
O.





1
— J
1





O
•x.
^k
Median Response Concentration*
Species
Redear sunftsh
Lepomls mlcrolophus
Redear sunflsh
Lepomls mlcrolophus
Redear sunflsh
Lepomls mlcrolophus
Green sunflsh
Lepomls cyanellus
Green sunflsh
Lepomls cyanellus
Redear sunflsh
Lepomls mlcrolophus
Redear sunflsh
Lepomls mlcrolophus
Redear sunflsh
Lepomls mlcrolophus
Redear sunflsh
Lepomls mlcrolophus
Carp
Catfish
Ictalurus punctatus
Catfish
Ictalurus punctatus
Catfish
Ictalurus punctatus
Catfish
Ictalurus punctatus
Catfish
Ictalurus punctatus
Chemical
monoamlne salt
monoamlne salt
monoamlne salt
copper salt
(25* wet table powder)
dlsodlum salt
(granular formulation)
dlamlne salt
dlamlne salt
dlamlne salt
dlsodlum salt
acid
dlsodlum salt
(liquid formulation)
dlsodlum salt
(granular formulation)
endothall
(17. 5X granular formulation)
Hydrothol 191
(53X liquid concentrate)
Aquathol K
(40. 3X liquid concentrate)
Test
Method
static.
unmeasured
static.
unmeasured
static.
unmeasured
static
static
static.
unmeasured
static.
unmeasured
static.
unmeasured
static
NR
static
static
static
static
static
24-Hour
0.81 mg/l
(0.78-0.84)
0.68 mg/l
(0.65-0.72)
0.73 mg/l
(0.69-0.80)
1.63 mg/l
(1.29-2.2)
NR
0.53 mg/l
(0.47-0.60)
0.56 nig/1
(0.52-0.62)
0.56 mg/l
(0.52-0.62)
NR
NR
NR
NR
3.4 mg/l
(2.4-4.7)
2.10 mg/l
>150 mg/l
48 -Hour
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
96 -Hour
NR
NR
NR
1.30 mg/l
(1.00-1.80)
NR
NR
NR
NR
125 mg/l
175 ppm
NR
NR
2.1 mg/l
(1.4-2.9)
0.49 mg/l
>150 mg/l
Comments
temperature = 24*C
hardness = 52.5 mg/l
temperature = 24*C
hardness = 210 mg/l
temperature = 24*C
hardness = 368.4 mg/l
temperature = 18*C
hardness = 44 mg/l
no observed effect at
10 mg/l after 12 days
temperature = 24*C
hardness = 52.5 mg/l
temperature = 24°C
hardness =210 mg/l
temperature = 24*C
hardness = 368.4 mg/l
NC
NC
no observed effect at
100 mg/l after 72 hours
no observed effect at
50 mg/l after 72 hours
temperature = 22*C
hardness = 40 mg/l
temperature = 18*C
hardness = 44 mg/l
temperature 12*C
hardness = 44 mg/l
Reference
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Mayer and
Ellersleck. 1986
Folmar. 1977
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Folmar. 1977
Plmental. 1971
Folmar. 1977
Folmar. 1977
Mayer and
Ellersleck. 1986
Mayer and
Ellersleck. 1986
Mayer and
Ellersleck. 1986

-------
TABLE 4-1 (conft.)
0
o>
00
Q.





00
1





04/11/89
Median Response Concentration*
Species
Catfish
Ictalurus punctatus
Yellow bullhead
Ictalurus nebulosus
Black bullhead
Ictalurus melas
Goldfish hybrid
Goldfish
Carasslus auratus
Goldfish
Carasslus auratus
Goldfish
Carasslus auratus
Goldfish
Carasslus auratus
Goldfish
Carasslus auratus
Goldfish
Carasslus auratus
Goldfish
Carasslus auratus
Goldfish
Carasslus auratus
Goldfish
Carasslus auratus
Goldfish
Carasslus auratus
Goldfish
Carasslus auratus

Chemical
Aqua t hoi K
(40. 3X liquid concentrate)
dlsodlum salt
dt sodium salt
acid
dlamlne salt
dlanlne salt
dlanlne salt
dlanlne salt
dlamlne salt
dlamlne salt
monoamlne salt
monoamlne salt
monoamlne salt
monoamlne salt
monoamlne salt

Test
Method
static
static
static
MR
static.
unmeasured
static.
unmeasured
static.
unmeasured
static.
unmeasured
static.
unmeasured
static.
unmeasured
static.
unmeasured
static.
unmeasured
static.
unmeasured
static.
unmeasured
static.
unmeasured

24-Hour
>100 ng/t
NR
NR
NR
0.86 mg/t
(0.76-0.98)
1.00 ng/t
(0.90-1.12)
0.82 ng/t
(0.14-0.91)
1.19 ng/t
(1.10-1.28)
1.17 ng/t
(1.03-1.33)
1.26 ng/t
(1.13-1.40)
0.81 ng/t
(0.74-0.88)
1.39 ng/t
(1.32-1.47)
NR
0.98 ng/t
(0.85-1.13)
NR

48-Hour
NR
NR
NR
NR
0.80 ng/t
(0.73-0.88)
0.86 ng/t
(0.81-0.92)
0.80 rag/l
(0.73-0.88)
0.97 mg/t
(0.87-1.08)
1.03 mg/t
(0.90-1.18)
1.15 mg/t
(1.06-1.25)
0.78 mg/t
(0.68-0.89)
1.23 mg/t
(1.16-1.31)
1.50 mg/t
(1.35-1.66)
0.95 mg/t
(0.85-1.06)
1.38 mg/t
(1.28-1.49)

96-Hour
>100 mg/t
170-175 ng/t
180-185 ng/t
175 ppm
NR
NR
NR
NR
NR
NR
NR
1.20 mg/t
(1.13-1.28)
NR
NR
NR

Comments
temperature = 22"C
hardness = 40 mg/t
NC
NC
NC
temperature ° 24"C
hardness = 52.5 mg/t
temperature = 24°C
hardness = 52.5 mg/t
temperature = 24°C
hardness = 210 mg/t
temperature = 24"C
hardness = 210 mg/t
temperature = 24°C
hardness = 368.4 mg/t
temperature ° 24*C
hardness = 368.4 mg/t
temperature = 24*C
hardness = 52.5 mg/t
temperature = 24°C
hardness = 52.5 rag/t
temperature = 24°C
hardness = 52.5 mg/t
temperature = 24°C
hardness = 210 mg/t
temperature = 24°C
hardness = 210 mg/t

Reference
Mayer and
Ellersteck. 1986
Folmar. 1977
folmar. 1977
Plmental. 1971
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Inglls and
Davis, 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Inglls and
Davis, 1973


-------
                                                                      TABLE  4-1  (cont.)
M
o»
00
Q.




1
hO
1
Median Response Concentration*
Species
Goldfish
Carasslus auratus
Goldfish
Carasslus auratus
Goldfish
Carasslus auratus
Goldfish
Carasslus auratus
Goldfish
Carasslus auratus
Fathead minnow
Plmephales pronelas
Bluntnose nlnnow
Plmephales notatus
Chemical
nonoamlne salt
nonoamlne salt
monoamtne salt
monoamtne salt
potassium salt
hydrothol 191
(53X liquid concentrate)
dlsodtum salt
Test
Method
static.
unmeasured
static.
unmeasured
static.
unmeasured
static.
unmeasured
static.
unmeasured
static
static
24 -Hour
1.28 mg/l
(1.20-1.36)
1.17 mg/t
(1.04-1.21)
NR
1.18 mg/l
(1.09-1.28)
NR
1.90 ng/t
NR
48-Hour
1.18 ng/t
(1.11-1.26)
1 .05 ng/t
(0.93-1.18)
1.52 ng/t
(1.38-1.67)
1.14 ng/t
(1.08-1.21)
NR
NR
NR
96-Hour
1.11 ng/t
(1.06-1.16)
NR
NR
1.08 ng/t
(1.02-1.14)
372 ng/t
(340-406)
0.75 ng/t
110-120 mg/t
Comments
temperature = 24*C
hardness =210 ng/t
temperature = 24*C
hardness = 368.4 mg/t
temperature « 24'C
hardness - 368.4 mg/t
temperature = 24*C
hardness = 368.4 mg/t
temperature = 20-23°C
hardness = 50 mg/t
temperature = 18*C
hardness = 44 mg/t
NC
Reference
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Inglls and
Davis. 1973
Berry. 1984
Mayer and
E Her sleek. 1986
Folmar, 1977
Bluntnose minnow
Plraephales notatus

Lake Emerald Shiner

Golden shiner
Notemlgonus crysoleucas
dtsodtum salt
(granular formulation)

cocoamlne salt

nonoamlne salt
(53X active Ingredient)
static
NR

flowthrough.
measured
   NR


0.12 ppm

   NR
Golden shiner             nonoamlne  salt
Notemlgonus crysoleucas    (53X active  Ingredient)
                              flowthrough.      NR
                              measured
NR


NR

NR



NR
NR


NR

NR



NR
no observed effect at
40 mg/t after 21 days

NC

120-hour LCso °-32
mg/t (0.19-0.46)
hardness = 279 mg/t

120-hour LC50 1.6
mg/t (1.2-2.0)
hardness - 20 mg/t
Folmar. 1977


Ptmental. 1971

Flnlayson. 1980



Flnlayson. 1980

o
^
•^
CO
10
Redfln shiner
Notropls lutrensls
Redfln shiner
Notropls lutrensls
Redslded shiner
Notropls umbratnis

dl sodium salt
dlsodtum salt
(granular formulation)
dtsodtum salt

static
static
static

NR
NR
NR

NR
NR
NR

95 ng/t
NR
105 ng/t

NC
no observed effect at
40 mg/t after 21 days
NC

Folmar.
Folmar.
Folmar.

1977
1977
1977


-------
TABLE 4-1 (cont.)
o
CO
o.






rs»
O
1






04/11/89
Median Response Concentration*
Species
Redslded shiner
Notropls umbratllls
Smallmouth bass
mlcropterus dolomleul
Smallmouth bass
mlcropterus dolomleul
Largemouth bass
Largemouth bass
Hlcropterus salmoldes
Hlcropterus salmoldes
Hlcropterus salmoldes
Hlcropterus salmoldes
Striped bass
Horone saxltllls
Salmon
Coho salmon
Oncorhynchus klsutch
Cutthroat trout
Salmo clarfcl
Rainbow trout
Salmo qalrdnerl
Rainbow trout
Salmo qalrdnerl
Rainbow trout
Salmo qalrdnerl

Chemical
dlsodlum salt
(granular formulation)
dlsodlum salt
(liquid formulation)
dtsodtum salt
acid
acid
dlsodlum salt
dlsodlum salt
dlsodlum salt
dlsodlum salt
(granular formulation)
dlsodlum salt
(15. 5X a.e.)
acid
Aquathol K
(40. 3X liquid concentrate)
Hydrothol 191
(53X liquid concentrate)
copper salt
dlmethylamtne salt
cocoamlne salt

Test
Method
static
static
static
NR
NR
static
static
static
static
static.
unmeasured
NR
static
static
NR
NR
static

24-Hour
NR
NR
NR
>560 ppm
NR
NR
NR
NR
NR
2000 ppm
(1850-2050)
NR
>100 mg/l
0.18 mg/t
(0.12-0.27)
NR
NR
NR

48-Hour
NR
NR
NR
NR
NR
NR
NR
NR
NR
1700 ppm
(1590-1820)
136 ppm
NR
NR
0.290 ppm
1.15 ppm
1.5 mg/t

96-Hour
NR
NR
NR
NR
120 ppm
NR
200 mg/t
100-125 mg/t
NR
710 ppm
(634-795)
NR
>100 mg/l
0.18 mg/l
(0.12-0.27)
NR
NR
NR

Comments
no observed effect at
40 mg/t after 21 days
no observed effect at
25 mg/t after 12 days
no observed effect at
10 mg/t after 12 days
NC
NC
no observed effect at
10 mg/t after 72 hours
soft water
NC
no observed effect at
10 mg/t after 21 days
temperature = 21 *C
hardness = 35 ppm
NC
temperature = 13*C
hardness = 44 mg/t
temperature » 10*C
hardness = 162 mg/t
NC
NC
NC

Reference
Folmar, 1977
Folmar. 1977
Folmar, 1977
Plmental. 1971
Plmental, 1971
Folmar. 1977
Folmar. 1977
Folmar. 1977
Folmar. 1977
Wellborn. 1971
Plmental. 1971
Mayer and
Ellersleck. 1986
Mayer and
Ellersleck. 1986
Plmental. 1971
Plmental. 1971
Folmar. 1977


