UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

     OFFICE OF

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date: 		06-MAR-2008

MEMORANDUM

SUBJECT:	Dicamba: Human-Health Risk Assessment for Proposed Section 3
New Uses on Sweet Corn.

Petition No. 0E6209

PC Code: 029801 	DP: 340156	Decision: 304187

Regulatory Action Type:  Section 3 Registration

Risk Assessment Type:  Single Chemical/Aggregate

FROM:	Mary Clock-Rust, Biologist

George F. Kramer, Ph.D., Senior Chemist

		Sarah Levy, Chemist

		P.V. Shah, Ph. D., Toxicologist

		Registration Action Branch 1 (RAB1)

RAB1/Health Effects Division (HED; 7509P)

THROUGH:	Dana Vogel, Branch Chief

		RAB1/ HED (7509P)

TO:		Dan Rosenblatt, RM 05

		Registration Division (RD; 7505P)

The HED of the Office of Pesticide Programs (OPP) is charged with
estimating the risk to human health from exposure to pesticides.  The RD
of OPP has requested that HED evaluate hazard and exposure data and
conduct dietary, occupational, residential, and aggregate exposure
assessments, as needed, to estimate the risk to human health that will
result from the proposed (and registered) uses of dicamba in/on sweet
corn.

A summary of the findings and an assessment of human-health risk
resulting from the proposed and registered uses of dicamba are provided
in this document.  The residue chemistry review was provided by George
Kramer (RAB1), the dietary exposure assessment was provided by Sarah
Levy (RAB1), the hazard assessment was provided by P.V. Shah, and the
risk assessment was provided by Mary Clock-Rust (RAB1).  The hazard
characterization and the occupational and residential exposure
assessments were taken from the dicamba reregistration eligibility
document (RED) (Memo, C. Olinger, D317720, 9/13/2005).

Table of Contents

  TOC \o \u  1.0     Executive Summary	  PAGEREF _Toc192560600 \h  3

2.0	Ingredient Profile	  PAGEREF _Toc192560601 \h  6

2.1	Summary of Registered/Proposed Uses	  PAGEREF _Toc192560602 \h  6

2.2	Structure and Nomenclature	  PAGEREF _Toc192560603 \h  7

3.0	Hazard Characterization and Dose-Response Assessment	  PAGEREF
_Toc192560604 \h  8

3.2	FQPA	  PAGEREF _Toc192560605 \h  10

3.2.1	Adequacy of the Toxicity Data Base	  PAGEREF _Toc192560606 \h  11

3.2.2	Evidence of Neurotoxicity	  PAGEREF _Toc192560607 \h  11

3.2.3	Developmental Toxicity Studies	  PAGEREF _Toc192560608 \h  11

3.2.4	Reproductive Toxicity Study	  PAGEREF _Toc192560609 \h  12

3.2.5	Additional Information from Literature Sources	  PAGEREF
_Toc192560610 \h  13

3.2.6	Pre-and/or Postnatal Toxicity	  PAGEREF _Toc192560611 \h  13

<IP_ADDRESS>	Determination of Susceptibility	  PAGEREF _Toc192560612 \h  13

<IP_ADDRESS>	Degree of Concern Analysis and Residual Uncertainties	  PAGEREF
_Toc192560613 \h  13

3.2.7	Recommendation for a Developmental Neurotoxicity Study	  PAGEREF
_Toc192560614 \h  14

3.2.8	FQPA Safety Factor for Infants and Children	  PAGEREF
_Toc192560615 \h  14

3.3	Classification of Carcinogenic Potential	  PAGEREF _Toc192560616 \h
15

3.4	Summary of Toxicological Doses and Endpoints for Use in Human Risk
Assessments	  PAGEREF _Toc192560617 \h  15

3.5	Recommendation for Aggregate Exposure Risk Assessments	  PAGEREF
_Toc192560618 \h  16

3.6	Endocrine Disruption	  PAGEREF _Toc192560619 \h  16

4.0	Dietary Exposure/Risk Characterization	  PAGEREF _Toc192560620 \h
17

4.1	Pesticide Metabolites and Degradates of Concern	  PAGEREF
_Toc192560621 \h  17

4.2	Environmental Fate	  PAGEREF _Toc192560622 \h  18

4.3	Drinking Water Residue Profile	  PAGEREF _Toc192560623 \h  18

4.4	Food Residue Profile	  PAGEREF _Toc192560624 \h  19

4.5	International Residue Limits	  PAGEREF _Toc192560625 \h  21

4.6	Dietary Exposure and Risk	  PAGEREF _Toc192560626 \h  21

4.6.1	Acute Dietary Exposure/Risk	  PAGEREF _Toc192560627 \h  22

4.6.2   Chronic Dietary Exposure/Risk	  PAGEREF _Toc192560628 \h  22

4.6.3	Cancer Dietary Risk	  PAGEREF _Toc192560629 \h  22

5.0	Residential (Non-Occupational) Exposure/Risk Characterization
PAGEREF _Toc192560630 \h  23

5.1	 Residential Handler Exposure and Risk	  PAGEREF _Toc192560631 \h
23

5.2	 Residential Post-Application Exposure and Risk	  PAGEREF
_Toc192560632 \h  23

6.0	 Aggregate Exposure and Risk Assessment/Characterization	  PAGEREF
_Toc192560633 \h  24

6.1	Acute Aggregate Risk	  PAGEREF _Toc192560634 \h  24

6.2	Short-term Aggregate Risk	  PAGEREF _Toc192560635 \h  24

6.3	 Chronic Aggregate Risk	  PAGEREF _Toc192560636 \h  25

7.0	Cumulative Risk Characterization/Assessment	  PAGEREF _Toc192560637
\h  25

8.0	Occupational Exposure/Risk Pathway	  PAGEREF _Toc192560638 \h  26

9.0	Data Needs and Label Recommendations	  PAGEREF _Toc192560639 \h  27

9.1	Toxicology	  PAGEREF _Toc192560640 \h  27

9.2	Residue Chemistry	  PAGEREF _Toc192560641 \h  27

9.3	Occupational and Residential Exposure	  PAGEREF _Toc192560642 \h  27

 1.0     Executive Summary

Dicamba (3,6-dichloro-o-anisic acid) is a selective benzoic acid
herbicide registered for the control of certain broadleaf weeds and
woody plants before their emergence.  It is an auxin agonist that is
readily translocated symplastically and apoplastically with accumulation
in meristemic regions of the plant.  Sensitive plants exhibit rapid
uncontrolled growth characterized by twisting and curling of stems and
petioles, stem elongation and swelling and leaf cupping.  Weed control
is generally achieved in 5 to 7 days.

Different forms of dicamba (acid and salt) have registered uses on
rights of way areas, asparagus, barley, corn (field and pop), grasses
grown in pasture and rangeland, oats, proso millet, rye, sorghum,
soybeans, sugarcane, and wheat.  There are residential uses on turf and
ornamentals.  Application rates range from 0.5 to 2.8 lb ae (acid
equivalent)/A.

A RED document was issued by HED on September 13, 2005 (Memo, C.
Olinger, D317720).  Some sections of the RED have been summarized in
this document.  For detailed information on dicamba, please refer to the
RED.

The current petition (0E6209) is a proposal for tolerances on sweet
corn, forage and stover.  A summary of the scientific databases and
estimated risks from the proposed use are included in this memorandum.

Hazard Assessment Summary

Dicamba has a low acute toxicity via oral, dermal or inhalation route
(Acute Toxicity Category 3 or 4).  It is an eye and dermal irritant but
it is not a skin sensitizer.  Consistent neurotoxic signs (e.g., ataxia,
decreased motor activity, impaired righting reflex and gait) were
observed in many studies in rats and rabbits at high doses.  There was
an increased incidence of abortion in the rabbit developmental toxicity
study at doses that also showed maternal toxicity.  In a two-generation
reproductive toxicity study, offspring toxicity was manifested as
decreased pup body weight gain in all generations at a dose lower than
the parental systemic toxicity no-observed adverse-effect level (NOAEL).
 Developmental studies in rats and rabbits showed no evidence
(qualitative or quantitative) for increased susceptibility following in
utero and/or pre-/post-natal exposure.  Following oral administration,
dicamba is rapidly absorbed and excreted in urine and feces.  Dicamba is
classified as “not likely to be carcinogenic to humans.”
Mutagenicity studies did not demonstrate evidence of mutagenic potential
for dicamba although some positive results were reported in published
literature.

Dose-Response Assessment

An acute neurotoxicity study in rats was selected for the general
population, including infants and children, as the basis for an endpoint
of concern for acute dietary risk assessment.  For short- and
intermediate-term incidental oral exposure and the chronic reference
dose (cRfD), a multi-generation reproductive toxicity study in rats was
selected based on impaired pup growth (decreased pup weights).

The dose and endpoint selected for dermal and inhalation risk assessment
for all durations was based on a multi-generation reproductive toxicity
study in rats.  The multi-generation reproductive toxicity study with a
longer duration and a NOAEL of 45 mg/kg/day is protective and
appropriate for short-, intermediate- and long-term dermal risk
assessments.  The 28-day dermal toxicity study in rats was not selected
for dermal risk assessment because the offspring effect in the
reproductive toxicity study was not measured in this study.  In
addition, the NOAEL (1000 mg/kg/day) in the 28-day dermal toxicity study
would not be protective of the reproductive-offspring effects in the rat
multi-generation reproductive toxicity study with a NOAEL of 45
mg/kg/day using a dermal-absorption factor of 15%.  Since an oral NOAEL
was selected, a 15% dermal-absorption factor was used for route-to-route
extrapolation for assessing dermal risk.

Food Quality Protection Act (FQPA)

There is no evidence of increased qualitative or quantitative
susceptibility following in utero exposure in the developmental
toxicities in rats and rabbits.  There was evidence of increased
quantitative susceptibility to the offspring following pre- / postnatal
exposure in the two-generation reproduction study in rats.  In that
study, offspring toxicity was manifested as decreased pup body weight
gain in all generations at a dose lower than the parental systemic
toxicity NOAEL.  However, the NOAEL of 45 mg/kg/day identified in this
study was chosen for risk assessments for all routes and exposure
durations other than acute oral exposures.  Since this NOAEL is the
lowest (most sensitive endpoint) in the dicamba toxicity data base, and
the dose-response observed in the study is well defined assuring that
this dose is a clear NOAEL, use of the NOAEL and endpoint for risk
assessment is protective for all observed toxic effects of the chemical.
 Therefore, there is low concern for the increased susceptibility
observed in the reproduction study since all appropriate risk
assessments utilize this endpoint.  Additionally, there is no increased
susceptibility observed in the developmental toxicity studies.

