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coumaphos Fact Sheet 9/89

Name of Chemical:  COUMAPHOS
Reason for Issuance:  REGISTRATION STANDARD
Date Issued:  SEPTEMBER 27 89
Fact Sheet Number:  207


                         1. DESCRIPTION OF CHEMICAL


Common Name:  Coumaphos

Chemical Family:  Organophosphate

Pesticide Type:  Insecticide/acaricide

Chemical Name:  O,O-diethyl 0-(3-chloro-4-methyl-2-oxo-
                2H-l-benzopyran-7-yl) phosphorothioate

Trade Names:  Bay 21/199, Asuntol, Muscatox, Resitox,
              Baymix, Meldane, Co-Ral and Negashunt

Other Chemical
Nomenclature:  0-3-chloro-4-methylcoumarin-7-yl O,O-diethyl
               phosphorothioate; 3-chloro-7-diethoxyphosphino-thioyloxy-
               4-methylcoumarin; 0-(3-chloro-4-methyl-2-oxo-2H-l-
               benzopyran-7-yl) O,O-diethyl phosphorothioate (Chemical
               Abstracts, 9th Collective Index); 3,chloro-7-hydroxy-
               4-methylcoumarin O-ester with 0,O-diethyl
               phosphorothioate (8th Collective Index); 0,3-chloro-4-
               methyl-2-oxo-2H-chromen-7-yl O-O-diethyl
               phosphorothioate; [0-(3-chloro-4-methyl-7-coumarinyl)]
               0,O-diethyl phosphorothioate; 0,O-diethyl 0-(3-chloro-4-
               methyl-7-courmarinyl) phosphorothioate; phosphorothioic
               acid 0-(3-chloro-4-methyl-2-oxo-2H-l-benzopyran-7-yl)
               O,O-diethyl ester; 3-chloro-4-methylumhelliferone, O-
               ester with 0,0-dietyl phosphorothioate; O,O-diethyl
               0-(3-chloro-4-methylumbelliferone thiophosphate

Year of Initial Registration:  1958

CAS Registry Number:  56-72-4
EPA Pesticide Chemical Code (Shaughnessy Number):  036501
U.S. Manufacturer:  Bayvet, a division of Cutter Laboratories


                    2. USE PATTERNS AND FORMULATIONS

     Coumaphos is applied as a direct animal treatment to control 
arthropod pests of beef cattle, dairy cattle, sheep, goats, horses and 
swine.  It is used to treat swine bedding.  Registered control claims 
are for face flies, horn flies, fly larvae, cattle grubs, ticks 
(including ear tick), lice, mites, screwworms, sheep keds and 
fleeceworms.  Methods of application consist of dusts, sprays, dips, 
pour-ons, dust bags and backrubber oilers.  Annual usage is  264,000 to 
525,600 lbs (1986 estimate).  The predominate use is on beef cattle 
(98%).   relatively small amount is used on dairy cattle (<2%) and swine 
(<1%). 

              3 CURRENT STATUS AND SUMMARY SCIENCE STATEMENT

     Toxicity data requirements for.registration of products containing 
coumaphos (including acute toxicity testing on end-use product 
formulations) have been met, except for a 21-day dermal toxicity study, 
a non-rodent chronic toxicity study, a reproduction study, and a 
structural chromosome aberration study. Technical coumaphos is highly 
acutely toxic by the oral and inhalation routes of exposure (Toxicity 
Category I and II, respectively) and moderately acutely toxic by the 
dermal route of exposure (Toxicity Category III) based on studies using 
rats, rabbits and guinea pigs.  Technical coumaphos causes only mild eye 
and dermal irritation (Toxicity Category III and IV, respectively), and 
is non-sensitizing.   End-use product formulations fall in a range of 
Toxicity Categories from I to III.  Coumaphos does not produce 
organophosphate-type delayed neurotoxicity, based on acute neurotoxicity 
testing in hens.  The oncogenic potential of coumaphos is satisfactorily 
defined.  In vitro microbial studies for gene mutation and DN damage 
coumaphos did not cause a mutagenic response, and when tested in the rat 
and mouse, there were no carcinogenic effects noted. Coumaphos is not a 
developmental toxicant, or teratogen based on findings in studies 
utilizing rats and rabbits.  Results of a chronic feeding study using 
rats show that cholinesterase (plasma and erythrocyte) is the primary 
target of coumaphos.  Decreased body weight gain is a secondary effect. 
In a rat metabolism study, coumaphos was rapidly excreted.  There were 
no dose-related changes in metabolism or evidence of 
activation/bioaccumulation.