-------
                                                                            TABLE 4-1 (cont.)
o
& Median Response Concentration*
g Species
Rainbow trout
Salmo qalrdnerl
Rainbow trout
Salmo qalrdnerl
Rainbow trout
Salmo qalrdnerl
Rainbow trout
Salmo qalrdnerl
Rainbow trout
Salmo qalrdnerl
Rainbow trout
Salmo galrdnerl
^ Rainbow trout
i Salmo qalrdnerl
Rainbow trout
Salrap qalrdnerl
Rainbow trout
Salmo qalrdnerl
Harlequin fish
Erlmyzon sucetta
Erlmyzon sucetta
Fowlers Toad
Bufo woodhousel fowlerl
Chemical
dl sodium salt
(granular formulation)
Aquathol K
(40. 3X liquid concentrate)
Aquathol K
(40. 3X liquid concentrate)
copper salt
(25X wet table powder)
endothall
(17. 5X granular formulation)
Endothall DES-I-CATE
(5.5X liquid concentrate)
Endothall Herbicide 282
(67. 9X liquid concentrate)
Hydrothol 191
(53X liquid concentrate)
potassium salt
(40. 3X liquid concentrate)
acid
phlsodlum salt
(liquid formulation)
dlsodlum salt
(granular formulation)
Hydrothol 191
(53X liquid concentrate)
Test
Method
static
static
static
static
static
static
static
static
static
NR
static
static
static
24 -Hour
NR
>420 mg/t
58 mg/t
(49-67)
0.35 mg/t
(0.27-0.45)
2.8 mg/t
(2.3-3.4)
0.50 mg/t
1.15 mg/t
0.81 mg/t
>560 mg/t
565 ppm
NR
NR
3.2 mg/t
(1.7-5.5)
48-Hour
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
96-Hour
NR
230 mg/t
(187-283)
32 mg/t
(22-46)
0.14 mg/t
(0.08-0.24)
1.8 mg/t
(1.2-2.5)
0.31 mg/t
0.98 mg/t
0.56 mg/t
450 mg/t
NR
NR
NR
1.2 mg/l
(0.4-3.4)
Comments
no observed effect at
10 mg/t after 21 days
temperature = 13*C
hardness = 44 mg/t
temperature = 12*C
hardness = 44 mg/t
temperature = 13*C
hardness = 44 mg/t
temperature = 12*C
hardness = 40 mg/t
temperature = 13"C
hardness = 44 mg/t
temperature = 13°C
hardness = 44 m/gt
temperature = 13*C
hardness = 44 mg/t
temperature = 13"C
hardness = 44 mg/t
NC
no observed effect at
25 mg/l after 12 days
no observed effect at
10 mg/t after 12 days
temperature = 15*C
hardness = 44 mg/l
Reference
Folmar. 1977
Mayer and
Ellersleck. 1986
Mayer and
Ellersleck, 1986
Mayer and
Ellersleck. 1986
Mayer and
Ellersleck, 1986
Mayer and
Ellersleck. 1986
Mayer and
Ellersleck. 1986
Mayer and
Ellersleck. 1986
Mayer and
Ellersleck. 1986
Plmetal. 1971
Folmar. 1977
Folmar. 1977
Mayer and
Ellersleck. 1986
2    *Values In parentheses represent 95X confidence Interval
-^
^    NR = Not reported; NC = no comment;  a.c.  = acid equivalent

-------
                              TABLE 4-2
Median Response Concentrations for Invertebrates Exposed to Endothall
GO
0.



r\J
ro
i




0
^^
^v
«^n
Median Response Concentration*
Species
Aquatic saw bugs
Asellus conrounls
Scud
Gammarus fasclatus
Scud
Ganmarus fasclatus
Scud
Gamtnarus fasclatus
Scud
Gamrearus lacustrls
Scud
Gammarus lacustrls
Scud
Gamrearus lacustrls
Scud
Gamaarus lacustrls
Scud
Hyallela azteca
Seed shrimp
Cypretta kawatal
Shrimp
Palaemonetes kadlakensts
Midge
Chlronlmus tentans
Chemical
dlpotasslum salt
cocoamlne salt
potassium salt
(40. W liquid
concentrate)
Hydrothol 47
(66. 7X liquid
concentrate)
dlpotasstum salt
endothall
dlsodlum salt
Hydrothol 191
(53X liquid
concentrate)
dlpotasslum salt
monohydrate acid
(99.9X)
Hydrothol 191
(53X liquid
concentrate)
monohydrate acid
(99.9X)
Test Method
flowthrough
flowthrough
static
static
NR
NR
static
static
flowthrough
static
static
static
24 -Hour
NR
3.1 ng/t
313 mg/l
1.50 Bg/t
(0.53-4.2)
>100 ppm
2 ppm
NR
2.00 mg/t
(1.6-2.7)
NR
180 mg/t
(141-230)
>0.10 ng/ft
354 mg/l
(161-780)
48-Hour
NR
2.1 mg/t
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
96 -Hour
NR
0.48 mg/t
313 mg/t
0.51 ng/t
(0.28-0.95)
NR
NR
>320 ppm
0.5 mg/t
(0.37-0.67)
NR
NR
0.05 mg/t
(0.02-0.12)
NR
Comments
temperature = 17°C
effective concentration
>10 ppm after 120 hours
NC
.temperature = 21 *C
hardness = 44 mg/t
temperature = IS'C
hardness = 272 mg/t
NC
NC
temperature = 59°F
temperature = 21*C
hardness = 272 mg/t
temperature = 17°C
effective concentration
>10 ppm after 120 hours
72-hour ECso =123 mg/t
(89.9-168)
temperature = 21 °C
hardness = 272 mg/t
72-hour ECso = 151
(112-203)
Reference
U1 11 lams
et al., 1984
Folroar. 1977
Mayer and
Ellersleck. 1986
Mayer and
Ellersleck. 1986
Plmental. 1971
Plmental. 1971
Nebeker and
Gaufln. 1964
Mayer and
Ellersleck. 1986
Williams
et al., 1984
Hansen and
Kawatskl. 1976
Mayer and
Ellersleck. 1986
Hansen and
Kawatskl. 1976

-------
                                                                             TABLE 4-2 (cont.)
0
co Species
n.
Stonefly
Pteronarcys callfornlca
Water flea
Daphnla maqna
Clams
Hercenarla nercenarla
Median Response Concentration*
Chemical
hydrothol 191
(53X liquid
concentrate)
acid
dl sodium salt
Test Method
24-Hour
static 5.75 mg/t
static 46 ppn
(36-57)
static NR
48-Hour
3.25 mg/t
NR
50 mg/l
96-Hour
NR
NR
NR
Comments
temperature = 15*C
hardness = 44 mg/l
26-hour median Immobili-
zation concentration
NC
Reference
Mayer and
I Hers leek. 1986
Crosby and
Tucker. 1966
Folmar. 1977
        (eggs)

       Clams
       Hercenarla mercenarla
        (larvae)

       Oyster
       Crassostrea vlrglnlca
dlsodlm salt
dlsodtum salt
static
static
NR
NR
NR
NR
NR
NR
effective concentration
>10 mg/t after 10 days
effective concentration
>25 mg/t after 12 days
Folmar. 1977
Folmar. 1977
to     *Values In parentheses  represent  95X confidence  Interval

       NC «= No comment;  NR = not  reported
 03
 vO

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Nebeker and  Gaufln  (1964) generated a  96-hour  LC5Q for scud exposed  to  the
dlsodlum  salt  of >320  ppm.   The 96-hour  LC5Q  for  scud  exposed to a  mono-
N,N-d1methyl cocoamlne  salt  formulation was  0.48  mg/l (Folmar,  1977).   The
26-hour median Immobilization concentration for Daphnla maqna exposed  to  the
acid was 46 ppm (Crosby and Tucker,  1966).
    Folmar (1976, 1978) assessed the avoidance  response of  rainbow  trout  (£.
galrdnerl)  fry  and mayfly  (Ephemerella walkerl)  nymphs  to the  dlpotasslum
salt of  endothall.   Organisms were placed  1n a flowthrough Y-shaped  avoid-
ance maze  15 minutes  before  the Introduction of endothall;  the distribution
of organisms between  each arm was  recorded  after  1 hour.   The Investigator
reported  that  neither  trout  nor mayflys  avoided  endothall at  the  highest
concentration tested (10 mg/a, active Ingredient).
4.1.2.    Chronic Effects on Fauna.
    4.1.2.1.   TOXICITY -- L1gour1   et  al.  (1983)   assessed the  effects   of
endothall  on  juvenile Chinook  salmon,  Onchorynchus tshawytscha.   Fish were
exposed  to endothall  1n  160-1  glass  aquaria that  received lake water at  a
flow rate of 1  l/mln, resulting  1n  a  complete   turnover  of   test  solution
every  5   hours.   Endothall  solutions  were dripped  Into  test  aquaria  from
MaMott  flasks  at  a rate of  1  mi/m1n.   Water  temperature  was  maintained  at
~16°C.   Endothall concentrations were measured  on  the first and  eighth days
of the  assays.   The  Investigators  reported  a  nominal  14-day   LC5Q  (and  95%
cofldence  limits) of  62.5 ppm (53.4-73.1)  as the  acid  equivalent (88.2%  ppm
of Aquathol K).  Surviving fish  exposed  to  lower concentrations of  endothall
demonstrated poor  survival when  transferred to seawater  during a  recovery
period.   F1sh  exposed to  >3  ppm endothall  for 14  days  experienced  80-100%
mortality  within 4  days  when   transferred   to seawater.    Conversely,  fish
transferred  to  freshwater  demonstrated  high  levels  of  survival   (>80%)
following  14 days of exposure to <55 ppm endothall.

0168d                               -24-                             04/19/89

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    4.1.2.2.   BIOACCUMULATION/BIOCONCENTRATION — S1kka   et    al.    (1975)
monitored  the  uptake of  14C-endothall  by blueglll sunflsh,  L.  macrochlrus.
F1sh  were  exposed  to  2  ppm  14C-endothall   1n  500 ml of  solution for  96
hours,  or  by  force-feeding  encapsulated  14C-endothall  at a  rate of  10  mg
endothall/kg bw.   The  quantity  and  distribution  of  14C  1n  force-fed  fish
was determined 48  hours after  feeding.  The  Investigators  reported  that <1%
of the  total amount  of  herbicide was taken up by  fish from water.  Fish fed
[14C]endothall   eliminated 73%  of  the  administered  dose  1n  the 48  hours
after   feeding.    The  Investigators  found  no   evidence   suggesting   that
bluegllls are capable of metabolizing endothall.
    Isensee  (1976)  assessed the  bloaccumulatlon  potential  of  endothall  In
aquatic  model  ecosystems.  Tests  were  conducted  In  glass  tanks  containing
4 i  of  water.   Before  the establishment  of test  microcosms,  soil  to  be
used  as  substrate  1n   the  system  was  treated  with  14C-endothall.    The
system  was  Inoculated with  Daphnla magna. snails  (Physa).  algae (Oedogonlum
cardlacum)  and  10  ml  of   old  aquarium  water  containing  a  variety  of
diatoms, protozoa and rotifers.  After  30  days,  2  mosqultoflsh were  added to
the  tanks  and all  organisms  were  harvested  3 days  later.   BR  values  were
based  on the  ratio  of  14C  In  tissue  versus that  1n water.   The  Investi-
gators  reported BR  values of  63, 36, 150  and 10  for  algae,  snails,  daphnlds
and fish, respectively.
    Serns (1977) reported that endothall  levels  1n tissues  of bluegllls from
a  pond  treated  with  5.0  mg/9.  potassium   endothall  were  not  detectable
(<0.01  mg/i)  3 days  after  treatment  of the pond,  despite water levels  of
4.9-3.4  mg/8.  from  days 3-10 after treatment.  Residue  levels of  0.02 and
0.04  mg/l  were  found  In  fish  tissues  2  hours  and  1  day,  respectively,
after  treatment  of the  pond.   Measured concentrations  of  endothall In the
water column for those time  periods were 6.2 and  4.9 mg/i, respectively.
0168d                               -25-                             04/19/89