Levels of Concern

The uncertainty factors (UFs) used in determining the acute and chronic
RfD exposure limits were 100x (10x for intraspecies variation and 10x
for interspecies extrapolation).  In addition to the 10x UF for
intraspecies variation and the 10x UF for interspecies extrapolation, an
additional 3x was applied to the acute dietary risk assessment for
general population for using a LOAEL in establishing the acute reference
dose (aRfD).

For all non-dietary risk assessments, HED’s level of concern (LOC) is
a margin of exposure (MOE) of 100 (10x UF for intraspecies variation and
10x UF for interspecies extrapolation).

Dietary Exposure

Several plant metabolism studies have been submitted for dicamba.
Generally there are two major plant metabolites
3,6-dichloro-5-hydroxybenzoic acid (5-OH dicamba) and
3,6-dichlorosalicylic acid (DCSA), which are structurally similar to the
parent compound and are included in the dietary risk assessment.

Dietary Exposure Evaluation Model (DEEM-FCID™), Version 7.76 default
processing factors, and 100 percent crop treated (CT) data were used in
the acute and chronic dietary assessments.  For both acute and chronic
dietary assessments, the general U.S. population and all population
subgroups have risk estimates which were not of concern to HED.  For the
acute assessment, the most highly exposed population subgroup is all
infants (<1 year old; 11% of the aPAD).  For the chronic assessment, the
most highly exposed population subgroup is children 1-2 years old (6.7%
of the cPAD).  The use of anticipated residues (ARs), empirical
processing factors, and crop treated information would refine further
HED’s exposure and risk estimates; however, refinement is not needed
at this time.  A cancer dietary risk assessment was not performed
because dicamba is not a carcinogen.

Drinking Water

Dicamba could potentially be found in drinking water.  Environmental
fate studies show that the major environmental degradate would be DCSA.
DCSA and 5-OH- dicamba are major metabolites, and in the case of DCSA, a
major degradate that could potentially be found in drinking water.
Sufficient drinking water monitoring data from surface water sources
were not available so estimated drinking water concentrations (EDWCs)
were determined for surface water resources using PRZM-EXAMS (Pesticide
Root Zone Model-Exposure Analysis Modeling System) from application to
sugarcane, which has the highest use rate.  Surface drinking water
estimates (dicamba and DCSA) were included in the dietary exposure
assessment.  For the purposes of the dietary exposure assessment, the
highest (i.e., most conservative) values were used for the acute (367
ppb; parent + DCSA) and chronic (13.75 ppb; parent + DCSA) assessments.

Residential Exposure

Exposure to dicamba may occur in residential settings from treatment of
turf around the home and at golf courses.  Risks to individuals were
assessed in the RED (D317720, 9/13/2005) and are summarized (Section 5.0
of this document).  Residential handler assessments were conducted for
homeowners applying dicamba to lawns.  All handler MOEs are at least 100
and are, therefore, not of concern to HED.  Residential post-application
assessments were conducted for adults doing yardwork or playing golf on
treated turf, and for children playing or consuming soil or pesticide
granules while playing on a treated lawn.  Even when exposures occur on
the day of treatment, all of the residential exposures are not of
concern to HED.  Residential exposure estimates were used to calculate
aggregate risk for the proposed use on sweet corn.

Aggregate Risk

FQPA requires EPA to aggregate exposures from food, water, and
residential settings.  Acute, short-term and chronic aggregate risks
were assessed.  Acute and chronic aggregate risk is made up of dietary
exposure only (food and drinking water).  Because dicamba is used on
home lawns, residential exposure was aggregated with dietary exposure
for the short-term aggregate risk assessment.  Conservative assumptions
were built into the aggregate risk assessments.  All aggregate risk
estimates are not of concern to HED.

Occupational Exposure

Occupational handler exposure based on the proposed use on sweet corn is
not expected to differ significantly from that previously assessed for
the existing uses on field corn.  Therefore, a separate occupational
handler risk assessment was not produced for this action on sweet corn.
For details on handler risks, see the Dicamba RED, D317720, 9/13/2005.
In the RED, risks for occupational exposures were estimated for
pesticide applicators as well as for people who may enter treated fields
after application.  MOEs were calculated for short/intermediate term
dermal and inhalation exposures using standard assumptions and unit
exposure data for a range of application methods and equipment.  The
unit exposure data were taken from the Pesticide Handlers Exposure
Database (PHED) and the Outdoor Residential Exposure Task Force (ORETF)
studies for professional lawn care operators.  All mixer/loader,
applicator and mixer/loader/applicator MOEs exceed the target of 100
with a single layer personal-protective equipment (PPE) and, therefore,
risks are not of concern to HED.

For the current proposal for use on sweet corn, post-application risk
was assessed because it is more common for workers to perform
post-application activities (such as detasseling and hand harvesting) in
sweet corn fields, compared to the minimal post-application activities
typically performed in field corn.  Risk for sweet corn detasseling and
hand harvesting result in an MOE of 130 on the day of application, which
is not of concern to HED.  All other post-application MOEs are above the
target MOE of 100.

Restricted-Entry Level (REI)

The Distinct® label (EPA Reg. No. 7969-150) lists an REI of 12 hours.
Dicamba is listed as Acute Toxicity Category II for Primary Eye
Irritation and Primary Skin Irritation.  The interim WPS REI for
compounds exhibiting Toxicity Category II effects for primary eye and
skin irritation is 24 hours (40 CFR Part 156 § 156.208 (c) (1) and (2).
 HED requests confirmation of the basis for a 12-hour REI for this
product, and recommends that dicamba labels reflect the appropriate REI.

Recommendations

Provided that the petitioner submits a revised Section F and the
appropriate REI is clarified and stated on labels, HED concludes there
are no residue chemistry or toxicology data requirements that would
preclude the establishment of a conditional registration for the use of
dicamba on sweet corn and the following permanent tolerances for
combined residues of dicamba and its 5-OH metabolite in/on:

Corn, sweet, forage

0.50 ppm

Corn, sweet, kernel plus cob with husks removed

0.04 ppm

Corn, sweet, stover

0.50 ppm

Conversion of the conditional registration to an unconditional
registration may be considered upon submission of additional field
residue trials.

2.0	Ingredient Profile

2.1	Summary of Registered/Proposed Uses

Dicamba (2-methoxy-3,6-dichlorobenzoic acid) is a selective benzoic acid
herbicide registered for the control of certain broadleaf weeds and
woody plants before their emergence.  It is an auxin agonist that is
readily translocated symplastically and apoplastically with accumulation
in meristemic regions of the plant.  Sensitive plants exhibit rapid
uncontrolled growth characterized by twisting and curling of stems and
petioles, stem elongation and swelling and leaf cupping.  Weed control
is generally achieved in 5 to 7 days.

Registered Uses

Different forms of dicamba (acid and salt) have registered uses on
rights of way areas, asparagus, barley, corn (field and pop), grasses
grown in pasture and rangeland, oats, proso millet, rye, sorghum,
soybeans, sugarcane, and wheat.  Application rates range from 0.5 to 2.8
lb ae/A.  Residential uses include broadcast and spot treatment on golf
courses and lawns.

There were approximately 434 active dicamba products formulated from 6
different forms.  Most products are made of the acid, dimethylamine and
sodium salt ester forms.  The products are formulated as liquids,
standard granules and water dispersible granules.  The residential
products are typically formulated as granular weed and feed formulations
or as liquids in concentrates or ready to use sprays.

Proposed Uses

  SEQ CHAPTER \h \r 1 Distinct® Herbicide (EPA Reg. No. 7969-150), a
multiple active ingredient water-dispersible granule (WDG) formulation
containing 21.4% diflufenzopyr and 55% dicamba, has selective
postemergence activity.  The maximum application rate for sweet corn is
0.125 lbs. ae/A and a maximum of 2 applications are permitted per
season.  The maximum seasonal use rate is 0.25 lbs. ae/A with a minimum
retreatment interval (RTI) of 2 weeks.  Surfactants (0.25% v/v) should
be added to the postemergence finished spray.  The spray volume is 3-50
gal/A by ground equipment.  The preharvest interval (PHI) is 32 days for
fresh corn and 72 days for stover.

The rotational crop restrictions listed on the label are 7 days for corn
and 120 days for all other crops.

The petitioner has proposed an adequate set of directions for use of
Distinct® on sweet corn.

2.2	Structure and Nomenclature  TC \l2 "2.2	Structure and Nomenclature

  SEQ CHAPTER \h \r 1

Table 2.2.  Dicamba Nomenclature

PC Code 029801

Chemical structure

Common name	Dicamba acid

Molecular Formula	C8H6Cl2O3

Molecular Weight	221.04

IUPAC name	3,6-dichloro-o-anisic acid

CAS name	3,6-dichloro-2-methoxybenzoic acid or
2-methoxy-3,6-dichlorobenzoic acid

CAS #	1918-00-9

Chemical structures of dicamba salts can be found in Attachment 2.

2.3	Physical and Chemical Properties  TC \l2 "2.3	Physical and Chemical
Properties

  SEQ CHAPTER \h \r 1

Table 2.3.  Physicochemical Properties of Dicamba.

Parameter	Value	Reference

Dicamba acid (PC Code 029801)

Melting point	114-116 ̊C (PAI)

90-100 ̊C (87% TGAI)	SRR Reregistration Standard, 6/30/89

pH	2.5-3.0 (87% TGAI)

	Density, bulk density, or specific gravity	1.57 g/mL at 25 ̊C (87%
TGAI)

	Water solubility	0.5 g/100 mL at 25 ̊C (PAI)

	Solvent solubility		g/100 mL at 25 ̊C (PAI)

dioxane				118.0

ethanol				92.2

isopropyl alcohol		76.0

methylene chloride		26.0

acetone				17.0

toluene				13.0

xylene				7.8

heavy aromatic naphthalene	5.2

	Vapor pressure	3.4 x 10-5 mm Hg at 25 ̊C (PAI)

	Dissociation constant, pKa	1.97 (PAI)

	Octanol/water partition coefficient	0.1 (PAI)

	UV/visible absorption spectrum	neutral:		  511 (275 nm)

acidic (pH 0-1):	1053 (281 nm)

basic (pH 13-14):	  469 (274 nm)	RD D266167, 6/26/00, B. Kitchens

3.0	Hazard Characterization and Dose-Response Assessment

Dicamba has a low acute toxicity via oral, dermal or inhalation route
(Acute Toxicity Categories 3 or 4).  It is an eye and dermal irritant
but it is not a skin sensitizer.  Dogs are generally considered to be
toxicologically more sensitive when exposed to dicamba.  Consistent
neurotoxic signs (e.g., ataxia, decreased motor activity, impaired
righting reflex and gait) were observed in many studies in rats and
rabbits at high doses.  There is an increased incidence of abortion in
the rabbit developmental toxicity study at doses that also showed
maternal toxicity.  In a two-generation reproductive toxicity study,
offspring toxicity was manifested as decreases in pup weight in all
generations at a dose lower than the parental systemic toxicity NOAEL.
Developmental studies in rats and rabbits showed no evidence
(qualitative or quantitative) for increased susceptibility following in
utero exposure of dicamba.  Dicamba is classified as “not likely to be
carcinogenic to humans” by the oral route.  Mutagenicity studies did
not demonstrate evidence of mutagenic potential for dicamba although
some positive results were reported in published literature.  Following
oral administration, dicamba is rapidly absorbed and excreted in urine
and feces without significant metabolism.

