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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

**WASHINGTON, D.C. 20460**

**OFFICE OF**

**PREVENTION, PESTICIDES**

**AND TOXIC SUBSTANCES**

June 22, 2006

**[MEMORANDUM]{.underline}**

SUBJECT: Dichlorvos (DDVP) HED Chapter of the Reregistration Eligibility
Decision Document (RED). PC Code: 084001, Case #: 0310, DP Barcode:
D330262

Regulatory Action: Phase 5 Reregistration

Risk Assessment Type: Single Chemical/Aggregate

FROM: Susan V. Hummel, Chemist, Branch Senior Scientist

Reregistration Branch IV

Health Effects Division (7509C)

and

William Dykstra, Ph. D., Toxicologist

David Hrdy, Biologist

David Jaquith, Industrial Hygienist

Reregistration Branch IV

Health Effects Division (7509C)

THROUGH: Ray Kent, Ph. D., Branch Chief

Reregistration Branch IV

Health Effects Division (7509C)

TO: Eric Olson, CRM #61

Special Review Branch

Special Review and Reregistration Division (7508C)

Attached please find the revised Human Health Risk Assessment for
dichlorvos (DDVP). The Risk Assessment uses some endpoints based on
human studies, found to be in compliance with the human studies rule.
This document has been revised to address error only comments provided
by the registrant (AMVAC). Additionally, on May 9, 2006, AMVAC requested
voluntary cancellation and/or amendments, through incorporation of terms
and conditions to current dichlorvos registrations. These modifications
are summarized below:

**[Voluntary deletion of the following]{.underline}**:

**Product Types**

1\. 100 gram (g) pest strip

2\. 21 g pest strip (contingent on the granting of registration for 16 g
pest strip)

3\. Total release fogger

**Use Patterns**

4\. Lawn, Turf, and Ornamentals

5\. Crack and Crevice

**Application Method**

6\. Mushroom house hand held fogger

7\. Greenhouse hand held fogger

8\. Warehouse hand held fogger

**[Label Amendments]{.underline}**

**Occupational Exposure \-- Applicators**

1\. Mushroom house Hose End Sprayer \-- add coveralls to personal
protective equipment requirements.

**Occupational \-- Post Application**

2\. Mushroom houses -- 18 hour re-entry interval (REI)

3\. Greenhouse \-- 12 hour REI

**Pest Strips**

Registrant will split its end use registrations so that there will be
one end use label for the large pest strips (65 g & 80 g) and another
for the small pest strips (10.5 g, 5.25 g, and a new 16 g)

**65 and 80 g pest strips**

Label language to read**:**

"For use in unoccupied areas; not for use in homes except garages,
attics, crawl spaces, and sheds occupied for less than 4 hours per day.

Also for use in boathouses, museum collections, animal buildings, and
milk rooms, or enclosed areas thereof, occupied for less than 4 hours
per day.

For use in unoccupied areas such as trash dumpsters, catch basins, bulk
raw grain bins, storage bins, insect traps, enclosed utility boxes, and
storage units. Also for use in non-perishable packaged and bagged and
bulk stored processed and raw agricultural commodities (including
soybeans, corn, grains, cocoa beans and peanuts).

Also for use in the following unoccupied structures, provided they are
unoccupied for more than 4 months immediately following placement of a
pest strip: vacation homes, cabins, mobile homes, boats, farm houses,
and ranch houses."

**16 g (new), 10.5 g, 5.25 g pest strips**

Label language to read:

"Within homes, use only in closets, wardrobes, and cupboards. Also for
use in storage units, garages, attics, crawl spaces, boathouses, museum
collections, garbage cans, trash dumpsters, animal buildings, milk
rooms, catch basins, bulk raw grain, and storage bins."

**Table of Contents**

**1.0** **Executive Summary** [5](#__RefHeading___Toc137619470)

**1.1 Use and Major Formulations** [5](#__RefHeading___Toc137619471)

**1.2 Regulatory History** [5](#__RefHeading___Toc137619472)

**1.3 Hazard Identification and Dose-Response Assessment**
[7](#__RefHeading___Toc137619473)

**1.4 Exposure/Risk Assessment and Risk Characterization**
[8](#__RefHeading___Toc137619474)

**1.5 Human Studies** [10](#__RefHeading___Toc137619475)

**2.0 Ingredient Profile** [11](#__RefHeading___Toc137619476)

**2.1** **Summary of Registered/Proposed Uses**
[11](#__RefHeading___Toc137619477)

**2.2** **Structure and Nomenclature**
[31](#__RefHeading___Toc137619478)

**2.3** **Physical and Chemical Properties**
[31](#__RefHeading___Toc137619479)

**3.0** **Metabolism Assessment** [33](#__RefHeading___Toc137619480)

**3.1** **Comparative Metabolic Profile**
[33](#__RefHeading___Toc137619481)

**3.2** **Nature of the Residue in Foods**
[33](#__RefHeading___Toc137619482)

**3.2.1.** **Description of Primary Crop Metabolism**
[33](#__RefHeading___Toc137619483)

**3.2.2** **Description of Livestock Metabolism**
[33](#__RefHeading___Toc137619484)

**3.2.3** **Description of Rotational Crop Metabolism, including
identification of major metabolites and specific routes of
biotransformation** [34](#__RefHeading___Toc137619485)

**3.3** **Environmental Degradation** [34](#__RefHeading___Toc137619486)

**3.4** **Summary of Residues for Tolerance Expression and Risk
Assessment** [36](#__RefHeading___Toc137619487)

**4.0 Hazard Characterization/Assessment**
[36](#__RefHeading___Toc137619488)

**4.1** **Hazard Characterization** [36](#__RefHeading___Toc137619489)

**4.2.1** **Adequacy of the Toxicity Data Base**
[42](#__RefHeading___Toc137619490)

**4.2.2** **Evidence of Neurotoxicity**
[42](#__RefHeading___Toc137619491)

**4.2.3** **Developmental Toxicity Studies**
[42](#__RefHeading___Toc137619492)

**4.2.4** **Reproductive Toxicity Study**
[42](#__RefHeading___Toc137619493)

**4.2.5 Pre-and/or Postnatal Toxicity**
[43](#__RefHeading___Toc137619494)

**4.3** **Hazard Identification and Toxicity Endpoint Selection**
[44](#__RefHeading___Toc137619495)

**4.3.1. Acute Reference Dose (aRfD)**
[44](#__RefHeading___Toc137619496)

**4.3.2.** **Chronic Reference Dose (cRfD)**
[46](#__RefHeading___Toc137619497)

**4.3.3.** **Incidental Oral Exposure (Short and Intermediate Term)**
[47](#__RefHeading___Toc137619498)

**4.3.4.** **Dermal Absorption** [48](#__RefHeading___Toc137619499)

**4.3.5.** **Dermal Exposure (Acute)**
[48](#__RefHeading___Toc137619500)

**4.3.6.** **Dermal Exposure (Short- and Intermediate- Term)**
[48](#__RefHeading___Toc137619501)

**4.3.7.** **Inhalation Exposure (Acute)**
[49](#__RefHeading___Toc137619502)

**4.3.8.** **Inhalation Exposure (Short and Intermediate Term)**
[49](#__RefHeading___Toc137619503)

**4.3.9.** **Inhalation Exposure (Long Term)**
[49](#__RefHeading___Toc137619504)

**4.3.10.** **Margins of Exposure** [50](#__RefHeading___Toc137619505)

**4.3.11.** **Recommendation for Aggregate Exposure Risk Assessments**
[51](#__RefHeading___Toc137619506)

**4.3.12.** **Classification of Carcinogenic Potential**
[51](#__RefHeading___Toc137619507)

**4.4** **FQPA Safety factor** [53](#__RefHeading___Toc137619508)

**4.5.** **Endocrine Disruption** [54](#__RefHeading___Toc137619509)

**5.0** **Public Health Data** [55](#__RefHeading___Toc137619510)

**5.1** **Incident Reports** [55](#__RefHeading___Toc137619511)

**5.2** **Other** [55](#__RefHeading___Toc137619512)

**6.0 Exposure Characterization/Assessment**
[57](#__RefHeading___Toc137619513)

**6.1** **Dietary Exposure/Risk Pathway**
[57](#__RefHeading___Toc137619514)

**6.1.1** **Residue Profile** [57](#__RefHeading___Toc137619515)

**6.1.2** **Acute and Chronic Dietary Exposure and Risk**
[61](#__RefHeading___Toc137619516)

**6.2** **Water Exposure/Risk Pathway**
[67](#__RefHeading___Toc137619517)

**6.3** **Residential (Non-Occupational) Exposure/Risk Pathway**
[74](#__RefHeading___Toc137619518)

**6.3.1** **Home Uses** [74](#__RefHeading___Toc137619519)

**6.3.2** **Recreational Uses** [79](#__RefHeading___Toc137619520)

**6.3.3** **Other (Spray Drift, etc.)**
[79](#__RefHeading___Toc137619521)

**7.0** **Aggregate Risk Assessments and Risk Characterization**
[84](#__RefHeading___Toc137619522)

**7.1** **Acute Aggregate Risk** [85](#__RefHeading___Toc137619523)

**7.2** **Short-Term Aggregate Risk** [86](#__RefHeading___Toc137619524)

**7.3** **Intermediate-Term Aggregate Risk**
[88](#__RefHeading___Toc137619525)

**7.4** **Long-Term Aggregate Risk** [88](#__RefHeading___Toc137619526)

**7.5** **Aggregate Cancer Risk** [89](#__RefHeading___Toc137619527)

**8.0** **Cumulative Risk Characterization/Assessment**
[89](#__RefHeading___Toc137619528)

**9.0 Occupational Exposure/Risk Pathway**
[90](#__RefHeading___Toc137619529)

**10.0 Data Needs and Label Requirements**
[104](#__RefHeading___Toc137619530)

**10.1** **Toxicology** [104](#__RefHeading___Toc137619531)

**10.3** **Residue Chemistry** [104](#__RefHeading___Toc137619532)

**10.4** **Occupational and Residential Exposure**
[104](#__RefHeading___Toc137619533)

**REFERENCES** [106](#__RefHeading___Toc137619534)

**Appendices** [115](#__RefHeading___Toc137619535)

**1.0 Toxicology Data Requirements**

**2.0 Toxicology Studies**

**3.0 Residue Chemistry Data Requirements**

**4.0 Tolerance Reassessment**

**1.0 Executive Summary**[]{#__RefHeading___Toc137619470 .anchor}

The Health Effects Division (HED) has conducted a human health risk
assessment for the active ingredient dichlorvos (2,2-dichlorovinyl
dimethyl phosphate), also known as DDVP, for the purposes of making a
reregistration eligibility decision. Cumulative risk assessment
considering risks from other pesticides or chemical compounds having a
common mechanism of toxicity is not addressed in this document. This
risk assessment updates the Phase 3 Preliminary Human Health Risk
Assessment, dated August 9. 2000, addresses the Public Comments
submitted in accordance with Phase 3 of the Tolerance Reassessment
Advisory Committee (TRAC) Organophosphate (OP) Pilot Process, and
additional error correction comments on a June 14, 2005 assessment, and
uses endpoints based on human studies for some scenarios. The
intentional dosing, human toxicity study used in this risk assessment
has been reviewed by EPA's Human Studies Review Board (HSRB), on April
5, 2006, as required by EPA's Human Subjects Protections rule, 40 CFR
part 26 (effective April 7, 2006). Exposures and risks for all exposure
scenarios have been recalculated. Exposure to dichlorvos from the use of
naled and trichlorfon (which metabolize to dichlorvos) is included in
this document.

**1.1 Use and Major Formulations**[]{#__RefHeading___Toc137619471
.anchor}

Dichlorvos is an organophosphate insecticide and fumigant registered for
use in controlling flies, mosquitos, gnats, cockroaches, fleas, and
other insect pests. Formulations of dichlorvos include pressurized
liquids, granulars, emulsifiable concentrates, total release aerosols,
and impregnated materials. Dichlorvos is applied with aerosols and
fogging equipment, with spray equipment, and through slow release from
impregnated materials, such as resin strips and pet collars.

Dichlorvos is registered to control insect pests on agricultural sites;
commercial, institutional and industrial sites; and for domestic use in
and around homes (i.e., resin strips) and on pets. Dichlorvos is used
preplant in mushroom houses, and postharvest in storage areas for bulk,
packaged and bagged raw and processed agricultural commodities, food
manufacturing/processing plants, animal premises, and non-food areas of
food-handling establishments. It is also registered for direct dermal
treatment of cattle and poultry, and swine, sheep, and goats.

The mechanism of pesticidal action of dichlorvos is inhibition of
cholinesterase. The Agency has determined that the adverse effects
caused by dichlorvos that are of primary concern to human health are
neurological effects related to inhibition of cholinesterase activity.

**1.2 Regulatory History** []{#__RefHeading___Toc137619472 .anchor}

The Agency initiated a Special Review for pesticide products containing
dichlorvos on February 24, 1988, by publishing Position Document 1 (PD
1). At that time, the Agency was concerned that exposure to dichlorvos
from registered uses posed an unreasonable carcinogenic risk and that
there were inadequate margins of exposure for cholinesterase inhibition
and liver effects to exposed individuals. After evaluation of
information submitted through the Special Review Process, the Agency
conducted another risk assessment for dichlorvos. In 1995, the Agency
concluded that dichlorvos posed carcinogenic risks of concern to the
general population from dietary exposure. The Agency also concluded in
1995 that dichlorvos posed risks of concern for cholinesterase
inhibition to residents and to individuals mixing, loading, and applying
this pesticide, as well as to those reentering treated areas.
Subsequently, the Agency issued a Preliminary Determination to Cancel
Certain Registrations and Draft Notice of Intent to Cancel the
dichlorvos uses which posed the greatest risks, also called Position
Document 2/3 or PD 2/3 (60 FR 50338, September 28, 1995). In its 1995
Preliminary Determination (PD 2/3), the Agency concluded that the risks
outweighed the benefits for most uses of dichlorvos and, therefore,
recommended a variety of measures to reduce those risks. The Agency
proposed cancellation of certain uses of dichlorvos and cancellation of
other uses unless certain labeling modifications were made to reduce
risk.

The PD 2/3 Federal Register Notice provided for a formal comment period,
which closed on December 28, 1995. Comments were received, and are
contained in a public docket identified as "OPP-30000/56." Major
comments to the PD 2/3 were submitted to the Agency by Amvac Chemical
Corporation, the Japanese Resin Strip Manufacturer's Association, grower
groups, and the general public. Some of the comments contained
additional data pertaining to the risks posed by dichlorvos.

The Agency has also identified newer exposure and toxicity data
pertaining to dichlorvos that have become available since publication of
the Notice of Preliminary Determination to Cancel certain Registrations
and Draft Notice of Intent to Cancel (PD 2/3). In addition to the newer
data and information described above, the Food Quality Protection Act of
1996 has effectively modified the considerations the Agency uses to
assess the risks of pesticides. Therefore, the Agency has re-evaluated
the toxicology and exposure databases for dichlorvos to make a
determination of potential special susceptibility of infants and
children, as mandated by FQPA. In addition, the Agency has reviewed new
information pertaining to dietary exposure and performed a refined
dietary exposure assessment. The Agency has also refined the
occupational and residential exposure assessment for dichlorvos with new
information and new methodologies that were previously unavailable.

The following issues pertaining to the ongoing dichlorvos risk
assessment were presented to the FIFRA Science Advisory Panel (SAP) on
July 28, 1998: (1) the selection of an FQPA safety factor for dichlorvos
and (2) how the Agency conducted the resin strip exposure assessment.

This risk assessment has been conducted for dichlorvos in conjunction
with the public review and comment process for all of the
organophosphate pesticides. The public process for dichlorvos was
initiated on December 3, 1998, when the Phase 1 risk assessment was
provided to the registrant for "error only" review. In Phase 2 of the OP
pilot process, the error correction comments from the registrant were
incorporated. On October 11, 2000, the Preliminary Risk Assessment for
dichlorvos was issued for public comment. This revision incorporates
Agency response to the public comments submitted in Phase 3 of the OP
pilot process. Comments on the dichlorvos Preliminary Risk Assessment
were received from Amvac, NRDC, and dichlorvos users. Additional
exposure analyses were conducted for different sizes of resin strips and
for pet collars. Comments were received from a second registrant "error
correction" comment period and from the HSRB from an April 5, 2006
meeting.

**1.3 Hazard Identification and Dose-Response
Assessment**[]{#__RefHeading___Toc137619473 .anchor}

The toxicology database for dichlorvos is complete with respect to the
OPPTS Guideline requirements. For acute toxicity, technical dichlorvos
was placed in Toxicity Categories II, I and II, respectively, for the
oral, dermal and inhalation routes and in Toxicity Category III and IV
for eye and dermal irritation, respectively. Dichlorvos did not cause
organophosphate induced delayed neurotoxicity (OPIDN) in the hen
following single or multiple (28 days) exposures. Following a single
oral dose to rats, dichlorvos was associated with a variety of
neurological and physiological changes. Subchronic and chronic oral
exposures in rats and dogs as well as chronic inhalation exposure in
rats resulted in significant decreases in plasma, red blood cell and/or
brain cholinesterase activity. The carcinogenic potential of dichlorvos
has been classified as "suggestive" under the 1999 Draft Agency Cancer
Guidelines and no quantitative assessment of cancer risk is required.
There was no evidence of increased susceptibility following *in utero*
exposures to rats and rabbits as well as pre/post natal exposure to
rats. Also, there was no evidence of abnormalities in the development of
the fetal nervous system in the frbrlopmrnysl/neurotoxicity studies
submitted to the Agency.

The toxicity endpoints used in this document to assess risks include
acute and chronic dietary reference doses (RfDs), and short‑,
intermediate‑ and long‑term dermal LOAELs and inhalation no observed
adverse affect levels (NOAELs). Endpoints based on human studies have
been used to assess some scenarios.

Inhibition of cholinesterase activity was the toxicity endpoint selected
for acute and chronic dietary, as well as, short term, intermediate
term, and long term (chronic) occupational and residential risk
assessments. The Uncertainty Factor(s) ranged from 30 to 100 depending
on the route and duration of exposures.

The HED dichlorvos team evaluated the hazard and exposure data to
determine if the FQPA10x safety factor should be retained, reduced or
removed focusing primarily on the following points: 1) the standard
developmental and reproductive toxicity studies and the developmental
neurotoxicity study submitted to the Agency showed no residual concern
for increased susceptibility of rats, or rabbits to *in utero* and/or
postnatal exposure to dichlorvos; 2) in single dose (acute) studies with
dichlorvos in rats, there were no differences with respect to either RBC
or brain cholinesterase inhibition between preweaning and adult rats; 3)
in repeated dose studies with dichlorvos in rats, young rats were no
more sensitive than adult rats with respect to inhibition of RBC and
brain cholinesterase; and 4) sufficient data were available to ensure
that the dietary (food and drinking water) and non-dietary (residential)
risk assessments do not underestimate potential exposures and risks for
infants and children from the use of dichlorvos. Some scenarios used
endpoints ased on a LOAEL, and the 3x uncertainty factor used is
considered part of the FQPA safety factor.

The dichlorvos team determined that there no residual concerns for
increased susceptibility of infants and children. An FQPA safety factor
of 1x is considered appropriate.

**1.4 Exposure/Risk Assessment and Risk
Characterization**[]{#__RefHeading___Toc137619474 .anchor}

Dietary exposure to dichlorvos residues may occur as a result of use of
dichlorvos on or at a variety of sites, including mushroom houses,
bulk-stored and packaged or bagged nonperishable processed and raw food,
commercial food processing plants, direct dermal pour-on treatment to
livestock, and livestock premises treatment. Two other pesticides, naled
and trichlorfon, degrade to dichlorvos through plant and animal
metabolism and other processes. Residues of dichlorvos from the use of
naled on crops are included in the dichlorvos dietary exposure
assessment. All trichlorfon field crop food uses have been canceled and
associated tolerances revoked; therefore, the Agency does not expect
measurable dichlorvos residues from use of trichlorfon on field crops.
The trichlorfon tolerances on livestock commodities remain; dermal use
on beef cattle is supported as an import use. Non-detectable dichlorvos
residues in livestock commodities are expected as a result of
trichlorfon use, and dichlorvos was not a significant metabolite in the
trichlorfon dermal metabolism study. Therefore, dietary (food) exposure
to dichlorvos residues resulting from use of trichlorfon is considered
negligible for the purposes of this risk assessment.

Most product and residue chemistry data requirements for dichlorvos have
been fulfilled. However, the reregistration data requirements for
storage stability (Guideline 860.1380), for meat, milk, poultry, and egg
studies (Guideline 860.1480), and directions for use (Guideline
860.1200) have not been fulfilled.

Dietary (food only) exposure estimates for dichlorvos have been refined
with residue data from USDA's Pesticide Data Program (PDP), FDA
surveillance monitoring data and FDA Total Diet Study (TDS) data.
Anticipated residues for dichlorvos have been revised to incorporate
these residue data. The acute and chronic dietary exposure analyses for
dichlorvos (including contribution from naled and negligible
contribution from trichlorfon) were conducted using the Dietary Exposure
Evaluation Model (DEEM) software. Acute dietary exposure did not exceed
the Agency's level of concern for the 99.9^th^ percentile of the
population. Chronic dietary exposure did not exceed 2% of the cPAD for
all subpopulations, which is below the Agency's level of concern of
100%.

The Environmental Fate and Effects Division (EFED) evaluated the
potential for dichlorvos to contaminate water from the use of
dichlorvos, naled or trichlorfon. EFED has limited ground water
monitoring data for dichlorvos, naled, and trichlorfon from the states
of California and Hawaii in the "Pesticides in Groundwater" database.
These data indicate that naled, dichlorvos, or trichlorfon have not been
detected in groundwater; however, these data were not targeted to the
pesticide use area. Therefore, the SCIGROW model was used to estimate
concentrations of dichlorvos, naled, and trichlorfon in groundwater. OPP
does not have any surface monitoring data on the concentrations of
dichlorvos, naled, or trichlorfon at the present time. Therefore, the
Tier II screening models PRZM and EXAMS with the Index Reservoir and
Percent Crop Area adjustment (IR-PCA PRZM/EXAMS) were used to estimate
surface water concentrations for dichlorvos resulting from the use of
naled, trichlorfon and dichlorvos.

Although PDP water monitoring data were available, and all samples had
non-detectable residues (LODs ranged from 6 to 22.5 ppt), these data
were not considered sufficiently representative. In the absence of
sufficient water monitoring data, estimated drinking water
concentrations (EDWCs) of dichlorvos from the use of dichlorvos, naled,
and trichlorfon in water were compared with Drinking Water Levels of
Comparison (DWLOCs) for acute or chronic systemic toxicity. EDWCs of
dichlorvos in ground and surface water were derived from conservative
screening level models. A DWLOC is a theoretical upper limit on a
pesticide's concentration in drinking water in light of total aggregate
exposure to a pesticide in food, drinking water, and through residential
uses. HED uses DWLOCs internally in the risk assessment process as a
surrogate measure of potential exposure associated with pesticide
exposure through drinking water.

Residential and occupational exposure scenarios can be described as
acute, short term (1-30 days), intermediate term (1 month to 6 months),
and long term or chronic (6 months to a lifetime). The dichlorvos
residential exposure scenarios for aerosol spray cans (both homeowner
application and post-application) are considered acute exposure
scenarios. Lawn post-application from treatment with trichlorfon is
considered a short-term exposure scenario. Resin pest strips and pet
flea collars are long term exposure scenarios. Occupational exposure
scenarios are typically acute or short-term, except for a few
intermediate term occupational exposure scenarios, applications in
mushroom houses and direct application to livestock.

Exposure assessments for a number of occupational and residential
scenarios were derived from limited data from the scientific literature,
textbooks, knowledge of cultural practices, and the Residential SOPs
(U.S. EPA, 1997a). Other estimates, particularly in the residential
environment, were derived from surrogate data from the Pesticide
Handlers Exposure Database (PHED, version 1.1), chemical specific data
included in the Outdoor Residential Exposure Task Force (ORETF)
database, Residential Exposure Joint Venture (REJV) data, and additional
chemical specific monitoring data, including biomonitoring of a urinary
metabolite, in combination with models and literature studies.

Residential exposure scenarios do not exceed the Agency's level of
concern. Residential exposure from the use of the pressurized aerosol
has been recalculated due to new data from the Residential Exposure
Joint Venture (REJV).

Residential and occupational exposures to dichlorvos may also result
from uses of naled and trichlorfon. The only naled residential use is a
mosquitocide public health use. For this use, the application rate of
naled is very low, and we expect that any dichlorvos formed dissipates
rapidly. Further discussion is found in the exposure assessment section
of this document. Approximately 25% of trichlorfon is expected to
degrade to dichlorvos at the pH of a typical lawn.

None of the aggregate risks exceed our level of concern, considering
food, water, and residential exposures, for all residential exposure
scenarios. Food and water exposure were very small compared to the
residential exposure estimates.

Occupational handler scenarios do not exceed the Agency's level of
concern, after voluntary cancellations, addition of additional PPE, and
longer reentry intervals (REIs).

**1.5 Human Studies**[]{#__RefHeading___Toc137619475 .anchor}

This risk assessment relies in part on data from studies in which adult
human subjects were intentionally exposed to a pesticide or other
chemical. These studies, listed below, have been determined to require a
review of their ethical conduct, and EPA is currently preparing these
ethics reviews in accordance with EPA Human Subjects Protections rule,
40 CFR part 26**.**

> Gledhill, A., 1997. Dichlorvos: A Single Blind, Placebo Controlled,
> Randomised Study to Investigate the Effects of Multiple Oral Dosing on
> Erythrocyte Cholinesterase Inhibition in Healthy Male Volunteers: Lab
> Project Number: CTL/P/5392: XH6063. Unpublished study prepared by
> Zeneca Central Toxicology Lab. 52 p. MRID 44248801.
>
> Emlay, D.; Rudolph, R. (1977) Determination of the Quantity of
> Carbaryl Removed by Petting Dogs Wearing 16% Carbaryl Dog Collars: Lab
> Project Number: TR‑506. Unpublished study prepared by Zoecon
> Industries, Inc. 14 p. {OPPTS 875.1500} MRID 45792201.
>
> Klonne, D. (1999) Integrated Report for Evaluation of Potential
> Exposures to Homeowners and Professional Lawn Care Operators Mixing,
> Loading, and Applying Granular and Liquid Pesticides to Residential
> Lawns: Lab Project Number: OMAOO5: OMAOO1: OMAOO2. Unpublished study
> prepared by Ricerca, Inc., and Morse Laboratories. 2213 p. (MRID
> 44972201) (ORETF study)
>
> McDonald, E., 1991. Indoor Fogger Dermal and Inhalation Exposure Study
> with DDVP: Lab Project Number: 4‑02‑333. Unpublished study prepared by
> British Columbia Research Corp. 331 p. MRID 41928801.
>
> The PHED Task Force, 1995. The Pesticide Handlers Exposure Database,
> Version 1.1. Electronic Database. Task Force members Health Canada, U.
> S. Environmental Protection Agency, and the National Agricultural
> Chemicals Association, released February, 1995.

In addition, the Human Subjects Protections rule requires that the
Gledhill study -- an intentional dosing, human toxicity study on which
EPA is relying in this risk assessment -- be reviewed by the Human
Studies Review Board (HSRB). The Agency presented the Gledhill study to
the HSRB at a meeting on April 2 -- 4, 2006. The HSRB discussed the
Gledhill study extensively during this meeting and has prepared a draft
written report summarizing its discussions. The Agency believes that the
oral comments of the HSRB and the draft report provided a sufficient
indication of the conclusions likely to appear in the HSRB's final
report that EPA could confidently move ahead. Accordingly, the Agency
has decided to issue this risk assessment prior to receiving the final
written report of the HSRB. The Agency will carefully review the HSRB's
final report on DDVP prior to issuing its final reregistration
eligibility decision to determine whether the HSRB's report contains
conclusions that warrant reconsideration of this risk assessment

> **2.0 Ingredient Profile**[]{#__RefHeading___Toc137619476 .anchor}

Dichlorvos is a chlorinated organophosphorus insecticide, with technical
and manufacturing use products registered to Amvac Chemical Corporation
and Drexel Chemical Company. Formulations and EPA Reg. Nos. are
summarized below in table 2.0.

**Table 2.0. Registered Manufacturing-Use Products of Dichlorvos, as
described in OPPIN.**

  -------------------- ------------------ -------------------------------
  **Formulation**      **EPA Reg. No.**   **Registrant**

  93% T                5481-96            Amvac Chemical Corporation

  98% T ^1,2^          5481-461           

  98% T ^1,2^          5481-462           

  90% FI ^3^           19713-353          Drexel Chemical Company
  -------------------- ------------------ -------------------------------

^1^ Repackaged from an EPA-registered product. We note that there is not
another EPA registered product containing 98% dichlorvos. This
discrepancy must be cleared up.

^2^ OPPIN currently identifies this product as an FI; however, it is
correctly identified as a T.

^3^ Sequentially transferred from EPA Reg. Nos. 8521-126, 904-396, and
44215-139.

T = Technical Product FI = Formulation intermediate

> **2.1 Summary of Registered/Proposed
> Uses**[]{#__RefHeading___Toc137619477 .anchor}

The basic producer of dichlorvos is Amvac Chemical Corporation.
According to an OPPIN search, conducted on 6/12/06, there are 98 active
end-use products (EPs) registered under FIFRA Section 3 containing
dichlorvos, 29 of which are registered to Amvac; there is one Special
Local Need (SLN) registration under FIFRA Section 24(c) associated with
these Amvac EPs, and one Special Local Need (SLN) registration under
FIFRA Section 24(c) associated with another EP. The registered food and
feed use patterns of dichlorvos EP labels subject to reregistration are
presented in table 2.1. Residential use patterns are discussed in
Section 6 of this document. Occupational use patterns are discussed in
Section 9 of this document. In addition, Amvac submitted copies of two
product labels for the technical formulation (EPA Reg. Nos. 5481-461 and
5481-462) which include directions for use for various sites.