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    Relnert and  Rodgers  (1986)  conducted field  trials  In Texas to  validate
models attempting  to predict the  fate of  dlpotasslum  endothall  In  natural
ponds.   They   also   attempted  to  estimate   fish BCFs  from  caged   blueglll
sunflsh, L.. macrochlrus.  held 1n  ponds treated with  2 mg/a.  The  Investi-
gators  reported  a  lack  of endothall  residues   1n  tissues  of  fish  held  1n
treated ponds  7  days after the  Initiation of treatment.  They  estimated  BCF
values  of   0.65-1.05 for   fish  from  regression  equations  using   a  water
solubility  of  1228 g/i and a log  KQW of 0.132.
4.1.3.   Effects on Flora.
    4.1.3.1.   TOXICITY  -- Walsh   (1972)  assessed  the   effects  of  the add
and amlne and  dlpotasslum  salts of  endothall on  photosynthesis  and growth of
four  species   of marine  algae,   Chlorococcum  sp.,  Dunallella  tertlolecta.
Isochrysls  galbana  and Phaeodactylum tMcornutum.   Effects  on photosynthesis
were  determined  by  monitoring   oxygen  evolution   from  log  phase  growth
cultures In the  presence  of endothall  at I0-m1nute  Intervals  for 90 minutes
on  a  photosynthesis-model  resplrometer.  Effects on growth  were determined
after  10 days for  cultures  maintained at  20°C  under  6000 lux  Illumination
with  alternating  12-hour  periods  of   light and   dark.   EC5Q  values were
calculated  based  on the  concentration  of the  product,  although the  percent
active  Ingredient  1n products used was not specified.   The  90-mlnute EC™
values  based  on  photosynthesis  for the  four  algal species  exposed  to  the
technical add  were 100,  425, 60  and  75 ppm,  respectively.   Photosynthetlc
EC,-  values  for the  amlne  and  dlpotasslum  salts for  each  species were
>1000 and >5000  ppm, respectively  for  a 90-m1nute  treatment  period.   Growth
EC5Q  values for  each spedes exposed  to  the technical  add were 50,  50,  25
and  15  ppm,   respectively,  after  90   minutes   of  treatment.   Growth EC5_
values for  species  exposed to the amlne  salt were 300,  450, 225 and  250 ppm,
0168d                               -26-                             04/11/89

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respectively,  after  90 minutes.   Growth  EC50  values for  algae exposed  to
the dlpotasslum salt  were  1500,  1500, 3000 and  500  ppm,  respectively,  after
90 minutes.
    Cain and Cain  (1983)  assessed the effects of  exposure  to  the amlne salt
of  endothall  (Hydrothol 191  as  N,N-d1methylalkylam1ne  salt,  53%)  on  zygo-
spore germination  and growth of  the  alga,  Chlamydomonas  moewusll.   Exposure
of  algal  cultures and  zygospores  to endothall  was  conducted on  1.5% agar
plates  to  which  endothall  had been  added.  Plates with  algal  cultures were
Incubated at 21°C  for 7 days  after  Inoculation.   Plates  with zygospores were
Incubated for 3 days.   Cell  counts  were  obtained by  first rinsing algae from
the  surface  of each  plate,  and  then homogenizing  suspensions   In  a  micro-
blender and  determining absorbance  readings  for  each  suspension at 565  nm
with  a  spectrophotometer.   Growth  was   expressed as  a percentage of  the
controls.    Endothall  concentrations  were  based  upon  concentration of  the
active  Ingredient.  The  Investigators  reported  I5Q  values  of  1.7 yM  for
growth  and  94  yM  for  zygospore germination.    Growth  of  cultures at  the
lowest  concentration  of   endothall   tested   (1   yM)   was   significantly
different  from the control  cultures.   The  minimum  alglcldal  concentration
was  7.5 yM  as  determined  by growth  and 9.0 yM  with respect  to  zygospore
germination.
    4.1.3.2.   BIOCONCENTRATION -- Relnert et al.  (1988) estimated  a water-
milfoil, Myrlophyllum splcatum,  BCF  for  the  dlpotasslum salt  of  endothall
from  a  regression  equation  designed for  use   In  situations  with  constant
exposure conditions for 96-120 hours.  The equation  was  generated  from data
collected  on an  aquatic   herbicide,  several organic compounds, a  floating
aquatic macrophyte and  log K  .  The Investigators   estimated a  BCF of 0.73
using a log KQW  of   0.132.   Previously, Relnert  et  al.  (1985)  and Relnert


0168d                               -27-                             04/19/89

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and Rodgers  (1986)  reported experimental BCF  values  of 3.9, 12.1  and  768.9
for  dlpotasslum  endothall  from  studies  conducted  with  milfoil  1n  1.1  m
diameter greenhouse  pools.  The Investigators discounted the 768.9  value  as
unrealistic  because  of  the   Inadvertent   analysis   of  endothall-tolerant
epiphytic algae present on the milfoil.
4.1.4.   Effects  on  Bacteria.   Pertinent  data  regarding  the  effects  of
exposure of aquatic  bacteria  to endothall were not located  In  the available
literature dted 1n Appendix A.
4.2.   TERRESTRIAL TOXICOLOGY
4.2.1.   Effects  on  Fauna.    Pertinent   data  regarding   the   effects   of
exposure of terrestrial fauna  to endothall were not  located  In  the available
literature cited 1n Appendix A.
4.2.2.   Effects  on  Flora.    Pertinent   data  regarding   the   effects   of
exposure of terrestrial flora  to Endothall were not  located  1n  the available
literature cited In Appendix A.
4.3.   FIELD STUDIES
    Yeo  (1970) assessed the effects  of the dlsodlum  or  dlpotasslum salts  of
endothall on aquatic weeds  and  fish  In 13 farm reservoirs  and plastic growth
pools  (122  cm2x60  cm deep)   stocked with  common  vegetation,  smallmouth
bass,  green  sunflsh  and  mosqultoflsh.  Calculated  Initial  concentrations
were  <3  ppm  1n  reservoirs  and <4  ppm 1n growth pools.  The  Investigators
reported  that  application  of endothall  to  the  reservoirs  controlled  a
variety  of  pondweeds  and  other  plants  but  did  not  affect populations  of
elodea,  duckweed, nHella and  chara.   The Investigators did  not  observe  any
mortalities  among  the  smallmouth  bass,  green   sunflsh   or  mosqultoflsh.
Effects  on  vegetation  In  growth  pools  were  similar to  those  observed  1n
reservoirs.  There were no  mortalities among bass and sunflsh  1n the growth


0168d                               -28-                             04/11/89

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pools;  several  mosqultoflsh  were  killed,  but  the  Investigators  did  not
attribute the mortalities to the endothall treatment of the pools.
    Serns (1975)  assessed  the effects of  the dlpotasslum salt  of  endothall
on  the  zooplankton community  of a 0.31  ha  pond  1n Wisconsin.  Control  and
treatment ponds  were  drained before  treatment  to  eliminate existing  fish
populations, and  were  then  allowed  to  refill from  a common  source.   Both
ponds were  restocked with  blueglll  sunflsh  at  a  rate of  20 males and  20
females  per hectare.  Dlpotasslum endothall was added  to  one of the ponds at
a  rate  of  5 mg/8.  (active  Ingredient)  at  the  end  of May  1973,  and  both
ponds were  monitored through  the  end  of  October  1973.   The  Investigators
reported  the presence  of  Cladocera  (Daphnla. CeModaphnla and  Chydorus).
cyclopold and  calanold  copepods,   and  ostracods   In  the  treatment  pond  at
densities equal   to  or  greater  than  those  found  1n  the  control  pond  at
various   times   over  the  course of  the   study  period.    The  Investigator
concluded that  there  no apparent effects  on  zooplankton  communities  In  the
pond as  a result of treatment with dlpotasslum endothall at 5 mg/fi,.
    Holmberg and  Lee (1976)  treated  a  0.32  ha  pond  with 5.0  mg/l  (active
Ingredient)   endothall.    The  Investigators  monitored  effects  on  vascular
plants  and  caged  and  natural  populations of  blueglll  sunflsh, L_.  macro-
chlrus.    Endothall  treatment effectively  eliminated  coontall,  Ceratophyllum
demersum. flat-stemmed  pondweed, Potamogeton zosterlformls.  sago  pondweed,
Potamogeton  pectlnatus.  milfoil, MyMophyllum  splcatum,  and  elodea,  Elodea
canadensls.   within  3  weeks of  treatment  at the  recommended  dosage.   The
treated   pond  was  eventually  taken  over  by chara,  Chara  sp.  There were  no
mortalities  among either  free  or caged bluegllls  at  the  endothall  treatment
level of 5 mg/8. within a few weeks following treatment.
0168d                               -29-                             04/19/89

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    Serns (1977) reported the results  of  long-term observations  of bluegllls
exposed  to  endothall   as  part  of  a  continuing  study  first  reported  by
Holmberg and Lee  (1976).   Bluegllls  were collected from control  and  treated
ponds  18 months  after  the  Initial   application  of  5 mg/a  of  endothall.
Percent survival of  bluegllls  stocked 1n the two  ponds  before treatment was
greater  1n  the control  pond than  1n  the  endothall-treated  pond,  although
growth  of  adult bluegllls  1n the  treated pond  was  less  than  that  1n  the
control pond.   The  difference was attributed  to  competition  as  a  result  of
greater density of  fish,  rather than  to a  toxic effect  from  exposure  to
endothall.   Length, weight, density and  standing  crop  of  young-of-year blue-
gills  spawned  In  both  ponds during  the observation period  were  equivalent;
there  were  no  perceptible  effects   on  reproduction  or  survival  of  first
generation  bluegllls.
    Beckmann et al.  (1984)  assessed  the  effects  of the dlpotasslum  salt  of
endothall on the  bacterial  populations  In  gravel-pH  ponds over  ~4  months.
Parameters  measured Included total bacterial numbers In  the water column and
respiration rates  of bacteria  collected from  the treated  pond.   Endothall
was  applied  to the  treatment pond  at a  target   concentration  of 0.3  ppm.
Respiration rates  were measured  1n  the  presence of  5 ppm endothall.   The
Investigators  reported  that  endothall  had  no  effect on total  bacterial
numbers present 1n  the control  and  treated ponds and  did  not significantly
alter respiration  rates of bacteria found 1n those ponds.
4.4.   AQUATIC  RISK ASSESSMENT
    The majority  of  studies assessing  the  toxldty of endothall  to  aquatic
organisms are  not  suitable for  use  1n developing water quality  criteria  by
the method of U.S. EPA/OWRS  (1985).   In many  Instances,  Investigators failed
to  Identify  the endothall salt  present  In  a formulation Identified  only  by

0168d                               -30-                             04/24/89

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Us tradename,  the  percentage  of active Ingredient 1n an  endothall  product,
the "Inert"  Ingredients 1n  an  endothall formulation, or  the material  upon
which an  LC5Q was  calculated  (formulation  or active  Ingredient).   Criteria
generated by  the method of  U.S. EPA/OURS  (1985)  do  not  permit the  use  of
data generated on formulated mixtures and emulslflable concentrates.
    Apparently,  the sodium  and  potassium  salts  are often  used  1n  field
treatments  for nuisance aquatic weed  control at  treament  dosages  of  2-5
mg/a..    The  acute  toxlclty  of  these   salts  appears   to  be   >100  mg/l,
suggesting a  low order of toxlclty  under  normal  use  conditions.   Addition-
ally,  experimental  evidence  suggests  that  the sodium and  potassium  salts  of
endothall are  not persistent  and do not bloaccumulate In  aquatic  organisms,
thereby reducing the potential for chronic exposure.
4.5.   SUMMARY
    The potassium and  sodium salts of endothall are  the  forms least  toxic  to
both  aquatic   vertebrates  and   Invertebrates,  with   96-hour  LC  s  of  >100
mg/i.    In  contrast, 96-hour  LC5Qs   for  the  amlne  and  copper  salts are  <1
mg/i for  a  variety  of  aquatic  organisms.   Water  hardness  did not  Influence
the toxlclty  of dlsodlum  or  dlamlne salts  to bluegllls  (Inglls and  Davis,
1973)  and pH  did not  affect  the toxlclty of Aquathol K to  bluegllls  (Mayer
and  Ellersleck, 1986).   The  toxlclty   of  Aquathol   K  to  blueglll  sunflsh
Increased 5-fold when  the  test  temperature  Increased from  7  to  24°C  (Mayer
and Ellersleck, 1986).
    The  14-day LC5Q of endothall to juvenile Chinook  salmon,  Onchorynchus
tshawytscha.  was  62.5  ppm (LlgouM  et  al.,  1983).   Surviving  fish  demon-
strated  poor  survival   when  transferred  to seawater  but good survival  when
transferred to freshwater.   The 10-day  growth  EC5Qs  for  various  species  of
marine algae exposed to the  amlne and dlpotasslum  salts  ranged from 225-3000
0168d                               -31-                             04/11/89

