•   530R86105
                               UALITY
              ADVISORY
                    PROPACHLOR
            Criteria  and  Standards  Di
       i v i s i D n
        Office of Water  Regulations and  Standards
                     United Stat
es
             Environmental  Protection Rgency
                    MRRCH  1  S 8 G

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                                  WATER QUALITY ADVISORY
                                         Number  9 .

                                          PROPACHLOR

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


                The advisory concentration for Propachlor  in ambient water for the
 0        protection  of  freshwater aquatic  life is estimated to be 8  ug/L. There
\        was no  review  of saltwater data,  so there  is no   advisory concentration
.^         for the  protection of  saltwater aquatic organisms.  Care  should be
          taken  in the application of this advisory,  with consideration of its
          derivation,  as  stated in 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
          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 Propachlor in ambient water for  the
          protection of human health is estimated to  be 466 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 Protection Agency
                               Region 5, Library (PL-12J)
                               77 West Jackson Boulevard, 12th Floor
                               Chicago, 1L  60604-3590

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      HUMAN HEALTH AND AQUATIC LIFE
          LITERATURE SEARCH AND
           DATA EVALUATION FOR
                PROPACHLOR
   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 	      5
CRITERIAEVALUATIONANDRECOMMENDATION 	      6
     Aquatic Toxicity 	     11
     Health Effects 	     11
REFERENCES 	     15


                            LIST OF TABLES

Table 1.   Summary of Aquatic Toxicity Literature
           Review of Propachlor 	      3
Table 2.   Summary of Health Effects Literature
           Review of Propachlor 	      7
Table 3.   Data Requirements Calculation of Aquatic Life
           Interim Criteria—Propachlor 	     13
Table 4.   Data Requirements for Calculation of Human Health
           Interim Criteria—Propachlor 	     14


                           LIST OF FIGURES

Figure  1.  Summary of Toxicity Data on Propachlor 	      4

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                    HUMAN HEALTH AND AQUATIC LIFE
                LITERATURE SEARCH AND DATA EVALUATION
                                 FOR
                              PROPACHLOR
                 U.S. ENVIRONMENTAL PROTECTION AGENCY
              OFFICE OF WATER REGULATIONS AND STANDARDS
                   CRITERIA AND STANDARDS DIVISION
                             INTRODUCTION


    Propachlor is classified as a chloroacetamide, a group of herbi-
cides which also includes CDAA and alachlor.  The chemical name is 2-
chloro-N-isopropylacetanilide  (McEwen and Stephenson, 1979).   The
product goes by the commercial names Ramrod and Bexton.   Major produ-
cers are Monsanto Company, United States; Dow Chemical Company, United
States; and Shen Hong Agricultural Chemical  Company,  Ltd., Taiwan.

    Propachlor acts as a selective herbicide by reducing  cell elonga-
tion and cell division  through inhibition of protein synthesis (Rejto
et al., 1984).   It  has been  suggested that propachlor prevents the
activation of amino acids and amino acyl-tRNA formation or interferes
with the transfer of amino acyl-tRNA to  the  polypeptide.   Selectivity
of propachlor is based on the plant's  ability to metabolize or detoxi-
fy the compound (Jaworski,  1969).   Propachlor can be applied to crops
under three different application regimes:   pre-emergence soil sur-
face, early post-emergence,  and preplant incorporated with furrow
irrigation.  Propachlor has been used  for selective weed control for
corn,  sorghum, soybeans, cotton,  and peanuts (McEwen and Stephenson,
1979).   It  is  especially effective against a wide spectrum of grassy
weeds  such as foxtail, bromegrass, cheatgrass and crabgrass,  and
certain broadleaf weeds such as pigweed and lambsquarter  (Jaworski,
1969) .

    Propachlor was introduced in 1965,  and its use surpassed that of
CDAA.  Lower volatility, lower water solubility, and greater activity
accounted for its popularity.  Propachlor ranks second to atrazine in
total  volume  sold  for use on corn.

    Propachlor is nonpersistent and degrades rapidly in both soil and
aquatic environments  (Yu et al., 1975;  McEwen and  Stephenson,  1979).
Bioaccumulation in aquatic organisms and in crops is minimal  (Yu et
al.,  1975;  Zhukova and Shirko,  1979).  Mammalian toxicity is low;
however, acute toxicity to  fish  is high (WSSA,  1979).