     The coumaphos data base for ecological effects testing is complete, 
with the exception of two special studies.  Based on the results of 
laboratory studies using birds, fish, and aquatic invertebrates, 
technical coumaphos is moderately acutely toxic to fish and very highly 
acutely toxic to birds and aquatic invertebrates.  Coumaphos is 
moderately toxic to birds on a subacute (dietary) basis. Aquatic 
invertebrates may be potentially exposed to hazardous levels of 
coumaphos resulting from washing-off of the material from the backs of 
newly treated cattle which have entered a body of water. Aquatic residue 
monitoring is required to assess the potential hazards.  Due to the 
potential for avian exposure resulting from birds feeding in cattle lots 
and on the backs of cattle, Tier I avian field testing is required to 
assess possible effects to birds resulting from the direct treatment to 
livestock.

     The environmental fate profile for coumaphos is adequately 
delineated for the registered use pattern, except for a groundwater 
assessment.  Coumaphos is relatively immobile in aged sandy loam soil, 
based on findings in a column leaching study. There are no immediate 
concerns for groundwater contamination from non-point source application 
of coumaphos.  However, the potential does exist for localized, point 
source contamination in animal treatment areas (particularly where 
animals are dipped), and as a result of associated disposal practices.  
Due to increased Agency sensitivity in the area of pesticides and 
groundwater contamination, environmental fate studies are required so 
that the Agency can assess coumaphos's potential for point source 
contamination.

     Most of the residue chemistry conclusions drawn in the 1981 
Standard have been reversed in the current Standard.  Residue chemistry 
data requirements were not imposed in the 1981 Standard.  Since issuance 
of that Standard, the Agency has published residue chemistry guidelines 
(Pesticide Assessment Guidelines, Subdivision 0, 1982, EPA-540/9-82-023) 
and other Federal Register (FR) Notices which provide a more stringent 
interpretation of the existing regulations.  As a result of these new 
guidelines, data are now required in the area of animal metabolism, 
storage stability and method validation.  No changes to coumaphos 
tolerances are indicated at this time.

     The Agency is unable to totally assess the safety of current 
tolerances and establish an acceptable daily intake (ADI) value for 
coumaphos because of the absence of chronic toxicity studies 
(reproduction and dog chronic toxicity), and outstanding residue 
chemistry data.   However, a preliminary dietary exposure analysis has 
been performed for coumaphos.  Based on the results of this analysis,  
current coumaphos tolerances are considered to be adequate to protect 
the public health.  When the remaining data requirements have been 
fulfilled, the Agency will perform a final reassessment of coumaphos 
tolerances.


Chemical/Physical Characteristics of the Technical Material

Empirical Formula:   C14H16ClO5PS
Molecular Weight:  362.8
Color:  grey to tan
Physical state:  powder to granules
Odor:  characteristic sulfur
Melting Point: 90 to 95 degrees C
Boiling Point:  20 degrees C at 10 to the minus 7 mmHg
Solubility:  (at 20 degrees C):  g/100 mL at 20 degrees C
             acetone                   23.82
             methylene chloride         6.39
             denatured alcohol         0.90
             xylenes                    0.90
             hexanes                    0.07
             water  insoluble at        0.002
             octanol                    0.13
             odorless mineral spirits   0.09
             diethyl phthalate         21.50
Vapor Pressure:  1 X 10 to the minus 7 mmHg
Density, Bulk Density, or
Specific Gravity:  granules: 30.06 lb/cu ft, loose; 30.85 lb/cu ft,
                   packed. mhammermilled: 24.35 lb/cu ft, loose; 30.51
                   lb/cu ft, packed
pH:  7.23 at 1 g/100 mL
Stability:  hydrolyses slowly under alkaline conditions; stable under
            normal storage conditions and use; incompatible with
            piperonyl butoxide
Storage Stability:  Stable (<6% loss) in glass vials up to 8 weeks at 
                    -12 to 50 degrees C, dry and at pH 4-10, at 83%
                    moisture, exposed to aluminum, and stainless steel;
                    stable exposed to sunlight for 4 days.

Toxicology Characteristics

Acute Oral:  Toxicity Category I (LD50 of greater than 240 mg/kg in
             males rats and 17 mg/kg in female rats)

Acute dermal:  Toxicity Category III (LD50 of greater than 2400
               mg/kg in rabbits

Acute inhalation:  Toxicity Category II (LC50 dose for a l-hour is 341
                   mg/m3 in female rats and greater than 1080 mg/m3 in
                   male rats)

Primary eye irritation:  Toxicity Category III, mild eye irritation
                         reported

Primary dermal irritation:  Toxicity Category IV, very minor dermal
                            irritation reported

Skin sensitization:  No observable evidence of dermal sensitization

Delayed Neurotoxicity:  Did not induce delayed neurotoxicity in an
                        acceptable study in hens.