+------------+-----+---------+---------------------------------------+
| **Table    |     |         |                                       |
| 2.1.       |     |         |                                       |
| Food/Feed  |     |         |                                       |
| Use        |     |         |                                       |
| Patterns   |     |         |                                       |
| on EP      |     |         |                                       |
| Labels     |     |         |                                       |
| Subject to |     |         |                                       |
| Rere       |     |         |                                       |
| gistration |     |         |                                       |
| for        |     |         |                                       |
| Dichlorvos |     |         |                                       |
| (Case      |     |         |                                       |
| 0310).**   |     |         |                                       |
+============+=====+=========+=======================================+
| **Site**   | Fo  | Appl    | Use Directions and Limitations^2^     |
|            | rmu | ication |                                       |
| > A        | lat | Rate,   |                                       |
| pplication | ion | ai ^1^  |                                       |
| > Type     |     |         |                                       |
|            | \[  |         |                                       |
|            | EPA |         |                                       |
|            | R   |         |                                       |
|            | eg. |         |                                       |
|            | No  |         |                                       |
|            | .\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Ag       |     |         |                                       |
| ricultural |     |         |                                       |
| c          |     |         |                                       |
| ommodities |     |         |                                       |
| (bulk      |     |         |                                       |
| storage of |     |         |                                       |
| non        |     |         |                                       |
| perishable |     |         |                                       |
| raw and    |     |         |                                       |
| processed  |     |         |                                       |
| ag         |     |         |                                       |
| ricultural |     |         |                                       |
| c          |     |         |                                       |
| ommodities |     |         |                                       |
| including  |     |         |                                       |
| raw        |     |         |                                       |
| grains,    |     |         |                                       |
| corn,      |     |         |                                       |
| soybeans,  |     |         |                                       |
| cocoa      |     |         |                                       |
| beans, and |     |         |                                       |
| peanuts)** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Premise  | 20% | 10.5 g  | Use of product where unwrapped food   |
| >          | I   | of      | is stored or allowing the strip to    |
|  treatment | mpr | p       | come in contact with food or cooking  |
|            |     | roduct/ | utensils is prohibited.               |
|            | \[5 |         |                                       |
|            | 481 | 50-100  |                                       |
|            | -33 | cu. ft  |                                       |
|            | 8\] |         |                                       |
|            |     | or      |                                       |
|            |     |         |                                       |
|            |     | 80 g of |                                       |
|            |     | p       |                                       |
|            |     | roduct/ |                                       |
|            |     |         |                                       |
|            |     | 9       |                                       |
|            |     | 00-1200 |                                       |
|            |     | cu. ft  |                                       |
+------------+-----+---------+---------------------------------------+
|            | 20% |         | Use in kitchens, restaurants, or      |
|            | I   |         | areas where food/feed are prepared or |
|            | mpr |         | processed, use in food/feed           |
|            |     |         | processing or food/feed manufacturing |
|            | \[5 |         | areas of food/feed processing and     |
|            | 481 |         | food/feed manufacturing plants are    |
|            | -34 |         | prohibited.                           |
|            | 4\] |         |                                       |
+------------+-----+---------+---------------------------------------+
|            | 20% |         | Use in kitchens, restaurants, or      |
|            | I   |         | areas where food is prepared or       |
|            | mpr |         | served and use in edible product      |
|            |     |         | areas of food processing plants are   |
|            | \[5 |         | prohibited.                           |
|            | 481 |         |                                       |
|            | -34 |         |                                       |
|            | 8\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Gre      |     |         |                                       |
| enhouses** |     |         |                                       |
| (not       |     |         |                                       |
| containing |     |         |                                       |
| food       |     |         |                                       |
| co         |     |         |                                       |
| mmodities) |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Fog      | 0   | 0.004   | Applications may be made using a cold |
| > a        | .37 | l       | aerosol generator. Hand held foggers  |
| pplication | lb/ | b/1,000 | are no longer permitted.              |
| >          | gal | cu. ft  |                                       |
| > \        | EC  |         |                                       |
| [hand-held |     |         |                                       |
| > fogger   | \[5 |         |                                       |
| > is no    | 481 |         |                                       |
| > longer   | -22 |         |                                       |
| > p        | 0\] |         |                                       |
| ermitted\] |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Mushroom |     |         |                                       |
| houses**   |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Fog      | 50% | 2%      | Applications may be made in           |
| > a        | FlC | f       | 1,1,1-trichloroethane using a cold    |
| pplication |     | inished | aerosol generator. Applications may   |
| >          | \[5 | spray   | be made twice a week during spawn     |
| > \        | 481 |         | run; thereafter use as needed. A      |
| [hand-held | -20 | \[6.25  | 1-day PHI has been established for    |
| > fogger   | 3\] | oz      | mushrooms.                            |
| > is no    |     | /10,000 |                                       |
| > longer   |     | cu.ft\] |                                       |
| > p        |     |         |                                       |
| ermitted\] |     |         |                                       |
+------------+-----+---------+---------------------------------------+
|            |     | 2%      | Applications may be made in           |
|            |     | f       | deodorized base kerosene using a cold |
|            |     | inished | aerosol generator. Applications may   |
|            |     | spray   | be made twice a week during spawn     |
|            |     |         | run; thereafter use as needed. A      |
|            |     | \[10    | 1-day PHI has been established for    |
|            |     | oz      | mushrooms.                            |
|            |     | /10,000 |                                       |
|            |     | cu.ft\] |                                       |
|            |     |         |                                       |
|            |     | 5       |                                       |
|            |     | g       |                                       |
|            |     | /10,000 |                                       |
|            |     | cu.ft   |                                       |
+------------+-----+---------+---------------------------------------+
|            | 0   | 0.004   | Applications may be made using a cold |
|            | .37 | l       | aerosol generator. Applications may   |
|            | lb/ | b/1,000 | be made twice a week during spawn     |
|            | gal | cu.ft   | run; thereafter use as needed.        |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -22 |         |                                       |
|            | 0\] |         |                                       |
+------------+-----+---------+---------------------------------------+
|            |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| Brush on   | 2   | 0.00125 | Coarse spray or paint on walls,       |
| /coarse    | lb/ | lb/100  | around doors, ventilators & cracks    |
| spray      | gal | sq ft   | before mushrooms come into            |
|            | EC  |         | production. Use as 0.5% solution -- 1 |
|            |     |         | pint of 0.5% solution per 100 sq ft., |
|            | \   |         | up to 10 days before crop emerges on  |
|            | [72 |         | soil beds. Do not spray inside walls  |
|            | -36 |         | after mushrooms appear on beds. After |
|            | 5\] |         | mushrooms appear, spray only the      |
|            | (   |         | outside of the building.              |
|            | can |         |                                       |
|            | cel |         |                                       |
|            | ed) |         |                                       |
+------------+-----+---------+---------------------------------------+
|            |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| >          |     |         |                                       |
|  **Tobacco |     |         |                                       |
| > Wa       |     |         |                                       |
| rehouse:** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Space    | 1   | 2%      | Fogging applications may be made with |
| >          | .59 | f       | odorless oil or other non-flammable   |
|  treatment | lb/ | inished | oil solvents known to be safe for use |
| > in       | gal | spray   | in tobacco warehouses. Applications   |
| > closed   | EC  |         | may be repeated as needed.            |
| >          |     | \[19-38 | Applications may be made only in      |
| warehouses | \[5 | fl.oz   | warehouses storing unfinished         |
| > \        | 481 | /10,000 | tobacco.                              |
| [Hand-Held | -20 | cu.ft\] |                                       |
| > Foggers  | 6\] |         |                                       |
| > are no   |     | or      |                                       |
| > longer   | 4   |         |                                       |
| > p        | lb/ | 10-20   |                                       |
| ermitted\] | gal | g       |                                       |
|            | EC  | /10,000 |                                       |
|            |     | cu. ft  |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 4\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .15 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 7\] |         |                                       |
|            |     |         |                                       |
|            | 8   |         |                                       |
|            | .39 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 1\] |         |                                       |
+------------+-----+---------+---------------------------------------+
|            | 0   | 0.37    | Fogging applications may be repeated  |
|            | .37 | lb/     | as needed. Applications may be made   |
|            | lb/ | 336,000 | only in warehouses storing unfinished |
|            | gal | cu.ft   | tobacco.                              |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -22 |         |                                       |
|            | 0\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Foo      |     |         |                                       |
| d-handling |     |         |                                       |
| esta       |     |         |                                       |
| blishments |     |         |                                       |
| (including |     |         |                                       |
| h          |     |         |                                       |
| ouseholds; |     |         |                                       |
| re         |     |         |                                       |
| staurants; |     |         |                                       |
| theaters;  |     |         |                                       |
| food       |     |         |                                       |
| processing |     |         |                                       |
| plants;    |     |         |                                       |
| industrial |     |         |                                       |
| plants;    |     |         |                                       |
| and        |     |         |                                       |
| war        |     |         |                                       |
| ehouses)** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Indoor   | 4   | 0.5%    | Applications may be made with         |
| >          | lb/ | f       | deodorized base oil or water using a  |
|  treatment | gal | inished | low pressure sprayer to treat         |
| >          | EC  | spray   | localized areas where insects may     |
| > Directed |     |         | infest around baseboards, cracks,     |
| > spray    | \[5 | 2.5     | walls, doors, window frames, and      |
| > a        | 481 | g/1000  | localized areas of floors. Use in     |
| pplication | -20 | cu. ft. | edible product areas of food          |
| >          | 4\] |         | processing plants, restaurants, or    |
| > Indoor   |     |         | other areas where food is             |
| >          | 20% |         | commercially prepared or processed    |
|  treatment | PrL |         | and use in serving areas while food   |
| >          |     |         | is exposed is prohibited              |
| > Remote   | \[4 |         |                                       |
| > Fog      | 700 |         | Application made by timer when        |
| > A        | 0-7 |         | buildings are unoccupied. Building    |
| pplication | 1\] |         | should be closed and ventilation kept |
|            |     |         | to a minimum. Lock all entrances, and |
|            |     |         | do not allow unprotected workers to   |
|            |     |         | enter the building when being         |
|            |     |         | treated.                              |
+------------+-----+---------+---------------------------------------+
| **Foo      |     |         |                                       |
| d-handling |     |         |                                       |
| esta       |     |         |                                       |
| blishments |     |         |                                       |
| (including |     |         |                                       |
| theaters;  |     |         |                                       |
| food       |     |         |                                       |
| processing |     |         |                                       |
| plants;    |     |         |                                       |
| industrial |     |         |                                       |
| plants;    |     |         |                                       |
| and        |     |         |                                       |
| war        |     |         |                                       |
| ehouses)** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Indoor   | 0   | 1%      | Fogging or misting applications may   |
| >          | .37 | f       | be made with deodorized base oil or   |
|  treatment | lb/ | inished | water using fogging or misting        |
| >          | gal | spray   | equipment to treat indoor areas.      |
| > Space    | EC  |         | Applications are to be made when the  |
| > spray    |     | \[1     | plants are not in operation. Food     |
| > a        | \[5 | gal     | should be removed and food-handling   |
| pplication | 481 | /64,000 | equipment covered prior to            |
| >          | -22 | cu.ft\] | application or washed with suitable   |
| > \        | 0\] |         | cleaner and potable water after       |
| [Hand-Held |     |         | application.                          |
| > Foggers  | 1   |         |                                       |
| > are no   | .59 |         |                                       |
| > longer   | lb/ |         |                                       |
| > p        | gal |         |                                       |
| ermitted\] | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 6\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 4\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .15 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 7\] |         |                                       |
|            |     |         |                                       |
|            | 2   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -33 |         |                                       |
|            | 4\] |         |                                       |
|            |     |         |                                       |
|            | 8   |         |                                       |
|            | .39 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 1\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Foo      |     |         |                                       |
| d-handling |     |         |                                       |
| esta       |     |         |                                       |
| blishments |     |         |                                       |
| \          |     |         |                                       |
| [including |     |         |                                       |
| areas for  |     |         |                                       |
| receiving, |     |         |                                       |
| storage,   |     |         |                                       |
| packing    |     |         |                                       |
| (canning,  |     |         |                                       |
| bottling,  |     |         |                                       |
| wrapping,  |     |         |                                       |
| boxing),   |     |         |                                       |
| preparing, |     |         |                                       |
| edible     |     |         |                                       |
| waste      |     |         |                                       |
| storage,   |     |         |                                       |
| and        |     |         |                                       |
| enclosed   |     |         |                                       |
| processing |     |         |                                       |
| systems    |     |         |                                       |
| (mills,    |     |         |                                       |
| dairies,   |     |         |                                       |
| edible     |     |         |                                       |
| oils,      |     |         |                                       |
| syrups),   |     |         |                                       |
| and        |     |         |                                       |
| serving    |     |         |                                       |
| areas\]**  |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Indoor   | 0   | 0.1%    | Applications may be made in water or  |
| > crack    | .25 | f       | oil and may be applied by directing   |
| > and      | lb/ | inished | small amounts into crack and          |
| > crevice  | gal | spray   | crevices, in points between different |
| >          | EC  |         | elements of construction, and between |
|  treatment |     |         | equipment legs and bases.             |
|            | \[5 |         | Applications in food areas other than |
|            | 481 |         | crack and crevice treatments are      |
|            | -21 |         | prohibited.                           |
|            | 7\] |         |                                       |
|            |     |         |                                       |
|            | 0.5 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -21 |         |                                       |
|            | 6\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| **No       |     |         |                                       |
| nfood/feed |     |         |                                       |
| areas of   |     |         |                                       |
| foo        |     |         |                                       |
| d-handling |     |         |                                       |
| esta       |     |         |                                       |
| blishments |     |         |                                       |
| \          |     |         |                                       |
| [including |     |         |                                       |
| garbage    |     |         |                                       |
| rooms,     |     |         |                                       |
| l          |     |         |                                       |
| avatories, |     |         |                                       |
| floor      |     |         |                                       |
| drains     |     |         |                                       |
| (sewers),  |     |         |                                       |
| entries    |     |         |                                       |
| and        |     |         |                                       |
| v          |     |         |                                       |
| estibules, |     |         |                                       |
| offices,   |     |         |                                       |
| locker     |     |         |                                       |
| rooms,     |     |         |                                       |
| machine    |     |         |                                       |
| rooms,     |     |         |                                       |
| boiler     |     |         |                                       |
| rooms,     |     |         |                                       |
| garages,   |     |         |                                       |
| mop        |     |         |                                       |
| closets,   |     |         |                                       |
| and        |     |         |                                       |
| storage    |     |         |                                       |
| (after     |     |         |                                       |
| canning or |     |         |                                       |
| bot        |     |         |                                       |
| tling)\]** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Indoor   | 0   | 0.5%    | Applications may be made with         |
| >          | .37 | f       | deodorized base oil or water using a  |
|  treatment | lb/ | inished | low pressure sprayer to treat         |
| >          | gal | spray   | localized areas where insects may     |
| > Directed | EC  |         | infest around baseboards, cracks,     |
| > spray    |     |         | walls, doors, window frames, and      |
| > a        | \[5 |         | localized areas of floors. Use in     |
| pplication | 481 |         | edible product areas of food          |
|            | -22 |         | processing plants, restaurants, or    |
|            | 0\] |         | other areas where food is             |
|            |     |         | commercially prepared or processed    |
|            | 1   |         | and use in serving areas while food   |
|            | .59 |         | is exposed are prohibited.            |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 6\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .15 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 7\] |         |                                       |
|            |     |         |                                       |
|            | 2   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -33 |         |                                       |
|            | 4\] |         |                                       |
|            |     |         |                                       |
|            | 8   |         |                                       |
|            | .39 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 1\] |         |                                       |
+------------+-----+---------+---------------------------------------+
|            | 4   | 0.5%    | Applications may be made with         |
|            | .48 | f       | deodorized base oil using a low       |
|            | lb/ | inished | pressure sprayer to treat localized   |
|            | gal | spray   | areas where insects may infest around |
|            | SC  |         | baseboards, cracks, walls, doors,     |
|            |     |         | window frames, and localized areas of |
|            | \[5 |         | floors. Use in food/feed handling     |
|            | 481 |         | areas of food/feed handling           |
|            | -20 |         | establishments, restaurants or other  |
|            | 2\] |         | areas where food is commercially      |
|            |     |         | prepared or served and use to treat   |
|            |     |         | non-perishable bagged or bulk raw or  |
|            |     |         | processed commodities is prohibited.  |
+------------+-----+---------+---------------------------------------+
|            | 10  | 0.5%    | For use in warehouses, silos, bulk    |
|            | lb/ | f       | bins, and food/feed processing,       |
|            | gal | inished | food/feed manufacturing, handling and |
|            | SC  | spray   | storage plants containing             |
|            |     |         | non-perishable, packaged or bagged    |
|            | \[5 |         | raw or processed food/feed            |
|            | 481 |         | commodities or bulk raw or processed  |
|            | -20 |         | food commodities. Applications may be |
|            | 0\] |         | made with deodorized base oil using a |
|            |     |         | low pressure sprayer to treat         |
|            |     |         | localized areas where insects may     |
|            |     |         | infest around baseboards, cracks,     |
|            |     |         | walls, doors, window frames, and      |
|            |     |         | localized areas of floors. Use of     |
|            |     |         | this product in food processing       |
|            |     |         | plants, food-handling areas of        |
|            |     |         | restaurants, or areas where food is   |
|            |     |         | prepared or served, and use to treat  |
|            |     |         | non-perishable bagged and or bulk     |
|            |     |         | stored raw or processed agricultural  |
|            |     |         | commodities are prohibited.           |
|            |     |         | Contamination of food, water, food    |
|            |     |         | containers, or cooking utensils is    |
|            |     |         | prohibited.                           |
+------------+-----+---------+---------------------------------------+
| **No       |     |         |                                       |
| nfood/feed |     |         |                                       |
| areas of   |     |         |                                       |
| foo        |     |         |                                       |
| d-handling |     |         |                                       |
| esta       |     |         |                                       |
| blishments |     |         |                                       |
| \          |     |         |                                       |
| [including |     |         |                                       |
| garbage    |     |         |                                       |
| rooms,     |     |         |                                       |
| l          |     |         |                                       |
| avatories, |     |         |                                       |
| floor      |     |         |                                       |
| drains     |     |         |                                       |
| (sewers),  |     |         |                                       |
| entries    |     |         |                                       |
| and        |     |         |                                       |
| v          |     |         |                                       |
| estibules, |     |         |                                       |
| offices,   |     |         |                                       |
| locker     |     |         |                                       |
| rooms,     |     |         |                                       |
| machine    |     |         |                                       |
| rooms,     |     |         |                                       |
| boiler     |     |         |                                       |
| rooms,     |     |         |                                       |
| garages,   |     |         |                                       |
| mop        |     |         |                                       |
| closets,   |     |         |                                       |
| and        |     |         |                                       |
| storage    |     |         |                                       |
| (after     |     |         |                                       |
| canning or |     |         |                                       |
| bot        |     |         |                                       |
| tling)\]** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Indoor   | 0   | 0.1%    | Applications may be made in water or  |
| > spot     | .25 | f       | oil and may be applied as a coarse    |
| >          | lb/ | inished | spray or with a paint brush to areas  |
|  treatment | gal | spray   | where pests hide (baseboard areas,    |
|            | EC  |         | around water pipes, surfaces behind   |
|            |     |         | and beneath sinks, lockers, tables,   |
|            | \[5 |         | pallets, and similar areas).          |
|            | 481 |         | Applications may be repeated as       |
|            | -21 |         | needed. Use of this product in edible |
|            | 7\] |         | product areas of food processing      |
|            |     |         | plants, restaurants, or other areas   |
|            | 0.5 |         | where food is commercially prepared   |
|            | lb/ |         | or processed and use in serving areas |
|            | gal |         | where food is exposed are prohibited. |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -21 |         |                                       |
|            | 6\] |         |                                       |
+------------+-----+---------+---------------------------------------+
|            | 1   | 0.5%    | Applications may be made in water and |
|            | .16 | f       | may be applied to areas where pests   |
|            | lb/ | inished | hide (around baseboards, cracks,      |
|            | gal | spray   | walls, door and window frames and     |
|            | EC  |         | localized areas of floors). Use of    |
|            |     |         | this product in food processing       |
|            | \[5 |         | plants, food-handling areas of        |
|            | 481 |         | restaurants, or areas where food is   |
|            | -20 |         | prepared or served, and use to treat  |
|            | 8\] |         | non-perishable bagged and or bulk     |
|            |     |         | stored raw or processed agricultural  |
|            |     |         | commodities are prohibited.           |
|            |     |         | Contamination of food, water, food    |
|            |     |         | containers, or cooking utensils is    |
|            |     |         | prohibited.                           |
+------------+-----+---------+---------------------------------------+
|            | 0   | 0.5%    | Applications may be made with a pump  |
|            | .5% | spray   | sprayer to areas where pests hide     |
|            | RTU |         | (dark corners of room and closets,    |
|            |     |         | cracks and crevices in walls, behind  |
|            | \[5 |         | and beneath sinks, stoves,            |
|            | 481 |         | refrigerators, cabinets, washing      |
|            | -24 |         | machines, cupboards, bookcases, and   |
|            | 0\] |         | around baseboards). Use of this       |
|            |     |         | product in food areas of              |
|            |     |         | food-handling establishments,         |
|            |     |         | restaurants, or other areas where     |
|            |     |         | food is commercially prepared or      |
|            |     |         | processed and use in serving areas    |
|            |     |         | where food is exposed or while        |
|            |     |         | facility is operating are prohibited. |
+------------+-----+---------+---------------------------------------+
| Indoor     | 4   | 1%      | Fogging or misting applications may   |
| treatment  | .48 | f       | be made with deodorized base oil      |
|            | lb/ | inished | using fogging or misting equipment to |
| > Space    | gal | spray   | treat indoor areas. Use in bottling   |
| > spray    | SC  |         | plants, food contact areas or meat    |
| > a        |     | \[1     | slaughter, and/or packing plants or   |
| pplication | \[5 | gal     | in frozen food plants is prohibited.  |
| >          | 481 | /64,000 |                                       |
| > \        | -20 | cu.ft\] |                                       |
| [Hand-Held | 2\] |         |                                       |
| > Foggers  |     |         |                                       |
| > are no   |     |         |                                       |
| > longer   |     |         |                                       |
| > p        |     |         |                                       |
| ermitted\] |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| **No       |     |         |                                       |
| nfood/feed |     |         |                                       |
| areas of   |     |         |                                       |
| foo        |     |         |                                       |
| d-handling |     |         |                                       |
| esta       |     |         |                                       |
| blishments |     |         |                                       |
| \          |     |         |                                       |
| [including |     |         |                                       |
| garbage    |     |         |                                       |
| rooms,     |     |         |                                       |
| l          |     |         |                                       |
| avatories, |     |         |                                       |
| floor      |     |         |                                       |
| drains     |     |         |                                       |
| (sewers),  |     |         |                                       |
| entries    |     |         |                                       |
| and        |     |         |                                       |
| v          |     |         |                                       |
| estibules, |     |         |                                       |
| offices,   |     |         |                                       |
| locker     |     |         |                                       |
| rooms,     |     |         |                                       |
| machine    |     |         |                                       |
| rooms,     |     |         |                                       |
| boiler     |     |         |                                       |
| rooms,     |     |         |                                       |
| garages,   |     |         |                                       |
| mop        |     |         |                                       |
| closets,   |     |         |                                       |
| and        |     |         |                                       |
| storage    |     |         |                                       |
| (after     |     |         |                                       |
| canning or |     |         |                                       |
| b          |     |         |                                       |
| ottling)\] |     |         |                                       |
| (co        |     |         |                                       |
| ntinued)** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| Indoor     | 10  | 1%      | For use in warehouses, silos, bulk    |
| treatment  | lb/ | f       | bins, and food/feed processing,       |
|            | gal | inished | food/feed manufacturing, handling and |
| > Space    | SC  | spray   | storage plants containing             |
| > spray    |     |         | non-perishable, packaged or bagged    |
| > a        | \[5 | \[1     | raw or processed food/feed            |
| pplication | 481 | gal     | commodities or bulk raw or processed  |
| >          | -20 | /64,000 | food commodities. Fogging or misting  |
| > \        | 0\] | cu.ft\] | applications may be made with         |
| [Hand-Held |     |         | deodorized base oil using fogging or  |
| > Foggers  |     |         | misting equipment to treat indoor     |
| > are no   |     |         | areas. Use in bottling plants, food   |
| > longer   |     |         | contact areas or meat slaughter,      |
| > p        |     |         | and/or packing plants or in frozen    |
| ermitted\] |     |         | food plants is prohibited. When using |
|            |     |         | in food processing, handling, and     |
|            |     |         | storage areas: (I) applications may   |
|            |     |         | be made only during times when plant  |
|            |     |         | is not in operation and no food       |
|            |     |         | products are exposed; if bulk,        |
|            |     |         | unpackaged food is exposed, it must   |
|            |     |         | be removed or covered prior to        |
|            |     |         | treatment; (ii) all food processing   |
|            |     |         | surfaces should be covered during     |
|            |     |         | treatment or thoroughly cleaned       |
|            |     |         | before using.                         |
+------------+-----+---------+---------------------------------------+
| > Indoor   | 0   | 0.5%    | Use as a space spray is prohibited.   |
| > premise  | .5% | spray   | Applications may be applied to areas  |
| >          | PrL |         | where pests hide (cracks, around      |
|  treatment |     |         | baseboards, cabinets, walls, and      |
|            | \[5 |         | woodwork) and repeated as necessary.  |
|            | 481 |         | Use of this product in edible product |
|            | -34 |         | areas of food processing plants,      |
|            | 0\] |         | restaurants, or other areas where     |
|            |     |         | food is commercially prepared or      |
|            |     |         | processed and use to treat            |
|            |     |         | non-perishable bagged and or bulk     |
|            |     |         | stored raw or processed agricultural  |
|            |     |         | commodities are prohibited.           |
|            |     |         | Contamination of utensils, food,      |
|            |     |         | water, and foodstuffs prohibited.     |
+------------+-----+---------+---------------------------------------+
|            | 20% | 10.5 g  | Use in kitchens, restaurants, or      |
|            | I   | of      | areas where food/feed are prepared or |
|            | mpr | p       | processed, use in food/feed           |
|            |     | roduct/ | processing or food/feed manufacturing |
|            | \[5 |         | areas of food/feed processing and     |
|            | 481 | 50-100  | food/feed manufacturing plants are    |
|            | -34 | cu. ft  | prohibited.                           |
|            | 4\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Animal   |     |         |                                       |
| Uses       |     |         |                                       |
| (P         |     |         |                                       |
| remises)** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Farm     |     |         |                                       |
| buildings  |     |         |                                       |
| (including |     |         |                                       |
| animal     |     |         |                                       |
| shelters,  |     |         |                                       |
| barns,     |     |         |                                       |
| around     |     |         |                                       |
| feed lots, |     |         |                                       |
| dairy      |     |         |                                       |
| barns,     |     |         |                                       |
| milk       |     |         |                                       |
| sheds,     |     |         |                                       |
| loafing    |     |         |                                       |
| pens, pig  |     |         |                                       |
| pens,      |     |         |                                       |
| poultry    |     |         |                                       |
| houses,    |     |         |                                       |
| hog barns, |     |         |                                       |
| stables,   |     |         |                                       |
| and other  |     |         |                                       |
| farm       |     |         |                                       |
| bu         |     |         |                                       |
| ildings)** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Premise  | 1   | 0.5%    | Applications may be made as a coarse, |
| >          | lb/ | f       | wet spray to all exterior and         |
|  treatment | gal | inished | interior surfaces, treating window    |
| >          | EC  | spray   | sills, around doors, fences, and      |
| > Directed |     |         | ledges or as a directed spray to      |
| > spray    | \[  | \[1     | floors, baseboards, crack and         |
| > a        | 548 | q       | crevices in wall, and along base of   |
| pplication | 1-4 | t/1,000 | walls. Applications may be made using |
|            | 1\] | sq.ft\] | water- or oil-based sprays;           |
|            |     |         | applications may be repeated as       |
|            |     |         | necessary. A 1-day preslaughter       |
|            |     |         | interval (PSI) has been established.  |
+------------+-----+---------+---------------------------------------+
|            | 2   | 0.5%    | Applications may be made as a coarse, |
|            | lb/ | f       | wet spray to surfaces, treating       |
|            | gal | inished | window sills, doorways, feed storage  |
|            | EC  | spray   | rooms, and alleyways. Applications    |
|            |     |         | may be made using water; applications |
|            | \[  | \[1     | may be repeated as necessary. Animals |
|            | 548 | q       | must be removed prior treatment.      |
|            | 1-7 | t/1,000 | Application in areas where animals    |
|            | 3\] | sq.ft\] | have received a direct application of |
|            |     |         | DDVP within the past 8 hours is       |
|            |     |         | prohibited.                           |
+------------+-----+---------+---------------------------------------+
|            | 0   | 0.5%    | Applications may be made as a coarse, |
|            | .37 | f       | wet spray to surfaces, treating       |
|            | lb/ | inished | window sills, doorways, feed storage  |
|            | gal | spray   | rooms, and alleyways. Applications    |
|            | EC  |         | may be made using water; applications |
|            |     | \[1     | may be repeated as necessary. Animals |
|            | \[5 | q       | may be present during treatment.      |
|            | 481 | t/1,000 | Contamination of water, feed or       |
|            | -22 | sq.ft\] | foodstuffs, milk or milking utensils  |
|            | 0\] |         | is prohibited.                        |
|            |     |         |                                       |
|            | 2   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 5\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 4\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Farm     |     |         |                                       |
| buildings  |     |         |                                       |
| (including |     |         |                                       |
| animal     |     |         |                                       |
| shelters,  |     |         |                                       |
| barns,     |     |         |                                       |
| around     |     |         |                                       |
| feed lots, |     |         |                                       |
| dairy      |     |         |                                       |
| barns,     |     |         |                                       |
| milk       |     |         |                                       |
| sheds,     |     |         |                                       |
| poultry    |     |         |                                       |
| houses,    |     |         |                                       |
| hog barns, |     |         |                                       |
| stables,   |     |         |                                       |
| and other  |     |         |                                       |
| farm       |     |         |                                       |
| buildings) |     |         |                                       |
| (co        |     |         |                                       |
| ntinued)** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Premise  | 1   | 0.5%    | Applications may be made as a coarse, |
| >          | .16 | f       | wet spray to surfaces, treating       |
|  treatment | lb/ | inished | window sills, doorways, feed storage  |
| >          | gal | spray   | rooms, and alleyways. Applications    |
| > Directed | EC  |         | may be made using diesel oil or       |
| > spray    |     | \[1     | water; applications may be repeated   |
| > a        | \[5 | q       | as necessary. Direct treatment of     |
| pplication | 481 | t/1,000 | animals or humans and contamination   |
|            | -20 | sq.ft\] | of water, feed or foodstuffs, milk or |
|            | 8\] |         | milking utensils are prohibited.      |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .59 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 6\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .15 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 7\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | .48 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 2\] |         |                                       |
|            |     |         |                                       |
|            | 8   |         |                                       |
|            | .39 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 1\] |         |                                       |
|            |     |         |                                       |
|            | 10  |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 0\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Premise  | 2   | 1%      | Fog applications may be made using    |
| >          | lb/ | f       | diesel oil. Animals must be removed   |
|  treatment | gal | inished | prior to treatment. Prior to          |
| >          | EC  | spray   | application, reduce air movement as   |
| > Space    |     |         | much as possible by closing doors,    |
| > spray    | \[  | \[0.5   | windows, and other openings.          |
| > a        | 548 | q       | Application in areas where animals    |
| pplication | 1-7 | t/8,000 | have received a direct application of |
| >          | 3\] | cu.ft\] | DDVP within the past 8 hours is       |
| > \        |     |         | prohibited.                           |
| [Hand-Held |     | or      |                                       |
| > Foggers  |     |         |                                       |
| > are no   |     | 0.5%    |                                       |
| > longer   |     | f       |                                       |
| > p        |     | inished |                                       |
| ermitted\] |     | spray   |                                       |
|            |     |         |                                       |
|            |     | \[1     |                                       |
|            |     | q       |                                       |
|            |     | t/8,000 |                                       |
|            |     | cu.ft\] |                                       |
+------------+-----+---------+---------------------------------------+
| **Farm     |     |         |                                       |
| buildings  |     |         |                                       |
| (including |     |         |                                       |
| animal     |     |         |                                       |
| shelters,  |     |         |                                       |
| barns,     |     |         |                                       |
| around     |     |         |                                       |
| feed lots, |     |         |                                       |
| dairy      |     |         |                                       |
| barns,     |     |         |                                       |
| milk       |     |         |                                       |
| sheds,     |     |         |                                       |
| poultry    |     |         |                                       |
| houses,    |     |         |                                       |
| hog barns, |     |         |                                       |
| stables,   |     |         |                                       |
| and other  |     |         |                                       |
| farm       |     |         |                                       |
| buildings) |     |         |                                       |
| (co        |     |         |                                       |
| ntinued)** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Premise  | 0   | 1%      | Fog applications may be made using    |
| >          | .37 | f       | diesel oil. Animals must be removed   |
|  treatment | lb/ | inished | prior to treatment. Prior to          |
| >          | gal | spray   | application, reduce air movement as   |
| > Space    | EC  |         | much as possible by closing doors,    |
| > spray    |     | \[0.5   | windows, and other openings.          |
| > a        | \[5 | q       | Application in areas where animals    |
| pplication | 481 | t/8,000 | have received a direct application of |
| >          | -22 | cu.ft\] | DDVP within the past 8 hours is       |
| > \        | 0\] |         | prohibited. Contamination of water,   |
| [Hand-Held |     | or      | feed or foodstuffs, milk or milking   |
| > Foggers  | 1   |         | utensils is prohibited.               |
| > are no   | .16 | 0.5%    |                                       |
| > longer   | lb/ | f       |                                       |
| > p        | gal | inished |                                       |
| ermitted\] | EC  | spray   |                                       |
|            |     |         |                                       |
|            | \[5 | \[1     |                                       |
|            | 481 | q       |                                       |
|            | -20 | t/8,000 |                                       |
|            | 8\] | cu.ft\] |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .59 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 6\] |         |                                       |
|            |     |         |                                       |
|            | 2   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 5\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 4\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .15 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 7\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | .48 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 2\] |         |                                       |
|            |     |         |                                       |
|            | 8   |         |                                       |
|            | .39 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 1\] |         |                                       |
|            |     |         |                                       |
|            | 10  |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 0\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Premise  | 1%  | 0.04    | Bait applications may be made to      |
| >          | G   | o       | clean floor areas, ground areas       |
|  treatment |     | z/1,000 | outside enclosures, window sills, or  |
|            | \   | sq.ft   | other areas where flies congregate.   |
|            | [54 |         | Applications are to be made in such a |
|            | 81- |         | manner that stock cannot come into    |
|            | 9\] |         | contact with bait.                    |
+------------+-----+---------+---------------------------------------+
| **Farm     |     |         |                                       |
| buildings  |     |         |                                       |
| (including |     |         |                                       |
| animal     |     |         |                                       |
| shelters,  |     |         |                                       |
| barns,     |     |         |                                       |
| around     |     |         |                                       |
| feed lots, |     |         |                                       |
| dairy      |     |         |                                       |
| barns,     |     |         |                                       |
| milk       |     |         |                                       |
| sheds,     |     |         |                                       |
| poultry    |     |         |                                       |
| houses,    |     |         |                                       |
| hog barns, |     |         |                                       |
| stables,   |     |         |                                       |
| and other  |     |         |                                       |
| farm       |     |         |                                       |
| buildings) |     |         |                                       |
| (co        |     |         |                                       |
| ntinued)** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Premise  | 1   | 1%      | Fog applications may be made with     |
| >          | lb/ | f       | animals present, provided a direct    |
|  treatment | gal | inished | animal treatment of DDVP has not been |
| >          | EC  | spray   | made in the past 8 hours.             |
| > Space    |     |         | Applications may be made using water  |
| > spray    | \[  | \[0.5   | or deodorized kerosene. Prior to      |
| > a        | 548 | q       | application, reduce air movement as   |
| pplication | 1-4 | t/8,000 | much as possible by closing doors,    |
| >          | 1\] | cu.ft\] | windows, and other openings.          |
| > \        |     |         |                                       |
| [Hand-Held |     |         |                                       |
| > Foggers  |     |         |                                       |
| > are no   |     |         |                                       |
| > longer   |     |         |                                       |
| > p        |     |         |                                       |
| ermitted\] |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Animal   |     |         |                                       |
| buildings  |     |         |                                       |
| (including |     |         |                                       |
| horse      |     |         |                                       |
| barns,     |     |         |                                       |
| calf       |     |         |                                       |
| parlors,   |     |         |                                       |
| hog        |     |         |                                       |
| parlors,   |     |         |                                       |
| stables,   |     |         |                                       |
| poultry    |     |         |                                       |
| houses,    |     |         |                                       |
| tack       |     |         |                                       |
| rooms, and |     |         |                                       |
| dog        |     |         |                                       |
| kennels)** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Premise  | 20% | 10.5 g  | Contamination of water, food or       |
| >          | I   | of      | foodstuffs, milk or milking equipment |
|  treatment | mpr | p       | is prohibited. Use of product where   |
|            |     | roduct/ | unwrapped food is stored or allowing  |
|            | \[5 |         | the strip to come in contact with     |
|            | 481 | 50-100  | food or cooking utensils is           |
|            | -33 | cu. ft  | prohibited.                           |
|            | 8\] |         |                                       |
+------------+-----+---------+---------------------------------------+
|            | 20% | 10.5 g  | Contamination of water, food or       |
|            | I   | of      | foodstuffs, milk or milking equipment |
|            | mpr | p       | is prohibited.                        |
|            |     | roduct/ |                                       |
|            | \[5 |         |                                       |
|            | 481 | 50-100  |                                       |
|            | -34 | cu. ft  |                                       |
|            | 4\] |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -34 |         |                                       |
|            | 8\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Milk     |     |         |                                       |
| rooms      |     |         |                                       |
| (including |     |         |                                       |
| bulk       |     |         |                                       |
| storage    |     |         |                                       |
| rooms)**   |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Premise  | 20% | 10.5 g  | Contamination of milk or milking      |
| >          | I   | of      | equipment is prohibited. Use of       |
|  treatment | mpr | p       | product where unwrapped food is       |
|            |     | roduct/ | stored or allowing the strip to come  |
|            | \[5 |         | in contact with food or cooking       |
|            | 481 | 50-100  | utensils is prohibited.               |
|            | -33 | cu. ft  |                                       |
|            | 8\] |         |                                       |
+------------+-----+---------+---------------------------------------+
|            | 20% | 10.5 g  | Contamination of milk or milking      |
|            | I   | of      | equipment is prohibited.              |
|            | mpr | p       |                                       |
|            |     | roduct/ |                                       |
|            | \[5 |         |                                       |
|            | 481 | 50-100  |                                       |
|            | -34 | cu. ft  |                                       |
|            | 4\] |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -34 |         |                                       |
|            | 8\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Feed     |     |         |                                       |
| lots,      |     |         |                                       |
| s          |     |         |                                       |
| tockyards, |     |         |                                       |
| corrals,   |     |         |                                       |
| and        |     |         |                                       |
| holding    |     |         |                                       |
| pens**     |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Outdoor  | 1   | 0.5%    | Applications may be made as an        |
| > premise  | lb/ | f       | overall mist spray to fences, feed    |
| >          | gal | inished | bunkers, shade areas, spillage areas, |
|  treatment | EC  | spray   | building walls, and other areas where |
|            |     |         | flies congregate. Applications may be |
|            | \[  | \[5     | made in water using a mist blower or  |
|            | 548 | gal/A\] | similar equipment at 3- to 14-day     |
|            | 1-4 |         | intervals.                            |
|            | 1\] | 0.2     |                                       |
|            |     | lb/A    |                                       |
+------------+-----+---------+---------------------------------------+
|            | 0   |         | Applications may be made as an        |
|            | .37 |         | overall mist spray to fences, feed    |
|            | lb/ |         | bunkers, spillage areas, and building |
|            | gal |         | walls. Applications may be made in    |
|            | EC  |         | diesel oil or water using a mist      |
|            |     |         | blower or similar equipment. Animals  |
|            | \[5 |         | may be present during treatment.      |
|            | 481 |         |                                       |
|            | -22 |         |                                       |
|            | 0\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .16 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 8\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .59 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 6\] |         |                                       |
|            |     |         |                                       |
|            | 2   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 5\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 4\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .15 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 7\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | .48 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 2\] |         |                                       |
|            |     |         |                                       |
|            | 8   |         |                                       |
|            | .39 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 1\] |         |                                       |
|            |     |         |                                       |
|            | 10  |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 0\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Poultry  |     |         |                                       |
| houses**   |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Premise  | 0   | 0.5%    | Applications may be made to manure,   |
| >          | .37 | f       | window sills, exterior walls,         |
|  treatment | lb/ | inished | interior walls, feed room floors, and |
|            | gal | spray   | walkways. Only crack and crevice      |
|            | EC  |         | treatments are permitted for indoor   |
|            |     | \[1     | use and applications are to be made   |
|            | \[5 | q       | out of reach of poultry (EPA Reg. No. |
|            | 481 | t/1,000 | 5481-41 only).                        |
|            | -22 | sq.ft\] |                                       |
|            | 0\] |         |                                       |
|            |     | Not     |                                       |
|            | 1   | sp      |                                       |
|            | lb/ | ecified |                                       |
|            | gal | on the  |                                       |
|            | EC  | 2       |                                       |
|            |     | lb/gal  |                                       |
|            | \[  | EC      |                                       |
|            | 548 | \[54    |                                       |
|            | 1-4 | 81-73\] |                                       |
|            | 1\] | product |                                       |
|            |     | label   |                                       |
|            | 1   |         |                                       |
|            | .16 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 8\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .59 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 6\] |         |                                       |
|            |     |         |                                       |
|            | 2   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[  |         |                                       |
|            | 548 |         |                                       |
|            | 1-7 |         |                                       |
|            | 3\] |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 5\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 4\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .15 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 7\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | .48 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 2\] |         |                                       |
|            |     |         |                                       |
|            | 8   |         |                                       |
|            | .39 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 1\] |         |                                       |
|            |     |         |                                       |
|            | 10  |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 0\] |         |                                       |
+------------+-----+---------+---------------------------------------+
|            | 1%  | 0.04    | Bait applications may be made to      |
|            | G   | o       | droppings under cages, on walkways,   |
|            |     | z/1,000 | window sills, alley ways, and other   |
|            | \   | sq. ft  | areas where flies congregate.         |
|            | [54 |         | Applications are to be made out of    |
|            | 81- |         | reach of birds.                       |
|            | 9\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Direct   |     |         |                                       |
| Animal     |     |         |                                       |
| Uses**     |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Cattle   |     |         |                                       |
| (beef and  |     |         |                                       |
| dairy)**   |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Animal   | 1   | 1%      | Application may be made in water as   |
| > mist     | lb/ | f       | an atomized spray uniformly           |
| > spray    | gal | inished | distributed over each animal. Do not  |
| >          | EC  | spray   | wet the skin.                         |
|  treatment |     |         |                                       |
|            | \[  | \[2 fl. |                                       |
|            | 548 | o       |                                       |
|            | 1-4 | z/anima |                                       |
|            | 1\] | l/day\] |                                       |
+------------+-----+---------+---------------------------------------+
|            | 2   | 0.5%    | Application may be made in water as   |
|            | lb/ | f       | an atomized spray uniformly           |
|            | gal | inished | distributed over each animal.         |
|            | EC  | spray   | Application more than once per day    |
|            |     |         | and application to calves less than 6 |
|            | \[  | \[4 fl. | months of age are prohibited.         |
|            | 548 | o       |                                       |
|            | 1-7 | z/anima |                                       |
|            | 3\] | l/day\] |                                       |
+------------+-----+---------+---------------------------------------+
|            | 0   | 1%      | Application may be made in deodorized |
|            | .37 | f       | base oil or water as an atomized      |
|            | lb/ | inished | spray uniformly distributed over each |
|            | gal | spray   | animal. Do not wet the hide.          |
|            | EC  |         | Application of more than 2 fl. oz.    |
|            |     | \[2 fl. | per animal per day and application to |
|            | \[5 | o       | calves less than 6 months of age are  |
|            | 481 | z/anima | prohibited. A 1-day PSI has been      |
|            | -22 | l/day\] | established (EPA Reg. Nos. 5481-204   |
|            | 0\] |         | and 5481-220 only).                   |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .16 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 8\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .59 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 6\] |         |                                       |
|            |     |         |                                       |
|            | 2   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 5\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 4\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .15 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 7\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | .48 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 2\] |         |                                       |
|            |     |         |                                       |
|            | 8   |         |                                       |
|            | .39 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 1\] |         |                                       |
|            |     |         |                                       |
|            | 10  |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 0\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Cattle   |     |         |                                       |
| (beef and  |     |         |                                       |
| dairy)     |     |         |                                       |
| (co        |     |         |                                       |
| ntinued)** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Animal   | 1   | 0.5%    | Applications may be made to the       |
| > face     | lb/ | bait    | animal\'s forehead daily for 14 days  |
| > paint    | gal | slurry  | and thereafter as needed.             |
| >          | EC  |         |                                       |
|  treatment |     | \[1     |                                       |
|            | \[  | tsp     |                                       |
|            | 548 | /face\] |                                       |
|            | 1-4 |         |                                       |
|            | 1\] |         |                                       |
+------------+-----+---------+---------------------------------------+
|            | 0   | 1% bait | Application is to be made as a 6-inch |
|            | .37 | slurry  | line to the animal\'s forehead with a |
|            | lb/ |         | paint brush.                          |
|            | gal | \[3     |                                       |
|            |     | mL      |                                       |
|            | \[5 | /face\] |                                       |
|            | 481 |         |                                       |
|            | -22 |         |                                       |
|            | 0\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .16 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 8\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .59 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 6\] |         |                                       |
|            |     |         |                                       |
|            | 2   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 5\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 4\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .15 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 7\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | .48 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 2\] |         |                                       |
|            |     |         |                                       |
|            | 8   |         |                                       |
|            | .39 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 1\] |         |                                       |
|            |     |         |                                       |
|            | 10  |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 0\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Cattle   |     |         |                                       |
| (beef and  |     |         |                                       |
| dairy)     |     |         |                                       |
| (co        |     |         |                                       |
| ntinued)** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Manure   | 0   | 0.5%    | Applications may be made in water to  |
| >          | .37 | f       | control maggots in manure piles and   |
|  treatment | lb/ | inished | garbage dumps.                        |
|            | gal | spray   |                                       |
|            | EC  |         |                                       |
|            |     | \[2     |                                       |
|            | \[5 | qt/100  |                                       |
|            | 481 | sq.ft\] |                                       |
|            | -22 |         |                                       |
|            | 0\] | or      |                                       |
|            |     |         |                                       |
|            | 1   | 1%      |                                       |
|            | lb/ | f       |                                       |
|            | gal | inished |                                       |
|            | EC  | spray   |                                       |
|            |     |         |                                       |
|            | \[  | \[1     |                                       |
|            | 548 | qt/100  |                                       |
|            | 1-4 | sq.ft\] |                                       |
|            | 1\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .16 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 8\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .59 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 6\] |         |                                       |
|            |     |         |                                       |
|            | 2   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[  |         |                                       |
|            | 548 |         |                                       |
|            | 1-7 |         |                                       |
|            | 3\] |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 5\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 4\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .15 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 7\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | .48 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 2\] |         |                                       |
|            |     |         |                                       |
|            | 8   |         |                                       |
|            | .39 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 1\] |         |                                       |
|            |     |         |                                       |
|            | 10  |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 0\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| *          |     |         |                                       |
| *Poultry** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Manure   | 1   | 0.5%    | Applications may be made in diesel    |
| >          | lb/ | f       | oil or deodorized kerosene to control |
|  treatment | gal | inished | flies and maggots in poultry          |
|            | EC  | spray   | droppings.                            |
|            |     |         |                                       |
|            | \[  | \[2     |                                       |
|            | 548 | qt/100  |                                       |
|            | 1-4 | sq.ft\] |                                       |
|            | 1\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Animal   |     |         |                                       |
| Uses -     |     |         |                                       |
| Oral       |     |         |                                       |
| Dosing     |     |         |                                       |
| (Drug      |     |         |                                       |
| Use)**     |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Swine**  |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Feed     | N/A | 12      | Application is to be made by mixing   |
| >          | ^3^ | .5-20.6 | active ingredient into feed and may   |
|  treatment |     | mg/kg   | be repeated in 4-5 weeks.             |
|            |     | body    |                                       |
|            |     | weight  |                                       |
+------------+-----+---------+---------------------------------------+
| **Wide     |     |         |                                       |
| Area and   |     |         |                                       |
| General    |     |         |                                       |
| Outdoor    |     |         |                                       |
| T          |     |         |                                       |
| reatment** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Outdoor  |     |         |                                       |
| areas      |     |         |                                       |
| (including |     |         |                                       |
| outside    |     |         |                                       |
| picnic     |     |         |                                       |
| areas,     |     |         |                                       |
| patios,    |     |         |                                       |
| and eating |     |         |                                       |
| areas of   |     |         |                                       |
| drive-in   |     |         |                                       |
| rest       |     |         |                                       |
| aurants)** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Outdoor  | 2   | 0.5-1%  | Applications may be made in           |
| > spray    | lb/ | f       | deodorized spray base oil and         |
| > a        | gal | inished | repeated monthly or as needed.        |
| pplication | SC  | spray   |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -33 |         |                                       |
|            | 4\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Outdoor  |     |         |                                       |
| areas      |     |         |                                       |
| (including |     |         |                                       |
| picnic     |     |         |                                       |
| grounds,   |     |         |                                       |
| parking    |     |         |                                       |
| areas,     |     |         |                                       |
| loading    |     |         |                                       |
| docks,     |     |         |                                       |
| refuse     |     |         |                                       |
| areas,     |     |         |                                       |
| garbage    |     |         |                                       |
| collection |     |         |                                       |
| and        |     |         |                                       |
| disposal   |     |         |                                       |
| areas,     |     |         |                                       |
| around     |     |         |                                       |
| drive-in   |     |         |                                       |
| re         |     |         |                                       |
| staurants, |     |         |                                       |
| food       |     |         |                                       |
| processing |     |         |                                       |
| plants,    |     |         |                                       |
| and        |     |         |                                       |
| war        |     |         |                                       |
| ehouses)** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Outdoor  | 1   | 0.5%    | Applications may be made in water and |
| > spray    | lb/ | f       | repeated as needed. Direct use on     |
| > a        | gal | inished | animals and contamination of feed,    |
| pplication | EC  | spray   | foodstuffs, or water are prohibited.  |
|            |     |         |                                       |
|            | \[  | \[1     |                                       |
|            | 548 | q       |                                       |
|            | 1-4 | t/1,000 |                                       |
|            | 1\] | sq.     |                                       |
|            |     | ft\]    |                                       |
+------------+-----+---------+---------------------------------------+
| **Outdoor  |     |         |                                       |
| areas      |     |         |                                       |
| (including |     |         |                                       |
| picnic     |     |         |                                       |
| grounds,   |     |         |                                       |
| parking    |     |         |                                       |
| areas,     |     |         |                                       |
| loading    |     |         |                                       |
| docks,     |     |         |                                       |
| refuse     |     |         |                                       |
| areas,     |     |         |                                       |
| garbage    |     |         |                                       |
| collection |     |         |                                       |
| and        |     |         |                                       |
| disposal   |     |         |                                       |
| areas,     |     |         |                                       |
| around     |     |         |                                       |
| drive-in   |     |         |                                       |
| re         |     |         |                                       |
| staurants, |     |         |                                       |
| food       |     |         |                                       |
| processing |     |         |                                       |
| plants,    |     |         |                                       |
| and        |     |         |                                       |
| w          |     |         |                                       |
| arehouses) |     |         |                                       |
| (co        |     |         |                                       |
| ntinued)** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Outdoor  | 0   | 0.5%    | Applications may be made in diesel    |
| > spray    | .37 | f       | oil or water and repeated as needed.  |
| > a        | lb/ | inished | Direct use on animals or humans and   |
| pplication | gal | spray   | contamination of water, food, food    |
|            | EC  |         | containers or cooking utensils are    |
|            |     | \[1     | prohibited.                           |
|            | \[5 | q       |                                       |
|            | 481 | t/1,000 |                                       |
|            | -22 | sq.     |                                       |
|            | 0\] | ft\]    |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .16 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 8\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .59 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 6\] |         |                                       |
|            |     |         |                                       |
|            | 2   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 5\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 4\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .15 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 7\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | .48 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 2\] |         |                                       |
|            |     |         |                                       |
|            | 8   |         |                                       |
|            | .39 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 1\] |         |                                       |
|            |     |         |                                       |
|            | 10  |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 0\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Outdoor  |     |         |                                       |
| areas      |     |         |                                       |
| (including |     |         |                                       |
| picnic     |     |         |                                       |
| grounds,   |     |         |                                       |
| parking    |     |         |                                       |
| areas,     |     |         |                                       |
| loading    |     |         |                                       |
| docks,     |     |         |                                       |
| refuse     |     |         |                                       |
| areas,     |     |         |                                       |
| garbage    |     |         |                                       |
| collection |     |         |                                       |
| and        |     |         |                                       |
| disposal   |     |         |                                       |
| areas,     |     |         |                                       |
| around     |     |         |                                       |
| drive-in   |     |         |                                       |
| re         |     |         |                                       |
| staurants, |     |         |                                       |
| food       |     |         |                                       |
| processing |     |         |                                       |
| plants,    |     |         |                                       |
| and        |     |         |                                       |
| w          |     |         |                                       |
| arehouses) |     |         |                                       |
| (co        |     |         |                                       |
| ntinued)** |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Outdoor  | 0   | 1%      | Fogging or misting applications may   |
| > fogging  | .37 | f       | be made with diesel oil or water      |
| > a        | lb/ | inished | using fogging or misting equipment to |
| pplication | gal | spray   | treat outdoor living areas, picnic    |
| >          | EC  |         | areas, backyard areas, patios,        |
| > \        |     | \[5-10  | loading docks, outdoor latrines,      |
| [Hand-Held | \[5 | pt/A\]  | parking areas, refuse areas around    |
| > Foggers  | 481 |         | service stations, open air drive-ins, |
| > are no   | -22 | or      | ice cream stands, and garbage         |
| > longer   | 0\] |         | collection and disposal areas. Use in |
| > p        |     | 0       | areas where food or feed crops are    |
| ermitted\] | 1   | .05-0.1 | growing is prohibited.                |
|            | .16 | lb/A    |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 8\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .59 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 6\] |         |                                       |
|            |     |         |                                       |
|            | 2   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 5\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | EC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 4\] |         |                                       |
|            |     |         |                                       |
|            | 1   |         |                                       |
|            | .15 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 7\] |         |                                       |
|            |     |         |                                       |
|            | 4   |         |                                       |
|            | .48 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 2\] |         |                                       |
|            |     |         |                                       |
|            | 8   |         |                                       |
|            | .39 |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 1\] |         |                                       |
|            |     |         |                                       |
|            | 10  |         |                                       |
|            | lb/ |         |                                       |
|            | gal |         |                                       |
|            | SC  |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -20 |         |                                       |
|            | 0\] |         |                                       |
+------------+-----+---------+---------------------------------------+
| **Catch    |     |         |                                       |
| basins**   |     |         |                                       |
+------------+-----+---------+---------------------------------------+
| > Outdoor  | 20% | One     | One strip (10.5 or 80 g of product)   |
| >          | I   | strip   | is to be suspended 10 inches above    |
|  treatment | mpr |         | water level for control of mosquitoes |
|            |     |         | breeding in catch basins.             |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -33 |         |                                       |
|            | 8\] |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -34 |         |                                       |
|            | 4\] |         |                                       |
|            |     |         |                                       |
|            | \[5 |         |                                       |
|            | 481 |         |                                       |
|            | -34 |         |                                       |
|            | 8\] |         |                                       |
+------------+-----+---------+---------------------------------------+

^1^ Application rates in brackets refer to amount of finished spray to
be applied per listed area.

^2^ The product label for EPA Reg. No. 5481-41 prohibits treatment of
more than 5 application sites per day and prohibits DDVP applications
more than once per week (we note that this is in conflict with use
directions for feedlots, stockyards, corrals, and holding pens which
allow applications to be made at 3-day intervals). A similar statement
was required to be added to the product label for EPA Reg. No. 5481-200.
No other products listed in this table bear this restriction.

^3^ DDVP is registered for use as an anthelmintic in swine feed; use
pattern is defined in 21 CFR §520.600(e)(2).

> **2.2 Structure and Nomenclature**[]{#__RefHeading___Toc137619478
> .anchor}

  ------------------- ----------------------------------------------------
  **TABLE 2.2. Test   
  Compound            
  Nomenclature**      

  Chemical Structure  ![](media/image2.wmf){width="1.7194444444444446in"
                      height="0.9368055555555556in"}

  Empirical Formula   C~4~H~7~Cl~2~O~4~P

  Common name         Dichlorvos (ISO) or DDVP

  Company             
  experimental name   

  IUPAC name          2,2‑dichlorovinyl dimethyl phosphate

  CAS name            2,2‑dichloroethenyl dimethyl phosphate

  CAS Registry Number 62-73-7

  End-use product/EP  Alco, Amvos

  Chemical Class      organophosphate

  Known Impurities of none
  Concern             

  PC Code No.         084001
  ------------------- ----------------------------------------------------

> **2.3 Physical and Chemical
> Properties**[]{#__RefHeading___Toc137619479 .anchor}

Dichlorvos is a liquid with high vapor pressure at room temperature and
is used for fumigation. The high vapor pressure suggests that residues
in food and environmental surfaces will dissipate rapidly.

+--------------------------+-----------------------------+-------------+
| **TABLE 2.3.             |                             |             |
| Physicochemical          |                             |             |
| Properties**             |                             |             |
+==========================+=============================+=============+
| Parameter                | Value                       | Reference   |
+--------------------------+-----------------------------+-------------+
| Molecular Weight         | 221.0                       |             |
+--------------------------+-----------------------------+-------------+
| Physical State           | liquid                      | 40798103    |
+--------------------------+-----------------------------+-------------+
| Boiling point/range      | 117 C at 10 mm Hg           | 40798103    |
+--------------------------+-----------------------------+-------------+
| pH                       | \~ 4 as 1% aqueous solution | 40798103    |
+--------------------------+-----------------------------+-------------+
| Specific gravity         | 1.424 at 25 C               | 40798103    |
+--------------------------+-----------------------------+-------------+
| Water solubility (20 C)  | \~1.5 g/100 g               | 40798103    |
+--------------------------+-----------------------------+-------------+
| Solvent solubility       | \~0.5% in glycerine;        | 40798103    |
| (temperature not         | miscible with aromatic      |             |
| specified)               | hydrocarbons, chlorinated   |             |
|                          | hydrocarbons, alcohols,     |             |
|                          | ketones, and esters.        |             |
|                          | Essentially insoluble in    |             |
|                          | kerosene and aliphatic      |             |
|                          | hydrocarbons                |             |
+--------------------------+-----------------------------+-------------+
| Vapor pressure (25 C)    | 0.032 mm Hg at 32 C         | 40798103    |
+--------------------------+-----------------------------+-------------+
| Dissociation constant,   | N/A                         |             |
| pKa                      |                             |             |
+--------------------------+-----------------------------+-------------+
| Octanol/water partition  | 38.4                        | 40798103    |
| coefficient,             |                             |             |
|                          | log K~OW~ = 1.58            |             |
| log K~OW~ (25 C)         |                             |             |
+--------------------------+-----------------------------+-------------+
| UV/visible absorption    | N/A                         |             |
| spectrum                 |                             |             |
+--------------------------+-----------------------------+-------------+

**3.0 Metabolism Assessment**[]{#__RefHeading___Toc137619480 .anchor}

> **3.1 Comparative Metabolic Profile**[]{#__RefHeading___Toc137619481
> .anchor}

A rat metabolism study has been conducted. The overall metabolic profile
suggests the involvement of the one-carbon pool biosynthetic pathway as
evidenced by the presence of a relatively large amount of radioactivity
in the form of expired ^14^CO~2~ and the presence of dehalogenated
metabolites as well as urea and hippuric acid. Plant metabolism studies
show that dichlorvos hydrolyzes to dimethyl phosphate and
dichloroacetaldehyde, and is incorporated into natural plant
constituents. Oral and dermal livestock metabolism studies show that
dichlorvos metabolizes to desmethyl dichlorvos in livestock animals. The
major environmental degradates were 2,2‑dichloroacetic acid,
2,2‑dichloroacetaldehyde, desmethyl dichlorvos, and glyoxylic acid.

> **3.2 Nature of the Residue in Foods**[]{#__RefHeading___Toc137619482
> .anchor}
>
> **3.2.1. Description of Primary Crop
> Metabolism**[]{#__RefHeading___Toc137619483 .anchor}

*Nature of the Residue - Plants* *(GLN 860.1300*): The reregistration
requirements for plant metabolism are fulfilled. The Agency determined
that the available data depicting the metabolism of naled in plants are
sufficient to delineate the metabolism of dichlorvos in plants because
dichlorvos is the initial metabolite of naled. In plants, naled is
metabolized to dichlorvos which is hydrolyzed to dimethyl phosphate and
dichloroacetaldehyde. Dimethyl phosphate is sequentially degraded to
monomethyl phosphate and inorganic phosphates, and dichloroacetaldehyde
is converted to 2,2‑dichloroethanol which is then conjugated and/or
incorporated into naturally occurring plant components. The residue of
concern in plant commodities is dichlorvos.

> **3.2.2 Description of Livestock
> Metabolism**[]{#__RefHeading___Toc137619484 .anchor}

*Nature of the Residue - Animals (GLN 860.1300):* The reregistration
requirements for animal metabolism are fulfilled. Acceptable studies
depicting the qualitative nature of the residue in ruminants and poultry
following dermal treatment with dichlorvos have been submitted and
evaluated. Because dichlorvos is the initial metabolite of naled, the
available metabolism studies reflecting oral dosing of ruminants and
hens with naled are sufficient to delineate the metabolism of orally
dosed dichlorvos in animals. The residue of concern in animal
commodities is dichlorvos.

In the lactating goat treated orally with naled, no naled or dichlorvos
was identified in milk (\<0.005 ppm) or tissues (\<0.05 ppm).
Dichloroethanol conjugates and desmethyl-dichlorvos were not identified
in milk (\<0.05 ppm). Liver and kidney contained up to 0.3 ppm
dichloroethanol conjugates and 0.1 ppm desmethyl-dichlorvos; other
tissues showed only traces of both of these metabolites.

In laying hens treated orally with naled, the sulfate conjugate of
dichloroethanol was the major component (0.1 ppm in fat to 10 ppm in
kidney) identified in all tissues. The parent compound, naled, was not
identified (\<0.01 ppm) in any tissues except gizzard. Naled plus mostly
dichlorvos were found in gizzard (0.6 ppm) after 2 hours in singly dosed
hens and as a minor metabolite (0.01-0.46 ppm) in tissue samples of
multi-dosed hens.

In both lactating goats and laying hens treated orally with naled, naled
is initially debrominated to yield dichlorvos. The major pathway is
cleavage of dichlorvos to dimethylphosphate and dichloroacetaldehyde. A
minor pathway is O-demethylation to form desmethyl‑dichlorvos. In part,
dichloroacetaldehyde is reduced to dichloroethanol which is conjugated
with endogenous sulfate to form the sulfate ester conjugate of
dichloroethanol. Dichloroacetaldehyde is dechlorinated and oxidized
sequentially to form glyoxal and then glyoxylic acid which is
incorporated into amino acids (glycine, alanine, serine, etc.) and
proteins.

Metabolism of dichlorvos in ruminants, following dermal exposure, is
adequately understood. Dichlorvos is extensively metabolized following
dermal exposure. No dichlorvos or primary metabolites of dichlorvos were
found in milk or tissues of treated goats, furthermore, incorporation of
^14^C into endogenous milk (as lactose) and tissue components (as
glycerol) of the treated goats was demonstrated.

Metabolism of dichlorvos in poultry, following dermal exposure, is
adequately understood. Dichlorvos is extensively metabolized following
dermal exposure. Limited amounts of dichlorvos and des‑methyl dichlorvos
were identified in breast muscle and fat, with the majority of the TRR
incorporated into tissue. Radioactivity found in internal tissues
accounted for 0.3% of the administered dose.

> **3.2.3 Description of Rotational Crop Metabolism, including
> identification of major metabolites and specific routes of
> biotransformation**[]{#__RefHeading___Toc137619485 .anchor}

Dichlorvos is not registered for field crop uses; therefore no
rotational crop data have been required.

> **3.3 Environmental Degradation**[]{#__RefHeading___Toc137619486
> .anchor}

**Dichlorvos.** A major route of dissipation is volatilization (vapor
pressure = 0.032 mm Hg at 32 C). Dichlorvos also appears to degrade
through aerobic soil metabolism and abiotic hydrolysis as well, but is
secondary to volatilization. Hydrolysis is pH dependant where the
half‑lives were 11 days at pH 5, 5 days at pH 7 and 21 hours at pH 9.
The major degradates were 2,2‑dichloroacetic acid,
2,2‑dichloroacetaldehyde, desmethyl dichlorvos, and glyoxylic acid.
Aerobic soil metabolism data showed a half‑life of 10 hours with the
major metabolite being 2,2‑dichloroacetic acid (62.8% of applied at 48
hours). Other metabolites present at less than 12% of applied were
2,2‑dichloroacetaldehyde, and dichloroethanol. Extensive mineralization
took place as CO~2~ accounted for 60% of applied at 360 hours
post‑treatment. Due to rapid degradation of dichlorvos
leaching/adsorption/desorption data were declared supplemental due to
the inability to establish a soil/solution phase equilibrium. However, a
soil TLC study (MRID 41354105) indicates that dichlorvos is moderately
mobile (K~d~\'s ranging 0.3 to 1.2) based on the

Heiling and Turner\'s mobility classification. The potential of
dichlorvos to leach to ground water is mitigated by its rapid
degradation. However, dichlorvos does have the potential to contaminate
surface waters because of a low K~oc~ value and high water solubility
(10 X 10^3^ ppm, or 1%). Substantial fractions of run‑off will more than
likely occur via dissolution in run‑off water rather than adsorption to
eroding soil. Dichlorvos should not be persistent in any surface waters
due to its susceptibility to rapid hydrolysis.

**Naled**. Chemical hydrolysis and biodegradation are the major
processes involved in the transformation of naled and its degradates in
the environment. While direct photolysis in water is not a major
degradative pathway for naled, indirect photolysis in the presence of
photosensitizer may play an important role in the photodegradation of
naled in aqueous media and soils. The degradate dichlorvos does not form
under abiotic hydrolysis nor by direct photolysis in water, but forms by
indirect photolysis in water and soils. In the presence of
photosensitizer in water, as much as 20% of the applied dose of naled
can be found as dichlorvos after 1 day, with rapid decline of dichlorvos
residues afterwards. Under aerobic conditions, naled mineralizes rapidly
to CO~2~ and degrades to dichloroacetic acid and dichloroethanol, but
dichlorvos is not detected. This is likely to be the result of the rapid
degradation and mineralization of any dichlorvos that may form from
naled. However, under anaerobic aquatic conditions, dichlorvos can be as
high as 15% of the applied naled dose after 1 day. The degradation of
dichlorvos, once formed, was slower than that of parent naled. During
the first 1‑2 days after application of naled, the half‑life of
dichlorvos was about 0.9 days.

**Trichlorfon.** Dichlorvos is formed from trichlorfon in both soil and
water by aerobic soil metabolism. Environmental fate data indicate that
trichlorfon degrades rapidly in aerobic soil (t~1/2~ 1.8 days) under
non‑sterile conditions; however, in a sterile soil, trichlorfon was
stable (t~1/2~ \> 40 days). Abiotic hydrolysis studies indicate that
trichlorfon degrades rapidly in aqueous media and that the rate of
conversion is pH dependent. The estimated half‑life of trichlorfon is 31
minutes at pH 9, and 34 hours at pH 7, and 104 days at pH 5. This
indicates the stability of trichlorfon under acidic conditions. The
maximum amount of dichlorvos formed from trichlorfon by aerobic aquatic
metabolism is approximately 56 percent of the amount of trichlorfon
originally applied at pH 8.5.

> **3.4 Summary of Residues for Tolerance Expression and Risk
> Assessment**[]{#__RefHeading___Toc137619487 .anchor}

Tolerances for residues of dichlorvos are published in 40 CFR 180.235.
The current tolerance expression includes only dichlorvos
\[2,2-dichlorovinyl dimethyl phosphate\].

  ------------------------------------------------------------------------
  **Table 3.6.                                        
  Summary of                                          
  Metabolites                                         
  and Degradates                                      
  to be included                                      
  in the Risk                                         
  Assessment and                                      
  Tolerance                                           
  Expression**                                        
  -------------- --------------- -------------------- --------------------
  Matrix                         Residues included in Residues included in
                                 Risk Assessment      Tolerance Expression

  Plants         Primary Crop    dichlorvos           dichlorvos

                 Rotational Crop N/A                  N/A

  Livestock      Ruminant        dichlorvos           dichlorvos

                 Poultry         dichlorvos           dichlorvos

  Drinking Water                 dichlorvos           Not Applicable
  ------------------------------------------------------------------------

**4.0 Hazard
Characterization/Assessment**[]{#__RefHeading___Toc137619488 .anchor}

> **4.1 Hazard Characterization**[]{#__RefHeading___Toc137619489
> .anchor}

Dichlorvos is a chlorinated organophosphate pesticide cholinesterase
inhibitor, which inhibits plasma, erythrocyte, and brain cholinesterase
in a variety of species, but does not cause organophosphate-induced
delayed neurotoxicity (OPIDN) in the hen. Concern for potential
developmental neurotoxicity arose based on a study in the open
literature (Mehl et al, 1994), which reported decreased total brain
weight in two litters of guinea pigs from dichlorvos-exposed dams.
However, in developmental neurotoxicity studies in rats, decreased brain
weight was not associated with gavage doses of dichlorvos administered
to pups during PNDs 8-22. In acute and 90-day neurotoxicity studies in
rats, there was no neuropathology associated with changes in FOB and
motor activity. Subchronic and chronic oral exposures in rats and dogs
as well as chronic inhalation exposure in rats resulted in significant
decreases in plasma, red blood cell and/or brain cholinesterase
activity. Repeated, oral subchronic exposures in male humans were
associated with statistically and biologically significant decreases in
red blood cell cholinesterase depression.

There was no evidence of increased susceptibility following *in utero*
exposure to rats and rabbits as well as pre/post natal exposure to rats
in developmental and reproduction studies. The FQPA safety factor was
reduced to 1x. Some scenarios used endpoints based on a LOAEL, and the
3x uncertainty factor used is considered part of the FQPA safety factor.

The carcinogenic potential of dichlorvos has been classified as
"suggestive" under the 1999 Draft Cancer Guidelines and no quantitative
assessment of cancer risk is required. Dichlorvos has been shown to be a
direct acting mutagen in *in vitro* mammalian test systems. Dichlorvos
seems to also have clastogenic activity in Chinese hamster ovary (CHO)
cells *in vitro* with or without metabolic activation. On the other
hand, studies showed that dichlorvos was not clastogenic in *in vivo*
micronucleus tests.

Inhibition of cholinesterase activity was the toxicity endpoint selected
to assess hazards for all acute and chronic dietary reference doses
(RfDs), as well as short-, intermediate-, and long-term (chronic) dermal
and inhalation occupational and residential risk assessments. The no
observed adverse effect levels (NOAELs), lowest observed adverse effect
levels (LOAELs), or BMDL~10~s were selected in light of Agency policy on
the use of toxicology studies employing human subjects. Therefore, HED
selected doses and endpoints for risk assessment based on both human and
animal studies.

+--------+----------------+----------+-----------------+--------------+
| Table  |                |          |                 |              |
| 4.1a   |                |          |                 |              |
| Acute  |                |          |                 |              |
| To     |                |          |                 |              |
| xicity |                |          |                 |              |
| of     |                |          |                 |              |
| Dich   |                |          |                 |              |
| lorvos |                |          |                 |              |
+--------+----------------+----------+-----------------+--------------+
| Gui    | Study Type     | MRID     | Results         | Toxicity     |
| deline |                | #(S).    |                 | Category     |
|        |                |          |                 |              |
| No.    |                |          |                 |              |
+--------+----------------+----------+-----------------+--------------+
| 870    | Acute Oral     | 00005467 | LD~50~ = 80     | II           |
| 1.1100 |                |          | mg/kg (M)       |              |
|        |                |          |                 |              |
|        |                |          | 56 mg/kg (F)    |              |
+--------+----------------+----------+-----------------+--------------+
| 87     | Acute Dermal   | 00005467 | LD~50~ = 107    | I            |
| 0.1200 |                |          | mg/kg (M)       |              |
|        |                |          |                 |              |
|        |                |          | [               |              |
|        |                |          | \>]{.underline} |              |
|        |                |          | 75 mg/kg (F)    |              |
+--------+----------------+----------+-----------------+--------------+
| 87     | Acute          | 00137239 | LC~50~[         | II           |
| 0.1300 | Inhalation     |          | \>]{.underline} |              |
|        |                |          | 0.198 mg/L      |              |
+--------+----------------+----------+-----------------+--------------+
| 87     | Primary Eye    | 00146921 | mild irritant   | III          |
| 0.2400 | Irritation     |          |                 |              |
+--------+----------------+----------+-----------------+--------------+
| 87     | Primary Skin   | 00146920 | mild irritant   | IV           |
| 0.2500 | Irritation     |          |                 |              |
+--------+----------------+----------+-----------------+--------------+
| 87     | Dermal         | none     | no study        | NA           |
| 0.2800 | Sensitization  |          | available       |              |
+--------+----------------+----------+-----------------+--------------+
| 87     | Acute Delayed  | 41004702 | Negative for    | NA           |
| 0.6100 | Neu            |          | acute delayed   |              |
|        | rotoxicity-Hen |          | neurotoxicity   |              |
+--------+----------------+----------+-----------------+--------------+
| 87     | Acute          | 42655301 | NOAEL = 0.5     | NA           |
| 0.6200 | Neurotoxicity- |          | mg/kg; LOAEL =  |              |
|        |                |          | 35 mg/kg        |              |
|        | Rat            |          | (changes in     |              |
|        |                |          | FOB, motor      |              |
|        |                |          | activity ) no   |              |
|        |                |          | neuropathology  |              |
+--------+----------------+----------+-----------------+--------------+