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    Propachlor is a light-tan colored solid with the following physi-
cal properties:

       Molecular Weight:                 211.69
       Melting Point:                    67-76°c
       Vapor Pressure:                   2.3 x I0~4mm Hg at 25°C
       Boiling Point:                    110°C at 0.03 mm Hg
       Solubility in Water              700 mgl at 20°C
       Decomposition Temperature        170°C
                           (WSSA,  1979;  Windholz et al.f 1983)


                           SCOPE OF SEARCH


    Sources were identified through a computerized literature search
of TOXLINE, TOXBACK, NTIS,  and Toxicology Data  Base focusing on con-
trolled, dose-response laboratory studies  from 1965 to  1985.

    Information was also sought on the quality  assurance/quality con-
trol measures employed including use of  controls,  replicate treat-
ments, and chemical analysis of test concentrations.  Other informa-
tion such as bioaccumulation/biomagnification,  food chain,  ecological,
and health effects data were obtained where available.

    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,  November 28,  1980) and "  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

    Acute toxicity tests with fish indicate that fish are very sensi-
tive to propachlor.  The 96-hour LC50 (median lethal concentration)
value was  0.49 ppm for fathead minnows and 1.30 ppm for bluegill
fingerlings  (Table  1,  Figure  1).  Office of Pesticide Programs  (OPP)
has noted  96 hour  LC50 concentrations of  0.167mg/L for rainbow trout,
>1.4mg/L (ppm) for  bluegill sunfish and 0.23mg/L for channel catfish
in an unpublished  registration  standard science chapter.

    A model  ecosystem experiment demonstrated that propachlor is rapi-
dly degraded, and that bioaccumuiation in aquatic organisms is minimal
(Yu et al., 1975).   Labeled propachlor was applied to the base of 7-

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day-old sorghum plants at a rate of 0.5 Ib/acre.  Analysis of water
after 33 days revealed the existence of seven metabolites and 0.4
percent of the parent compound.   However,  neither the parent compound
nor any degradation products was detected in organisms.   Snails,
however, contained an unknown metabolite which was not identified.
There was no evidence that propachlor or its degradation products was
magnified in the food chain as total radioactivity in algae, mosquito,
and fish decreased in that  order from  0.21 to 0.015 ppm.

    Strateva  (1976)  recommended a maximum permissible concentration of
1 ppm in waters supporting fish.  However,  no additional information
regarding basis for this recommendation or data used in obtaining this
value was provided.

    Office Office of Pesticide  Programs of U.S.  EPA characterizes
propachlor as highly toxic to coldwater fish, and highly to moderately
toxic to warmwater fish and freshwater invertebrates.

                            Health Effects

    Mammalian toxicity of propachlor is low  (McEwen and Stephenson,
1979).   LD50 (median  lethal dose)  values ranged from 290 to >5010
mg/kg and varied with species tested and route of exposure  (Table  2).
Acute oral LD50 values  for rats ranged from  710  to  1,800 mg/kg. Let-
hal doses caused weakness, salivation, tremors, collapse, and coma.
Inhalation studies on rats with  Satecid (65 percent propachlor) repor-
ted an LC50 value of 6,000 mg/m3 after a 4-hour exposure period and a
14-day observation period  (Holnar and Paksy,  1978).   The acute oral
LD50 value for the mouse  is 290 mg/kg and for the rabbit ranges from
392 to >5,010 mg/kg.  Dermal application of propachlor to both species
produces strong irritating effects on skin and eye mucosa, erythema,
edema,  and penetrating ulcer  (Lehotsky et al., 1979).  The percuta-
neous LD50 value for the  rabbit  was 380 mg/kg in this study.

    A NOEL of 13.3 mg/kg/day was obtained for the dog after a 90-day
exposure period (Federal Register, 1982).   A NOEL of 10 mg/kg/day for
cattle and 5  mg/kg/day for sheep was obtained after a 10-day exposure
period  (Palmer, 1972).

