Document ID: EPA-HQ-OPP-2006-0820-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-10-18T04:00Z

EPA Registration Division contact: Barbara Madden (703) 305-6463 

2E6504

Summary of Petitions

	EPA has received a pesticide petition (2E6504) from Interregional
Research Project #4 (IR-4), Rutgers, The State University of New Jersey,
500 College Road East, Suite 201 W, Princeton, NJ 08540 proposing,
pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act
(FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180.189 by establishing
a tolerance for residues of coumaphos, O, O-Diethyl
O-(3-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-yl) phosphoro-thioate and
its oxygen analog (coumaphoxon;  O, O-Diethyl
O-(3-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-yl) phosphate in or on the
raw agricultural commodities honey at 0.1 parts per million (ppm) and
honeycomb at 100 ppm. EPA has determined that the petition contains data
or information regarding the elements set forth in section 408(d)(2) of
the FFDCA; however, EPA has not fully evaluated the sufficiency of the
submitted data at this time or whether the data supports granting of the
petition.  Additional data may be needed before EPA rules on the
petition.

A. Residue Chemistry                                       

. There are no registered uses for coumaphos on agricultural crops, or
ornamentals.   Therefore, plant metabolism data are not necessary or
required.  Coumaphos strips will be used in bee hives.  Of the two bee
products (honey and honeycomb), only honey is listed as part of animal
(human) diet per EPA’s Table 1.  Raw Agricultural and Processed
Commodities and Feedstuffs Derived from Crops.  The nature of the
coumaphos residues in rat and ruminant is adequately understood.  The
residues of concern in animals are  combined residues of coumaphos and
its oxygen analog (coumaphoxon), as specified in 40 CFR 180.189.

. Two different LC/MS/MS  methods, one each for honey and  honeycomb
(beeswax), were developed to measure the residues of coumaphos and its
oxygen analog.  The analytical methods have successfully passed EPA
compliant independent laboratory validation tests.   Due to a unique
specificity of the LC/MS/MS technique, no separate confirmatory
procedure is needed for coumaphos and its oxygen analog  in  honey or
honeycomb.  Coumaphos and its oxygen analog were found to be stable for
at least 18 months in honey and beeswax when frozen.  In addition, both
coumaphos and its oxygen analog have been evaluated using the
multi-residue methodologies as published in Pesticide Analytical Manual,
Volume I.  

. Two field trials were conducted for the determining the magnitude of
coumaphos residues in honey and honeycomb following bee hive treatment
with coumaphos bee strips (CheckMite+®) for the control of varroa mites
and the small hive beetle.

   

i)  In a field trial designed to determine the worst-case coumaphos
residues,  test sites with each test site consisting of five  healthy
commercial honey bee colonies (Apis mellifera L.) were used.  One
application of the CheckMite+ strips was made to one test site by
hanging two 10% coumaphos strips in the brood chamber of each of the
colonies.  The bee colonies at another the test site served as controls.
 Each colony in the study received a honey super on the top of the brood
chamber.  The coumaphos strips remained in the brood chambers of the
treated bee hives for 45 days during the honey flow.  

After the 45-day treatment period, the strips were removed along with
the honey supers.  

Honey and beeswax samples were collected randomly from each honey super
per colony.    In addition, few honey samples were taken from the brood
chambers.  The honey samples were taken from the brood nest frames
adjacent to the treatment strips as the worst-case. Immediately after
sampling, a new empty honey super was placed above the brood nest of
each of the colonies.  Sampling was repeated 13 days later by taking one
honey and one beeswax sample from each honey super per colony as
described above. 

Honey and beeswax samples were analyzed for the magnitude of residues
of coumaphos and its oxygen analog using the analytical methods
described above.  The maximum combined residues of coumaphos and its
oxygen analog in any single analysis from any sampling interval were
0.071 ppm in honey super honey, 0.073 ppm in brood chamber honey, 43 ppm
in honey super wax and 51 ppm in brood chamber wax.  The limit of
quantitation (LOQ) for each analyte was 0.01 ppm in honey and 0.5 ppm in
beeswax.  

ii)   The second field trial for the magnitude of coumaphos residues was
performed near Algoa (Texas).  In this trial, plastic strips
(CheckMite+®) impregnated with 5%, 7.5% or 10% coumaphos were used for
the control of varroa mites and the small hive beetle in processed honey
and comb honey production trials.