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ppm  (Walsh,  1972).   No  short- or  long-term  effects  were  observed  among
natural  populations  of  organisms   1n  ponds  or  reservoirs  treated with  <5
mg/8, endothall.
    Experimental evidence  suggests  that endothall 1s  not  likely to bloaccu-
mulate  In  aquatic  organisms.   Slkka  et al.  (1975)  reported  that  bluegllls
took  up <1%  of  the available  herbicide  from water  over  a  96-hour  period.
Isensee  (1976)  reported bloaccumulatlon  ratios  of  63, 36,  150 and  10  for
algae,  snails,  daphnlds  and  fish.    Serns   (1977)   was  unable  to  detect
endothall residues 1n tissues of bluegllls  from a pond that had been treated
3  days  earlier with  endothall  to  give a  concentration of 5  mg/l.   Relnert
and Rodgers  (1986) were unable to detect  endothall   residues  In  tissues  of
bluegllls  from a  reservoir  that  had  been treated  7  days  earlier  with  2
mg/B,  endothall.    Relnert   et  al.   (1988)   reported  BCFs  of   3.9,  12.1  and
768.9 for  the dlpotasslum  salt  of  endothall  1n  watermllfoll,  but  discounted
the highest value because of experimental  errors.
0168d                               -32-                             04/19/89

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                              5.  PHARMACOKINETICS
5.1.   ABSORPTION
    Six adult Wlstar  rats  weighing 250-260 g (two males)  or  172-206 g (four
females)  were  prefect  diets   containing  unlabeled endothall  (5  ppm) for  2
weeks   before   single   gavage  administration   of    14C-labeled   endothall
dissolved  1n  20%  ethanol  (5  mg/kg)  (Soo et  al.,  1967).   As  Indicated  1n
Section  5.4.,   total   recovery  of  radioactivity  1n  the  feces,  urine  and
expired CO-  at 48 or 72  hours following  treatment ranged  from  95.7-99.1%
of  the administered  dose.   Most  of  the  radioactivity,  84.8-91.1%  of  the
administered dose,  was excreted 1n  the  feces,  and  the  balance  was  excreted
1n  the urine (5.7-6.9%) and expired COp.   Approximately  20% of  the radio-
activity  1n  the  feces  was  shown   to  be  unchanged  endothall,  with  the
remainder  bound  In  some  unknown  form  (Section  5.3.).   The  Investigators
presumed  that the  remaining  radioactivity was due to an  endothall  conjugate.
However,  since  bound  endothall 1n the  feces does not necessarily mean  that
the endothall was  conjugated, and  biliary excretion  of  endothall  appears  to
be  Insignificant  (Section  5.4.),  U seems  likely  that  the  bound endothall
was unabsorbed  endothall  that  was adsorbed onto  gastrointestinal contents.
Low levels of  radioactivity  1n tissues other than the stomach and .Intestine
and slow  tissue elimination  rates also seem to  Indicate  that  only  a small
proportion of the  administered  dose  was  absorbed  (Section  5.2.).  Therefore,
results of  this study  suggest that   endothall  was poorly absorbed  from the
gastrointestinal  tract.    Intestinal  diffusion  or  secretion of  endothall,
however, or conjugation of endothall  1n the Intestines could have occurred.
    An  additional  nine female Wlstar  rats  were given 1 mg  of 14C-endothall
by gavage, and were killed at 1,  2,  4,  6,  8, 12, 24, 48 or 72 hours.  Eleven
different organs  were removed and freeze-drled,  and  their radioactivity was

0168d                               -33-                             04/19/89

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measured.  Analysis  of  the specific radioactivity and  total  accumulation  In
each tissue  Indicated that only a small proportion of  the  administered  dose
was absorbed.  Peak  tissue concentrations of  radioactivity  were  found  In the
animal  that  was  sacrificed  1  hour after  treatment  (Section  5.2.).   This
Indicates  that  absorption  of   endothall  occurred largely  within the  first
hour.
5.2.   DISTRIBUTION
    Nine female Wlstar  rats  were given  1  mg of 14C-endothall by  gavage and
sacrificed at  1,  2,  4,  6, 8,  12,  24,  48  or 72  hours (Soo et  al.,  1967).
Peak  tissue  concentrations  of  radioactivity  were   reached In  all  of  11
tissues  sampled  except  the  Intestine  within  1  hour  posttreatment.   The
radioactivity was  highest  1n  the stomach  and Intestine (-98% of  the  admin-
istered dose).  Approximately 1% of the administered dose  was found  In  both
the  liver  and  kidney;  trace  amounts  were found  1n  the blood,  lung,  heart,
spleen,  muscle  and  brain.   Radioactivity  was  not   detected 1n  body  fat,
reflecting the hydrophlUc nature of the compound.   Clearance was monophaslc
from  the  Intestine  (half-time  of  14.4  hours)  and liver (half-time of  21.6
hours), and blphaslc from  the stomach  (half-times  of  2.2 and 14.4 hours) and
kidney  (half-times  of 1.6 and  34.6 hours).   No residual  radioactivity  was
seen at 72 hours 1n any  organ  other  than the Intestine.
    In  order  to determine the  possible secretion of Ingested endothall  In
milk, two pregnant female  rats  were given  unlabeled  endothall (0.2 mg/day In
10% sucrose) by means of a medicine dropper  for  the  last week of gestation,
and were  then  given 14C-endothall  (0.4  mg/day In 10%  sucrose solution)  for
5  days  after  the  pups were born.   Analysis of  stomach  contents  and  tissues
of  12  pups   of  various  ages   showed  no  radioactivity,   suggesting  that
endothall was not  secreted In  the milk  of a lactatlng female rat.


0168d                               -34-                             04/19/89

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5.3.   METABOLISM
    Six  rats  that  were  administered  5  mg/kg  14C-labeled  endothall  by
gavage  excreted  84.8-91.1% of  the administered  radioactivity 1n  the  feces
(Soo et  al.,  1967) (Section  5.4.).   Alcohol  extraction and  paper  chromato-
graphy  of  the  feces showed that  "20% of the fecal radioactivity was  due to
unchanged  endothall  and 80%  was  bound  In  some form  (I.e.,  unextractable).
The  Investigators   presumed  that  the  latter  radioactivity  was  due  to  an
endothall  conjugate.   As  biliary   excretion   seems   to   be  Insignificant
(Section 5.4.),  U 1s  likely that the  bound  endothall was  not  conjugated,
although conjugation  1n the  Intestine  could  have occurred.   Urinary  radio-
activity accounted  for  5.9-6.9% of  the  administered  dose.   The radioactivity
recovered  1n the  urine appeared  to  be unchanged endothall.   A  small  amount
of  the  administered   radioactivity  (2.6-2.8%)  was  converted  to  CO,,  and
expired  1n the breath.  Since gastrointestinal  absorption  of  endothall  seems
to  be  poor,  It Is  possible that  the  CO- resulted from metabolism  by  Intes-
tinal microorganisms.   There  were no apparent  gender-related differences 1n
the fate of endothall.
5.4.   EXCRETION
    A 5  mg/kg  dose of  14C-endothall  was administered to  six  rats  by  gavage
(Soo et  al., 1967)  (see Section  5.1.).   Radioactivity  1n  the  feces  accounted
for 64.5-71.2, 17.7-20.7 and  0.1-0.5% of the administered  dose  after  24, 48
and 72  hours, respectively.   Since  levels of radioactivity In the liver  were
not  very large compared with the administered  dose (see  Section  5.2.), 1t
was concluded that  biliary excretion  does not  seem to  be  significant.   Dally
recovery of  radioactivity  1n the urine accounted  for  3.4-6.8,  0.3-0.6 and
0.1-0.2% of  the  administered  dose after 24, 48  and  72  hours, respectively.
0168d                               -35-                             04/19/89

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Less  than  3% of  the  administered dose  (2.6-2.8%)  was  found 1n  expired  CO-
after 24  hours;  radioactivity 1n  the  expired  air was not detected  after  48
and  72  hours.   Excretion  1n  the  feces, urine  and expired air,  therefore,
occurred  largely  1n the first 24 hours  and  was essentially complete  after
48-72  hours, as  total  recovery  varied  from  95-99%.   Endothall  was  not
excreted 1n the milk (see Section 5.2.).
5.5.   SUMMARY
    Data obtained from rats  of both  sexes  treated with  a single oral dose of
14C-endothall suggest  that  gastrointestinal absortlon  1s  poor  (Soo  et  a!.,
1967).  Peak  tissue concentrations  occurred  within  1   hour  In  all  tissues
sampled except  the  Intestine.  The absorbed radioactivity  occurred  predomi-
nately  1n  the stomach and  Intestine  (~99% of  the administered  radioactiv-
ity).  About  1%  of  the administered radioactivity  occurred  1n  the liver  and
kidneys.   Radioactivity  was  not  found In fat  or milk, and was  essentially
eliminated from  all  tissues  within 72 hours.   At  least 85% of  the  adminis-
tered dose was  excreted 1n  the  feces, but ~20%  of this was unchanged  com-
pound and  80% was bound In  some  form.   It  seems more likely that  the  bound
form  1s  endothall  that  Is  adsorbed  onto  gastrointestinal  contents  rather
than  an  endothall conjugate.  Small  quantities  were excreted  1n the  urine
(~6%), apparently as unchanged compound, and 1n the  breath  as CO- (~3%).
0168d                               -36-                             04/19/89

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                                 6.  EFFECTS
6.1.   SYSTEMIC TOXICITY
6.1.1.   Inhalation  Exposure.   Pertinent  data  regarding  the  effects  of
Inhaled  endothall  were  not  located  1n  the  available  literature  cited  1n
Appendix A.
6.1.2.   Oral Exposure.
    6.1.2.1.   SUBCHRONIC — Rats  were  given  1000  or  10,000  ppm  d1sodium
endothall  1n the diet  for  4 weeks (BMeger, 1953a).  Using  a  body  weight  of
0.4 kg,  a dally food  consumption of  20  g,  and  the  ratio of  the  molecular
weight of  endothall  to dlsodlum endothall,  these concentrations  can  be  con-
verted  to  equivalent   doses   of  endothall  1on  of  40  mg/kg/day  and   400
mg/kg/day.  At  the  low dose,  there were  slight  liver degeneration  and  focal
hemorrhaglc areas  In the kidney.  At  the high dose, most of  the  rats  died
within 1 week.
    Nine male dogs  (one  dog per  dose) were  given capsules  containing 1-50 mg
dlsodlum  endothall/kg/day  (0.8-40  mg/kg/day of  endothall  1on) for  6 weeks.
01 sodium  endothall  doses  of  >20  mg/kg/day resulted  1n  death  1n  all  dogs
within 11  days, and  erosion and  hemorrhages of  the  stomach (Brleger,  1953b).
Congestion of the stomach and edema  of  the  stomach  and  upper Intestines  were
common  1n all   dogs.   The  Investigators  suggested that  the lesions In  the
stomach  of dogs  resulted  from the  administration  of the  undiluted  test
substance without food.
    6.1.2.2.   CHRONIC — Beagle dogs (four/sex/group)  were  fed 0,  100,  300
or  800  ppm dlsodlum endothall  1n  the  diet (equivalent  to 0, 2, 6  or 16  mg
endothall  1on/kg/day)  for  24 months  (Keller,  1965; Pennwalt  Agchem, n.d.).
Values for hematology,  BSP  clearance, SGOT, urlnalysls,  weight  gain and  food
consumption  1n  treated animals  were  not   significantly   different   from


0168d                               -37-                             06/19/89

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controls.   Relative  and absolute  stomach and  small  Intestine weights were
Increased at  the two  higher doses,  but  extensive hlstopathologlcal  exami-
nation  of  rats  receiving  the  highest   dose   revealed  no  compound-related
lesions,  except  Increased  mucosal  gland  activity  In  the stomach and  slight
edema In the region  of the pylorls.   No effects  were  noted  at 2 mg/kg/day.
    No  toxic  effects were noted  1n female  rats  (strain unspecified)  given
<2500 ppm d1 sodium   endothall  1n the  diet for  2  years  (equivalent  to 100
mg/kg/day of  the endothall  1on  assuming  food  Intake of  20 g/day  and mean
body weight of 0.4 kg) (BMeger,  1953b).
6.1.3.   Other   Relevant   Information.    A  suicide   occurred  with   acute
1ngest1on of  -100 mg endothall  1on/kg (Allender,  1983).  Repeated  vomiting
was  consistent  with  1ngest1on  of  an Irritant.   The autopsy showed  focal
edema and focal  hemorrhages  In the  lungs  and gross hemorrhage of  the  gastro-
intestinal tract.
    Male  Swiss-Webster  mice,  weighing 20-25 g  (numbers  not  specified), were
Injected  IntraperUoneally with  a  single  dose  of  75 mg/kg  endothall  and  10
mg/kg cantharldlc  add  (Grazlano  and Caslda,  1987).   (Cantharldlc  acid  1s
similar  In  structure  to endothall  and both compounds cause  similar  signs  of
acute toxlclty.)  This  dose was  lethal, usually producing  death within 60-90
minutes.   Animals  that  were  sacrificed   by  cervical dislocation  after   45
minutes  had  significantly Increased  liver  weights  (-36%)  and  hepatic  hemo-
globin  levels (~100%).   Hepatic  glycogen  metabolism  Increased,  while  hepatic
ATP concentrations decreased.  No  changes  were  seen  1n  hepatic GSH  content,
mlcrosomal I1p1d peroxldatlon, hepatic trlglycerldes  or  SGPT  levels.
    An  oral  (gavage) LD,.  for  adult  Sherman   rats  was reported  to be   57
mg/kg  for males  and 46  mg/kg  for  females for  the add form (Galnes and
Under,  1986).   In  another  study  with  rats,   the  ID™  for  orally  admin-
istered  endothall 1n the add form was  38-51   mg/kg  and as  the sodium salt