+-----------------------+---------+-----------------------------------+
| **Table 4.1b.         |         |                                   |
| Guideline Toxicology  |         |                                   |
| Studies for           |         |                                   |
| Dichlorvos in         |         |                                   |
| Experimental          |         |                                   |
| Animals**             |         |                                   |
+=======================+=========+===================================+
| **Guideline No./Study | **MRID  | **Results**                       |
| Type**                | No.**   |                                   |
+-----------------------+---------+-----------------------------------+
| Acute Oral            | 4       | ChEI NOAEL (RBC and Brain) = not  |
| Cholinesterase        | 5805701 | established                       |
| Inhibition Study      |         |                                   |
| (1^st^) in Adult SD   | Acc     | ChEI LOAEL (RBC and Brain) = 2.1  |
| Rats/ 870.1100        | eptable | mg/kg/day                         |
| (non-guideline)       |         |                                   |
+-----------------------+---------+-----------------------------------+
| Acute Oral            | 4       | ChEI NOAEL (RBC and Brain) = 1    |
| Cholinesterase        | 5805702 | mg/kg                             |
| Inhibition Study      |         |                                   |
| (2^nd^) in Adult SD   | Acc     | ChEI LOAEL (RBC and Brain) = not  |
| Rats/ 870.1100        | eptable | established                       |
| (non-guideline)       |         |                                   |
+-----------------------+---------+-----------------------------------+
| Acute Oral            | 4       | [RBC Cholinesterase               |
| Cholinesterase        | 5805703 | Inhibition]{.underline}           |
| Inhibition Study      |         |                                   |
| (3^rd^) in Adult      | Acc     | NOAEL = 1 mg/kg                   |
| Wistar Rats/ 870.1100 | eptable |                                   |
| (non-guideline)       |         | LOAEL = 5 mg/kg                   |
|                       |         |                                   |
|                       |         | BMD/BMDL~10~ = 1.7/1.3 (M) mg/kg  |
|                       |         |                                   |
|                       |         | BMD/BMDL~10~ = 1.5/1.2 (F) mg/kg  |
|                       |         |                                   |
|                       |         | [Brain Cholinesterase             |
|                       |         | Inhibition]{.underline}           |
|                       |         |                                   |
|                       |         | NOAEL = 1 mg/kg                   |
|                       |         |                                   |
|                       |         | LOAEL = 5 mg/kg                   |
|                       |         |                                   |
|                       |         | BMD/BMDL~10~ = 1.6/1.0 (M) mg/kg  |
|                       |         |                                   |
|                       |         | BMD/BMDL~10~ = 1.6/0.8 (F) mg/kg  |
+-----------------------+---------+-----------------------------------+
| Acute Oral            | 4       | [RBC Cholinesterase               |
| Cholinesterase        | 5842301 | Inhibition]{.underline}           |
| Inhibition Study in   |         |                                   |
| Preweaning Wistar Rat | Acc     | ChEI NOAEL (RBC) = not            |
| Pups/870.1100         | eptable | established                       |
| (non-guideline)       |         |                                   |
|                       |         | ChEI LOAEL (RBC) = 1 mg/kg        |
|                       |         |                                   |
|                       |         | Postnatal day 8 BMD/BMDL~10~ =    |
|                       |         | 1.8/1.3 (M) mg/kg;                |
|                       |         |                                   |
|                       |         | Postnatal day 8 BMD/BMDL~10~ =    |
|                       |         | 1.5/1.0 (F) mg/kg;                |
|                       |         |                                   |
|                       |         | [Brain Cholinesterase             |
|                       |         | Inhibition]{.underline}           |
|                       |         |                                   |
|                       |         | ChEI NOAEL (Brain) = 1 mg/kg      |
|                       |         |                                   |
|                       |         | ChEI NOAEL (Brain) = 5 mg/kg      |
|                       |         |                                   |
|                       |         | Postnatal day 8 BMD/BMDL~10~ =    |
|                       |         | 1.8/1.5 (M) mg/kg;                |
|                       |         |                                   |
|                       |         | Postnatal day 8 BMD/BMDL~10~ =    |
|                       |         | 2.2/1.6 (F) mg/kg;                |
+-----------------------+---------+-----------------------------------+
| Time Course of        | 4       | Brain and RBC enzyme activities   |
| Cholinesterase        | 6153303 | were maximally inhibited one hour |
| Inhibition in         |         | after single dosing in both adult |
| Preweaning and Adult  | Acc     | and preweaning female rats.       |
| Wistar Rats/870.8223  | eptable | Thereafter, ChE inhibition in     |
| (Non-Guideline)       |         | both compartments decreased to    |
|                       |         | approximately control levels by 8 |
|                       |         | hours post dosing.                |
+-----------------------+---------+-----------------------------------+
| Repeat Dose           | 4       | PND18 BMD /BMDL~10~=1.41/1.66     |
| Cholinesterase        | 6153304 | mg/kg/d RBC ChEI (M)              |
| Inhibition Study in   |         |                                   |
| Preweaning (PND 18)   | Acc     | PND48 BMD /BMDL~10~=1.31/1.63     |
| and Adult (PND 48)    | eptable | mg/kg/d RBC ChEI (M)              |
| Wistar                |         |                                   |
| Rats/(Non-Guideline)  |         | PND18 BMD /BMDL~10~=0.83/1.47     |
|                       |         | mg/kg/d RBC ChEI (F)              |
|                       |         |                                   |
|                       |         | PND48 BMD /BMDL~10~=1.26/1.55     |
|                       |         | mg/kg/d RBC ChEI (F)              |
|                       |         |                                   |
|                       |         | PND18 BMD /BMDL~10~=1.40/1.50     |
|                       |         | mg/kg/d Brain ChEI (M)            |
|                       |         |                                   |
|                       |         | PND48 BMD /BMDL~10~=0.76/1.46     |
|                       |         | mg/kg/d Brain ChEI (M)            |
|                       |         |                                   |
|                       |         | PND18 BMD /BMDL~10~=1.80/2.02     |
|                       |         | mg/kg/d Brain ChEI (F)            |
|                       |         |                                   |
|                       |         | PND48 BMD /BMDL~10~=1.26/1.55     |
|                       |         | mg/kg/d Brain ChEI (F)            |
+-----------------------+---------+-----------------------------------+
| Dichlorvos: A single  | 4       | [RBC cholinesterase               |
| blind, placebo        | 4248801 | inhibition]{.underline}           |
| controlled,           |         |                                   |
| randomized study to   | Acc     | LOAEL = 0.1 mg/kg/day             |
| investigate the       | eptable |                                   |
| effects of multiple   |         | NOAEL = not established           |
| oral dosing on        |         |                                   |
| erythrocyte           |         |                                   |
| cholinesterase        |         |                                   |
| inhibition in healthy |         |                                   |
| male volunteers       |         |                                   |
| (non-guideline)       |         |                                   |
+-----------------------+---------+-----------------------------------+
| Dichlorvos: A study   | 4       | [RBC cholinesterase               |
| to investigate        | 4317901 | inhibition]{.underline}           |
| erythrocyte           |         |                                   |
| cholinesterase        | Unacc   | NOAEL = not determined (missed    |
| inhibition following  | eptable | time of peak effect)              |
| oral administration   |         |                                   |
| to healthy male       |         |                                   |
| volunteers            |         |                                   |
| (non-guideline)       |         |                                   |
+-----------------------+---------+-----------------------------------+
| Dichlorvos: A study   | 4       | [RBC cholinesterase               |
| to investigate the    | 4248802 | inhibition]{.underline}           |
| effect of a single    |         |                                   |
| oral dose on          | Unacc   | NOAEL = not determined (missed    |
| erythrocyte           | eptable | time of peak effect)              |
| cholinesterase        |         |                                   |
| inhibition in healthy |         |                                   |
| male volunteers       |         |                                   |
| (non-guideline)       |         |                                   |
+-----------------------+---------+-----------------------------------+
| Dermal                | 4       | Dermal absorption rate for        |
| Absorption/870.7600   | 1435201 | dichlorvos was estimated to be    |
|                       |         | approximately 11% in 10 hours of  |
|                       | Acc     | exposure.                         |
|                       | eptable |                                   |
+-----------------------+---------+-----------------------------------+
| 28-Day Delayed        | 4       | Cholinesterase inhibition (brain  |
| Neurotoxicity-        | 3433501 | ChEI)                             |
| Hen/870.6100          |         |                                   |
|                       | Acc     | NOAEL = 0.1 mg/kg/day             |
|                       | eptable |                                   |
|                       |         | LOAEL = 0.3 mg/kg/day             |
|                       |         |                                   |
|                       |         | No neuropathology.                |
+-----------------------+---------+-----------------------------------+
| 90-Day Subchronic     | 4       | NOAEL = 0.1 mg/kg/day             |
| Oral Toxicity -       | 1004701 |                                   |
| Rat/870.3100          |         | LOAEL = 1.5 mg/kg/day (plasma and |
|                       | Acc     | RBC ChEI)                         |
|                       | eptable |                                   |
+-----------------------+---------+-----------------------------------+
| 90-Day                | 4       | NOAEL = 0.1 mg/day                |
| Neurotoxicity -       | 2958101 |                                   |
| Rat/870.6200          |         | LOAEL = 7.5 mg/kg/day (plasma,    |
|                       | Acc     | red blood cell (RBC) and brain    |
|                       | eptable | ChEI).                            |
+-----------------------+---------+-----------------------------------+
| Chronic               | 4       | NOAEL = 0.05 mg/kg/day            |
| -Feeding-Dog/870.4100 | 1593101 |                                   |
|                       |         | LOAEL = 0.1 mg/kg/day (plasma and |
|                       | Acc     | RBC ChEI in both sexes).          |
|                       | eptable |                                   |
+-----------------------+---------+-----------------------------------+
| 2-Year Inhalation     | 00      | BMD/BMDL~10~ = 0.15/0.07 mg/m^3^  |
| toxicity/             | 057695, | RBC ChEI (F) BMD/BMDL~10~ =       |
| carcinogenicity -     | 0       | 0.14/0.04 mg/m^3^ RBC ChEI (M)    |
| Rat/870.4200          | 0632569 |                                   |
|                       |         | BMD/BMDL~10~ = 0.29/0.29 mg/m^3^  |
|                       | Acc     | Brain ChEI (F)                    |
|                       | eptable |                                   |
|                       |         | BMD/BMDL~10~ = 0.31/0.30 mg/m^3^  |
|                       |         | Brain ChEI (M)                    |
+-----------------------+---------+-----------------------------------+
| Chronic toxicity/     | 4       | NOAEL = Not established           |
|                       | 0299401 |                                   |
| Carcinogenicity-F344  |         | LOAEL = 4.0mg/kg/day (plasma and  |
| Rats (NTP             | Acc     | RBC ChEI)                         |
| study)/870.4300       | eptable |                                   |
|                       |         | Suggestive evidence of            |
|                       |         | carcinogenicity (mononuclear cell |
|                       |         | leukemia in male rats)            |
+-----------------------+---------+-----------------------------------+
| Carcinoge             | 4       | NOAEL = Not established           |
| nicity-Mouse/870.4200 | 0299401 |                                   |
|                       |         | LOAEL = 10 mg/kg/day (plasma and  |
|                       | Acc     | RBC ChEI in males)                |
|                       | eptable |                                   |
+-----------------------+---------+-----------------------------------+
| Developmental         | 4       | Maternal toxicity NOAEL = 3       |
| Toxicity-Rat/870.3700 | 1951501 | mg/kg/day                         |
|                       |         |                                   |
|                       | Acc     | > LOAEL = 21 mg/kg/day            |
|                       | eptable |                                   |
|                       |         | (clinical signs, decreased body   |
|                       |         | weight gain and reductions in     |
|                       |         | food consumption and efficiency)  |
|                       |         |                                   |
|                       |         | Developmental toxicity NOAEL =    |
|                       |         | [\>]{.underline} 21 mg/kg/day     |
|                       |         | (HDT)                             |
+-----------------------+---------+-----------------------------------+
| Developmental         | 4       | Maternal toxicity NOAEL = 0.1     |
| Tox                   | 1802401 | mg/kg/day                         |
| icity-Rabbit/870.3700 |         |                                   |
|                       | Acc     | > LOAEL = 2.5 mg/kg/day           |
|                       | eptable |                                   |
|                       |         | (mortality, decreased body weight |
|                       |         | gain at LOAEL)                    |
|                       |         |                                   |
|                       |         | Developmental toxicity NOAEL=     |
|                       |         | [\>]{.underline} 7 mg/kg/day      |
|                       |         | (HDT)                             |
|                       |         |                                   |
|                       |         | ChEI was not measured in main     |
|                       |         | study                             |
|                       |         |                                   |
|                       |         | Range-Finding: Doses were 0, 0.1, |
|                       |         | 1.0, 2.5, 5.0, 10 mg/kg/day       |
|                       |         |                                   |
|                       |         | Maternal toxicity ChE NOAEL = 0.1 |
|                       |         | mg/kg/day                         |
|                       |         |                                   |
|                       |         | ChE LOAEL = 1.0 mg/kg/day         |
+-----------------------+---------+-----------------------------------+
| Reproductive          | 4       | Parental/Systemic NOAEL = 2.3     |
| Toxicity -            | 2483901 | mg/kg/day                         |
| Rat/870.3800          |         |                                   |
|                       | Acc     | > LOAEL = 8.3 mg/kg/day           |
|                       | eptable |                                   |
|                       |         | (decreased % of females with      |
|                       |         | estrous cycle and increased % of  |
|                       |         | females with abnormal cycling)    |
|                       |         |                                   |
|                       |         | Offspring NOAEL = 2.3 mg/kg/day   |
|                       |         |                                   |
|                       |         | > LOAEL = 8.3 mg/kg/day           |
|                       |         |                                   |
|                       |         | (reduced \# dams bearing litter,  |
|                       |         | fertility index, pregnancy index  |
|                       |         | and pup weight).                  |
+-----------------------+---------+-----------------------------------+
| Preliminary           | 4       | Systemic NOAEL = 7.5 mg/kg/day    |
| Developmental         | 6153301 | Maternal                          |
|                       |         |                                   |
| Neurotoxicity -       | Acc     | Systemic LOAEL = not identified   |
| Rat/(Non-Guideline)   | eptable | Maternal                          |
|                       |         |                                   |
|                       |         | RBC ChEI NOAEL = 0.1 mg/kg/day    |
|                       |         | Maternal                          |
|                       |         |                                   |
|                       |         | RBC ChEI LOAEL = 1.0 mg/kg/day    |
|                       |         | Maternal                          |
|                       |         |                                   |
|                       |         | Brain ChEI NOAEL = 1.0 mg/kg/day  |
|                       |         | Maternal                          |
|                       |         |                                   |
|                       |         | Brain ChEI LOAEL = 7.5 mg/kg/day  |
|                       |         | Maternal                          |
|                       |         |                                   |
|                       |         | Systemic NOAEL = 7.5 mg/kg/day    |
|                       |         | Offspring                         |
|                       |         |                                   |
|                       |         | Systemic LOAEL = not identified   |
|                       |         | Offspring                         |
|                       |         |                                   |
|                       |         | RBC ChEI NOAEL = 1.0 mg/kg/day    |
|                       |         | Fetuses (GD 22)                   |
|                       |         |                                   |
|                       |         | RBC ChEI LOAEL = 7.5 mg/kg/day    |
|                       |         | Fetuses (GD 22)                   |
|                       |         |                                   |
|                       |         | Brain ChEI NOAEL = 1.0 mg/kg/day  |
|                       |         | Fetuses (GD 22)                   |
|                       |         |                                   |
|                       |         | Brain ChEI LOAEL = 7.5 mg/kg/day  |
|                       |         | Fetuses (GD22)                    |
|                       |         |                                   |
|                       |         | Offspring (Pups) did not          |
|                       |         | demonstrate ChEI during PND 2-22  |
+-----------------------+---------+-----------------------------------+
| Developmental         | 4       | Maternal toxicity NOAEL = 7.5     |
| Neurotoxicity -       | 6153302 | mg/kg/day (HDT)                   |
| Rat/870.6300          |         |                                   |
|                       | Acc     | No treatment related effects      |
|                       | eptable |                                   |
|                       |         | Developmental toxicity NOAEL= 1.0 |
|                       | (Study  | mg/kg/day                         |
|                       |         |                                   |
|                       | RR0886) | LOAEL = 7.5 mg/kg/day             |
|                       |         |                                   |
|                       |         | (increases in auditory startle    |
|                       |         | reflex habituation Vmax in PND 23 |
|                       |         | high dose males in both studies)  |
|                       |         |                                   |
|                       |         | ChEI was not measured in main     |
|                       |         | study                             |
+-----------------------+---------+-----------------------------------+
| Developmental         | 4       | Maternal NOAEL is 7.5 mg/kg/day   |
| Neurotoxicity -       | 6239801 | (HDT). A maternal LOAEL was not   |
| Rat/870.6300          |         | established.                      |
|                       | Acc     |                                   |
|                       | eptable | Offspring/developmental NOAEL is  |
|                       |         | 1.0 mg/kg/day (based on study     |
|                       | (Study  | RR0886) and the                   |
|                       |         | Offspring/developmental LOAEL is  |
|                       | RR0988) | 7.5 mg/kg/day (based on both      |
|                       |         | studies RR0886 and RR0988) with   |
|                       |         | the effect being increases in     |
|                       |         | auditory reflex habituation Vmax  |
|                       |         | in PND 23 high dose males in both |
|                       |         | studies.                          |
+-----------------------+---------+-----------------------------------+
| Mutagenicity/Genetic  | Acc     | Dichlorvos has been shown to be a |
| Toxicity Test         | eptable | direct acting mutagen by common   |
| Guidelines-870.5000   |         | *in vitro* bacterial genetic      |
|                       |         | toxicity assays and in *in vitro* |
|                       |         | mammalian test systems.           |
|                       |         | Conflicting evidence was seen for |
|                       |         | clastogenic activity *in vivo*.   |
+-----------------------+---------+-----------------------------------+
| Me                    | 4       | The overall metabolic profile     |
| tabolism-Rat/870.7485 | 1228701 | suggests the involvement of the   |
|                       |         | one-carbon pool biosynthetic      |
|                       | 4       | pathway as evidenced by the       |
|                       | 1839901 | presence of a relatively large    |
|                       |         | amount of radioactivity in the    |
|                       | Acc     | form of expired ^14^CO~2~ and the |
|                       | eptable | presence of dehalogenated         |
|                       |         | metabolites as well as urea and   |
|                       |         | hippuric acid.                    |
+-----------------------+---------+-----------------------------------+

**4.2 FQPA Hazard Considerations**

> **4.2.1 Adequacy of the Toxicity Data
> Base**[]{#__RefHeading___Toc137619490 .anchor}

The toxicology database for dichlorvos is complete. The FQPA database
includes acceptable developmental studies in rats and rabbits, an
acceptable 2-generation rat reproduction study, two developmental
neurotoxicity studies, and single dose gavage cholinesterase studies in
adult and preweaning rats and repeat dose gavage studies in young adult
and preweaning rats.

> **4.2.2 Evidence of Neurotoxicity**[]{#__RefHeading___Toc137619491
> .anchor}

There is a concern for neurotoxicity resulting from exposure to
dichlorvos. Dichlorvos is a chlorinated organophosphate pesticide
cholinesterase inhibitor, which inhibits plasma, erythrocyte, and brain
cholinesterase.

> **4.2.3 Developmental Toxicity
> Studies**[]{#__RefHeading___Toc137619492 .anchor}

In the rat study (MRID 41951501), the maternal toxicity LOAEL was 21
mg/kg/day based on clinical signs of toxicity, reduced body weight gain,
and food efficiency; the maternal NOAEL was 3 mg/kg/day. The
developmental LOAEL was not established; the NOAEL was 21 mg/kg/day.

In the rabbit developmental study (MRID 41802401), groups of NZW rabbits
(16/dose) received oral administration of dichlorvos (97%) in distilled
water at dose levels of 0, 0.1, 2.5, or 7.0 mg/kg/day during gestation
days 7 through 19, inclusive. The maternal LOAEL was 2.5 mg/kg/day based
on maternal deaths and decreased body weight gain; the NOAEL was 0.1
mg/kg/day. No developmental toxicity was noted; therefore, the NOAEL for
developmental toxicity was 7 mg/kg/day.

> **4.2.4 Reproductive Toxicity Study**[]{#__RefHeading___Toc137619493
> .anchor}

In a two generation reproduction study in rats (MRID 42483901), the
parental/systemic NOAEL was 2.3 mg/kg/day and the LOAEL was 8.3
mg/kg/day based on a decreased incidence of estrous cycling and
increased abnormal cycling in F1 females, reduced water intake in both
sexes, and decreased plasma, and RBC ChE activity at all dosage levels
in both sexes in both generations. In addition brain ChE was decreased
in both sexes at 2.3 mg/kg/day. The NOAEL for brain ChE was 0.6
mg/kg/day and the NOAEL for plasma and RBC ChE depression was less than
0.6 mg/kg/day. The NOAEL/LOAEL for reproductive/offspring toxicity
2.3/8.3 mg/kg/day based on a decrease in the number of dams bearing
litters, reduced fertility indices, pregnancy index, and pup body
weights on lactation Day 4 in both F1 matings. The offspring were not
examined for effects on cholinesterase.

**4.2.5 Pre-and/or Postnatal Toxicity**[]{#__RefHeading___Toc137619494
.anchor}

There is no concern for pre- and/or postnatal toxicity resulting from
exposure to dichlorvos. There was no evidence for increased
susceptibility of the rat and rabbit offspring to prenatal or postnatal
exposure to dichlorvos (MRID 41951501, 41802401 and 42483901,
respectively) . In both rat and rabbit developmental studies, no
developmental effects were observed. In the reproduction study, the
parental/systemic NOAEL/LOAEL was 2.3/8.3 mg/kg/day which was identical
to the reproductive/offspring NOAEL/LOAEL. In the DNT studies, at doses
much higher than used for regulation, increase in auditory startle
reflex habituation Vmax in PND 23 high dose males was noted.

> **4.2.5.1 Determination of Susceptibility**

The mode of action for dichlorvos is neurotoxicity through the
inhibition of cholinesterase via phosphorylation of the active site of
the enzyme. Inhibition of cholinesterase provides the most sensitive
endpoint for dichlorvos. There are acute and repeated dosing studies
which evaluate cholinesterase inhibition in juvenile and young adult
rats. The Agency has completed a benchmark dose (BMD) analysis of these
data. The Agency's draft BMD technical guidance indicates that the BMD
approach is a preferable alternative to the NOAEL/LOAEL approach (USEPA,
2000). The Office of Pesticide Programs is increasing its use of BMD
techniques in its hazard assessments and risk characterizations for use
in developing points of departure and in considering relative
sensitivity of adult and juvenile animals. BMDs are preferred over the
NOAEL/LOAEL as NOAELs/LOAELs are highly dependent on dose selection in
that they are limited to the doses included in a study. BMD analysis
also considers the entire dose response curve and not just a single
point. Moreover, the NOAEL/LOAEL approach does not account for the
uncertainty in the estimate of the dose‑response. The dichlorvos BMD
analysis was developed using the exponential model provided in EPA's
OPCum Risk software. The application of the exponential model to
cholinesterase data from OPs and *N*-methyl carbamate pesticides has
been reviewed by the FIFRA Scientific Advisory Board on multiple
occasions. This model and the supporting computer code are publicly
available for download, review, and use at
[www.epa.gov/pesticides/cumulative/EPA_approach_methods.htm.]{.underline}

The Agency calculated the estimated dose to result in 10% inhibition
(BMD~10~) and the lower 95% confidence limit on the BMD~10~ (BMDL~10~).
Brain and RBC ChE data from acute dosing to post-natal day 8 (PND8) and
young adult rats were extracted from MRID nos. 45805703 and 45842301.
The acute BMDs~10~ range from approximately 1.3 mg/kg to 2.0 mg/kg for
each compartment, sex and age group. Regarding repeated exposures, brain
and RBC ChE data from the repeated dosing studies in juvenile and young
adult rat were extracted from MRID nos. 46433201 and 46153304. As
described in detail in the Data Evaluation Record (DER) for these
studies, the ChE activity measurements in some control groups are
unusually high for the laboratory which conducted the repeated exposure
study. The registrant, AMVAC, provided historical control values for
brain and RBC ChE activity. BMD estimates were developed using both the
concurrent and pooled historical control values. It is preferred to
evaluate relative sensitivity using concurrent

controls however in this case use of the historical control values
provides helpful characterization. Overall, for the repeated exposure,
the BMDs ranged from approximately 0.5 mg/kg to 1.2 mg/kg when using the
historical or concurrent controls and are thus similar between
compartments, sexes and age groups.

> **4.2.5.2 Degree of Concern Analysis and Residual Uncertainties for
> Pre and/or Post-natal Susceptibility**

Based on the BMD analysis summarized above, the dichlorvos risk
assessment team has determined that the FQPA Safety Factor can be
reduced to **1X** for acute and repeated exposures of dichlorvos. The
BMD estimates are similar for juvenile and adult rats, and thus
indicates no sensitivity to young animals (Lowit, A., 2006).

**4.2.6. Traditional Safety Factors**

Any traditional safety factors other than that standard uncertainty
factors, the interspecies extrapolation factor, and the intraspecies
variability factor, are considered to be FQPA safety factors. For
dichlorvos, a LOAEL from a human 21-day oral study is used as an
endpoint for short term residential exposure scenarios. The LOAEL to
NOAEL factor of 3x is considered to be an FQPA Safety Factor.

> **4.3 Hazard Identification and Toxicity Endpoint
> Selection**[]{#__RefHeading___Toc137619495 .anchor}

**4.3.1. Acute Reference Dose (aRfD)**[]{#__RefHeading___Toc137619496
.anchor} **- General Population**

[Study Selected]{.underline}: Acute Cholinesterase Study in Rats
Non-guideline

> [MRID]{.underline}: 45805703
>
> [Title]{.underline}: Dichlorvos: Third Acute cholinesterase inhibition
> study in rats; Twomey, K. June 26, 2002.
>
> [Executive Summary]{.underline}: In the third acute oral
> cholinesterase toxicity study in rats (MRID 45805703*)*, groups of 15
> male and 15 female Wistar-derived rats were administered single oral
> doses of dichlorvos (purity of 99.0%) at dose levels of 0 (control), 1
> mg/kg, or 5 mg dichlorvos/kg on Day 1 of the study. Nine males were
> dosed with 35 mg dichlorvos/kg, but due to the severe cholinergic
> signs, no further dosing at this level was conducted. Two additional
> groups of 15 females were dosed with 0 or 15 mg dichlorvos/kg as a
> single oral dose. All animals were observed prior to the start of the
> study and on Day 1 at time of expected peak effect (30 minutes post
> dose) for any changes in clinical condition. Body weights were
> measured at Day 1, 8, and 15. At scheduled termination at 1 hour post
> dosing, 5/sex/dose animals were sacrificed and brains were removed and
> weighed. Cardiac blood samples were taken **post mortem** for
> determination of erythrocyte cholinesterase activity. The cerebellum,
> cerebral cortex, hippocampus, half and remainder of the brain were
> dissected out and sent for determination of cholinesterase activity.
> Dose analysis measurements were acceptable. On day 1 of dosing, severe
> toxicity in 9 males of the high-dose group (35 mg/kg) was observed.
> Four of these males were killed for humane reasons within 1 hour of
> dosing. Those sacrificed and the remaining animals in this group
> displayed some or all of the following signs: decreased activity,
> irregular breathing, clonic convulsions, fasiculations, prostration,
> decreased righting and splay reflexes, and salivation. One female
> dosed with 15 mg/kg had miosis and fasiculations. There were no
> meaningful (i.e., miosis) treatment related clinical signs in animals
> of the 1 or 5 mg/kg dose groups. Body and brain weight comparisons
> between treated groups of both sexes and their respective controls
> were not statistically significantly affected. Statistically
> significant cholinesterase depression occurred at the following doses
> in blood or brain segments for each sex: cerebellum (males, 35 mg/kg;
> females, 5 and 15 mg/kg), cortex (males, 5 and 35 mg/kg; females, 5
> and 15 mg/kg), hippocampus (males, 35 mg/kg; females, 5 and 15 mg/kg),
> remainder (males 35 mg/kg; females 5 and 15 mg/kg), half-brain (males,
> 35 mg/kg; females, 5 and 15 mg/kg), erythrocyte (males, 5 and 35
> mg/kg; females, 5 and 15 mg/kg). There was no meaningful
> cholinesterase depression at 1 mg/kg on erythrocyte or brain segments
> for both sexes killed at 1 hour post-dosing on day 1 or on day 8 or
> day 15 in comparison to controls. Due to a lack of cholinesterase
> inhibition in some animals on day 1, the animals scheduled for
> cholinesterase measurement on day 8 and 15 were sacrificed.
>
> **The LOAEL for erythrocyte and brain cholinesterase inhibition is 5
> mg/kg in both sexes. The NOAEL for erythrocyte and brain
> cholinesterase inhibition is 1 mg/kg in both sexes.**
>
> This acute oral cholinesterase toxicity study is classified
> **acceptable/non-guideline**. This study **does satisfy** the
> requirement (modified OPPTS 870.1100; OECD 401) for an acute oral
> cholinesterase toxicity study on the technical.
>
> [Dose and endpoint for establishing the aRfD]{.underline}: A Benchmark
> Dose Analysis (BMD) was conducted for the dichlorvos cholinesterase
> inhibition data by RRB4 (Daiss B., 2004). The Agency's BMDS program
> (Benchmark Dose Software version 1.3.2) was used to derive the
> BMDL~10~, the estimated dose that results in 10% inhibition of
> cholinesterase, and the BMDL~10~, the lower 95% confidence interval on
> the BMDL~10~, for the RBC cholinesterase data. For this analysis, the
> polynomial continuous model default option of relative deviation was
> used for the benchmark response (BMR) type, with a corresponding BMR
> factor of 0.1 used as a basis for BMD and BMDL~10~ derivation.
>
> The BMDL~10~ of 0.8 mg/kg based on Day 1 female brain ChE depression
> was selected as the lowest value of all the studies available which
> were analyzed by BMD.
>
> A second BMD analysis was done for dichlorvos to be used in the OP
> cumulative analysis. This BMD analysis was done using the OPCumRisk
> software. Similar results were obtained. The decision algorithm and
> technical details of the \"basic\" exponential model used in this BMD
> analysis can be obtained at
> [www.epa.gov/scipoly/sap/2001/september/rpfappendix1.pdf]{.underline}
>
> [Uncertainty factor]{.underline}: 100 (10x for interspecies
> differences and 10x for intraspecies variation).
>
> [FQPA Safety Factor:]{.underline} The FQPA Safety Factor has been
> reduced to 1x, since BMD analysis of studies with pup and adult ChE
> depression results did not demonstrate any substantial numerical
> differences in BMDL values (all values were approximately 1 mg/kg) for
> either RBC or brain cholinesterase.
>
> [Comments about Study/Endpoint/Uncertainty Factor:]{.underline} There
> are no specific issues of concern in the assessment of the rat acute
> cholinesterase studies.
>
> **4.3.2. Chronic Reference Dose
> (cPAD)**[]{#__RefHeading___Toc137619497 .anchor}

[Study Selected]{.underline}: Chronic Toxicity-Dog 870.4100 (formerly
§83-1b)

[MRID No.]{.underline} 41593101

> [Executive Summary:]{.underline} In a chronic feeding study, groups of
> beagle dogs were administered dichlorvos by capsule for 52 weeks at
> dose levels of 0, 0.1, 1.0 and 3.0 mg/kg/day. The 0.1 mg/kg/day dose
> was lowered to 0.05 mg/kg/day on day 22 due to the inhibition of
> plasma cholinesterase noted after 12 days (plasma cholinesterase was
> decreased in males (21.1%) and females (25.7%) at week 2 in the 0.1
> mg/kg/day group). At time points after week 2, plasma cholinesterase
> activity was only significantly reduced in males (39.1 to 59.2%) and
> females (41.0 to 56.7%) in the mid-dose group and in males (65.1 to
> 74.3%) and females (61.1 to 74.2%) in the high dose group. Although
> RBC cholinesterase activity was reduced in males (23.6%) and females
> (50.1%) at week 6 in the low-dose group, this was believed to be an
> effect on RBC cholinesterase of the higher dose of 0.1 mg/kg/day. Much
> lower levels of inhibition were observed in this group after week 6.
> At time points after week 6, RBC cholinesterase activity was only
> significantly decreased in males (43.0 to 53.9) and females (38.0 to
> 51.9) in the mid-dose group and in males (81.2 to 86.9%) and females
> 79.2 to 82.5%) in the high-dose groups. Brain cholinesterase activity
> was significantly reduced in males (22%) in the mid-dose group and in
> males (47%) and females (29%) in the high dose group. The NOAEL was
> 0.05 mg/kg/day and the LOAEL was 0.1 mg/kg/day based on plasma and RBC
> cholinesterase inhibition in males and females.
>
> [Dose and Endpoint for Establishing cRfD:]{.underline} NOAEL = 0.05
> mg/kg based on plasma and RBC cholinesterase inhibition in males and
> females at 0.1 mg/kg/day (LOAEL).
>
> [Uncertainty Factor:]{.underline} 100x (10x for interspecies
> variation, 10x for intraspecies extrapolation)
>
> [FQPA Safety Factor:]{.underline} 1x.
>
> [Comments about Study/Endpoint/Uncertainty Factor]{.underline}: The
> human data (discussed in the next section) were not used since RBC
> cholinesterase inhibition did not demonstrate a steady state
> (equilibrium) by the end of the study at three weeks, i.e. the
> inhibition of cholinesterase was progressive and a NOAEL was not
> achieved. This conclusion was supported by the HSRB.
>
> **4.3.3. Incidental Oral Exposure (Short
> ­Term)**[]{#__RefHeading___Toc137619498 .anchor}

**[Incidental Oral Exposure: Short-Term (1-30 days)]{.underline}**

> [Study Selected:]{.underline} Subchronic oral toxicity study in human
> subjects § Non-guideline
>
> [MRID No.:]{.underline} 44248801
>
> [Executive Summary:]{.underline} In a single blind oral study 6 fasted
> male volunteers were administered 7 mg of dichlorvos in corn oil
> (equivalent to approximately 0.1 mg/kg/d) via capsule daily for 21
> days. Three control subjects received corn oil as a placebo. Baseline
> values for RBC cholinesterase activity for each study participant were
> determined. After dosing started, RBC cholinesterase activity was
> monitored on days 2, 4, 7, 9, 11, 14, 16, and 18, then on day 25 or 28
> post dosing. No clinical signs attributable to administration of
> dichlorvos was reported. Mean RBC cholinesterase activity was
> statistically significantly reduced in treated subjects on days 7, 11,
> 14, 16, and 18. These values were 8, 10, 14, 14, and 16 percent below
> the pre-dose mean. Under the study conditions, a LOAEL for RBC
> cholinesterase inhibition was established at 0.1 mg/kg/d. A NOAEL was
> not established.
>
> [Dose and Endpoint for Risk Assessment:]{.underline} The LOAEL of 0.1
> mg/kg/d based on statistically significant decreases in RBC
> cholinesterase inhibition.
>
> [Comments about Study/Endpoint:]{.underline} The human study was
> selected because it is a subchronic study of appropriate duration and
> is the lowest LOAEL established for RBC cholinesterase inhibition in a
> repeated oral exposure to dichlorvos. Uncertainty factors account for
> intraspecies variability (10x). Since the study was conducted in human
> subjects, there was no need to account for interspecies extrapolation.
>
> [FQPA Safety Factor:]{.underline} 3x A 3x for lack of a NOAEL is
> considered an FQPA safety factor.
>
> [Target MOE:]{.underline} 30
>
> **4.3.4. Dermal Absorption**[]{#__RefHeading___Toc137619499 .anchor}

[Dermal Absorption Factor:]{.underline} The dermal absorption rate for
dichlorvos was estimated to be approximately 11% in 10 hours of exposure
based on an acceptable dermal absorption study in rats (MRID 41435201).

> **4.3.5. Dermal Exposure (Acute)**[]{#__RefHeading___Toc137619500
> .anchor}

[Study Selected]{.underline}: Acute Cholinesterase Study in Rats
Non-guideline

> [MRID]{.underline}: 45805703 (see discussion under Section 4.3.1 Acute
> Reference Dose)
>
> [Target MOE:]{.underline} 100
>
> **4.3.6. Dermal Exposure (Short-, Intermediate-, and Long-
> Term)**[]{#__RefHeading___Toc137619501 .anchor}

[Study Selected:]{.underline} Subchronic oral toxicity study in human
subjects § Non-guideline

> [MRID No.:]{.underline} 44248801
>
> [Executive Summary:]{.underline} (See discussion above)
>
> [Dose and Endpoint for Risk Assessment:]{.underline} The LOAEL of 0.1
> mg/kg/d based on statistically significant decreases in RBC
> cholinesterase inhibition.
>
> [Comments about Study/Endpoint:]{.underline} The human study was
> selected because it is a subchronic study of appropriate duration and
> is the lowest LOAEL established for RBC cholinesterase inhibition in a
> repeated oral exposure to dichlorvos. Since the study was conducted in
> human subjects, there was no need to account for the interspecies
> extrapolation. Uncertainty factors account for intraspecies
> variability (10x).
>
> [FQPA Safety Factor:]{.underline} 3x A 3x for lack of a NOAEL is
> considered an FQPA safety factor.

[Target MOE]{.underline}: 30

> **4.3.7. Inhalation Exposure (Acute)**[]{#__RefHeading___Toc137619502
> .anchor}

[Study Selected]{.underline}: Acute Cholinesterase Study in Rats
Non-guideline

> [MRID]{.underline}: 45805703 (see discussion under Section 4.3.1 Acute
> Reference Dose)

[Target MOE]{.underline}: 100, or 30 if RfC methodology is used. If RfC
methodology is used, the interspecies extrapolation factor is reduced
from 10x to 3x.

> **4.3.8. Inhalation Exposure (Short and Intermediate
> Term)**[]{#__RefHeading___Toc137619503 .anchor}

[Study Selected:]{.underline} Subchronic oral toxicity study in human
subjects § Non-guideline

> [MRID No.:]{.underline} 44248801 (See discussion above under dermal
> exposure)
>
> [Comments about Study/Endpoint]{.underline}: The uncertainty factors
> are the same as discussed above under Dermal Exposure.
>
> **4.3.9. Inhalation Exposure (Long
> Term)**[]{#__RefHeading___Toc137619504 .anchor}

[Study Selected]{.underline}: 2-year Rat Inhalation/carcinogenicity
870.4200a (formerly §83-2a)

[MRID No.]{.underline} 0057695, 00632569

> [Executive Summary]{.underline}: The critical study for inhalation
> risk assessment for Dichlorvos is an inhalation carcinogenicity study
> in rats. Groups of 50/sex/group Carworth rats were exposed to
> atmospheres containing Dichlorvos vapor for 23 hours/day, 7 days/week
> at concentrations of 0, 0.05, 0.5, and 5 mg/m^3^ equivalent to 0.055,
> 0.5, and 5.0 mg/kg/day for 2 years. Animals were observed for clinical
> signs of toxicity, hematology, and clinical chemistry. Plasma, RBC and
> brain cholinesterase activity were determined at study termination.
> There were no toxic signs, and no organ weight or organ to body weight
> changes, or hematological changes attributable to administration of
> Dichlorvos. Body weights were significantly decreased in mid and high
> dose males up to study termination, and in high dose females
> throughout the study. Plasma, RBC, and brain cholinesterase activity
> were significantly reduced in the mid and high dose groups (76, 72,
> and 90 and 83, 68, and 90 percent of control in mid dose males and
> females, and to 38, 4, and 21, and 22, 5, and 16 percent of control in
> the high dose male and female groups, respectively). RBC
> cholinesterase activity was reduced to 88 percent of control in the
> low dose females. The BMD~10~ for RBC cholinesterase inhibition in
> female rats was 0.15 mg/m^3^ and the BMDL~10~ was 0.07 mg/m^3^.
>
> [Comments about Study/Endpoint:]{.underline} This is the same
> inhalation study which has been used by the Agency RfD/RfC Work Group
> in deriving the Reference Concentration (RfC) for Dichlorvos. An
> Agency RfC document is available on IRIS.
>
> The BMDL~10~ of 0.07 mg/m^3^ (or 0.00007 mg/L) was selected for
> chronic inhalation risk assessment scenarios. Uncertainty factors
> account for intraspecies variation (10x) and 3x for interspecies
> variation. (The interspecies extrapolation factor is reduced to 3x
> when the endpoint is expressed in concentration units (RfC
> methodology)).
>
> [FQPA Safety Factor:]{.underline} 1x

[Target MOE:]{.underline} 30

> **4.3.10. Margins of Exposure**[]{#__RefHeading___Toc137619505
> .anchor}

A summary of target Levels of Concern for dichlorvos risk assessment is
provided in Table 4.3.10.

+-----------------+------------+------------+-------------+------------+
| **Table 4.3.10. |            |            |             |            |
| Target Levels   |            |            |             |            |
| of Concern      |            |            |             |            |
| (i.e., Margins  |            |            |             |            |
| of Exposure)    |            |            |             |            |
| for Dichlorvos  |            |            |             |            |
| Exposure        |            |            |             |            |
| Scenarios**     |            |            |             |            |
+=================+============+============+=============+============+
| **Route**       | **Acute**  | **Sh       | **Intermed  | **L        |
|                 |            | ort-Term** | iate-Term** | ong-Term** |
| **Duration**    | **(\<1     |            |             |            |
|                 | Day)**     | **(1-30    | **(1 - 6    | **(\> 6    |
|                 |            | Days)**    | Months)**   | Months)**  |
+-----------------+------------+------------+-------------+------------+
| **Occupational  |            |            |             |            |
| (Worker)        |            |            |             |            |
| Exposure**      |            |            |             |            |
+-----------------+------------+------------+-------------+------------+
| **Dermal**      | 100        | 30         | 30          | N/A        |
+-----------------+------------+------------+-------------+------------+
| **Inhalation**  | 100/30\*   | 30         | 30          | N/A        |
+-----------------+------------+------------+-------------+------------+
| **Residential   |            |            |             |            |
| (Non-Dietary)   |            |            |             |            |
| Exposure**      |            |            |             |            |
+-----------------+------------+------------+-------------+------------+
| **Oral**        | 100        | 30         | N/A         | N/A        |
+-----------------+------------+------------+-------------+------------+
| **Dermal**      | 100        | 30         | 30          | 30         |
+-----------------+------------+------------+-------------+------------+
| **Inhalation**  | 100/30\*   | N/A        | N/A         | 30         |
+-----------------+------------+------------+-------------+------------+

**\* The higher target MOE is used when the endpoint is expressed in
mg/kg/day (for exposure during application). The lower target MOE is
used when the endpoint is expressed in concentration units (RfC
methodology, used for post-application risk assessment). There is no
long term residential inhalation exposure during application.**

> For short- and intermediate- term oral and dermal exposures, the
> uncertainty factor is based on the conventional uncertainty factor of
> 10X for intraspecies variability. No factor is needed for interspecies
> extrapolation because the endpoint is based on a human study. A 3x
> factor for lack of a NOAEL is considered an FQPA safety factor.

For short- and intermediate- term inhalation exposure, the uncertainty
factor is based on the conventional uncertainty factor of 10x for
intraspecies extrapolation, 3x for the use of a LOAEL. For long term
inhalation exposure, the uncertainty factor is based on the conventional
uncertainty factor of 10x for intraspecies extrapolation, 3x for
interspecies extrapolation (based on air concentrations), The FQPA
safety factor is reduced to 1x for residential exposure assessments.

For acute inhalation exposure, the uncertainty factor is based on the
conventional uncertainty factor of 100x (10X for interspecies
extrapolation and 10x for intraspecies variability), when the endpoint
is expressed in mg/kg/day. When the endpoint is expressed in
concentration units, the interspecies extrapolation factor is reduced to
3x. The FQPA Safety Factor has been reduced to 1x. The target MOE is 30.

> **4.3.11. Recommendation for Aggregate Exposure Risk
> Assessments**[]{#__RefHeading___Toc137619506 .anchor}

Under FQPA, when there are potential residential exposures to the
pesticide, aggregate risk assessment must consider exposures from
residues in food commodities and drinking water, as well as exposures
arising from non-dietary sources (e.g., incidental oral, dermal and
inhalation exposures) from the residential scenarios. Since there are
residential uses of dichlorvos and the effect is cholinesterase
inhibition for all endpoints, aggregation of risk from non dietary
sources is required. Since the target MOEs differ, aggregation of risk
will be assessed using the aggregate risk index (ARI). The target ARI is
1.

> **4.3.12. Classification of Carcinogenic
> Potential**[]{#__RefHeading___Toc137619507 .anchor}

Dichlorvos has been classified as a category C carcinogen based
primarily on increased incidences of forestomach tumors in female mice
and mononuclear cell leukemia (MCL) in male Fischer 344 rats. Both tumor
types have been used at various times to derive q~1~\* s for
quantitation of cancer risk. After lengthy deliberations and
consultations with EPA's Scientific Advisory Panel (SAP) and cancer
experts with the National Toxicology Program, HED's Cancer Assessment
Review Committee has classified dichlorvos as "suggestive" and not
requiring quantitation of cancer risks based on the following rationale:

> 1\) MCL in the male Fischer rat has certain properties in terms of
> variability and reliability which limit its usefulness for human risk
> assessment.
>
> 2\) The forestomach tumors in mice observed at gavage doses causing
> inhibition of plasma and red blood cell cholinesterase and cholinergic
> signs, are also limited in their use for human risk assessment.
>
> 3\) The fact that dichlorvos is only positive by the gavage route and
> negative by the inhalation route, which is the major route of human
> exposure, indicates that any classification by the oral route may be
> limited since localized effects in the forestomach may not be
> applicable to human risk assessment.

4.  **Summary of Toxicology Endpoint Selection for Dichlorvos**

+-----------+---------+-------------+----------+----------------------+
| **Table   |         |             |          |                      |
| 4.4.      |         |             |          |                      |
| Summary   |         |             |          |                      |
| of        |         |             |          |                      |
| Toxi      |         |             |          |                      |
| cological |         |             |          |                      |
| Doses and |         |             |          |                      |
| Endpoints |         |             |          |                      |
| for       |         |             |          |                      |
| D         |         |             |          |                      |
| ichlorvos |         |             |          |                      |
| for Use   |         |             |          |                      |
| in        |         |             |          |                      |
| Dietary   |         |             |          |                      |
| and       |         |             |          |                      |
| Non-Occ   |         |             |          |                      |
| upational |         |             |          |                      |
| Human     |         |             |          |                      |
| Health    |         |             |          |                      |
| Risk      |         |             |          |                      |
| Asse      |         |             |          |                      |
| ssments** |         |             |          |                      |
+===========+=========+=============+==========+======================+
| **E       | **Point | **Uncer     | **Level  | **Study and          |
| xposure** | of      | tainty/FQPA | of       | Toxicological        |
|           | Depa    | Safety      | Concern  | Effects**            |
| **S       | rture** | Factors**   | for Risk |                      |
| cenario** |         |             | Asse     |                      |
|           |         |             | ssment** |                      |
+-----------+---------+-------------+----------+----------------------+
| Acute     | B       | UF~A~ = 10x | **Acute  | Rat acute oral       |
| Dietary   | MDL~10~ |             | RfD** =  | cholinesterase       |
|           | = 0.8   | UF~H~ = 10x | 0.008    | studies - RBC and    |
| (General  | mg      |             | m        | Brain ChE            |
| p         | /kg/day | FQPA SF =   | g/kg/day | depression. NOAEL =  |
| opulation |         | 1x          |          | 1 mg/kg/day, LOAEL = |
| including |         |             | **aPAD** | 5 mg/kg/day, BMD =   |
| infants   |         |             | = 0.008  | 1.6 mg/kg/day for    |
| and       |         |             | m        | brain ChE depression |
| children) |         |             | g/kg/day | (F)                  |
+-----------+---------+-------------+----------+----------------------+
| Chronic   | NOAEL=  | UF~A~ = 10x | *        | 1-Year Dog study     |
| Dietary   | 0.05    |             | *Chronic |                      |
|           | mg      | UF~H~ = 10x | RfD** =  | LOAEL = 0.1          |
| (All      | /kg/day |             |          | mg/kg/day based on   |
| pop       |         | FQPA SF =   | 0.0005   | Plasma and RBC ChE   |
| ulations) |         | 1x          | m        | depression           |
|           |         |             | g/kg/day |                      |
|           |         |             | **cPAD** |                      |
|           |         |             | = 0.0005 |                      |
|           |         |             | m        |                      |
|           |         |             | g/kg/day |                      |
+-----------+---------+-------------+----------+----------------------+
| S         | LOAEL=  | UF~H~= 10x  | **Resid  | Human 21-day oral    |
| hort-Term | 0.1     |             | ential** | study                |
|           | mg      | FQPA SF =   | LOC MOE  |                      |
| I         | /kg/day | 3x (UF~L~)  | = 30     | LOAEL = 0.1          |
| ncidental |         |             |          | mg/kg/day based on   |
| Oral      |         |             |          | RBC ChE depression   |
| (1-30     |         |             |          |                      |
| days)     |         |             |          |                      |
+-----------+---------+-------------+----------+----------------------+
| Acute     | B       | UF~A~ = 10x | **Resid  | Rat acute oral       |
| Dermal    | MDL~10~ |             | ential** | cholinesterase       |
| and Acute | = 0.8   | UF~H~ = 10x | LOC MOE  | studies - RBC and    |
| I         | mg      |             | = 100    | Brain ChE            |
| ncidental | /kg/day | FQPA SF =   |          | depression. NOAEL =  |
| Oral      |         | 1x          |          | 1 mg/kg/day, LOAEL = |
|           | dermal  |             |          | 5 mg/kg/day, BMD =   |
|           | absorpt |             |          | 1.6 mg/kg/day for    |
|           | ion=11% |             |          | brain ChE depression |
|           |         |             |          | (F)                  |
+-----------+---------+-------------+----------+----------------------+
| Short-,   | Oral    | UF~H~ = 10x | **Resid  | Human 21-day oral    |
| Interme   | study   |             | ential** | study                |
| diate-and | LOAEL=  | FQPA SF =   | LOC MOE  |                      |
| Long-Term |         | 3x (UF~L~)  | = 30     | LOAEL = 0.1          |
| Dermal    | 0.1     |             |          | mg/kg/day based on   |
|           | mg      |             |          | RBC ChE depression   |
|           | /kg/day |             |          |                      |
|           |         |             |          |                      |
|           | dermal  |             |          |                      |
|           | absorpt |             |          |                      |
|           | ion=11% |             |          |                      |
+-----------+---------+-------------+----------+----------------------+
| Acute     | Oral    | UF~A~ = 10x | **Resid  | Rat acute oral       |
| I         | study   |             | ential** | cholinesterase       |
| nhalation | B       | UF~H~ = 10x | LOC MOE  | studies - RBC and    |
| (1 day)   | MDL~10~ | or 3x\*\*   | =        | Brain ChE            |
|           | = 0.8   |             | 10       | depression. NOAEL =  |
|           | mg      | FQPA SF =   | 0/30\*\* | 1 mg/kg/day, LOAEL = |
|           | /kg/day | 1x          |          | 5 mg/kg/day, BMD =   |
|           |         |             |          | 1.6 mg/kg/day for    |
|           | (inh    |             |          | brain ChE depression |
|           | alation |             |          | (F)                  |
|           | abs     |             |          |                      |
|           | orption |             |          |                      |
|           | rate =  |             |          |                      |
|           | 100%)   |             |          |                      |
|           |         |             |          |                      |
|           | Air     |             |          |                      |
|           | concen  |             |          |                      |
|           | tration |             |          |                      |
|           | Equ     |             |          |                      |
|           | ivalent |             |          |                      |
|           | = 0.8   |             |          |                      |
|           | mg      |             |          |                      |
|           | /m^3^\* |             |          |                      |
+-----------+---------+-------------+----------+----------------------+
| Short-    | Oral    | UF~H~ = 10x | **Resid  | Human 21-day oral    |
| and       | study   |             | ential** | study                |
| Intermed  | LOAEL=  | FQPA SF =   | LOC MOE  |                      |
| iate-term |         | 3x (UF~L~)  | = 30     | LOAEL = 0.1          |
| I         | 0.1     |             |          | mg/kg/day based on   |
| nhalation | mg      |             |          | RBC ChE depression   |
| of vapors | /kg/day |             |          |                      |
|           | UF=30   |             |          |                      |
|           |         |             |          |                      |
|           | Concen  |             |          |                      |
|           | tration |             |          |                      |
|           | equi    |             |          |                      |
|           | valent= |             |          |                      |
|           | 0.35    |             |          |                      |
|           | mg      |             |          |                      |
|           | /m^3^\* |             |          |                      |
+-----------+---------+-------------+----------+----------------------+
| Short-    | LOAEL=  | UF~H~ = 10x | **Resid  | Human 21-day oral    |
| and       | 0.1     |             | ential** | study                |
| Intermed  | mg      | FQPA SF =   | LOC MOE  |                      |
| iate-Term | /kg/day | 3x (UF~L~)  | = 30     | LOAEL = 0.1          |
|           |         |             |          | mg/kg/day based on   |
| I         |         |             |          | RBC ChE depression   |
| nhalation |         |             |          |                      |
| during    |         |             |          |                      |
| ap        |         |             |          |                      |
| plication |         |             |          |                      |
+-----------+---------+-------------+----------+----------------------+
| Long-Term | B       | UF~A~ = 10x | Res      | 2-year Rat           |
| I         | MDL~10~ |             | idential | Inhalation           |
| nhalation | = 0.07  | UF~H~ =     | LOC = 30 |                      |
| of vapors | mg/m^3^ | 3x\*\*      |          | BMD = 0.15 mg/m^3^   |
|           |         |             |          | based on RBC ChE     |
|           |         | FQPA SF =   |          | depression (F)       |
|           |         | 1x          |          |                      |
+-----------+---------+-------------+----------+----------------------+
| Cancer    | "sugg   |             |          |                      |
| (oral,    | estive" |             |          |                      |
| dermal,   | e       |             |          |                      |
| in        | vidence |             |          |                      |
| halation) | of      |             |          |                      |
|           | c       |             |          |                      |
|           | arcinog |             |          |                      |
|           | enicity |             |          |                      |
|           | not     |             |          |                      |
|           | quant   |             |          |                      |
|           | ifiable |             |          |                      |
|           | under   |             |          |                      |
|           | the     |             |          |                      |
|           | 1999    |             |          |                      |
|           | Draft   |             |          |                      |
|           | Agency  |             |          |                      |
|           | Cancer  |             |          |                      |
|           | Gui     |             |          |                      |
|           | delines |             |          |                      |
+-----------+---------+-------------+----------+----------------------+

Point of Departure (POD) = A data point or an estimated point that is
derived from observed dose-response data and used to mark the beginning
of extrapolation to determine risk associated with lower environmentally
relevant human exposures. NOAEL = no observed adverse effect level.
LOAEL = lowest observed adverse effect level. UF = uncertainty factor.
UF~A~ = extrapolation from animal to human (intraspecies). UF~H~ =
potential variation in sensitivity among members of the human population
(interspecies). UF~L~ = use of a LOAEL to extrapolate a NOAEL. UF~S~ =
use of a short-term study for long-term risk assessment. UF~DB~ = to
account for the absence of key date (i.e., lack of a critical study).
FQPA ~SF~ = FQPA Safety Factor. PAD = population adjusted dose (a =
acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC
= level of concern. N/A = Not Applicable

\* Calculation of concentration equivalent BMDL~10~ and LOAEL

Acute Inhalation BMDL~10~

0.8 mg/kg/day x 0.35 kg / 0.34 m^3^/day = 0.8 mg/m^3^

Short- and Intermediate- term inhalation of vapors LOAEL

0.1 mg/kg/day x 70 kg / 20 m^3^/day = 0.35 mg/m^3^

\*\*Since the NOAEL is expressed in concentration units (RfC
methodology), the interspecies extrapolation factor is 3x (for the acute
and long term inhalation scenarios), for a total UF of 30 for acute
inhalation and long term inhalation. The residential target MOE is 30
for acute inhalation, since the FQPA safety factor has been reduced
to 1. The Residential target MOE is 30 for long term inhalation, since
the FQPA safety factor is 1.

**4.4 FQPA Safety factor**[]{#__RefHeading___Toc137619508 .anchor}

The HED dichlorvos team evaluated the hazard and exposure data to
determine if the FQPA10x safety factor should be retained, reduced or
removed focusing primarily on the following points:

-   The standard developmental and reproductive toxicity studies and the
    developmental neurotoxicity study submitted to the Agency showed no
    residual concern for sensitivity or susceptibility of rats, or
    rabbits to *in utero* and/or postnatal exposure to dichlorvos;

-   In repeated dose studies with dichlorvos in rats, young rats were
    less sensitive than adult rats with respect to inhibition of RBC
    cholinesterase; in repeated dose studies with dichlorvos in rats,
    based on the BMD analysis, there was no difference between young
    rats and adult rats with respect to inhibition of brain
    cholinesterase; in repeated dose studies, the BMDs are similar
    between compartments, sexes and age groups.