Nine test sites, each consisting of four standard honey bee colonies
(Apis mellifera L.) were used in this study.  Some test sites were used
for processed honey production and other sites were used for comb honey
production.  In the processed honey production trial, bee hives at one
site served as control.  Other bee hives were each treated with two 10%
coumaphos strips for the control of varroa mites and one 10% coumaphos
strip for controlling the small hive beetle.  The treatment materials
remained in the bee hives for 45 days, after which time all coumaphos
strips were removed from the hives.  After a withdrawal period of 14
days, honey supers were added to each brood chamber for honey
collection.  Honey was collected in the supers for 36 days.  For each
colony, honey from the honey supers was harvested by using a commercial
extractor, and samples of extracted honey and beeswax were taken for
residue analysis. 

In the comb honey production trial, bee hives at one site served as
control.  At one test site, each hive was treated with two 10% coumaphos
strips for varroa mite control and one 10% coumaphos strip under a cover
for controlling the small hive beetle.  At one test site, each bee hive
received one 10% coumaphos strip under a cover for the small hive beetle
control.  The treatment materials in the bee hives at the above two test
sites remained for 45 days, after which time the treatment materials
were removed from the brood chambers.  After a withdrawal period of 14
days, honey supers were added for honey collection to the brood chamber
of each colony.  At this time, the bee hives at the fourth site were
each treated with one 10% coumaphos strip for the small hive beetle
control and honey supers were added for honey collection.  Thirty-six
days later, honey and beeswax from the honey supers in all four sites
were harvested, and small sub-samples were taken for residue analysis.  

The maximum combined residues of coumaphos and its oxygen analog in any
single analysis from the sampling interval were 0.011 ppm in honey from
the processed honey trial, <0.5 ppm in the beeswax from the processed
honey trial, and (0.5 ppm in the comb honey (honey  plus honeycomb
combined).

B. Toxicological Profile

. Coumaphos technical is highly acutely toxic via the oral and
inhalation routes of exposure.  The rat acute oral LD50 = >17
milligram/kilogram (mg/kg) (category I) and the rat acute inhalation
LC50 =  > 0.038 milligram/Liter (mg/L) (category I).  It is moderately
toxic via the dermal route of exposure (the rat acute dermal LD50 = >
2000 mg/kg (category III); and the technical coumaphos was mildly
irritating to the eye (category III) and was not a skin irritant
(category IV) in rabbits. Coumaphos was not a dermal sensitizer in
rabbits and guinea pigs.  Coumaphos is classified as a Group E chemical,
indicating that it is “Not Likely” to be carcinogenic in humans via
relevant routes of exposure.

. [i)  Gene mutation - A Salmonella/microsome study was conducted. 
Coumaphos was not mutagenic when tested at levels up to 12,500 ug/plate
with and without metabolic activation in Salmonella typhimurium strains
TA1535, TA1537, TA100, and TA98. 

ii)   Structural chromosomal aberration - Coumaphos was tested in a
mouse-micronucleus test at different levels up to 1920 mg/kg by gavage. 
Negative results were obtained at 480 mg/kg.  Cytotoxicity was observed
at dose levels above 480 mg/kg.  Mortality was observed at higher dose
level making the results uninterpretable.

iii)  Direct DNA damage and repair - A Pol A test on Escherichia coli
was conducted.  Coumaphos was not mutagenic when tested at levels up to
5000 ug/plate with and without metabolic activation

. [i)  In a two-generation reproduction study, rats were fed diets
containing coumaphos at  0, 0.07, 0.3, or 1.79 mg/kg/day (males) and 0,
0.08, 0.34 or 2.02 mg/kg/day (females), respectively.  There was no
increased sensitivity to pups over the adults.  For parental/systemic
toxicity, the NOAEL was 1.79 mg/kg/day, (HDT); a LOAEL was not
established.  For reproductive toxicity, the NOAEL was 1.79 mg/kg/day; a
LOAEL was not established.