0168d                               -38-                              06/19/89

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was 182-197 mg/kg  (Slmslman  et al., 1976;  Worthing  and Walker,  1983).  The
Intraperltoneal L05Q  for mice  was  reported  to  be  14  mg/kg for  the add
form (Matsuzawa et al., 1987).  An Intravenous Injection of 5 mg/kg d1sodium
endothal 1s fatal  to dogs and rabbits (Goldstein, 1952; Srensek and Woodard,
1951).
6.2.   CARCINOGENICITY
6.2.1.    Inhalation.    Pertinent  data   regarding   the  cardnogenlclty  of
Inhaled  endothall   were not  located 1n  the  available  literature  dted  1n
Appendix A.
6.2.2.    Oral.  No  statistically  significant  Increase 1n number  of   tumors
was seen  In  rats  fed diets  containing  2500 ppm d1 sodium endothall (equiva-
lent  to  endothall  1on  at   100  mg/kg/day)  for   2  years  (Brleger,  1953b);
however,  this  study  probably did  not  use  contemporary   cancer  testing
methodology.
6.2.3.    Other   Relevant   Information.    Endothall   was    positive    for
transformation In BALB/c 3T3 cells (Litton  B1onet1cs,  1981).  Pertinent data
regarding the  cardnogenlclty of endothall  administered by other routes were
not located 1n the available  literature  dted  1n  Appendix A.
6.3.   MUTAGENICITY
    Endothall  was not mutagenlc 1n  S.  typhlmuMum with or without metabolic
activation  (Table  6-1)  (Andersen  et al.,  1972;  Remondelll  et  al.,   1986;
Microbiological  Associates,   1980b),   In   Neurospora  crassa  (Sandier  and
Hamllton-Byrd, 1981), and for sister chromatld exchange  1n human lymphocytes
(Vlgfusson, 1981).   Mixed  results were  obtained 1n Drosophlla melanogaster
(WHson et al., 1956; Sandier and  Ham1Hon-Byrd,  1981).
6.4.   TERATOGENICITY
    Pregnant  rats  (25-26 group) were given oral doses  of  0, 10,  20  or  30
mg/kg/day  of   aqueous  endothall  technical  (0,  8,  16  or  24 mg  endothall

0168d                               -39-                            06/19/89

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                                                                                       1ABIF 6-1

                                                               Mulagenlclty  and  Genotoxlcily Summary lable for Endothall
00
o.
Assay
Reverse mutation

Reverse mutation
Reverse mutation


forward mutation

Mutagcnlcity assay

i
g Sister chromatld
i exchange
Point mutation

Sex-linked
recessive lethal

Sex-linked
recessive lethal

Indicator/Organism
Salmonella typhlmurlum
8 mutants
S. typhlmurluro
S. typhlmurlum
TA98. TA100. TA1537.
TA9?. 1A2637
S. typhlmurluro
1A98, 1A100
Neurospora crassa


human lymphocytes

BALB/313 clone A31
mouse cells
Orosophila melanoqaster


D. melanogaster


Purity
technical

technical
technical


technical

?8.6X acid
equivalent

28. 6X acid
equivalent
technical

"commercial"


28.6% acid
equivalent

Application
plate

NR
plate Incorpora-
tion

tube Incubation

NR


cell culture

cell culture

vapor exposure
of adults and
larval feeding
NR


Concentration/Dose
1-5 pi

NR
<5.0 ing/plate


NR

NR


NR

NR

vapor. NR/feeding.
100 and 250 ppm

NR


Activating Response
System
»S9
-
,S9 - 1
fS9 - 1
-

»S9 - 1
-
NR - '
1

NR

none - 1
i
NA * (both vapor 1
and larval)

NA
1
                                                                                                                                                           Reference
                                                                                                                                                      Andersen el  al.,
                                                                                                                                                      197?

                                                                                                                                                      Microbiological
                                                                                                                                                      Associates,  1980a

                                                                                                                                                      RemondelII et al.,
                                                                                                                                                      1986
                                                                                                                                                      Remondel11  et  al..
                                                                                                                                                      1986

                                                                                                                                                      Sandier  and
                                                                                                                                                      Hamilton-Byrd, 1981

                                                                                                                                                      Vigfusson.  1981
                                                                                                                                                      Microbiological
                                                                                                                                                      Associates,  1980b

                                                                                                                                                      Wilson et  al..  1956
                                                                                                                                                      Sandier  and
                                                                                                                                                      Hamllton-Byrd,  1981
             *It was unclear  whether  positive result occurred both with and without metabolic activation.

             NR =  Not reported;  NA  =  not applicable
CD
CD

-------
1on/kg/day)  on  gestation   days  6-19  (Science  Applications,  Inc.,   1982).
Maternal deaths  occurred at  the  two higher  doses,  but  the  fetuses  of  the
surviving  dams  exhibited  no  signs  of  teratogenldty  or fetotoxldty.   No
effects were observed on the dams or fetuses  at  the  low dose.   A  NOAEL  of 10
mg endothall  technlcal/kg/day  (8  mg/kg/day of endothall  1on) was  Identified
from this study for teratogenlc effects  based  on  maternal  effects.
6.5.    OTHER REPRODUCTIVE EFFECTS
    Hale and  female  rats were  fed diets containing dlsodlum  endothall  at 0,
100,  300 or  2500 ppm (equivalent  to 0. 4,  12 or 100 mg/kg/day of  endothall
1on)  until they  were 100 days  old (Scientific Associates, 1965).   They were
mated  and  the offspring  were maintained  on  the  same  diet,  again for  100
days, when they were mated.  The  third generation was treated similarly.   At
the  low  dose,  there was no effect;  at  the middle  dose level, the pups  had
reduced  body  weights at 21  days  of age.   At the  high dose, the  pups  died
within  1  week  of  birth and  this  dosage was  discontinued.  A  NOAEL  for
reproductive effects of 4 mg 1on/kg/day  was Identified.
6.6.    SUMMARY
    Minimal  data  were  located In   the  available  literature regarding  the
health  effects  of  endothall.   Acute toxlclty appears  to be  substantially
greater  for  the  add  form  than  for the  dlsodlum salt.   Oral LD5Q  values
for  rats of  38-57 mg/kg have  been  reported for  the add  form  (Worthing  and
Walker,  1983;  Galnes  and Under,  1986)  and 182-197 mg/kg have  been reported
for  the  dlsodlum salt.   Acute exposure  to  large doses  Is extremely Irritat-
ing  and causes   erosion  and  hemorrhage   of  the  stomach  (Allender,   1983;
Brleger, 1953b).
    Subchronlc  data suggest  that  dogs  may be  more  sensitive  than rats  to
oral exposure  to endothall.  In  a  dietary study,  rats  succumbed  to  dosages


0168d                               -41-                             06/19/89

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of  the  Ion of  400  mg/kg/day and  exhibited liver and  kidney lesions  at  40
mg/kg/day  (Brleger,  1953a).   Dogs  treated  by capsule,  however,  died  at  20
mg/kg/day d1sodium endothall  (16 mg/kg/day  endothall  Ion)  and had congestion
and  edema  of  the   stomach  at  0.8  mg/kg/day  of  endothall  Ion  (Brleger,
1953b).   The  Investigators  suggested  that  the  lesions  1n  the  stomach
resulted from the administration of the undiluted test solution without food.
    There are notable discrepancies between  the  subchronlc and chronic data.
For example,  no  toxic  effects were reported  1n  a  2-year  dietary  study where
rats were  exposed  to 2500 ppm dlsodlum endothall  (100  mg/kg  bw/day of endo-
thall Ion)  (Brleger, 1953b).  In a  2-year  dietary  study using dogs (4/dose),
elevated  relative  and  absolute  stomach  and  small  Intestine weights  were
Increased with dlsodlum  endothall  at  300 and  800 ppm (6  and  16 mg/kg/day  of
endothall  1on),  but  no  effects  were observed  at 100  ppm  (2 mg/kg/day of the
1on) (Keller, 1965; Penwalt Agchem, n.d.).
    Developmental toxlclty studies using rats  suggest that the dams are more
susceptible  than the fetuses  to oral  administration of  endothall  (Science
Applications, Inc.,  1982).   In  a dietary study, pregnant  rats were given  0,
8, 16 or  24 mg  endothall  1 on/kg/day on gestation days 6-19.  Maternal deaths
occurred  at  the  two higher  doses but  the  fetuses  of  the   surviving dams
exhibited   no  signs  of  teratogenlclty  or  fetotoxldty.   A  NOAEL  of   8
mg/kg/day  was  Identified  from  this  study  for  teratogenlclty  based  on
maternal effects.
    In a  3-generatlon reproductive  study, no effects  were observed when rats
were  exposed  to dlsodlum endothall  1n  the diet that  provided  a  dosage  of
endothall  1on at  4  mg/kg/day  (Scientific  Associates, 1965).   In  the same
3-generat1on  study,  however,  pups  In  the 12 mg/kg/day group had reduced body
weights and pups In 100 mg/kg/day group died within a week of  birth.


0168d                               -42-                             06/19/89

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    Endothall  has not been adequately tested for  carclnogenldty.   There was
no evidence of  cardnogenlcHy  In  rats  fed diets containing dlsodlum  endo-
thall at <2500  ppm  (100 mg/kg/day of  the  1on)  for 2  years  1n an  early  study
(Brleger, 1953b).   Endothall Induced  malignant transformation of  BALB/c 3T3
cells  (Utton   B1onet1cs,  Inc.,  1981).    Endothall  was  not  mutagenk   1n
microorganisms    (Andersen   et   al.,   1972;   RemondelH   et   al.,   1986;
Microbiological  Associates, 1980a;  Sandier  and Ham1lton-Byrd,  1981) and  In
human  lymphocytes  (Vlgfusson,   1981).    Mixed  results  were  obtained   1n
Drosophla (Wilson et al.,  1956;  Sandier and Ham1lton-Byrd,  1981).
0168d                               -43-                             06/19/89

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                            7.   EXISTING GUIDELINES
7.1.   HUMAN
    The verified IRIS oral  RfD  1s 0.02 mg/kg/day  (U.S.  EPA,  1986d),  based on
a  NOEL  for  gastrointestinal  effects  In  dogs  In  a  2-year  feeding  study
(Pennwalt Agchem, n.d.;  Keller,  1965).
    U.S. EPA  (1987a)  derived a Lifetime Health  Advisory of 0.14  mg/l  based
on  the  ADI  set by U.S.  EPA Office  of Pesticide Programs of 0.02  mg/kg/day.
The 1- and 10-day  HAs  for  a 10 kg  child are 0.8 mg/l  based on  a  NOAEL  of 8
mg/kg/day for  the  absence  of fetal  and  maternal  effects 1n rats  exposed to
endothall acid orally for 13 days (Science Applications,  1982).  The DUEL 1s
0.7 mg/l  based  on  the  2-year  study using  dogs  (Keller, 1965).   Endothall
1s  Included In a 11st of 83 chemicals required to be regulated by  the Agency
under a 1986 amendment of the Safe Drinking Water  Act (U.S.  EPA,  1987b).
    An Interim tolerance of 0.2 ppm has been established  for  Its residues 1n
potable  water  resulting  from  use   of  endothall  salts  to  control  aquatic
plants  (U.S.  EPA,  1987c).   Tolerances In raw agricultural commodities  are
0.1 ppm 1n cottonseed and potatoes  and 0.05  ppm  1n rice grain  and  rice straw
(U.S. EPA, 1982).  The RQ 1s 1000 (U. S.  EPA, 1985).
7.2.   AQUATIC
    Guidelines  and  standards  for   the  protection  of  aquatic  life  from
exposure to endothall were  not  located In the available  literature  cited In
Appendix A.
0168d                               -44-                             06/19/89

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                             8.  RISK ASSESSMENT

    Statements  concerning  available  literature  1n  this  document  refer  to
published, quotable sources and  are  1n  no way meant  to  Imply  that  confiden-
tial business  Information  (CBI), which this  document could not address,  do
not exist.  From examination of  the bibliographies of the  CBI  data,  however,
1t  was  determined  that CBI  data  that  would  alter  the  approach  to  risk
assessment or the risk assessment values presented herein do not exist.
8.1.   CARCINOGENICITY
8.1.1.    Inhalation.   No  data  were  available  to  assess  the  carcinogenic
potential  of endothall by  the  Inhalation route.
8.1.2.    Oral.  Rats  fed <100 mg 1on/kg/day for  2 years had no significant
Increase 1n number of  tumors (Brleger, 1953b).
8.1.3.    Other  Routes.  No  data were  available  to  assess the  carcinogenic
potential  of endothall from other routes.
8.1.4.    Weight of  Evidence.  No data were available  regarding  the  carclno-
genldty  of  endothall In humans.   Rats fed <100 mg  lon/kg/day for 2  years
had no  significant  Increase In  number  of  tumors (Brleger, 1953b), but  the
adequacy  of  this  study as  a cancer  bloassay cannot   be  evaluated because  of
the lack  of  the primary report.   Also, H  1s  likely that this early  study
did not  use contemporary cancer testing methodology.   The animal  data  are
Insufficient.  Therefore,  endothall Is  assigned  to  EPA Group D, not classi-
fiable as  to human cardnogenlclty  (U.S. EPA, 1986a).   This   1s consistent
with the  classification assigned  by  the Agency 1n  an earlier evaluation
(U.S.  EPA, 1987a).
8.1.5.    Quantitative   Risk  Estimates.    No  q^*  can   be   derived  because
endothall  1s assigned  to EPA Group  D.