An acute neurotoxicity study in rats was selected for the general
population, including infants and children, for an endpoint of concern
for a single oral exposure risk assessment.  For the short- and
intermediate-term incidental oral exposure and the chronic RfD, a
multi-generation reproductive toxicity study in rats was selected based
on impaired pup growth (decreased pup weights).

The dose and endpoint selected for dermal and inhalation risk assessment
for all durations was based on a multi-generation reproductive toxicity
study in rats.  The multi-generation reproductive toxicity study with a
longer duration and a NOAEL of 45 mg/kg/day is protective and
appropriate for short-, intermediate- and long-term dermal risk
assessments.  The 28-day dermal toxicity study in rats was not selected
for dermal risk assessment because the offspring effect in the
reproductive toxicity study was not measured in this study.  In
addition, the NOAEL (1000 mg/kg/day) in the 28-day dermal toxicity study
would not be protective of the reproductive-offspring effects in the rat
multi-generation reproductive toxicity study with a NOAEL of 45
mg/kg/day using a dermal-absorption factor of 15%.  Since an oral NOAEL
was selected, a 15% dermal-absorption factor was used for route-to-route
extrapolation for assessing dermal risk.

The UFs used in determining the acute and chronic RfD exposure limit
were 100x (10x for intraspecies variation and 10x for interspecies
extrapolation).  An additional 3x was applied to acute dietary risk
assessment for general population for using a LOAEL instead of a NOAEL.
The 3X is considered adequate because a comparison with the rat
developmental toxicity study that had similar clinical signs with a
NOAEL of 160 mg/kg/day after 10 days of treatment indicates that the
NOAEL for the acute neurotoxicity study is unlikely to be more than
3-fold lower than the LOAEL (ACN LOAEL/3 = 100 mg/kg; rat developmental
study NOAEL = 160 mg/kg). Therefore, it was determined that an
uncertainty factor of 3 for extrapolation of LOAEL to NOAEL was adequate
(TXR No. 0050280).

The acute toxicity profile for dicamba is presented in Table 3.0.

Table 3.0.	Acute Toxicity of Dicamba

OPPTS Guideline	Study Type	MRID	Results	Toxicity Category

870.1100	Acute oral toxicity / rat	00078444	LD50 = > 2740 mg/kg 	III

870.1200	Acute dermal toxicity / rat	00241584	LD50 = > 2000 mg/kg	III

870.1300	Acute inhalation toxicity / rat	00263861	LC50 = > 5.3 mg/L	IV

870.2400	Primary eye irritation / rabbit 	00241584	Irritant	II

870.2500	Primary dermal irritation / rabbit	00237955	Irritant	II

870.2600	Dermal sensitization / guinea pig	00263861	Non-Sensitizer	--

3.1	Mode of Action, Metabolism, Toxicokinetic Data

Multiple studies describing the metabolism or the pharmacokinetic of
dicamba in rats have been submitted to the Agency.  The metabolism study
in rats showed that following oral administration, dicamba is rapidly
absorbed and excreted.  Over 95% is excreted in the urine and the
compound is not metabolized or accumulated by the tissues.

The plasma pharmacokinetic studies in rats showed that absorption of
radiolabeled dicamba was rapid, with peak plasma concentrations found
within 2 hours of treatment.  Absorption was not saturated, even at the
highest dose, as indicated by increasing plasma concentrations with
doses.  However, the increase in plasma concentration was non-linear and
disproportionate from one dose to the next doses, which is consistent
with saturation of excretion.  No significant treatment-related
differences between the sexes or time of radiolabel administration were
found.  Another plasma pharmacokinetic study suggested that dicamba acts
as an inhibitor of renal anion transport.

3.2	  SEQ CHAPTER \h \r 1 FQPA

Summary

The database is adequate in terms of endpoint studies and dose response
information to select appropriate endpoints for prenatal or postnatal
risk for infants and children.  There is no evidence (qualitative or
quantitative) of increased susceptibility following in utero exposure in
the developmental toxicity studies in rats and rabbits.  There was
evidence of increased sensitivity to the offspring following pre- /
postnatal exposure in the two-generation reproductive toxicity study in
rats.  In that study, offspring toxicity was manifested as decreased pup
body weight in all generations at a dose lower than the parental
systemic toxicity NOAEL.  However, the degree of concern is low for the
quantitative susceptibility because the risk assessment was based on the
very same effect seen in the pups with a definitive NOAEL. There are no
concerns or residual uncertainties for pre- and postnatal toxicity.

After considering the available toxicity data, the risk assessment team
determined that a DNT is not required based on the following reasons:
(1) although clinical signs of neurotoxicity were seen in pregnant
animals, no evidence of developmental anomalies of the fetal nervous
system were observed in the prenatal  developmental toxicity studies, in
either rats or rabbits, at maternally toxic doses up to 300 or 400
mg/kg/day, respectively; (2) there were no evidence of behavioral or
neurological effects on the offspring in the two-generation reproductive
toxicity study in rats; (3) the ventricular dilation of the brain in the
combined chronic toxicity and carcinogenicity study in rats was only
observed in females at the high dose after two years exposure.  The
significance of this observation is questionable since no similar
histopathological finding was seen in the subchronic neurotoxicity
study.  In addition, the dicamba risk assessment team evaluated the
quality of the exposure data; and, based on these data, recommended that
the FQPA SF be reduced to 3x for acute dietary risk assessment for the
use of a LOAEL instead of a NOAEL and 1x for all other risk assessments.

3.2.1	Adequacy of the Toxicity Data Base

The following studies are available in the toxicity database:

	- Developmental toxicity studies in rats and rabbits (acceptable).

	- Two-generation reproductive toxicity study in rats (acceptable).

	- Acute and subchronic neurotoxicity studies in rats (acceptable).

The toxicity profile for dicamba is presented in Attachment 1 to this
memorandum.

3.2.2	Evidence of Neurotoxicity

There is evidence of neurotoxicity resulting from exposure to dicamba.
In the acute neurotoxicity study, clinical signs of neurotoxicity
consisted of impaired gait and righting reflex, decreased arousal and
rears/minutes, and rigidity upon handling were observed at 300 mg/kg bw
or above.  At higher dose levels, the effects were more pronounced with
additional effects.  The subchronic neurotoxicity study in rats showed
rigid body tone, impaired righting reflex and gait at 768 mg/kg.

In the developmental toxicity studies in rats, ataxia, stiffening of the
body when touched, and decreased motor activity were seen at 400 mg/kg
in the dams.  The developmental toxicity study in rabbits showed that at
150 mg/kg the dams presented signs of ataxia, rales and decreased motor
activity.

A two-generation reproductive toxicity study demonstrated tense/stiff
body tone and slow righting reflex in the dams from both generations at
the 450 mg/kg dose level.  It should be noted that the signs of
neurotoxicity were consistent across several studies.

3.2.3	Developmental Toxicity Studies

In a developmental toxicity study (MRID No. 00084024), pregnant (CD
Charles River) rats (25/dose group) received gavage administration of
dicamba (85.3%) in corn oil at dose levels of 0, 64, 160, or 400
mg/kg/day during gestation days 6 through 19.   Maternal toxicity
limited to the high dose (400 mg/kg/day) was characterized by mortality
in three gravid dams and one non-gravid dam that exhibited neurotoxic
signs prior to death; clinical signs of nervous system toxicity that
included ataxia, salivation, stiffening of the body when held, and
decreased motor activity; statistically significant (p<0.05) decreases
in body weight gain during the dosing period; and concomitant decreases
in food consumption.  Dicamba had no effect on any of the cesarean
parameters.  For maternal toxicity, the NOAEL was 160 mg/kg/day and the
LOAEL was 400 mg/kg/day based on mortality, clinical signs, body weight
changes and decreases in food consumption.  No treatment-related fetal
gross external, skeletal or visceral anomalies (malformations or
variations) were seen at any dose level.  For developmental toxicity,
the NOAEL was >400 mg/kg/day; a LOAEL was not established.  This study
is classified acceptable/guideline (OPPTS 870.3700a) and satisfies the
requirements for a developmental toxicity study in the rat.

In a developmental toxicity study (MRID No. 42429401), inseminated New
Zealand White (NZW) rabbits (19-20/dose) were given oral capsules
containing dicamba (90.5%) at dose levels of 0, 30, 150, or 300
mg/kg/day from days 6 through 18 of gestation.  No maternal or
developmental toxicity was observed at 30 mg/kg/day.  At 150 mg/kg/day,
maternal toxicity was characterized by abortion (5%) and clinical signs
such as ataxia, rales, decreased motor activity.  At 300 mg/kg/day
maternal toxicity was manifested by abortions (20%), clinical signs,
decreased body weight and body weight gain and food consumption.
Developmental toxicity at 300 mg/kg/day was manifested by irregular
ossification of the nasal bones of the skull.  At 150 mg/kg/day,
increased incidence of abortion was observed and was considered
developmental toxicity.  In a range-finding study, NZW rabbits were
dosed at 0, 62.5, 125, 250, or 500 mg/kg/day from days 6 through 18 of
gestation.  No maternal or developmental toxicity was observed at 62.5
mg/kg/day.  Treatment-related maternal toxicity was manifested by
mortality, increased resorptions and reduction in the litter size at 500
mg/kg/day.  Clinical signs occurred at 125, 250, and 500 mg/kg/day.
Cesarean sections revealed no treatment-related differences between
treated and control groups, and no external malformation or variations
were seen in any of the fetuses of the treated does.  Based on the
results of these studies, the NOAEL for maternal toxicity was 62.5
mg/kg/day and the LOAEL was 150 mg/kg/day based on increased incidences
of abortion and clinical signs (i.e., decreased motor activity, ataxia).
 For developmental toxicity, the NOAEL was 62.5 mg/kg/day and the LOAEL
was 150 mg/kg/day based on increased incidence of abortion.  This study
is classified acceptable/guideline (OPPTS 870.3700b; OECD 414) and
satisfies the requirements for a developmental toxicity study in the
rabbit.

