530R86106
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          ADVISORY
              METOLACHLOR
        Criteria and  Standards  Division
     Office of Water  Regulations  and  Standard
                 United States
         Environmental Protection  F^gency
                MRRCH   1  9 8 G

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                                  WATER QUALITY ADVISORY
                                         Number  6 .


                                         METOLACHLOR

                               Criteria and Standards Division
                          Office of Water Regulations and Standards
                        United States Environmental Protection Agency


c •               The advisory concentration for Metolachlor  in ambient water for
x"'j          the protection of freshwater aquatic life is estimated to be 100
^          ug/L.  No saltwater data were reviewed for this advisory, and no
            advisory concentration  for the protection of saltwater aquatic
            organisms is estimated. Care should be taken in the application of
*./          this advisory, with consideration of its derivation, as stated in
 V          the  attached support  document.

                A value given to  protect aquatic life can be derived from no
            observed effect  levels (NOEL), the  lowest concentration found in the
            data which has been observed to cause acute or  chronic toxicity or
 t          other experimental data which may be applicable. When there is no
  •*         valid experimental evidence,  a value may be derived from a model which
           uses structure-activity relationships (SAR)  as  its basis. The  advisory
           concentrations  should be used with caution,  since they are derived
           from minimal  experimental evidence,  or in the case of SAR derived
           values,  no data on the specific chemical.

               The advisory concentration for Metolachlor in ambient water for
           the protection  of human health is  estimated  to be 44 ug/L, based on
           data and  information which are available to U.S.  EPA.  Care should be
           taken in  the  application of this  advisory,  with consideration of its
           derivation,  as stated in the attached support document.

               An advisory concentration can be derived from a number of sources:
           The Office of Drinking  Water Health Effects Advisories; Acceptable
           Daily Intake(ADI)  values from EPA; Office of Pesticides  and  Toxic
           Substances risk assessments;  Carcinogen Assessment Group(CAG)  cancer
           risk estimates;  risk estimates derived  from  the open  literature;  or
           other sources which will be given in the support document. The
           advisory  concentrations derived from these sources will  vary in
           confidence and usefulness,  based  on the amount and quality of data
           used as well  as the assumptions behind the original estimates. The
           user is advised to read the background  information carefully to
           determine the strengths or deficiencies of the values given  in the
           advisory.
                             U S  Environmental Prelection Agency
                             Region 5, Library (PL-12J)
                             77 West Jackson Boulevarjd, 12th Floor
                             Chicago, IL 60604-3590

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      HUMAN HEALTH AND AQUATIC LIFE
        LITERATURE SEARCH AND DATA
           BASE EVALUATION FOR
               METOLACHLOR
   U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF WATER REGULATIONS AND STANDARDS
     CRITERIA AND STANDARDS DIVISION
         Washington, D.C.  20460

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                         TABLE OF CONTENTS
INTRODUCTION  	    1
SCOPE OF SEARCH  	   2
SUMMARY OF FINDINGS 	   2
  Aquatic  Toxicity  	   2
  Health Effects  	   7
CRITERIA EVALUATION AND RECOMMENDATION 	  11
  Aquatic  Life  	  11
  Health Effects  	  15
REFERENCES  	  17
                           LIST OF TABLES

Table 1.    Summary of Aquatic Toxicity Literature  Review
           of Metolachlor 	   3
Table 2.    Summary of Health Effects Literature Review
           of Metolachlor 	   8
Table3.  Values Used to Calculate  the Final  Value  	  12
Table 4.    Data  Requirements for Calculation of Aquatic Life
           Interim  Criteria--Metolachlor  	  14
Table 5.    Data  Requirements for Calculation of Human Health
           Interim  Criteria — Metolachlor  	  16
                          LIST OF FIGURES

Figure 1.  Summary  of  Toxicity  Data for Metolachlor

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                    HUMAN HEALTH AND AQUATIC  LIFE
                      LITERATURE SEARCH AND DATA
                         BASE EVALUATION  FOR
                             METOLACHLOR


                 U.S.  ENVIRONMENTAL PROTECTION AGENCY
              OFFICE OF WATER REGULATIONS AND STANDARDS
                   CRITERIA AND STANDARDS DIVISION
                       Washington,  D.C.   20460


                             INTRODUCTION


    Metolachlor [2-chloro-N-(2 ethyl-6-methylphenyl)-N-(2-methoxy-l-
methylethyl)acetamide] is a selective herbicide used to control annual
grass weeds, yellow nutsedge, and certain broadleaf species in corn
production.  Corps which are sufficiently  tolerant  to metolachlor  are
soybeans, peanuts, potatoes, and certain vegetables (WSSA, 1979).
Metolachlor is manufactured under the name Dual  and is packaged in 6
and 8 Ib/gallon emulsifiable concentrates.  Metolachlor  is also
manufactured under the trade names  of  Bicep  , Primagram  ,  Primextra  ,
CGA-24705,  Codal and Milocep when it is combined with  other herbicides
such as propazine and atrazine which  increase the  spectrum of  its
effectiveness.  It was developed by Ciba-Giegy in  Basle, Switzerland,
and patented in 1973 and 1976  (EPA, 1980).