0168d                               -45-                             04/19/89

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8,2.   SYSTEMIC TOXICITY
8.2.1.   Inhalation  Exposure.   No  data   were   available  to  assess   the
systemic toxldty of endothall from Inhalation.
8.2.2.   Oral Exposure.
    8.2.2.1.   LESS THAN  LIFETIME  EXPOSURE (SUBCHRONIC) — Subchronlc  oral
data  consist  of a  4-week  study using  rats and a  6-week study using  dogs.
These studies were  available  only  as very  brief reviews  by  U.S. EPA  (1987a)
of  the  Confidential Business  Information  (CBI)  studies  from  the  Office  of
Pesticides  Program files.   In  the rat  study,  dietary  dlsodlum  endothall
provided dosages  of endothall 1on  of  40  or 400 mg/kg/day  (BHeger,  1953a).
Most  rats at 400 mg/kg/day died  within  1  week;  liver  degeneration  and hemor-
rhaglc  areas  1n  the  kidneys  were  reported at  40  mg/kg/day.   Dogs  treated
with  dlsodlum endothall  1n  capsules died  and had erosions  and  hemorrhage 1n
the  stomach at  doses  >20  mg/kg/day  (16  mg/kg/day  of  the 1on)   (Brleger,
1953b).  Stomach  lesions were observed at  1  mg/kg/day  dlsodlum  endothall,
the lowest dose tested.  The  Investigators  suggested  that the  lesions 1n the
stomachs of dogs at very low  dosages resulted  from  the  administration of the
undiluted test material without  food (U.S.  EPA, 19866).  These data  suggest
that  dogs  are more sensitive than  rats  to endothall,  but  are  Insufficient
for derivation of an RfD for  subchronlc oral  exposure.   The chronic  oral RfD
of  0.02  mg/kg/day  (Section  8.2.2.2.) 1s adopted as the  subchronlc  oral  RfD.
Confidence In the key  study  Is medium  (U.S. EPA,  1986d),  which  1s  apparently
due 1n  part  to  the limited number  of animals per dose  and  the  limited  range
of  doses.   Confidence  1n the  data  base and RfD  also are medium  (U.S.  EPA,
1986d).
0168d                               -46-                             06/19/89

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    8.2.2.2.   CHRONIC EXPOSURES — Chronic  data  for  endothall  are  limited
to two 2-year  CBI  studies  using rats and dogs.  Brleger  (1953b) reported  no
effects  In  rats  fed  a  diet  containing dlsodlum endothall  at  2500 ppm  (100
mg/kg bw/day of  endothall  1on).   In dogs fed dlsodlum endothall 1n the  diet
at 0,  100,  300  or  800 ppm  (dosages  of  endothall  1on  of 0,  2, 6 or  16
mg/kg/day),  elevated  stomach  weights  were  observed  at  >300  ppm,  but  no
effects  were  observed  at  100  ppm  (2  mg/kg/day)  (Keller,  1965; Pennwalt
Agchem, n.d.).  U.S. EPA (1986d, 1987a) derived an  RfD for  endothall  of  0.02
mg/kg/day  by applying  an  uncertainty  factor  of  100 (10  for  Interspedes
differences, 10  for Intraspedes differences)  to  the dog  NOEL  of 2  mg/kg/
day.   Stomach  lesions were observed  1n dogs treated  with  0.8 mg  endothall
lon/kg/day by capsule for 6 weeks (Brleger,  1953b).  Although  lower than the
2 mg/kg day  NOEL,  this LOAEL  Is an  Inappropriate basis for  an  RfD  because  of
the bolus method of treatment (capsule without  food), which does  not repre-
sent environmental  exposure.   However,  unprotected endothall applicators  or
members of  the general  population near  application  sites could swallow low
doses of endothall  following  dust exposure (I.e.,  by mucodllary clearance).
The  RfD  of  0.02 mg/kg/day,  which  Is  verified  and available  on  IRIS  (U.S.
EPA,   1986d),  therefore,  Is  adopted  as  the  RfD   for  chronic  exposure  to
endothall for  the  purposes  of  this  document.   Confidence 1n the  key study,
data base and RfD are medium (U.S.  EPA, 1986d).
0168d                               -47-                             06/19/89

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                          9.  REPORTABLE QUANTITIES
9.1.   BASED ON SYSTEMIC TOXICITY
    The  systemic  toxldty of  endothall  was  discussed In  Chapter  6.   Data
from  these  studies  relevant for  derivation of  CSs  are summarized In  Table
9-1.  In  the  24-month study using  dogs,  slight edema and  Increased  mucosal
gland activity  were  observed  at  a dosage  of  16  mg/kg/day endothall  1on;
Increased absolute  and  relative  weights of  the stomach and  small  Intestine
were reported at 6  mg/kg/day (Keller, 1965;  Pennwalt  Agchem,  n.d.).   Conges-
tion  and  edema of  the stomach  and edema  of  the upper  Intestines  at 1  mg
dlsodlum endothall/kg/day and death at 20 mg/kg/day  reported  In  a  6-week  dog
study by BMeger  (1953b) 1s  not  Included  In  Table  9-1  because  undiluted
compound  had   been  administered  In  capsules  not  accompanied  by  food,  a
protocol not  relevant  to  environmental  exposure.  Death observed In  rats  at
10,000  ppm  dlsodlum endothall  1n the diet  and the liver and kidney  lesions
at  1000  ppm In  the  diet  In the  4-week  rat  study by BMeger  (1953a)  are  not
Included because the study duration was  too  short.
    Composite scores  for  the  effects presented  1n  Table 9-1 are  calculated
1n  Table  9-2.   The  CS of 7.6  for Increased relative and absolute weight  of
stomach and  small  Intestine  In  dogs  (Keller,  1965; Pennwalt Agchem,  n.d.},
equivalent  to an RQ of 1000,  Is  chosen to  represent  the  chronic toxldty of
endothall (Table 9-3).
9.2.   BASED ON CARCINOGENICITY
    Cancer  data  for endothall  (see Section 6.2.)  consist  of the  statement
that rats fed  diets containing  2500 ppm dlsodlum endothall  for  2  years  (100
mg  endothall  1on/kg/clay)  had no  significant  Increase  In  tumor  Incidence,  but
the  adequacy  of this  study  cannot be  evaluated.   Endothall Is assigned  to
EPA  Group D.   Because hazard  ranking 1s not  possible  for Group  D  compounds,
a cancer-based RQ cannot be assigned to  endothall.
0168d                               -48-                            04/19/89

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cr
oo
                                                     TABLE 9-1

                      Toxlclty Summary for Oral Exposure to Endothall Using the Beagle Doga»b
No. /Sex Exposure
Transformed
Animal Dosec
(mg/kg/day)
Equivalent
Human Dosed
(mg/kg/day)
Response
     4/sex
     4/sex
800 ppm dlsodium
endothall In diet
for 24 months

300 ppm dlsodium endothall
In diet for 24 months
16
9.1
                     3.4
Slight edema and In-
creased mucosal gland
activity In stomach

Increased absolute
and relative weights
of stomach and small
Intestine
    aSource: Keller,  1965;  Pennwalt Agehem, n.d.

    Reference  body weight  for dogs = 12.7 kg  (U.S. EPA, 1986c)

    Expressed  as endothall  Ion

    dThe  transformed animal  dose Is multiplied  by the cube  root  of the  ratio of the  animal  body weight  to
     reference  human  body weight  (70 kg).
o
-f*
CO
to

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                                  TABLE 9-2

               Composite Scores for Endothall Ion Using the Doga

Animal Dose
(mg/kg/day)
Chronic
Human MEOb
(mg/day)

RVd Effect


RVe CS RQ

    16
637       1.3    Slight edema  and In-
                 creased mucosal  gland
                 activity In stomach

238       1.9    Increased absolute
                 and relative  weight
                 of stomach and small
                 Intestine
5     6.5    1000
                                                            4      7.6     1000
aSource: Keller, 1965; Pennwalt Agchem,  n.d.

Equivalent human  dose  multiplied by 7,0  kg  to express MED  as  mg/day for  a
 70 kg human
0168d
                   -50-
         04/19/89

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                                  TABLE 9-3
                                  ENOOTHALL
          Minimum  Effective Dose  (MED) and Reportable Quantity  (RQ)
Route:
Dose*:
Effect:
RVd:
RVe:
Composite Score:
RQ:
Reference:
oral
238 tug/day
Increased stomach and small Intestine weights
1.9
4
7.6
1000
Keller 1965; Pennwalt Agchem, n.d.
*Equ1valent human dose
0168d
            -51-
04/19/89

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0168d                               -52-                             04/19/89

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0168d                               -53-                             04/19/89

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0168d                              -54-                             04/19/89

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0168d                               -55-                             04/19/89

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0168d                               -56-                             04/19/89

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0168d                               -58-                             04/19/89

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Scientific  Associates.    1965.   Three  generation  rat  reproductive  study,
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0168d                               -59-                             04/19/89

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Soo, A.,  I.  "Mnsley  and  S.C. Fang.   1967.   Metabolism of  14C-endothall  1n
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Regulations.   40 CFR 180.293.


0168d                               -60-                             04/19/89

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U.S. EPA.  1984.   Methodology  and  Guidelines for Ranking Chemicals  Based  on
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Register.  51(185): 33992-34003.

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Criteria and Assessment Office, Cincinnati,  OH.

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Criteria and Assessment Office, Cincinnati,  OH.

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Office of Drinking Water, Washington  DC.   NTIS  PB88-113543.


0168d                               -61-                              07/14/89

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U.S. EPA.  1987b.  Drinking Water, Proposed  Substitution  of  Contaminants  and
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the Safe Drinking Water Act.   Federal Register.   40  CFR part  141.

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193.180.

U.S. EPA/OWRS  (Office of  Water Regulations and Standards).  1985.   Guide-
lines for Deriving Numerical National Water  Quality  Criteria for  the  Protec-
tion of Aquatic Organisms and Their Uses.   U.S.  EPA,  Washington,  DC.   106  p.

USITC  (U.S.  International  Trade Commission).  1987.   1986 Synthetic  Organic
Chemicals United States  Production and  Sales.   USITC Publ. 2009,  Washington,
DC.  p. 185,  190.

Vlgfusson,  N.V.  1981.   Evaluation of the mutagenlc potential of  Aquathol  K
by  Induction  of  sister  chromatld  exchanges  1n  human  lymphocytes jm  vitro.
Report to Municipality of Metropolitan  Seattle,  Seattle,  WA.  (Cited  In U.S.
EPA, 1987a)

Walsh,   G.E.   1972.   Effects of herbicides  on  photosynthesis and growth  of
marine unicellular algae.  Hyacinth Control J.   0: 45-48.