3.2.4	Reproductive Toxicity Study

In a two-generation reproductive toxicity study (MRID 43137101),
Sprague-Dawley rats (32 or 28/group) received dicamba technical (86.5%)
in the diet at dose levels of 0, 500, 1500, or 5000 ppm (0, 40, 122, or
419 mg/kg/day for males and 0, 45, 136 or 450 mg/kg/day for females,
respectively) for two generations.  Systemic toxicity was observed at
5000 ppm, manifested as clinical signs in dams from both generations
during lactation (tense/stiff body tone and slow righting reflex) and
significantly increased relative liver to body weights (112% of control)
in both generations and sexes, adults as well as weanlings.  The
increase (107%) in relative kidney weights observed at 1500 and/or 5000
ppm were not considered to be toxicologically significant due to lack of
corroborative gross or histopathological lesions in the kidneys.  Sexual
maturation among male pups in the F1 generation was significantly
delayed at 5000 ppm.  Similar effects were not seen in females.
Significantly decreased pup body weights were observed in all
generations and matings at 1500 ppm (86 - 90% of control) and at 5000
ppm (74 - 94% of control) throughout lactation.  For parental systemic
toxicity, the NOAEL was 122 and 136 mg/kg/day for males and females,
respectively, and the LOAEL was 419 and 450 mg/kg/day, in males and
females, respectively, based on clinical signs of neurotoxicity.  For
reproductive toxicity, the NOAEL was 122 mg/kg/day and the LOAEL was 419
mg/kg/day based on delayed sexual maturation in F1 males.  For offspring
toxicity, the NOAEL was 45 mg/kg/day and the LOAEL was 136 mg/kg/day
based on decreased pup body weight.  This study is classified as
acceptable/guideline and satisfies the guideline requirements (OPPTS
870.3800; OECD 416) for a two-generation reproductive toxicity study in
the rat.

3.2.5	Additional Information from Literature Sources

No additional relevant toxicity studies from published literature were
identified.

3.2.6	Pre-and/or Postnatal Toxicity

<IP_ADDRESS>	Determination of Susceptibility

The pre- and postnatal toxicology database for dicamba includes rat and
rabbit developmental toxicity studies and a two-generation reproduction
toxicity study in rats.  There was no evidence (qualitative or
quantitative) of increased susceptibility following in utero exposure in
the developmental toxicity studies in rats and rabbits. There was
evidence of increased sensitivity of the offspring following
pre-/postnatal exposure in the two-generation reproduction study in
rats.  In that study, offspring toxicity was manifested as decreased pup
body weight in all generations at a dose lower than the parental
systemic toxicity NOAEL.  However, there is low concern and there are no
residual uncertainties for the increased susceptibility for the
following reasons.  The NOAEL of 45 mg/kg/day identified in this study
was chosen for risk assessments for all routes and exposure durations
other than acute oral exposures.  Since this NOAEL is the lowest (most
sensitive endpoint) in the dicamba toxicity data base, and the dose
response observed in the study is well defined, assuring that this dose
is a clear NOAEL, use of the NOAEL and endpoint for risk assessment is
protective for all observed toxic effects of the chemical.  The endpoint
(decreased pup body weight) is not expected to occur as a result of a
single (acute) exposure and was, therefore, not deemed appropriate for
assessing acute oral exposures.

<IP_ADDRESS>	Degree of Concern Analysis and Residual Uncertainties

The degree of concern is low for the quantitative susceptibility seen in
the 2-generation reproduction study in rats because the risk assessment
was based on the most sensitive endpoint with a definitive NOAEL.  There
are no concerns or residual uncertainties for pre- and postnatal
toxicity.

3.2.7	Recommendation for a Developmental Neurotoxicity Study

After considering the available toxicity data, the risk assessment team
determined that a DNT is not required based on the following reasons:
(1) although clinical signs of neurotoxicity were seen in pregnant
animals at high doses, no evidence of developmental anomalies of the
fetal nervous system were observed in the prenatal  developmental
toxicity studies, in either rats or rabbits, at maternally toxic doses
up to 300 or 400 mg/kg/day, respectively; (2) there were no evidence of
behavioral or neurological effects on the offspring in the
two-generation reproductive toxicity study in rats; (3) the ventricular
dilation of the brain in the chronic toxicity study was only observed in
females at the high dose after two years exposure.  The significance of
this observation is questionable since no similar histopathological
finding was seen in the subchronic neurotoxicity study.

3.2.8	FQPA Safety Factor for Infants and Children

EPA has determined that reliable data show that it would be safe for
infants and children to reduce the FQPA safety factor to 3X for acute
oral exposures and to 1X for all other routes and durations of exposure.
 That decision is based on the following findings:

	i. The toxicity database for dicamba is complete.

	ii. Consistent neurotoxic signs (e.g., ataxia, decreased motor
activity, impaired righting reflex and gait) were observed in many
studies in rats and rabbits at high doses.  After considering the
available toxicity data, EPA determined that there is no need for a
developmental neurotoxicity study or additional UFs to account for
neurotoxicity for the following reasons: (1) although clinical signs of
neurotoxicity were seen in pregnant animals, no evidence of
developmental anomalies of the fetal nervous system were observed in the
prenatal developmental toxicity studies, in either rats or rabbits, at
maternally toxic doses up to 300 or 400 mg/kg/day, respectively; (2)
there was no evidence of behavioral or neurological effects on the
offspring in the two-generation reproduction study in rats; (3) the
ventricular dilation of the brain in the combined chronic toxicity and
carcinogenicity study in rats was only observed in females at the high
dose after two years’ exposure.  The significance of this observation
is questionable, since no similar histopathological finding was seen in
the subchronic neurotoxicity study.

	iii. There is no evidence that dicamba results in increased
susceptibility in in utero  rats or rabbits in the prenatal
developmental toxicity studies.  Although there is quantitative evidence
of increased susceptibility in the two-generation reproduction study in
rats, the degree of concern is low because there is a well established
offspring toxicity NOAEL in the study and the risk assessment team did
not identify any residual uncertainties after establishing toxicity
endpoints and traditional UFs to be used in the risk assessment of
dicamba for all routes and durations of exposure, except acute oral
exposures.

	iv. EPA selected an endpoint from the acute neurotoxicity study in rats
for use in assessing acute oral exposures.  In this study, neurotoxicity
was seen in both sexes at the lowest dose tested, 300 mg/kg/day.  Since
a NOAEL was not established in the study, EPA has determined that an
FQPA safety factor of 3X must be used in acute oral risk assessments for
dicamba to account for uncertainty arising from the use of LOAEL instead
of NOAEL. EPA has reduced the factor from 10X to 3X based on the
following considerations.  A comparison of the acute neurotoxicity (ACN)
study with the rat developmental toxicity study that showed similar
clinical signs and a NOAEL of 160 mg/kg/day after 10 days of treatment
indicates that the NOAEL for the acute neurotoxicity study is unlikely
to be more than 3- fold lower than the LOAEL (ACN LOAEL/3 = 100 mg/kg;
rat developmental study NOAEL = 160 mg/kg). Therefore, it was determined
that an uncertainty factor of 3X for extrapolation of LOAEL to NOAEL was
adequate.

	v. There are no residual uncertainties identified in the exposure
databases. The dietary food exposure assessments were performed based on
100%CT and tolerance-level residues.  Conservative ground and surface
water modeling estimates were used.  Similarly, conservative Residential
SOPs were used to assess post-application exposure of children as well
as incidental oral exposure of toddlers.  These assessments will not
underestimate the exposure and risks posed by dicamba.

  SEQ CHAPTER \h \r 1 3.3	Classification of Carcinogenic Potential

In accordance with the EPA Final Guidelines for Carcinogen Risk
Assessment (March 29, 2005), dicamba is classified as not likely to be
carcinogenic to humans.  This was based on negative cancer studies in
rats and mice which were tested at adequate dose levels to assess the
carcinogenicity of dicamba (TXR No. 0053647).

3.4	Summary of Toxicological Doses and Endpoints for Use in Human Risk
Assessments  TC \l3 "3.5.11	Summary of Toxicological Doses and Endpoints
for [Chemical] for Use in Human Risk Assessments

Levels of concern for dicamba risk assessments are presented in Table
3.4.1.  Endpoints and doses selected for risk assessment are shown below
in Table 3.4.2.

  SEQ CHAPTER \h \r 1

Table 3.4.1  Summary of Levels of Concern for Risk Assessment

Route	Duration

	Acute

(1 day)	Short-Term

(1-30 Days)	Intermediate-Term

(1 - 6 Months)	 Long-Term

(> 6 Months)

Occupational (Worker) Exposure

Dermal	NA	100	100	100

Inhalation	NA	100	100	100

Residential (Non-Dietary) Exposure

Oral	300	100	100	N/A

Dermal	300	100	100	100

Inhalation	300	100	100	100

N/A = Not Applicable

Table 3.4.2. Summary of Toxicology Endpoint Selection for Dicamba

Exposure

Scenario	Dose Used in Risk Assessment, UF	 FQPA SF* and Level of Concern
for Risk Assessment	Study and Toxicological Effects

Acute Dietary

(General population including infants and children	LOAEL = 300 mg/kg/day

UF = 300

Acute RfD = 1 mg/kg/day	FQPA SF = 1X

aPAD = acute RfD

              FQPA SF

= 1.0 mg/kg/day	Acute Neurotoxicity Study in Rats

LOAEL = 300 mg/kg/day (LDT) based on clinical signs of neurotoxicity.

Chronic Dietary

(All populations)	NOAEL= 45 mg/kg/day

UF = 100

Chronic RfD =

0.45 mg/kg/day	FQPA SF = 1X

cPAD =

chronic RfD

FQPA SF

= 0.45 mg/kg/day	Multi-generation reproductive toxicity study in rats

LOAEL=136 mg/kg/day based on impaired pup growth (decreased pup
weights).

Short- (1 - 30 Days) and Intermediate- (1-6 months) Term Incidental Oral

	Oral

NOAEL= 45 mg/kg/day	Residential LOC for MOE = 100	Multi-generation
reproductive toxicity study in rats

See above, under chronic dietary.

Short-, Intermediate- and Long- (>6 months) Term Dermal

	Oral

NOAEL= 45 mg/kg/day

(Dermal-absorption rate = 15%)	Residential

LOC for MOE = 100

Occupational

LOC for MOE = 100	Multi-generation reproductive toxicity study in rats

See above, under chronic dietary.