    Metalachlor is a white  to tan liquid at room temperature with the
following physical properties:  (EPA,  1980)

       Boiling point:   100 °C
      Vapor pressure:   10~5 min Hg  at  20  °C
           Stability:   half-life of a  0.25 percent aqueous
                       solution at  1OO °C is  30 hours  at pH3,  18
                       hours at pH7,  and  1.5  hours at  pH 10
    Specific gravity:   1.085 + 0.005  at  20 °C
 Solubility in water:   530 ppm at 20  °C.

    Metolachlor belongs  to  a category of herbicides known  as chloro-
acetamides which inhibit growth and reduce cell division and enlarge-
ment.  Metolachlor is a soil-applied herbicide and its particular mode
of action is inhibition of  root elongation (Ashton and Crafts, 1981).
It is usually applied on or incorporated into the soil at a rate  of
1.5-3.0  Ib  active ingredient per acre  during  or soon after planting
but before sprouts emerge (EPA,  1980).  Metolachlor has been shown to
be resistant to hydrolysis and rapid  metabolism  in soil.   It also has
the tendency to leach extensively  in  low-organic  soils  (EPA, 1980).

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    The most significant toxicity of metolachlor to nontarget species
has been with aquatic organisms,  particularly fish (Buccafusco,  1978;
Sachsse and Ullman, 1974).   Consequently,  present concerns focus on
releases of metolachlor into aquatic environments.  Research needs
include the identification of quantities of metolachlor which could
reach aquatic systems unchanged by leaching or runoff from farm  fields
and the resultant effects of metolachlor on those aquatic systems.


                           SCOPE OF SEARCH

    Sources were identified through a computerized literature search
of TOXLINE, the Toxicological Data Base,  TOXBACK, and NTIS files and
through manual bibliographical searches of the available literature.
The computerized literatures searches included published literature
from 1965 to the present.   Most of the sources cited in this document
were listed in an EPA (1980)  document,  Metolachlor-Pesticide Registra-
tion Standard, which cited sources that were  not published in the open
literature but were evaluated by the EPA for validity.  The search
focused on controlled dose-response  studies.

    When available, information was obtained on the quality
assurance/quality control  (QA/QC) measures employed in the laboratory
and field studies, specifically their use of controls, replicate
treatments, and chemical analysis of test concentrations.  Information
also was sought on the bioaccumulation/biomagnification of metolachlor
and other food chain, ecological, and health effects.

    Studies were evaluated with respect to guidelines established by
the U.S.  EPA in "Guidelines and Methodology Used in Preparation  of
Health Effect Assessment Chapters of the Consent Decree Water Quality
Criteria Documents" (FR 45:79347, Nov. 28,  1980), and the "Guidelines
for Deriving Numerical National Water Quality Criteria for the
Protection of Aquatic Life and Their Uses  (Stephan et al., 1985).  The
search was not intended to be exhaustive,  however it was intended to
be thorough in its coverage of accessible,  relevant data sources
required for meaningful criteria development.

                         SUMMARY OF FINDINGS

                           Aquatic Toxicity

    Most of the aquatic toxicity data were taken from a registration
document for metolachlor (Table  1).  The numbers presented in the
document were from studies which were not published in journals  or
government reports, but were reviewed  by EPA prior to acceptance of
the chemical for registration.  Although the orginal reports of  the
studies were not available,  it was assumed that EPA required
acceptable QA/QC measures.

    According to the registration document (EPA, 1980),  there are no
data available on the toxicity of metolachlor to freshwater algae or
aquatic plant species.  However, Ellgehausen et al.  (1980) present

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data on the bioaccumulation of metolachlor in aquatic organisms
including the alga Scenedesmus acutus.  In order to establish exposure
concentrations for the bioaccumulation study, they determined a no-
effect-level  of  0.1 ppm for this species after an unspecified period
of exposure.   Other details on the acute toxicity study were not
provided.