-   Some exposure scenarios are based on a LOAEL.

```{=html}
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```
-   The dietary food exposure assessment utilizes a combination of
    monitoring data, field trial data, and tolerance level residues.
    Percent crop treated information is used where available. These data
    will not underestimate chronic exposures/risks.

-   The dietary drinking water assessment (Tier 2 estimates) utilizes
    values generated by model and associated modeling parameters which
    are designed to provide conservative, health protective, high-end
    estimates of water concentrations.

-   The residential exposure assessment utilizes dichlorvos specific
    monitoring data, activity specific transfer coefficients and
    chemical-specific turf transferable residue (TTR) studies for the
    post-application turf scenario (use of trichlorfon). The refined
    residential assessment is based on reliable data and is unlikely to
    underestimate exposure/risk.

The dichlorvos team concluded that the FQPA Safety Factor can be reduced
to 1x, except for short term oral and dermal scenarios, for which the
FQPA factor is retained at 3x to account for the lack of a NOAEL.

> **4.5. Endocrine Disruption**[]{#__RefHeading___Toc137619509 .anchor}

EPA is required under the 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 (EDSP). In the available toxicity
studies on dichlorvos, there was no estrogen, androgen, and/or thyroid
mediated toxicity. When additional appropriate screening and/or testing
protocols being considered under the Agency's EDSP have been developed,
dichlorvos may be subjected to further screening and/or testing to
better characterize effects related to endocrine disruption.

**5.0 Public Health Data**[]{#__RefHeading___Toc137619510 .anchor}

The Agency has conducted a review of reported poisoning incidents
associated with human exposure to dichlorvos. The Agency has consulted
the following data bases for the poisoning incident data on the active
ingredient dichlorvos: (1) the OPP Incident Data System, which contains
anecdotal reports of incidents from various sources, including
registrants, other federal and state health and environmental agencies
and individual consumers, submitted to OPP since 1992, (2) Poison
Control Center Data for 28 organophosphate and carbamate chemicals for
the years 1985 through 1992, (3) California Department of Food and
Agriculture reports (superceded by the Department of Pesticide
Regulation), which contain uniform data on suspected pesticide
poisonings collected since 1982, and (4) National Pesticide
Telecommunications Network (NPTN), which is a toll-free information
service supported by OPP. In addition, the Agency has received public
comments regarding poisoning incidences associated with dichlorvos as
comments to the Proposed Notice of Intent to Cancel (PD 2/3) and in
Phase 3 of the RED process. Specific comments on incidences were
received from Amvac Chemical Corporation, the Japanese Resin Strip
Manufacturer's association, and two private citizens, Arturo Haran and
Eric Levine.

Exposure to dichlorvos has resulted in poisoning incidents. Dichlorvos
has widespread use patterns in the home and agricultural environments.
Many of these uses (e.g., poultry houses) are atypical of most
organophosphates, which make it difficult to compare the risk. According
to California data, it appears that a majority of cases involved
illnesses to workers indoors that entered a facility previously
fumigated with dichlorvos. Often exposure results from inadequate
ventilation before persons are allowed in or near the treated area or
lack of proper personal protective equipment (PPE).

Dichlorvos can cause systemic illness, including respiratory effects, to
individuals who are exposed after fumigation.

> **5.1 Incident Reports**[]{#__RefHeading___Toc137619511 .anchor}

Incidents with dichlorvos are discussed in a separate review. Blondell,
J and Spann, M. 1998. More recent information is available. However, the
more recent information is very similar to that reported in 1998, and
doesn't change our conclusions (J. Blondell, personal communication with
S. Hummel, 1/4/2005).

> **5.2 Other**[]{#__RefHeading___Toc137619512 .anchor}

The Agency received additional information on poisoning incidents
associated with dichlorvos as comments to the PD 2/3 and to Phase 3 of
the RED. Specific comments on incidents were received from Amvac
Chemical Corporation, the Japanese Resin Strip Manufacturer's
Association, and two private citizens, Arturo Haran and Eric Levine.
Amvac submitted a review of human incident data for Dichlorvos (Feiler
1995), and the Japanese Resin Strip Manufacturer's Association submitted
data on poisoning incidences involving dichlorvos resin strips. Arturo
Haran submitted an anecdotal report of health effects and Eric Levine
submitted a comment about the potential carcinogenicity of dichlorvos.
The Agency has reviewed this new information (Blondell 1996). The
Agency's conclusions are summarized below.

Data reported by the American Association of Poison Control Centers
(AAPCC) concerning exposure to single products with dichlorvos often
contain other active ingredients. AAPCC reported 21,006 exposures to
single products containing dichlorvos. Most of these exposures involve
homeowner use products that contained dichlorvos in combination with
other insecticides such as propoxur, pyrethrins, or piperonyl butoxide.
In these cases involving dichlorvos in combination with other pesticides
it is incorrect to attribute any resulting toxicity solely to
dichlorvos.

Dichlorvos resin strips account for a very small proportion of total
incidents, about 33 cases per year (1% of total incidences). Incident
reports involving exposure to resin strips usually do not involve any
significant acute symptoms that would require medical treatment
(Blondell 1996).

Eric Levine commented on epidemiological evidence linking use of
dichlorvos resin strips with childhood cancer. Two epidemiologic studies
have reported an association between exposure to dichlorvos resin strips
and childhood cancer. These studies by Liess and Savitz (1995) and Davis
et al (1993) have been reviewed by the Agency (Blondell 1996). Reviews
of these studies have identified biases and confounders that could
explain the observed associations. The Agency concludes that the biases
are a more likely explanation for the findings of increased cancer than
exposure to resin strips. Additional studies that correct for the
control of potential biases and problems of exposure determination are
needed before an association between dichlorvos and childhood cancer can
be established.

A statistically significant excess risk for prostate cancer and
dichlorvos exposure was reported in the recent Agricultural Health Study
(AHS) by Alavanja et al., (2003). The reported excess risk was based on
a small number of cases (n=16) and only seen in the men who had a family
history of prostate cancer. The odds ratio reported was 1.75, (75%
excess) with confidence interval 1.0‑3.06, meaning the risk could be as
high as 206%. Dichlorvos was one of seven chemicals positive for
prostate cancer among fifty chemicals tested. There is no AHS chemical
specific report on dichlorvos at this time. Follow‑up studies are
planned to examine the interaction effect on family history and genetic
susceptibility factors. The AHS is a prospective pesticide epidemiology
study that includes over 90,000 certified pesticide applicators and
their families from Iowa and North Carolina. Additional analyses will
examine dichlorvos findings, as part of the high pesticide exposure
event studies and work practices assessments. Dichlorvos is not one of
the current National Health and Nutrition Examination Surveys (NHANES)
chemicals being examined by the Centers for Disease Control (CDC)
National Center for Health Statistics (NCHS).

**6.0 Exposure
Characterization/Assessment**[]{#__RefHeading___Toc137619513 .anchor}

> **6.1 Dietary Exposure/Risk Pathway**[]{#__RefHeading___Toc137619514
> .anchor}
>
> **6.1.1 Residue Profile**[]{#__RefHeading___Toc137619515 .anchor}

The reregistration requirements for plant and livestock metabolism are
fulfilled. The Agency determined that the available data depicting the
metabolism of naled in plants are sufficient to delineate the metabolism
of dichlorvos in plants because dichlorvos is the initial metabolite of
naled. In plants, naled is metabolized to dichlorvos which is hydrolyzed
to dimethyl phosphate and dichloroacetaldehyde. Dimethyl phosphate is
sequentially degraded to monomethyl phosphate and inorganic phosphates,
and dichloroacetaldehyde is converted to 2,2‑dichloroethanol which is
then conjugated and/or incorporated into naturally occurring plant
components. The residue of concern in plant commodities is dichlorvos.

Acceptable studies depicting the qualitative nature of the residue in
ruminants and poultry following dermal treatment with dichlorvos have
been submitted and evaluated. Because dichlorvos is the initial
metabolite of naled, the available metabolism studies reflecting oral
dosing of ruminants and hens with naled are sufficient to delineate the
metabolism of orally dosed dichlorvos in animals. The residue of concern
in animal commodities is dichlorvos.

Adequate field trial and processing data are available for the
reregistration of dichlorvos, although not all the field trial data are
adequately supported by storage stability data, and there is an
outstanding data requirement for a dermal study in swine. Finite
residues are reported in the field trials, but residues are generally
non-detectable in monitoring data. Non-detectable residues were
generally reported in livestock tissues, milk, and eggs. Adequate
enforcement analytical methods are available in PAM I and II. Dichlorvos
is recovered by PAM I Luke multiresidue method (protocol D), provided
"early eluter" conditions are used. The Pesticide Analytical Manual
(PAM) Vol. II lists a GC method (with flame photometric detection;
Method I) for the determination of dichlorvos in plant and animal
commodities. An additional GC method (Method II) using electron capture
detection is listed for the determination of dichlorvos and naled in
plant and animal commodities; this method is also an enforcement method
for naled. A GC method using microcoulometric detection is listed as
Method A. This method determines total residues of dichlorvos and naled
via conversion of naled residues to dichlorvos; however, the method can
be modified to determine naled and dichlorvos separately. Data
collection methods were similar to the available enforcement methods,
and were adequately validated.

Dietary exposure to dichlorvos residues may occur as a result of use on
or at a variety of sites, including mushroom houses, warehouses
containing bulk-stored and packaged or bagged nonperishable processed
and raw food, commercial food processing plants, groceries, direct
animal treatment, and livestock premise treatment. As a result,
dichlorvos residues may be found in bulk stored and packaged or bagged
non perishable processed or raw food. Dichlorvos residues may also be
found in mushrooms and in livestock commodities, such as meat, milk,
meat byproducts, poultry, and eggs. In addition, a dichlorvos registrant
has expressed interest in supporting use on tomatoes.

Two other pesticides, naled and trichlorfon, degrade to dichlorvos
through plant and livestock metabolism, and non-biological reactions.
The Agency does not expect measurable dichlorvos residues from
trichlorfon because all trichlorfon food uses on field crops have been
canceled and associated tolerances revoked, and non-detectable residues
were found in livestock dermal studies.

Three factors will significantly affect dietary exposure to dichlorvos
from registered uses of naled; these include the pre-harvest interval
(PHI), the condition and length of storage, and cooking and processing.
Plant metabolism studies show that dichlorvos residues are formed 1 to 3
days after treatment with naled; however, dichlorvos residues decline to
less than the limit of detection (0.01 to 0.05 ppm) 7 days after
treatment. In general, registered uses of naled have PHIs of less than 7
days. Because of the short PHIs for naled products, measurable residues
of dichlorvos may be present in the diet from naled treated food. As a
result, the dietary (food) exposure assessment for dichlorvos includes
residues of dichlorvos resulting from the application of naled.

Dietary exposure estimates for acute and chronic dietary exposure
assessments have been refined with residue data from USDA's Pesticide
Data Program (PDP), FDA surveillance monitoring data, and FDA Total Diet
Study (TDS) data, processing and cooking studies, and percent of crop
treated information.

Sources of data to estimate the levels of residues of pesticides in food
include the following: tolerances (legal limits), controlled field trial
data, Food and Drug Administration (FDA) surveillance and compliance
monitoring data, FDA Total Diet Study data (market basket survey based
on a random sampling of residues on food in grocery stores), US
Department of Agriculture (USDA) Pesticide Data Program (PDP), and
USDA/FSIS (Food Safety Inspection Service) livestock monitoring data
(Hummel, 1998a, Hummel 2000). The estimated levels of residues can then
be adjusted for the effects of processing using processing studies,
including commercial processing studies, washing studies, cooking
studies, and residue degradation studies. Of these sources, the Agency
relied on tolerance levels and field trial data (adjusted for the
effects of processing and cooking) to estimate dietary exposure to
dichlorvos in the PD 2/3. At the time of the PD 2/3, the monitoring data
available for dichlorvos were very limited. In this updated assessment,
anticipated residues based on some tolerances plus field trial and
monitoring data were used.

**(a). *Field Trial Data***. Data from controlled field trials which
reflect currently registered uses are available for mushrooms. Data from
direct dermal treatments to cattle and poultry are discussed in the
Dichlorvos Registration Standard. Field trial data are available for
packaged or bagged food, use in food manufacturing and processing
facilities, and for secondary residues in livestock commodities.
Adequate field trial data are not available for tomatoes.

**(b). *FDA Surveillance and Compliance Monitoring Data*.** The FDA
Surveillance and Compliance Monitoring Program is designed to ensure
that pesticide residues do not exceed established tolerances. Naled and
dichlorvos are included in the FDA surveillance and compliance
monitoring programs. However, dichlorvos is only detected using the Luke
method on non-fatty foods, and only when \"early eluter\" column
conditions are used (low column temperature). Thus, the number of
samples analyzed for dichlorvos is low compared to the samples analyzed
for other pesticides, although the number of analyses done by FDA that
will detect dichlorvos have increased significantly in the last few
years. FDA Surveillance and Compliance monitoring data were obtained
from FDA for 1990 through 1998. From 1994 through 1998, FDA analyzed
over 3000 surveillance monitoring samples for dichlorvos. The limit of
quantitation (LOQ) for dichlorvos in fruits and vegetables is
approximately 0.01 ppm, and the limit of detection (LOD), approximately
0.003 ppm.

All residues of dichlorvos reported were non-detectable, with the
following exceptions: three samples of strawberries (which had low
levels of detectable residues of dichlorvos), one sample of red
raspberries (0.08 ppm dichlorvos); one tomato sample from Mexico with a
trace residue (\> LOD, but \<LOQ); one sample of garbanzo beans from S.
Korea with a trace residue; and 0.03 ppm on one sample of cantaloupe
from Honduras. All residues of naled reported were non-detectable, with
the following exceptions: 3 samples of strawberries with residues of
0.1, 0.2, and 0.43 ppm naled.

**(c). *FDA Total Diet Study Data (TDS).*** The FDA Total Diet Study
Program is designed to measure trends in pesticide residues. Since 1982,
approximately four market baskets per year have been collected in a
large city in one of four regions of the country. The region of the
country in which the market basket samples are collected rotates so that
samples are collected in all four regions over one year. FDA summarizes
the data expressed as daily intakes for 8 age-sex groups (infants, young
children, male and female teenagers, male and female adults, and male
and female older persons). Each market basket has consisted of 234-265
individual food items prepared as ready to eat foods (washed and
cooked). Individual foods are analyzed separately. Although the TDS
includes sampling of meats and poultry, dichlorvos could not be analyzed
in these commodities using the TDS analytical methods.

Historically, the Agency has not used FDA Total Diet Study data for
exposure assessment purposes because the number of samples is limited
(approximately four samples per year of each of 234 - 265 individual
food items since 1982), samples are only collected in large cities, and
the treatment history is unknown. The TDS does not include minor crops.
However, a total of 43 market basket surveys are now available for
1982 - 1996. Among the commodities collected in the TDS, there were
approximately 35 non-fatty commodities analyzed which were similar to
crackers and cereals, approximately 11 baked goods which were made from
flour, sugar, and dried eggs, 4 coffee and 1 tea commodities, plus
raisins, prunes, and cooked eggs. These are commodities that are or are
produced from 'bulk stored' and 'packaged and bagged' commodities, and
may have been treated with dichlorvos closer to the point of consumption
than the wheat grain samples collected by USDA in their Pesticide Data
Program.

By grouping the commodities (generally along crop group
classifications), there were more than 100 samples per group of
commodities analyzed. The Agency has used extrapolation among members of
crop groups in the past when using monitoring data. For example,
monitoring data for oranges could be extrapolated to all citrus
(tangerines, tangelos, grapefruit, lemons, and limes), provided the use
pattern for citrus is the same.

Dichlorvos is not listed specifically as one of the pesticides recovered
in the analyses for the FDA Total Diet Study. However, all of the Total
Diet Study samples were analyzed using temperature programming which
would allow detection of \"early eluters.\" Therefore, if dichlorvos is
present, it would be detected, and one detectable residue of dichlorvos
was reported. The LOD for dichlorvos in total diet samples is 0.001 ppm
(personal communication, B. McMahon, FDA).

**(d). *USDA Pesticide Data Program Data*.** The USDA Pesticide Data
Program (PDP) collects residue data primarily for fresh fruits and
vegetables, plus wheat grain, beef commodities, poultry commodities, and
milk. A few canned and frozen commodities have been tested. Samples are
collected in terminal markets and large distribution centers. The
commodities included in the PDP changes annually. Sampling dates and
sites are selected at random following a statistically designed sampling
plan. Participating laboratories meet rigorous quality assurance/quality
control (QA/QC) criteria including following good laboratory practices
(GLP), a check sample program, and confirmation of residue findings.
Sampling and analyses are done through a cooperative agreement with nine
states and two USDA laboratories. These states represent about 50% of
the population of the US and a large percentage of the fresh fruits and
vegetables grown in the US. Food commodities collected in the PDP are
prepared as normally would be done for consumption, washed and peeled,
although not cooked. Canned and frozen commodities are not further
cooked before analysis, although they may have been blanched or cooked
in the canning or freezing process.

The USDA PDP analyzes for dichlorvos, which would include dichlorvos
resulting from naled since the analytical method used generally converts
naled to dichlorvos prior to or during the analysis. The LOD for the
analyses varied, depending on the laboratory conducting the analyses,
and ranged from 3 ppb to 280 ppb. All samples analyzed for dichlorvos
had non-detectable residues, except for (1) one peach sample analyzed in
1992, which had a dichlorvos residue of 0.059 ppm; (2) one green bean
sample analyzed in 1994, which had a dichlorvos residue of 0.012 ppm;
(3) one grape sample analyzed in 1996, which had a dichlorvos residue of
0.003 ppm, which was below the LOQ; (4) one milk sample analyzed in
1996, which had a dichlorvos residue of 0.003 ppm, which was below the
LOQ; (5) one pear sample analyzed in 1997, which had a dichlorvos
residue of 0.005 ppm, which was below the LOQ; and (5) 15 strawberry
samples in 1998, on which the maximum dichlorvos residue was 0.02 ppm.
PDP data were used in the dichlorvos dietary exposure assessment for
commodities which could be treated with naled, beef commodities, poultry
commodities, and for milk. The PDP data on wheat grain were not used,
because packaged and bagged commodities made from wheat grain could have
been treated again with dichlorvos after the PDP samples would have been
collected. The PDP does not analyze for naled because initial method
validation indicated that naled is converted to dichlorvos during the
analysis. The PDP does, however, identify unknown residues, and would
report a residue of naled if found.

**(e). *Processing and Cooking Study Data*.** Residues for raw
commodities can be modified by processing factors to account for changes
during commercial or other processing and cooking. Processing, cooking
and decline (half-life) studies were available for cocoa beans, dry
pinto beans, tomato juice, ground roasted coffee beans, raw hamburger
meat, raw eggs, and raw whole milk. The resulting cooking factors were
used to reduce the Agency\'s estimate of residues for these commodities
and were translated to other commodities based on similarity of cooking
time and temperature. Additional cooking studies were available and
discussed in the Residue Chemistry Chapter of the Registration Standard.
Half-lives of dichlorvos in various commodities ranged from 0 to over
1,000 hours. The reduction of dichlorvos upon cooking appeared to be
related to the length of time and temperature used in cooking. Residues
were adjusted based on these cooking factors to obtain the Anticipated
Residue Estimate for the cooked commodity.

**(f). *Percent of crop treated data.*** OPP has refined its estimates
of dietary exposure for various commodities based on percent of crop
treated. The Biological and Economic Analysis Division (BEAD) of OPP
provided updated percent of crop treated (% CT) information that were
incorporated into the acute dietary (food) exposure analysis as
appropriate (Hummel, et. al. 2000). Where a range of percent crop
treated estimates are supplied for this analysis, the upper end of that
range is assumed for acute dietary (food) exposure analysis, and the
typical or average % CT is used for the chronic dietary (food) exposure
analysis.

> **6.1.2 Acute and Chronic Dietary Exposure and
> Risk**[]{#__RefHeading___Toc137619516 .anchor}

Anticipated residues are a realistic estimate of actual pesticide
residues in foods based on available data. Reliable data are available
for dichlorvos, including the USDA's PDP data, the FDA Total Diet Study
and the FDA monitoring data. These data were not available at the time
of the PD 2/3, Notice of Intent to Cancel, published in 1995.
Anticipated residues used in the dietary risk assessment are presented
in separate memo (Hummel S, Hrdy D, and Sahafayen M, 2000). The methods
for deriving anticipated residues for dichlorvos are described below.

**(a) *From Use of Dichlorvos***. All dichlorvos tolerances in 40 *CFR*
§180.235 were evaluated as potential sources of dichlorvos residues. For
the updated dichlorvos dietary exposure assessment, FDA Total Diet Study
data were used for residues resulting from the use of dichlorvos per se,
where appropriate, by grouping similar commodities made from grain
products, sugar, dried eggs, coffee and tea, and dried fruits. These are
summarized below.

*Raw Agricultural Commodities.* The following uses have been canceled by
AMVAC: tomatoes, cucumbers, lettuce, and radishes, and the associated
tolerances recommended for revocation. Therefore, these uses are not
included in the exposure assessment. One dichlorvos registrant has
proposed supporting use on tomatoes, and tomatoes still appears on one
product label, EPA Reg. No. 5011‑49. No residue data were provided to
support this use. No detectable residues of dichlorvos were detected on
tomatoes in 1996-1998 in the PDP or from 1994-1998 in the FDA
Surveillance Monitoring Program.

*Meat, Milk, Poultry and Eggs.* Residues in livestock tissues, including
milk and eggs, may result from consumption of dichlorvos treated
livestock feeds, direct dermal treatments, livestock premise treatments,
or from use as a drug in swine. Livestock metabolism studies done at
exaggerated rates in ruminants and poultry have demonstrated that oral
ingestion of dichlorvos, naled, and trichlorfon by cattle and poultry
will not result in detectable residues. This conclusion can be
translated to the drug use of dichlorvos in swine. Secondary residues in
livestock and poultry from consumption of treated feed fall under
category 3 of 40 CFR §180.6(a), having no reasonable expectation of
finite residues. Data reflecting dichlorvos direct livestock treatments
are discussed in the Residue Chemistry Chapter of the Dichlorvos
Registration Standard. Data from direct dermal studies indicate that
detectable residues are not expected, except in skin. Residues are
non-detectable (\<0.01 ppm) in cattle tissue and milk, and
non-detectable (\<0.05 ppm) in poultry tissues and eggs. For the PD 2/3
dietary exposure assessment, the Agency used one-half the limit of
detection as the residue estimate in both cases.

PDP monitoring data were available for meat (beef and poultry)
commodities, and milk. Non-detectable residues of dichlorvos were found
in all beef commodities (\<0.001 ppm) and poultry commodities (\<0.006
ppm), Ratios of dichlorvos residues found in livestock tissues in dermal
metabolism studies to residues of dichlorvos found in milk in the
livestock dermal metabolism studies were calculated. These ratios were
then used with the PDP monitoring data in milk to estimate residues of
dichlorvos in livestock tissues (lower than the PDP limit of
quantitation for beef commodities). The dietary exposure estimates in
poultry commodities are based on the non-detectable residues (\<0.006
ppm) reported in PDP monitoring data. A cooking factor of 0.3x was then
applied. The dietary exposure estimate for eggs was the non-detectable
residue found in cooked eggs in the FDA Total Diet Study.

*Bulk Stored, Packaged or Bagged Commodities, Food and Feed Handling
Uses.* The anticipated residues used in the Dichlorvos PD 2/3 exposure
assessment for packaged, bagged or bulk stored food were based on field
studies submitted by AMVAC (Hummel 1994b). Residue data were submitted
for many commodities. For those commodities where data were not
submitted, the Agency translated residue data from similar commodities.
For example, data on dry beans are translated to other legumes; data on
wheat flour are translated to all flours and meals, etc. In addition,
residue data were provided for corn and oats at various points during
processing, and for flour, sugar, dried milk, dried eggs, shortening,
and baking mix from a treated manufacturing facility. Bulk stored
commodities are assumed to be uncovered when treated. Although pesticide
labels state that bulk or unpackaged foods should be covered or removed
before spraying, it is not possible to assess the effect of covering
food since the type of material used in the cover is not specified and
the manner in which food is covered would vary considerably. Therefore,
food is assumed to be uncovered, which is likely to overestimate
residues. Since the proportion of commodities stored in bulk vs.
packaged/bagged is unknown, the anticipated residues are based the
residues found in packaged/bagged food, because foods are expected to be
packaged/bagged closer to the time of consumption.

FDA TDS data were used for the dichlorvos dietary exposure assessment on
grain products and sugar, eggs, coffee and tea. In the 43 samples of 126
commodities in which dichlorvos would be detected, only one sample had a
detectable residue, one sample of rye bread at 0.01 ppm, which is below
the LOQ of 0.03 ppm.

The tolerances in 40 *CFR* §180.235 for nonperishable packaged, bagged
or bulk raw food and for packaged or bagged nonperishable processed
foods (formerly in 40 *CFR* §185.1900) do not refer to specific
commodities. Therefore, the Agency has developed a list of commodities
likely to be treated with dichlorvos that are covered by tolerances.
Because these tolerances were established to cover residues resulting
from use at different sites (for example, wheat could be treated in its
raw form in a silo, later as flour, during processing into cake mixes,
and finally as a stored packaged commodity), cancellation of any one of
the site-specific uses does not necessarily eliminate the risk of a
commodity from dichlorvos treatment. The Agency did not combine the
residues from different sites in creating the anticipated residues,
although the cumulative residues from treating a commodity at different
sites were considered in the estimation of percent of crop treated for
the PD 2/3; however, the Agency position has changed. Now we expect that
sufficient time will pass between treatments that only the maximum
residue from one type of treatment needs to be considered.

\(b\) ***From Use of Naled*.** All naled tolerances in 40 *CFR* §180.215
were evaluated as potential sources of dichlorvos residues. Anticipated
residues are based on either tolerance level equivalents or field trials
or monitoring data from FDA (Regulatory monitoring or Total Diet Study)
or USDA (PDP). These data sources were used for both acute and chronic
dietary exposure estimates. Naled and dichlorvos residue estimates were
reduced when data were available to account for the effects of washing,
cooking, and processing. In addition, wide area application of naled in
mosquito and fly control use could result in residues potentially on all
crops in the Agency\'s DEEM software. The Agency did not include all
these crops in its estimate of anticipated dichlorvos residues for the
chronic dietary exposure assessment. Although it is possible that
dichlorvos residues could occur on any raw agricultural commodity from
this use of naled, it is unlikely that residues would be found on all
commodities. As a result, this inclusion of residues of dichlorvos from
all raw crops would present a possible source of overestimation of
dietary exposure. A sensitivity analysis was conducted for naled and
dichlorvos from naled, done separately from the dichlorvos risk
assessment, showing that the mosquito and fly control use was not a
substantial source of exposure.

\(c\) ***From Use of Trichlorfon*.** All trichlorfon tolerances in 40
*CFR* 180.198 were evaluated as a potential source of dichlorvos
residues. All tolerances for trichlorfon have been revoked, with the
exception of tolerances in beef cattle commodities, which are being
retained to cover potential residues from imported meat commodities. In
trichlorfon cattle feeding studies, residues of trichlorfon and
dichlorvos were non-detectable (\<0.05 ppm) in livestock commodities at
pre-slaughter intervals of 1, 3, and 7 days (T. Morton, 1999). This
would result in residue estimates of the same order of magnitude as
those for dichlorvos alone and naled-derived dichlorvos. Measurable
residues of dichlorvos from the use of trichlorfon are not expected,
because it has no crop tolerances or registered crop food uses (Hummel,
1998b), and non-detectable residues are expected on livestock
commodities.

**6.1.2.1 Acute Dietary Exposure and Risk**

A DEEM analysis was performed to estimate acute dietary exposure and
risk from dichlorvos; and to estimate dietary exposures and risks for
chronic systemic toxicity from residues of dichlorvos (Hummel, S. V., D.
Hrdy, M. Sahafayen. 2000). Because dichlorvos residues on food may be
derived from use of either dichlorvos or naled, the dietary risk
analyses included both dichlorvos and naled-derived dichlorvos.
Trichlorfon-derived dichlorvos was considered. All domestic field crop
uses of trichlorfon have been canceled. The trichlorfon tolerances have
been revoked, except for tolerances in livestock commodities, which were
retained as import uses. The DEEM analyses were done for all
commodities supported for reregistration.

A highly refined acute dietary analysis was performed, which combined
the acute exposure from dichlorvos residues resulting from the use of
dichlorvos, naled-derived dichlorvos (including residues of naled, which
could be converted in the body to dichlorvos), but excluding the naled
public health mosquito use (Hummel, et. al. 2000). Residues of
dichlorvos from the use of trichlorfon were estimated to be negligible.
For assessing risk use of dichlorvos, anticipated residues based on
field trials and monitoring data were used. For assessing risk from
naled-derived dichlorvos, anticipated residues based on some tolerances,
some field trials, and monitoring data were used. The acute
probabilistic dietary analyses used individual food consumption as
reported by respondents in the USDA 1989-91 Continuing Survey of Food
Intake by Individuals (CSFII) in the DEEM software. Results are
reported as a percentage of the aPAD for the 99.9^th^ percentile of the
population. The % aPAD is calculated as the ratio of the exposure to the
aPAD (% aPAD = exposure/aPAD x 100%).

Highly refined anticipated residues which incorporated percent of crop
treated (% CT), monitoring data from the PDP, the FDA Surveillance
Monitoring Program, the FDA TDS, field trial data, and a few tolerances
were used to estimate acute dietary exposure. The acute exposure/risk
estimate did not exceed HED's level of concern for either the general US
population or any of the sub-populations. The sub-population with the
highest exposure was children 1-6 with estimated exposure of 4% of the
aPAD (0.000021 mg dichlorvos/kg bwt/day), while the estimated exposure
for the U. S. Population was 2% of the aPAD (0.000009 mg dichlorvos/kg
bwt/day) at the 99.9th percentile. The results are provided in Table
6.2.1.1.

  ------------------- ------- ------------ --------- ------------ --------- ------------ ---------
  **Table 6.1.2.1.                                                                       
  Acute Dietary (Food                                                                    
  Only) Tier 3                                                                           
  Exposure and Risk                                                                      
  Estimates for                                                                          
  Dichlorvos.**                                                                          

  Population          aPAD,   95th                   99th                   99.9th       
  Subgroup^a^         mg/kg   Percentile             Percentile             Percentile   

                              Exposure,    \%        Exposure,    \%        Exposure,    \%
                              mg/kg        aPAD^b^   mg/kg        aPAD^b^   mg/kg        aPAD^b^

  U.S. pop - all      0.008   0.000018     0.23      0.000044     0.6       0.000145     1.8
  seasons:                                                                               

  All infants (\<1            0.000022     0.28      0.000087     1.0       0.000308     3.8
  year):                                                                                 

  Children (1-6               0.000034     0.43      0.000076     1.0       0.000334     4.2
  years):                                                                                

  Children (7-12              0.000022     0.28      0.000050     0.6       0.000167     2.1
  years):                                                                                

  Females (13-50              0.000013     0.16      0.000032     0.4       0.000085     1.1
  years):                                                                                
  ------------------- ------- ------------ --------- ------------ --------- ------------ ---------

^a^ Population subgroups shown include the U.S. general population, and
those of infants, children, and women of child-bearing age.

^b^ % aPAD = Exposure (mg/kg) ÷ aPAD (mg/kg) × 100

**6.2.1.2. Chronic Dietary Exposure**

A refined DEEM chronic exposure analysis was conducted using percent
crop treated data and anticipated residues to calculate the chronic
dietary exposure estimate for the general population and all subgroups
(Hummel, et. al. 2000). Anticipated residues were based on monitoring
data from the FDA TDS, the FDA Surveillance Monitoring Program, and from
the PDP. Therefore, the Agency has high confidence in the residue data
used to estimate chronic dietary exposure.

As mentioned above, OPP has refined its estimates of dietary exposure
for various commodities based on percent of crop treated. OPP has
refined its estimates of dietary exposure for various commodities using
processing factors to account for changes in residue levels during
commercial or other processing and during cooking.

Highly refined anticipated residues (which also incorporated % CT
information, monitoring data from the PDP and the FDA Surveillance
Monitoring Program, and field trial data) were used to estimate chronic
dietary exposure. The chronic exposure/risk estimate did not exceed
HED's level of concern for either the general US population or any of
the sub-populations. The resulting risk estimate for all sub-populations
and the general US population was below 100% of the cPAD. The
sub-population with the highest exposure was children 1-6 with 1% of the
chronic population adjusted dose (cPAD) (0.0000013 mg dichlorvos/kg
bwt/day), while the estimated risk to the U.S. Population was \<1% of
the cPAD (0.0000007 mg residue/kg bwt/day). The results are provided
below in Table 6.2.1.2.

+--------------------------+------------+----------------+------------+
| **Table 6.2.1.2. Chronic |            |                |            |
| Dietary (Food Only) Tier |            |                |            |
| 3 Exposure and Risk      |            |                |            |
| Estimates for            |            |                |            |
| Dichlorvos.**            |            |                |            |
+--------------------------+------------+----------------+------------+
| Population Subgroup^1^   | cPAD,      | Exposure,      | \% cPAD    |
|                          | mg         | mg/kg/day      |            |
|                          | /kg/day^2^ |                |            |
+--------------------------+------------+----------------+------------+
| U.S. Population (total)  | 0.0005     | 0.0000007      | \<1        |
+--------------------------+------------+----------------+------------+
| All infants (\< 1 year)  |            | 0.0000013      | 1          |
+--------------------------+------------+----------------+------------+
| Children 1-6 yrs         |            | 0.0000013      | 1          |
+--------------------------+------------+----------------+------------+
| Children 7-12 yrs        |            | 0.0000007      | \<1        |
+--------------------------+------------+----------------+------------+
| Females 13-50 yrs        |            | 0.0000003      | \<1        |
+--------------------------+------------+----------------+------------+
| ^1^ Population subgroups |            |                |            |
| shown include the U.S.   |            |                |            |
| general population, and  |            |                |            |
| those of infants,        |            |                |            |
| children, and women of   |            |                |            |
| child-bearing age, and   |            |                |            |
| other, representative    |            |                |            |
| populations whose        |            |                |            |
| exposure exceeds that of |            |                |            |
| the U.S. general         |            |                |            |
| population.              |            |                |            |
|                          |            |                |            |
| ^2^ % cPAD = Exposure    |            |                |            |
| (mg/kg) ÷ cPAD (mg/kg) × |            |                |            |
| 100                      |            |                |            |
+--------------------------+------------+----------------+------------+

**6.2.1.3. Dietary Cancer Risk Estimates**

No dietary cancer risks for dichlorvos were estimated. The carcinogenic
potential of dichlorvos has been classified as "suggestive" under the
1999 Draft Agency Cancer Guidelines and no quantitative assessment of
cancer risk is required. (Diwan, S. 2000).

**6.2.2. Uncertainties in Dietary Exposure Assessment**

The Agency believes the exposure and risk assessment presented in this
document is the most refined to date for acute and chronic dietary
exposure to dichlorvos as a result of use of dichlorvos, naled, and
trichlorfon. However, there are some uncertainties associated with this
exposure assessment as follows:

(a). The dietary exposure analyses relied primarily on monitoring data
obtained either "at the farm gate," in the case of FDA surveillance
monitoring data, or in regional distribution warehouses for PDP data.
Residues potentially present on items purchased at roadside produce
stands or farmer's markets are not represented in this analysis.
Although cooking data were available and were used, there may be
differences in the amount of reduction of dichlorvos residues as a
result of cooking.

(b). Samples collected for the FDA Total Diet Study were collected in
supermarkets in only four cities per year. Residues found in food in
other locations may be different.

(c). Very little monitoring data are available for fumigated
commodities. Extensive translation was done from one fumigated commodity
to another.

(d). For the commodities for which field trial data were used, the
residues of dichlorvos are probably over-estimated. Dichlorvos is
expected to dissipate fairly rapidly.

> **6.2 Water Exposure/Risk Pathway**[]{#__RefHeading___Toc137619517
> .anchor}

Dichlorvos residues can be present in ground and/or surface water as a
result of use of three pesticides: dichlorvos (DDVP), naled, and
trichlorfon (dichlorvos is a degradate of naled and trichlorfon). The
Environmental Fate and Effects Division (EFED) discussed the
environmental fate of dichlorvos, naled and trichlorfon and evaluated
the potential for dichlorvos to contaminate water from these sources
(Abdel‑Saheb I., 2003, Jones, R. D., 2006). The environmental fate
properties of dichlorvos, naled, and trichlorfon are indicators of the
potentials of these compounds to migrate to ground or surface water.
These fate properties are described below.

**6.2.1 Fate Properties of Dichlorvos, Naled, and Trichlorfon**

**6.2.1.1. Dichlorvos**

The major mode of dissipation of dichlorvos is volatilization from soils
because dichlorvos has a vapor pressure of 1.2 X 10^-2^ mm Hg under
field conditions. Also, acceptable laboratory studies indicate rapid
dissipation through volatilization. Dichlorvos appears to degrade
through aerobic soil metabolism and abiotic hydrolysis as well, but
these processes are secondary to volatilization. Hydrolysis is pH
dependent where the half-lives were 11 days at pH 5, 5 days at pH 7 and
21 hours at pH 9. Aerobic soil metabolism data showed a half-life of 10
hours; 2,2-dichloroacetic acid was the major metabolite. An acceptable
soil TLC study indicates that dichlorvos is moderately mobile (K~d~\'s
ranging 0.3 to 1.2), based on the Heiling and Turner\'s mobility
classification. The potential of dichlorvos to leach to ground water is
mitigated by its rapid degradation. Dichlorvos has the potential to
contaminate surface waters because of a low K~oc~ value and high water
solubility (10 x 10^3^ ppm, or 1 %). Substantial fractions of run-off
will more than likely occur via dissolution in run-off water rather than
adsorption to eroding soil. Despite the potential for contamination,
dichlorvos should not be persistent in any surface waters due to its
susceptibility to rapid hydrolysis and volatilization.

**6.2.1.2. Naled**

Chemical hydrolysis and biodegradation are the major processes involved
in the transformation of naled and its degradates in the environment.
Dichlorvos forms from naled by indirect photolysis in water and soil. In
the presence of photosensitizer in water, as much as 20% of the applied
dose of naled can be found as dichlorvos after 1 day, with rapid decline
of dichlorvos residues afterwards. Under anaerobic aquatic conditions,
dichlorvos can be as high as 15% of the applied naled dose after 1 day.
The degradation of dichlorvos formed from naled under anaerobic
conditions is slower (half-life 0.9 days) than under aerobic conditions.

**6.2.1.3. Trichlorfon**

Dichlorvos is formed from trichlorfon in soil by aerobic soil
metabolism, and in water hydrolysis studies. Environmental fate data
indicate that trichlorfon degrades rapidly in aerobic soil (t~1/2~ \~
1.8 days) under non-sterile conditions; however, in a sterile soil,
trichlorfon was stable (t~1/2~ \> 40 days). Trichlorfon degradation is
strongly influenced pH. In the hydrolysis study at 25° C, the
trichlorfon degradation half‑life was 104 days at pH 5; 34 hours at pH
7; and 31 minutes at pH 9. The maximum measured dichlorvos formed from
trichlorfon also varied with pH, with a maximum percentage converted of
2.1% at pH 5; 25% at pH 7; and 52% at pH 9. The formation of dichlorvos
from trichlorfon is not a \'hydrolysis reaction\' per se, but a
dehydrochlorination. The other degradates found in the hydrolysis study
are des‑methyldichlorvos, and dichloroacetaldehyde, resulting from
hydrolysis of dichlorvos directly. There is no acceptable field
dissipation study for trichlorfon, because the submitted studies had
recovery problems.

**6.2.2. Groundwater**

EFED has limited monitoring data on the concentrations of dichlorvos,
naled or trichlorfon in groundwater. Validated monitoring data for
dichlorvos, naled, and trichlorfon are available for the states of
California and Hawaii from the Pesticides in Groundwater Database (USEPA
1992). These data indicated that naled, dichlorvos, or trichlorfon have
not been detected in groundwater. However, the monitoring studies were
not targeted to the pesticide use area. These data are presented in
Table 6.2.2a. below.

  ----------------- ----------------- ----------------- -----------------
  Table 6.2.2a.                                         
  Groundwater                                           
  monitoring data                                       
  for Dichlorvos,                                       
  Naled, and                                            
  Trichlorfon                                           
  showing number of                                     
  wells sampled                                         
  (number of wells                                      
  with residues)                                        
  (USEPA 1992)                                          

                    Naled             Dichlorvos        Trichlorfon

  California        83 (0)            20(0)             280 (0)

  Hawaii            3 (0)             7 (0)             
  ----------------- ----------------- ----------------- -----------------

Because the groundwater monitoring data for dichlorvos are limited, EFED
used the Tier I **SCI-GROW** screening model to estimate concentrations
of dichlorvos in groundwater. This model predicts that dichlorvos,
naled, and trichlorfon will not be found in significant concentrations
in groundwater. Concentrations of these compounds were calculated based
on a maximum annual application rate of 0.2 lb a.i./acre for dichlorvos
(wide area treatment), 9.375 lb a.i/acre for naled (the maximum seasonal
use rate on Cole crops, 5 applications of 1.87 lb a.i./acre), and 3
times per year at 8.17 lb a.i./acre for trichlorfon (turf). The amount
of dichlorvos formed as a degradate of naled was estimated to be 20% of
naled. Therefore, a conservative dichlorvos use rate was estimated by
using naled's use rate multiplied by 0.20. The amount of dichlorvos
formed as a degradate of trichlorfon was estimated to be 56% of
trichlorfon, which is the maximum percent of dichlorvos (56%) formed as
a trichlorfon degradate determined from the trichlorfon aerobic aquatic
metabolism at pH 8.5. The amount of dichlorvos formed as a trichlorfon
degradate was estimated by multiplying the maximum application rate for
trichlorfon (8.17 lb a.i/acre) by 56%. Because groundwater
concentrations of dichlorvos were estimated using a Tier I screening
model, EFED has moderate confidence in the groundwater assessment.

Table 6.2.2b. Estimated Dichlorvos Concentrations in Groundwater.

  ----------------------------- -----------------------------------------
  **Source of Dichlorvos        **Modeled Groundwater Concentration,
  Residues**                    μg/L**

  Dichlorvos Applied 1/week     0.004

  Dichlorvos Applied Every      0.015
  Other Day                     

  Dichlorvos (from Naled)       0.0002

  Dichlorvos (from Trichlorfon) 0.01
  ----------------------------- -----------------------------------------

There may be exceptional circumstances under which groundwater
concentrations could exceed the SCI-GROW estimates. However, such
exceptions should be quite rare since the SCI-GROW model is based
exclusively on maximum groundwater concentrations from studies conducted
at sites and under conditions which are most likely to result in
groundwater contamination. The groundwater concentrations generated by
SCI-GROW are based on the largest 90-day average recorded during the
sampling period. Since there is relatively little temporal variation in
groundwater concentrations compared to surface water, the concentrations
can be considered as appropriate for acute and chronic risk assessment.

**6.2.3. Surface Water**

Dichlorvos may reach surface water as a result of use of three
pesticides: dichlorvos (DDVP), naled and trichlorfon. In the event that
all of these pesticides are used in the same use area, then the
contribution for each chemical should be incorporated in any risk
assessment.

OPP does not have any surface water monitoring data on the
concentrations of dichlorvos, naled, or trichlorfon at the present time.
Therefore, the Tier II PRZM/EXAMS model was used for dichlorvos, naled
and trichlorfon. The turf scenario with the Index Reservoir and Percent
Crop Area adjustment (IR‑PCA PRZM/EXAMS) was used to estimate surface
water concentrations for trichlorfon.

The results from the index reservoir represent potential drinking water
exposure from a specific area (Illinois) with specific cropping
patterns, weather, soils, and other factors. Use of the index reservoir
for areas with different climates, crops, pesticides used, sources of
water (e.g. rivers instead of reservoirs, etc), and hydrogeology creates
uncertainties. In general, because the index reservoir represents a
fairly vulnerable watershed, the exposure estimated with the index
reservoir will likely be higher than the actual exposure for most
drinking water sources. However, the index reservoir is not a worst case
scenario; communities that derive their drinking water from smaller
bodies of water with minimal outflow, or with more runoff prone soils
would likely get higher drinking water exposure than estimated using the
index reservoir. Areas with a more humid climate that use a similar
reservoir and cropping patterns may also get more pesticides in their
drinking water than predicted using this scenario.

A single steady flow has been used to represent the flow through the
reservoir. Discharge from the reservoir also removes chemical so this
assumption will underestimate removal from the reservoir during wet
periods and overestimates removal during dry periods. This assumption
can underestimate or overestimate the concentration in the pond
depending upon the annual precipitation pattern at the site.

The index reservoir scenario uses the characteristics of a single soil
to represent the soil in the basin. In fact, soils can vary
substantially across even small areas, and this variation is not
reflected in these simulations.

The index reservoir scenario does not consider tile drainage. Areas that
are prone to substantial runoff are often tile drained. Tile drainage
contributes additional water and in some cases, additional pesticide
loading to the reservoir. This may cause either an increase or decrease
in the pesticide concentration in the reservoir. Tile drainage also
causes the surface soil to dry out faster. This will reduce runoff of
the pesticide into the reservoir. The watershed used as the model for
the index reservoir (Shipman City Lake) does not have tile drainage in
the cropped areas.

Turf was used as the site of interest for trichlorfon. General outdoor
uses were used as the site of interest for dichlorvos. Eight crops were
simulated for naled. The modeling results indicate that all these
compounds have the potential to contaminate surface waters by runoff,
for short periods of time especially in areas with large amounts of
annual rainfall. However, based on its environmental fate
characteristics, naled will degrade/dissipate rapidly (t~1/2~ \< 1 day),
trichlorfon and dichlorvos will persist slightly longer (t~1/2~ 1.4 and
\~ 5 days, respectively). Mitigation practices that reduce runoff could
be effective in reduction of these chemicals transport into surface
waters.

  -------------------------------- ------------------- -------------- --------------------
  **Table 6.2.3a. Estimated                                           
  Drinking Water Concentrations in                                    
  Surface Water for Dichlorvos,                                       
  Dichlorvos from Naled, and                                          
  Dichlorvos from Trichlorfon use                                     
  on Turf using Tier II                                               
  PRZM/EXAMS.**                                                       

                                   **model EDWCs                      
                                   (µg/L)**                           

                                   **Dichlorvos^1^**   **from         **from
                                                       Naled^2^**     Trichlorfon^3^\***

  **Surface water/ peak (90^th^    **3.46**            **33.0**       **60**
  percentile annual daily max. for                                    
  acute exposure analysis)**                                          

  **Surface water/ 90^th^          **0.17**            **1.83**       **1.56**
  percentile annual mean for                                          
  chronic exposure analysis**                                         

  **use(s) modeled**               **4 applications @  **5            **3 applications @
                                   0.20 lb ai/acre,    applications @ 8.2 lb ai/acre,
                                   spray appl.**       1.87 lb        spray appl.**
                                                       ai/acre, spray 
                                                       appl.**        

  **PCA**                          **0.87**                           
  -------------------------------- ------------------- -------------- --------------------

**^1^ Dichlorvos from wide area treatment**

**^2^ Naled from treatment of brassica crops**

**^3^ Trichlorfon turf treatment**

**\* Dichlorvos from trichlorfon is adjusted for a 25% conversion at pH
7, a pH typical of soils growing turf.**

The maximum amount of dichlorvos formed from naled is approximately 20%
of the applied naled. Therefore, a conservative dichlorvos use rate was
selected as naled's use rate multiplied by 0.20.

The application rate used on turf for trichlorfon based on 25 percent
conversion to dichlorvos adjusted for differences in MW. A maximum of
25% degradation of trichlorfon to dichlorvos was assumed because 25%
degradation was the maximum observed in a hydrolysis study at pH 7, a pH
typical of soils used to grow turf.

Table 6.2.3b shows the input parameters used in PRZM/EXAMS.

  ----------------------------- --------------- --------------- ----------------
  **Table 6.2.3b. Input                                         
  parameters for Dichlorvos,                                    
  Dichlorvos from Naled, and                                    
  Dichlorvos from Trichlorfon                                   
  used in PRZM/EXAMS models.**                                  

                                **Dichlorvos                    
                                Information**                   

  **Chemical**                  **From Naled**  **From          **Dichlorvos**
                                                Trichlorfon**   

  PC Code for parent chemical   34401           57901           84001

  Molecular weight (g/mole)     220.9           220.9           220.9

  Solubility (ppm)              10000           10000           10000

  Hydrolysis half-life, pH 7    5.2             5.2             5.2
  (days)                                                        

  Soil Photolysis half-life     0.65            0.65            0.65
  (days)                                                        

  Aerobic Soil Metabolism       0.42            0.42            0.42
  half-life (days)                                              

  Aerobic Aquatic Metabolism    no data         no data         no data
  half-life (days)                                              

  Soil Organic Carbon           37              37              37
  Partitioning (K~oc~)(l/kg)                                    

  Use                           Brassica        Turf            Wide Area
                                                                Treatment

  Application Rate (lb a.i.     1.87            8.2             0.20
  /acr/yr)                                                      

  Number Of Applications/year   5               3               4

  Interval between appl. (day)  30              7               30

  Application Method            Spray           Spray           Spray
  ----------------------------- --------------- --------------- ----------------

**6.2.4. Drinking Water Risk Estimates**

The Pesticide Data Program (PDP) in USDA-Agricultural Marketing Service
has sampled finished drinking water collected after disinfection, and
just before distribution to customers, from community water systems in a
few states from 2001 through 2004, and raw and finished drinking water
from community water systems in a few states in 2004. In 2001, PDP
analyzed 214 finished drinking water samples from CA and NY. In 2002 and
2003, PDP sampled 371 and 699 finished drinking water samples,
respectively, in CA, CO, KS, NY, and TX. In 2004, PDP sampled raw and
finished water from 171 community water systems from MI, NC, OH, OR, PA,
and WA. Dichlorvos was one of the analytes. No detectable residues of
dichlorvos were found at limits of detection (LOD) of 0.4 - 22.5
pptrillion. Naled and trichlorfon were not among the analytes tested,
but PDP would have detected dichlorvos coming from naled and
trichlorfon.

The PDP monitoring of water from community water systems does not
reflect the drinking water consumed by the population for the following
reasons:

\- The PDP samples large community water systems in a limited number of
states. The sampling sites are not necessarily in dichlorvos, naled, and
trichlorfon use areas, and the data may not be reflective of drinking
water concentrations in areas of high dichlorvos use.

\- The community water systems sampled by PDP are generally deep ground
water or surface water systems. The PDP does not sample individual,
private wells. Use of the PDP data would not be protective of people
whose drinking water source is a private well.

The Agency currently lacks sufficient water-related exposure data from
monitoring to complete a quantitative drinking water exposure analysis
and risk assessment for dichlorvos. Therefore, the Agency is presently
relying on computer-generated estimated environmental concentrations
(EDWCs). The Tier II PRZM/EXAMS model turf scenario with the Index
Reservoir and Percent Crop Area adjustment (IR‑PCA PRZM/EXAMS) was used
to generate EDWCs for surface water and SCI-GROW (an empirical model
based upon actual monitoring data collected for a number of pesticides
that serve as benchmarks) predicts EDWCs in ground water. These models
take into account the use patterns and the environmental profile of a
pesticide, but do not include consideration of the impact that
processing raw water for distribution as drinking water would likely
have on the removal of pesticides from the source water. The primary use
of these models by the Agency at this stage is to provide a coarse
screen for determining that pesticides residues (and metabolites) in
water are not of concern.

For any given pesticide, the SCI-GROW model generates a single EDWC for
pesticide concentration in ground water. That EDWC is used in
assessments of both acute and chronic dietary risk. It is not unusual
for the ground water EDWC to be significantly lower than the surface