Cholinesterase activity was measured in adults and pups.  There was
dose-related decreases in plasma and red blood cell cholinesterase
activity in dams at 0.34 and 2.02 mg/kg/day.  Generally, no differences
were seen on day 47 and day 91 measurements.  Brain levels were
biologically significantly inhibited in Fo and F1 adult females at 2.02
mg/kg/day, and in Fo adult males at 1.79 mg/kg/day.  In pups, no
significant changes in red blood cell or brain cholinesterase activity
were seen on day 4, but on day 21 changes were seen at 2.02 mg/kg/day. 
In F1 pups, plasma and red blood cell ChE inhibition of 38-44% was seen,
while in F2 pups, only plasma was affected (31-44%).  The only
significant brain inhibition in pups was an 8% decrease in F1 females on
day 21.  The NOAEL was 0.3 mg/kg/day for cholinesterase inhibition in
dams and in pups on day 21.

ii)  The developmental toxicity studies in rats and rabbits summarized
below showed no evidence of additional sensitivity to young rats or
rabbits following pre- or postnatal exposure to coumaphos and comparable
NOAELs were established for adults and offspring.

a)  In a developmental toxicity study pregnant rats received oral doses
of coumaphos at 0, 1, 5 or 25 mg/kg/day during gestation days 6 through
15.   For maternal toxicity, the NOAEL was 5 mg/kg/day  and the LOAEL
was 25 mg/kg/day based on clinical signs of cholinesterase inhibition. 
For developmental toxicity, the NOAEL was 25 mg/kg/day (HDT); a LOAEL
was not established.  There was no evidence of teratogenicity.

b)  In a developmental toxicity study, pregnant rabbits were given
single oral dose of coumaphos at 0, 0.25, 2, or 18 mg/kg/day during
gestation days 7 through 19.  For maternal toxicity, the NOAEL was 2
mg/kg/day and the LOAEL was 18 mg/kg/day based on mortality (2/17) and
cholinergic signs.  For developmental toxicity, the NOAEL was 18
mg/kg/day (HDT); a LOAEL was not established.  There was no evidence of
teratogenicity.]

[i)  In a 13-week feeding study, coumaphos was orally administered in
the diet to rats equivalent to 0, 0.2, 0.5 or 1.0 mg/kg/day dose rate. 
Plasma, erythrocyte (RBC) and brain cholinesterase (ChE) levels were
determined at 3, 8 and 13 weeks. 

Brain ChE was not inhibited at any time.  The LEL for cholinesterase
inhibition was determined at or lower than 0.2 mg/kg/day based on RBC
ChE inhibition.  The NOEL for cholinesterase inhibition is less than 2
ppm.  No signs of systemic toxicity were observed at any dose. The
systemic LEL and NOEL were greater than 1.0 mg/kg/day. 

ii)  In a 21-day subchronic dermal toxicity study,  coumaphos was
administered to male and  female rats at dose levels of 0, 2, 4, 20 or
100 mg/kg/day.  Plasma, erythrocyte (RBC) and brain cholinesterase (ChE)
levels were determined.  The LEL for cholinesterase inhibition was 2
mg/kg/day based on RBC and plasma ChE.  The NOEL for cholinesterase
inhibition was less than 2 mg/kg/day.  Signs of systemic toxicity
occurred at 20 mg/kg/day and above and included muscle fasciculation in
males. The systemic LEL was 20 mg/kg/day based on muscle fasciculation
and tremors. The systemic NOEL was established at 4 mg/kg/day.

This study in combination with a second study (see below) was accepted
by EPA by using lower doses in females.

iii)  In a 21-day dermal study, coumaphos was administered to female
rats at dose levels equivalent to 0, 0.1, 0.5, 1.1 or 2.1 mg/kg/day.  At
1.1 mg/kg/day, RBC ChE was inhibited (24 and 28% for the two highest
doses).  The LEL for cholinesterase inhibition was 1.1 mg/kg/day based
on inhibition of RBC ChE in females. The NOEL for cholinesterase
inhibition was 0.5 mg/kg/day.  There was no systemic toxicity observed
at any dose level. The systemic LEL appeared greater than 2.1 mg/kg/day.
The systemic NOEL was 2.1 mg/kg/day (4 mg/kg/day based on a separate
study).  This study was considered acceptable when taken together with
the study cited above.  When the two studies were considered together,
the NOEL and LEL for systemic effects were determined to be at 4 and 20
mg/kg/day, respectively.  The NOEL and LEL for cholinesterase inhibition
were determined at 0.5 and 1.1 mg/kg/day, respectively.