    The only acceptable study (lethal concentration for 50 percent of
test organisms)  on the toxicity of metolachlor to invertebrates
(Figure 1)  was a 48-hour LC50 of 25.1  ppm (Vilkas,  1976,  as cited in
EPA, 1980).   The EPA determined that results from this test were
adequate to characterize the toxicity of metolachlor to invertebrates.
Ellgehausen et al. (1980)  determined a no-effect-level for Daphnia
magna of 0.1  ppm;  however,  no QA/QC measures other than concentration
measurement were reported.   Toxicity data on other species of
invertebrates were not available.

    Most of the toxicity data on fish species were from the EPA
registration document (EPA, 1980).   The  EPA approved studies genera-
ting LC50 data for bluegill sunfish (10.0  ppm) and rainbow trout  (3.9
ppm).   Acute  studies exposing fathead minnows,  crucian carp,  channel
catfish, as well  as a flow-through test exposing fathead minnows were
judged inadequate by the EPA  (EPA, 1980).  In a separate study,
Ellgehausen et al.  (1980) determined a no-effect-level for catfish,
Ictalurus me].as,  of  0.1 ppm after  96 hours of exposure.  Again, there
was no report of quality assurance measures other than concentration
measurement.

    A chronic test of the effects of 97.4 percent metolachlor on
reproduction of the fathead minnow reported a maximum acceptable
toxicant concentration  (MATC) between 0.78 and 1.60 ppm (Dionne, 1978,
as cited in EPA,  1980).   When the fish were exposed to concentrations
higher than the MATC, significantly fewer  first and second generation
fry survived.

    Metolachlor  was reported to accumulate in algae, Daphnia and fish
tissues after exposure times ranging from 90 minutes for algae to 96
hours for catfish (Ellgehausen et  al., 1977 and 1980).   However, the
concentrations were significantly  reduced  after depuration periods in
all three cases.   The primary source of  the accumulated metolachlor
was water,  rather than contaminated food organisms.  In accumulation
studies of 30-70  days of exposure using catfish  (Smith, 1977) and
bluegills  (Barrows, 1974),  metolachlor accumulated in the fish during
the exposure period and  dropped to  significantly  lower levels after
depuration.   A bioaccumulation factor was not calculated in any of the
studies because metolachlor was rapidly metabolized.

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                            Health Effects

    Many studies have been conducted on the health effects  of
metolachlor (Table 2),  but the studies were not published in open
literature.  The data evaluated in this section were taken  from
studies cited in the pesticide registration document  for metolachlor
(EPA, 1980).

    Mammalian acute toxicity studies have shown the LDSOs for
metolachlor to  range from 0.3->10,000 mg/kg depending on  the route of
exposure (oral,  dermal)  and the species of  test animal (rat, rabbit)
(EPA,  1980).  These values also are representative of the toxicity
data from tests of the emulsif iable concentrates of 6 or 8  Ib
metolachlor/gal.  Toxicity studies on beagle dogs showed an "emetic
dose" of 19.0 mg/kg.  This level was  not sufficiently toxic to
establish an acute LC50  (AMRI, 1974b).

    Draise tests conducted on rabbits using both technical  grade
metolachlor and the 8 Ib/gal emulsifiable concentrate produced
moderate but reversible  irritation and corneal opacity in the  eyes.
The 6 Ib/gal emulsifiable concentrate, however, produced an
irreversible corneal opacity  in the rabbit eye.  Because the amount of
active ingredient in the 6  Ib/gal  emulsifiable concentrate  is less
than that in the 8 Ib/gal, it is likely that the irritation was due to
the inert ingredients of the emulsifiable concentrate rather than to
metolachlor.  Another acute effect of technical grade metolachlor was
a positive skin sensitization reaction when applied through
intradermal injection in guinea pigs  (Sachsse, 1977).

    Metolachlor apparently does not accumulate in mammals because it
is rapidly absorbed and metabolized.  Studies have shown ingested
metolachlor to be completely metabolized in rats, goats,  and poultry
with no unchanged metolachlor detected in the urine or feces  (Hambock,
1974).   The metabolic pathway of metolachlor is not yet understood
(EPA, 1980).

    A chronic feeding study exposing dogs to metolachlor over  a 6-
month period reported a no-observed-effect-level  (NOEL) of  100 ppm
(EPA, 1980).   Another chronic study showed  metolachlor to produce no
oncogenic effects in mice at a level  of  3000 ppm  (IBT, 1975).  Kennedy
(1976)  performed a 2-year feeding study on rats which showed no
oncogenic effects.  However,  the integrity of the rat study was
questioned by EPA because of protocol deficiencies and lack of
concentration verification.   The study was  redone and the results
indicate the possibility of neoplasm  formation at high (3000 ppm)
doses.   OPP considers the study to be core  minimum,  and have
tentatively set the non-neoplastic NOEL at 30 ppm.  Tests on the
mutagenicity and fetotoxicity of metolachlor have also produced nega-
tive results  (Arni and Miller,  1976;  Ciba  Geigy  Ltd., 1976; Fritz,
1976) .