water EDWCs. The tier II PRZM/EXAMS model provides long duration (up to
36-year) pesticide concentrations in surface water and is mainly used
when a refined EDWC is needed.

> **6.3 Residential (Non-Occupational) Exposure/Risk
> Pathway**[]{#__RefHeading___Toc137619518 .anchor}

Dichlorvos is registered for several residential uses. Residential
handlers may be exposed to dichlorvos during application of dichlorvos
in pressurized aerosol spray cans. Residential post application exposure
may occur after use of the following products containing dichlorvos:
pressurized aerosol spray can, resin pest strips, and pet flea collars.
Residential post application exposure to dichlorvos may also occur after
lawn treatment with trichlorfon. Residential Exposure and Risk Estimates
are summarized in Table 6.3 below. Information sources and major
assumptions for each residential scenario are described below, with
additional information in the table endnotes. Additional information is
available in the referenced documents (Jaquith D., 1993b, Jaquith D
1998a through n, Jaquith D. 1999 through d, Jaquith, D, 2000, and
Jaquith, D., 2001 and 2003). Dichlorvos exposure from the use of Naled
is covered by the Naled Risk Assessment. Dichlorvos exposure from the
use of trichlorfon is included in this document. Although residential
bystander exposure could result from the use of naled, both on field
crops and as a mosquitocide, any exposure to dichlorvos from the use of
naled would be covered by the Naled Risk Assessment.

Residential Scenarios which were evaluated were of acute, short term, or
long term duration. A BMDL~10~ of 0.8 mg/kg/day from a rat acute oral
cholinesterase study is used for the acute oral, dermal, and inhalation
risk assessment. An 11% dermal absorption is assumed for the dermal risk
assessment. The target MOE for residential acute risk assessments is
100.

A LOAEL of 0.1 mg/kg/day from a human 21-day oral study is used for
short term incidental oral, dermal, and inhalation (during application)
risk assessment. An 11% dermal absorption is assumed for the dermal risk
assessment. The target MOE for residential short term risk assessments
is 30.

A BMDL~10~ of 0.07 mg/m^3^ from a 2 year rat inhalation study is used
for the long term, post-application inhalation risk assessment. The
target MOE for residential long term inhalation risk assessment is 30.

> **6.3.1 Home Uses**[]{#__RefHeading___Toc137619519 .anchor}
>
> **6.3.1.1. Residential Handler**

**(a). Pressurized Aerosol Spray Can**

The exposure assessment for pressurized spray cans was derived from data
in the Pesticide Handlers Exposure Database (PHED V1.1) and the
Residential SOPs for aerosol application. Residential use of pressurized
aerosol product is based on application of 2 ounces from an aerosol can
of 0.5 percent dichlorvos (Jaquith 2001; Jaquith 1998f; REJV, 2002).
This is an acute exposure scenario.

Pressurized aerosol products containing dichlorvos do not list any
clothing requirements; therefore the Agency is assuming that dichlorvos
is applied during hot weather when an individual will be wearing the
least amount of clothing (i.e., shorts, short sleeve shirt, and shoes).
Using the Residential SOPs, unit dermal exposures were 220 mg/lb ai
handled, and 1.3 mg / lb ai handled for inhalation exposure (adjusted
for the NAFTA breathing rate of 1.0 m^3^/hr, with an absorbed dermal
dose of 0.00022 mg/kg/day. Respiratory exposure was estimated to be 1.2
x 10^-5^ mg/kg/day. The total exposure was 2.3 x 10^-4^ mg/kg/day, with
an MOE of 3500 (target MOE = 100), which is not of concern.

**6.3.1.2. Residential Post-application**

**(a). Pressurized Aerosol**

Post application data from a total release fogger application were used
as a surrogate for the post application exposure from pressurized
aerosol applications. The total release fogger treatments in the home
have been canceled. However the data are still being used to assess the
use of the aerosol spray, after adjustment for application rate.

Indoor residential post-application exposures for short term exposure
scenarios were derived from a single study measuring the exposures of
individuals performing defined activity patterns (20 minute
Jazzercise^®^ routine) following the activation of a total release
fogger, containing dichlorvos. This study provides a conservative
estimate for short term exposure scenarios from indoor applications of
dichlorvos (Jaquith 1993b). The multi-phase study measured deposition on
whole body dosimeters and (in a separate phase) the urinary
concentrations of the metabolite dimethyl phosphate (DMP), a metabolite
of dichlorvos. The biomonitoring gave estimates of exposure of 14 μg/kg.

In order to estimate the potential oral exposure from hand to mouth
activity of children, the amount of dichlorvos measured on the hands in
the passive dosimetry phase was considered to be available for
ingestion. The passive dosimetry dose on the hands had to be added
because the Jazzercise^®^ routine does not include hand-to-mouth
activity. The estimated exposure due to hand to mouth ingestion, was
0.61 μg/kg (Jaquith 1998k), or a total exposure of 15 μg/kg when the
potential oral component was included. This is considered to be a
short-term exposure scenario. This study only measured exposures to
adults; however, exposure to children is expected to be similar to that
of an adult.

For post-application exposure and risk estimates from the use of the
pressurized aerosol, it was assumed that there would be 2 oz of product
(containing 0.5% ai) used in a 1000 sq. ft. house (from the Residential
Exposure Joint Venture (REJV) survey (REJV, 2002)). This amount was
compared to the amount that was used for a total release fogger, and the
ratio used to adjust the amount of the biomonitoring study that was
conducted. The MOE was 100, which is not of concern, compared to the
target MOE of 30.

**(b). Resin Pest Strips**

Several sizes of resin pest strips are marketed. The full size, room
size strip is 65 or 80 g, containing 12.1 or 14.9 g of dichlorvos, used
to treat 1000 ft ^3^. The full size strip may no longer be used in
spaces occupied more than 4 hours per day. Examples of spaces which may
not be occupied more than 4 hours per day were attics, crawl spaces, and
garages. Other sizes of resin pest strips are the large closet strip, 16
g, containing 3.0 g dichlorvos; the small closet strip, 10.5 g,
containing 1.8 g dichlorvos, and the cupboard strip, 5.25 g, containing
0.97 g dichlorvos.

The dichlorvos label for the smaller size resin strips will have these
limitations.

> "Only available in the following sizes: 16 g (0.56 oz), 10.5 g (0.37
> oz), and 5.25 g (0.9 oz) pest strip sizes"
>
> *Household use*. "Use only in Closets, Wardrobes, and Cupboards. Do
> not use in areas of a home where people will be present for an
> extended period of time (e.g., Living Room, Family Room). Do not use
> in any rooms or closets of rooms where infants, children and the sick
> or aged are or will be present for any extended period of confinement.
> Do not use where unwrapped food is stored, or allow the strip to come
> into contact with food or cooking utensils. Do not allow children or
> pets to play or sleep in these areas when treatment is in progress."
>
> *Storage Units, Attics, Garages, Sheds, and Enclosed Crawl Spaces*.
> "Do not use in areas of a home where people will be present for an
> extended period of time. \[Keep\] out of reach of children and pets,
> in an open space of an enclosed area, away from windows."
>
> The largest pest strip, 100 g, will no longer be registered. The large
> 80 g and 65 g pest strips will be separated into a separate
> registration, where the label will state:
>
> "Only available in 65 g and 80 g pest strip sizes."
>
> "DIRECTIONS FOR USE" "For use in unoccupied areas, not for use in
> homes except garages, attics, crawl spaces, and sheds occupied for
> less than 4 hours per day.
>
> "Also for use in the following unoccupied structures, provided they
> are unoccupied for more than 4 months immediately following placement
> of a pest strip: vacation homes, cabins, mobile homes, boats, farm
> houses, and ranch houses."

Respiratory exposures resulting from the use of resin pest strips were
estimated using a study found in the scientific literature (Collins and
DeVries, 1973). Fifteen homes were monitored at various time intervals
for a period of 91 days. Air monitoring was done in one place in each of
the homes, in the same room with the full sized resin pest strip (80 or
100 g strips). A decay curve measuring the decline of airborne residues
was derived for each of these homes. The resulting equations were
integrated over a 91 day period and an average concentration was
calculated (Jaquith 1998a, 1999d, and 2000). The average air
concentration, over this time period was estimated to be 0.015 mg/m^3^.
Smaller sized resin strips placed in a closet or cupboard would be
expected to have lower concentrations by direct proportion, assuming
that the residue of dichlorvos in the air would equilibrate between the
closet or cupboard and the room.

Margins of Exposure were calculated for the resin pest strips using the
90 day average air concentration in the house (0.015 mg/m^3^) from a 65
-80 g pest strip containing 12.09 - 14.9 g dichlorvos in a 1000 ft^3^
room (Collins, R. D. and DeVries, D. M. 1973), and the BMDL~10~ from a
chronic rat inhalation study of 0.07 mg/m^3^, based on RBC
cholinesterase, and 23 hours of exposure. The margins of exposure will
vary, depending on the exposure time and the size of the pest strip, as
shown in Table 6.3.1.2. below.

+-----------------------+----------+---------+-----------+-----------+
| **Table 6.3.1.2.      |          |         |           |           |
| Exposures/MOEs for    |          |         |           |           |
| dichlorvos resin      |          |         |           |           |
| strips, based on size |          |         |           |           |
| of resin strip and    |          |         |           |           |
| time exposed**        |          |         |           |           |
|                       |          |         |           |           |
| BMDL~10~: 0.07        |          |         |           |           |
| mg/m^3^ for RBC       |          |         |           |           |
| cholinesterase from 2 |          |         |           |           |
| year rat inhalation   |          |         |           |           |
| study                 |          |         |           |           |
|                       |          |         |           |           |
| Exposure duration: 23 |          |         |           |           |
| hours per day, 7 days |          |         |           |           |
| a week                |          |         |           |           |
|                       |          |         |           |           |
| 90-day average        |          |         |           |           |
| concentrations of     |          |         |           |           |
| 0.015 mg/m^3^         |          |         |           |           |
|                       |          |         |           |           |
| Target MOE = 30       |          |         |           |           |
+-----------------------+----------+---------+-----------+-----------+
|                       |          |         |           |           |
+-----------------------+----------+---------+-----------+-----------+
|                       |          |         |           |           |
+-----------------------+----------+---------+-----------+-----------+
|                       |          |         |           |           |
+-----------------------+----------+---------+-----------+-----------+
|                       |          |         |           |           |
+-----------------------+----------+---------+-----------+-----------+
| Size of Resin Strip   | Full     | Closet  | Closet    | Cupboard  |
|                       | size     |         |           |           |
+-----------------------+----------+---------+-----------+-----------+
| g product             | 65       | 16      | 10.5      | 5.25      |
+-----------------------+----------+---------+-----------+-----------+
| g dichlorvos          | 12.09    | 3.0     | 1.95      | 0.975     |
+-----------------------+----------+---------+-----------+-----------+
| Hours exposed per day | Margin   |         |           |           |
|                       | of       |         |           |           |
|                       | Exposure |         |           |           |
|                       | (MOE)    |         |           |           |
+-----------------------+----------+---------+-----------+-----------+
| 1                     | 110      | 470     | 660       | 1300      |
+-----------------------+----------+---------+-----------+-----------+
| 2                     | 54       | 240     | 330       | 660       |
+-----------------------+----------+---------+-----------+-----------+
| 4                     | **27**   | 120     | 170       | 330       |
+-----------------------+----------+---------+-----------+-----------+
| 6                     | **18**   | 78      | 110       | 220       |
+-----------------------+----------+---------+-----------+-----------+
| 8                     | **13**   | 60      | 83        | 170       |
+-----------------------+----------+---------+-----------+-----------+
| 10                    | **11**   | 35      | 67        | 130       |
+-----------------------+----------+---------+-----------+-----------+
| 12                    | **9**    | 40      | 55        | 110       |
+-----------------------+----------+---------+-----------+-----------+
| 14                    | **8**    | 34      | 48        | 95        |
+-----------------------+----------+---------+-----------+-----------+
| 16                    | **7**    | **30**  | 42        | 83        |
+-----------------------+----------+---------+-----------+-----------+
| 18                    | **6**    | **26**  | 37        | 74        |
+-----------------------+----------+---------+-----------+-----------+
| 20                    | **5**    | **24**  | 33        | 67        |
+-----------------------+----------+---------+-----------+-----------+
| 22                    | **5**    | **21**  | **30**    | 60        |
+-----------------------+----------+---------+-----------+-----------+
| 24                    | **4**    | **20**  | **28**    | 55        |
+-----------------------+----------+---------+-----------+-----------+

The MOEs in table 6.3.1.2 are calculated as follows.

MOE = [0.07 mg/m^3^]{.underline} x [23 hr/day]{.underline} x [65 g
dichlorvos in full size strip]{.underline}

0.015 mg/m^3^ Hr exposed per day g dichlorvos in product

The dichlorvos label has been changed to allow use of resin strips in
areas occupied up to 4 hours per day (garages, attics, ...) . Although
this use would be allowed by the label, there is no expectation that
individuals will actually be exposed at this level routinely.

AMVAC has proposed a study to measure air concentrations from use of the
smaller resin strips in closets and cupboards. The study has been
required by California, but not EPA. A protocol was submitted by the
registrant to EPA and reviewed (Jaquith, 2003a). The Agency's comments
were provided to AMVAC. Some suggestions were made to improve the study,
including diagrams of the houses, placement of the air monitors, and
monitoring of fabric in the closets with a closet sized strip. To date,
the study has not been submitted to EPA.

**(c). Pet Flea Collars**

A flea collar is placed on the pet's neck to protect the pet from fleas
over the life of the collar. It is expected that the flea collar will be
replaced when it is no longer efficacious, which is assumed to be 120
days.

In this assessment, inhalation exposure was estimated for the flea
collars, considering them to be a mobile resin strip, because the
formulation is similar to the resin strip formulation. A dog collar,
containing 2.2 g dichlorvos, would contain (2.2/12.1) or 18 % of the
amount of dichlorvos contained in a full sized resin strip. The air
concentration in the room with the pet is estimated to average 0.0027
mg/m^3^ for 8 hours per day.

In addition, dermal exposure and children's hand-to-mouth exposure
assessments were done, using a draft ExpoSAC policy. The calculations
for the assessment are shown in the footnote for table 6.3. The dermal
exposure was estimated to contribute 0.0011 mg/kg/day and hand-to-mouth
exposure was estimated to be 0.0001 mg/kg/day.

Combining the dermal and hand‑to‑mouth exposure results in an exposure
estimate of 0.0012 mg/kg/day, and an MOE of 83. The inhalation MOE is
74, and the total MOE is 39, which is greater than the target MOE of 30,
and not of concern.

**(d). Lawns and Turf - Post-Application**

**[Dichlorvos from the use of Naled.]{.underline}** Naled is used as a
mosquitocide, and may result in residues on home lawns. This use was
considered in the Naled Risk Assessment.

**[Dichlorvos from the use of Trichlorfon]{.underline}. P**ost
application exposure to dichlorvos from the use of trichlorfon has been
assessed. (Leighton, T., 2000). This is a short-term exposure scenario.
Trichlorfon is applied to home lawns at 8.2 lb ai/acre as a granular
formulation, which is watered in with 0.25\" water. The assessment for
dichlorvos from trichlorfon use utilized an environmental fate model to
predict residues of a parent and a metabolite, based on the trichlorfon
half-life from a trichlorfon turf transferable residue study (TTR) and
the dichlorvos half-lives from a turf transferable residue study for
dichlorvos. The turf assessment has been modified to assume 25%
degradation of trichlorfon to dichlorvos, based on the 25% maximum
conversion in a hydrolysis study of trichlorfon at pH 7, a pH typical of
home lawns. Trichlorfon degrades less at lower pH's and up to 50% at pH
8.4 (Jones, R. D., 2006).

Hand-to-mouth residues were estimated using the Residential SOPs.
Trichlorfon was applied at 8.1 lb ai/A (registered rate is 8.2 lb ai/a).
The initial TTR of trichlorfon was 0.0829 μg/cm^2^. Exposure from
hand-to-mouth activity for toddlers was added to arrive at total
estimated exposure. The maximum amount of dichlorvos was estimated to
occur 11 hours after application. (Leighton, 2000). Toddler dermal plus
hand to mouth MOEs ranged from 430 to 710, compared to a target MOE of
30.

Inhalation exposure from this scenario could not be assessed, because
air concentrations in the breathing zone of toddlers were not provided
in the trichlorfon study. For comparison purposes, inhalation estimates
from the equivalent dichlorvos dermal exposure is provided in the table.
These inhalation exposure estimates are expected to overestimate
inhalation exposure because of differences in the application method
between dichlorvos and trichlorfon, and because the maximum dichlorvos
formed was predicted to occur 11 hours after application. "Wetting in"
the trichlorfon granules is expected to reduce the amount of dichlorvos
available for volatilization (Jones, R. D., 2006).

A trichlorfon TTR study with analyses for dichlorvos in the turf and in
the toddler breathing zone above the turf (18\") is being requested to
confirm these exposure estimates. The study must be conducted at an
appropriate pH (approx. 7). A field dissipation study may be
substituted, provided it meets these requirements.

> **6.3.2 Recreational Uses**[]{#__RefHeading___Toc137619520 .anchor}

The dichlorvos and trichlorfon turf uses could also be recreational
uses. They are addressed above in Section 6.3.1 Home uses. The same
exposures would be expected for recreational uses as home lawn uses.

> **6.3.3 Other (Spray Drift, etc.)**[]{#__RefHeading___Toc137619521
> .anchor}

**Spray drift is always a potential source of exposure to residents
nearby to spraying operations. This is particularly the case with aerial
application, but, to a lesser extent, could also be a potential source
of exposure from ground application methods. However, there are no field
crop applications employed for dichlorvos. The Agency has been working
with the Spray Drift Task Force, EPA Regional Offices and State Lead
Agencies for pesticide regulation and other parties to develop the best
spray drift management practices. On a chemical by chemical basis, the
Agency is now requiring interim mitigation measures for aerial
applications that must be placed on product labels/labeling. The Agency
has completed its evaluation of the new data base submitted by the Spray
Drift Task Force, a membership of U.S. pesticide registrants, and is
developing a policy on how to appropriately apply the data and the
AgDRIFT computer model to its risk assessments for pesticides applied by
air, orchard airblast and ground hydraulic methods. After the policy is
in place, the Agency may impose further refinements in spray drift
management practices to reduce off‑target drift with specific products
with significant risks associated with drift.**

+-----------------+----+---------+-----+--------+-----+---+-----+-----+
| **Table 6.3.    |    |         |     |        |     |   |     |     |
| Summary of      |    |         |     |        |     |   |     |     |
| Residential     |    |         |     |        |     |   |     |     |
| Exposure and    |    |         |     |        |     |   |     |     |
| Risk Estimates  |    |         |     |        |     |   |     |     |
| for             |    |         |     |        |     |   |     |     |
| Dichlorvos**    |    |         |     |        |     |   |     |     |
+=================+====+=========+=====+========+=====+===+=====+=====+
| **USES**        | *  | **EXP   | **C |        |     | * |     | *   |
|                 | *N | OSURE** | urr |        |     | * |     | *MO |
|                 | OT |         | ent |        |     | C |     | E** |
|                 | ES | **PATTE | Ex  |        |     | u |     |     |
|                 | ** | RN^1^** | pos |        |     | r |     |     |
|                 |    |         | ure |        |     | r |     |     |
|                 |    |         | (   |        |     | e |     |     |
|                 |    |         | mg/ |        |     | n |     |     |
|                 |    |         | kg/ |        |     | t |     |     |
|                 |    |         | day |        |     | M |     |     |
|                 |    |         | )** |        |     | O |     |     |
|                 |    |         |     |        |     | E |     |     |
|                 |    |         |     |        |     | * |     |     |
|                 |    |         |     |        |     | * |     |     |
+-----------------+----+---------+-----+--------+-----+---+-----+-----+
|                 |    |         | *   | **     | **T | * | **  | **T |
|                 |    |         | *De | Inhala | ota | * | Inh | ota |
|                 |    |         | rma | tion** | l** | D | ala | l** |
|                 |    |         | l** |        |     | e | tio |     |
|                 |    |         |     |        |     | r | n** |     |
|                 |    |         |     |        |     | m |     |     |
|                 |    |         |     |        |     | a |     |     |
|                 |    |         |     |        |     | l |     |     |
|                 |    |         |     |        |     | * |     |     |
|                 |    |         |     |        |     | * |     |     |
+-----------------+----+---------+-----+--------+-----+---+-----+-----+
| **RESIDENTIAL   |    |         |     |        |     |   |     |     |
| EXPOSURE** All  |    |         |     |        |     |   |     |     |
| Target MOEs for |    |         |     |        |     |   |     |     |
| all Residential |    |         |     |        |     |   |     |     |
| Scenarios are   |    |         |     |        |     |   |     |     |
| 30, except for  |    |         |     |        |     |   |     |     |
| acute dermal    |    |         |     |        |     |   |     |     |
| and handler     |    |         |     |        |     |   |     |     |
| exposure        |    |         |     |        |     |   |     |     |
| scenarios,      |    |         |     |        |     |   |     |     |
| where the       |    |         |     |        |     |   |     |     |
| target MOE is   |    |         |     |        |     |   |     |     |
| 100.            |    |         |     |        |     |   |     |     |
+-----------------+----+---------+-----+--------+-----+---+-----+-----+
| **RESIDENTIAL   | 2  |         |     |        |     |   |     |     |
| HANDLER**       |    |         |     |        |     |   |     |     |
+-----------------+----+---------+-----+--------+-----+---+-----+-----+
| **(a)           | 3  | Acute   | 0   | 0.     | 0   | 3 | 67  | 3   |
| Pressurized     |    |         | .00 | 000012 | .00 | 6 | 000 | 500 |
| aerosol spray   |    |         | 022 |        | 023 | 0 |     |     |
| can**           |    |         |     |        |     | 0 |     |     |
+-----------------+----+---------+-----+--------+-----+---+-----+-----+
| **RESIDENTIAL   |    |         |     |        |     |   |     |     |
| POS             |    |         |     |        |     |   |     |     |
| T-APPLICATION** |    |         |     |        |     |   |     |     |
+-----------------+----+---------+-----+--------+-----+---+-----+-----+
| **(a)           | 4  | Sho     | D   |        | 0   |   |     | 100 |
| Pressurized     |    | rt-term | ose |        | .00 |   |     |     |
| aerosol         |    |         | is  |        | 098 |   |     |     |
| (toddler)**     |    |         | 0   |        |     |   |     |     |
|                 |    |         | .90 |        |     |   |     |     |
| **Same rate as  |    |         | μg/ |        |     |   |     |     |
| fogger**        |    |         | kg/ |        |     |   |     |     |
|                 |    |         | day |        |     |   |     |     |
| **Adjusted      |    |         | ba  |        |     |   |     |     |
| rate**          |    |         | sed |        |     |   |     |     |
|                 |    |         | on  |        |     |   |     |     |
|                 |    |         | u   |        |     |   |     |     |
|                 |    |         | rin |        |     |   |     |     |
|                 |    |         | ary |        |     |   |     |     |
|                 |    |         | di  |        |     |   |     |     |
|                 |    |         | met |        |     |   |     |     |
|                 |    |         | hyl |        |     |   |     |     |
|                 |    |         | ph  |        |     |   |     |     |
|                 |    |         | osp |        |     |   |     |     |
|                 |    |         | hat |        |     |   |     |     |
|                 |    |         | e + |        |     |   |     |     |
|                 |    |         | i   |        |     |   |     |     |
|                 |    |         | nci |        |     |   |     |     |
|                 |    |         | den |        |     |   |     |     |
|                 |    |         | tal |        |     |   |     |     |
|                 |    |         | o   |        |     |   |     |     |
|                 |    |         | ral |        |     |   |     |     |
|                 |    |         | of  |        |     |   |     |     |
|                 |    |         | 0.  |        |     |   |     |     |
|                 |    |         | 038 |        |     |   |     |     |
|                 |    |         | μg/ |        |     |   |     |     |
|                 |    |         | kg/ |        |     |   |     |     |
|                 |    |         | day |        |     |   |     |     |
+-----------------+----+---------+-----+--------+-----+---+-----+-----+
| **(b) Resin     | 5  | Lon     | N/A | 0.015  |     |   | 27  | 27  |
| pest strips**   |    | g-term, |     | mg     |     |   |     |     |
|                 |    | Inh     | N/A | /m^3^. |     |   | 34  | 34  |
| **Full size     |    | alation |     |        |     |   |     |     |
| strip 65 g (4   |    |         | N/A | 0.0048 |     |   | 48  | 48  |
| hr exposure)**  |    |         |     | mg     |     |   |     |     |
|                 |    |         | N/A | /m^3^. |     |   | 95  | 95  |
| **Smaller       |    |         |     |        |     |   |     |     |
| strips (14 hr   |    |         |     | 0.0024 |     |   |     |     |
| exposure)**     |    |         |     | m      |     |   |     |     |
|                 |    |         |     | g/m^3^ |     |   |     |     |
| **Closet strip  |    |         |     |        |     |   |     |     |
| 16 g**          |    |         |     | 0.0012 |     |   |     |     |
|                 |    |         |     | mg     |     |   |     |     |
| **Small Closet  |    |         |     | /m^3^. |     |   |     |     |
| strip 10.5g**   |    |         |     |        |     |   |     |     |
|                 |    |         |     |        |     |   |     |     |
| **Cupboard      |    |         |     |        |     |   |     |     |
| strip 5.25g**   |    |         |     |        |     |   |     |     |
+-----------------+----+---------+-----+--------+-----+---+-----+-----+
| **(c) Pet flea  | 6  | Lo      | 0.0 | 0.     |     | 8 | 74  | 39  |
| collars**       |    | ng-term | 012 | 000949 |     | 3 |     |     |
|                 |    |         |     | m      |     |   |     |     |
| **t             |    |         |     | g/m^3^ |     |   |     |     |
| oddler(includes |    |         |     |        |     |   |     |     |
| h               |    |         |     |        |     |   |     |     |
| and-to-mouth)** |    |         |     |        |     |   |     |     |
+-----------------+----+---------+-----+--------+-----+---+-----+-----+
| **(d) Lawns,    | 7  | A       |     |        |     |   |     |     |
| Trichlorfon use |    | lthough |     |        |     |   |     |     |
| 8.1 lb ai/A     |    | inh     |     |        |     |   |     |     |
| Pos             |    | alation |     |        |     |   |     |     |
| t-application** |    | e       |     |        |     |   |     |     |
|                 |    | xposure |     |        |     |   |     |     |
|                 |    | is not  |     |        |     |   |     |     |
|                 |    | as      |     |        |     |   |     |     |
|                 |    | sessed, |     |        |     |   |     |     |
|                 |    | rough   |     |        |     |   |     |     |
|                 |    | es      |     |        |     |   |     |     |
|                 |    | timates |     |        |     |   |     |     |
|                 |    | were    |     |        |     |   |     |     |
|                 |    | made by |     |        |     |   |     |     |
|                 |    | com     |     |        |     |   |     |     |
|                 |    | parison |     |        |     |   |     |     |
|                 |    | with    |     |        |     |   |     |     |
|                 |    | dic     |     |        |     |   |     |     |
|                 |    | hlorvos |     |        |     |   |     |     |
|                 |    | turf    |     |        |     |   |     |     |
|                 |    | study,  |     |        |     |   |     |     |
|                 |    | which   |     |        |     |   |     |     |
|                 |    | we      |     |        |     |   |     |     |
|                 |    | expect  |     |        |     |   |     |     |
|                 |    | to      |     |        |     |   |     |     |
|                 |    | result  |     |        |     |   |     |     |
|                 |    | in an   |     |        |     |   |     |     |
|                 |    | over-e  |     |        |     |   |     |     |
|                 |    | stimate |     |        |     |   |     |     |
|                 |    | of the  |     |        |     |   |     |     |
|                 |    | e       |     |        |     |   |     |     |
|                 |    | xposure |     |        |     |   |     |     |
|                 |    | & risk. |     |        |     |   |     |     |
+-----------------+----+---------+-----+--------+-----+---+-----+-----+
| **Toddler -     |    | Sho     | 0   | not    |     | 4 | \   |     |
| high end**      |    | rt-term | .00 | as     |     | 3 | (10 |     |
|                 |    | (adding | 023 | sessed |     | 0 | 0\) |     |
|                 |    | inc     |     |        |     |   |     |     |
|                 |    | idental |     |        |     |   |     |     |
|                 |    | oral of |     |        |     |   |     |     |
|                 |    | 0.0004  |     |        |     |   |     |     |
|                 |    | mg      |     |        |     |   |     |     |
|                 |    | /kg/day |     |        |     |   |     |     |
+-----------------+----+---------+-----+--------+-----+---+-----+-----+
| **Toddler - low |    |         | 0   | not    |     | 7 | \   |     |
| end**           |    |         | .00 | as     |     | 1 | (15 |     |
|                 |    |         | 014 | sessed |     | 0 | 0\) |     |
+-----------------+----+---------+-----+--------+-----+---+-----+-----+

NOTES: The following notes define the assumptions used in calculating
the margins of exposure.

Risk is expressed as a Margin of Exposure (MOE)

MOE = [NOAEL]{.underline} , where both the NOAEL and the Exposure are
expressed in common units

Exposure

1\. Doses and toxicological endpoints for assessment of short term
dermal, incidental oral and inhalation (applicator) residential risks
are based on an oral LOAEL of 0.1 mg/kg/day from a human 21-day repeated
dose study. A dermal absorption factor of 11% was used in assessing
risks from dermal exposure. The applicator is assumed to weigh 70 kg.
The target MOE for these scenarios is 30 (10x for intraspecies
variability, 3x for use of the LOAEL).

> Doses and toxicological endpoints for assessing risks from long-term
> inhalation of dichlorvos vapors are based on an inhalation BMDL~10~ of
> 0.07 mg/m^3^ from a 2 year rat inhalation study. The target MOE for
> this scenario is 30 (10x for intraspecies variability, 3x for
> interspecies extrapolation).
>
> Acute Dermal and Inhalation endpoints are based on the 0.8 mg/kg/day
> BMDL~10~ from a rat acute oral cholinesterase study, with an 11%
> dermal absorption factor for the dermal exposure. The target MOEs are
> 100 (10x for interspecies extrapolation, and 10x for intraspecies
> variability)

2\. Residential handler assumptions. An average resident applicator
weighs 70 kg and has a respiratory volume of 1.0 m^3^ /hour (NAFTA value
for moderate activity). Assume applicator wears short pants, short
sleeves, and no gloves.

3\. Pressurized aerosol spray - residential handler. Residential use of
pressurized aerosol product is based on application of 2 ounces of 0.5
percent dichlorvos pressurized aerosol (0.00063 lb ai). Pressurized
aerosol products containing dichlorvos do not have any clothing
requirements; therefore EPA is assuming that dichlorvos is applied
during hot weather when an individual will be wearing only shorts, short
sleeve shirt, and shoes. From the Residential SOPs unit dermal exposures
are 220 mg/lb ai handled, and 1.3 mg / lb ai handled for inhalation
exposure (after correction for the NAFTA breathing rate). The risk
assessment is based on application by a 70 kg resident applicator.
(Jaquith, 2001).

> Dermal exposure = 220 mg/lb ai handled x 0.005 x 2 oz/16 oz/lb x 0.11
> (dermal absorption factor) ÷ 70 kg = 0.00022 mg/kg/day

Inhalation Exposure = 1.3 mg/lb ai x 0.000625 lb ai ÷ 70 kg = 1.2 E-5
mg/kg/day

> Total exposure = 0.00022 + 0.000012 = 0.00023 mg/kg/day

Total MOE = 0.8/0.00023 = 3500

4\. Pressurized Aerosol - Post application. The assessment is based on
biomonitoring data (urinary excretion of DMP from exposure to
dichlorvos) from the use of the Total Release Fogger and represents the
total dose to the individual from all routes. To account for children's
hand-to-mouth exposure, an estimate of incidental oral exposure was
obtained by assuming that all material on hands (from passive dosimetry
data) is available for ingestion. (Jaquith, 1998k) The oral exposure
from passive dosimetry is added to the dermal exposure from
biomonitoring. (Jaquith, 1993b) Children, performing the same activities
as adults were considered to have the same exposure as an adult on a mg
per kg basis.

Total Exposure (μg/kg/day) = Biomonitoring Exposure ( μg/kg/day) +
Hand-to-mouth Exposure ( μg/kg)

= 15 μg/kg/day + 0.61 μg/kg = 16 μg/kg

In the biomonitoring study, an average of 1.7 mg dichlorvos was released
into a room of 16.8 m^2^

A lower application rate is used for the pressurized aerosol, compared
to the total release fogger. The risk assessment is done by using the
results of the biomonitoring study, and the ratio of the application
rate expected to be used for the pressurized aerosol to the rate that
was used in the biomonitoring study.

The 2 oz application rate for the pressurized aerosol in a typical 1000
sq ft house is from the REJV data.

Application rate for aerosol = [2 oz x 0.5%]{.underline} = 6.2 x 10^-7^
lb/ sq. ft.

16 oz x 1000 ft^2^

Application rate in biomonitoring study = [0.77 g
dichlorvos]{.underline} = 9.9 x 10^-6^ lb/sq. ft.

16.8 m^2^ x (3.2 ft /m) ^2^ x 454 g/lb

Ratio of application rates = [6.2 x 10^-7^ lb/ sq. f]{.underline}t. =
0.063

9.9 x 10^-6^ lb/sq. ft

Total Exposure incl. Hand-to-mouth = 15.6 μg/kg/day x 0.063 = 0.98
μg/kg/day

MOE = [0.1 mg/kg/day]{.underline} = 100 (Target = 30)

0.00098 mg/kg/day

5\. Resin Strips MOEs were based on the average air concentration (0.015
mg/m^3^) in 15 houses over a 90-day period (Collins and DeVries 1973, in
Jaquith 1998h) and the BMDL~10~ of 0.07 mg/m^3^ from 2 year rat
inhalation study. Exposure estimates are adjusted to 14 hours in the
house. Exposure estimates for smaller resin strips assume air
concentrations are proportional to the weight of the ai in the strip.
The target MOE for inhalation exposure is 100.

> MOE (full sized strips) = 0.07/0.015 x 23 hr exposure/14 hr = 8

Table 6.3.1.2 shows Exposures and MOEs for different exposure times to
different sizes of resin pest strips.

6\. Inhalation assessment assumes that a flea collar is like a mobile
resin strip, and the resident spends 8 hours per day in the room with
the pet. The air concentration is obtained by proportion based on the
ratio of ai in the collar to the ai in the full sized resin strip. MOEs
for many different times of exposure are found in Table 6.3.1.2.

> A full size resin strip of 65 g (12.09 g ai) results in an air
> concentration of 0.015 mg/m^3^. The point of departure (POD) is 0.07
> mg/m^3^ from 23 hours of exposure. The inhalation exposure is

0.015 mg/m^3^ x [2.2 g dichlorvos]{.underline} x [8 hr]{.underline} =
0.000949 mg/m^3^

12.09 g ai 23 hr The MOE is 0.07 mg/m^3^ / 0.000949 mg/m^3^ = 74

> Dermal exposure is estimated as follows from draft ExpoSAC policy

The amount of dichlorvos available per dog per day is 2.2 g in the
collar, divided by the 120 days that the collar is effective, 2.2 g x
1000 mg/g/120 days = 18.3 mg/dog/day.

The draft ExpoSAC policy assumes 20% of the residue is transferrable,
but a carbaryl study (MRID 45792201) showed 2.6% transferrable.

[18.3 mg/dog/day x .026 transferrable]{.underline} = 0.00008 mg/ cm^2^
transferrable residue

5986 cm^2^ surface area on a 30 lb dog

A child is assumed to hug a dog and contact 1875 cm^2^ of the dog's fur.
The dermal absorption is 11%. A toddler is assumed to weigh 15 kg.

[0.00008 mg/ cm^2^ transferrable residue x 1875 cm^2^ x .11 dermal
absorption factor]{.underline} = 0.0011 mg/kg/day

15 kg child

> For the hand-to-mouth component, 1 event per hour is assumed. The
> surface area of a child's hand which goes into the mouth is 20 cm^2^ .
> The child is assumed to play with the dog for 2 hours per day. The
> saliva extraction factor is 50%.

[0.00008 mg/ cm^2\ ^]{.underline} x[1 event/hr x 20 cm^2^ x 0.5 x 2
hr/day]{.underline} = 0.0001 mg/kg/day

15 kg child

Combining the dermal and hand-to-mouth exposure results in an exposure
estimate of 0.0012 mg/kg/day, and an MOE of 83

> 7\. The calculations for incidental oral and dermal exposure to
> children playing on turf have been updated to be consistent with the
> revised Residential SOPs. Activities on the lawn are assumed to start
> 1 hour or more after spraying, and last 2 hours per day.
>
> The assessment for dichlorvos from trichlorfon use relied on the
> dichlorvos half‑lives from the same TTR study for dichlorvos,
> trichlorfon total transferable residues (TTR) residues from a
> trichlorfon DFR study, and the Residential SOPs. TTRs of dichlorvos
> were estimated using the calculated half‑lives of trichlorfon and
> dichlorvos (0.53 hours- 3.7 hours). The calculations were done using a
> spreadsheet‑based model developed by EFED to estimate the decay rate
> of a chemical and its degradate applied to short grass for single or
> multiple applications. The initial trichlorfon concentration was
> derived from a Trichlorfon TTR study. A first order decay assumption
> is used to determine the concentration at each day after initial
> application based on the concentration resulting from the initial and
> additional applications. Exposure from hand‑to‑mouth activity for
> toddlers was added to arrive at total estimated exposure. (Leighton,
> 2000). The formulas are presented below. (a) is the exponential form,
> and (b) is the log transformed versions.
>
> \(a\) C~pT~ = C~pi~e^-k1T^
>
> \(b\) In (C~pT~/C~pi~) = k~1~T
>
> For the degradate C~d~, = (k~1~C~pi~)e^-k1T^ -e^-k2T^)/(k~2~k~1~)
>
> Where:
>
> C~pT~ = parent concentration at time T = day T.
>
> C~pi~ = parent concentration at time T = day zero (0.0138 bcg/cn from
> trichiorton HR study; MRID 45067201).
>
> k~1~ = parent degradation rate constant determined from the
> trichlorfon TTR study using half life data of 0.93 and 2.5 days (MRID
> 45067201).
>
> k~2~ = DDVP degradation rate constant determined from the DDVP TTR
> studies using a half life of 0.156 days (MRIDs 44591901, 44610501, and
> 44794901).
>
> The high end exposure (daily dermal dose) for dichlorvos from
> trichlorfon, adjusting for 25% conversion to dichlorvos was 0.00019
> mg/kg/day. Hand-to-mouth exposure was 0.00004 mg/kg/day, totaling
> 0.00023 mg/kg/day.
>
> This results in an MOE of [BMDL~10~]{.underline} = [0.8
> mg/kg/day]{.underline} = 3500
>
> Exposure 0.00023 mg/kg/day
>
> The inhalation MOEs presented in the table are based on the ratio of
> the dermal exposure to dichlorvos after treatment of dichlorvos to the
> dermal exposure to dichlorvos after treatment with trichlorfon. These
> estimates are expected to overestimate the exposure and risk.

**7.0 Aggregate Risk Assessments and Risk
Characterization**[]{#__RefHeading___Toc137619522 .anchor}

The Food Quality Protection Act amendments to the Federal Food, Drug,
and Cosmetic Act (FFDCA, Section 408(b)(2)(A)(ii)) require that for
establishing a pesticide tolerance \"that there is reasonable certainty
that no harm will result from aggregate exposure to pesticide chemical
residue, including all anticipated dietary exposures and other exposures
for which there are reliable information.\" Aggregate exposure is the
total exposure to a single chemical (or its residues) that may occur
from all sources. Typically these are dietary (i.e., food, and drinking
water), residential and other non‑occupational sources, and from all
known or plausible exposure routes (oral, dermal and inhalation).

In an aggregate assessment, estimated exposures from relevant sources
are added together and compared to quantitative estimates of hazard
(e.g., a NOAEL, LOAEL, BMDL, or PAD), or the risks themselves can be
aggregated. When aggregating estimated exposures and risks from various
sources, HED considers both the route and duration of exposure.
Aggregate risk assessments are typically conducted for acute (1 day),
short‑term (1‑30 days), intermediate‑term (30 days to 6 months), and
chronic (6 months to lifetime) exposure.

Dichlorvos residues may be present in water and/or food as a result of
use of three pesticides: dichlorvos (DDVP), naled, and trichlorfon.
Dichlorvos is a degradate of naled and trichlorfon. The Environmental
Fate and Effects Division (EFED) evaluated the potential for dichlorvos
to contaminate water from these sources. The environmental fate
properties of dichlorvos, naled, and trichlorfon are an indicator of the
potential of these compounds to migrate to ground or surface water. EFED
has limited monitoring data on the concentrations of dichlorvos, naled,
or trichlorfon in groundwater. Validated monitoring data for dichlorvos,
naled, and trichlorfon are available for the states of California and
Hawaii from the Pesticides in Groundwater Database, and from a few other
states in the PDP. These data indicated that neither naled, dichlorvos,
nor trichlorfon, have been detected in groundwater nor drinking water;
however, these data were not targeted to the pesticide use area. OPP
does not have sufficient ground or surface water monitoring data on the
concentrations of dichlorvos, naled, or trichlorfon at the present time.
Therefore, the Tier I screening model SCI-GROW was used to estimate
ground water concentrations for naled, trichlorfon and dichlorvos. The
Tier II PRZM/EXAMS model was used to estimate drinking water
concentrations from surface water.

A probabilistic acute dietary exposure assessment was conducted without
the water contribution. The chronic dietary exposure assessment was also
conducted without the water contribution. Sufficient water modeling data
were available to use for probabilistic assessment if needed.

For residential exposure and risk assessment, deterministic exposure
assessments were done. Exposure estimates for a number of occupational
and residential scenarios were derived from limited data from the
scientific literature, textbooks, and knowledge of cultural practices.
Other estimates, particularly in the residential environment, were
derived from chemical specific monitoring data, including biomonitoring,
in combination with models and literature studies.

The route of exposure which results in the greatest exposure to
residents depends on the use pattern. For resident applicators and
reentry after use of an aerosol spray, the dermal route of exposure
results in the highest estimated risk. For the pest strip and reentry
onto lawns, the inhalation risk is estimated to be the highest. In
general, the residential risks are estimated to be much higher than food
and water combined.

Drinking Water Levels of Comparison (DWLOCs). For dichlorvos (and most
pesticide active ingredients), water monitoring data are considered
inadequate to determine surface and ground water drinking water exposure
estimates, so model estimates have been used to estimate residues in
drinking water (Estimated Drinking Water Concentrations, or EDWCs, see
Table 6.2.3a and 6.2.3b). In order to determine if aggregate risks are
of concern, HED then calculates drinking water levels of comparison, or
DWLOCs. The DWLOC is the maximum amount of a pesticide in drinking water
that would be acceptable in light of combined exposure from food and
residential pathways. The calculated DWLOCs are then compared to the
EDWCs provided by EFED; if model-derived EDWCs exceed the DWLOCs for
surface or ground water, there may be a concern for exposure to residues
in drinking water.

HED has calculated drinking water levels of comparison (DWLOCs)
associated with acute and chronic exposure to dichlorvos in drinking
water. These DWLOCs are compared with the estimated drinking water
concentrations (EDWCs) of dichlorvos in water.

> **7.1 Acute Aggregate Risk**[]{#__RefHeading___Toc137619523 .anchor}

The acute aggregate risk estimate to dichlorvos includes exposures from
food and drinking water. Although there are several acute residential
exposure scenarios, these will be included in the short term aggregate
risk assessment because it is highly unlikely that high exposure from
food, water, and residential use will co-occur. For the highly refined
acute probabilistic dietary exposure analysis, PDP and FDA monitoring
data and FDA TDS data were used to the greatest extent possible, along
with field trial data, cooking and processing factors, and degradation
studies to assess dietary exposures.

The acute DWLOC for dichlorvos includes aggregate exposure from food and
water only. The DWLOC~acute~ was calculated for the general population,
All Infants, Children (1-6 years) who are the most highly exposed
population subgroup, and for females (13-50 years). Acute water
exposures and DWLOC calculations are summarized in Table 7.2.4.1. below.

DWLOC~acute~ (μg/L) = [acute drinking water exposure (mg/kg/day) x body
weight (kg)]{.underline}

> Water consumption (L/day) x (10^-3^ mg/μg)

where body weight is 70 kg for adults, 60 kg for females (13-50) and 15
kg for children and water consumption is 2 L per day for adults and 1 L
per day for children.

acute water exposure = aPAD - acute food exposure

where aPAD is 0.008 mg/kg/day.

+-----------+---------------+---------+-------------+---------------+
| **Table   |               |         |             |               |
| 7.1.      |               |         |             |               |
| Summary   |               |         |             |               |
| of        |               |         |             |               |
| DWL       |               |         |             |               |
| OC~acute~ |               |         |             |               |
| Cal       |               |         |             |               |
| culations |               |         |             |               |
| for       |               |         |             |               |
| Dich      |               |         |             |               |
| lorvos.** |               |         |             |               |
+-----------+---------------+---------+-------------+---------------+
| **DEEM    | **Acute       | **Acute | **Allowable | **Maximum**   |
| P         | Dietary       | aPAD,   | Water       |               |
| opulation | Exposure to   | mg/k    | Exposure,   | **            |
| S         | Dichlorvos at | g/day** | mg/kg/day   | EDWC~acute~** |
| ubgroup** | 99.9^th^      |         | DW          |               |
|           | %tile,        |         | LOC~acute~, | **μg/L**      |
|           | mg/kg/day**   |         | μg/L**      |               |
+-----------+---------------+---------+-------------+---------------+
| **US      | **0.00014**   | **      | **280**     | **60**        |
| Pop       |               | 0.008** |             |               |
| ulation** |               |         |             |               |
+-----------+---------------+---------+-------------+---------------+
| **All     | **0.00031**   | **      | **120**     | **60**        |
| Infants** |               | 0.008** |             |               |
+-----------+---------------+---------+-------------+---------------+
| *         | **0.00033**   | **      | **120**     | **60**        |
| *Children |               | 0.008** |             |               |
| (1-6)**   |               |         |             |               |
+-----------+---------------+---------+-------------+---------------+
| **Females | **0.000085**  | **      | **240**     | **60**        |
| (13-50)** |               | 0.008** |             |               |
+-----------+---------------+---------+-------------+---------------+

For acute drinking water exposure, the modeled groundwater
concentrations of 0.0002 to 0.015 μg/L for dichlorvos resulting from the
use of dichlorvos, naled, and trichlorfon are not of risk concern, when
compared to the DWLOC~ACUTE~, shown above in Table 7.1. There is no risk
concern from the estimated drinking water concentration of dichlorvos in
surface water, resulting from the use of dichlorvos, of 3.46 μg/L, from
naled, of 33.0 μg/L, nor from trichlorfon, of 60 μg/L.

> **7.2 Short-Term Aggregate Risk**[]{#__RefHeading___Toc137619524
> .anchor}

The short‑term aggregate risk estimate includes chronic dietary (food
and water) from dichlorvos uses, and acute and short‑term
non‑occupational exposures (i.e., residential/recreational uses).

There are two short-term residential exposure scenarios which could be
aggregated with food and water: the application of the aerosol spray and
the resulting post-application exposure , and post-application exposure
to dichlorvos from turf treatment with trichlorfon. Since the exposures
from the aerosol spray and the exposures from treated lawns are so
short-lived (a week or less), it is extremely unlikely that an
individual would be exposed concurrently. Accordingly, two separate
aggregate scenarios are presented. It should be noted that the
contribution of food and water to the short-term aggregate risk is
considered to be negligible occupying less than one percent of the risk
cup. Consequently, the short-term aggregate risk is mainly a result of
the residential exposures presented in each of the scenarios.

The first scenario includes the residential use of the aerosol spray
can. Exposure from the application of the aerosol spray is considered to
be negligible (i.e., an MOE of 3500 was calculated vs. a target MOE of
100) with the majority of the exposure occurring post- application. The
MOE calculated from post-application exposures was 100 vs. the target
MOE of 30. When these residential exposures are combined (aggregated)
with the exposures from food and water and compared to the short-term
endpoint, our risk level of concern is not exceeded.

<table>
<colgroup>
<col style="width: 11%" />
<col style="width: 9%" />
<col style="width: 7%" />
<col style="width: 10%" />
<col style="width: 11%" />
<col style="width: 7%" />
<col style="width: 11%" />
<col style="width: 10%" />
<col style="width: 8%" />
<col style="width: 10%" />
</colgroup>
<tbody>
<tr class="odd">
<td colspan="10"><strong>Table 7.2. Short-Term Aggregate Risk and DWLOC
Calculations</strong></td>
</tr>
<tr class="even">
<td rowspan="2"><strong>Population</strong></td>
<td colspan="9"><p><strong><em>Short</em>-Term Scenario (post
application from spraying with an aerosol can)</strong></p>
<p><strong>Target MOE = 30</strong></p>
<p><strong>Short-term LOAEL = 0.1 mg/kg/day</strong></p></td>
</tr>
<tr class="odd">
<td><p><strong>Target Aggregate</strong></p>
<p><strong>MOE</strong></p></td>
<td><p><strong>MOE</strong></p>
<p><strong>Food<sup>1</sup></strong></p></td>
<td><strong>MOE residen-tial<sup>2</sup></strong></td>
<td><p><strong>Aggregate MOE</strong></p>
<p><strong>(food and residential)<sup>3</sup></strong></p></td>
<td><p><strong>MOE</strong></p>
<p><strong>Water<sup>4</sup></strong></p></td>
<td><p><strong>Allowable water exposure<sup>5</sup></strong></p>
<p><strong>(mg/kg/day)</strong></p></td>
<td><p><strong>Ground Water EDWC<sup>6</sup></strong></p>
<p><strong>(ppb)</strong></p></td>
<td><p><strong>Surface Water</strong></p>
<p><strong>EDWC<sup>6</sup></strong></p>
<p><strong>(<em>ppb</em>)</strong></p></td>
<td><p><strong>DWLOC<sup>7</sup></strong></p>
<p><strong>(µg/L)</strong></p></td>
</tr>
<tr class="even">
<td><strong>Adult Female</strong></td>
<td>30</td>
<td>330000</td>
<td>100</td>
<td>100</td>
<td>43</td>
<td>0.0023</td>
<td>0.01</td>
<td>1.83</td>
<td>69</td>
</tr>
<tr class="odd">
<td><strong>Child</strong></td>
<td>30</td>
<td>77000</td>
<td>100</td>
<td>100</td>
<td>43</td>
<td>0.0023</td>
<td>0.01</td>
<td>1.83</td>
<td>34</td>
</tr>
</tbody>
</table>

^1^ MOE food = \[(short or intermediate-term oral NOAEL)/(chronic
dietary exposure)\] = 0.1mg/kg/day/0.0000003 mg/kg/day for adult females
= 330000

= 0.1 mg/kg/day/0.0000013 mg/kg/day = 77000

^2^ MOE residential = \[(short or intermediate-term oral
NOAEL)/(residential exposure)\]

^3^ Aggregate MOE (food and residential) = 1÷\[ \[(1÷MOE food) + (1÷MOE
oral) + (1÷MOE dermal) + (1÷MOE inhalation)\]\]

^4^ Water MOE = 1÷ \[\[(1÷ Target Aggregate MOE) - (1÷Aggregate MOE
(food and residential)\]\]

^5^ Allowable water exposure = Short or Intermediate Term Oral NOAEL ÷
MOE water

^6^ The crop producing the highest level was used.

^7^ DWLOC(µg/L) = [\[allowable water exposure (mg/kg/day) x body weight
(kg)\]]{.underline}

\[water consumption (L) x 10-3 mg/µg\]

Where body weight = 15 kg for a child, and 60 kg for a woman.

The other scenario involves the post-application exposure to dichlorvos
from the use of trichlorfon on turf. As discussed previously, data from
trichlorfon are not available to calculate exposures resulting from this
use and the Agency has used available data and modeling from dichlorvos
to estimate these exposures. The MOEs calculated did not exceed our
level of concern (i.e., were greater than our target MOE of 30) and the
Agency expects that, given the negligible contribution from food and
water, short-term aggregate risks do not exceed our level of concern.
Data for the use of trichlorfon on turf will be required to confirm
these conclusions.

> **7.3 Intermediate-Term Aggregate
> Risk**[]{#__RefHeading___Toc137619525 .anchor}

The intermediate‑term aggregate risk estimate includes chronic dietary
(food and water) from dichlorvos uses, and intermediate‑term
non‑occupational exposures (i.e., residential/ recreational uses). There
are no residential/recreational uses with an intermediate‑term exposure
scenario. Therefore, intermediate‑term aggregate risks were not
evaluated.

> **7.4 Long-Term Aggregate Risk**[]{#__RefHeading___Toc137619526
> .anchor}

The long-term aggregate risk estimate for dichlorvos combines chronic
exposures from food, drinking water, and long-term residential
exposures. There are two long-term residential scenarios: resin strips
and pet (flea) collars. While it is possible that an individual could be
exposed concurrently to dichlorvos from the use of resin strips, have a
pet that wears a dichlorvos collar and consume food and drink water with
dichlorvos residues, the probability of these simultaneous exposures is
fairly low, especially considering the market share of these residential
uses. Consequently, two separate scenarios are discussed for long-term
aggregate risk.

The contribution of dichlorvos in food occupies less than one percent of
the risk cup for long-term exposure. When potential exposure to water is
added, approximately 23 percent of the risk cup is occupied leaving 77
percent (equating to an MOE of 39) for any additional exposures
resulting from residential use.

The first scenario considers the pet collar. As discussed previously in
this document, the Agency has made a number of conservative assumptions
in deriving a risk estimate for this use. Included in these assumptions
is that the pet collar acts as a miniature resin strip which results in
inhalation exposure proportional to that of larger resin strips and that
the pet is in the same room as an individual for 8 hours a day.
Additionally, exposures were calculated based on dermal contact (from
hugging and petting activities) as well as incidental oral (hand to
mouth) exposures exhibited by children. The inhalation MOE is calculated
to be 74 and the dermal and incidental oral MOE of 83 for a comined MOE
of 39 vs. our target MOE of 30. Therefore, the long-term aggregrate risk
does not exceed our level of concern given that this conservative
estimate from the pet collar does not exceed the amount left in the risk
cup after considering food and water.

The second scenario considers the largest resin strip. The registrant
recently voluntarily amended its registration to limit where these
strips can be used. No use will be permitted in living areas and the
labeling warns of exposure to the strips for more than 4 hours. The
Agency believes that given the location of where these strips may be
used (e.g., attics, crawl spaces, garages, etc), exposure times will be
much less than 4 hours a day and/or that daily exposure (repeated
exposure) may not be likely depending on the site of application (e.g.,
crawl spaces). Consequently, considering the room available in the risk
cup after consideration of food and water and that exposures are not
expected either daily or for significant periods of time, our risk of
concern is not exceeded from this long-term exposure scenario.

> **7.5 Aggregate Cancer Risk**[]{#__RefHeading___Toc137619527 .anchor}

No aggregate cancer risk assessment is needed. Dichlorvos shows
"suggestive" evidence of carcinogenicity under the 1999 Draft Agency
Cancer Guidelines. No quantitation is required. No aggregate cancer risk
assessment is required.

**8.0 Cumulative Risk
Characterization/Assessment**[]{#__RefHeading___Toc137619528 .anchor}

Section 408(b)(2)(D)(v) of the Federal Food, Drug, and Cosmetic Act
(FFDCA), as amended by the Food Quality Protection Act (1996) stipulates
that when determining the safety of a pesticide chemical, EPA shall base
its assessment of the risk posed by the chemical on, among other things,
available information concerning the cumulative effects to human health
that may result from dietary, residential, or other non‑occupational
exposure to other substances that have a common mechanism of toxicity.
The reason for consideration of other substances is due to the
possibility that low‑level exposures to multiple chemical substances
that cause a common toxic effect by a common mechanism could lead to the
same adverse health effect as would a higher level of exposure to any of
the other substances individually. A person exposed to a pesticide at a
level that is considered safe may in fact experience harm if that person
is also exposed to other substances that cause a common toxic effect by
a mechanism common with that of the subject pesticide, even if the
individual exposure levels to the other substances are also considered
safe.

Dichlorvos is a member of the organophosphate (OP) class of pesticides.
Other members of this class of pesticides are numerous and include
azinphos methyl, chlorpyrifos, chlorpyrifos‑methyl, diazinon,
dichlorvos, dicrotophos, dimethoate, disulfoton, methamidophos,