. [i)   In a 2-year chronic feeding/carcinogenicity study in rat,
coumaphos was fed to groups of rats at dose levels equivalent to 0,
0.05, 0.25 or 1.22 mg/kg/day in males and at 0, 0.07, 0.36 or 1.70
mg/kg/day in females.   The systematic NOEL and LEL were  0.36 mg/kg/day
and 1.70 mg/kg/day in females, respectively, based on decreased body
weight gain.   The NOEL (ChE) and LEL (ChE) were established at 0.36
mg/kg/day and 1.70 mg/kg/day in females, respectively. 

There was no evidence of carcinogenicity at any dose. Dosing was
adequate to evaluate carcinogenic potential.

ii)  In a carcinogenicity study, coumaphos was administered to groups of
rats at dose levels of 10 or 20 ppm in the diet for 103 weeks.  Body
weights of female rats were slightly lower than the controls at 10 and
20 ppm. Decreases in male body weight was observed at 20 ppm.  No other
toxic manifestations were apparent.  There was no evidence that
administration of coumaphos was associated with an increase in tumors.
Dosing was considered adequate to evaluate carcinogenic potential.

iii)  In a carcinogenicity study, coumaphos  was administered to groups
of mice at dose levels at 10 and 20 ppm in the diet for 103 weeks.  No
toxic manifestations were apparent.  There was no evidence that
administration of coumaphos was associated with an increase in tumors.
Dosing was considered adequate to evaluate carcinogenic potential based
on range-finding data.  It was expected that ChE would have been
inhibited if the measurement was evaluated.

iv)  In a 1-year feeding study in dogs,  Beagles were fed coumaphos diet
equivalent to 0.025, 0.775, or 2.295 mg/kg/day (males), and 0.024,
0.705, or 2.478 mg/kg/day (females), respectively.  Control groups
received untreated diet.  Plasma, erythrocyte and brain cholinesterase
(ChE) activity was monitored in the study. Based upon significant and
biologically relevant depression of RBC ChE and plasma ChE activity
levels in dogs, this study provided a NOEL of 0.025 mg/kg/day and a LEL
of 0.7 mg/kg/day.

There were no other treatment related systemic changes at any dose
level. The systemic NOEL was 2.3 mg/kg/day and the LEL was greater than
2.3 mg/kg/day.

Carcinogenicity Classification - Coumaphos was classified by the HED
RfD/Peer review Committee on October 13, 1994 as a "Group E" , i.e., no
evidence of noncarcinogenicity for humans, based on adequate studies in
two animal species.] 

. [Radiolabeled  coumaphos was administered to rats at dose levels of
1.0 mg/kg intravenously and 1.0 and 15.0 mg/kg, orally. A fourth group
received 1.0 mg/kg coumaphos daily for 14 days.   The plasma half life
ranged from 2.35 to 3.30 hours at 1.0 mg/kg (including the repeated dose
group) and 2.93 to 5.30 hours at 15.0 mg/kg.  

Urinary excretion was rapid with 63-87% of the administered dose being
excreted within 24 hours. 76-96% of the administered dose was excreted
within 168 hours.  Tissue residues were highest in fat, kidney, liver
and muscle. The urine contained 5 to 8 metabolites and the feces
contained 5 to 7 metabolites. The major metabolite was chlorferone (the
hydroxylated leaving group).  Coumaphos represented 0.1% of the urinary
metabolites.  Coumaphos represented 0.2% of the fecal metabolites when
administered intravenously.  However, when administered orally coumaphos
represented approximately 15 to 55% of the fecal metabolites.  The range

varied depending on whether coumaphos was administered as a single dose
or repeated dose.]