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-------
                CRITERIA EVALUATION AND RECOMMENDATION

                             Aquatic Life

    While the data base required to derive criterion lacks  approxi-
mately half of the information needed according to the guidelines
specified in Stephan,  et al (1985),  sufficient  data were  found  to
calculate an advisory concentration.

    An Aquatic Life Criterion consists of a Criterion Maximum Concen-
tration (CMC)  and a Criterion Continuous Concentration (CCC).

    The CMC is equal to one-half the Final Acute Value (FAV).  An
estimated Final Acute Value was  calculated using the following
equations.

                Final Acute Value   = eA


where:

            A   = S( 0.05)  + L

            L      (In GMAV - S( ( p))/4)

          S2  =  ((In GMAV)2)  - (( (In GMAV))2/4)
                          cp}  _ ( ( ( p) ) 2 /^^
          GMAV  = Genus Mean Acute Value (the geometric mean of the
                  species mean acute values for the genus)

            P   = Cumulative probability as R/N+1

            R   = Rank from "1" for the
                  lowest to "N" for the highest GMAV.

    The Genus Mean Acute Values (GMAVs) were obtained from the
reviewed literature  (Table 1).   The values used in calculating the
estimated FAV are presented in Table 3.  There are as  mentioned above,
insufficient data to calculate a criterion, but the incomplete data
base can be used in calculating an advisory.

    Substituting values from Table 3 into the formulae gave an
estimated Final Acute Value  of 0.77 ppm.

    An estimated maximum concentration  for metolachlor was  calcu-
lated according to the following:

     Maximum concentration = Final Acute Value
                             0.77 = 0.39 ppm.
                               2

                                 11

-------



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-------
    The estimated Final Chronic Value is equal  to the estimated FAV
divided by the Final Acute-Chronic Ratio.   Data for calculating an
Acute-Chronic Ratio were available only for fathead minnows (Table 1):

                     9.2 ppm  =7.96
                      1.17 ppm

The ratio is based on an acute 96-hr  LC50  from  a fathead minnow test
and the geometric mean of the Maximum Acceptable Toxicant
Concentration (EPA,  1980).

    The estimated advisory concentration was calculated by the
following:


         Advisory concentration =     Final Acute Value
                                   Final  Acute-Chronic Ratio

                                = 0.77 ppm =0.10 ppm.
                                  7.9

    Because there currently are no acceptable data on plants, a Final
Plant Value cannot be calculated.  Similarly, a Final Residue Value
cannot be calculated because data on  either FDA levels  in  fish or
long-term wildlife acceptable daily  intake have not been located.
While there is bioaccumulation information available, as was previous-
ly mentioned, none of the studies allows determination  of  a bioaccumu-
lation factor.  Therefore, the estimated advisory concentration is
equal to 0.10 ppm because it is the only chronic value  calculated.

    Because these estimates were derived from a partial data base  they
cannot be rigorously applied, but should be used as guidance in inter-
preting levels of metholachlor in environmental samples.

    These estimates were derived from an acceptable, yet partial,  data
base.  The acceptability of many of the test  results was  assumed.   The
estimates could be improved with expansion of the data base.  The
estimates provided here are not rigorous in their derivation but can
be used to provide guidance in the interpretation of concentrations of
metolachlor  found  in environmental samples.

    The data set for calculating a criterion  is currently  lacking  the
following elements (Table 4):  LCSOs for a benthic crustacean, an
aquatic insect species, a phylum other than Arthropoda  or  Chordata,
and another insect family; acute/chronic data on an  invertebrate and
another freshwater species; acceptable test results with a freshwater
algae or an aquatic vascular plant.
                                  13

-------
TABLE 4.  DATA REQUIREMENTS FOR CALCULATION OF AQUATIC LIFE
          INTERIM CRITERIA—METOLACHLOR
                                Available Data
     Criterion Requirements
       Aquatic Toxicity

Acute test results from tests on:

  a.  A salmonid  (class Osteichthyes)      YES


  b.  A warm water species commercially    YES
      or recreationally important
      (class Osteichthyes)

  c.  Another family in the phylum         YES
      Chordata (fish, amphibian, etc.)