Short-, Intermediate- and Long-Term Inhalation	Oral

NOAEL= 45 mg/kg/day

(Inhalation absorption rate= 100%)	Residential

LOC for MOE = 100

Occupational

LOC for MOE = 100	Multi-generation reproductive toxicity study in rats

See above, under chronic dietary.

Cancer

(Oral, dermal, inhalation)	Dicamba is classified as not likely to be
carcinogenic to humans.

3.5	Recommendation for Aggregate Exposure Risk Assessments

A common toxicological endpoint (decreased pup growth) of concern was
identified for short-, intermediate- and long-term durations via the
oral, dermal (oral equivalent) and inhalation (oral equivalent) routes.
Therefore, the aggregate exposure risk assessment should include
exposure across the oral, dermal and inhalation routes as appropriate
for the populations of concern.

3.6	Endocrine Disruption  TC \l2 "3.6	Endocrine disruption

EPA is required under the Federal Food, Drug and Cosmetic Act (FFDCA),
as amended by FQPA, to develop a screening program to determine whether
certain substances (including all pesticide active and other
ingredients) may have an effect in humans that is similar to an effect
produced by a naturally occurring estrogen, or other such endocrine
effects as the Administrator may designate.  Following recommendations
of its Endocrine Disruptor and Testing Advisory Committee (EDSTAC), EPA
determined that there was a scientific basis for including, as part of
the program, the androgen and thyroid hormone systems, in addition to
the estrogen hormone system.  EPA also adopted EDSTAC’s recommendation
that the Program include evaluations of potential effects in wildlife.
For pesticide chemicals, EPA will use FIFRA and, to the extent that
effects in wildlife may help determine whether a substance may have an
effect in humans, FFDCA authority to require the wildlife evaluations.
As the science develops and resources allow, screening of additional
hormone systems may be added to the Endocrine Disruptor Screening
Program.

4.0	Dietary Exposure/Risk Characterization  TC \l1 "5.0	Dietary
Exposure/Risk Characterization

4.1	Pesticide Metabolites and Degradates of Concern

  SEQ CHAPTER \h \r 1 A summary of dicamba metabolites and environmental
degradates to be included in the dietary risk assessment and tolerance
expression may be found in Table 4.1.  DCSA and 5-OH- dicamba are major
metabolites, and in the case of DCSA, a major degradate that could
potentially be found in drinking water.  Specific toxicity data are not
available for either of these compounds.  Based on their structural
similarity to the parent, the risk assessment team has concluded that
they may have similar toxicity as the parent, and should be included in
the dietary risk assessment.

Table 4.1	Summary of Dicamba Metabolites and Degradates to be included
in the Risk Assessment and Tolerance Expression 1

Matrix	Residues included in Risk Assessment	Residues included in
Tolerance Expression

Plants

	Primary Crop - Most grains	Dicamba and 5-OH Dicamba	Dicamba and 5-OH
Dicamba

	Primary Crop – Asparagus	Dicamba and DCSA	Dicamba and DCSA

	Primary Crop - Soybean and Aspirated Grain Fractions	Dicamba, DCSA, and
5-OH Dicamba	Dicamba, DCSA, and 5-OH Dicamba

	Rotational Crop	Not Required 2	Not Required 2

Livestock

	Ruminant	Dicamba and DCSA	Dicamba and DCSA

	Poultry	Not Required	Not Required

Drinking Water

	Dicamba and DCSA	Not Applicable

1 Nomenclature of metabolites/degradates:  3,6-dichloro-5-hydroxybenzoic
acid = 5-OH; 3,6-dichloro-2-hydroxybenzoic acid = 3,6-dichlorosalicylic
acid = DCSA;

2 Tolerances and dietary risk assessment are not required provided the
registrants specify a 120-day plant-back interval (PBI).

4.2	Environmental Fate

Reference: Memo, Ibrahim Abdel-Saheb, D317705, 5/31/2005.

Aerobic soil metabolism is the main degradative process for dicamba.  A
single observed half-life for dicamba was six days; with formation of
the intermediate non-persistent degradate DCSA.  DCSA degraded at
roughly the same rate as dicamba; the final metabolites were carbon
dioxide and microbial biomass.  Dicamba is stable to abiotic hydrolysis
at all pH's and photodegrades slowly in water and on soil.  Dicamba is
more persistent under anaerobic soil:water systems in the laboratory,
with a half-life of 141 days.  The major degradate under anaerobic
conditions was DCSA, which was persistent, comprising > 60% of the
applied after 365 days of anaerobic incubation.  No other anaerobic
degradates were present at > 10% during the incubation.   There are no
acceptable data for the aerobic aquatic metabolism of dicamba;
supplemental information indicates that dicamba degrades more rapidly in
aquatic systems when sediment is present.

Dicamba is very soluble (6100 ppm) and very mobile (Koc = 13.4) in the
laboratory.  Because dicamba is not persistent under aerobic conditions,
very little dicamba could be expected to leach to groundwater.  If any
dicamba did reach anaerobic ground water, it would be somewhat
persistent (due to its anaerobic half-life of 141 days); any DCSA that
reached ground water would be expected to persist.  Results from two
acceptable field dissipation studies conducted with dimethylamine salt
of dicamba, indicated that dicamba dissipated with a half-life range of
4.4 to 19.8 days.  The DCSA was the major degradate in both studies.
Both, dicamba and its degradate (DCSA) were found in soil segments
deeper than 10 cm.

Dicamba is not expected to bioaccumulate in aquatic organisms because it
is an anion at environmental pHs (pKa = 1.9).

4.3	Drinking Water Residue Profile

The most recent drinking water assessment was performed for the RED in
2005 (see reference above).  EFED has stated that the sugarcane use
results in the highest drinking water exposure potential.  Therefore,
the drinking water estimates for sugarcane from the RED were used to
estimate dietary exposure to dicamba from food and drinking water
sources.

The Tier II screening models PRZM and EXAMS with the Index Reservoir and
Percent Crop Area adjustment (IR-PCA PRZM/EXAMS) were used to determine
estimated surface water concentrations of dicamba and its degradate
DCSA.  The combined values for parent dicamba and DCSA are 367 ppb (or
0.367 ppm; acute) and 13.75 ppb (or 0.1375 ppm; chronic).

Results from the SCI-GROW screening model predict that the maximum
chronic and acute concentration of parent dicamba acid, and its
degradate DCSA in shallow ground water is not expected to exceed 0.016
µg/L, and 0.0081µg/L, respectively, for the current maximum seasonal
use rate on sugarcane.   Surface water concentrations are shown below in
Table 4.3.

Table 4.3. Drinking Water Estimates for Dicamba and DCSA

Crop

(application method)

Model EDWCs  (μg/L)

Dicamba

DCSA

Acute

One-in-10-year annual mean

36 year overall mean

Acute

One-in-10-year annual mean

36 year overall mean

Surface Water

FL-Sugarcane (Ground)

357

13

5.23

10.1

0.75

0.4

FL-Sugarcane (Aerial)

346

12.9

5.38

10.9

0.813

0.47

LA-Sugarcane (Ground)

233

9.74

3.13

8.79

0.66

0.32

LA-Sugarcane (Aerial)

230

9.74

3.44

9.74

0.73

0.39

Note that these estimates assume one application @ 2.8 lb ai/A (parent);
and 0.446 lb ai/A (DCSA) and a crop area factor of 0.87

4.4	Food Residue Profile

Background

Interregional Research Project No. 4 (IR-4) has submitted a petition on
behalf of the Agricultural Experiment Stations of MN, ND and WI
proposing the following permanent tolerances for the combined residues
of the herbicide dicamba and its 5-OH metabolite in/on the following raw
agricultural commodities (RACs):

Proposed Tolerances

Corn, sweet, forage	1.0 ppm

Corn, sweet, fresh	0.1 ppm

Corn, sweet, stover	1.0 ppm

Tolerances for residues of dicamba and its 5-OH metabolite have been
established for corn grain, corn forage, corn fodder, wheat grain, wheat
straw, barley grain, and barley straw at 0.5 ppm; and for field corn
forage, field corn stover and popcorn stover at 3.0 ppm (40 CFR §
180.227(a)).  Tolerances for dicamba and its 2-OH metabolite (DCSA) have
been established at 0.05 ppm for soybeans; 0.1 ppm for soybean hay and
soybean forage; and on cattle, goats, hogs, horses, and sheep meat, fat,
and meat byproducts at 0.2 ppm, liver and kidney at 1.5 ppm, and milk at
0.3 ppm (40 CFR §180.227(b)).

Nature of the Residue

Plants:  The nature of the residue in plants is adequately understood
(F. Griffith, 02-MAY-1996, PP#6F4604, D220469).  The residues to be
regulated in barley, corn, cotton, oats, wheat, and grasses are dicamba
and its 5-OH metabolite; in asparagus the residues to be regulated are
dicamba and DCSA; and in soybeans and aspirated grain fractions, the
residues to be regulated are dicamba, 5-OH dicamba and DCSA.

Livestock:  The nature of the residue in ruminants and poultry is
adequately understood (L. Cheng, 07-MAR-1996, D204482).  The residues to
be regulated in livestock are dicamba and its DCSA metabolite.

Residue Analytical Methods

The petitioner has presented an adequately validated capillary GC
methods with electron capture detection (GC/ECD) residue analytical
method to determine the magnitude of dicamba and 5-OH dicamba residues
in plant commodities (barley, corn, cotton, cotton processed fractions,
pasture grass, peanut, sorghum, soybean, sugar cane, tomato, tomato
processed fractions, wheat and wheat processed fractions).  Pesticide
Analytical Manual (PAM) Volume II lists Method I and II, GC/ECD, for the
enforcement of tolerances on dicamba and its metabolite 5-OH dicamba
in/on plant commodities and milk.

Multiresidue Method

Documentation from the FDA, PAM Volume I, Appendix II and Table 201-D,
shows that dicamba is partially recovered (71 - 76%) using Protocol B.

Crop Field Trials

A total of 9 field residue trials were conducted in Regions 1 (1 trial),
2 (1 trial), 3 (1 trial), 5 (3 trials), 6 (1 trial), 10 (1 trial) and 12
(1 trial).  The number and location do not match that suggested in Table
5 of OPPTS Test Guidelines Series 860.1500 for sweet corn:  12 trials
conducted in Regions 1 (2 trials), 2 (1 trial), 3 (1 trial), 5 (5
trials), 10 (1 trial), 11 (1 trial) and 12 (1 trial).  The petitioner
previously submitted the results of 20 field corn residue trials.  HED
can generally translate field corn forage and stover data to sweet corn.
 However, in this case, translation is not appropriate as the
application rate in the field corn trials was >10X the maximum proposed
sweet corn application rate.