Subchronic non-rodent/rodent studies:  None available.  Not required
       since chronic data supercede need for subchronic testing.

21-day dermal toxicity:  Required Study

Chronic toxicity:  Dog study is required.  Rat study NOEL is 0.07 mg/kg
                   for decreased cholinesterase activity.

Oncogenicity:  The mouse and rat chronic toxicity/oncogenicity studies
               did not reveal any evidence that coumaphos is oncogenic.

Mutagenicity:  Negative in all areas of mutagenicity tested.  A
               structural chromosomal abberation study is required.

Teratogenicity:  Rat teratology study NOEL and LEL were 5 and 25 mg/kg
                 (based on the observation of cholinergic effects),
                 respectively.  The developmental NOEL was greater than
                 25 mg/kg (HDT).  Rabbit teratology study maternal NOEL
                 and LEL were 2.0 and 18.0 mg/kg, respectively;
                 developmental NOEL was greater than 18.0 mg/kg (HDT).

Reproduction:  Required study

Metabolism:  In a rat metabolism study, coumaphos was rapidly excreted.

No dose-related changes in metabolism or evidence of activation/
bioaccumulation were noted in this study.


Environmental Characteristics

     Based on the results of a column leaching study, coumaphos can be 
characterized as persistent, but immobile in sandy loam soils.  There 
are no immediate concerns for groundwater contamination from non-point 
source application of coumaphos.  However, the potential does exist for 
localized, non-point source contamination in animal treatment areas 
(particularly where animals are dipped), and as a result of associated 
disposal practices.  In order to evaluate the potential for point source 
contamination, special studies are required: a photodegradation study in 
soil, a photodegradation study in water, an adsorption/desorption study, 
a hydrolysis study  and a retrospective field dissipation study.

Ecological Characteristics

     Based on the results of acceptable laboratory data, technical 
coumaphos is characterized as highly to very highly toxic to birds, 
moderately toxic to fish and highly toxic to aquatic invertebrates:

- Acute LD50 (mallard): 29.4 mg/kg
- Acute LD50 (pheasant): 7.94 mg/kg
- Dietary LC50:
  401 ppm (mallard)
  82 ppm (bobwhite)
- Freshwater invertebrates toxicity (96-hr LC50) for amphipods: 0.15 ppb
- Fish acute toxicity (96-hr LC50) for rainbow trout: 5000 ppb

     Results of laboratory testing, in conjunction with theoretical 
monitoring, indicate that aquatic invertebrates may be potentially 
exposed to hazardous levels of coumaphos resulting from washing-off of 
the material from the backs of newly treated cattle which have entered a 
body of water, such as a pond or stream.  To evaluate the potential 
risk, a residue monitoring study is required.  There is a potential for 
avian exposure resulting from birds feeding in cattle feedlots and on 
the backs of cattle.  Tier I avian field testing is required to assess 
possible effects to birds resulting from direct treatment to livestock.


Tolerance Assessment

     U.S. tolerances are established for residues of the insecticide 
coumaphos, 0,O-diethyl 0-(3-chloro-4-methyl-2-oxo-2H-l-benzopyran-7-yl) 
phosphorothioate, and its oxygen analog, 0,0-diethyl 0-3-chloro-4-
methyl-2-oxo-2H-l-benzopyran-7-yl-phosphate, in or on raw agricultural 
products as follows (40 CFR 180.189):
    -- 1 ppm in or on meat, fat, and meat byproducts of cattle, goats,
       hogs, horses, poultry(1), and sheep
    -- 0.5 ppm in milk fat (reflecting negligible residues in milk)
    -- 0.1 ppm in eggs

     Most of the residue chemistry conclusions drawn in the 1981 
Standard have been reversed.  No residue chemistry data requirements 
were imposed in the 1981 Standard.  Since issuance of that Standard, the 
Agency has published residue chemistry guidelines (Pesticide Assessment 
Guidelines, Subdivision 0, 1982, EPA-540/9-82-023) and other FR Notices 
which provide a more stringent interpretation of the existing 
regulations.  As a result of these new guidelines, data are now needed 
in the area of animal metabolism, storage stability and method 
validation.