  d.  A planktonic crustacean              YES
      (cladoceran, copepod, etc.)

  e.  Benthic crustacean  (ostracod,         NO
       isopod, scud, crayfish, etc.)

  f.  Insect  (mayfly, dragonfly,            NO
      damselfly,  stonefly, mosquito, etc.)

  g.  Phylum other than Arthropoda/         NO
      Chordata (Rotifera, Annelida,
      Mollusca)

  h.  Another family of insect              NO

Acute-chronic ratios with species from
three different families:

  a.  One fish                             YES

  b.  One invertebrate                      NO

  c.  Acutely sensitive freshwater animal   NO
      species

Acceptable test results from a test with:

  a.  Freshwater algae                      NO

  b.  A vascular plant                      NO

Bioaccumulation factor with a freshwater    NO
species (if a maximum permissible tissue
concentration is available)
Acceptability of
Available Data
                                                        YES
                                                   EPA approved

                                                        YES
                                                   EPA approved
                                                        YES
                                                   EPA approved

                                                        YES
                                                   EPA approved
                                                        YES
                                                   EPA approved
                            14

-------
                            Health  Effects


    Standards exist for tolerance limits of metolachlor residues in
raw agricultural commodities (40 CFR 180.368).   These levels range
from 0.02  ppm to 3.0 ppm  in  fruits, vegetables, and  livestock.

    A no-observed-effect-level  (NOEL) of 100 ppm  has been determined
based on a 6-month dog feeding  study (U.S.  EPA, 1980).

    According to the methods outlined in "Guidelines and Methodology
Used in Preparation of Health Effects Assessment  Chapters of the
Consent Decree Water Quality Criteria Documents," ideally a NOAEL,
LOEL, or LOAEL would be used to  derive an ADI.  However, only the NOEL
for metolachlor is available.  The Office of Pesticide Programs calcu-
lated an ADI using the NOEL (U.S.  EPA,  1980).  A safety factor of 2000
is applied to the NOEL because there are no long-term or acute data on
humans and few studies on experimental animals with  no indication of
carcinogenicity (EPA,  1980;  Federal Register.  1980)  (Table 5).  Using
the data from the dog study, a dietary exposure of 100 ppm parts food
is equivalent to a NOEL of  2.5 mg/kg/day.  Applying  the safety factor
of 2000 and the average adult human weight  (70 kg),  instead of 60 kg
used by OPP,  the ADI is calculated  as follows:


                  ADI  = (2.5 mg/kg/day)(70  kg) =  0.088 mg/day.
                                 2000


The ADI is then divided by 2 I/day (average adult human water consump-
tion) to arrive at an interim advisory concentration of 0.044 mg/L.
This value does not reflect consumption of  fish contaminated with
metolachlor, but given the  low bioconcentration estimate due to rapid
depuration and metabolism, the advisory is  expected  to be protective
in the event of consumption of contaminated organisms.

    This estimate is based on a  study approved by the EPA. All other
data used in derivation of the criteria are from unpublished studies
whose QA/QC measures are  unknown.   The estimate, therefore,  should not
be considered firm,  but rather as an  interim value to provide guidance
until more data become available.
                                  15

-------
       TABLE 5.  DATA REQUIREMENTS FOR CALCULATION OF HUMAN HEALTH
                 INTERIM CRITERIA—METOLACHLOR


     Criterion Requirements                                 Acceptability
      Human Health Effects              Available Data    Of Available Data

NonThreshold:
   Carcinogen                               YES                ?
   Tumor.incidence tests (Incidence   Noncarcinogenic
     of tumor formation significantly
     more than the control for at
     least one dose level), or
   Data set which can be used to            NA*
     estimate carcinogenic risk, or
   Lifetime average exposure tests, or      NA
   Human epidemiology studies               NA
     (if available, not required)

 Threshold:
   Noncarcinogens                           YES                YES
                                                          EPA approved
   No observed adverse effect level         NO**               —**
     (at least 90-day), or
   Lowest observed effect level             NO

   Lowest observed adverse effect level     NO

Acceptable Daily Intake:                    YES                YES
   Daily water consumption                  YES           EPA Approved
   Daily fish consumption                   YES           EPA Approved
   Bioconcentration factor                  NO
   Nonfish dietary intake                   NO
   Daily intake by inhalation               NO

Threshold Limit Value:                      NO
   (Based on 8-hour time-weighted
   average concentrations in air)

Inhalation Studies:                         NO
   Available pharmacokinetic data
   Measurements of absorption efficiency
   Comparative excretion data
* Not applicable.
? - Results equivocal.
** NOEL available (EPA approved).
                                  16

-------
                              REFERENCES


Ashton, F. M.,  and A. S. Crafts, 1981.  Mode of action of herbicides.
Wiley Interscience Publication.  New York, 525 pp.