Wellborn, J.   1971.  Tox1c1ty of some compounds  to  striped bass  flngerllngs.
Prog. Fish-Cult.   33(1):  32-36.
0168d                               -62-                             07/14/89

-------
Ullllams, E.H., E.L. Mather  and  S.M.  Carter.  1984.  Toxlclty  of  the  herbi-
cides  endothall  and dlquat  to  benthlc Crustacea.   Bull.  Environ.  Contain.
Toxlcol.  33(4):  418-422.

Wilson,  S.M.,  A.   Daniel  and G.B.  Wilson.   1956.   Cytologlcal and  genetic
effects of the defoliant endothall.  J.  Hered.   47:  151-154.

Worthing, C.R. and S.B.  Walker,  Ed.    1983.   The  Pesticide Manual, 7th  ed.
British Crop Protection Council,   p. 234.

WSSA  (Weed Science Society  of  America).  1983.  Herbicide Handbook,  5th  ed.
WSSA, Champaign,  IL.  p. 208-210.

Yeo,  R.R.  1970.   Dissipation  of endothall  and effects on  aquatic weeds  and
fish.  Weed Sd.    18(2): 282-284.
0168d                               -63-                             04/19/89

-------
                                  APPENDIX A

                              LITERATURE  SEARCHED



    This  HEED  Is  based  on  data  Identified  by  computerized  literature

searches of the following:

              CHEMLINE
              TSCATS
              CASR online (U.S. EPA Chemical Activities Status Report)
              TOXLINE
              TOXLIT
              TOXLIT 65
              RTECS
              OHM TADS
              STORET
              SRC Environmental Fate Data Bases
              SANSS
              AQUIRE
              TSCAPP
              NTIS
              Federal Register
              CAS ONLINE (Chemistry and Aquatic)
              HSDB
              SCISEARCH
              Federal Research In Progress


These  searches  were  conducted  In  Hay,  1988,  and  the following  secondary

sources were reviewed:
    ACGIH  (American  Conference of Governmental  Industrial  Hyglenlsts).
    1986.  Documentation  of the  Threshold  Limit Values  and  Biological
    Exposure Indices, 5th ed.  Cincinnati, OH.

    ACGIH  (American  Conference of Governmental  Industrial  Hyglenlsts).
    1987.  TLVs:  Threshold  Limit Values for  Chemical  Substances  1n  the
    Work  Environment  adopted   by   ACGIH   with   Intended  Changes  for
    1987-1988.  Cincinnati,  OH.  114 p.

    Clayton,  G.D. and  F.E.  Clayton,  Ed.    1981.   Patty's  Industrial
    Hygiene  and  Toxicology,  3rd rev.  ed.,  Vol.  2A.   John  Wiley  and
    Sons, NY.  2878 p.

    Clayton,  G.D. and  F.E.  Clayton,  Ed.    1981.   Patty's  Industrial
    Hygiene  and  Toxicology,  3rd rev.  ed.,  Vol.  2B.   John  Wiley  and
    Sons, NY.  p. 2879-3816.
0168d                               -64-                             04/19/89

-------
    Clayton,   G.D.  and  F.E.  Clayton,  Ed.   1982.   Patty's  Industrial
    Hygiene and  Toxicology,  3rd  rev.  ed.,  Vol.  2C.   John  Wiley  and
    Sons, NY.   p.  3817-5112.

    Grayson,  M. and  D. Eckroth,  Ed.   1978-1984.  Klrk-Othmer  Encyclo-
    pedia of  Chemical Technology, 3rd ed.  John  Wiley  and  Sons,  NY.   23
    Volumes.

    Hamilton,  A.  and H.L. Hardy.  1974.   Industrial Toxicology,  3rd  ed.
    Publishing Sciences Group, Inc.,  Littleton,  MA.   575 p.

    IARC  (International  Agency  for   Research  on Cancer).   IARC  Mono-
    graphs on  the  Evaluation  of  Carcinogenic  Risk   of  Chemicals  to
    Humans.  IARC,  WHO, Lyons, France.

    Jaber, H.M.,  W.R.  Mabey,  A.T.  Lieu,  T.W.   Chou  and  H.L.  Johnson.
    1984.   Data  acquisition   for  environmental  transport   and   fate
    screening  for compounds  of Interest  to  the Office of  Solid Waste.
    EPA  600/6-84-010.    NTIS  PB84-243906.    SRI  International,   Menlo
    Park, CA.

    NTP  (National Toxicology  Program).   1987.    Toxicology  Research  and
    Testing  Program.   Chemicals  on   Standard  Protocol.   Management
    Status.

    Ouellette,  R.P.  and  J.A.  King.    1977.    Chemical  Week  Pesticide
    Register.   McGraw-Hill  Book Co.,  NY.

    Sax, I.N.   1984.   Dangerous Properties of Industrial Materials,  6th
    ed.  Van  Nostrand Relnhold Co.,  NY.

    SRI  (Stanford  Research  Institute).   1987.    Directory of  Chemical
    Producers.   Menlo Park,  CA.

    U.S.  EPA.   1986.   Report  on Status  Report  In  the Special Review
    Program,   Registration   Standards   Program  and   the  Data  Call   1n
    Programs.   Registration  Standards and  the   Data  Call   1n  Programs.
    Office of  Pesticide Programs,  Washington,  DC.

    USITC  (U.S.   International  Trade  Commission).    1986.   Synthetic
    Organic Chemicals.   U.S.   Production  and Sales,  1985, USITC  Publ.
    1892, Washington,  DC.

    Verschueren,  K.   1983.   Handbook of  Environmental Data  on  Organic
    Chemicals,  2nd ed.   Van Nostrand  Relnhold Co., NY.

    Wlndholz,  M.,  Ed.  1983.   The Merck Index,  10th ed. Merck and Co.,
    Inc., Rahway,  NJ.

    Worthing,  C.R.  and S.B.  Walker,  Ed.   1983.  The  Pesticide  Manual.
    British Crop  Protection Council.   695  p.
0168d                               -65-                             04/19/89

-------
    In addition,  approximately  30  compendia  of aquatic  toxldty  data were

reviewed,  Including the following:


    Battelle's   Columbus  Laboratories.   1971.   Mater  Quality Criteria
    Data   Book.    Volume  3.   Effects   of  Chemicals   on   Aquatic  Life.
    Selected Data  from the Literature through  1968.   Prepared for the
    U.S.  EPA under Contract No.  68-01-0007.  Washington,  DC.

    Johnson, W.W.  and  M.T. Flnley.   1980.  Handbook  of  Acute ToxUHy
    of Chemicals  to   Fish  and  Aquatic  Invertebrates.    Summaries  of
    Toxldty Tests  Conducted at  Columbia  National  Fisheries Research
    Laboratory.    1965-1978.   U.S.  Dept.  Interior,  Fish  and Wildlife
    Serv.  Res.  Publ.  137,  Washington,  DC.

    HcKee, J.E.  and H.W.  Wolf.   1963.   Water  Quality Criteria, 2nd ed.
    Prepared  for  the   Resources   Agency  of   California,  State  Water
    Quality Control Board.  Publ.  No.  3-A.

    Plmental, D.  1971.   Ecological Effects of  Pesticides  on  Non-Target
    Species.  Prepared  for the U.S.  EPA,  Washington, DC.   PB-269605.

    Schneider,  B.A.  1979.  Toxicology Handbook.  Mammalian and Aquatic
    Data.   Book 1: Toxicology Data.  Office of  Pesticide  Programs, U.S.
    EPA,  Washington,  DC.   EPA 540/9-79-003.  NTIS PB 80-196876.
0168d                               -66-                            04/19/89

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                                                 APPENDIX  B



                                        Summary Table for Endothall
er
co
O.
Species
Inhalation Exposure
Subchronlc ID
Chronic ID
Cardnogenlclty ID
Oral Exposure
i
T' Subchronlc dog
Chronic dog
Cardnogenlclty ID
REPORTABLE QUANTITIES
Based on Chronic Toxlclty:
o
vD
a Based on Cardnogenlclty:
IO

Exposure Effect RfD or q-j*

ID ID ID
ID ID ID
ID ID ID

100 ppm dl sodium endothall NOEL for 0.02
In the diet for 2 years stomach effects mg/kg/day
(2 mg endothall 1 on/kg/day)
100 ppm dl sodium endothall NOEL for 0.02
In the diet for 2 years stomach effects mg/kg/day
(2 mg endothall lon/kg/day)
ID ID ID

1000
ID

Reference

ID
ID
ID

Keller, 1965;
Pennwalt
Agchem, n.d.
Keller. 1965;
Pennwalt
Agchem, n.d.
ID

Keller, 1965;
Pennwalt
Agchem, n.d.
NA
ID = Insufficient data;  NA = not applicable

-------
                                  APPENDIX C
            DOSE/DURATION RESPONSE GRAPH FOR EXPOSURE TO ENDOTHALL
C.I.  DISCUSSION
    A dose/duration-response  graph  for oral exposure  to  endothall  generated
by  the  method  of Crockett  et  al.  (1985)  using the  computer  software  by
Durkln and  Meylan (1988) under  contract  to ECAO-C1nc1nnat1 1s  presented  In
Figure C-l.  Data  used  to generate this graph  are presented  1n Section C.2.
In  the  generation of this  figure, all  responses are classified as  adverse
(FEL, AEL  or  LOAEL)  or  nonadverse (NOEL  or  NOAEL)  for plotting.   For oral
exposure the ordlnate expresses  dosage  as  human equivalent  dose.  The animal
dosage  1n  mg/kg/day  Is  multiplied  by the  cube root  of  the  ratio of  the
animal:human body  weight to  adjust  for species  differences  In  basal  meta-
bolic rate  (Mantel  and  Schnelderman,  1975).   The result 1s  then multiplied
by  70 kg,  the  reference  human  body  weight, to express  the human equivalent
dose as  mg/day  for a 70  kg human.
    The  boundary  for adverse  effects  (solid  line)  Is drawn by  Identifying
the  lowest  adverse effect  dose or concentration  at  the  shortest  duration  of
exposure at which an adverse  effect  occurred.  From  this  point  an Infinite
line  Is  extended  upward  parallel  to the  dose axis.   The  starting  point  Is
then  connected  to the  lowest  adverse  effect  dose  or concentration at  the
next longer duration  of  exposure that has an  adverse  effect  dose or  concen-
tration  equal to  or  lower than  the previous  one.  This  process 1s  continued
to  the lowest adverse effect dose or concentration.   From  this point a line
1s  extended to the  right,  parallel  to the  duration axis.   The  region  of
adverse  effects  lies above the adverse effects boundary.
    Using the envelope  method,  the boundary  for  no adverse  effects  (dashed
line) 1s drawn by  Identifying  the  highest  no  adverse effects  dose or concen-
tration.   From  this  point a  line  parallel to  the duration axis  1s extended

0168d                               -68-                             04/19/89

-------
 n
 1C
 E
 v

 W
 tfi
 C
 Ci
 =
 9
 Z
 C
      10000
1000 • r
        10
                   r^
          e.00001


(Oral  Exposure)
                               .x.

                  4-
q-

                 8.0881        8.881         0.01          0.1

                      HUMAN EQUIU  DURATION (fPact ion lifespan)

                                 ENVELOP METHOD
                                                                             -M
                                         1   2
       Key:    F  -  PEL
              L  -  LOAEL
              N  -  NOEL
              Solid line - Adverse Effects Boundary
              Dashed line - No Adverse Effects Boundary
                                    FIGURE C-l

            Dose/Duration - Response Graph for Oral  Exposure to Endothall
                                  Envelope Method
    0168d
                                -69-
                                                                      04/19/89

-------
to  the  dose  or  concentration axis.   The starting point  Is  then connected  to
the next  lower  or  equal  no adverse effect dose or concentration at a  longer
duration of  exposure.  When  this  process can no  longer  be  continued,  a  line
Is  dropped parallel  to  the dose or concentration axis  to  the  duration axis.
The region of no adverse effects  lies  below  the  no  adverse effects boundary.
At  both ends of the  graph  between  the  adverse effects and  no adverse  effects
                                                                      /
boundaries  are  regions  of  ambiguity.   The  area  (1f   any)  resulting  from
Intersection of  the adverse  effects  and  no adverse  effects  boundaries  1s
defined as the region of contradiction.
    In  the censored  data method, all no  adverse  effect  points  located 1n the
region  of  contradiction  are  dropped  from consideration and the  no  adverse
effect  boundary Is redrawn so  that  1t  does not  Intersect the adverse  effects
boundary and no  region  of contradiction  Is  generated.   This  method  results
1n  the most conservative definition of  the no adverse effects region.
    Figure C-l  presents the  dose/duration-response  graph  generated   by  the
envelope method.   The adverse effects boundary  Is  defined  by a  lethal  dose
In  humans  (Allender, 1983,   Rec.  #8),   a  LD,Q  value  In  rats (Slmslman  et
al., 1976; Worthing  and Walker  1983, Rec. #11),  and  a LOAEL for  gastrointes-
tinal  effects  In  dogs  administered a  capsule providing 0.8 mg/kg/day for 2
years  (Brleger, 1953b, Rec. #7).  The no adverse  effects boundary 1s  defined
by  a  NOEL for  rats  In  a  2-year  diet study  (Brleger,  1953b,  Rec. #3).   As
Indicated  In Figure C-l,  almost  all of the points  for this chemical  fall
within  the region  of contradiction.  This Is  attributable  to the  LOAEL (Rec.
#7) and NOEL (Rec.  #3)  described above, which  appear  to  be-  outliers.   The
LOAEL   1s  based on a study  of low confidence  that  used  a bolus method  of
treatment, and  the  NOEL   1s  based on  a study  of  Indeterminate  confidence
using  a species that may  not be the most sensitive.  The  LOAEL was  not  used


0168d                                -70-                             04/19/89

-------
as  the  basis for  an  RfD because  the  method  of treatment was  Inappropriate

(Section 8.2.2.2.).   If  the LOAEL  Is  considered  to be an outlier, then  the

NOEL  that  serves  as  the  basis  for the RfD  for  subchronlc and chronic  oral

exposure  (Keller,   1965;  Pennwalt  Agchem,  n.d.,  Rec.  #1)  will  not  occur

within  the  region   of   contradiction.    Insufficient   data   are   available

(because of  the outlying points)  to  redraw  the  graph  by the  censored  data
                                                                      ,i
method to eliminate the region of contradiction.