    A no observed effect level (NOEL) of 13.3 mg/kg/day was obtained
for rats after a 90-day exposure period  (Federal Register,  1982).
Results from  a chronic study indicated that there is a  low-cumulative
and high adaptive effect with clinical changes (weight loss, changes
in peripheral blood, redox processes, and protein metabolism) and
pathomorphological dystrophic changes  in the liver  and kidneys.
Disturbances in liver function were also observed after dermal
application of 50-500 mg/kg propachlor.  Dermal application of Ramrod
in solution at a 0.5-1 percent concentration, however,  was nontoxic
after a 90-day exposure period.   Adamis and  Lehotzky (1980) studied
the effect of propachlor at 10 ug/L 7 x 106 cells on rat peritoneal
macrophages and found that lactate dehydrogenase activity decreased
while membrane permeability  increased, which was suggested to be the
basis for the development  of  toxic skin reactions.

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    Several studies provided evidence of the mutagenic properties  of
propachlor (NIOSH, 1979; Gentile et al.,  1977;  Gopalan et al.;  1981;
Lippens et al.,  1983;  Plewa et al.,  1984).   Positive  mutagenic  effects
were reported in a rat sperm morphology test (672 ppm)  and mouse
cytogenetic analyses  (10 ppm).   Propachlor caused anaphase bridge
formation, chromosome condensation,  and mitostatic effects in Vicia
faba.   Propachlor following plant activation caused a significant
increase in the mitotic gene conversion in Saccharomyces cerevisiae.
There was no effect on induction of  sex-linked  recessive lethals  in
Drosophila melanoqaster or induction of mutation in Salmonella  typhi-
murium with or without rat liver 59 microcomal activation.

    Information on the carcinogenicity of propachlor was not found;
however,  information regarding the effect of propachlor on cancer  cell
growth was available.   Propachlor at a concentration of 3 x 10   M
inhibited cell proliferation of L1210 mouse leukemia cells by 50
percent.  This effect was  reversible when cells were cleansed of
propachlor.  Inhibition of protein synthesis by propachlor was  sugges-
ted as  the mechanism  of action  (Zilkah et al.,  1981).  Studies  using
flow cytometric analysis found that propachlor caused lizio cells to
accumulate in the GI phase of the cell cycle.

    Several case  reports have shown that exposure to propachlor causes
skin irritation in humans.  Workers engaged in  propachlor production
or application have  developed eczema  and dermatitis  (Jung, 1979;
Dombay  and Farkasdy,  1978).   One death was attributed to propachlor
exposure; however, no information regarding the circumstances was
provided  (Done,  1979).


              
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                           Aquatic Toxicity


    Little information on aquatic  toxicity is available.  Results of
two aquatic tests with fish were reported  in the  literature, but no
information on methodology used was provided.   Strateva (1976) recom-
mended a water quality standard of 1 ppm in waters supporting  fish,
but no documentation for this standard was provided.  A water quality
advisory of 8 ug/L is proposed,  using the  96-hour LC50  concentration
of 0.167 ppm for rainbow trout reported by OPP, denied by 2, then by
10 to'give an approximate safe chronic value.

    Table 3 lists the data items required by  EPA  guidelines (Stephan
et al.,  1985)  for the application  of formulae  to  be used to obtain
component values for aquatic life  criteria development.  The current
lack of appropriate data prevents  calculation of  an Aquatic Life
Criterion until  further information is obtained (Table 3).   Acute
toxicity tests are needed for a salmonid,  a warm  water species commer-
cially  or recreationally  important, another family in the phylum
Chordata, a planktonic crustacean, a benthic  crustacean, an insect, a
phylum  other than Arthropoda/Chordata, and another family  of insect.
Acute-chronic ratios are needed for a fish, an invertebrate, and an
acutely sensitive freshwater animal species.   Acceptable test results
from a test with a freshwater algae and a vascular plant are needed in
addition to a bioaccumulation factor  for a freshwater species.