Code of Federal Regulations, 1984.   Metolachlor:   tolerances for
residues on raw agricultural  commodities.  180.368.

Ellgehausen, H.,  J. A.  Guth, H. 0. Esser, 1980.  Factors determining
the bioaccumulation potential of pesticides in the individual
compartments of aquatic food chains.  Ecotoxic and Environ. Safety,
4:134-157.

Environmental Protection Agency, 1980.   Metolachlor:  pesticide
registration standard.   EPA/SPRD-80/520,  National  Technical
Information Service, Springfield, Virginia.   183 pp.

Federal Register, 1982.  Tolerances and exemptions from tolerances for
pesticide chemicals in or on raw agricultural commodities:
metolachlor.  FR  47:10536;  23932.

Federal Register, 1980.  Guidelines and methodology used in prepara-
tion of health effect  assessment chapters of  the consent decree water
quality criteria  documents.   FR 45:79347.

Stephan,  C.  E., D. I.  Mount, D. J. Hansen, J. H. Gentile,  G. A.
Chapman, W. A.  Brungs,  1985.   Guidelines for  deriving numerical
national water quality criteria  for the protection of aquatic
organisms  and their uses.  U.S.  Environmental Protection Agency,
Office of Research and Development, Environmental Research
Laboratories, Duluth,  Minnesota.

Weed Science Society of America  (WSSA), 1979.  Herbicide handbook.
Weed Science Society of America, Champaign, Illinois,   pp.  274-279.

       REFERENCES AS CITED IN EPA,  1980 METOLACHLOR;  PESTICIDE
                        REGISTRATION STANDARDS

Affiliated Medical  Research, Incorporated, 1974a.   Acute dermal LD50
of CGA-24705-technical  in  rabbits:  Contract  No.  120-2255-34.
Received September 26, 1974 under 5G1553.  (Unpublished study prepared
for Ciba-Geigy Corp.,  Greensboro, NC; CDL:   112840-E.)

Affiliated Medical  Research,  Incorporated, 1974b.  Emetic dose 50 in
beagle dogs with  CGA-24705-technical:  Contract No.  120-2255-34.
Received September  26,  1974, Greensboro, NC;  CDL:   112840-C.

Affiliated Medical  Research, Incorporated, 1974c.  Twenty-one day
repeated dermal toxicity of CGA-24705-6E in rabbits:   Contract No.
120-2255-34.   Received September 26, 1974 under 56/553.  (Unpublished
study prepared for  Ciba-Geigy  Corp., Greensboro, NC;  CDL:   112840-Q.)

                                  17

-------
Affiliated Medical  Research,  Incorporated,  1974d.  Evaluation of CGA-
24705 technical  (FL 740408) as a potential  skin  sensitizer in the
guinea pig:  Contract No.  120-2255-34.  Receved  September  26,  1974
under 5G1553.  (Unpublished report  prepared for Ciba-Geigy, Corp.,
Greensboro, NC;  CDL:   112840-K.)

Affiliated Medical  Research,  Incorporated (1974e).  Acute  inhalation
study of CGA-24705-6E for  albino rats:   Contract No.  121-2253-34.
Unpublished study received September 26,  1974  under  5G 1533;  prepared
for Ciba-Geigy Corp.,  Greensboro, NC; CDL:   112840-M.

Ami, P., and D.  Miller,  1976.   Salmonella/mammalian-microsome
mutagenicity test with CGA 24705  (test  for  mutagenic properties  in
bacteria):   PH 2.632.   Received January 19,  1977 under 7F1913.
(Unpublished study prepared by  Ciba-Geigy,  Ltd., Basle,  Switzerland;
CDL:  95768-B.)

Barrows, M.  E.,  1974.   Exposure  of  Fish to  14C-CGA-24705.
Accumulation distribution, and  elimination  of  14C residues.   Report
No. 73019-3.   (Unpublished study received March  27,  1975 under 5F1606;
prepared by EG&G, Bionomics Environmental Consultants  for  Ciba-Geigy
Corporation,  Greensboro, NC;  CDL:   94376-E.)

Bathe, R.,  1973.   Acute oral LD50 of  technical CGA-24705 in the rat:
Project No. Siss 2979.  Received  September  26,  1974  under 5G1553.
(Unpublished study prepared by  Ciba-Geigy Corp.,  Ltd.,  Basle,
Switzerland; CDL:   112840-A.)