methidathion, monocrotophos, naled, oxydemeton-methyl, phorate, phosmet,
pirimiphos‑methyl, and trichlorfon to name a few. EPA considers
organophosphates to express toxicity through a common biochemical
interaction with cholinesterase which may lead to a myriad of
cholinergic effects and, consequently the organophosphate pesticides
should be considered as a group when performing cumulative risk
assessments. HED published the final guidance that it now uses for
identifying substances that have a common mechanism of toxicity (FR
64(24) 5796‑5799, February 5, 1999) "Proposed Guidance of Cumulative
Risk Assessment for Chemicals that have a Common Mechanism of Toxicity"
was made available for public comment in the Federal Register (65 FR
40644, June 30, 2000 . The Agency presented this approach to the
FIFRA/FQPA Science Advisory Panel in late September, 2000. The SAP
reviewed revised methods used to conduct a preliminary cumulative risk
assessment for organophosphate pesticides in 2002 (US EPA, 2002), found
at http://www.epa.gov/scipoly/sap/2002/index.htm.

The Agency has completed a cumulative risk assessment for OPs, (US EPA,
2001) and a revised cumulative risk assessment for OPs, (US EPA, 2002a)
which can be found on the Agency\'s web site
http://www.epa.gov/pesticides/cumulative/rra‑op/. It assesses the
cumulative effects of exposure to multiple OPs, including dichlorvos.

Dichlorvos is closely related to naled and trichlorfon, which are
members of the organophosphate class of pesticides. Naled and
trichlorfon both metabolize or degrade to dichlorvos in food, water, or
the environment. Therefore, FQPA requires OPP to estimate aggregate risk
from consumption of food and water, containing dichlorvos derived from
naled and trichlorfon and from residential exposure to dichlorvos from
the use of those pesticides. The current assessment addressed only the
risks posed by dichlorvos, resulting from the uses of dichlorvos, naled,
and trichlorfon.

**9.0 Occupational Exposure/Risk
Pathway**[]{#__RefHeading___Toc137619529 .anchor}

Risk is expressed as a Margin of Exposure (MOE)

MOE = [NOAEL]{.underline}

Exposure

where both the NOAEL and the Exposure are expressed in the same units
(mg/kg/day for dermal or inhalation exposure during application or
mg/m^3^ for exposure to dichlorvos vapors). Dermal exposures include a
dermal absorption factor of 11%, because the exposure is compared to an
oral NOAEL. The target MOE for occupational scenarios varies from 30 to
100. (See Table 4.4).

The risk assessment has been changed from previous versions to use the
North American Free Trade Agreement (NAFTA) recommended breathing rate
of 1.0 m^3^ /hr rather than the rate recommended in the guidelines or
the default breathing rate used in PHED. This change increases the
inhalation MOEs, and therefore decreases the estimated risk to
occupational and residential handlers. The risk assessment uses the
recommended body weight of 70 kg for the acute, short term, and
intermediate term risk assessments.

AMVAC has requested voluntary cancellation of the following uses.

Mushroom house, greenhouse, and warehouse hand held fogger

Lawn, Turf, and Ornamental uses

Total release fogger

Crack and Crevice uses

The following label changes will be made:

A Restricted Entry Interval (REI) of 18 hours for mushroom houses, and
12 hours for greenhouse uses.

Toxicological Doses and Endpoints for Occupational Exposure Assessment
are presented in Table 9.0. Occupational exposure and risk estimates for
applicators are presented in Table 9.1 below. Occupational
post-application exposure and risk estimates are presented in Table 9.2
below.

+-----------+------------+---------+----------+----------------------+
| **Table   |            |         |          |                      |
| 9.0.      |            |         |          |                      |
| Summary   |            |         |          |                      |
| of        |            |         |          |                      |
| Toxi      |            |         |          |                      |
| cological |            |         |          |                      |
| Doses and |            |         |          |                      |
| Endpoints |            |         |          |                      |
| for       |            |         |          |                      |
| D         |            |         |          |                      |
| ichlorvos |            |         |          |                      |
| for Use   |            |         |          |                      |
| in        |            |         |          |                      |
| Occ       |            |         |          |                      |
| upational |            |         |          |                      |
| Human     |            |         |          |                      |
| Health    |            |         |          |                      |
| Risk      |            |         |          |                      |
| Asse      |            |         |          |                      |
| ssments** |            |         |          |                      |
+===========+============+=========+==========+======================+
| **E       | **Point of | **Unce  | **Level  | **Study and          |
| xposure** | D          | rtainty | of       | Toxicological        |
|           | eparture** | Fa      | Concern  | Effects**            |
| **S       |            | ctors** | for Risk |                      |
| cenario** |            |         | Asse     |                      |
|           |            |         | ssment** |                      |
+-----------+------------+---------+----------+----------------------+
| Acute     | BMDL~10~ = | UF~A~ = | **Occupa | Rat acute oral       |
| Dermal    | 0.8        | 10x     | tional** | cholinesterase       |
|           | mg/kg/day  |         | LOC MOE  | studies - RBC and    |
|           |            | UF~H~ = | = 100    | Brain ChE            |
|           | dermal     | 10x     |          | depression. NOAEL =  |
|           | abso       |         |          | 1 mg/kg/day, LOAEL = |
|           | rption=11% |         |          | 5 mg/kg/day, BMD =   |
|           |            |         |          | 1.6 mg/kg/day for    |
|           |            |         |          | brain ChE depression |
|           |            |         |          | (F)                  |
+-----------+------------+---------+----------+----------------------+
| Short-,   | Oral study | UF~H~ = | **Occupa | Human 21-day oral    |
| Interme   | LOAEL=     | 10x     | tional** | study                |
| diate-and |            |         | LOC MOE  |                      |
| Long-Term | 0.1        | UF~L~ = | = 30     | LOAEL = 0.1          |
| Dermal    | mg/kg/day  | 3x      |          | mg/kg/day based on   |
|           |            |         |          | RBC ChE depression   |
|           | dermal     |         |          |                      |
|           | bso        |         |          |                      |
|           | rption=11% |         |          |                      |
+-----------+------------+---------+----------+----------------------+
| Acute     | Oral study | UF~A~ = | **Occupa | Rat acute oral       |
| I         | BMDL~10~ = | 10x     | tional** | cholinesterase       |
| nhalation | 0.8        |         | LOC MOE  | studies - RBC and    |
| (1 day)   | mg/kg/day  | UF~H~ = | =        | Brain ChE            |
|           |            | 10x or  | 10       | depression. NOAEL =  |
|           | (          | 3x\*\*  | 0/30\*\* | 1 mg/kg/day, LOAEL = |
|           | inhalation |         |          | 5 mg/kg/day, BMD =   |
|           | absorption |         |          | 1.6 mg/kg/day for    |
|           | rate =     |         |          | brain ChE depression |
|           | 100%)      |         |          | (F)                  |
|           |            |         |          |                      |
|           | Air        |         |          |                      |
|           | con        |         |          |                      |
|           | centration |         |          |                      |
|           | Equivalent |         |          |                      |
|           | = 0.8      |         |          |                      |
|           | mg/m^3^\*  |         |          |                      |
+-----------+------------+---------+----------+----------------------+
| Short-    | Oral study | UF~H~ = | **Occupa | Human 21-day oral    |
| and       | LOAEL=     | 10x     | tional** | study                |
| Intermed  |            |         | LOC MOE  |                      |
| iate-term | 0.1        | UF~L~ = | = 30     | LOAEL = 0.1          |
| I         | mg/kg/day  | 3x      |          | mg/kg/day based on   |
| nhalation | UF=30      |         |          | RBC ChE depression   |
| of vapors |            |         |          |                      |
|           | Con        |         |          |                      |
|           | centration |         |          |                      |
|           | e          |         |          |                      |
|           | quivalent= |         |          |                      |
|           | 0.35       |         |          |                      |
|           | mg/m^3^\*  |         |          |                      |
+-----------+------------+---------+----------+----------------------+
| Short-    | LOAEL= 0.1 | UF~H~ = | **Occupa | Human 21-day oral    |
| and       | mg/kg/day  | 10x     | tional** | study                |
| Intermed  |            |         | LOC MOE  |                      |
| iate-Term |            | UF~L~ = | = 30     | LOAEL = 0.1          |
|           |            | 3x      |          | mg/kg/day based on   |
| I         |            |         |          | RBC ChE depression   |
| nhalation |            |         |          |                      |
| during    |            |         |          |                      |
| ap        |            |         |          |                      |
| plication |            |         |          |                      |
+-----------+------------+---------+----------+----------------------+
| Long-Term | BMDL~10~ = | UF~A~ = | **Occupa | 2-year Rat           |
| I         | 0.07       | 10x     | tional** | Inhalation           |
| nhalation | mg/m^3^    |         | LOC = 30 |                      |
| of vapors |            | UF~H~ = |          | BMD = 0.15 mg/m^3^   |
|           |            | 3x\*\*  |          | based on RBC ChE     |
|           |            |         |          | depression (F)       |
+-----------+------------+---------+----------+----------------------+
| Cancer    | "s         |         |          |                      |
| (oral,    | uggestive" |         |          |                      |
| dermal,   | evidence   |         |          |                      |
| in        | of         |         |          |                      |
| halation) | carci      |         |          |                      |
|           | nogenicity |         |          |                      |
|           | not        |         |          |                      |
|           | qu         |         |          |                      |
|           | antifiable |         |          |                      |
|           | under the  |         |          |                      |
|           | 1999 Draft |         |          |                      |
|           | Agency     |         |          |                      |
|           | Cancer     |         |          |                      |
|           | Guidelines |         |          |                      |
+-----------+------------+---------+----------+----------------------+

Point of Departure (POD) = A data point or an estimated point that is
derived from observed dose-response data and used to mark the beginning
of extrapolation to determine risk associated with lower environmentally
relevant human exposures. NOAEL = no observed adverse effect level.
LOAEL = lowest observed adverse effect level. UF = uncertainty factor.
UF~A~ = extrapolation from animal to human (intraspecies). UF~H~ =
potential variation in sensitivity among members of the human population
(interspecies). UF~L~ = use of a LOAEL to extrapolate a NOAEL. UF~S~ =
use of a short-term study for long-term risk assessment. UF~DB~ = to
account for the absence of key date (i.e., lack of a critical study).
MOE = margin of exposure. LOC = level of concern. N/A = Not Applicable

\* Calculation of concentration equivalent BMDL~10~ and LOAEL

Acute Inhalation BMDL~10~

0.8 mg/kg/day x 0.35 kg / 0.34 m^3^/day = 0.8 mg/m^3^

Short- and Intermediate- term inhalation of vapors LOAEL

0.1 mg/kg/day x 70 kg / 20 m^3^/day = 0.35 mg/m^3^

\*\*Since the NOAEL is expressed in concentration units (RfC
methodology), the interspecies extrapolation factor is 3x (for the acute
and long term inhalation scenarios), for a total UF of 30 for acute
inhalation and long term inhalation.

**9.0.1. Mushroom House**

**(a). Application**

Application of dichlorvos to mushroom houses may be made by coarse spray
and paint-on applications. Foggers would be permitted if the applicator
is outside the mushroom house. The exposures for coarse spray
applications were derived from ORETF data. The Outdoor Residential
Exposure Task Force (ORETF) has recently completed several surrogate
mixer/loader/applicator studies addressing lawn care operators (LCOs).
(Bangs, 2001; Jaquith, 2001). The hose-end sprayer scenario from the
ORETF studies will be used to estimate exposures to applicators in
mushroom houses. Estimates of the surface areas that would be painted or
sprayed during dichlorvos application were derived from mushroom culture
textbooks and are considered to be conservative (Jaquith 1998d and n).
This application scenario is considered to be intermediate term (several
months) because a single individual may treat different mushroom houses
on different days due to the cyclic nature of mushroom culture.

*Coarse Spray and Paint-on Applications.* For the coarse spray, data
from the ORETF lawn care study were used; protective clothing varied
with the application method, and included long pants, long sleeved shirt
and gloves, or coveralls plus long pants, long sleeved shirt and gloves.
The label does not specify protective clothing needed. Dermal and
inhalation exposure and total exposure resulting in an MOE of 46 is not
considered to be of concern, compared to the target MOE of 30. If an
additional layer of protective clothing were added, the absorbed dermal
dose would be cut approximately in half, and the MOE of 88 would be
adequate.

**(b). Post-application**

For reentry exposure, it was assumed that a worker reenters a ventilated
mushroom house 12 or 24 hours after treatment and is exposed for 8
hours. This is a short term exposure because workers may be exposed
multiple times on subsequent days. The MOE at a 12 hour REI of 23 is
less than the target MOE of 30, and is of concern. The MOE at a 24 hour
REI of 58 is greater than the target MOE of 30, and is not of concern.
AMVAC has submitted an amendment, changing the label REI to 18 hours.

**9.0.2. Greenhouse**

**(a). Application**

There are currently no end use product labels with directions for use
for greenhouses. However, the technical label for Dichlorvos allows use
of up to 2.0 g/1000 cu. ft. Previously, smoke generators were
registered, and were considered to result in negligible applicator
exposure since the applicator vacates the premises immediately upon
activation of the smoke generator. This application scenario is
considered to be short term because treatment would not be expected to
occur in a given greenhouse more than once a week. The baseline MOE is
46, which is not of concern.

**(b). Post-application**

The dermal exposure for reentry into greenhouses following the use of
dichlorvos was obtained using data from a greenhouse culture textbook,
data on turf transferable residues from a chlorpyrifos/dichlorvos study
(Goh, K. S., et. al. 1986), and a standard transfer coefficient of 2500
cm^2^/hr, from ExpoSAC Policy 003. Inhalation exposure estimates were
modeled assuming the initial concentration at the maximum rate, assuming
first order kinetics and an air exchange rate from a textbook
(Mastalerz, 1977). This is considered to be a short-term exposure
scenario (Jaquith, 1998d).

The total daily dermal exposure that would occur after a 2 hour REI is
estimated to be 1.2 μg/kg/day. The dichlorvos concentrations available
for inhalation exposure were modeled (Jaquith, 1998d), and
concentrations depended on the ventilation used. The estimated
respiratory component of exposure would be 0.00035 mg/m^3^. The
resulting MOE with a 2 hour REI of 78 is not of concern, compared to the
target MOE of 30. At a 12 hr REI, the total MOE is \>650 and is not of
concern, compared to the target MOE of 30.

> **9.0.3. Domestic Animal Premises (food and nonfood) and Direct Animal
> Sprays, Feedlots, Manure Treatment, Garbage Dumps, and Baits**

**(a). Application**

Dairy barn application and direct application to dairy cattle were used
as the reference facility for these exposure assessments (Jaquith
1998l). There are no data addressing the use of dichlorvos in other
types of animal facilities. Worker exposure from direct application to
animals is based on dairy cattle treatment. Although permitted on
product labels, the Agency does not believe that direct application to
livestock animals with a handheld sprayer is used. Rather, some type of
automated equipment is used to apply dichlorvos directly to animals.
Space and premise treatments also help control insects on animals. Since
several registered products provide guidance on use with a handheld
sprayer, the exposure and risk are estimated here for that application
method, which is expected to result in a much higher exposure than
automated methods. While some labels indicate that daily application
(probably for direct application to cattle) is allowable, the use
assessment indicates that the material is applied at 2 week intervals
(Dow, M., 1985). This assessment assumes daily applications over several
months, and is therefore considered to be an intermediate term scenario.

[Cattle]{.underline}. Exposure assessments for direct application to
dairy cattle using hand-held sprayers as a surface spray or space spray
were conducted using PHED V1.1. Applicators were assumed to be wearing
long sleeved shirt, long pants, and gloves. Gloves are not currently
required on the label. Absorbed dermal doses were estimated to range
from 0.009 to 0.22 μg/kg/day and respiratory doses from 0.008 to 0.039
μg/kg/day, depending on application equipment. These total MOEs would
range from 440 to 59000, and are not considered to be of concern.

[Poultry]{.underline}. Applicator exposure data for cattle cannot be
extrapolated to poultry, because of the different application method and
less frequent applications. Individual animals are less likely to be
treated directly and the equipment is more likely to be automated. As a
result, exposure from applying dichlorvos to poultry is expected to be
much lower than for cattle. Therefore, no separate assessment has been
done.

[Domestic Animal Premises]{.underline}. Barn sizes were obtained from
the dichlorvos Qualitative Use Assessment (QUA) (Dow, M., 1985).
Assuming that a worker wears long sleeve shirt, long trousers, shoes and
impervious gloves at a minimum, risks from dichlorvos application to
domestic animal premises are lower than the risks from direct
application to cattle, with total MOEs from 440 to 5900, and do not
exceed the Agency's level of concern. Gloves are not currently required
on all dichlorvos labels.

[Feedlots]{.underline} include stockyards, corrals, holding pens and
other areas where large groups of animals are contained. EPA assumes
that some type of power sprayer capable of treating a large number of
animals in a short time is probably used. A short application time
period in an outdoor or partially enclosed area would minimize exposure
to less than that of dairy applications.

[Manure Treatment]{.underline}. The application equipment used for
manure applications may be similar to those used in a dairy barn;
however, the application time would probably be less and the treated
area would be well ventilated ‑ either outdoors or in a partially
enclosed area. The MOE for applicators is expected to be greater than
the target MOE for manure use.

**(b). Reentry**

There are no data addressing potential reentry into animal facilities.
Re-entry exposure to animal premises would not be expected to exceed
reentry exposure for greenhouses, and would be expected to be
considerably less, since animal premises are usually outdoors or well
ventilated, where minimal dermal contact is expected.

**9.0.4. Food Manufacturing Plant, Warehouse Treatment**

**(a). Application**

Dichlorvos can be applied to warehouses with wall-mounted automatic
foggers. Exposure to mixer/loaders through automatic application is
expected to be negligible; however, there would still be reentry
exposure.

**(b). Post-application**

In estimating reentry exposure, EPA assumed 24 hours elapsed before
reentry is allowed, the label REI; and that workers in food
manufacturing plants spend 8 hours per day in the treated area, and 2
hours per day in warehouses. Absorbed dermal exposure was measured for
the hands only, which is likely to be the greatest route of dermal
exposure, and represents an average of the total exposure measured for
three work stations, and was negligible compared to the inhalation
exposure. This exposure scenario was considered to be acute due to rapid
dissipation of dichlorvos (1 day) and sporadic use. (Jaquith, D., 2000a;
Jaquith, D, 1993c).

The dermal exposure estimate is 0.00022 mg/kg/day for food manufacturing
plants. The mean air concentration of dichlorvos in a food manufacturing
plant is estimated to be 0.053 mg/m^3^ , 24 hours after application,
which results in an exposure of 0.006 mg/kg/day. The estimated air
concentration in a warehouse after a 24 hour REI is 0.074 mg/m^3^ . This
is an acute exposure scenario with an MOE of 130 (target MOE is 100) for
food manufacturing plants, and 650 for warehouses, neither of which is
of concern.

**9.0.5. Railcars and Trucks**

**(a). Application**

Dichlorvos can be applied to railcars and trucks as a fog or as a
surface spray. This is a short term exposure scenario. One to ten
railcars or trucks could be treated in a single day. Application with a
surface spray would have MOEs of 320, compared to a target MOE of 30,
which would not be of concern.

**(b). Post-application**

In estimating reentry exposure, EPA assumed 6 hours elapsed before
reentry is allowed, and that workers could spend 1 hour per truck or
railcar and could load 4 railcars or trucks per day. Workers loading
rail cars or trucks would not be expected to have dermal exposure to
dichlorvos. The air concentration was estimated using initial air
concentrations calculated from the application rate, and assuming
ventilation similar to a food processing establishment. This exposure
scenario was considered to be short term due to rapid dissipation of
dichlorvos. (Jaquith, D., 2005). The air concentration 6 hours after
treatment is estimated to be 0.018 mg/m^3^. The MOE would be 94, which
is not of concern, compared to the target MOE of 30. There is
considerable uncertainty about the air exchange rate. Under the
conditions described, the air exchange rate could be as low as 1/3 per
hour.

**9.0.6. Insect Traps**

Exposure is believed to be negligible since the pesticide is in the form
of an impregnated strip in a sealed package, which is opened and the
applicator leaves, and the traps are placed in outdoor areas (such as
forests) where there is no human exposure.

**9.0.7. Occupational Uses of Resin Strips**

The dichlorvos label contains the following use patterns and
restrictions.

> *Garbage Cans, Trash Dumpsters, Catch Basins, Utility Enclosures.*
> Keep lid on can and dumpster closed.
>
> *Animal Buildings, Milk Rooms*. Do not contaminate food, water or
> foodstuffs. Do not contaminate milk or milking equipment.
>
> *Agricultural Commodities*: *Bulk Storage of raw grains, corn,
> soybeans, cocoa beans, and peanuts*. No restrictions.
>
> *Reptile Houses and Terrariums*. Make sure that the reptiles can not
> touch or contact the strip.

Exposure to dichlorvos from these use patterns is expected to be small
compared to the use of resin strips in homes, provided that workers are
in the facilities treated for short periods of time. Refer to table 6.3
for exposure and risk information.

<table>
<colgroup>
<col style="width: 21%" />
<col style="width: 4%" />
<col style="width: 9%" />
<col style="width: 5%" />
<col style="width: 7%" />
<col style="width: 8%" />
<col style="width: 7%" />
<col style="width: 8%" />
<col style="width: 7%" />
<col style="width: 6%" />
<col style="width: 8%" />
<col style="width: 6%" />
</colgroup>
<thead>
<tr class="header">
<th colspan="12">Table 9.1 Occupational Applicator Exposure and Risk
Estimates<sup>1</sup></th>
</tr>
<tr class="odd">
<th>Scenario</th>
<th>End-note</th>
<th>Duration</th>
<th># ai/day</th>
<th>Dermal unit exposure</th>
<th>Inhalation unit exposure</th>
<th>Dermal Exposure</th>
<th>Inhalation Exposure</th>
<th>Total Exposure</th>
<th>Dermal MOE</th>
<th>Inhalation MOE</th>
<th><p>Total</p>
<p>MOE</p></th>
</tr>
</thead>
<tbody>
<tr class="odd">
<td>Mushroom house &amp; Greenhouse</td>
<td>2</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td>- ORETF Hose End Sprayer</td>
<td></td>
<td>Intermediate term</td>
<td>2.6</td>
<td>0.52</td>
<td>0.001</td>
<td>0.00212</td>
<td>0.00004</td>
<td>0.0022</td>
<td>47</td>
<td>2700</td>
<td>46</td>
</tr>
<tr class="odd">
<td>- ORETF Hose End Sprayer + coveralls</td>
<td></td>
<td>Intermediate term</td>
<td>2.6</td>
<td>0.27</td>
<td>0.001</td>
<td>0.00110</td>
<td>0.00004</td>
<td>0.00061</td>
<td>91</td>
<td>2700</td>
<td>88</td>
</tr>
<tr class="even">
<td>Direct animal treatment</td>
<td>3</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>- Hand Held Sprayer</td>
<td></td>
<td>Intermediate term</td>
<td>0.092</td>
<td>0.17</td>
<td>0.017</td>
<td>0.000025</td>
<td>0.000023</td>
<td>0.000047</td>
<td>4100</td>
<td>4400</td>
<td>2100</td>
</tr>
<tr class="even">
<td>- Backpack Sprayer (471)</td>
<td></td>
<td>Intermediate term</td>
<td>0.092</td>
<td>2.6</td>
<td>0.017</td>
<td>0.000376</td>
<td>0.000023</td>
<td>0.000399</td>
<td>270</td>
<td>4400</td>
<td>250</td>
</tr>
<tr class="odd">
<td>- Backpack Sprayer (416)</td>
<td></td>
<td>Intermediate term</td>
<td>0.092</td>
<td>0.27</td>
<td>0.017</td>
<td>0.000039</td>
<td>0.000023</td>
<td>0.000062</td>
<td>2600</td>
<td>4400</td>
<td>1600</td>
</tr>
<tr class="even">
<td>- Portable Sprayer on Cart</td>
<td></td>
<td>Intermediate term</td>
<td>0.092</td>
<td>0.69</td>
<td>0.052</td>
<td>0.000100</td>
<td>0.000068</td>
<td>0.000168</td>
<td>1000</td>
<td>1500</td>
<td>600</td>
</tr>
<tr class="odd">
<td>Dairy barns - space spray</td>
<td>4</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td>- Hand Held Sprayer</td>
<td></td>
<td>Short term</td>
<td>0.033</td>
<td>0.17</td>
<td>0.017</td>
<td>0.000009</td>
<td>0.000008</td>
<td>0.000017</td>
<td>11000</td>
<td>12000</td>
<td>5900</td>
</tr>
<tr class="odd">
<td>- Backpack Sprayer (471)</td>
<td></td>
<td>Short term</td>
<td>0.033</td>
<td>2.6</td>
<td>0.017</td>
<td>0.000135</td>
<td>0.000008</td>
<td>0.000143</td>
<td>740</td>
<td>12000</td>
<td>700</td>
</tr>
<tr class="even">
<td>- Backpack Sprayer (416)</td>
<td></td>
<td>Short term</td>
<td>0.033</td>
<td>0.27</td>
<td>0.017</td>
<td>0.000014</td>
<td>0.000008</td>
<td>0.000022</td>
<td>7100</td>
<td>12000</td>
<td>4500</td>
</tr>
<tr class="odd">
<td>- Portable Sprayer on Cart</td>
<td></td>
<td>Short term</td>
<td>0.033</td>
<td>0.69</td>
<td>0.052</td>
<td>0.000036</td>
<td>0.000025</td>
<td>0.000060</td>
<td>2800</td>
<td>4100</td>
<td>1700</td>
</tr>
<tr class="even">
<td>Dairy barns - surface spray</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>- Hand Held Sprayer</td>
<td></td>
<td>Short term</td>
<td>0.053</td>
<td>0.17</td>
<td>0.017</td>
<td>0.000014</td>
<td>0.000013</td>
<td>0.000027</td>
<td>7100</td>
<td>7600</td>
<td>3700</td>
</tr>
<tr class="even">
<td>- Backpack Sprayer (471)</td>
<td></td>
<td>Short term</td>
<td>0.053</td>
<td>2.6</td>
<td>0.017</td>
<td>0.000217</td>
<td>0.000013</td>
<td>0.000230</td>
<td>460</td>
<td>7600</td>
<td>440</td>
</tr>
<tr class="odd">
<td>- Backpack Sprayer (416)</td>
<td></td>
<td>Short term</td>
<td>0.053</td>
<td>0.27</td>
<td>0.017</td>
<td>0.000022</td>
<td>0.000013</td>
<td>0.000036</td>
<td>4400</td>
<td>7600</td>
<td>2800</td>
</tr>
<tr class="even">
<td>- Portable Sprayer on Cart</td>
<td></td>
<td>Short term</td>
<td>0.053</td>
<td>0.69</td>
<td>0.052</td>
<td>0.000057</td>
<td>0.000039</td>
<td>0.000097</td>
<td>1700</td>
<td>2500</td>
<td>1000</td>
</tr>
<tr class="odd">
<td>Rail cars and trucks</td>
<td>5</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td>- Surface Spray</td>
<td></td>
<td>Short term</td>
<td>0.28</td>
<td>0.67</td>
<td>0.0032</td>
<td>0.00030</td>
<td>0.000013</td>
<td>0.00031</td>
<td>330</td>
<td>7700</td>
<td>320</td>
</tr>
<tr class="odd">
<td>Feedlots</td>
<td>6</td>
<td>Short term</td>
<td colspan="9" rowspan="3">No data; not expected to exceed dairy barn
exposure</td>
</tr>
<tr class="even">
<td>Manure</td>
<td>7</td>
<td>Short term</td>
</tr>
<tr class="odd">
<td>Garbage Dumps</td>
<td>8</td>
<td>Short term</td>
</tr>
<tr class="even">
<td></td>
<td></td>
<td></td>
<td colspan="9"></td>
</tr>
</tbody>
</table>

NOTES: The parameters and assumptions used in calculating the margins of
exposure are found in the endnotes below

,

Risk is expressed as a Margin of Exposure (MOE)

MOE = [NOAEL]{.underline} , where both the NOAEL and the Exposure are
expressed in mg/kg/day or mg/m^3^

Exposure

The target MOE for occupational exposure scenarios is 30.

1.  Occupational Exposure assumptions. An average worker weighs 70 kg
    and has a respiratory volume of 1.0 m^3^ /hour (NAFTA Value). At a
    minimum, the following protective clothing was used in the exposure
    scenarios: gloves, long-sleeve shirt, long pants

2.  Mushroom Houses and Greenhouses

> Mushroom Houses - coarse spray. A typical mushroom operation is
> believed to consist of 10 houses, each with a volume of 30000 ft^3^
> (850 m^3^). The label does not specify protective clothing needed. If
> an individual treats all 10 houses at a rate of 2 grams per 1000 ft^3^
> the amount handled in a day would be:

Amount handled (lb ai/day) = [30000 ft^3^/house x 10 houses/day x 2
g/1000 ft^3^]{.underline} = 1.3 lb ai/day

454 g/lb ai

> Workers are assumed to be wearing a single layer of clothing and
> gloves. A second assessment was done for applicators wearing
> coveralls. Data from the ORETF lawn care study were used (liquid
> formulation, hose end sprayer).
>
> AMVAC does not have a coarse spray registered. There was a canceled
> product, EPA Reg. No. 72-375 that had use directions for the coarse
> spray or paint-on application to mushroom houses. The use specified
> 0.25 lb of a 0.5% solution to treat 100 sq ft. If we assume that a
> typical mushroom house is 6000 sq ft, the amount handled per day would
> be about1.5 lb ai/day. Thus, the mushroom/greenhouse assessment
> presented in this table estimates a somewhat higher exposure than what
> would be expected.

Greenhouse ‑ The average greenhouse has an estimated volume was 85,000
ft^3.^ A typical operation was assumed to consist of 10 greenhouses
which could be treated in a single day. Treatment was estimated to be
3.75 minutes per house or 26 minutes (0.44 hrs) per day. Dichlorvos is
applied at the rate of 1.4 grams of active ingredient per 1,000 ft^3^.
Workers were assumed to be a single layer of clothing and gloves.
Treatment would not be expected to occur in a given greenhouse more than
once a week, resulting in a short term exposure scenario. Workers are
assumed to weigh 70 kg. The unit exposures were 14 mg/lb ai handled for
dermal exposure, and 0.19 mg/lb ai handled for inhalation exposure.

> The typical application rate for dichlorvos in a greenhouse is 1.4 g
> per 1000 ft^3^. The amount handled per greenhouse would be:

Amount handled (lb ai/greenhouse) = 1.4 g ai/1000 ft^3^ x 85000
ft^3^/greenhouse

= 120 g ai/greenhouse = 0.26 lb ai/greenhouse

The amount handled per day would be:

Amount handled (lb ai/day) = 0.26 lb ai/greenhouse x 10 greenhouses/day
= 2.6 lb ai/day

3.  Domestic Food/Non-food Animals (non-poultry). Worker exposure from
    direct application to animals is based on dairy cattle treatment. A
    one percent solution of dichlorvos is applied with a handheld
    sprayer. An average herd of dairy cattle consists of 65 head, each
    requiring 24 seconds to spray, two times per day during treatment.
    Fly control is required from May to October with application
    expected to be occurring weekly rather than 2 x per day during this
    time (26 times per year). Although permitted on product labels, EPA
    does not believe that direct application with a handheld sprayer is
    used. Rather, some type of automated equipment is used to apply
    dichlorvos directly to animals. Space and premise treatments also
    help control insects on animals. Since several registered products
    provide guidance on use with a handheld sprayer, the exposure and
    risk are estimated here for that application method, which is
    expected to result in a much higher exposure than automated methods.
    The exposure assessment for direct application to dairy cattle using
    a handheld sprayer was conducted using PHED V1.1. Applicators were
    assumed to wear long sleeve shirts, long pants, and gloves.

> Domestic Food/Non-food Animals (poultry). Data for cattle cannot be
> extrapolated to poultry, because of the different application method
> and less frequent applications. However, individual animals are less
> likely to be treated directly and the equipment is more likely to be
> automated. As a result, exposure from applying dichlorvos to poultry
> is expected to be much lower than for cattle, and no separate
> assessment is done.

4.  Domestic Animal Premises - Dairy Barns. An average dairy barn has
    the dimensions 30 ft x 100 ft x 9 ft (total area covered is 5,340
    ft^2^ ). (Dow, M., 1985). Dichlorvos is applied at two week
    intervals for 22 weeks, one barn per day. A 1.0 percent solution of
    dichlorvos is applied using a low pressure hand sprayer at a rate of
    0.0115 lb a.i. per 1000 ft^2^. A worker wears long sleeve shirt,
    long trousers, shoes and impervious gloves at a minimum. The unit
    exposure varies depending on the equipment used.

5.  Rail cars and trucks. Calculation is shown for treating 10 rail cars
    or trucks per day. Dermal absorption is assumed to be 11 percent.
    Applicators are assumed to wear long sleeve shirts, long pants,
    gloves, and a respirator (90% protection). Coveralls, although
    required on some labels, are not included for surface application.
    An applicator treating 10 rail cars per day handles 0.28 lb ai/day.
    The dermal unit exposure is 0.67 mg/lb ai, and the inhalation unit
    exposure is 0.0032 mg/lb ai.

0[.28 lb dichlorvos x 0.67 mg/lb ai x 0.11 (dermal absorpting
factor)]{.underline} = 0.00030 mg/kg/day

70 kg applicator

[0.28 lb dichlorvos x 0.0032 mg/lb ai]{.underline} = 0.000013 mg/kg/day

70 kg applicator

6\. Feedlots include stockyards, corrals, holding pens and other areas
where large groups of animals are contained. EPA assumes that some type
of power sprayer capable of treating a large number of animals in a
short time is probably used. A short application time period in an
outdoor or partially enclosed area would minimize exposure to less than
that of dairy applications.

7\. Manure. The MOE is expected to be greater than 100 for manure use.
Application equipment may be similar to those used in a dairy barn;
however, the application time would probably be less and the treated
area would be well ventilated - either outdoors or in a partially
enclosed area.

8\. Garbage Dumps. Exposure at a garbage dump is believed to be less
than dairy exposure.

+---------------+-----+--------+-------+----------+------+------+-----+
| **Table 9.2.  |     |        |       |          |      |      |     |
| Summary of    |     |        |       |          |      |      |     |
| Occupational  |     |        |       |          |      |      |     |
| Pos           |     |        |       |          |      |      |     |
| t-Application |     |        |       |          |      |      |     |
| Exposure and  |     |        |       |          |      |      |     |
| Risk          |     |        |       |          |      |      |     |
| Estimates for |     |        |       |          |      |      |     |
| Dichlorvos**  |     |        |       |          |      |      |     |
+===============+=====+========+=======+==========+======+======+=====+
| **USES**      | **N | **EXPO | **Cu  |          | *    |      | *   |
|               | OTE | SURE** | rrent |          | *Cur |      | *MO |
|               | S** |        | Exp   |          | rent |      | E** |
|               |     | **     | osure |          | M    |      |     |
|               |     | PATTER | (mg   |          | OE** |      |     |
|               |     | N^1^** | /kg/d |          |      |      |     |
|               |     |        | ay)** |          |      |      |     |
+---------------+-----+--------+-------+----------+------+------+-----+
|               |     |        | **Der | **Inha   | **   | **   | **T |
|               |     |        | mal** | lation** | Derm | Inha | ota |
|               |     |        |       |          | al** | lati | l** |
|               |     |        |       |          |      | on** |     |
+---------------+-----+--------+-------+----------+------+------+-----+
| OCCUPATIONAL  | 1   | Target |       |          |      |      |     |
| EXPOSURE      |     | MOEs   |       |          |      |      |     |
|               |     | for    |       |          |      |      |     |
|               |     | all    |       |          |      |      |     |
|               |     | short  |       |          |      |      |     |
|               |     | term   |       |          |      |      |     |
|               |     | post   |       |          |      |      |     |
|               |     | -appli |       |          |      |      |     |
|               |     | cation |       |          |      |      |     |
|               |     | Occupa |       |          |      |      |     |
|               |     | tional |       |          |      |      |     |
|               |     | Sce    |       |          |      |      |     |
|               |     | narios |       |          |      |      |     |
|               |     | are    |       |          |      |      |     |
|               |     | 30,    |       |          |      |      |     |
|               |     | and    |       |          |      |      |     |
|               |     | for    |       |          |      |      |     |
|               |     | acute  |       |          |      |      |     |
|               |     | post   |       |          |      |      |     |
|               |     | -appli |       |          |      |      |     |
|               |     | cation |       |          |      |      |     |
|               |     | scen   |       |          |      |      |     |
|               |     | arios, |       |          |      |      |     |
|               |     | are    |       |          |      |      |     |
|               |     | 100.   |       |          |      |      |     |
+---------------+-----+--------+-------+----------+------+------+-----+
| i\. Mushroom  | 2   |        |       |          |      |      |     |
| house         |     |        |       |          |      |      |     |
+---------------+-----+--------+-------+----------+------+------+-----+
| Reentry       |     | Shor   | 0     | 0.044    | 450  | 24   | 23  |
| (12-hour REI) |     | t-term | .0002 | mg/m^3^  |      |      |     |
+---------------+-----+--------+-------+----------+------+------+-----+
| Reentry       |     | Shor   | 0     | 0.016    | 450  | 66   | 58  |
| (24-hour REI) |     | t-term | .0002 | mg/m^3^  |      |      |     |
+---------------+-----+--------+-------+----------+------+------+-----+
| ii\.          | 3   |        |       |          |      |      |     |
| Greenhouse    |     |        |       |          |      |      |     |
+---------------+-----+--------+-------+----------+------+------+-----+
| Reentry (2    |     | Shor   | 0     | 0.00035  | 80   | 3000 | 78  |
| hour REI)     |     | t-term | .0012 | mg/m^3^  |      |      |     |
+---------------+-----+--------+-------+----------+------+------+-----+
| Reentry (12   |     | Shor   | 0.    | \        | 800  | \>   | \>  |
| hour REI)     |     | t-term | 00012 | <0.00035 |      | 3000 | 650 |
|               |     |        |       | mg/m^3^  |      |      |     |
+---------------+-----+--------+-------+----------+------+------+-----+
| Reentry (24   |     | Shor   | \<0.  | \        | \    | \>   | \>  |
| -hour REI)    |     | t-term | 00012 | <0.00035 | >800 | 3000 | 650 |
|               |     |        |       | mg/m^3^  |      |      |     |
+---------------+-----+--------+-------+----------+------+------+-----+
| iii\. Food    | 4   | acute  | 0.    | 0.053    | 3600 | 130  | 130 |
| Manufacturing |     |        | 00022 | mg/m^3^  |      |      |     |
| Plant -       |     |        |       |          |      |      |     |
| Reentry (24   |     |        |       | (0.006   |      |      |     |
| hour REI)     |     |        |       | mg       |      |      |     |
|               |     |        |       | /kg/day) |      |      |     |
+---------------+-----+--------+-------+----------+------+------+-----+
| iv\.          | 5   | acute  | 0.    | 0.074    | 3600 | 800  | 650 |
| Warehouse     |     |        | 00022 | mg/m^3^  |      |      |     |
| treatment -   |     |        |       |          |      |      |     |
| Reentry (24   |     |        |       | (0.001   |      |      |     |
| hour REI, 1   |     |        |       | mg       |      |      |     |
| hr exposure)  |     |        |       | /kg/day) |      |      |     |
+---------------+-----+--------+-------+----------+------+------+-----+
| v\. Railcars  | 6   | Shor   |       | 0.0187   |      | 94   | 94  |
| and trucks    |     | t-term |       | mg/m^3^  |      |      |     |
|               |     |        |       |          |      |      |     |
| (8 hr REI)    |     |        |       | (0.0010  |      |      |     |
|               |     |        |       | mg       |      |      |     |
|               |     |        |       | /kg/day) |      |      |     |
+---------------+-----+--------+-------+----------+------+------+-----+

NOTES: The following notes define the assumptions used in calculating
the margins of exposure.

1.  Risk is expressed as a Margin of Exposure (MOE)

MOE = [NOAEL]{.underline} ,where both the NOAEL and the Exposure are
expressed in mg/kg/day or mg/m^3^

Exposure

The target MOE for all short term post-application occupational exposure
is 30, and for all acute post-application scenarios is 100.

Occupational Exposure assumptions. An average worker weighs 70 kg and
has a respiratory volume of 1.0 m^3^ /hour (NAFTA Value). At a minimum,
the following protective clothing was used in the exposure scenarios:
gloves, long-sleeve shirt, and long pants. Addition of a respirator to
the PPE requirements would reduce estimated inhalation exposure by 90%,
which would not change the MOEs by more than a factor of 2.

2.  Mushroom Houses - reentry. For reentry exposure, it was assumed that
    a worker reenters a ventilated mushroom house 12 or 24 hours after
    treatment and is exposed for 8 hours. The post‑application exposures
    for mushroom houses were derived from a study conducted by the
    California Department of Food and Agriculture (CDFA) (now the
    California EPA) in which air and surface residues were measured in
    mushroom houses where dichlorvos had been applied (Maddy 1981,
    Jaquith 1998d). This was a limited study measuring surface residues
    and air concentrations in 2-4 mushroom houses over 24 hours.

> Wipe sampling was only conducted in 2 mushroom houses, preventing any
> analysis of the distribution of surface residues in these facilities.
> The highest surface concentration, 0.026 μg/cm^2^, was reported 3
> hours after application. The last sampling point was at 12 hours after
> application, when the surface residues averaged 0.007 μg/cm^2^. There
> was no clear trend in the air concentrations. Air samples were
> collected at 30 minutes, and 1, 3, 6, 12, and 24 hours. Only two
> samples were taken at the 24 hour sampling period. The air
> concentrations of dichlorvos averaged 0.022, 0.044, and 0.016 mg/m^3^,
> at 6, 12, and 24 hours after treatment, respectively. The transfer
> coefficient was obtained from the ExpoSAC policy 003, to be 2500
> cm^2^/hr. Because of the aeration pattern of mushroom houses, the
> volatility of dichlorvos, and dissipation of dichlorvos in mushroom
> houses, this is considered to be a short term exposure scenario.
> Respirators are not worn during reentry.

Dermal Exposure (μg/kg/day) = 0.007 μg/cm^2^ x 2500 cm^2^ /hr x 8 hr/day
x 1/70 kg x 0.11 (Absorb)

= 0.22 μg/kg/day

= 0.00022 mg/kg/day

Estimated dermal post-application risk = [NOAEL]{.underline} = [0.1
mg/kg/day]{.underline} = 450 (Target MOE = 30, ARI = 450/30 = 15)

Exposure 0.00022 mg/kg/day

> The inhalation risk estimate includes a factor to adjust for the hours
> of exposure. The endpoint converted to concentration units assumed 24
> hours exposure per day. Workers in mushroom houses are exposed for 8
> hours.
>
> Estimated inhalation post-application risk = [NOAEL]{.underline} =
> [0.35 mg/m^3^]{.underline} x [24hr]{.underline} = 24 (Target MOE = 30)

(12 hour REI) Exposure 0.044 mg/m^3^ 8 hr

The label REI is now 18 hours.

3\. Greenhouse - reentry. The dermal exposure for reentry into
greenhouses following the use of dichlorvos was obtained using data from
a greenhouse culture textbook, data on turf transferable residues from a
chlorpyrifos/dichlorvos turf study (Goh, K. S., et. al. 1986), and a
transfer coefficient of 2500 cm^2^/hr, from the ExpoSAC Policy 003.
Inhalation exposure estimates were modeled assuming the initial
concentration at the maximum rate, assuming first order kinetics and an
air exchange rate from a textbook (Mastalerz, 1977). This is considered
to be a short-term exposure scenario (Jaquith, 1998d).

> The dislodgeable foliar residues reported in the Goh study were 0.04
> μg/cm^2^, 2 ‑ 6 hours after application, and 0.004 μg/cm^2^, 10 hours
> after application of 2 g dichlorvos/1000 ft^3^.

The total daily dermal exposure that would occur after a 2 hour REI is
estimated to be:

Dermal Exposure (μg/kg/day) = 0.04 μg/cm^2^ x 2500 cm^2^ /hr x 8 hrs/day
x 0.11 (dermal absorption factor) x 1/70 kg = 1.25 μg/kg/day (0.00125
mg/kg/day)

> Dermal MOE = [NOAEL]{.underline} = [0.1 mg/kg/day]{.underline} = 80
>
> Exposure 0.00125 mg/kg/day
>
> Estimated inhalation post-application risk = [NOAEL]{.underline} =
> [0.35 mg/m^3^]{.underline} x [24 hr]{.underline} = 3000

(2 hour REI) Exposure 0.00035 mg/m^3^ 8 hr

4\. Reentry - Food manufacturing plant. Dichlorvos can be applied to
food processing facilities with wall-mounted automatic foggers. In
estimating reentry exposure to food processing facilities, EPA assumed
24 hours elapsed before reentry is allowed, as required on labels; and
that workers spend 8 hours per day on the day following treatment.
Dichlorvos is applied at the rate of 2.0 grams active ingredient per
1,000 ft^3^ over a period of 125 minutes per application. Hand rinses
were done and air concentrations were measured at 0, 3, 6, 10, 22, and
42 hours after application. Dermal exposure was measured for the hands
only and represents an average of the total exposure measured for three
work stations. Because significant exposure occurs for only one day and
occurs sporadically, this is considered an acute reentry scenario and
MOEs are calculated using the BMDL~10~ of 0.8 mg/kg for inhibition of
rat cholinesterase.

> The dermal exposure calculated in the original review (Jaquith 1993c),
> 0.00027 mg/kg/day, has been corrected for the application rate
> (2.0/2.4), resulting in a dermal exposure estimate of 0.00022
> mg/kg/day.

The dermal MOE = 0.8/.00022 = 3600

> Mean air concentrations of dichlorvos in a food handling establishment
> following treatment using a fogger at 2.4 g ai/1000 ft^3^. Means
> include samples from all sites and two different heights. (Jaquith,
> D., 2000a; Jaquith, D, 1993c).
>
> Hours After Application Mean Conc. (mg/m^3^) Conc. Corrected for
> application rate (mg/m^3^)
>
> 0 10.0 8.3
>
> 3 2.7 2.2
>
> 6 0.62 0.52
>
> 10 0.37 0.31
>
> 22 0.13 0.11
>
> 42 0.052 0.043
>
> An exponential decay curve C = C~0~ x e^-kt^ was fit to the data where
> C~0~ = 0.93 mg/m^3^ and k = 0.10 /hour. The corresponding equation for
> average concentration over the interval from t~1~ to t~2~ is C~avg~ =
> C~0~ x (e^-kt1^ - e-^kt2^) / k(t~2~-t~1~). For the interval from 24 to
> 32 hours, the average concentration is 0.053 mg/m^3^. The dose on a
> mg/kg basis is:

Dose (mg/kg) = 0.053 mg/m^3^ x 1.0 m^3^/hr x 8 hr ÷ 70 kg = 0.006 mg/kg.

> The acute inhalation MOE is: MOE = 0.8 ÷ 0.006 = 130

5\. Reentry - warehouse. Dichlorvos can be applied to food warehouses
with wall-mounted automatic foggers. In estimating reentry exposure to
warehouse facilities, EPA assumed 24 hours elapsed before reentry is
allowed, as required on labels; and that workers spend 60 minutes per
day in the treated area. Dichlorvos is applied at the rate of 2.0 grams
active ingredient per 1,000 ft^3^ over a period of 125 minutes per
application. Dermal exposure was measured for the hands only and
represents an average of the total exposure measured for three work
stations. Because significant exposure occurs for only one day and
occurs sporadically, this is considered an acute reentry scenario and
MOEs are calculated using the BMDL~10~ of 0.8 mg/kg for inhibition of
rat cholinesterase.

The dermal exposure is described in footnote (4).

> The methodology for inhalation exposure and risk are described in
> footnote (4). Assuming a worker reenters a treated warehouse 24 hours
> after application and works for one hour, the average dichlorvos
> concentration in the interval from 24 to 25 hours is 0.074 mg/m^3^.
> The dose on a mg/kg basis is:

0.074 mg/m^3^ x 1.0 m^3^/hr x 1 hr / 70 kg = 0.0010 mg/kg/day

> MOE = [0.8 mg/kg/day]{.underline} = 800

0.0010 mg/kg/day

6\. Reentry - railcars and trucks. Dichlorvos can be applied to railcars
and trucks as a space spray, or as a surface spray. Some labels allow up
to 2 g ai/1000 ft^3^, others allow up to 2.5 g ai/1000 ft^3^. The
initial concentration of dichlorvos from 2.5 g ai/1000 ft^3^ would be 88
mg/m^3^. The concentration at later time intervals can be calculated
from the equation, C~t~ = C~0~ x e^-kt^, where k = 1, based on an
assumed air exchange rate of 1 air change per hour. In estimating
reentry exposure, EPA assumed 8 hours elapsed before reentry is allowed,
and that workers could spend 1 hour per truck or railcar and could load
4 railcars or trucks per day. Workers loading rail cars or trucks would
not be expected to have dermal exposure to dichlorvos. The air
concentration was estimated using initial air concentrations calculated
from the application rate, and assuming ventilation similar to a food
processing establishment (k=1). This exposure scenario was considered to
be short term due to rapid dissipation of dichlorvos. (Jaquith, D.,
2005).

Integrating the equation for a period of 8 to 9 hours,

C~t~ = -88 mg/m^3^ x (e^-9^ - e^-8^) = 0.0187 mg/m^3^

0.0187 mg/m^3^ x 1.0 m^3^/hr x 1 hr/truck x 4 trucks / 70 kg = 0.0011
mg/kg/day

> MOE = [0.1 mg/kg/day]{.underline} = 94

0.0011 mg/kg/day

> There is considerable uncertainty about the air exchange rate. Under
> the conditions described, the air exchange rate could be as low as 1/3
> per hour

**10.0 Data Needs and Label
Requirements**[]{#__RefHeading___Toc137619530 .anchor}

> **10.1 Toxicology**[]{#__RefHeading___Toc137619531 .anchor}

There are no outstanding toxicology data requirements.

> **10.2 Product Chemistry**

The discrepancy in the percent of active ingredient in several of the
technicals must be resolved.

> **10.3 Residue Chemistry**[]{#__RefHeading___Toc137619532 .anchor}

The residue chemistry database for dichlorvos is reasonably complete.
All labels must conform to the use pattern reflected in the residue data
submitted. The following data requirements remain outstanding.

***GLN 860.1380: Storage Stability Data***

The Reregistration requirements for storage stability data are not
fulfilled. Information pertaining to the storage intervals and
conditions of samples of the following commodities, from studies that
were reviewed in the Residue Chemistry Chapter of the Guidance Document,
must be submitted: packaged and bagged raw agricultural commodities and
processed food; bulk stored raw agricultural commodities; milk; eggs;
and meat, fat, and meat byproducts of dairy cows and poultry.
Alternatively, the registrant may demonstrate that there are sufficient
residue data which are supported by storage stability data to support
all registered uses of dichlorvos.

The available storage stability data indicate that residues of
dichlorvos are stable under frozen storage conditions for up to 90 days
in/on plant commodities, up to 4.5 months in/on peanuts, and up to 8
weeks in animal commodities.

***GLN 860.1480: Meat, Milk, Poultry, Eggs***

The Reregistration requirements for data pertaining to this guideline
topic are not completely fulfilled. A dermal magnitude of the residue
study must be submitted for swine. No additional data are required for
milk and edible tissues of ruminants, and for eggs and edible tissues of
poultry. Swine use is on the labels for EPA Reg. Nos. 572-246 and
47000-130.

> **10.4 Occupational and Residential
> Exposure**[]{#__RefHeading___Toc137619533 .anchor}

All labels must conform to the parameters used in this risk assessment.
Protective clothing requirements at least as stringent as that used in
this risk assessment must be added to the label. Labels permitting
fogging must be clarified to state that hand-held foggers are not
permitted, and that the applicator must be outside the treated area
during application.

The greenhouse exposure study requirement has been satisfied by a
generic study on malathion, which allowed the Agency to determine a
transfer coefficient for harvesting greenhouse grown cut flowers. MRID
46513901, (Dole, T and M. Lloyd, 2005)

[Dichlorvos from trichlorfon.]{.underline}

Outstanding exposure data requirements exist for trichlorfon. A TTR
study with analyses for trichlorfon and dichlorvos in the turf and in
the toddler breathing zone above the turf (18\") is requested to confirm
the exposure estimates in this document. The study must be conducted at
an appropriate pH (approx. 7). A field dissipation study may be
substituted, provided it meets these requirements.

***GDLN 875.2100 Foliar Residue Dissipation Study (replaces GDLN
132-1(a))***

***GDLN 875.2400 Dermal Exposure (replaces GDLN 133-3, Dermal Passive
Dosimetry)***

***GDLN 875.2500 Inhalation Exposure (replaces GDLN 133-4, Inhalation
Passive Dosimetry)***

**REFERENCES**[]{#__RefHeading___Toc137619534 .anchor}

Abdel‑Saheb I. 1998. Drinking Water Assessment for Dichlorvos (Revised).
May 21, 1998.

Abdel‑Saheb I. 2001. Drinking Water Assessment for Dichlorvos (Revised),
Nov 13, 2001.

Abdel‑Saheb I. 2003. Drinking Water Assessment for Dichlorvos (Revised),
March 16, 2003.

Alavanja MCR, Samanic C, Dosimeci M, Lubin J, Tarone R, Lynch CF, Knott
C, Thomas K, Hoppin JA, Barker J, Coble J, Sandler DP, Blair A. (2003).
Use of agricultural pesticides and prostate cancer risk in the
Agricultural Health Study cohort. American Journal of Epidemiology,
157(9), 800‑814.

Bangs, G. 2001. Summary of HED's Reviews of Outdoor Residential Exposure
Task Force (ORETF) Chemical Handler Exposure Studies; MRID 44972201.
ORETF Study Numbers OMA001, OMA002, OMA003, OMA004., DP Barcode D261948,
memo dated April 30, 2001.

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Berge, G.N.; Fonnum, F.; Soli, N.; Sognen, E. 1987 b. Neurotoxicological
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Dow, M. 1985. DDVP (Vapona) QUA, Memorandum to D. Pillitt (RD) dated
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Dykstra, W. 2003. Acute Cholinesterase Studies in Rats with Technical
Dichlorvos (DDVP). DP Barcode: D288142, D287150. TXR 0051385. May 19,
2003.

Dykstra, W. 2004. DDVP Human Inhalation Study (Arizona II), DP Barcode:
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2004.

Dykstra, W. 2004. DDVP Human Inhalation Study (Arizona II). DP Barcode:
287238. TXR 0052550. May 17, 2004.

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D298913, PC Code: 084001. MRID:46239801 (repeat), 46153302 (main study),
46153301 (preliminary study). TXR 0052375. February 8, 2005.

Dykstra, W. 2005b. Review of Developmental Neurotoxicity Studies. DP
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45805701, 45805702, 45805703 (acute-adult), 45842301 (acute-preweaning),
46153304 (repeated). TXR 0052712. February 8, 2005.

Dykstra, W. 2005c. Weight of Evidence Comparison of Human and Animal
Toxicology Studies and Endpoints for DDVP. DP Barcode: 312212. TXR
0053055. June 23, 2005.

Dykstra, W. 2005d. Re-evaluation of DNT Studies for DDVP-Combined
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ExpoSAC, 1998. Science Advisory Council for Exposure, Policy #: 003,
Agricultural Default Transfer Coefficients, May 7, 1998.

ExpoSAC, 2001. Science Advisory Council for Exposure, Policy #: 11.
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ExpoSAC, 2001a. Draft policy on Pet Collar Exposure Assessment, December
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Goh, K.S, S. Edmiston, K.T. Maddy, D.D. Meinders and S Margetich (1986)
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0H2477; prepared by Associates in Laboratory Medicine, P.C., submitted
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Hummel S. V. 1998b. Dichlorvos (084001). Anticipated Residues for
Dichlorvos resulting from use of Dichlorvos and Naled. June 15, 1998.

Hummel, S. V. 1998c. Dichlorvos (084001). Product and Residue Chemistry
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Hummel S. V. 2000. Dichlorvos (084001). Refined Anticipated Residues and
Acute Dietary Exposure and Risk for Residues of Dichlorvos resulting
from use of Dichlorvos and Naled. April 7, 2000.

Hummel, S. V., D. Hrdy, M. Sahafayen. 2000. Dichlorvos (084001). Refined
Anticipated Residues and Dietary Exposure and Risk for Residues of
Dichlorvos resulting from use of Dichlorvos, Trichlorfon, and Naled.
June 7, 2000.

Hummel, S. 2005. Dichlorvos (DDVP) HED Chapter of the Reregistration
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Barcode: D302286. January 31, 2005.

Jaeger R. 1989. Transmittal of the Final FIFRA Science Advisory Panel
Report on the September 28-29 Meeting. Memo to D. Campt. October 16,
1989.

Jaquith D. 1987a. Exposure Assessment for Dichlorvos. August 4, 1987.

Jaquith D. 1987b. Refinement of Exposure Assessment for Dichlorvos.
August 7, 1987.

Jaquith D. 1987c. Further Refinement of Exposure Assessments for
Dichlorvos. August 14, 1987.

Jaquith D. 1993a. Revisions to Exposure Assessment for Dichlorvos. April
15, 1993.

Jaquith D. 1993b. Assessment of Exposures of Residents to Dichlorvos
Applied as a Total Release Fogger. MRID 41928801. May 10, 1993.

Jaquith D. 1993c. Review of Exposure Monitoring Study for Use of DDVP in
Food Processing Establishments, DP Barcode D191571, December 6, 1993.

Jaquith D. 1996.  Response to Public Comments on Dichlorvos PD 2/3. June
4, 1996.

Jaquith D. 1998a. Exposures from Dichlorvos (DDVP) Resin Strips.
D246131. March 5, 1998.

Jaquith D. 1998b. Re-entry Exposures to Dichlorvos Resulting from
Application to Residential Turf and Recreational Areas. D246126. March
16, 1998.

Jaquith D. 1998c. Exposures to Dichlorvos (DDVP) from Flea Collars.
March 18, 1998.

Jaquith D. 1998d. Exposure Assessment for Dichlorvos (DDVP) Applied to
Greenhouse and Mushroom Houses. April 22, 1998.

Jaquith D. 1998e. Exposure to Dichlorvos resulting from the Use of Bait
Products. D246128. April 28, 1998.

Jaquith D. 1998f. Inhalation Exposures from Dichlorvos (DDVP) Resin
Strips. June 12, 1998.

Jaquith D. 1998g. Revised Applicator Exposures to Dichlorvos resulting
from Crack and Crevice Use and the Use of Aerosol Products. D261140.
April 30, 1998.

Jaquith D. 1998h. Revisions of Exposures from Dichlorvos (DDVP) Resin
Strips. D250069. September 30, 1998.

Jaquith D. 1998i. Exposures to Dichlorvos Resulting from the Use of Bait
Products. D251336. January 27, 1999.

Jaquith D. 1998j. Response to Comments from EXPOSAC on Exposure
Assessment for Dichlorvos (DDVP) from Flea Collars. D 246127. November
6, 1998.

Jaquith D. 1998k. Response to EXPOSAC Comments on Exposure Assessment
for Total Release Foggers Containing Dichlorvos (DDVP). D251333.
December 31, 1998.

Jaquith D. 1998l. Revised Applicator Exposures to Dichlorvos (DDVP)
Resulting from Dairy Barn and Animal Spray Uses. D251330. January 27,
1999.

Jaquith D. 1998m. Response to Comments from the EXPOSAC and Others on
Assessment of Re-entry Exposures to Dichlorvos Resulting from
Application to Residential Turf and Recreation Areas. D251909. January
28, 1998.

Jaquith D. 1998n. Revised Exposure Assessment for Greenhouses and
Mushroom Houses. D251337. January 27, 1999.

Jaquith, D. 1999a. Response to Amvac Comments on HED Interim Risk
Assessment for DDVP. D255064. March 17, 1999.

\\