HED requests that the petitioner submit an additional 3 sweet corn
residue trials conducted in Regions 1 (1 trial), 5 (1 trial) and 11 (1
trial).  Permanent tolerances and a conditional registration may be
established while these trials are conducted.  Based on the available
data, the following tolerance for residues of the herbicide dicamba and
its 5-OH metabolite are appropriate for this petition:

Recommended Tolerances

Corn, sweet, forage	0.50 ppm

Corn, sweet, kernel plus cob with husks 	0.04 ppm

Corn, sweet, stover	0.50 ppm

A revised Section F is required.

Processed Food/Feed

As there are no processed commodities associated with sweet corn,
processing studies are not required to support the subject petition.

Meat, Milk, Poultry, Eggs (MMPE)

Given that there are already dicamba tolerances established on major
livestock feed items at high levels (i.e., aspirated grain fractions at
5100 ppm, grass forage at 125 ppm and wheat forage at 20 ppm), HED
concludes that the dietary burden to livestock will not be affected by
the use of dicamba on sweet corn.  Therefore, the existing MMPE
tolerances have not been reassessed.

Confined and Field Accumulation in Rotational Crops

Based on the results of a confined rotational crop study (memo S. Chun &
W. Donovan, 25-JUN-1998; D228694), HED has concluded that the plantback
intervals specified on the Distinct® label (7 days for corn and 120
days for all other crops) are appropriate.

4.5	International Residue Limits TC \l3 "5.1.11	International Residue
Limits

There is neither a Codex proposal, nor Canadian or Mexican limits for
residues of dicamba in/on sweet corn.  Therefore, a compatibility issue
is not relevant to the proposed tolerance.

Dietary Exposure and Risk

Memo, S. Levy, D347355.

 TC \l2 "5.2  Dietary Exposure and Risk

 FCID™, Version 2.03 which incorporates consumption data from USDA’s
Continuing Surveys of Food Intakes by Individuals (CSFII), 1994-1996 and
1998.  The 1994-96, 98 data are based on the reported consumption of
more than 20,000 individuals over two non-consecutive survey days.
Foods “as consumed” (e.g., apple pie) are linked to EPA-defined food
commodities (e.g., apples, peeled fruit - cooked; fresh or N/S; baked;
or wheat flour - cooked; fresh or N/S, baked) using publicly available
recipe translation files developed jointly by USDA/ARS and EPA.  For
chronic exposure assessment, consumption data are averaged for the
entire U.S. population and within population subgroups.  Based on
analysis of the 1994-96, 98 CSFII consumption data, which took into
account dietary patterns and survey respondents, HED concluded that it
is most appropriate to report risk for the following population
subgroups: the general U.S. population, all infants (<1 year old),
children 1-2, children 3-5, children 6-12, youth 13-19, adults 20-49,
females 13-49, and adults 50+ years old.

For chronic dietary exposure assessment, an estimate of the residue
level in each food or food-form (e.g., orange or orange juice) on the
food commodity residue list is multiplied by the average daily
consumption estimate for that food/food form to produce a residue intake
estimate.  The resulting residue intake estimate for each food/food form
is summed with the residue intake estimates for all other food/food
forms on the commodity residue list to arrive at the total average
estimated exposure.  Exposure is expressed in mg/kg body weight/day and
as a percent of the cPAD.  This procedure is performed for each
population subgroup.  A cancer dietary assessment was not conducted
because dicamba was classified as not likely to be carcinogenic to
humans.

The acute and chronic dietary exposure assessments were conducted using
tolerance-level residues, DEEM default processing factors and 100% CT
information for all registered and proposed use sites.  Drinking water
values were incorporated directly into the acute and chronic dietary
assessments.

Table 4.6.  Summary of Dietary Exposure and Risk for Dicamba.

Population Subgroup	Acute Dietary1

(95th Percentile)	Chronic Dietary1

	Dietary Exposure (mg/kg/day)	%aPAD*	Dietary Exposure (mg/kg/day)	%
cPAD*

U.S. Population (total)	0.044066	4.4	0.012091	2.7

All Infants (< 1 year old)	0.109311   	11	0.020233	4.5

Children 1-2 years old	0.076605   	7.6	0.030196	6.7

Children 3-5 years old	0.068164   	6.8	0.027604	6.1

Children 6-12 years old	0.048314   	4.8	0.018991	4.2

Youth 13-19 years old	0.032048   	3.2	0.011752	2.6

Adults 20-49 years old	0.034236   	3.4	0.009961	2.2

Adults 50+ years old	0.026832   	2.7	0.007616	1.7

Females 13-49 years old	0.031439   	3.1	0.008935	2.0

1 Acute dietary endpoint of 1.0 mg/kg/day applies to the general U.S.
population and all population subgroups.  Chronic dietary endpoint of
0.45 mg/kg/day applies to the general U.S. population and all population
subgroups.

*  The highest %aPAD and %cPAD are bolded.

4.6.1	Acute Dietary Exposure/Risk  TC \l3 "5.2.1  Acute Dietary
Exposure/Risk

For the acute assessment, the most highly exposed population subgroup is
all infants (<1 year old; 11% of the aPAD).  The acute assessment
concludes that the acute dietary exposure estimates is not of concern to
HED for the general U.S. population or any population subgroup.  The use
of ARs, empirical processing factors, and %CT data would refine further
HED’s exposure and risk estimates; however, refinement is not needed
at this time.

4.6.2   Chronic Dietary Exposure/Risk

For the chronic assessment, the most highly exposed population subgroup
is children 1-2 years old (6.7% of the cPAD).  The chronic assessments
conclude that chronic dietary exposure estimates are not of concern to
HED for the general U.S. population or any population subgroup.  The use
of ARs, empirical processing factors, and %CT data would refine further
HED’s exposure and risk estimates; however, refinement is not needed
at this time.

4.6.3	Cancer Dietary Risk  TC \l3 "5.2.3  Cancer Dietary Risk

A cancer dietary-exposure assessment was not conducted because dicamba
was classified as not likely to be carcinogenic to humans.

5.0	Residential (Non-Occupational) Exposure/Risk Characterization

Residential uses of dicamba have been previously assessed by HED for the
RED (Memo, D317701, T. Dole, 08/26/2005).  Conclusions from the last
residential risk assessment have been summarized below.  Residential
exposures were aggregated with dietary exposure in Section 6.0 of this
document (episodic ingestion of granules was not aggregated).  For
details on the assumptions and data used to estimate risks, see the
08/26/2005 memo cited above.

5.1		Residential Handler Exposure and Risk

Dicamba is registered for use on residential sites, including home lawns
and golf courses.   Residential dicamba products are typically
formulated as dry weed and feed products, as liquid concentrates or as
ready-to-use sprays.  Spot and broadcast treatments are both included on
dicamba labels.  Exposures are expected to be short-term in duration for
broadcast treatments because the label allows only two broadcast
treatments per year.  Exposures are also expected to be short-term in
duration for spot treatments because the labels recommend repeat
applications in two to three weeks.

In the last risk assessment, seven handler exposure scenarios were
assessed for homeowner application to lawns.  The scenario with the
highest exposure is for residential handlers who mix/load and apply
dicamba using a hose-end sprayer (mix your own).  Dermal and inhalation
exposure is 0.012 mg/kg/day and results in an MOE of 3,800.  All
residential handler exposure scenarios are not of concern to HED.

5.2		Residential Post-Application Exposure and Risk

Several post-application residential exposure scenarios were assessed
for dicamba in the last risk assessment, including toddlers playing on
treated turf.  The highest three of these are summarized below.

Short-term exposure for toddlers playing on treated turf

Short-term exposure for residents doing yardwork on treated turf

Acute exposure for toddlers from incidental oral ingestion of granules

Details on the post-application risk assessments can be found in the
last risk assessment (D317701, 08/26/2005).   In summary, for children,
incidental oral exposure (hand-to-mouth, object-to-mouth and soil
ingestion) was combined with dermal exposure.  For adults, risk is based
on dermal exposure only (inhalation exposure is expected to be
negligible).  Estimated risks for all scenarios are not of concern to
HED.  The results of the residential post-application risk assessment
are shown below in Table 5.2.

Table 5.2. Residential Post-Application Risks for Dicamba1

Population and Exposure Scenario	Route(s) of Exposure	Exposure
(mg/kg/day)	Risk Estimate (MOE)

Short-term Risk

Toddlers Playing	Dermal, Hand-to-Mouth, Object-to-Mouth, Soil Ingestion
0.014	3,200

Adults Doing Yardwork	Dermal	0.0037	12,000

Episodic Granule Ingestion

Toddlers	Oral Ingestion	0.2	1,500

1. MOE = NOAEL/exposure; NOAEL = 45 mg/kg/day.

6.0		Aggregate Exposure and Risk Assessment/Characterization

In accordance with the FQPA, HED must consider and aggregate (add)
pesticide exposures and risks from three major sources: food, drinking
water, and residential exposures.  In an aggregate assessment, exposures
from relevant sources are added together and compared to quantitative
estimates of hazard, or the risks themselves can be aggregated.  When
aggregating exposures and risks from various sources, HED considers both
the route and duration of exposure.  Since residential exposure is
expected, aggregate exposure consists of exposure from residential, food
and drinking water sources.

Acute and chronic aggregate risks were assessed based on dietary
exposure from food and drinking water sources.  Since there are
residential uses, short-term aggregate risks were assessed, but
intermediate-term aggregate risks were not considered as residential
exposure is not expected to occur for more than 30 days.  Cancer
aggregate risk was not assessed since dicamba is not a carcinogen.

6.1	Acute Aggregate Risk

It is HED policy not to aggregate acute residential exposures with acute
dietary exposures, since it is unlikely that these types of exposures
would occur in the same day.  Thus, the acute dietary assessment in
Section 4.6 represents acute aggregate risk.  As stated in Section 4.6,
the acute dietary exposure assessment was conducted using
tolerance-level residues, DEEM default processing factors and 100% CT
information for all registered and proposed use sites.  Drinking water
values were incorporated directly into the assessment.

The most highly exposed population subgroup is all infants (<1 year old;
11% of the aPAD).  These assessments conclude that the acute and chronic
dietary exposure estimates are not of concern to HED for the general
U.S. population or any population subgroup.  The use of ARs, empirical
processing factors and percent crop treated data would refine further
HED’s exposure and risk estimates; however, refinement is not needed
at this time.  Acute aggregate risk is not of concern to HED for any
population.