Buccafusco, R.  J.,  1978a.   Acute toxicity test results  of  CGA-24705 to
bluegill  sunfish (Lepomis  macrochirus).  Report No.  BW-78-181.
Received July  13,  1978  under  100.597.   (Unpublished  study  prepared  by
EG&G, Bionomics.)

Buccafusco, R.  J.,  1978b.   Acute toxicity test results  of  CGA-24705 to
rainbow trout  (SaJmo  gairdneri).  Report No. BW-78-6-186.   Received
July  13, 1978  under 100-597.  (Unpublished  study prepared  by EG&G
Bionomics; submitted  by Ciba-Geigy Corp.,  Greensboro,  NC., CDL:
234396.)

Ciba-Geigy, Limited,  1976.  Reproduction study CGA 24705 Tech.:   Rat:
Seg.  II.   (test  for teratogenic or embryotoxic  effects).  PH  2.632.
Received January 18,  1978  under 7F913.   (Unpublished study including
Addendum;  CDL: 96717-A;  96717-B.)

Dionne,  E., 1978.  Chronic toxicity of  CGA-24705 to  the fathead  minnow
(Pimephales promelas); Received December 13,  1978 under 100-587.
(Prepared by EG&G Bionomics for Ciba-Geigy  Corporation, Greensboro,
NC; CDL:  236620.)

Ellgehausen, H.,  1977.  Project Report  3/77:   Uptake,  transfer,  and
degradation of CGA  24705  (Dual.)  by aquatic organisms.  AC 2.52.
Received February 6,  1978  under 100-583.  (Unpublished study prepared
by  Ciba-Geigy  Ltd.,  Basle,  Switzerland; CDL:  232789-C.)

                                  18

-------
Fink, R.,  1974.   Eight-day dietary LC50 - bobwhite quail technical
CGA-24705:  Project No. 108-111.  Received September  26, 1974  under
5G1553.    (Unpublished study by Truslow Farm,  Inc., for  Ciba-Geigy
Corp.,  Greensboro, NC;  CDL:   112840-P.)

Fink, R.,  1976.   Acute oral LD5Q- mallard duck:   CGA-24705  technical:
Final report.  Received November 23,  ;976 under 100-587.   (Unpublished
study prepared by Truslow Farm,  Inc.,  for  Ciba-Geigy Corp.,
Greensboro, NC;  CDL:   226955-D.)

Fritz,  H., 1976.   Reproduction study CGA 24705  Tech.  Rat:   Seg.  II:
(test for teratogenic or  embryotoxic effects):   PH 2.632.  Received
January 19, 1977 under  7F1913.   (Unpublished  study prepared  by Ciba-
Geigy Ltd., Basle, Switzerland;  CDL:   95768-A.)

Hambock,  H.,  1974.  Project Report No.  1/74:  Distributions,
degradation,  and  excretion of CGA 24  705 in the rat:   AC 2.52.
Received  November 25,  1975 under 5G1553.  (Unpublished  report  prepared
by Ciba-Geigy Ltd.,  Basle,  Switzerland;  CDL:   94217-K.)

Industrial Bio-Test Laboratories,  Inc., 1975.  Report to Ciba-Geigy
Corporation:   acute dust inhalation toxicity  study with CGA-24705 and
CGA-18762  (1:1)  15G (FL-751873) in albino rats:   IBT  No.  663-07826.
(Unpublished study received February 9,  1976  under 100-EUP-44;
prepared  for Ciba-Geigy Corporation,  Greensboro, NC;  CDL:   96495-B.)

Kennedy,  G. L.,  1976.   Letter  (dated December 13,  1976.  relative  to
the 2-year carcinogencity study  of CGA 24705  in albino mice (IBT No.
8531-07925) |  to George Rolofson.   (Unpublished  study  received  January
19, 1977  under 7F1913;  prepared  by Industrial Bio-Test  Laboratories,
Inc.,  for Ciba-Geigy  Corp., Greensboro, NC;  CDL:  94221-C.)

Nham, D.,  and W.  A.  Harrison,   1977.  Report to  Ciba-Geigy  Corporation:
Acute oral toxicity study with Dual. 8E in albino rats:  IBT No.  8530-
10822.   study received  November  8,  1977 under 100-EUP-159;  prepared by
Industrial Bio-Test Laboratories,  Inc.,  for  Ciba-Geigy Corp.,
Greensboro, NC; including Addendum A - Validation by Ciba-Geigy Corp.;
CDL:  232191-A.)