Jaquith, D. 1999b. Examination of Recent Submissions from Amvac
regarding Dichlorvos (DDVP) and Rationale for Not Including Them in the
Exposure/Risk Assessment. May 27, 1999.

Jaquith, D., 1999c. Dislodgeable Foliar Residues and Exposure Assessment
for Residential/Recreational Turf Applications of Dichlorvos (DDVP), PC
Code 084001, Barcodes D248456, D248596, D255253, August 13, 1999.

Jaquith, D., 1999d. Calculation Error - Dichlorvos Resin Strips,
D257002, August 16, 1999.

Jaquith, D, 2000. Dichlorvos (DDVP) Resin Strip Exposure Assessment for
Individuals Exposed for a 2 Hour Period, PC Code 084001. July 21, 2000.

Jaquith, D., 2000a. Revision of Exposure Assessment for DDVP applied to
Warehouses and Food Processing Plants. D226572. June 7, 2000.

Jaquith, D., 2001. Response to Comments on the Preliminary Risk
Assessment (PRA) for Dichlorvos (PC Code 084001, DP Barcode D271993).
May 31, 2001.

Jaquith, D., 2003. Addendum to Residential Turf Assessment for
Dichlorvos (DDVP) PC Code 084001, DP Barcode D288914. March 28, 2003.

Jaquith, D., 2003a. Review of Protocol for Study Monitoring Indoor Air
Concentrations of DDVP Using Pest Strips in Confined and Unoccupied
Areas. DP Barcode D288575. March 14, 2003.

Jaquith, D., 2005. Exposure Assessment for Workers Applying DDVP to Rail
Cars and Stationary Trucks and Subsequently Loading Cargo onto the
Treated Vehicles (PC Code 084001, DPBarcode D289191), January 27, 2005.

Johnston, Jason , et al., A Re‑analysis of Observations on Occupants of
Arizona Homes Containing 20% Vapona Insecticide Resin Strips (Arizona II
Home Study):, Exponent, Inc. December 4, 2002. Exponent, Inc.
(Washington, D.C.).Laboratory Study No. Dichlorvos 02‑01. MRID 45812001.
Unpublished.

Jones, R. D., 2006. Qualitative Assessment of Human Exposure to
Dichlorvos formed from Trichlorfon through Drinking Water and Inhalation
Routes. EPA Memorandum to Dayton Eckerson and Sue Hummel, dated May 17,
2006.

Kent, R. 2001. Use of Human Toxicity Studies on Dichlorvos (DDVP) to
Decrease the Interspecies Scaling Factor (PC Code 084001, DP Barcode
D278926). TXR: 0050250. November 1, 2001.

Khasawinah, A. and Diwan, S. 1999. Trichlorfon and Dichlorvos (DDVP):
Reassessment of the Requirements for the Prenatal Developmental Studies
in Guinea Pig - Report of the Hazard Identification Assessment Review
Committee. August 10, 1999. HED Document No. 013989.

Klonne, D. (1999) Integrated Report for Evaluation of Potential
Exposures to Homeowners and Professional Lawn Care Operators Mixing,
Loading, and Applying Granular and Liquid Pesticides to Residential
Lawns: Lab Project Number: OMAOO5: OMAOO1: OMAOO2. Unpublished study
prepared by Ricerca, Inc., and Morse Laboratories. 2213 p. (MRID
44972201)

Knox, B.; Askaa, J.; Basse, A.; Bitsch, V.; Mandrup, M.; Ottosen, H.;
Overby, E.; Pedersen, K.; Rasmussen, F. 1978. Congenital ataxia and
tremor with cerebellar hypoplasia in piglets borne by sows treated with
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Exposure/Risk Assessment. PC Code 057901. DP Barcode D268125. August 9,
2000.

Lewis. P. 1998. Transmittal of the Final Report of the FIFRA Scientific
Advisory Panel Meeting Held July 29-30, 1998. Memorandum to M. Mulkey,
Director, Office of Pesticide Programs.

Lowit, A. 2006. Benchmark Dose Analysis of cholinesterase inhibition
data in neonatal adult rats (MRID 46688914) following exposure to DDVP.
June 9, 2006.

Maddy KT, Schneider F, Lowe J, Ochi E, Frederickson S, and Margotich S.
1981. Vapona (DDVP) Exposure Potential to Workers in Mushroom houses in
Ventura County, California in 1981. HS-861. As cited in Jaquith 1998d.

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Wiley & Sons, New York, Table 2.1, page 14.

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Trichlorfon and other organophosphates on prenatal brain development in
the guinea pig. Neurochem. Res. 19(5):569‑574.

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Livestock(GLN 860.1300), Residue Analytical Method (GLN 860.1340),
Storage Stability Data (GLN 860.1380), Magnitude of Residue in Livestock
(GLN 860.1480), and Residue Depletion after Dermal Application (GLN
860.1300). DP Barcode \# D244279, D254894. Case 0104; MRID Nos.
44500701, 44500702, 44500703, 44500704, 44781401, June 24, 1999.

Morton, T. 2000. Trichlorfon (057901): HED Revised Preliminary Risk
Assessment for Trichlorfon. DP Barcode D268728. Case 0104. September 19,
2000.

Nigg, H. N., J. H. Stamper, W. D. Mahon. 1987. Pesticide Exposure to
Florida Greenhouse Applicators. Grant No. CR-810743. Sponsored by EPA.

Parker RD, Nelson, HP, and Jones D. 1995. GENEEC: a Screening Model for
Pesticide Environmental Exposure Assessment. The International Symposium
on Water Quality Monitoring. American Society of Agricultural Engineers.
P. 485.

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REJV, 2002. Residential Exposure Joint Venture, electronic database,
study period May 2001 - April 2002.

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Exposure and Risk Analyses. Addendum to Human Health Risk Assessment. DP
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Hazard Identification Assessment Review Committee. June 3, 1998.

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Schaible, S. 1994. and Chronic Dietary Exposure Analysis for Dichlorvos.
December 2, 1994.

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Review of 28 day Neurotoxicity Study. April 9, 1998.

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to Dichlorvos, and their relevance to Dichlorvos risk assessment (MRID
44308001). April 10, 1998.

Sette, W. F. 1999a. DDVP (084001): Response to AMVAC letter of 1/19/99
related to EPA\'s basis for concern for potential developmental
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May 3, 1999.

Stewart J. 1993. Review of Human Toxicology Data on Dichlorvos (DDVP).
TXR 010157. Memorandum dated April 8, 1993.

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Stewart 1996a. Dichlorvos Special Studies. MRID 42880101, 42881101. May
30, 1996.

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Severity of Mononuclear Cell Leukemia observed in Male fisher 344 Rats
in the Two Year Carcinogenicity Study. MRID 43565601. June 20, 1996

Stewart J. 1996. Dichlorvos. Transmittal of the Quantitative Risk
Assessment and Response to Registrant's questions concerning
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Stewart J. and W. Burnam 1996. Fifth Carcinogenicity Peer Review of
Dichlorvos. Tox Chem \# 328, PC Code 084001. August 28, 1996.

Stewart J. 1997. Toxicology Branch Response to Public Comments on the PD
2/3 for Dichlorvos. April 16, 1997.

Stewart J. 1998. Review of Toxicity Studies on Dichlorvos Using Human
Volunteers. March 24, 1998. MRIDs 44317901, 4416201, 44248801, 44248802.

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Environmental Protection Agency, Office Of Pesticides, Prevention, and
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Residential Exposure Assessments. December 19, 1997. (See also ExpoSAC,
2001)

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Scientific Issues Being Considered by the Agency in Connection with DDVP
(Dichlorvos) Risk Issues. pp 14-26 .

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report. Risk Assessment Forum, Office of Research and Development, U.S.
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http://www.epa.gov/pesticides/cumulative/rra‑op/

**Appendices**[]{#__RefHeading___Toc137619535 .anchor}

**1.0 TOXICOLOGY DATA REQUIREMENTS**

The toxicology data requirements (40 CFR 158.340) for food uses for
dichlorvos are in Table 1. Use of the new guideline numbers does not
imply that the new (1998) guideline protocols were used.

+-----------------------------------------+-------------+-------------+
| **Test**                                | **          |             |
|                                         | Technical** |             |
+=========================================+=============+=============+
|                                         | *           | **          |
|                                         | *Required** | Satisfied** |
+-----------------------------------------+-------------+-------------+
| 870.1100 Oral Toxicity                  | yes         | yes         |
|                                         |             |             |
| 870.1200 Dermal Toxicity                | yes         | yes         |
|                                         |             |             |
| 870.1300 Inhalation Toxicity            | yes         | yes         |
|                                         |             |             |
| 870.2400 Primary Eye Irritation         | yes         | yes         |
|                                         |             |             |
| 870.2500 Primary Dermal Irritation      | yes         | yes         |
|                                         |             |             |
| 870.2600 Dermal Sensitization           | yes         | yes         |
+-----------------------------------------+-------------+-------------+
| 870.3100 Oral Subchronic (rodent)       | yes         | yes         |
|                                         |             |             |
| 870.3150 Oral Subchronic (nonrodent)    | yes         | yes^a^      |
|                                         |             |             |
| 870.3200 21-Day Dermal                  | no          | yes         |
|                                         |             |             |
| 870.3250 90-Day Dermal                  | no          |             |
|                                         |             |             |
| 870.3465 90-Day Inhalation              | yes         |             |
+-----------------------------------------+-------------+-------------+
| 870.3700a Developmental Toxicity        | yes         | yes         |
| (rodent)                                |             |             |
|                                         | yes         | yes         |
| 870.3700b Developmental Toxicity        |             |             |
| (nonrodent)                             | yes         | yes         |
|                                         |             |             |
| 870.3800 Reproduction                   |             |             |
+-----------------------------------------+-------------+-------------+
| 870.4100a Chronic Toxicity (rodent)     | yes         | yes^b^      |
|                                         |             |             |
| 870.4100b Chronic Toxicity (nonrodent)  | yes         | yes         |
|                                         |             |             |
| 870.4200a Oncogenicity (rat)            | yes         | yes^b^      |
|                                         |             |             |
| 870.4200b Oncogenicity (mouse)          | yes         | yes         |
|                                         |             |             |
| 870.4300 Chronic/Oncogenicity           | yes         | yes         |
+-----------------------------------------+-------------+-------------+
| 870.5100 Mutagenicity---Gene Mutation - | yes         | yes         |
| bacterial                               |             |             |
|                                         | yes         | yes         |
| 870.5300 Mutagenicity---Gene Mutation - |             |             |
| mammalian                               | yes         | yes         |
|                                         |             |             |
| 870.5xxx Mutagenicity---Structural      | yes         | yes         |
| Chromosomal Aberrations                 |             |             |
|                                         |             |             |
| 870.5xxx Mutagenicity---Other Genotoxic |             |             |
| Effects                                 |             |             |
+-----------------------------------------+-------------+-------------+
| 870.6100a Delayed Neurotox. (hen)       | yes         | yes         |
|                                         |             |             |
| 870.6100b 90-Day Neurotoxicity (hen)    | no          | yes         |
|                                         |             |             |
| 870.6200a Neurotox. Screening Battery   | yes         | yes         |
| (rat)                                   |             |             |
|                                         | yes         | yes         |
| 870.6200b 90 Day Neuro. Screening       |             |             |
| Battery (rat)                           | yes         |             |
|                                         |             |             |
| 870.6300 Developmental Neurotoxicity    |             |             |
+-----------------------------------------+-------------+-------------+
| 870.7485 General Metabolism             | yes         | yes         |
|                                         |             |             |
| 870.7600 Dermal Penetration             | yes         | yes         |
+-----------------------------------------+-------------+-------------+
| Special Studies for Ocular Effects      | no          |             |
|                                         |             |             |
| > Oral (rat)                            | no          |             |
| >                                       |             |             |
| > Subchronic Oral (rat)                 | no          |             |
| >                                       |             |             |
| > Six-month Oral (dog)                  |             |             |
+-----------------------------------------+-------------+-------------+

a = subchronic (oral) dog study is satisfied by chronic dog study

b = chronic toxicity in rats and oncogenicity in rats are satisfied by
chronic toxicity/carcinogenicity rat study

**2.0 REFERENCES FOR TOXICOLOGY STUDIES**

**[Alternative Selection for Acute RfD:]{.underline}**

**[Study Selected]{.underline}: Acute Cholinesterase Study - Humans
Non-guideline**

**[MRID]{.underline}: 44248802**

**[Title]{.underline}:** Dichlorvos: A Study to Investigate the Effect
of a Single Oral Dose on Erythrocyte Cholinesterase Inhibition in
Healthy Male Volunteers; Gledhill, AJ; March 25, 1997

**[Executive Summary]{.underline}:** Dichlorvos was administered in a
single oral dose of 70 mg (equivalent to 1 mg/kg bw) in corn oil by
capsule to fasted young healthy male volunteers. Prior to dosing,
baseline RBC cholinesterase activity was measured on study days -22,
-20, -18, -15, -13, -11, -8, -6, -4 and immediately prior to dosing. The
study subjects were medically supervised for clinical signs and body
temperature changes for 24 hours and for RBC cholinesterase inhibition
for up to fourteen days after administration of the DDVP capsules.
Plasma cholinesterase was not measured in this study.

Under study conditions, no adverse clinical signs or changes in body
temperature were reported. When the group mean RBC cholinesterase
activities were analyzed, there were statistically significant
reductions (p≤0.01) from the predose mean on days 5/6, day 7, and day
14. These statistically significant reductions represent percent
decreases of 10, 12, and 11%, respectively. No reduction in RBC
cholinesterase activity was apparent at other reporting periods. The
individual predose values used to calculate the mean RBC cholinesterase
activity varied by 17% for volunteer 1, 16% for volunteer 2, 6% for
volunteer 3, 10% for volunteer 4, 7% for volunteer 5, and 9% for
volunteer 6.

The NOAEL for RBC cholinesterase depression is 1.0 mg/kg bw and a LOAEL
was not established in the study.

Although the study results indicate that a significant decrease in mean
RBC cholinesterase was first observed at 5/6 days after treatment, with
significance also seen at 7 and 14 days posttreatment, measurements at
posttreatment days 1 and 3 were not significantly different from
baseline. These results are inconsistent with known information on the
chemical. Namely, given the rapid bioavailability and metabolism of
dichlorvos, it is unlikely that a significant decrease in RBC
cholinesterase would first be observed at day 5/6 posttreatment and not
also at days 1 and 3 posttreatment. The statistical significance
observed could be attributed to variation among individual participants.

[Lack of information on time of peak effect.]{.underline}

In the acute human study, the first cholinesterase measurement was
recorded 24 hours after dosing. In the study (MRID 46153303) on the
measurement of RBC and brain ChE activity in pre-weaning and adult
female rats treated with a single dose of 15 mg/kg dichlorvos,
time-course data demonstrate that the time of peak effect for both RBC
and brain ChE measurements is 1-3 hours post-dosing. Therefore, the
absence of biologically significant RBC ChE depression in the human
study may be due to the absence of blood sampling at the time of peak
effect (1-3 hours), since in the human study, the first measurement did
not occur until 24 hours after dosing.

Based on the information on time to peak effect, we conclude that the
lack of cholinesterase measurements prior to 24 hours post-treatment in
the acute human study may have influenced the apparent NOAEL. We have
therefore opted not to use the acute human study for regulatory
purposes.

**[CITATION]{.underline}: G. Milburn (2003) Dichlorvos: developmental
neurotoxicity study in rats. Central Toxicology Laboratory, Alderley
Park, Macclesfield, Cheshire, UK. Laboratory report number
CTL/RR0886/Regulatory/Report, November 10, 2003. MRID 46153302.
Unpublished.**

> **G. Milburn (2003) Dichlorvos: preliminary developmental
> neurotoxicity study in rats. Central Toxicology Laboratory, Alderley
> Park, Macclesfield, Cheshire, UK. Laboratory report number
> CTL/RR00885/Regulatory/Report, October 13, 2003. MRID 46153301.
> Unpublished.**

**[SPONSOR]{.underline}: Amvac Chemical Corporation.**

**[EXECUTIVE SUMMARY]{.underline}:**

In a developmental neurotoxicity study (2003, MRID 46153302, study
RR0886) Dichlorvos (99.0% a.i., batch #ST120700) was administered to 30
time-mated female Alpk:APfSD (Wistar-derived) rats per group by gavage
in de-ionized water at dose levels of 0, 0.1, 1.0, or 7.5 mg/kg bw/day
from gestation day (GD) 7 through postnatal day (PND) 7 and direct
treatment of the F1 offspring was carried out during PND 8-22,
inclusive. On PND 5, litters were culled to 8 pups (4/sex as closely as
possible), and litters containing fewer than 7 pups and/or fewer than 3
pups of each sex were removed from the study. The dams were subjected to
a functional observational battery (FOB) on GDs 10 and 17 and on PNDs 2
and 9. The F1 offspring were observed for attainment of preputial
separation or vaginal patency. Animals were allocated from within
litters for use in the following investigations: functional
observational battery assessments (PNDs 5, 12, 22, 36, 46, and 61);
locomotor activity assessment (PNDs 14, 18, 22, and 60); auditory
startle habituation (PNDs 23 and 61), water maze testing (PND 24-27 or
PND 59-62); and post mortem investigations including brain weight,
neuropathology, and morphometry (PNDs 12 and 63). Dosing was based on a
preliminary developmental neurotoxicity study in rats (MRID 46153301).

One high-dose female was sacrificed on LD 3 due to clinical signs
(pallor, piloerection, and slightly hunched posture and thin appearance)
and had a pale liver at necropsy. One mid-dose female died on GD 24 due
to parturition difficulties. There were no treatment-related effects on
maternal body weight, FOB parameters, or gestation length. The maternal
NOAEL is 7.5 mg/kg/day, the highest dose tested. A maternal LOAEL was
not established.

During LD 1-5, the control, low-, mid-, and high-dose groups,
respectively, had pup mortality of 22.6, 17.4, 17.5, and 28.1%, and
there were total litter losses of 20.0, 10.0, 17.9, and 18.5% of the
litters in these same respective groups. There were 2 total litter
resorptions in the high-dose group. The number of litters available
which were used for F1 offspring was 23, 21, 21, and 14 and the
viability indices were 77.4, 82.6, 82.5, and 69.0% for the control, low,
mid, and high dose groups, respectively.

Due to the low number of pups available in the high dose group, it was
necessary to combine this study (RR0886) with a repeat study (2004, MRID
46239801; study No. RR0988) consisting of controls and a dose level of
7.5 mg/kg in order to have sufficient pups for all assessments.

The DNT Committee determined that the two DNT studies combined (RR0886
and RR0988) had acceptable numbers of total pups examined in the
controls and high dose groups (\> 35 pups/sex examined in combined
studies) and, therefore, the developmental results of the combined
studies could be evaluated for the NOAEL/LOAEL. The classification of
the studies taken together was changed from unacceptable/non-guideline
to Acceptable/non-guideline. A comparison of the developmental findings
showed that the auditory startle reflex habituation Vmax in PND 23 high
dose males in study RR0886 had statistically significant increases
(37-49%) in 4 out of 5 blocks and study RR0988 had increases (7-15%),
although not statistically significant, in this same Vmax parameter in
PND 23 high dose males in 5 out of 5 blocks in comparison to controls
for each study.

Therefore, the developmental/offspring NOAEL was determined to be 1.0
mg/kg/day (based on study RR0886) and the developmental/offspring LOAEL
was 7.5 mg/kg/day (based on both studies RR0886 and RR0988) with the
effect being increases in auditory startle reflex habituation Vmax in
PND 23 high dose males in both studies.

This study when combined with the accompanying study is classified
Acceptable/non-guideline and may be used for regulatory purposes. It
does satisfy the guideline requirement for a developmental neurotoxicity
study in rats \[OPPTS 870.6300, §83-6; OECD 426 (draft)\], pending
review of the positive control data.

**[CITATION]{.underline}: G.M. Milburn (2004) Dichlorvos: supplemental
developmental neurotoxicity study in rats. Central Toxicology
Laboratory, Alderley Park, Macclesfield, Cheshire, UK SK10 4TJ.
Laboratory report number CTL/RR0988/Regulatory/Report, January 28, 2004.
MRID 46239801. Unpublished.**

**[SPONSOR]{.underline}: Amvac Chemical Corporation.**

**[EXECUTIVE SUMMARY]{.underline}:** In a preliminary developmental
neurotoxicity study (MRID 46153301) Dichlorvos (99.0% a.i., batch
#ST120700) was administered by gavage in de-ionized water to 15
time-mated female Alpk:APfSD (Wistar-derived) rats per dose at dose
levels of 0, 0.1, 1.0, or 7.5 mg/kg bw/day from gestation day (GD) 7
through postnatal day (PND) 22. In-life observations included maternal
clinical signs, body weight, and food consumption (during gestation) and
the number, survival, clinical signs, and body weight of the pups.
Erythrocyte (RBC) and whole brain acetylcholinesterase (AChE) activities
were measured as follows: in 5 dams/group on GD 22; in 5 dams/group on
PND 22; in selected fetuses from the dams killed on GD 22 (blood from
sufficient fetuses to attain adequate pooled sample volume and whole
brain from 4 fetuses/sex/litter); and in 5 pups/sex/group (1 per litter
where possible) on each of PNDs 2, 8, 15, and 22. Plasma AChE activity
was not measured.

There were no maternal deaths during the study. Three dams had abnormal
clinical signs: one control dam with piloerection on day 26; one
mid-dose dam with observations of paleness (days 24-26), hunched,
subdued behavior (day 26), and a total litter loss by day 26 (LD 3); and
one high-dose dam with irregular breathing on days 25-27. There were no
treatment-related effects on maternal food consumption, maternal body
weight, or gestation length. The study author mentioned body weight
decreases in high-dose dams beginning on LD 11, but these were of
insufficient magnitude to be considered biologically significant (just
3-4% less than controls). Under the conditions of this study, the LOAEL
for maternal systemic toxicity (other than acetylcholinesterase
inhibition) is not identified, and the NOAEL is greater than or equal to
7.5 mg/kg bw/day.

There were no treatment-related effects on the overall proportion of
pups born alive, the mean percentage of live pups per litter, or live
litter size on LD 1. Pup survival, body weight, and clinical signs were
unaffected by treatment. Two dams had total litter losses: one mid-dose
dam had a total litter loss by LD 3, and one low-dose dam had a total
litter loss (of 1 pup) by LD 2. An increased proportion of male pups in
the mid-dose group (64.8% vs. 46.2% for controls; p\<0.01) was
considered incidental to treatment because there was no similar finding
at the highest dose level. Under the conditions of this study, the LOAEL
for offspring toxicity (other than acetylcholinesterase inhibition) is
not identified, and the NOAEL is greater than or equal to 7.5 mg/kg
bw/day.

In maternal animals, RBC AChE activity was biologically significantly
inhibited at the mid- and high-dose treatment levels on GD 22 by 25% and
48%, respectively (p\<0.01) and on LD 22 by 24% and 50%, respectively
(p\<0.05 and p\<0.01). RBC AChE activity was also inhibited in high-dose
male and female (GD 22) fetuses by 28% (p\<0.5) \[p\<0.05\] and 21%
(n.s.), respectively. There were no treatment-related effects on RBC
AChE activity in male or female pups. The LOAEL for dichlorvos
erythrocyte acetylcholinesterase inhibition in maternal rats is 1.0
mg/kg bw/day, with a NOAEL of 0.1 mg/kg bw/day. The LOAEL for
erythrocyte acetylcholinesterase inhibition in offspring or fetuses is
7.5 mg/kg bw/day (based on male and female fetuses on GD 22), and the
NOAEL is 1.0 mg/kg bw/day.

In maternal animals, whole brain AChE activity was biologically
significantly inhibited in high-dose animals on GD 22 and LD 22 by 59%
and 67%, respectively (p\<0.01). Brain AChE activity was also inhibited
in high-dose male and female (GD 22) fetuses by 16% (p\<0.5) \[p\<0.05\]
and 21%, respectively (p\<0.01). There were no treatment-related effects
on brain AChE activity in male or female pups. The LOAEL for brain
acetylcholinesterase inhibition in maternal animals is 7.5 mg/kg bw/day,
with a NOAEL of 1.0 mg/kg bw/day. The LOAEL for brain
acetylcholinesterase inhibition in offspring or fetuses is 7.5 mg/kg
bw/day (based on male and female fetuses on GD 22), and the NOAEL is 1.0
mg/kg bw/day.

Based on the results of this study, dose levels of 0, 0.1, 1.0, and 7.5
mg/kg bw/day were chosen for the main study.

**[CITATION]{.underline}: Milburn, G.M.. (2003) Dichlorvos: time course
of cholinesterase inhibition in pre-weaning and adult rats. Central
Toxicology Laboratory, Cheshire, UK SK10 4TJ. Doc. No.
CTL/AR7310/Regulatory/Report. 26-SEPT-2003. MRID 46153303.
Unpublished.**

> **Twomey, K. (2002) Dichlorvos (DDVP): Acute cholinesterase inhibition
> study in rats. Central Toxicology Laboratory, Cheshire, UK SK104T3.
> Laboratory report number CTL/AR7079/SUM/Regulatory/Report; Study No.
> AR7079, 30-MAY-2002. MRID 45805701. Unpublished.**
>
> **Twomey, K. (2002) Dichlorvos (DDVP): Second acute cholinesterase
> inhibition study in rats. Central Toxicology Laboratory, Cheshire, UK
> SK104TJ. Laboratory report number CTL/AR7126/SUM/Regulatory/Report;
> Study No. AR7126, 19-JUNE-2002. MRID 45805702. Unpublished.**
>
> **Twomey, K. (2002) Dichlorvos (DDVP): Third acute cholinesterase
> inhibition study in rats. Central Toxicology Laboratory, Alderley
> Park, Macclesfield, Cheshire, UK SK104TJ. Laboratory report number
> CTL/AR7138/Regulatory/Report; Study No. AR7138, 26-JUNE-2002. MRID
> 45805703. Unpublished.**
>
> **Moxon, M.E. (2002) Dichlorvos: Acute cholinesterase inhibition study
> in pre-weaning rats. Central Toxicology Laboratory, Cheshire, UK
> SK104T3. Laboratory report number CTL/AR7147/Regulatory/Report; Study
> No. AR7147, 22-NOV-2002. MRID 45842301. Unpublished.**
>
> **Moxon, M.E. (2003) Dichlorvos: Repeat dose cholinesterase inhibition
> study in pre-weaning and young adult rats. Central Toxicology
> Laboratory, Cheshire, UK SK104TJ. Laboratory report number
> CTL/KR1490/Regulatory/Report; Study No. KR1490, 24-OCT-2002. MRID
> 46153304. Unpublished.**

**[SPONSOR]{.underline}: AMVAC, Los Angeles, CA**

**[EXECUTIVE SUMMARY]{.underline}:** In a series of special comparative
cholinesterase inhibition (ChEI) studies, Dichlorvos (DDVP; 99% a.i.,
lot #ST 120700) was administered by gavage to groups of either
Sprague-Dawley or Wistar rats. For time-course evaluation (MRID
46153303) 5 females/group were given a single oral dose of 0 or 15 mg/kg
on PND 15 or 42 and sacrificed 1, 3, 8, 24, or 72 hours later. In three
acute studies (MRIDs 45805701, 45805702, 45805703) groups of 5 adult
rats/sex were given a single oral dose of 0, 1, 5, 15, or 35 mg/kg and
sacrificed one hour post-dosing or on post-dosing days 8 and 15. In a
fourth acute study, groups of 5 pre-weaning rats/sex were given a single
oral dose of 0, 1, 5, or 15 mg/kg on PND 8, 15, or 22 and terminated one
hour post-dosing. Finally repeated administration was studied by giving
seven daily doses of 0, 0.1, 7.5, or 15 mg/kg/day to groups of 5
rats/sex beginning on either PND 12 or 42; animals were sacrificed one
hour after the last dose. RBC and brain ChE activities were measured in
all animals in each study. Plasma enzyme activity was not measured in
any study.

Based on the analytical data for MRID 45805701, the low-dose animals
were actually dosed with 2.1 mg/kg, rather than the desired dose of 1.0
mg/kg/day. For the remaining studies, the analytical data indicated that
the mixing procedure was adequate and that the difference between
nominal and actual dosage to the study animals was acceptable for all
studies.

At a single dose of 35 mg/kg, one female died with cholinergic signs and
four males were killed for humane reasons due to severe toxicity. The
remaining animals of both sexes given 35 mg/kg displayed some or all of
the following signs: decreased activity, lachrymation, miosis, irregular
breathing, clonic convulsions, tremors/fasciculations, prostration,
decreased righting and splay reflexes, and salivation. A single dose of
15 mg/kg resulted in miosis and fasciculations in one adult female, and
tremors in one male and one female on PND 8 and one female on PND 22. No
treatment related clinical signs were observed in animals of the 1 or 5
mg/kg dose groups following acute exposure.

Following repeated exposure of pre-weaning rats, tremors were observed
in 5/5 males and 5/5 females at 15 mg/kg/day on 3-5 days of the dosing
interval. In young adult rats at 15 mg/kg/day, tremors were observed in
3/5 males and 5/5 females on one to four days of the dosing interval. In
addition, tremors were seen in one adult male after the last dose of 7.5
mg/kg/day. No clinical signs of toxicity were observed in the remaining
groups.

Acute exposure to doses ≥5 mg/kg resulted in clear dose-related
inhibition of enzyme activity in both compartments in all groups. At 1
mg/kg, RBC enzyme activity was significantly inhibited in PND 8 females,
and PND 15 males and females, but not adults. Brain enzyme activity from
animals treated with 1 mg/kg was not significantly inhibited in adult or
pre-weaning males and females. Although there was inhibition of brain
enzyme activity at the low dose in MRID 45805701, the actual analytical
dose at this level was 2.1 mg/kg and not 1 mg/kg. Repeat of the 1 mg/kg
dose level was identified as a NOAEL for brain enzyme inhibition as
demonstrated in other acute studies.

Two studies included recovery groups held for up to 15 days
post-exposure. RBC enzyme activity of males and females treated with 35
mg/kg remained slightly inhibited by 9-15% at 8 days after exposure.
This is not considered biologically significant. No inhibition of RBC
enzyme activity was seen at any other dose at 8 or 15 days post-dosing.
Brain enzyme activity was not affected at any dose during the recovery
interval. Brain and RBC enzyme activities were maximally inhibited one
hour after dosing in both adult and pre-weaning female rats. Thereafter,
ChE inhibition in both compartments decreased to approximately control
levels by 8 hours post-dosing.

Dose-related inhibition of RBC and brain ChE activities was also
apparent after repeated dosing in both adult and pre-weaning rats.
Biologically significant inhibition of RBC enzyme activity (\>50%)
occurred at doses of 7.5 and 15 mg/kg/day in both sexes of adults and
pre-weaning and at the low dose for adult animals (11-17%). Brain enzyme
activity was statistically and biologically inhibited in both sexes at
doses of 7.5 and 15 mg/kg/day for adults (\>50%) and at all doses for
pups (\>20%).

> [For acute exposure]{.underline}:

the adult LOAEL for brain ChEI is 5 mg/kg for males and females

the adult NOAEL for brain ChEI is 1 mg/kg for males and females;

the offspring LOAEL for brain ChEI is 5 mg/kg (both sexes)

the offspring NOAEL for brain ChEI is 1 mg/kg (both sexes)

the adult LOAEL for red blood cell ChEI is 5 mg/kg (both sexes)

the adult NOAEL for red blood cell ChEI is 1 mg/kg (both sexes);

the offspring LOAEL for red blood cell ChEI is 1 mg/kg (both sexes)

the offspring NOAEL for red blood cell ChEI is not identified.

For acute exposure, the overall adult LOAEL for cholinesterase
inhibition in rats is 5 mg/kg based on enzyme inhibition in brain and
red blood cells; the adult NOAEL is 1 mg/kg.

For acute exposure, the overall offspring LOAEL for cholinesterase
inhibition in rats is 1 mg/kg based on enzyme inhibition in red blood
cells; the offspring NOAEL was not identified.

[For repeated exposure]{.underline}:

the adult LOAEL for brain ChEI is 7.5 mg/kg/day (both sexes)

the adult NOAEL for brain ChEI is 0.1 mg/kg/day;

the offspring LOAEL for brain ChEI is 0.1 mg/kg/day (both sexes)

the offspring NOAEL for brain ChEI is not identified;

the adult LOAEL for red blood cell ChEI is 0.1 mg/kg/day (both sexes)

the adult NOAEL for red blood cell ChEI is not identified;

the offspring LOAEL for red blood cell ChEI is 7.5 mg/kg/day (both
sexes)

the offspring NOAEL for red blood cell ChEI is 0.1 mg/kg/day;

For repeated exposure, the overall adult LOAEL for cholinesterase
inhibition in rats is 0.1 mg/kg/day based on enzyme inhibition in red
blood cells; the adult NOAEL is not identified.

For repeated exposure, the overall offspring LOAEL for cholinesterase
inhibition in rats is 0.1 mg/kg/day based on enzyme inhibition in brain;
the offspring NOAEL is not identified.

The cholinesterase activity measurements following an acute oral dose of
dichlorvos demonstrate approximately equal susceptibility between
juvenile and adult rats. In contrast, results from repeated exposures
show that juvenile rats are more susceptible than adults for brain ChEI.
In pups the brain ChE activity appeared to be more sensitive than RBC
enzyme activity. This susceptibility for brain cholinesterase was
observed in terms of the dose level at which an effect was observed
(i.e., the LOAEL for brain cholinesterase inhibition was lower for
juveniles than for adults). However, the LOAEL for RBC enzyme inhibition
was lower for adults than for juvenile rats. The fact that brain enzyme
activity in young animals was the most sensitive to inhibition by the
test article is of concern for potential developmental neurotoxicity.

Taken together these studies are classified Acceptable/Non-guideline for
the determination of RBC and brain cholinesterase activities following
treatment with dichlorvos in adult and juvenile rats. Main deficiencies
include omission of plasma measurements and lack of assessment in dams
and fetuses on GD 20.

**[870.6100 (81-7) Acute Delayed Neurotoxicity - Hen. MRID
41004702]{.underline}**

**CITATION: Beavers, J.; Driscoll, C.; Dukes, V.; et al. (1988) DDVP: An
Acute Delayed Neurotoxicity Study in Chickens: Final Report: Project No.
246‑103. Unpublished study prepared by Wildlife International Ltd. 86 p.
(MRID 41004702**

**EXECUTIVE SUMMARY:** In an acceptable acute delayed neurotoxicity
study (MRID 41004702), groups of ten chickens were exposed either to
vehicle (distilled water), DDVP at 16.5 mg/kg, or the positive control,
Tri-*o*-tolyl Phosphate (TOCP), at 600 mg/kg in corn oil. All birds
treated with DDVP were administered an intramuscular injection of
atropine sulfate at 5 mg/kg concurrent with DDVP dosing (the oral LD~50~
value of DDVP in chickens not administered atropine is reported at 16.15
mg/kg); atropine also was administered at 2 mg/kg on an individual basis
as needed to DDVP-treated birds.

After 21 days, DDVP-treatment and vehicle control birds were redosed
(with atropine

treatment as previously) and observed for an additional 21 days before
sacrifice. TOCP-treated birds were sacrificed 21 days after the initial
dose.

During the first forced locomotor activity evaluation on day 3, two hens
(G30 and G37)

of the DDVP-treated group displayed slight to moderate ataxia, and
refused to walk or perform the second walk. By day 7 (the second
evaluation) hen G37 was noted as being slightly ataxic when dropped,
appeared normal during the hop, but refused to walk alone. This bird
appeared normal when standing or walking in a group, but refused to move
when alone; this hen continued to refuse to walk alone at each
evaluation except for day 25. On days 36 and 39, the same hen also
refused to hop. However, when observed in a group, this bird did not
appear ataxic, and appeared to move in a normal manner.

On histopathological examination, bird G37 showed swelling of the axis
cylinder and nerve fiber degeneration in the sciatic nerve. Nerves from
5/10 positive control (TOCP-treated) hens showed evidence of peripheral
neuropathy, while those from 5/10 hens showed no significant neural
degenerative lesions; however, 3/5 of these hens had exhibited slight to
moderate ataxia during locomotor assessments. In summary, there were no
brain or spinal cord degenerative changes in any of the control, TOC, or
DDVP-treated groups. However, there were sciatic nerve degenerative
changes in 0/10, 5/10, and 1/10 in the negative control, TOCP, and DDVP
groups, respectively.

Although the authors considered the results equivocal, the findings have
been interpreted by HED as indicating a positive result for DDVP for
acute delayed neurotoxicity.

**[870.3100 (82-1) 13-Week Gavage Study in Sprague-Dawley Rats - MRID
41004701]{.underline}**

**CITATION: Kleeman, J. (1988) 13‑Week Gavage Toxicity Study with DDVP
in Rats: Final Report: Project ID: HLA 6274‑102. Unpublished study pre‑
pared by Hazleton Laboratories America, Inc. 294 p. MRID 41004701.**

**EXECUTIVE SUMMARY:** In an acceptable 13-week subchronic study (MRID
41004701), Crl:CD^R^(SD)BR rats, 10/sex/group, were gavaged with 0, 0.1,
1.5 or 15 mg DDVP/kg/day, 5 days/week, \"for at least 13 weeks.\" The
following (Table 5) summarizes possible effects:

Table 5.

+--------------------+----+----+-----+-----+-----+-----+-----+-----+
| Effect             | Co |    | 0.1 |     | 1.5 |     | 15  |     |
|                    | nt |    | mg  |     | mg  |     | mg  |     |
|                    | ro |    |     |     | DD  |     | DD  |     |
|                    | ls |    | DD  |     | VP/ |     | VP/ |     |
|                    |    |    | VP/ |     | kg/ |     | kg/ |     |
|                    |    |    | kg/ |     | day |     | day |     |
|                    |    |    | day |     |     |     |     |     |
+--------------------+----+----+-----+-----+-----+-----+-----+-----+
|                    | M  | F  | M   | F   | M   | F   | M   | F   |
+--------------------+----+----+-----+-----+-----+-----+-----+-----+
| Reduced RBC count, | \- | \- | \-  | \-  | \+  | \-  | \+  | \+  |
| hemoglobin &       |    |    |     |     |     |     |     |     |
| hematocrit         |    |    |     |     |     |     |     |     |
|                    |    |    |     |     |     |     |     |     |
| Week 14            |    |    |     |     |     |     |     |     |
+--------------------+----+----+-----+-----+-----+-----+-----+-----+
| Higher Mean        | \- | \- | \-  | \-  | \-  | \-  | \-  | \+  |
| Corpuscular        |    |    |     |     |     |     |     |     |
|                    |    |    |     |     |     |     |     |     |
| Volume             |    |    |     |     |     |     |     |     |
+--------------------+----+----+-----+-----+-----+-----+-----+-----+
| Higher Cholesterol | \- | \- | \-  | \-  | \-  | \-  | \+  | \-  |
+--------------------+----+----+-----+-----+-----+-----+-----+-----+
| Reduced Plasma ChE | \- | \- | \-  | \-  | \+  | \+  | \+  | \+  |
|                    |    |    |     |     |     |     |     |     |
| Week 7             | \- | \- | \-  | \-  | \+  | \+  | \+  | \+  |
|                    |    |    |     |     |     |     |     |     |
| Week 14            |    |    |     |     |     |     |     |     |
+--------------------+----+----+-----+-----+-----+-----+-----+-----+
| Reduced RBC ChE    | \- | \- | \-  | \-  | \+  | \+  | \+  | \+  |
|                    |    |    |     |     |     |     |     |     |
| Week 7             | \- | \- | \-  | \+  | \+  | \+  | \+  | \+  |
|                    |    |    |     |     |     |     |     |     |
| Week 14            |    |    |     |     |     |     |     |     |
+--------------------+----+----+-----+-----+-----+-----+-----+-----+
| Reduced Brain ChE  | \- | \- | \-  | \-  | \-  | \-  | \+  | \+  |
|                    |    |    |     |     |     |     |     |     |
| (termination)      |    |    |     |     |     |     |     |     |
+--------------------+----+----+-----+-----+-----+-----+-----+-----+

In addition, salivation and/or urine stains were noted in some high-dose
males and females at approximately 30 to 60 minutes post-dosing.
According to Table 12 (p. 52) of MRID 41004701, at terminal sacrifice
2/10 high-dose and 1/10 low-dose females (but no control females) had
generalized retinal atrophy. On page 79 \"unilateral retinal
degeneration\" occurred in 1/9 control females, 1/10 in the low-dose
group, 0/10 in the mid-dose, and 2/10 in the high-dose. Males in the
high-dose group had a noticeably (but not significantly) elevated mean
liver weight at termination (14.14 g vs. a control value of 12.46 g).
However, the mean liver-to-body weight ratio was significantly (p ≤
0.05) elevated (to a value of 0.0293 vs. a control value of 0.0267).

> The following mean plasma and RBC cholinesterase measurements were
> obtained for

weeks 7 and 14:

Table 6.

+-------------+---------------+------------+------------+------------+
|             | Males (Week   |            | Females    |            |
|             | 7)            |            | (Week 7)   |            |
+-------------+---------------+------------+------------+------------+
| Dosage      | Plasma ChE    | RBC ChE    | Plasma ChE | RBC ChE    |
|             |               |            |            |            |
| Level       | mu/mL         | mu/mL      | mu/mL      | mu/mL      |
|             |               |            |            |            |
| (mg/kg/day) | Mean (S.D.)   | Mean       | Mean       | Mean       |
|             |               | (S.D.)     | (S.D.)     | (S.D.)     |
+-------------+---------------+------------+------------+------------+
| 0           | 318 (67.3)    | 1195       | 813        | 1269       |
|             |               | (163.1)    | (326.2)    | (246.9)    |
+-------------+---------------+------------+------------+------------+
| 0.1         | 285 (32.0)    | 1166       | 933        | 1148       |
|             |               | (244.3)    | (382.1)    | (125.9)    |
+-------------+---------------+------------+------------+------------+
| 1.5         | 226\*(48.5)   | 90         | 692 (89.7) | 95         |
|             |               | 3\*(138.0) |            | 6\*(145.8) |
+-------------+---------------+------------+------------+------------+
| 15          | 112\*(24.2)   | 62         | 3          | 7          |
|             |               | 9\*(109.3) | 38\*(79.0) | 40\*(95.4) |
+-------------+---------------+------------+------------+------------+

> \*Reported as statistically significant, with p ≤ 0.05.
>
> Data are from Tables 13 and 14, p. 53 and 54 of MRID 41004701.
>
> Table 7.

+----------------+------------+------------+------------+------------+
|                | Males      |            | Females    |            |
|                | (Week 14)  |            | (Week 14)  |            |
+----------------+------------+------------+------------+------------+
| Dosage         | Plasma ChE | RBC ChE    | Plasma ChE | RBC ChE    |
|                |            |            |            |            |
| Level          | mu/mL      | mu/mL      | mu/mL      | mu/mL      |
|                |            |            |            |            |
| (mg/kg/day)    | Mean       | Mean       | Mean       | Mean       |
|                | (S.D.)     | (S.D.)     | (S.D.)     | (S.D.)     |
+----------------+------------+------------+------------+------------+
| 0              | 314 (56.7) | 1358       | 1091       | 1321       |
|                |            | (145.5)    | (462.0)    | (82.3)     |
+----------------+------------+------------+------------+------------+
| 0.1            | 282 (59.9) | 1247       | 1150       | 12         |
|                |            | (113.9)    | (485.2)    | 12\*(81.4) |
+----------------+------------+------------+------------+------------+
| 1.5            | 259 (69.9) | 1014\*     | 1020       | 10         |
|                |            | (62.6)     | (257.0)    | 02\*(81.5) |
+----------------+------------+------------+------------+------------+
| 15             | 2          | 78         | 57         | 8          |
|                | 04\*(45.1) | 7\*(103.6) | 5\*(142.2) | 74\*(86.8) |
+----------------+------------+------------+------------+------------+

> \*Reported as statistically significant, with p ≤ 0.05.
>
> Data are from Tables 13 and 14, p. 53 and 54 of MRID 41004701.

According to MRID 41004701 (p. 29): \"The apparent decrease of
inhibitory effect at week 14 \[as compared to week 7\] may have been due
to a longer post-treatment interval before blood collection and partial
recovery of cholinesterase activity.\"

> The following mean brain cholinesterase measurements were obtained at
> termination:
>
> Table 8.

+----------------------+-----------------------+-----------------------+
| Dosage               | Males                 | Females               |
|                      |                       |                       |
| Level                | Brain ChE             | Brain ChE             |
|                      |                       |                       |
| (mg/kg/day)          | mu/mL                 | mu/mL                 |
|                      |                       |                       |
|                      | Mean (S.D.)           | Mean (S.D.)           |
+----------------------+-----------------------+-----------------------+
| 0                    | 1105 (376.6)          | 1338 (490.0)          |
+----------------------+-----------------------+-----------------------+
| 0.1                  | 1213 (656.4)          | 1290 (376.2)          |
+----------------------+-----------------------+-----------------------+
| 1.5                  | 1060 (183.2)          | 1290 (336.5)          |
+----------------------+-----------------------+-----------------------+
| 15                   | 791\*(290.0)          | 680\*(216.6)          |
+----------------------+-----------------------+-----------------------+

\*Reported as statistically significant, with p ≤ 0.05.

In the review \[HED Doc. No. 007448\] it is stated that: \"The data
presented demonstrate that administration of DDVP at doses of 0, 0.1,
1.5 and 15 mg/kg\[/day\] resulted in no adverse effect on body weight or
food consumption. Although hematology parameters were reduced, it is
doubtful whether the reductions were biologically significant, because
the reductions were within ten percent of control values. Plasma and RBC
cholinesterase activity \[sic\] were reduced in mid and high dose
animals, and RBC cholinesterase activity was reduced in 0.1
mg/kg\[/day\] females at 14 weeks. However, the investigators did not
consider the RBC cholinesterase reduction in low dose females to be
biologically significant since it was less than ten percent below
control. The reduction of brain cholinesterase activity in high dose
male and female rats at study termination was biologically
significant.\"

\"No other changes were seen in the test animals which could be
attributed to administration of the test compound. The increased
liver/body \[weight\] ratio seen in high dose males was not accompanied
by any body weight or enzyme changes.\"

The data presented support a LOAEL of 1.5 mg/kg\[/day\] based on
cholinesterase inhibition (plasma and RBC in females and RBC in males).
The NOAEL is 0.1 mg/kg\[/day\]. A NOAEL of 1.5 mg/kg/day may be defined
based on decreased brain cholinesterase activity in both sexes.

**[870.6100 (82-5) Subchronic Neurotoxicity Study in Hens - MRID
43433501]{.underline}**

**CITATION: Redgrave, V. (1994) DDVP: 28‑Day Neurotoxicity in the
Domestic Hen: Lab Project Number: AVC 1/921405: RAD 2/942053.
Unpublished study prepared by Huntingdon Research Centre, Ltd. 465 p.
MRID 43433501.**

**EXECUTIVE SUMMARY:** Groups of 21 adult domestic hens were given oral
daily doses by gavage of 0, 0.3, 1.0, or 3.0 mg DDVP/kg in distilled
water. Fourteen birds from each group were treated for 28 days; an
interim sacrifice of 6 birds/group was performed on day 49 and the final
sacrifice of 6 birds/ group was performed on day 77. Satellite groups of
three birds from each original group of 21 were sacrificed on day 4 and
day 30 for brain cholinesterase and brain and spinal cord neurotoxic
esterase activity. An additional group of four birds was administered
0.1 mg DDVP/kg for 28 days for cholinesterase determination only. A
positive control group of 21 hens was administered 7.5 mg TOCP/kg, and
sacrificed as described above.

Mortality occurred in 1 bird in the 1.0 mg/kg dose group and in 4 birds
in the 3.0 mg/kg dose group. Subdued behavior, unsteadiness, and
vomiting were observed in the 3.0 mg/kg group shortly after dosing from
day 4 to day 29. Clinical signs were also observed in 2 birds after
dosing with 1.0 mg/kg on days 2 and 14. No delayed motor ataxia was
observes, and there was no clear evidence of organophosphate induced
delayed neuropathy. Decreased body weight was observed during the first
14 days of dosing at 1.0 and 3.0 mg/kg, but compensatory increases
occurred from day 14 onward. Brain cholinesterase activity was decreased
at day 4 in the 1.0 mg/kg and 3.0 mg/kg dose groups (44% and 63%
decrease, respectively, compared to controls); and, at day 30, brain
cholinesterase was dose-dependently decreased by 26%, 34%, and 54% in
the 0.3, 1.0, and 3.0 mg/kg dose groups, respectively. A slight increase
in minimal axonal degeneration was observed at 1.0 and 3.0 mg/kg. The
positive control responded appropriately.

A LOAEL of 0.3 mg/kg can be defined based on decreased brain
cholinesterase activity. The NOAEL is 0.1 mg/kg/day. A NOAEL of 0.3
mg/kg is defined based on axonal degeneration of more than one level of
the spinal cord at 1.0 mg/kg and above of DDVP.

This study meets the guideline requirements of 82-5 and is classified as
Acceptable.

**[870.3200 (83-2a) Two Year Gavage Study in F344 Rats. NTP TR 342, MRID
40299401]{.underline}**

**CITATION: Chan, P. (1987) NTP Technical Report on the Toxicology and
Carcinogenesis Studies of Dichlorvos (CAS No. 62‑73‑7) in F344/N Rats
and B63F1 Mice: (Gavage Studies): NTP TR 342. Draft Technical Report of
July, 1987 prepared for public review and comment. US Dept. of Health
and Human Services, Public Health Service, Publication No. NIH 88‑2598.
239 p. MRID 40299401.**

**EXECUTIVE SUMMARY:** In an oncogenicity gavage study (MRID 40299401),
4 or 8 mg/kg/day dichlorvos (DDVP) (97.8-98.2% a.i., lot SDC-092179,
batch 01) in corn oil (Mazola® "100% pure") was administered as 5 mL/kg
to 60 F344 rats/sex/dose 5 days/week for 103 weeks followed by a
one-week observation period. The controls received corn oil only. Five
rats/sex/dose were used only for plasma and RBC cholinesterase (ChE)
determination after 6, 12, 24, 36, 52, 78, and 104 weeks and 5
rats/sex/dose were used for brain and sciatic nerve histology at study
termination. The doses employed were based on results of a 13-week
subchronic study where 10 rats/sex/dose were given 0, 2, 4, 8, 16, 32,
or 64 mg/kg/day DDVP. All rats given 32 or 64 mg/kg/day and some rats
given 16 mg/kg/day had tremors, diarrhea, and convulsions and died
during the study, whereas the surviving rats had no clinical signs or
weight loss.

Mortality and weekly body weight gains were similar in treated and
control animals. Clinical signs among treated males included brown fur
around the nose, mouth, and anal areas, leaning head, and diarrhea, and
among treated females included vaginal discharge, wet fur in peri-anal
or pelvic area, and diarrhea. From 6-78 weeks, plasma ChE levels in the
4 and 8 mg/kg/day treated groups were lower than the respective control
levels by 52-72% and 53-72% in males and by 75-85% and 82-88% in
females, respectively. At 104 weeks, plasma ChE among treated groups of
both sexes were only 4-18% below controls, perhaps due to the
intervening week without treatment. RBC ChE levels were more variable:
values were decreased (13-65%) in both dose group females for weeks 6-78
and in the high-dose males (17-90%) for weeks 24-104, but in the
low-dose males were decreased (34-49%) only for weeks 36-78. Treatment
time did not appear to be directly related to ChE inhibition. No gross
lesions were found in the control or treated animals. The incidences of
hepatic cytoplasmic vacuolation, renal tubule mineralization, and
adrenal cortical vacuolation were increased in high-dose males and of
pancreatic (acinar) atrophy were increased in high-dose females (p ≤
0.05); it was unclear whether these effects were treatment-related.
Results of the brain and sciatic nerve histology examinations were not
given.

Under the conditions of this study, 4 mg/kg/day was identified as the
LOAEL for both sexes of rats based on decreased RBC and plasma ChE
levels. A NOAEL was not identified.

Treatment-related neoplastic lesions were seen in both sexes of rats.
Males had an increased incidence (p ≤ 0.05) of lung adenoma (8
mg/kg/day), mononuclear cell leukemia (both doses), and pancreatic
acinar adenoma (both doses). Females had an increased incidence of
mammary gland fibroadenoma (p ≤ 0.05 for both doses); an additional
high-dose female had mammary gland fibroma.

This study was classified as "supplementary for chronic study; minimum
for oncogenicity" when the Data Evaluation Report was originally
prepared (1987). Although this study did not follow the "Subdivision F"
guidelines for chronic toxicity, the most sensitive end-point for
toxicity, namely ChE inhibition, was measured and used as a basis for
NOAEL. Therefore, this study should be valid for performing risk
assessment.

**[870.3200 (83-2b) Two Year Gavage Study in B6C3F1 Mice. NTP TR 342.
MRID 40299401]{.underline}**

**[CITATION:]{.underline} Chan, P. (1987) NTP Technical Report on the
Toxicology and Carcinogenesis Studies of Dichlorvos (CAS No. 62‑73‑7) in
F344/N Rats and B63F1 Mice: (Gavage Studies): NTP TR 342. Draft
Technical Report of July, 1987 prepared for public review and comment.
US Dept. of Health and Human Services, Public Health Service,
Publication No. NIH 88‑2598. 239 p. MRID 40299401**

**EXECUTIVE SUMMARY:** In an oncogenicity gavage study (MRID 40299401),
dichlorvos (DDVP) (97.8-98.2% a.i., Lot SDC-092179, batch 01) in corn
oil (Mazola® "100% pure") was administered to 60 B6C3F1 mice/sex/dose 5
days/week for 103 weeks followed by a one-week observation period. Males
were given 10 or 20 mg/kg/day DDVP, females 20 or 40 mg/kg/day DDVP, and
controls corn oil only; the dosing volume was 10 mL/kg. Five mice/sex
dose were used only for plasma and RBC cholinesterase (ChE)
determination after 6, 12, 24, 36, 52, 78, and 104 weeks and 5
mice/sex/dose were used for brain and sciatic nerve histology at study
termination. The doses employed were based on results of a 13-week study
where 10 mice/sex/dose were given 0, 5, 10, 20, 40, 80, or 160 mg/kg/day
DDVP; all males and 9 females given 160 mg/kg/day died during the study.
The survivors had no dose-related body weight changes, toxic signs, or
significant pathology.

No treatment-related mortality or body weight changes were observed,
however, all male mice used for ChE determination died when blood was
withdrawn at 24 weeks. Reported clinical signs consisted of a slight
increase of left pelvic masses in high dose males and of distended
abdomens in treated females. Plasma ChE levels in males were 54-62% and
69-76% lower than controls at 10 and 20 mg/kg/day, respectively, from
6-24 weeks (death of mice precluded further analysis). Plasma ChE levels
in females were 64-73% and 79-90% lower than controls at 20 and 40
mg/kg/day, respectively from weeks 6-78, but were similar to or higher
than controls at week 104, perhaps due to the intervening week without
treatment. RBC ChE levels were more variable: levels were decreased
(26-46%) at week 24 in both sexes and by 11-33% at weeks 36, 52, and 104
in females, but were similar to or greater than controls at weeks 6 and
12 (both sexes, both doses) and 78 (females, both doses). Treatment time
did not appear to be directly related to ChE inhibition. No
treatment-related gross or microscopic lesions were found and no lesions
were seen in the animals used to investigate brain and sciatic nerve
histology.

Under the conditions of this study, a LOAEL of 10 mg/kg/day was
identified based on the decreased RBC and plasma ChE levels in males. A
NOAEL was not identified.

The incidence of forestomach squamous cell papilloma was increased in
high dose males (5/50 vs. 1/50 for controls, p = 0.06) and females
(18/50 vs. 5/50 for controls, p ≤ 0.05); forestomach carcinoma also
occurred in 2/50 high-dose females. Three high-dose males each had one
unusual neoplasm: glandular stomach carcinoid/carcinoma, duodenal
adenocarcinoma, or a duodenal adenomatous polyp.

This oncogenicity study was classified as "core-minimum" when the Data
Evaluation Report was originally prepared (1987).

**[870.4200 (83-2) 80-Week Feeding/Carcinogenicity study in Rats -
TXR007765, NCI, 1977]{.underline}**

**EXECUTIVE SUMMARY:** In an 80-week feeding/carcinogenicity study (NCI,
1977), groups of fifty 36-43 day old Osborne-Mendel rats/sex were
administered DDVP (94%) at dose levels (time-weighted average) of 150 or
326 ppm (7.5 and 16.3 mg/kg/day by standard convention methods). The
dosage for the high-dose group was 1000 ppm (50 mg/kg/day) for the first
3 weeks and was then changed to 300 ppm (15 mg/kg/day) for the remaining
77 weeks due to toxicity. A matched control group of 10 rats/sex was
included. The pooled control group consisted of 60 male and 60 female
rats. All animals were observed twice daily for signs of toxicity,
weighed at regular intervals, and palpated for masses at each weighing.
Gross and microscopic examination of all major tissues, organs and gross
lesions were made from sacrificed animals, and where feasible, from
animals found dead. Rats were sacrificed at 110-111 weeks.

Severe signs of toxicity including tremors, rough hair coat, diarrhea
and poor appearance were observed in the 1000 ppm DDVP group during the
first 3 weeks. All groups showed slight or moderate degrees of toxicity
during the first year. Treated animals showed an increased frequency of
toxic signs during the second year consisting of rough hair coats,
epistaxis, hematuria, alopecia, dark urine, bloating and abdominal
distension. No compound-related mortality was reported. Survival was 64%
and 76% in males in the low- and high-dose groups, respectively, for
over 105 weeks. Survival was 80% and 84% in females in the low- and
high-dose groups, respectively, for over 105 weeks. During the first
year and a half, body weights of male and female rats in the high-dose
group were consistently lower than the low-dose and matched control
groups. Thyroid follicular hyperplasia was increased in males in the
low-dose group (7%) and high-dose group (10%) when compared to controls
(0%). The incidence of alveolar macrophages was increased in treated
males (14-28%) and treated females (42-44%) when compared to controls
(0-10%). The incidence of interstitial fibrosis of the myocardium was
increased in treated males (24-32%) and treated females (30-38%) when
compared to controls (10%). Malignant fibrous histiocytoma was increased
in male rats in the low-dose group (8%) and high-dose group (16%) when
compared to pooled controls (3%, linear trend p=0.018). This neoplasm
occurred in 10% of the matched controls. Under the conditions of the
study, DDVP was not demonstrated to be carcinogenic in rats.

The study is Unacceptable-Guideline and does not satisfy the guideline
requirement (series 83-2) for a carcinogenicity study in rats. Too few
animals (10/sex) were used as matched controls and only 2 dose levels
were employed.

**[870.4200 (83-2) 94-Week Feeding/Carcinogenicity Study in B~6~C~3~F~1~
Mice - TXR 007765, NCI, 1977]{.underline}**

**EXECUTIVE SUMMARY:** In a 94-week feeding/carcinogenicity study (NCI,
1977), groups of fifty B~6~C~3~F~1~ mice/sex, 35-36 days of age, were
administered DDVP (94%) at dose levels (time-weighted average) of 318 or
635 ppm (47.7 and 95.3 mg/kg/day by standard convention methods). The
dosage levels for the low- and high-dose mice were 1000 and 2000 ppm
(150 and 300 mg/kg/day) for the first 2 weeks, then reduced to 300 and
600 ppm (45 and 90 mg/kg/day) for the remaining 78 weeks. A matched
control group of 10 mice/sex was included. The pooled control group
consisted of 100 males and 80 females. All animals were examined twice
daily for signs of toxicity, weighed at regular intervals, and palpated
for masses at each weighing. Gross and microscopic examination of all