. NA 

.  NA 

C.  Aggregate Exposure

Food. Coumaphos is an acaricide currently registered in the U.S. for use
on livestock animals for the control of arthropod pests.  Tolerances
have been established (40 CFR 180.189) for the combined residues of
coumaphos (O,O-diethyl O-3-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-yl
phosphorothioate) and its oxygen analog, coumaphoxon (O,O-diethyl
O-3-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-yl phosphate), in or on
meat, fat, and meat byproducts of cattle, goats, hogs, horses, and
sheep, and in milk.  Tolerances are set at 1.0 ppm in livestock tissues
and 0.5 ppm in milk-fat residues.  Although tolerances are still listed
in the most recent  CFR (revised July 1, 2001) for sheep and goats (1.0
ppm), the use of coumaphos on sheep and goat is no longer supported by
Bayer (the technical registrant) in the U.S.  The USDA does wish to
maintain these tolerances for a small number of sheep and goats imported
in the U.S. from Mexico.  The dietary risk assessment conducted by
Bayer, nevertheless included the use on sheep and goats to be supportive
of USDA's interest in continuing this use on a limited scale.  Bayer
used the following  toxicological dose and endpoints (LOAEL 2.0
mg/kg/day, UF = 300, giving the acute RfD = 0.007 mg/kg/day; NOAEL 0.025
mg/kg/day, UF = 100, giving the chronic RfD = 0.00025 mg/kg/day) for
conducting the acute and chronic dietary risk assessments for coumaphos.
 For coumaphos dietary risk assessment, the FQPA SF = 1 is established
by EPA.

Bayer performed the acute and chronic dietary exposure analysis for
coumaphos by using the Dietary Exposure Evaluation Model (DEEM(, version
7.76).  The DEEM analysis evaluated the individual food consumption as
reported by respondents in the USDA 1994-6/98 nationwide Continuing
Surveys of Food Intake by Individuals (CSFII) and accumulated exposure
to the chemical for each commodity.  The anticipated residue values
(ARs) were calculated from field trial data for estimation of both acute
and chronic dietary exposures for all livestock commodities, with the
exception of milk.  The residue values used for milk were taken from the
USDA's PDP 1997 and 1998 monitoring data which showed no detectable
residues in milk out of 750 samples tested. 

The DEEM analysis included the following percent livestock treated (PLT)
information: 4% beef including lean meat without removable fat, beef
fat, beef liver, beef byproducts, kidney; 1% horse including lean meat;
1% hog including meat, hog fat, hog liver, hog byproducts; 1% veal
including lean meat without removable fat, veal fat, veal liver, veal
meat by-products, veal kidney; 4% milk; sheep and goats (0.1% each); and
40% honey.  

For honey, the average value determined in a Bayer field trial for the
combined residues of coumaphos and its oxygen analog for three replicate
samples representing the worst-case residues  was used for both acute
and chronic dietary exposure assessment.  This is because all honey food
forms are classified as partially blended commodity (HED SOP 99.6
Classification of Food Forms with Respect to Level of Blending, August
20, 1999).  The average coumaphos residues in honey was 0.043 ppm.  The
concentration factor of 0.6  was considered for coumaphos residues for
processed honey. This value was determined by a laboratory honey
processing study conducted by Bayer.  This laboratory study showed
average 40% reduction in coumaphos residues after honey processing. 

Both the acute and chronic analyses for coumaphos are highly refined
(Tier 3 Monte-Carlo) estimate of dietary exposure from residues in food
with 500 iterations and seed of 10 for acute and chronic analysis.  Both
acute and chronic dietary exposures were each evaluated at the 99.9th
percentile for the overall U.S. population and various population
subgroups.  The results of the acute and chronic dietary exposure
analysis performed by Bayer are summarized below.

a)  Acute exposure.  For the acute dietary exposure analysis evaluated
at the 99.9th percentile, the most highly exposed population subgroup,
children 1-6 years, had an exposure equal to 18.3% of the aRfD (acute
reference dose) and a margin of exposure (MOE) of 1558 at the 99.9th
percentile.  The acute dietary exposure occupied 8.7% of the aRfD for
the U.S. population, 4.4% of the aRfD for females 13 through 50 years
old, 17% of the RfD for all infants less than 1 year old; the infant
sub-population at greatest exposure, and 18.3% of the aRfD for children
1-6 years old, the children sub-population at greatest exposure. 
Milk-based water was the most critical commodity for the acute dietary
analysis, and it contributed 71% to the acute exposure of the children
1-6 years subgroup.  However, there have been no detects of coumaphos
residues in 750 samples of milk products in the USDA Pesticide Data
Program (PDP) for the years 1996 through 1998. The Tier 3 Monte Carlo
acute dietary exposure estimates were all below EPA's level of concern
for the overall U.S. population as well as the various population
subgroups.

b) Chronic exposure.   For the chronic dietary exposure analysis
evaluated at 99.9th percentile, the most highly exposed population
subgroup, children 1-6 years, had an exposure equal to 13.3% of the cRfD
(chronic reference dose) for children 1-6 years old. The critical
commodities contributing to the chronic exposure of the children 1-6
years subgroup were dairy products (8.7%) and meat (4.5%).   The chronic
dietary exposure utilized  4.5% of the RfD for the U.S. population, 4.5%
of the RfD for all infants less than 1 year old.  The Tier 3 chronic
dietary exposure estimates for the overall U.S. population as well as
the various population subgroups were all below EPA's level of concern.