Nham, D.,  and W.  A. Harrison,  1977. Report to Ciba-Geigy Corp.:
Acute dermal toxicity study with Dual.  8E  in  albino  rabbits:  IBT No.
8530-10822.  (Unpublished study received November 8,  1977  under  100-
EUP-59;  prepared  by Industrial Bio-Test Laboratories, Inc.,  for  Ciba-
Geigy Corp.,  Greensboro, NC; including Addendum  B  - Validation by
Ciba-Geigy Corp.; CDL:   232191-B.)

Sachsse,  K.,  1973a.   Irritation  of technical  CGA-24705  in  the  rabbit
eye:  Project No. Siss  2979.   (Unpublished study received  September
26, 1974  under 5G1553;  prepared  by Ciba-Geigy Ltd., Basle,
Switzerland; CDL:   112840-G.)
                                   19

-------
U.S. Environmental Protection Agency
Region 5, Library (PL-12J)
77 West Jackson Boulevarjd, 12th Floor
Chicago, IL  60604-3590

-------
Sachsse,  K.,  1973b.   Skin irritation in the rabbit after single
application of technical  CGA-24705:   Project No.  Siss 2979.
(Unpublished study received September 26, 1974 under  5G1553; prepared
by Ciba-Geigy Ltd.,  Basle Switzerland;  CDL:   112840-1.)

Sachsse,  K.,  1977.   Skin sensitizing (Contact Allergenic) effect  in
guinea pigs of technical  CGA-24705.   Project No.  Siss 5726.
(Unpublished study received October 17, 1977; prepared by Ciba-Geigy
Ltd.,  Basle; Switzerland.)

Sachsse,  K.,  and Ullman,  L.,  1974.  Acute toxicology  to rainbow trout,
crucian carp, channel catfish, bluegill, and guppy of technical CGA-
24705:  Project No. Siss  3516.  (Unpublished  study received September
26, 1974 under 5G1553;  prepared by  Ciba-Geigy, Ltd.,  Basle,
Switzerland; that includes a  cable  from Ciba-Geigy Corp., Greensboro,
NC on fish name change;  CDL:   112840-N.)

Scibor,  G.,  1977a.   Report to Ciba-Geigy Corporation:  Eye irritation
tests with Dual 8E in albino  rabbits:   IBT  No. 8530-1082.
(Unpublished study received November  8, 1977  under 100-EUP-59;
prepared by Industrial  Bio-Test Laboratories, Inc., for Ciba-Geigy
Corp., Greensboro,  NC;  including Addendum D - Validation by Ciba  Geigy
Corp.; CDL:   232191-D.)

Scibor,  G.,  1977b.   Report to Ciba-Geigy Corporatio26, 1974 under
5G1553;  prepared by Ciba-Geigy, Ltd.,  Basle, Switzerland; that
includes a cable from Ciba-Geigy  Corp., Greensboro, NC on fish name
change;  CDL:  112840-N.)

Scibor,  G.,  1977a.   Report to Ciba-Geigy Corporation:  Eye irritation
tests with Dual 8E in albino  rabbits:   IBT  No. 8530-1082.
(Unpublished study received November  8, 1977  under 100-EUP-59;
prepared by Industrial  Bio-Test Laboratories, Inc., for Ciba-Geigy
Corp., Greensboro,  NC;  including Addendum D - Validation by Ciba-Giegy
Corp., CDL:   232191-D.)

Scibor,  G.,  1977b.   Repot to Ciba-Geigy Corporation:  Primary skin
irritation test with Dual, BE in  albino rabbits:   IBT No. 8530-10822.
(Unpublished study received November  8, 1977  under 100-EUP-059;
prepared by Industrial  Bio-Test Laboratories, Inc., for Ciba-Geigy
Corp., Greensboro,  NC,  including Addendum E - Validation by Ciba  Geigy
Corp.; CDL:   232191-E.)

Smith, K. S.,  1,977.   Report:   catfish  bioaccumulation study following
exposure to 14c-metolachlor  in a  soil/water/fish ecosystem.   7E-6506.
(Unpublished study received February  6, 1978  under 100-583; prepared
by Cannon Laboratories,  Inc.,  for Ciba-Geigy Corp., Greensboro, NC;
CDL:   232789-U.)

Vilkas,   A. G.,  1976.  Acute toxicity of CGA-24705 technical to the
water flea Daphnia magna.  Received November 23,  1976 under  100-587.
(Unpublished study prepared by Aquatic Environmental  Sciences, Union
Carbide Corp.,  for Ciba-Geigy  Corp., Greensboro,   NC;  CDL:   226955-C.)

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