__________________________

(1) There are no longer any federally registered uses for 
poultry/poultry houses.  Therefore, the Agency intends to revoke the 
tolerances for poultry and eggs.


     The Provisional Acceptable Daily Intake (PADI) for coumaphos is 
0.0007 mg/kg/day and is based on the 2-year rat feeding/oncogenicity 
study NOEL of 0007 mg/kg/day (based on plasma cholinesterase inhibition 
in females) and uncertainty factor of 100.  The Anticipated Residue 
Contribution (ARC) for the United States population is 0.000127 
mg/kg/day, occupying 18.2% of the PADI.  The two highest calculated 
exposures for the population subgroups are children 1 to 6 years of age 
[ARC occupies 33.6% of the PADI] and children 7 to 12 years of age [ARC 
occupies 25.6% of the PADI].  Based on these calculations, coumaphos 
applied at the currently registered application rates would not be 
expected to exceed established tolerances.

     The Agency is unable to totally assess the safety of current 
tolerances and establish an acceptable daily intake (ADI) value for 
coumaphos because of the absence of chronic toxicity studies 
(reproduction and dog chronic toxicity), and outstanding data in the 
area of animal metabolism, method validation and storage stability.  
When the required data have been submitted and evaluated, the Agency 
will perform a final reassessment of coumaphos tolerances.


              4. SUMMARY OF REGULATORY POSITIONS AND RATIONALES

-  The Agency is not initiating a Special Review for coumaphos.  No 
Special Review concerns were identified for this chemical by the Agency 
during its review of the current data base.

-  The Agency is classifying coumaphos 11.6% EC and 42% flowable 
concentrate end-use products as restricted use due to acute oral 
hazards.

-  The Agency will approve new food/feed tolerances for coumaphos on a 
case-by-case basis.

-  Environmental fate testing is required to evaluate the potential for 
coumaphos to impact groundwater or surface water resulting from point 
source application.

-  A special aquatic residue monitoring study is required.

-  Special Tier I avian field testing is required.

-  The Agency will revoke the poultry and egg tolerances, since 
coumaphos is no longer federally registered for use on poultry or in 
poultry houses.

-  Unique labeling statements are required:

   -- Restricted-use classification is required for coumaphos
      11.6% EC and 42% flowable concentrate formulations.

   -- Special disposal instructions are required for products
      bearing directions for use a livestock dip treatment.

   -- Labels bearing directions for use on goats and sheep must
      be amended to specify a preslaughter interval (PSI) of 3 days.

   -- Product labels must bear revised and updated fish and wildlife
      statements.

   -- Worker safety and protective clothing statements are required for 
products falling in Toxicity Category I or II. 

   -- Each end-use product label must be revised to reflect the
      appropriate signal word and precautionary statements assigned to
      it based on the results of acceptable acute toxicity testing.

   -- Revised labeling must be submitted for those products which do not
      contain directions for use specifying a maximum single application
      rate expressed in terms of: (l) amount of active ingredient per
      animal; (2) a maximum seasonal application rate or number of
      applications permitted per season; and (3) a minimum interval
      between applications, revised labeling must be submitted.

                 5. SUMMARY OF OUTSTANDING DATA REQUIREMENTS


Toxicology

21-Day Dermal Toxicity                          1 Year
Dog Chronic Toxicity                            4 Years
Reproduction Study                              4 Years
Chromosome Aberration                           1 Year


Environmental Fate/Exposure

Photodegradation in Water and Soil              1 Year
Adsorption/Desorption                           2 Years
Special Retrospective Field Dissipation Study   2 "
Hydrolysis Study                                1 "


Fish and Wildlife

Monitoring for Aquatic Invertebrate
Mortality and Residues in Water                 3 Years
Tier I avian field testing                      3 Years


Residue Chemistry

Metabolism data - Animals                       1 Years
Residue Analytical Methods                       1 "
Storage Stability Data                          1 "


Product Chemistry

Remaining Data Gaps                             1-2 Years


                         6.  CONTACT PERSON AT EPA

George LaRocca.
Product Manager (15)
Insecticide-Rodenticide Branch
Registration Division (H7505C)
Environmental Protection Agency
Washington, DC  20460
Tel. No. (703) 557-24006

DISCLAIMER: THE INFORMATION PRESENTED IN THIS CHEMICAL INFORMATION FACT 
SHEET IS FOR INFORMATIONAL PURPOSES ONLY AND MAY NOT BE USED TO FULFILL 
DATA REQUIREMENTS FOR PESTICIDE REGISTRATION AND REREGISTRATION.