6.2	Short-term Aggregate Risk

The short term aggregate assessment is comprised of exposure from food,
water and residential activities (handler and post-application).
Average food and water exposure estimates were used in the assessment.
HED conducted a conservative short-term aggregate assessment that
assumed adults handle dicamba during lawn treatment as well as become
exposed through the diet and post-application activity on a treated
lawn.  The residential handler scenario that resulted in the highest
exposures, mix/load/apply with a (mix your own) hose-end sprayer, was
combined with exposure from the yardwork post-application scenario for
the adult assessment, while exposure from the toddler playing on turf
scenario was used in the assessment for children.

The results of all of the short-term aggregate assessments are presented
in Table 6.2.  HED is generally not concerned if the MOEs exceed the
target which, for this assessment, is 100.  The MOEs for all scenarios
are greater than 100 and are not of concern to HED.  As stated in the
previous section, these are likely to be overestimates and the actual
exposures are likely to be much lower.

Table 6.2.	Short-Term Aggregate Risk Calculations For Dicamba

Population	Food + Water Exposure

mg/kg/day	Incidental Oral Exposure, mg/day	Dermal Dose, mg/kg/day
Combined Exposure, mg/kg/day1	MOE

Food + Water+ Incidental Oral + Dermal2

Adult:

Residential Handler and Post-Application3

	0.012	0	0.016	0.028	1,600

Child:

Post-Application

(1-2 years old)	0.030	0.0078	0.0062	0.044	1,000

Combined exposure includes dermal, inhalation (for handlers only), and
dietary exposure.

The short-term NOAEL of 45 was used to calculate the MOE
(NOAEL/exposure=MOE).  The LOC is 100.

Dietary exposure from the general adult population subgroup was used as
this group had the highest dietary exposure of any adult subgroup.

6.3		Chronic Aggregate Risk

Since the residential uses of dicamba are not expected to occur over the
long-term (or chronic) duration, chronic aggregate risk is comprised of
dietary exposure only, from food and water sources.  The chronic dietary
assessment in Section 4.6 represents chronic aggregate risk.  As stated
in Section 4.6, the chronic dietary exposure assessment was conducted
using tolerance-level residues, DEEM default processing factors and 100%
CT information for all registered and proposed use sites.  Drinking
water values were incorporated directly into the assessment.

The most highly exposed population subgroup is children 1-2 years old
(6.7% of the cPAD).  Chronic aggregate risk is not of concern to HED for
any population.

7.0	Cumulative Risk Characterization/Assessment

Unlike other pesticides for which EPA has followed a cumulative risk
approach based on a common mechanism of toxicity, EPA has not made a
common mechanism of toxicity finding for dicamba and any other
substance, and dicamba does not appear to produce a toxic metabolite
produced by other substances.  For the purposes of this tolerance
action, therefore, EPA has not assumed that dicamba does not have a
common mechanism of toxicity with other substances.  For information
regarding EPA’s efforts to determine which chemicals have a common
mechanism of toxicity and to evaluate the cumulative effects of such
chemicals, see the policy statements released by EPA’s Office of
Pesticide Programs concerning common mechanism determinations and
procedures for cumulating effects from substances found to have a common
mechanism on EPA’s website at   HYPERLINK
http://www.epa.gov/pesticides/cumulative/.
http://www.epa.gov/pesticides/cumulative/.

8.0	Occupational Exposure/Risk Pathway  TC \l1 "9.0	Occupational
Exposure/Risk Pathway

Distinct® herbicide is proposed for control of annual and perennial
broad leaf weed species in sweet corn.  Distinct® is a WDG herbicide
that is comprised of 0.20 lb ae diflufenzopyr per pound of product and
0.50 lb ae dicamba per pound of product.  The proposed new uses comprise
an amendment to the EPA Registered Product No. 7969-150 which is
registered for use on field corn and non-crop areas.

For sweet corn, applications may be made from pre-plant to
post-emergence when corn is up to 24" tall.  For biannual or perennial
weeds, make applications when weeds are in the rosette stage before
bolting, in the bud stage or in the fall prior to a killing frost.

Table 8.  Use Pattern Summary of Proposed New Uses of Distinct®
Herbicide on Sweet Corn.

Formulation

Wettable Granule; dicamba 0.50 lb ae/ lb product.

Use Site

Sweet Corn

Application Method

Ground

Maximum Application Rate* pounds ae/A

Sweet corn - 0.25 lb product/A

Seasonal max -

Sweet corn 0.375 lb product/A

Frequency/Timing

Two applications/season; 14 day RTI

PHI

Sweet corn = 72 days dry grain and stover; 32 days for ears and stover.

REI

Label lists 12 hours, needs clarification- see below.

Manufacturer

BASF Corporation

* Sweet corn max rate = 4 oz product/A = 0.25 lb product/A * 0.50 lb
ae/lb product dicamba = 0.125 lb ae/A

Occupational exposure based on the proposed use on sweet corn is not
expected to differ significantly from that previously assessed for the
existing uses on field corn.  Therefore, a separate occupational risk
assessment was not produced for the sweet corn use.  Instead, the reader
is directed to the last risk assessment (Memo, C. Olinger, D317720,
9/13/2005).  A summary of the results of occupational risks is presented
below.

Occupational Handler Risk

MOEs for occupational handler exposure were calculated for
short/intermediate term dermal and inhalation exposures using standard
assumptions and unit exposure data.  The unit exposure data were
generally taken from PHED and ORETF studies for professional lawn care
operators.  All of the mixer/loader MOEs exceed the target of 100 with
single layer PPE (i.e., baseline clothing with gloves) and are not of
concern to HED.   The MOEs for applicators are above 100 with baseline
or single-layer PPE.  The MOEs for the mixer/loader/applicators are
acceptable with single-layer PPE and the MOEs for the flaggers are
acceptable with baseline PPE.  Dicamba labels typically require baseline
clothing with waterproof gloves.

Occupational Post-Application Risk

Post-application exposure to re-entry workers may occur to workers
performing activities in treated fields.  In the last occupational
exposure assessment (for the RED), post-application activities in field
corn were assessed.  The highest transfer coefficient (TC) for field
corn is 400 cm2/hr for weeding and scouting activities in medium mature
plants.  Post-application activities in sweet corn are expected to
result in higher exposure than those for field corn and include hand
harvesting and corn detasseling, which have a TC of 17,000 cm2/hr.  Risk
for sweet corn detasseling and hand harvesting result in an MOE of 130
on day 0, which is not of concern to HED.  All other post-application
MOEs are above the target MOE of 100 on Day 0.

The Distinct® label (EPA Reg. No. 7969-150) lists an REI of 12 hours.
Dicamba is listed as Acute Toxicity Category II for Primary Eye
Irritation and Primary Skin Irritation.  The interim WPS REI for
compounds exhibiting Toxicity Category II effects for primary eye and
skin irritation is 24 hours (40 CFR Part 156 § 156.208 (c) (1) and (2).
 HED requests confirmation of the basis for a 12-hour REI for this
product.

9.0	Data Needs and Label Recommendations  TC \l1 "10.0	Data Needs and
Label Recommendations

9.1	Toxicology  TC \l2 "10.1	Toxicology

No data needs.

9.2	Residue Chemistry  TC \l2 "10.2	Residue Chemistry

Additional sweet corn field residue trials.

Revised Section F.

9.3	Occupational and Residential Exposure  TC \l2 "10.3	Occupational and
Residential Exposure

HED recommends that RD clarify the appropriate REI for dicamba.

Attachment 1: Toxicity Profile for Dicamba

Attachment 2: Chemical Structures for Dicamba and its Salts

  SEQ CHAPTER \h \r 1

Attachment 1: Toxicity Profile for Dicamba

Guideline No./ Study Type/	MRID Nos.

Doses/Classification	Results

870.3100

Subchronic Oral

- Rat	44623101 (1997)

(0, 500, 3000, 6000, 12000 ppm)

M:0,40.1,238.7,479.4,1000 mg/kg/day

F:0,43.2,266.4,535.6,1065.3 mg/kg/day

Acceptable/Guideline	NOAEL= 479.4/535.6 mg/kg/day(M/F).

LOAEL= 1000/1065.3 mg/kg/day (M/F) based on clinical signs, decr. body
weight gains, incr. liver wt and incr. hepatocyte hypertrophy and
hepatocellular pigmentation.

870.3200

28-Day dermal toxicity

- Rat	45814501 (2002)

0,30,300,1000 mg/kg/day (M/F)

Acceptable/Guideline	NOAEL= 1000 mg/kg/day (HDT)

LOAEL= not determined.

870.3700a

Prenatal developmental

- Rat 	00084024 (1981)

0,64,160,400 mg/kg/day (GD 6-19)

Acceptable/Guideline	Maternal: NOAEL= 160 mg/kg/day; LOAEL= 400
mg/kg/day based on Incr. mortality, clinical signs, decr. body weight
gains, decr. food consumption.

Developmental: NOAEL= 400 mg/kg/day (HDT), LOAEL not established.

870.3700b

Prenatal developmental

- NZW Rabbit	42429401 (1992)

0,30,150,300 mg/kg/day (GD 6-18)

Range-finding:

0,62.5,125,250,500 mg/kg/day (GD 6-18)

Acceptable/Guideline	Maternal: NOAEL= 62.5 mg/kg/day, LOAEL= 150
mg/kg/day based on incr. abortion, clinical signs (decr. motor activity,
ataxia).

Developmental: NOAEL= 62.5 mg/kg/day, LOAEL= 150 mg/kg/day based on
incr. abortion.

870.3800

Reproduction and fertility effects

- Rat

	43137101 (1993)

(0,500,1500,5000 ppm)

M: 0,40,122,419 mg/kg/day

F: 0,45, 136, 450 mg/kg/day

Acceptable/Guideline	Parental/Systemic:

NOAEL= 122/136 mg/kg/day (M/F); LOAEL= 419/450 mg/kg/day (M/F) based on
clinical signs (slow righting reflex).

Reproductive:

NOAEL=122 mg/kg/day; LOAEL= 419 mg/kg/day based on delayed sexual
maturation in F1 males.

Offspring:

NOAEL=45 mg/kg/day; LOAEL= 136 mg/kg/day based on impaired pup growth
(decr. pup weights) in all generations during lactation period.

870.4200a

Chronic Toxicity/ Carcinogenicity

-Rat	00146150 (1985)

(0,50,250,2500 ppm)

M: 0,2,11,107 mg/kg/day

F: 0,3,13,127 mg/kg/day

Acceptable/Guideline	NOAEL= 107/127 mg/kg/day (M/F), LOAEL was not
established.

Not carcinogenic.

The study is considered adequate for evaluating the carcinogenic
potential.

870.4100b

Chronic toxicity

- dog	40321102 (1986)

(0,100,500,2500 ppm)

0,2,11,52 mg/kg/day

Acceptable/Guideline	NOAEL=52 mg/kg/day (HDT).