  Bayer has  generated new data on the adsorption/desorption of
coumaphos and its oxygen analog (coumaphoxon) in four U.S. soils.  The
results of this study showed Koc values ranging from  749.7 to 4,102.7
for coumaphoxon, and from 1845.4 to 10,232.6 for coumaphos.   Using the
new data and FIRST and SCI-GROW models for analysis, the estimated
environmental concentrations (EEC's) of coumaphos in surface water and
ground water, respectively, for acute exposures are estimated to be 6.7
ppb for surface water and 0.01 ppb for ground water.  The EEC's for
chronic exposures are estimated to be 1.7 ppb for surface water and 0.01
ppb for ground water.  Information related to the Agency suggests that
most of the coumaphos residual resulting from dip use on livestock is
collected and transported to concrete-lined evaporation pits thereby
negating any potential for ground water contamination.  For this 
reason, these EECs are very conservative exposure assessment for
coumaphos. 

 

Coumaphos is not registered for use on any sites that would result in
residential exposure.  The term “residential” is used here to refer
to non-occupational, non-dietary exposure (e.g., for lawn and garden
pest control, indoor pest control, termiticides, and flea and tick
control on pests).

D. Cumulative Effects

Coumaphos is in a family of pesticides known as organophosphates.  EPA
has concluded that organophosphates share a common mechanism of toxicity
and thus have a cumulative toxic effect (A Common Mechanism of Action:
The Organophosphate Pesticides, 11/2/98, USEPA).  Under normal
circumstances, the Agency would not consider establishing a tolerance
for an organophosphate product prior to completing the cumulative
assessment for this class of pesticide.  However, EPA has considered the
potential cumulative effects of coumaphos, and EPA concluded the risks
posed by granting this tolerance are so small that they are effectively
indistinguishable from the overall aggregate risk of coumaphos, much
less the overall cumulative risk posed by the organophosphates.  The
dire need for this use, combined with its infinitesimal risk, make it
clear the use of CheckMite+® will not have any additive effect on the
cumulative risk of organophosphates.

E.  Safety Determination

. Based on the exposure assessment described above and on the
completeness and reliability of the toxicity data, it can be concluded
that the exposure estimates from all label and the proposed use in
beehives of coumaphos are 8.66% of aRfD (aPAD) and 4.5% of cRfD (cPAD)
for dietary exposures.  EPA generally has no concerns for exposures
below 100 percent of the PAD.  Thus, it can be concluded that there is
reasonable certainty that no harm will result from aggregate exposure to
coumaphos residues.

. The Agency has reviewed all toxicology studies submitted and has
determined that the toxicity data base is essentially complete.  The
FQPA Safety Factor was reduced to 1X.  The toxicity database includes an
acceptable two-generation reproduction study in tars, acceptable
prenatal developmental toxicity studies in rats and rabbits, and
acceptable acute and subchronic neurotoxicity studies in rats.  These
studies show no increased sensitivity to fetuses as compared to maternal
animals following acute in utero exposure in the developmental rat and
rabbit studies and no increased sensitivity to pups as compared to
adults in a multi-generation reproduction study in rats.  There was no
evidence of abnormalities in the development of the fetus nervous system
in the pre/postnatal studies. 

Using the same exposure assumptions as employed for the determination in
the general population, it has been calculated that the percent of the
RfD that will be utilized by aggregate exposure to residues of coumaphos
is <13.3% of cRfD and 18.26% of aRfD for children 1-6 years (the most
impacted sub-population).  Therefore, based on the completeness and
reliability of the toxicity database and the conservative exposure
assessment, Bayer concludes that there is a reasonable certainty that no
harm will result to infants and children from aggregate exposure to
coumaphos residues.

F.  International Tolerances

There are no Codex tolerances for coumaphos, therefore there are no
harmonization issues with this tolerance.

 PAGE  9 

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