                            Health Effects


    According to  a tolerance  and  exemption notice published by U.S.
EPA on  propachlor (FR 47:28230,  June 30,  1982), an  acceptable daily
intake  (ADI)  level can be derived  from the no  observed effect level
(NOEL)  reported by Monsanto in a 90-day feeding study of dogs.  A
water quality criterion can be derived from the ADI by taking  into
account the fact that 2 liters of  water is the assumed daily consum-
ption rate of a  70 kg man.  U.S.   EPA currently recommends  the use of
chronic toxicity studies for deriving long-term exposure criterion for
water quality.  No observed adverse effect levels (NOAEL) or lowest
observed adverse  effect levels  (LOAEL) are also the ideal basis for
deriving criterion.   Using-the NOEL from the  90-day feeding study, the
ADI is calculated as follows:

               ADI = (13.3 mq/kg/day)  (70  kg)  = 0.931 mg/day
                                  1000

where:             13.3 mg/kg/day  = NOEL from 90-day  study
                           70 kg  = assumed weight of a man
                            1,000  = uncertainty factor.
                                  11

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The uncertainty factor of 1,000  is  justified on the basis that there
are no long-term or acute toxicity data for humans, and there are only
scanty results (e.g., no  chronic toxicity studies) on experimental
animals with no indication of carcinogenicity  (FR 45:79353,  November
28, 1980).   The water quality advisory  (A) for propachlor is calcu-
lated as follows:


                   A = 0.931 mg/day = 0.466 mg/L
                        2 I/day

where:  0.931 mg/day = ADI
             2 I/day = assumed water consumption  rate of 70 kg man.


    This advisory does not take  into account additional exposures that
could occur through consumption  of contaminated fish, becuase no
bioconcentration factor was found  in this literature search.  The Yu
et al.,  (1975).  Model  ecosystem study  showed little biomagnification,
and, based on this one would not expect the advisory to be
significantly different if consumption  of fish were included.
Additional information on the health effects of propachlor is still
needed to completely fulfill guideline requirements (Table  4).  NOAEL
and LOAEL values are needed for  several species to refine the ADI
estimate.   Teratology,  and reproductive studies also are needed.
Chronic toxicity assays also are appropriate to confirm the ADI esti-
mate.
                                  12

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     TABLE 3.  DATA REQUIREMENTS FOR CALCULATION OF AQUATIC LIFE
               INTERIM CRITERIA — PROPACHLOR

 Data Requirements               Available Data     Acceptability
  Aquatic Toxicity               for Propachlor   of Available Data

Acute test results from tests on:

  A salmonid (class Osteichthyes)       NO                	

  A warm water species                  YES               NO
  commercially or recreationally
  important  (class Osteichthyes)

  Another family in the phylum          YES               NO
  Chordata (fish, amphibian, etc.)

  A planktonic crustacean               NO                	
  (cladoceran,  copepod, etc.)

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

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

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

  Another family of insect              NO                	

Acute-chronic ratios with species from
three different families:

  One fish                              NO                	

  One invertebrate                      NO                	

  Acutely sensitive freshwater          NO                	
  animal species

Acceptable test results from a test with:

  Freshwater algae                      NO                	

  A vascular plant                      NO                	

Bioaccumulation factor with a fresh-    NO                	
water species  (if a maximum permissible
tissue concentration  is available)


                                  13

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         TABLE 4.   DATA REQUIREMENTS FOR CALCULATION OF HUMAN
                   HEALTH INTERIM CRITERIA — PROPACHLOR
  Data Requirements
 Human Health Effects

Non-Threshold:
                                Available Data
                                for Propachlor
  Acceptability
of Available Data
                                           a
Carcinogen                             NO
Tumor incidence tests (Incidence of    NA'
  tumor formation significantly more
  than the control for at least one
  dose level),  or
Data set which give the highest        NA
  estimate of carcinogenetic risk,  or
Lifetime average exposure tests, or    NA
Human epidemiology studies             —
  (if available, not required)
Threshold:
  Non-carcinogens                        YES
  Noobserved adverseeffeet level     N0°
    (at least 90-day),  or
  Lowest observed effect level           NO
  Lowest observed adverse effect level   NO

Acceptable Daily Intake:                 YES

  Daily water consumption                YES


  Daily fish consumption                 YES
                                                         _— (b)
  Bioconcentration factor                NO
  Non-fish dietary intake                NO
  Daily intake by inhalation             NO

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

Inhalation Studies:
  Available pharmacokinetic data         NO
  Measurements of absorption efficiency  NO
  Comparative excretion data             NO

  a) NA - Not applicable.
  b) NOEL is available (EPA approved).
                                                         YES
                                                   (EPA approved)
                                                         YES
                                                   (EPA approved
                                                    assumption)
                                                         YES
                                                   (EPA approved)
                                                    assumption)
                                  14

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