C.2  DATA USED TO GENERATE DOSE/DURATION-RESPONSE  GRAPHS

Oral Exposure
Chemical Name:
CAS Number:
Document Title:
Document Number:
Document Date:
Document Type:
   Endothall
   145-73-3
   Health and Environmental Effects Document on Endothall
   SRC-TR-88-172
   8-30-88
   HEED
RECORD #1: Species: Dogs
Sex: Both
Effect: LOAEL
Route: Food
Number Exposed:
Number Responses:
Type of Effect:
SHe of Effect:
Severity Effect:




8
NR
WGTIN
COLON
4
Dose: 6.000
Duration Exposure: 24.0 months
Duration Observation: 24.0 months






Comment:
Citation:
Administered as d1sodium salt. 2, 6 or 16 mg 1on/kg.
Increased stomach and small Intestine weight at 6 and 16,
slight pylork edema at 16.  No effect on SGOT, BSP clearance,
hematol, urlnalysls or other hlsto.

Keller, 1965; Pennwalt Agchem, n.d.
0168d
                     -71-
04/19/89

-------
RECORD #2:
Comment:


Citation:
Species:
Sex:
Effect:
Route:
Dogs
Both
NOEL
Food
Dose:                  2.000
Duration Exposure:     24.0 months
Duration Observation:  24.0 months
Number Exposed:     8
Number Responses:   NR
Type of Effect:     WGTIN
Site of Effect:     COLON
Severity Effect:    4

See previous record.  Relative and absolute stomach and7 small
Intestine weights were not Increased.

Keller, 1965; Pennwalt Agchem, n.d.
RECORD #3:



Species:
Sex:
Effect:
Route:
Rats
Female
NOEL
Food
Dose:
Duration
Duration


Exposure:
Observation:

100.000
2.0 years
2.0 years

Comment:
Comment:
Citation:
               Number Exposed:
               Number Responses:
               Type of Effect:
               Site of Effect:
               Severity Effect:
                    NR
Administered as dlsodlum salt.  Doses were 100 mg 1 on/kg/day
and lower (NOS).  No toxic effects noted but endpolnts
examined were not specified.  Study summarized In ODW Health
Advisory.
Citation:
RECORD #4:
Brleger,
Species:
Sex:
Effect:
Route:
)953b
Rats
NR
FEL
Food

Dose:
Duration
Duration

Exposure:
Observation:

400.000
4.0 weeks
4.0 weeks
Number Exposed:     NR
Number Responses:   NR
Type of Effect:     MORTL
Site of Effect:     BODY
Severity Effect:    10

Administered as dlsodlum salt.  Doses were 40 and 400 mg Ion/
kg/day.  Most rats died within 1 week.  Not specified 1f liver
or kidney effects occurred.  Study summarized 1n ODW Health
Advisory.

Brleger, 1953a
0168d
                     -72-
                                           04/19/89

-------
RECORD #5:
Comment:


Citation:
Species:
Sex:
Effect:
Route:
Rats
NR
LOAEL
Food
               Number  Exposed:      NR
               Number  Responses:    NR
               Type of Effect:      OEGEN
               SHe of Effect:      LIVER
               Severity Effect:     6
Dose:
Duration Exposure:
Duration Observation:
                             NR
                             NR
                             HEMOR
                             KIDNY
                             6
40.000
4.0 weeks
4.0 weeks
See previous record.   Slight  liver  degeneration and focal
hemorrhaglc areas  In  the  kidneys.

BMeger, 1953a
RECORD #6:



Species:
Sex:
Effect:
Route:
Dogs
Hale
PEL
Capsul
Dose:
Duration
Duration


Exposure:
Observation:

20.000
11.0 days
11.0 days

Comment:
Citation:
Number Exposed:      1
Number Responses:    1
Type of Effect:      DEATH
SHe of Effect:      BODY
Severity Effect:     10

Administered as  dlsodlum  salt.   Doses:  0.8-40 mg 1on/kg/day
(1 dog/dose).  Death 1n all  dogs within 11 days at >20.
Stomach erosion  and hemorrhage  at dosage >20 mg 1on/kg/day.
Study summarized 1n ODW Health  Advisory.

BMeger, 1953b
RECORD #7:



Species:
Sex:
Effect:
Route:
Dogs
Hale
LOAEL
Capsul
Dose:
Duration
Duration


Exposure:
Observation:

0.800
6.0 weeks
6.0 weeks

Comment:
Citation:
Number Exposed:      1
Number Responses:    1
Type of Effect:      HYPRT
SHe of Effect:      COLON
Severity Effect:    3

See previous record.  Stomach  congestion,  edema of stomach and
upper Intestine  common 1n all  dogs.   Additional Information
not reported.

BMeger, 1953b
0168d
                     -73-
                                          04/19/89

-------
RECORD #8:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Humans
Hale
PEL
Oral (NOS)
Dose:                  100.000
Duration Exposure:      1.0  days
Duration Observation:   1.0  days
Number Exposed:     1
Number Responses:   1
Type of Effect:     DEATH
SHe of Effect:     BODY
Severity Effect:    10
                                                      /
Suicide due to 1ngest1on of estimated 7-8 g  of  dlsodlum  salt
(-100 mg Ion/kg).  Repeated vomiting.  Focal  edema  and
extensive hemorrhages  1n the lungs  and gastrointestinal  tract

Al lender, 1983
RECORD #9:



Species:
Sex:
Effect:
Route:
Rats
Male
PEL
Gavage
Dose:
Duration
Duration


Exposure:
Observation:

57.000
1.0 days
14.0 days

Comment:
Citation:
Number Exposed:     NR
Number Responses:   NR
Type of Effect:     DEATH
Site of Effect:     BODY
Severity Effect:    10

1059.  Peanut oil vehicle.   Rats observed 14 days  or  until
recovery.  Minimum 10 rats/dose and 4 doses; design of  assay
with endothall not specifically reported.

Galnes and Under, 1986
RECORD #10:



Species:
Sex:
Effect:
Route:
Rats
Female
PEL
Gavage
Dose:
Duration
Duration


Exposure:
Observation:

46.000
1.0 days
14.0 days

Comment:

Citation:
Number Exposed:     NR
Number Responses:   NR
Type of Effect:     DEATH
Site of Effect:     BODY
Severity Effect:    10

1059.  See previous record.

Galnes and Under, 1986
0168d
                     -74-
                                           04/19/89

-------
RECORD #11
Comment:


Citation:
 Species:
 Sex:
 Effect:
 Route:
Rats
NR
PEL
Oral (NOS)
Dose:                   38.000
Duration Exposure:      1.0  days
Duration Observation:   2.0  days
 Number  Exposed:     NR
 Number  Responses:   NR
 Type  of  Effect:     DEATH
 SHe  of  Effect:     BODY
 Severity Effect:    10

 LD5Q  reportedly 38-51 mg add/kg In 48 hours.  Additional
 Information not reported.  Primary source not available.

.Slmslman et al., 1976; Worthing and Walker, 1983
RECORD #12: Species: Rats
Sex: Femal
Effect: PEL
Route: Oral
*
Number Exposed:
Number Responses
Type of Effect:
SHe of Effect:
Severity Effect:

e

(NOS)

25
: 2
DEATH
BODY
10
Dose: 16.000
Duration Exposure: 14.0 days
Duration Observation: 14.0 days







Comment:
Citation:
 Treated  on  gestation days 6-19.  Doses:  8, 16, 24 mg/kg/day.
 25-26/group.   10 maternal deaths at 24 mg/kg/day.  2 maternal
 deaths at 16 mg/kg/day.  No fetal developmental/toxic effects
 1n  surviving dams; exam day not reported.  Prom ODW HA.

 Science  Applications,  Inc., 1982
RECORD #13: Species: Rats
Sex: Femal
Effect: NOEL
Route: Oral
Number Exposed:
Number Responses
Type of Effect:
SHe of Effect:
Severity Effect:

e

(NOS)
25
: 0
DEATH
BODY
10
Dose:
Duration Exposure:
Duration Observation:

NR
NR
TERAD . .
FETUS

8.000
14.0 days
14.0 days






Comment:


Citation:
 See  previous  record.
 fetotoxlc  effects.
           No maternal deaths.   No teratogenlc  or
 Science  Applications,  Inc.,  1982
0168d
                      -75-
                                           04/19/89

-------
RECORD #14:
Comment:
Species:
Sex:
Effect:
Route:
Rats
Both
PEL
Food
Dose:
Duration Exposure:
Duration Observation:
100.000
128.0 days
128.0 days
Citation:
Number Exposed:     NR
Number Responses:   NR
Type of Effect:     REPRO
Site of Effect:     OTHER
Severity Effect:    10
                                                      /
Administered as d1sodium salt.   Doses:   4,  12,  100 mg Ion/kg/
day.  100 days of treatment prior to mating.   Pups died  within
1 week of birth and treatment discontinued.   Other Indices  not
reported.

Scientific Associates, 1965
RECORD #15:



Species:
Sex:
Effect:
Route:
Rats
Both
LOAEL
Food
Dose:
Duration
Duration


Exposure:
Observation:

12.000
128.0 days
142.0 days

Comment:
Citation:
Number Exposed:     NR
Number Responses:   NR
Type of Effect:     REPRO
SHe of Effect:     OTHER
Severity Effect:    4

See previous record.  Three generation study;  each generation
treated for 100 days prior to mating.   Reduced body weights  In
pups at 21 days of age.  No effect on  survival.  Other  Indices
not reported.

Scientific Associates, 1965
0168d
                     -76-
                                           04/19/89

-------
RECORD #16:
Comment:
Citation:
Species:
Sex:
Effect:
Route:
Rats
Both
NOEL
Food
Dose:
Duration Exposure:
Duration Observation:
4.000
128.0 days
142.0 days
Number Exposed:     NR
Number Responses:   NR
Type of Effect:     REPRO
SHe of Effect:     OTHER
Severity Effect:    4

See previous record.  No effect on survival  or  body weight  of
pups.  NOEL for reproductive effects but other  Indices  not
reported.  Study summarized In ODW Health Advisory.

Scientific Associates, 1965
NR = Not reported
0168d
                     -77-
                                           04/19/89

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            UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                              29 !9R°
SUBJECT:
FROM:
TO:
Health and Environmental Effects Document for
Endothall

William H. Farland, Ph.D.
Director
Office of Health and Environmental
  Assessment (RD-689)

Matthew Straus
Chief, Waste Characterization Branch
Office of Solid Waste (OS-330)
     I am forwarding copies of the Health and Environmental
Effects Document  (HEED) for Endothall.

     The HEEDs support listings under RCRA, as well as provide
health-related limits and goals for emergency and remedial
actions under CERCLA.  These documents represent scientific
summaries of the pertinent available data on the environmental
fate and mammalian and aquatic toxicity of each chemical at an
extramural effort of about $10K.  The attached document has been
reviewed within OHEA, by staff in OPP and OTS, and by two
external scientists.                                 „-  '

     Should you wish to see any of the files related tor the
development of the HEEDs, please call Chris DeRosa at
FTS:  684-7531.

Attachment

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