870.4200b

Carcinogenicity

- mouse	40872401 (1988)

(0,50,150,1000,3000 ppm)

M: 0,5.5,17.2,108,358 mg/kg/day

F: 0,5.8,18.8,121,354 mg/kg/day

Acceptable/Guideline	NOAEL=358/354 mg/kg/day (M/F), LOAEL was not
established.

Not carcinogenic.

The study is considered adequate for evaluating the carcinogenic
potential.

870.5100

Gene Mutation

Salmonella typhimurium	00143001(1979)

Acceptable/Guideline	Not mutagenic.

870.5395

Chromosome aberration (CHO)	40321101 (1986)

Acceptable/Guideline	Chromosome aberrations were not induced in a
cultured CHO cells at concentrations of 2330, 1170, 590, and 300 µg/mL
either with or without S-9 activation.

870.5550

Unscheduled DNA synthesis (UDS)	00143001 (1979)

Acceptable/Guideline	No evidence of UDS at levels 0.1 to 3000 µg/mL.

870.6200

Acute Neurotoxicity

- Rat	42774104 (1993)

0,300,600,1200 mg/kg

Acceptable/Guideline	NOAEL was not established, LOAEL=300 mg/kg based on
severe neurological signs (impaired respiration, rigidity upon handling,
prodding, or dropping, impaired gait and righting reflex in both sexes.

870.6200

Subchronic neurotoxicity

- Rat  	43245210 (1994)

(0,3000,6000,12000 ppm)

M:0,197.1,401.4,767.9 mg/kg/day

F: 0,253.4,472.0,1028.9 mg/kg/day

Acceptable/Guideline	NOAEL= 401.4/472.0 mg/kg/day (M/F);

LOAEL= 767.9/1028.9 mg/kg/day (M/F) based on rigidity body tone,
slightly impaired righting reflex and gait.

870.6300

Developmental Neurotoxicity

-Rat	Not Required.

	870.7485

Metabolism

	00028261(1967)

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  SEQ CHAPTER \h \r 1

Attachment 2: Chemical Structures for Dicamba and its Salts

PC Code 029801

Chemical structure

Common name	Dicamba acid

Molecular Formula	C8H6Cl2O3

Molecular Weight	221.04

IUPAC name	3,6-dichloro-o-anisic acid

CAS name	3,6-dichloro-2-methoxybenzoic acid or
2-methoxy-3,6-dichlorobenzoic acid

CAS #	1918-00-9

PC Code 029802

Chemical structure

Common name	Dicamba dimethylamine salt (DMA salt)

Molecular Formula	C10H13Cl2NO3

Molecular Weight	266.1

CAS #	2300-66-5

PC Code 029806

Chemical structure

Common name	Dicamba sodium salt (Na salt)

Molecular Formula	C8H5Cl2NaO3

Molecular Weight	243.0

CAS #	1982-69-0

PC Code 128931

Chemical structure

Common name	Dicamba diglycolamine salt (DGA salt)

Molecular Formula	C12H17Cl2NO5

Molecular Weight	326.18

CAS #	104040-79-1

PC Code 128944

Chemical structure

Common name	Dicamba isopropylamine salt (IPA salt)

Molecular Formula	C11H15Cl2NO3

Molecular Weight	280.15

CAS #	55871-02-8

PC Code 129043

Chemical structure

Common name	Dicamba potassium salt (K salt)

Molecular Formula	C8H5Cl2KO3

Molecular Weight	259.1

CAS #	10007-85-9

Human Health Risk Assessment for Dicamba D340156

Page   PAGE  32  of   NUMPAGES  32

Page   PAGE  1  of   NUMPAGES  32


[Federal Register Volume 84, Number 46 (Friday, March 8, 2019)]
[Proposed Rules]
[Pages 8485-8486]
[FR Doc No: 2019-04268]

=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF COMMERCE

Bureau of Industry and Security

15 CFR Part 774

[Docket No. 181010936-8936-01]
RIN 0694-AH66

Request for Public Comments Regarding Review of Commerce Control
List for Items Transferred From United States Munitions List Categories
IV and XV

AGENCY: Bureau of Industry and Security, Commerce.

ACTION: Advanced notice of proposed rulemaking.

-----------------------------------------------------------------------

SUMMARY: As part of its work with the National Space Council, the
Bureau of Industry and Security, Department of Commerce requests public
comment to inform its review of the controls implemented in recent
revisions to Categories IV and XV of the United States Munitions List
(USML) and the related transfer of items to the Department of
Commerce's Commerce Control List (CCL). These items include launch
vehicles, guided missiles, ballistic missiles, rockets, torpedoes,
bombs, and mines; and spacecraft and related articles. BIS's review
seeks to ensure that the CCL describes these items clearly, captures
those items in normal commercial use, accounts for technological
developments, and implements the national security and foreign policy
objectives of the United States properly.

DATES: Comments must be received by BIS no later than April 22, 2019.

ADDRESSES: Comments may be submitted through the Federal rulemaking
portal (http://www.regulations.gov). The regulations.gov ID number for
this rule is BIS-2018-0029. All comments (including any personally
identifying information) will be made available for public inspection
and copying.

FOR FURTHER INFORMATION CONTACT: For questions regarding launch
vehicles, guided missiles, ballistic missiles, rockets, torpedoes,
bombs, and mines (Export Control Classification Numbers (ECCNs) 0A604,
0B604, 0D604, 0E604, 9A604, 9B604, 9D604, and 9E604), contact Jeffrey
Leitz, Senior Staff Engineer, Munitions Control Division, Office of
Strategic Industries and Economic Security at<PHONE_NUMBER> or
<EMAIL_ADDRESS>For questions regarding spacecraft and
related items (ECCNs 9A515, 9B515, 9D515, and 9E515), contact Dennis
Krepp, Director, Sensors and Aviation Division, Office of National
Security and Technology Transfer Controls at<PHONE_NUMBER> or
<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

Background

    The Bureau of Industry and Security (BIS), Department of Commerce,
maintains the CCL under the Export Administration Regulations (EAR). To
ensure controls align with the national security and foreign policy
objectives of the U.S. Government, the USML and the CCL must be
regularly reviewed and updated to account for technological
developments, issues related to the practical application of these
controls, and changes in the military and commercial applications of
items covered by the USML or by the corresponding ``600 series'' and
9x515 ECCNs on the CCL.
    Consistent with the objectives in Space Policy Directive-2
(available at https://www.whitehouse.gov/presidential-actions/space-policy-directive-2-streamlining-regulations-commercial-use-space/),
this Advanced Notice of Proposed Rulemaking (ANPRM), seeks public
comments to inform a review of those items on the CCL implemented in
connection with the recent removal of articles from Categories IV (79
FR 34, January 2, 2014) and XV (82 FR 2889, January 10, 2017) of the
USML and the placement of those items on the CCL. BIS seeks to ensure
the CCL includes clear descriptions, captures items in normal
commercial use, takes into account technological developments, and
implements the national security and foreign policy objectives of the
United States properly.
    In particular, BIS seeks comment on ways to thoughtfully streamline
export control regulations for both the U.S. commercial space industry
as well as our international partners to lower administrative burden,
decrease regulatory compliance costs as well as increase exports
thereby bolstering the U.S. space commercial sector and industrial
base.

Request for Comments

    1. For technologies controlled under ECCN 9A515--examples include
habitats, planetary rovers, and planetary systems such as
communications and power--what factors or specific technologies should
be considered for movement to a different ECCN or paragraph under ECCN
9A515 with less stringent licensing requirements?
    2. The USG is considering further refinement or updated controls on
the various technologies listed below. Are there additional specific
space-related technologies not described in the list which warrant
further review by State or Commerce given their current or anticipated
near term commercial applications?
    [cir] Satellite thrusters (bi-propellant, electric, and liquid
apogee engines);
    [cir] gyroscopes;
    [cir] inertial navigation systems;
    [cir] large aperture earth observation cameras;
    [cir] spacecraft antenna systems and adaptive Global Navigation
Satellite System (GNSS) antennas;
    [cir] suborbital systems with propulsion systems currently
controlled under USML;
    [cir] kapton tape;
    [cir] star trackers; and
    [cir] astrocompasses.
    3. NASA continues to pursue development of the future Lunar
Gateway, which may be described in USML Category XV(a). If moved to the
CCL, what would be the appropriate controls to apply to items
associated with the Lunar Gateway, e.g., ECCNs 9A515 or 9A004?
    4. Are there technologies controlled in the USML for either
Category IV and XV, which are not currently described or not described
with sufficient clarity which the commenter believes should be
controlled under the EAR? While this notice discusses specific items
based on initial communications with industry, the list is not
exhaustive and commenters are encouraged to provide additional examples
within both USML categories.
    5. Are there specific defense articles which have entered into
normal commercial use since the most recent revisions? If so, please
provide sufficient detail in describing and identifying the article to
support your claim. Commenters may include documentation to support
this claim, e.g., product information demonstrating what is currently
in the market (web pages describing products and product brochures), or
scientific and industry articles, in particular those also describing
trends in commercial products, that resulted from new technologies or
manufacturing methods.
    6. Are there defense articles for which commercial use is proposed,
intended, or anticipated in the next five years? If so, provide
sufficient detail in describing and identifying the article to support
your claim. Commenters may include documentation to support this claim,
e.g., product development or marketing information describing what
products will soon to be in the market (web pages describing products
under development, press releases related to products under
development) or scientific and industry articles, in particular those
describing new products that may soon enter the market place as a
result of new technologies or manufacturing methods.
    7. Are there other technical issues for these items which BIS
should address, e.g., the addition of technical notes or defined terms
used in the control parameters to make the controls easier to
understand and apply consistently?
    8. What are the cost savings to private entities by shifting
control of additional specific commercial items from the USML to the
CCL? To the extent possible, please quantify the current cost of
compliance with USML control of an item and any cost savings if a
particular change was implemented. Cost savings could include time
saved in terms of regulatory uncertainty over whether certain items are
regulated as on the USML or the CCL. This reduced uncertainty, under
the ``bright line'' approach of the USML to CCL review process, would
allow both BIS and industry to avoid spending hours and resources on
case by case determinations for certain items. As much as possible,
please quantify time saved, reduction in compliance costs, and
reduction in paperwork.
    Please note general comments on other aspects of the CCL are
outside of the scope of this inquiry.

    Dated: February 22, 2019.
Richard E. Ashooh,
Assistant Secretary for Export Administration.
[FR Doc. 2019-04268 Filed 3-7-19; 8:45 am]
 BILLING CODE 3510-33-P