major tissues, organs and gross lesions were made from sacrificed
animals and, where feasible, from animals found dead. The mice were
sacrificed at 92-94 weeks.

Initially, mice fed DDVP exhibited severe signs of toxicity: tremors,
rough coat, diarrhea and poor general appearance. After doses were
reduced, the behavior and appearance of treated mice were comparable to
controls. Survival was 92% and 90% in males in the low- and high-dose
groups, respectively. Survival was 74% and 84% in females in the low-
and high-dose groups, respectively. The body weight of male and female
mice in the high-dose group was generally lower after the initial growth
phase than the low-dose and control groups. Two squamous-cell carcinomas
of the esophageal epithelium occurred, 1 in a low-dose male and 1 in a
high-dose female. Two low-dose males had focal hyperplasia of the
esophageal epithelium. And one high-dose female had a papilloma of the
esophageal epithelium. There was insufficient information to establish
the association of esophageal tumors with DDVP treatment. Under the
conditions of the study, DDVP was not demonstrated to be carcinogenic in
mice.

The study is Unacceptable-Guideline and does not satisfy the guideline
requirement (series 83-2) for a carcinogenicity study in mice. Too few
animals (10/sex) were used as matched controls and only two dose levels
were employed.

**[870.4100 (83-1b) 52-Week Chronic Oral Toxicity Study in Dogs. MRID
41593101]{.underline}**

**CITATION: Markiewicz, V. (1990) A 52‑Week Chronic Toxicity Study on
DDVP in Dogs: Lab Project Number: 2534/102. Unpublished study prepared
by Hazleton Laboratories America, Inc. 431 p. MRID 41593101**

**EXECUTIVE SUMMARY:** In a chronic oral toxicity study (MRID 41593101),
dichlorvos (DDVP) (purity not given but was 97.3% in the preceding range
finding study; Lot No. 802097) was administered to 4 beagle
dogs/sex/dose by capsule for 52 weeks at doses of 0, 0.1, 1.0, or 3.0
mg/kg/day. Due to excessive plasma cholinesterase inhibition at week 2,
the low dose was changed from 0.1 to 0.05 mg/kg/day in both sexes on
treatment day 22 to achieve a NOAEL.

No dogs died during the study. Clinical signs included ataxia,
salivation, and dyspnea in one high-dose male on one day during week 33
and emesis in three high-dose females and one male and/or female at most
other doses. Cumulative body weight gains were lower than that of
controls only in the high-dose males, from approximately weeks 1-8. No
treatment-related effects were noted on the food consumption,
ophthalmoscopic examination, hematology, urinalysis, gross or
microscopic pathology, organ weights, or clinical chemistry except for
cholinesterase (ChE) measurements. After 2 weeks of treatment, plasma
ChE levels were 21-26% lower than pretreatment values for both sexes
given 0.1 mg/kg/day DDVP, prompting the dose decrease to 0.05 mg/kg/day
on day 22. At subsequent test weeks (6, 13, 26, 39, and 52), plasma ChE
levels in the low-dose group were within 12% of pretreatment values.
Plasma ChE levels of dogs given 1.0 and 3.0 mg/kg/day DDVP were
decreased 39-59% and 61-74%, respectively, throughout the study in both
sexes. RBC ChE levels were decreased in low-dose dogs at week 6 (24% in
males and 50% in females), likely due to effects of the earlier higher
dose of 0.1 mg/kg/day, but were within 13% of pretreatment values at all
other time points. At 1.0 or 3.0 mg/kg/day DDVP, RBC ChE levels in both
sexes were lowered 33-65% and 67-94%, respectively, throughout the
study. The % inhibition of neither plasma nor RBC ChE appeared to change
with time. Brain ChE measurements taken at termination were comparable
to concurrent controls for the low dose groups but were decreased at
both 1.0 mg/kg/day (22%, p ≤ 0.05 in males; 7%, N.S. in females) and 3.0
mg/ kg/day (47% in males and 29% in females, p ≤ 0.05 for both).

Under the conditions of this study, the NOAEL was identified as 0.05
mg/kg/day for both sexes. The L0EL was 1.0 mg/kg/day, based on the
inhibition of plasma and RBC ChE levels in both sexes and the inhibition
of brain ChE in males. It should be noted that the actual LOAEL could be
as low as 0.1 mg/kg/day since plasma ChE was decreased by nearly 25%
after the initial administration of this dose to the low-dose group
during the first two weeks.

This study was classified as acceptable (guideline) for satisfying the
guideline requirement for a chronic oral toxicity study (83-1b) in dogs.

**[870.3700 (83-3a) Developmental Oral Toxicity Study in SD
Rats.]{.underline}**

**CITATION: Tyl, R.; Marr, M.; Myers, C. (1991) Developmental Toxicity
Evaluation of DDVP Administered by Gavage to CD (Sprague‑Dawley) Rats:
Lab Project Number: 60C‑4629‑10/20. Unpublished study prepared by
Research Triangle Inst. 305 p. MRID 41951501**

**EXECUTIVE SUMMARY:** In a developmental toxicity study (MRID
41951501), 25 pregnant Sprague-Dawley rats per group were administered
Dichlorvos (96.86% a.i.; Lot No. 802097) by gavage at doses of 0, 0.1,
3.0, or 21.0 mg/kg/day on gestation days (GD) 6-15, inclusive. On GD 20,
all dams were sacrificed and all fetuses were examined for external
anomalies. Approximately one-half of all fetuses were examined for
visceral anomalies and the remainder stained and examined for skeletal
anomalies.

All animals survived until scheduled sacrifice. There was no evidence of
maternal toxicity at 0.1 or 3.0 mg/kg/day. At the high dose, clinical
signs of toxicity were indicative of cholinesterase inhibition. All
high-dose dams exhibited tremors at some time during the dosing period.
Other anticholinesterase-related signs of toxicity included prone
positioning, hindlimb splay, circling, vocalization, excitability,
hypoactivity, and labored respiration among others.

Absolute maternal body weights of the high-dose dams were significantly
(4-6%; p ≤ 0.05) lower than the controls on GD 9, 12, and 15 and body
weight gains during the dosing period were significantly (p ≤ 0.01)
decreased by 28%. Food consumption and food efficiency of high-dose dams
were significantly (p ≤ 0.01) less than the controls during the dosing
interval and overall (GD 0-20).

Therefore, the maternal toxicity LOAEL is 21 mg/kg/day based on clinical
signs of toxicity, reduced body weight gain, and food consumption and
efficiency. The maternal toxicity NOAEL is 3 mg/kg/day.

No treatment-related effects were observed for gravid uterine weights,
number of fetuses/litter, pre- and post-implantation loss, numbers of
corpora lutea/dam, number of implantations/dam, resorptions/dam, fetal
body weights, or fetal sex ratios. There were no developmental
malformations/variations in any fetus that were attributed to treatment.

Therefore, the developmental toxicity NOAEL is ≥21 mg/kg/day and the
developmental toxicity LOAEL was not identified.

This study is classified as Acceptable (guideline) and satisfies the
guideline requirements for a developmental toxicity study (83-3a) in
rats.

**[870.3700 (83-3b) Developmental Oral Toxicity Study in New Zealand
Rabbits.]{.underline}**

**CITATION: Tyl, R.; Marr, M.; Myers, C. (1991) Development Toxicity
Evaluation of DDVP Administered by Gavage to New Zealand White Rabbits:
Lab Project Number: 60C‑4629‑30/40. Unpublished study prepared by
Research Triangle Institute. 247 p. MRID No. 41802401**

**EXECUTIVE SUMMARY:** In a developmental (teratology) toxicity study
(MRID 41802401), 16 pregnant New Zealand rabbits per group were
administered Dichlorvos (97% purity; Lot No. 802097) by gavage at doses
0, 0.1, 2.5, or 7.0 mg/kg/day on gestation days (GD) 7-19. (Dose
selection was based on a range-finding study in which maternal toxicity,
including increased mortality (5/8 died), decreased weight gain, and
clinical signs, were manifested at the highest tested dose of 10
mg/kg/day.) At study termination (GD 30), the number of does with live
fetuses was 14, 12, 11, and 9 in each of the control, 0.1, 2.5, and 7.0
mg/kg/day group, respectively. On GD 30, all surviving dams were
euthanized and all fetuses were weighed and examined for external,
skeletal, and visceral anomalies.

Maternal toxicity (dose-dependent) was evident in the form of
dose-dependent increased mortality (four and two died in the high and
mid-dose groups, respectively), decreased mean body weight gain and
typical anticholinesterase-related clinical observations. Mean body
weight gain during the dosing period (GD 7-19) was 67% and 58% below
control in the mid and high dose groups, respectively. Mean body weight
gain during the entire gestation period (corrected for gravid uterine
weight) was variable where, compared to the control group, it was higher
in the low and mid dose groups (by 140% and 45%, respectively) and lower
(54%, p\<0.05) in the high dose group. There were no abortions but two
does in the low-dose group had premature deliveries (GD 23 and 30).

Therefore, based on mortality, and other effects, the maternal toxicity
LOAEL is 7.0 mg/kg/day; the maternal toxicity NOAEL is 2.5 mg/kg/day.

There were no statistically significant treatment-related differences in
the number (per doe) of corpora lutea, implantations, live fetuses,
resorptions, or dead fetuses. Though not indicated to be significantly
different than the control group, the low-dose group had fewer
implantations/doe (4.9 ± 0.8 vs. 7.0 ± 0.8) and fewer live fetuses/doe
(4.8 ± 0.8 vs. 6.5 ± 0.8). There were no apparent developmental
malformations or variations that could be attributed to treatment.

Therefore, the developmental toxicity NOAEL is \>7 mg/kg/day and the
developmental toxicity LOAEL was not identified.

This study was classified as Core Minimum where all criteria were
satisfied except for the minimum number (12) of available does/group
which, due to mortality in the mid and high dose groups, were 11 and 9,
respectively. The reviewer of this study also indicated that individual
data on corpora lutea were not submitted.

**[870.3800 (83-4) Two-Generation Reproduction Study in SD Rats. MRID
No. 42483901]{.underline}**

**CITATION: Tyl, R.; Myers, C.; Marr, M. (1992) Two‑Generation
Reproductive Toxicity Study of DDVP Administered in Drinking Water to CD
(Sprague‑Dawley) Rats: Final Report: Lab Project Number 60C‑4629‑170.
Unpublished study prepared by Research Triangle Institute. 1225 p. MRID
No. 42483901**

**EXECUTIVE SUMMARY:** In a 2-generation reproduction study (MRID
42483901) DDVP (96.86%) was administered to 30 CD (Sprague-Dawley)
rats/sex/dose in their drinking water at concentrations of 0, 5, 20 and
80 ppm. Equivalent dosages were the following:

Table 10.

+----------+-------------+-------------+-------------+---------------+
| Water    | F0 & F1 ♂   | F0 & F1 ♀   | F0 & F1 ♀   | F0 & F1 ♀     |
|          |             |             |             |               |
| Conc.    | (μg/kg/day) | prebreeding | gestation   | lactation     |
|          |             |             |             |               |
| (ppm)    |             | (μg/kg/day) | (μg/kg/day) | (μg/kg/day)   |
+----------+-------------+-------------+-------------+---------------+
| 5.0      | 476-500     | 650-660     | 564-590     | 930-1176      |
+----------+-------------+-------------+-------------+---------------+
| 20.0     | 1923-1952   | 2432-2673   | 2124-2420   | 4280-4596     |
+----------+-------------+-------------+-------------+---------------+
| 80.0     | 6897-7528   | 9370-9472   | 7035-8150   | 13238-17468   |
+----------+-------------+-------------+-------------+---------------+

After at least 10 weeks of continuous exposure, rats were randomly mated
within treatment groups to produce the F1 generation; after mating the
F0 males were necropsied. F1 litters were culled to 8 pups (4 ♀, 4 ♂
when possible) on post natal day 8 and weaned on day 21. Ten
weanlings/sex/dose were necropsied and 30 weanlings/sex/dose were
selected as F1 parents with at least 11-week prebreeding exposure to
DDVP in their water. These rats were about 14-17 weeks old when mated
and their F2(a) litters were culled to 8 pups/litter on post natal day
8. At weaning, 10 F2(a) weanlings/sex/dose level were necropsied.

Due to poor reproductive performance (not treatment or dose-related), F1
females were evaluated for vaginal estrus cyclicity and then rebred with
untreated males to produce F2(b) litters which were culled on PND 8 (8
pups/litter) and necropsied (10/sex/dose) after weaning.

[Systemic toxicity]{.underline}: A NOAEL for cholinesterase inhibition
in parental animals was not observed. Cholinesterase levels were
dose-dependently decreased in plasma (by 3.6 to 57.4%), erythrocytes (by
7.0 to 60.5%), and brain (by 1.1 to 60.3%) from F0 and F1 animals and,
overall, females were more sensitive than males. No ChE measurements
were done on the F2(a) or F2(b) progeny. Water consumption was also
reduced in the 80 ppm dosed animals.

[Reproductive toxicity]{.underline}: No effects on reproductive
parameters were observed in the F0 mating, although mean pup body weight
in the 80 ppm group at weaning (day 21) was significantly lower than
controls (57.02 vs. 62.29 g). In the first mating of the F1 animals,
incidences of pregnancies were low (controls: 17/30; 5 ppm: 14/30; 20
ppm: 16/30; 80 ppm: 11/30). Mean pup body weight in the 80 ppm group at
weaning was noticeably (not significantly) lower than controls (52.22
vs. 57.43 g). As stated in the report conclusions: \"Parental
reproductive parameters were slightly affected in F1 animals at 80 ppm,
although these changes did not achieve statistical significance.
Offspring survival was also slightly reduced at 80 ppm, associated with
accompanying maternal toxicity seen at this dose level.\"

Results of the estrous cyclicity assessment showed that in the 80 ppm F1
group, there was a statistically significant decrease in the percent of
females cycling (63.3%, control 86.2%) accompanied by increased abnormal
cycling (68.4%, control 16%).

In the F2(b) mating, incidences of pregnancies were still relatively low
(controls: 19/29; 5 ppm: 19/30; 20 ppm: 17/30; 80 ppm: 13/30); in terms
of pregnancies/confirmed copulations incidences were: controls: 19/25
(76%); 5 ppm: 19/27 (70.4%); 20 ppm: 17/27 (63%); 80 ppm: 13/26 (50%).

The LOAEL for systemic toxicity \[drinking water administration\] is 5
ppm (488 μg/kg/day in males, 577 μg/kg/day in females), based on RBC and
plasma cholinesterase inhibition. The NOAEL is \<5 ppm (\<488 μg/kg/day
in males, \<577 μg/kg/day in females).

The reproductive LOAEL \[drinking water administration\] is 80 ppm (7592
μg/kg/day) based on the lack of cycling and abnormal cycling due to
persistent or prolonged estrus. In addition, parental reproductive
parameters (decreased pregnancy and fertility, and decreased live
litters and survival) were slightly affected in F1 animals at 80 ppm,
although these changes did not achieve statistical significance.
Offspring survival was also slightly reduced. The reproductive NOAEL is
20 ppm (4438 μg/kg/day).

**[81-8ss Acute Oral Neurotoxicity Study in Rats.]{.underline}**

**CITATION: Lamb, I. (1993) An Acute Neurotoxicity Study of Dichlorvos
in Rats: Final Report (Text and Summary Data): Lab Project Number:
WIL‑188003. Unpublished study prepared by WIL Research Labs., Inc. 984
p. MRID 42655301**

**EXECUTIVE SUMMARY:** In an acute oral neurotoxicity study (MRID
42655301), a single gavage dose of dichlorvos (97.8% a.i., lot #80209)
was administered in deionized water to 12 Sprague-Dawley rats/sex/ group
at 0, 0.5, 35, or 70 mg/kg. The animals were observed for up to 14 days.
Functional Observational Battery (FOB) tests were done pretest and on
study days 0 (15 minutes after compound administration), 7 and 14.
Animals surviving to study termination were sacrificed and perfused *in
situ* for neurohistopathological evaluation. All animals were
necropsied.

Two high-dose males and five high-dose females died within four hours of
compound administration. All other animals survived until study
termination. No body weight effects were observed. The FOB and motor
activity effects (described below) of dichlorvos were most prevalent
10-20 minutes post-dosing and had essentially resolved by days 7 and 14.
Statistically significant (p\<0.05) postural alterations, tremors,
salivation, and changes in fur appearance and skin color were observed
in mid- and high-dose males and females. High-dose males exhibited an
increased incidence (p\<0.05) of exophthalmus. Group mean time to first
step was significantly (p\<0.01) increased in high-dose males (31.7 sec)
and females (18.3 sec). Treatment-related (p\<0.05) decreased group mean
rearing, impaired mobility, abnormal gait, and decreased arousal level
were also observed in mid- and high-dose males and females. Dose-related
(p\<0.05) alterations of touch, tail pinch, pupil response and air
righting reflex were observed in mid- and high-dose males and in
high-dose females. Dose-related decreased hindlimb resistance (mid- and
high-dose, p\<0.05), grip strength (high-dose, p\<0.01), and rotarod
performance (mid- and high-dose, p\<0.01) were observed in male and
female rats. Decreased (p\<0.01) mean body temperature was observed in
mid- and high-dose males and females, and increased (p\<0.01) group mean
catalepsy values were observed in high-dose animals of both sexes. No
brain weight, brain dimension, or neurohistopathological effects were
observed.

Under the conditions of this study, the LOAEL for dichlorvos is 35 mg/kg
and the NOAEL is 0.5 mg/kg based on changes in the FOB, decreased motor
activity, and decreased body temperature. This study is classified as
acceptable (guideline) for an acute neurotoxicity study in rats
(81-8ss).

**[81-8ss Subchronic Oral Neurotoxicity Study in Rats.]{.underline}**

**CITATION: Lamb, I. (1993) A Subchronic (13 Week) Neurotoxicity Study
of Dichlorvos in Rats: Final Report: Lab Project Number: WIL‑188004.
Unpublished study prepared by WIL Research Labs, Inc. 1199 p. MRID
42958101.**

**EXECUTIVE SUMMARY:** In a subchronic oral neurotoxicity study (MRID
42958101), dichlorvos (97.87% a.i., lot No. 802097) was administered in
deionized water to 15 Sprague-Dawley rats/sex/group at gavage doses of
0, 0.1, 7.5, or 15.0 mg/kg/day for 90 days. Within each dose group, 10
rats/sex were allocated for brain cholinesterase determination and 5
rats/sex were allocated for neuropathology evaluation. Additionally,
blood samples were collected for cholinesterase measurements prestudy
and on study weeks 3, 7, and 13. Five rats/sex/dose from the
cholinesterase group and 5/sex/dose from the neuropathology group were
evaluated with the Functional Observational Battery (FOB) and motor
activity tests pretest and on study weeks 3, 7, and 12. Body weight and
food consumption were measured weekly.

There was no treatment-related mortality. Mean body weight in high-dose
females was consistently lower than the control (11-21%) throughout the
study. No body weight effects were observed in any other animals, and
there was no treatment-related effect on food consumption. Tremors,
salivation, exophthalmos, lacrimation, and clear material on the
forelimbs were observed in high-dose males and females approximately 15
minutes post-dosing. Rales, chromodacryorrhea, and red/yellow/orange
material around the nose and mouth were also seen in high-dose rats.
Tremors were observed in three mid-dose males and nine mid-dose females.
Generally, the clinical signs occurred during the third week of
treatment in the mid-dose animals, and as early as the first week of
dosing and throughout the study in the high-dose rats. Cholinesterase
activity was decreased in mid- and high-dose male and female rats as
follows: plasma 30-58%; erythrocyte 8-35%; brainstem and brain cortex
10-16%. There were no treatment-related effects in the FOB or motor
activity tests. No treatment-related neurohistopathological lesions and
no apparent changes in brain weight or size were observed.

Based on decreased cholinesterase activity and clinical cholinergic
signs, the LOAEL for dichlorvos is 7.50 mg/kg and the NOAEL is 0.1
mg/kg. This study is classified as acceptable (guideline) for a
subchronic neurotoxicity study in rats (81-8ss).

**g. [Mutagenicity]{.underline}**

**[Mutagenicity Studies with Positive Results]{.underline}**

Several in vitro and in vivo mutagenicity studies were reviewed and
presented to the Cancer Peer Review Committee (CPRC) by Kerry Deerfield
in a Memorandum entitled, "Review of the in vivo mutagenicity studies
concerning Dichlorvos" (dated August 10, 1988). Another review may be
found in the more recent Memorandum entitled, "Fifth carcinogenicity
peer review of Dichlorvos" by Jocelyn Stewart (dated August 28, 1996).
Though lacking sufficient detail, these two reviews provide some
information about the types and variety of mutagenicity/ genotoxicity
studies that were considered by the Agency since DDVP has been
registered.

DDVP has been shown to be a direct acting mutagen by common in vitro
bacterial genetic toxicity assays. For instance, DDVP is mutagenic in
the base-substitution Salmonella strain, TA100 as well as in the E. coli
WP2 mutation assay (Moriya et al., 1983). In this study, 238 pesticides
including DDVP were tested by the Ames plate incorporation method in
five Salmonella strains (TA1535, TA100, TA1537, TA1538, and TA98) as
well as in E. Coli (WP2 hcr) both in the presence or absence of an S-9
metabolizing system. DDVP (technical, unknown purity) was added (0.1 mL
in DMSO) at 0, 100, 500, 1,000, 5,000 or 10,000 µg/plate and all plates
were incubated for two days at 37°C prior to counting revertant
colonies. In Salmonella TA100, DDVP gave rise to a dose-dependent
response from 100 to 5000 µg/plate with a maximum increased mutation of
nearly 4.5-fold over control in the absence of S-9 activation while
complete toxicity was seen at the highest dose tested. Addition of S-9
metabolizing system reduced the mutation frequency to a maximum of
nearly 2-fold (at 5000 µg/plate) over background. DDVP was also positive
in E. coli WP2 hcr, though no actual data were provided. The other
tested strains failed to respond to DDVP in the presence or absence of
S-9 activation. Therefore, DDVP was shown to be a direct acting mutagen
in TA100 (and in E. coli WP2 hcr) where, compared to 44 other direct
acting mutagens in the same study, DDVP ranked 26 with a mutagenic
potency of 0.027 revertants/nmole (most and least potent were Captan in
TA100 and ETU in TA1535 scoring 93.7 and 0.00065 revertants/nmole,
respectively) (Moriya et al., 1983).

A single dose of apparently 5000 µg DDVP (\>97% a.i.) in cultures of E.
coli (B/r WP2 and WP2 hcr) and in S. typhimurium (TA1535 and TA1538) was
tested with or without S-9 metabolic activation. (According to HED doc.
\# 007765, p. 143, 0.1 mL of pesticide solution containing 22.6 µM DDVP
was used. However, the author of this document interprets this to mean
that 22.6 µmoles, equaling 5000 µg, of DDVP in 0.1 mL solution was used;
otherwise, the amount of DDVP in 0.1 mL of the 22.6 µM solution would be
only 0.5 µg.) Water served as negative (solvent) control. In the absence
of S-9 activation, DDVP was positive in both the E. coli and TA1535
strains (10-30 fold increased revertants above background). S-9
metabolic activation abolished DDVP's mutagenicity in TA1535 but not in
E. coli (Moriya et al., 1978).

This study was considered acceptable despite using one dose only and no
reporting of concurrent control values (HED doc. \# 007765).

Positive mutation findings were also reported in two E. coli WP2 strains
(trp^-^ and the plasmid-containing CM881) in another study which only
tested DDVP (a.i. not specified) at concentrations from 0.1 µg/mL (in
the agar incorporation method) to 2000 µg/mL (in the treat and plate
method) in the absence of S-9 metabolic activation. DDVP induced
reversion by base substitution in both the agar (5 µg/mL agar) or the
standard treat and plate method (2000 µg/mL) (Bridges, 1978).

This study was judged inconclusive as a comprehensive test of
mutagenicity because it was not also performed with mammalian metabolic
activation (HED doc. \# 007765).

An earlier study screened 11 S. typhimurium histidine-requiring strains
and seven E. coli tryptophan-requiring strains by spot testing DDVP (%
a.i. not specified) and 139 other organophosphorus compounds by adding
5-10 µl of each chemical to each bacterial strain and counting
revertants compared to controls after 48 and 72 hr incubation at 37°C.
Results were represented qualitatively using +/- designation. DDVP was
positive (+) in strains that were designed to detect base-pair
substitution mutagens (such as TA1530, TA1535, WP2, uvrA, and WP67) but
was negative (-) in strains that detect frame-shift mutagens (e.g.,
TA1536, TA1537, and TA1538) (Hanna and Dyer, 1975). This study was
judged acceptable without metabolic activation but, overall, was
considered inconclusive (HED doc. \# 007765).

In addition, DDVP is a direct acting mutagen in some in vitro mammalian
test systems. For instance, in the forward mutation assay at the TK
locus (L5178Y/TK^+/-^) of cell cultured mouse lymphoma cells, DDVP
(technical, 97.5% a.i., Lot No. 11381-23-5) was tested in up to 20 doses
ranging from 0.0089 to 1.0 µl/mL, both in the presence or absence of
metabolic activation. Concurrent negative controls (DMSO) and positive
controls were run using ethylmethanesulfonate (EMS) for nonactivated and
7,12-dimethylbenz\[a\]anthracene (DMBA) for activated cultures. The test
article was completely cytotoxic (0% growth) at doses ≥ 1 µl/mL and,
therefore doses ≤ 0.33 µl/mL were used to ascertain cloning and
mutagenesis. In the absence of metabolic activation, there was a
dose-related (0.024- 0.33 µl/mL) increase in mutant frequencies of
2.3-13.3 times that of DMSO control. Addition of metabolic activation
seemed to diminish the mutation frequency where at the two highest
tested doses of 0.24 and 0.18 µl/mL the mutant frequency was 3.7 and 2.7
times DMSO, respectively. Similar results were seen when the test was
repeated in a second series of experiments with and without metabolic
activation. Positive control chemicals elicited appropriate responses
where, relative to solvent control, mutant frequency was induced by 6.8
to 16.3x with EMS in nonactivated cultures and by 2.2 to 6.3x with DMBA
in S-9 activated cultures (Microbiological Associates, Inc., Study
No.T-5211.702003, dated 10/14/86, Acc. No. 265524).

This study was considered acceptable (TXR \# 005663).

Positive results were also described in another TK mouse lymphoma
forward mutation assay where DDVP (% a.i. not specified) was tested at
seven concentrations ranging from 6.25-250 nl/mL in the absence of
metabolic activation only. No cells survived at the two highest doses of
200 and 250 nl/mL but at the dose 100 nL/mL the mutant frequency was
7.6x the solvent control (EtOH) while the positive control
(methylmethanesulfonate) responded appropriately yielding 5.4x the
mutation frequency of EtOH. A repeat test gave similar qualitative
results. (Study performed by Litton Bionetics under contract to
NTP/NIEHS, report dated 8/27/85, Acc. No. 259463).

Despite the apparent direct acting mutagenicity results by DDVP, this
study was considered inconclusive as a "comprehensive mutagenicity test
in this system" because no S-9 metabolic activation was done (TXR \#
004376).

DDVP seems to also have clastogenic activity by inducing chromosomal
aberrations (AB), sister chromatid exchanges (SCE), and polyploidy in
cultured Chinese hamster ovary (CHO) cells (Tezuka et al., 1980). To
3x10^5^ pre-cultured CHO cells, DDVP (a.i. \> 98%) in DMSO (final
concentration of solvent in culture was kept to 1%) was added at a final
DDVP concentration of 0, 1x10^-4^, 2x10^-4^, 5x10^-4^, and 1x10^-3^ M.
After adding 5-bromomodeoxyuridine to a final concentration of 2 µM,
each culture was incubated for 26.5 hr in the dark. All doses were run
in duplicate using established procedures, where 50 and 100 metaphases
were generally used for scoring and detecting SCEs and ABs,
respectively, at each concentration. There was a statistically
significant (\<0.001) dose-dependent increase in the mean number of
SCE/cell with a maximum increase over control of nearly 5-fold at the
5x10^-4^M concentration (no data was available at the highest dose
tested and no explanation given). Chromosomal aberrations also were
induced (p\<0.001) at the 5x10^-4^M DDVP concentration where, of 100
scored cells, AB were found in 34 cells compared to 9/200 for control
and 4/100 for each of the two lowest DDVP doses (no data and no
explanation were available for the highest dose tested). There were no
cells with 10 or more AB per cell. Increased polyploidy was also
observed at the three lowest DDVP doses (no data was available for the
highest dose) where the per cent of examined cells with polyploidy
ranged from 9.3 to 15.7 %, compared to 2.5% in control cells. According
to the "Discussion" in this article, previous studies with DDVP in
cultured human lymphocytes or fibroblasts did not show inductions of SCE
or AB, and this apparent divergence with the results of this study was
attributed to possible differences in sensitivity among the different
test systems (Tezuka et al., 1980).

According to a Memorandum (dated August 10, 1988) entitled, "Review of
in vivo mutagenicity studies concerning Dichlorvos" that was presented
to the Cancer Peer Review Committee (CPRC) by Kerry Deerfield, DDVP is
also clastogenic (causing AB and SCE) in CHO cells with or without
metabolic activation (NTP draft report, 1987, TR 342, NIH pub. No.
88-2598). \[The review by K. Dearfield mistakenly cites that the test
system in the above study by Tezuka et al., 1980 used V79 cells (hamster
fibroblasts) rather than CHO cells.\] This NTP study is not available to
this reviewer to clarify and provide more details.

As shown below, however, an in vivo study by Microbiological Associates,
Inc. (Study dated 9/26/85) failed to show that DDVP has clastogenic
activity in mice.

**[Mutagenicity Studies with Negative Results]{.underline}**

In a micronucleus test, DDVP (98.5% a.i., in corn oil) was administered
(i.p.) at 0 (vehicle), 4, 13, or 40 mg/kg/day to adult CD-1 mice
(5/sex/dose/scheduled sacrifice) on two consecutive days and bone marrow
polychromatic erythrocytes (PCE) were examined for micronuclei at 30,
48, and 72 hr after the last dose. A group (5/sex) of positive control
mice were administered (i.p.) a single dose (0.15 mg/kg) of the mutagen
triethylene melamine (TEM) in water at 30 hr prior to killing. From a
preliminary DDVP dose-range finding study (8 doses from 1 to 100 mg/kg)
the LD~50~ for both sexes is 56 mg/kg. In the main assay, two males and
three females in the high dose group and one male in the mid dose group
died prior to scheduled killing. (Dead animals in the high dose group
were replaced.) Also lethargy and tremors were seen in the high dose
group. Therefore, a clinical MTD seems to have been achieved.

In none of the 18 DDVP test groups were micronuclei significantly
increased (range 0-1.2 per 1000 scored PCE) compared to negative control
(0-1). There was a significant response in the TEM positive control
group with a mean of 15.6 (males) and 13.2 (females) micronuclei/1000
PCE. (Microbiological Associates, Inc., Study dated 8/15/85)

This study was classified as acceptable/current guideline (HED doc. \#
004376).

In another in vivo mutagenicity study, DDVP (98.5% a.i., in corn oil)
was tested for sister chromatid exchange (SCE) induction in B6C3F1 mice
(5/sex/group) which were implanted (s.c.) with 50 mg bromodeoxyuridine
pellet four hours prior to receiving a single injection (i.p.) of 0
(corn oil), 3, 10, or 30 mg DDVP/kg. Dose-selection for this study was
based on a preliminary study in which mice received one of eight doses
ranging from 1-100 mg DDVP/kg where the combined (male/female) LD~50~
was calculated as 47 mg/kg. A positive control group (5/sex) received an
i.p. injection of cyclophosphamide (CP) at 10 mg/kg in water. After 24
hours, bone marrow from both femurs was removed and processed to
determine SCE by standardized methods where fifty second-division
metaphase cells per animal were scored for SCE. No animals died in the
main SCE assay and no clinical signs of toxicity were observed except
for lethargy in the high dose group. The mean SCE/cell/animal were
similar among all animals in the negative control and the DDVP-treated
groups (males: 4.9-5.9/females: 5.6-6.3); also the mitotic indices (% of
metaphase cells in first, second, and third division) in all DDVP
treated groups were comparable to the negative control group indicating
that there was no cell cycle delay even at the highest DDVP dose. As
expected, CP was positive with a mean SCE/cell/ animal of 29.9 in males
and 18.1 in females. (Microbiological Associates, Inc., Study dated
9/26/85)

This study was classified as acceptable and HED concluded that "although
no evidence for target cell toxicity (mitotic delay) was reported even
at a dose causing clinical toxicity, the study was otherwise conducted
adequately, and thus the negative results for SCE are supportable." (HED
doc. \# 004376)

This reviewer partly disagrees since the highest tested dose of 30 mg/kg
was below the MTD as judged by an LD~50~ of 47 mg/kg (preliminary study)
and a lack of clinical signs of toxicity with the exception of lethargy.

Another in vivo study (MRID no. 42619901) assessed the potential for
genotoxic effects in the germ cells and in bone marrow in male ICR mice
(10/group) by administering daily oral (gavage) doses of 0, 12.5, 25, or
50 mg/kg/day of DDVP (a.i. 98.1%, dissolved in water to give a constant
dosing volume of 20 mL/kg) for five consecutive days. Cyclophosphamide
(CP) was also administered (10 mice/group) at a single oral dose of 40
or 150 mg/kg (in water, dosing volume 20 mL/kg). All animals also
received a single i.p. injection (1.6 mg/kg) of the spindle inhibitor
colchicine two hours before killing. Bone marrow cells and spermatogonia
were prepared according to established procedures; from each animal,
fifty metaphase cells were examined, structural aberrations were
recorded, and the mitotic index (MI) was determined. There were no
indication of a clastogenic effect in either germinal (spermatogonia) or
somatic cells (bone marrow) harvested 24 hours following the final
administration of the test material. The positive control group
responded appropriately. The reviewer of this study concluded that the
maximally tolerated dose was achieved based on a preliminary test where
there was 80 % mortality after a single dose of 70 mg DDVP/kg (100%
mortality after a single dose of ≥ 90 mg/kg); furthermore, the five
repeated doses of DDVP "allowed a slightly reduced dosing load while
challenging the animals without excessive mortality" as was seen at
≥70mg/kg.

This study (MRID No. 42619901) was judged acceptable and, therefore, it
satisfied the requirement for in vivo cytogenetic mutagenicity data (HED
doc. \# 010446).

**h. [Metabolism]{.underline}**

**CITATION: Cheng, T. (1989) Metabolism of (Carbon 14)‑DDVP in Rats:
Project ID HLA 6274‑105. Unpublished study prepared by Hazleton
Laboratories America, Inc. 322 p. MRID 41228701.**

> **Cheng, T. (1991) Supplement to: Metabolism of carbon 14\|‑DDVP in
> Rats (Preliminary and Definitive Phases) (\...): Lab Project Number:
> HLA 6274‑105‑1. Unpublished study prepared by Hazleton Laboratories
> America, Inc. 89 p. MRID 41839901.**

**EXECUTIVE SUMMARY:** Groups of Sprague-Dawley rats (5/sex/group) were
administered a single dose of 20 µC~i~ \[^14^C\]DDVP (radiolabelled at
the vinyl position and purified to 100%) either intravenously (1 mg/kg),
orally (1 or 20 mg/kg; low and high doses, respectively), or orally (1
mg/kg) after 15 daily oral doses of unlabeled DDVP (1 mg/kg) and a
control group (2/sex) were orally dosed with water (vehicle). Of the
total orally administered dose (low or high), nearly 88-94% was absorbed
through the gastrointestinal tract and, within 24 hr, nearly 43-57% of
the original dose (low or high) was eliminated in expired air and
excreta. After seven days, the total excreted/air expired recovery was
approximately 60-77%; and, of the original dose, 11-17% was recovered in
urine/cage washes, 4-7% in feces, and 41-58% as expired ^14^CO~2~. The
relative amounts of radioactivity retained in carcass, liver, and other
tissues combined were 13-26%, 3-5%, and 1-2%, respectively. During the
seven days post-dosing period (low or high single dose), males expired
slightly less ^14^CO~2~ than females (41-45% vs. 52-54%, respectively).
The excretion patterns were similar after i.v. or oral administration
and little, if any, other differences relating to sex or dose were found
in the excretion or distribution of \[ ^14^C\]DDVP. Of the five
radiolabelled compounds that were detected in urine, two were identified
by mass spectrometry as hippuric acid (HA) and urea. Relative to total
urinary radioactivity, the concentration of HA ranged from 6.8-10.5 %
(low dose group) to 4.2-5.6 % (high dose group), while the amount of
urea was 19.6-33.1% (low dose group) and 41.1-51.1% (high dose group).
Urea and HA also seemed to be present in feces, albeit at lower
concentrations than were found in urine. Three other urinary compounds
were not identified but were assumed to be dehalogenated metabolites.
Other metabolites, representing nearly 8 to 19% of total urinary
radioactivity, were considered to be glucuronide conjugates (not
identified).

The overall metabolic profile suggests the involvement of the one-carbon
pool biosynthetic pathway as evidenced by the presence of a relatively
large amount of radioactivity in the form of expired ^14^CO~2~ and the
presence of dehalogenated metabolites as well as urea and hippuric acid.
These studies (MRID \# 41228701 and 41839901) were considered acceptable
and should satisfy the guideline requirement for a metabolism study (HED
doc. \# 008132 and 009444).

It should be noted that the above metabolism summary was based on the
specified subject MRID and HED documents and, as a result, subtle
differences or disagreements (for instance, relative amounts of
metabolites) are inevitable between this summary and other metabolism
summaries (e.g., the document dated August 28, 1996 and entitled, "fifth
carcinogenicity peer review of dichlorvos" prepared by Joycelyn
Stewart).

It should also be pointed out that, according to the IRIS summary on
dichlorvos dated 09/01/96, there are several additional published
studies on the availability, distribution, and metabolism following
administration of DDVP by different routes to different species.

**I. [Human Studies]{.underline}**

**CITATION: Gledhill, A. (1997) Dichlorvos: A Study to Investigate the
Effect of a Single Oral Dose on Erythrocyte Cholinesterase Inhibition in
Healthy Male Volunteers: Lab Project Number: CTL/P/5393: XH6064.
Unpublished study prepared by Zeneca Central Toxicology Lab. 44 p. MRID
44248802.**

> **Gledhill, A. (1997) Dichlorvos: A Single Blind, Placebo Controlled,
> Randomised Study to Investigate the Effects of Multiple Oral Dosing on
> Erythrocyte Cholinesterase Inhibition in Healthy Male Volunteers: Lab
> Project Number: CTL/P/5392: XH6063. Unpublished study prepared by
> Zeneca Central Toxicology Lab. 52 p. MRID 44248801.**
>
> **Gledhill, A. (1997) Dichlorvos: A Study to Investigate Erythrocyte
> Cholinestrase Inhibition Following Oral Administration to Healthy Male
> Volunteers: Lab Project Number: XH5170: Y09341: C05743. Unpublished
> study prepared by Zeneca Central Toxicology Lab. 104 p. MRID
> 44416201.**

**EXECUTIVE SUMMARY:** Dichlorvos (lot no. 608002S074, a.i. 98%,
dissolved in corn oil and packed in capsule) was administered in a
single oral dose of 70 mg (equivalent to 1 mg/kg) to six fasted young
healthy male volunteers. RBC cholinesterase (ChE) activity was measured
prior to dosing on days -22, -20, -18, -15, -13, -11, -8, -6, -4, and 0
(immediately prior to dosing), and after DDVP administration on days 1,
3, 5/6, 7, and 14. All subjects were medically supervised for clinical
signs and body temperature changes for twenty four hours after dosing.
Under the study conditions, no adverse clinical signs and no body
temperature variations were reported. Mean RBC ChE activity was
statistically significantly inhibited by 12% or less on days 5/6, day 7,
and day 14. The reduction in RBC ChE was not considered to be
biologically meaningful.

This study is considered non-guideline (MRID \# 44248802).

In a single blind oral study, each of six fasted male volunteers was
administered a daily dose of 7 mg DDVP (equivalent to about 0.1
mg/kg/day) in corn oil via a capsule over 21 days. Three control
subjects received corn oil as a placebo. The activity of RBC ChE was
measured for each participant prior to dosing, to establish baseline
levels, and also after dosing on days 2, 4, 7, 9, 11, 14, 16, 18, 25,
and 28. There were no reported toxicity attributable to DDVP
administration. Compared to pre-dosing mean value, the mean RBC ChE
activity was statistically significantly reduced by 8, 10, 14, 14, and
16 percent on days 7, 11, 14, 16, and 18, respectively. Under the study
conditions, the LOAEL for RBC ChE inhibition was established at 0.1
mg/kg/day (MRID No. 44248801). As discussed below, this study was used
for intermediate-term dermal exposure risk assessment.

In another human study (MRID 44416201), DDVP (lot no. 402010A, a.i.,
98%, dissolved in corn oil and packed in a capsule) was administered to
each of six fasted healthy male Caucasian males over two experimental
phases where each phase was followed by repeated measurements of RBC
ChE. In the first phase, volunteers ingested a capsule of 35 mg DDVP on
day 1, and on day 8 or 9 they received a corn oil capsule and finally
they received another 35 mg DDVP capsule, eight or nine days after the
corn oil. Measurements of RBC ChE were performed pretest (days -7, -5,
and -3) and after administration of each DDVP capsule (24, 72, 120, and
168 hr post each dose) or corn oil (at 24, 72, and 120 hr). Adverse
physical signs and symptoms including body temperature were recorded for
each volunteer. After 24 hr and 120 hr of the first DDVP dosing, group
mean RBC ChE activities were significantly depressed to 88% (not 93% as
reported by original reviewer in DER #22) and 90 %, respectively, of
predosing levels. (There seems to be an error in computing the day 1
group mean ChE level after the first DDVP dosing which should be 15098
I.U., or 88%, instead of 15908 I.U., or 93%, as shown in Table 2 of DER
#22.) However, following the second dose of DDVP, there were no
statistically significant changes in group mean RBC ChE activity at any
time (94 - 98% of predose activity). Also, no changes in ChE values were
seen after dosing with corn oil (96 - 105% of predosing). Individual
post-dose ChE activity ranged from 80% to 103% (not 85 to 100% as per
DER #22) of predose values at all reporting periods. There were no
changes in body temperature and no symptoms were attributed to DDVP.

In the second phase of this study, the same volunteers were administered
repeated daily doses of 21 mg DDVP for 12 or 14 days and RBC ChE
activity was monitored every two or three days up to day 29, and also on
days 33, 40 and 55 (Table 3, DER #22) or on days 33, 40, 47, and 54,
instead of days 33, 40 and 55 (as specified under Section 2 entitled
"Study Design" in DER #22). Plasma was also prepared from all blood
samples and immediately frozen and stored at -20°C; however, plasma ChE
was not measured. Compared to the group mean pretest value, group mean
RBC ChE activity was significantly decreased (\<0.01) from day 5 through
day 33, reaching a minimum of 69% on day 22 after which it seemed to
gradually recover until the last measurement on day 54 (or 55) when it
was 91% of pretest activity. Four of the six subjects reported various
symptoms; one felt tired (days 5-9) with headache and nausea (day 6),
another felt anxious one hour after the first dose, a volunteer had an
abdominal colic (day 12), and one subject developed an upper respiratory
tract infection (days 7 thru 12). Despite the fact that these symptoms
(with the possible exception of upper respiratory tract infection) are
typical indicators of cholinesterase poisoning, the investigators ruled
out DDVP as a possible cause.

According to DER #22, the HED study reviewer concluded that, based on no
decrease in RBC ChE in phase 1, NOAEL is 35 mg/person (or 0.5 mg/kg for
an average 70 kg person). This reviewer, however, does not think that
NOAEL was achieved since, compared to pretest value, the group mean RBC
ChE was statistically significantly depressed to 88% (day 1) and 90%
(day 5) and also because, at day 1, one individual (# IV) had this
enzyme activity drop to nearly 80% of pretest level (Table 1 in DER
#22); furthermore, the reported physical symptoms in four subjects
(three if the upper respiratory tract infection is deemed unrelated)
appear to be characteristic of ChE poisoning. In phase 2, based on the
steady decline in RBC ChE activity, the original HED reviewer concluded
that "NOAEL has not been established for this portion of the study."

This study is considered non-guideline (MRID No. 44416201).

Other human studies (journal articles) were also reviewed and were
considered supplementary due to employing too few subjects and/or
lacking individual data (Stewart, 1993; HED document No. 010157 and
Dannon, 1998)

3.  **Residue Chemistry Science Assessments for Reregistration of
    Dichlorvos.**

+--------------------------+------------+----------+------------------+
| GLN: Data Requirements   | Current    | Must     | References ^1^   |
|                          | T          | Ad       |                  |
|                          | olerances, | ditional |                  |
|                          | ppm \[40   | Data Be  |                  |
|                          | CFR\]      | Su       |                  |
|                          |            | bmitted? |                  |
+==========================+============+==========+==================+
| 860.1200: Directions for | N/A = Not  | Yes ^2^  |                  |
| Use                      | Applicable |          |                  |
+--------------------------+------------+----------+------------------+
| 860.1300: Plant          | N/A        | No       | 00013545,        |
| Metabolism               |            |          | 00074844,        |
+--------------------------+------------+----------+------------------+
| 860.1300: Animal         | N/A        | No       | 00013546,        |
| Metabolism               |            |          | 00066696,        |
|                          |            |          | 00117261,        |
|                          |            |          | 00117262,        |
|                          |            |          | 00126462,        |
|                          |            |          | 00126463,        |
|                          |            |          | 42721601 ^3^,    |
|                          |            |          | 42951701 ^4^     |
+--------------------------+------------+----------+------------------+
| 860.1340: Residue        |            |          |                  |
| Analytical Methods       |            |          |                  |
+--------------------------+------------+----------+------------------+
| \- Plant commodities     | N/A        | No       | 00042702,        |
|                          |            |          | 00042704,        |
|                          |            |          | 00042706,        |
|                          |            |          | 00047472,        |
|                          |            |          | 00049086,        |
|                          |            |          | 00049971,        |
|                          |            |          | 00049975,        |
|                          |            |          | 00051556,        |
|                          |            |          | 00074706,        |
|                          |            |          | 00074777,        |
|                          |            |          | 00107572,        |
|                          |            |          | 00115993,        |
|                          |            |          | 00117747,        |
|                          |            |          | 00118115,        |
|                          |            |          | 00139845         |
+--------------------------+------------+----------+------------------+
| \- Animal commodities    | N/A        | No       | 00042702,        |
|                          |            |          | 00042704,        |
|                          |            |          | 00049086,        |
|                          |            |          | 00049087,        |
|                          |            |          | 00049975,        |
|                          |            |          | 00060469,        |
|                          |            |          | 00060470,        |
|                          |            |          | 00060472,        |
|                          |            |          | 00074706,        |
|                          |            |          | 00115939,        |
|                          |            |          | 00115993,        |
|                          |            |          | 00117257,        |
|                          |            |          | 00117747,        |
|                          |            |          | 00118113,        |
|                          |            |          | 00118592,        |
|                          |            |          | 00118639,        |
|                          |            |          | 00140392         |
+--------------------------+------------+----------+------------------+
| 860.1360: Multiresidue   | N/A        | No       | 42611001 ^5^     |
| Methods                  |            |          |                  |
+--------------------------+------------+----------+------------------+
| 860.1380: Storage        | N/A        | Yes ^6^  | 00074776,        |
| Stability Data           |            |          | 00076809,        |
|                          |            |          | 00140392,        |
|                          |            |          | 43377701 ^7^     |
+--------------------------+------------+----------+------------------+
| 860.1500: Crop Field     |            |          |                  |
| Trials                   |            |          |                  |
+--------------------------+------------+----------+------------------+
| [Root and Tuber          |            |          |                  |
| Vegetables               |            |          |                  |
| Group]{.underline}       |            |          |                  |
+--------------------------+------------+----------+------------------+
| \- Radishes              | 0.5        | No ^8^   | 00118572,        |
|                          |            |          | 00119536         |
|                          | \[18       |          |                  |
|                          | 0.235(a)\] |          |                  |
+--------------------------+------------+----------+------------------+
| [Leafy Vegetables        |            |          |                  |
| (except *Brassica*       |            |          |                  |
| Vegetables)              |            |          |                  |
| Group]{.underline}       |            |          |                  |
+--------------------------+------------+----------+------------------+
| \- Lettuce               | 1 ^8^      | No ^8^   | 00033139,        |
|                          |            |          | 00082271,        |
|                          | \[18       |          | 00118572,        |
|                          | 0.235(a)\] |          | 00119536         |
+--------------------------+------------+----------+------------------+
| [Fruiting Vegetables     |            |          |                  |
| (except Cucurbits)       |            |          |                  |
| Group]{.underline}       |            |          |                  |
+--------------------------+------------+----------+------------------+
| \- Tomatoes              | 0.05 ^9^   | No ^8^   | 00033144,        |
|                          |            |          | 00107572,        |
|                          | \[18       |          | 00115993,        |
|                          | 0.235(a)\] |          | 00117686,        |
|                          |            |          | 00118169,        |
|                          |            |          | 00118572         |
+--------------------------+------------+----------+------------------+
| [Cucurbit Vegetables     |            |          |                  |
| Group]{.underline}       |            |          |                  |
+--------------------------+------------+----------+------------------+
| \- Cucumbers             | 0.5 ^9^    | No ^8^   | 00082271,        |
|                          |            |          | 00107572,        |
|                          | \[18       |          | 00118572         |
|                          | 0.235(a)\] |          |                  |
+--------------------------+------------+----------+------------------+
| [Miscellaneous           |            |          |                  |
| Commodities]{.underline} |            |          |                  |
+--------------------------+------------+----------+------------------+
| \- Mushrooms             | 0.5 ^9^    | No       | 00074658,        |
|                          |            |          | 00117686,        |
|                          | \[         |          | 00117690         |
|                          | 180.235(a) |          |                  |
+--------------------------+------------+----------+------------------+
| \- Tobacco               | None       | No ^10^  |                  |
|                          | e          |          |                  |
|                          | stablished |          |                  |
+--------------------------+------------+----------+------------------+
| 860.1520: Processed      |            |          |                  |
| Food/Feed                |            |          |                  |
+--------------------------+------------+----------+------------------+
| \- Corn, field           | 0.5        | No       | 42993501 ^13^    |
|                          | (processed |          |                  |
|                          | food) ^10^ |          |                  |
|                          | \[         |          |                  |
|                          | 185.1900\] |          |                  |
+--------------------------+------------+----------+------------------+
| \- Cottonseed            | 0.5        | No       | 42993501 ^13^    |
|                          | (processed |          |                  |
|                          | food) ^11^ |          |                  |
|                          |            |          |                  |
|                          | \[         |          |                  |
|                          | 185.1900\] |          |                  |
+--------------------------+------------+----------+------------------+
| \- Rice                  | 0.5        | No       | 42993501 ^13^    |
|                          | (processed |          |                  |
|                          | food) ^11^ |          |                  |
|                          |            |          |                  |
|                          | \[         |          |                  |
|                          | 185.1900\] |          |                  |
+--------------------------+------------+----------+------------------+
| \- Peanuts               | 0.5        | No       | 42952601 ^7^     |
|                          | (processed |          |                  |
|                          | food) ^11^ |          |                  |
|                          |            |          |                  |
|                          | \[         |          |                  |
|                          | 185.1900\] |          |                  |
+--------------------------+------------+----------+------------------+
| \- Soybeans              | 0.5        | No       | 42993501 ^13^    |
|                          | (processed |          |                  |
|                          | food) ^11^ |          |                  |
|                          |            |          |                  |
|                          | \[         |          |                  |
|                          | 185.1900\] |          |                  |
+--------------------------+------------+----------+------------------+
| \- Wheat                 | 0.5        | No       | 42993501 ^13^    |
|                          | (processed |          |                  |
|                          | food) ^11^ |          |                  |
|                          |            |          |                  |
|                          | \[         |          |                  |
|                          | 185.1900\] |          |                  |
+--------------------------+------------+----------+------------------+
| 860.1480: Meat, Milk,    |            |          |                  |
| Poultry, Eggs            |            |          |                  |
+--------------------------+------------+----------+------------------+
| \- Milk and the Fat,     | 0.02 (milk | Yes ^12^ | 00115945,        |
| Meat, and Meat           | and the    |          | 00116436,        |
| Byproducts of Cattle,    | fat, meat, |          | 43037401 ^13^    |
| Goats, Hogs, Horses, and | and meat   |          |                  |
| Sheep                    | byproducts |          |                  |
|                          | of cattle, |          |                  |
|                          | goats,     |          |                  |
|                          | horses,    |          |                  |
|                          | and sheep) |          |                  |
|                          |            |          |                  |
|                          | \[18       |          |                  |
|                          | 0.235(a)\] |          |                  |
|                          |            |          |                  |
|                          | 0.1        |          |                  |
|                          | (edible    |          |                  |
|                          | tissue of  |          |                  |
|                          | swine)     |          |                  |
|                          |            |          |                  |
|                          | \[18       |          |                  |
|                          | 0.235(b)\] |          |                  |
+--------------------------+------------+----------+------------------+
| \- Eggs and the Fat,     | 0.05       | No       | 00118639,        |
| Meat, and Meat           |            |          | 00119537,        |
| Byproducts of Poultry    | \[18       |          | 00139843,        |
|                          | 0.235(a)\] |          | 00139844,        |
|                          |            |          | 43047901 ^13^    |
+--------------------------+------------+----------+------------------+
| 860.1400: Water, Fish,   | None       | No       |                  |
| and Irrigated            | e          |          |                  |
|                          | stablished |          |                  |
| Crops                    |            |          |                  |
+--------------------------+------------+----------+------------------+
| 860.1460: Food Handling  |            |          |                  |
+--------------------------+------------+----------+------------------+
| \- Food Service          | None       | No       |                  |
| Establishments           | e          |          |                  |
|                          | stablished |          |                  |
+--------------------------+------------+----------+------------------+
| \- Grain Processing and  | 0.5 (RAC)  |          | 42768702 ^13^,   |
| Manufacturing            | ^14^       |          | 42775901 ^13^,   |
| Establishments           |            |          | 42878801 ^13^,   |
|                          | \[18       |          | 42910801 ^13^,   |
|                          | 0.235(a)\] |          | 42910901 ^13^    |
+--------------------------+------------+----------+------------------+
| \- Bulk Stored Raw and   | 0.5 (RAC)  | No       | 00117747,        |
| Processed Commodities    | ^14^       |          | 42916601 ^7^     |
| ^15^                     |            |          |                  |
|                          | \[18       |          |                  |
|                          | 0.235(a)\] |          |                  |
+--------------------------+------------+----------+------------------+
| > \- Bulk stored peanuts | 0.5        | No       | 43003101 ^7^     |
| > ^15^                   |            |          |                  |
|                          | \[18       |          |                  |
|                          | 0.235(a)\] |          |                  |
+--------------------------+------------+----------+------------------+
| \- Packaged and Bagged   | 0.5 (RAC,  | No       | 00056593,        |
| Raw and Processed        | ≤6%        |          | 00056595,        |
| Commodities              | fat) ^11^  |          | 00056596,        |
|                          |            |          | 42853701 ^7^     |
|                          | 2 (RAC,    |          |                  |
|                          | \>6% fat)  |          |                  |
|                          | ^11^       |          |                  |
|                          |            |          |                  |
|                          | \[18       |          |                  |
|                          | 0.235(a)\] |          |                  |
|                          |            |          |                  |
|                          | 0.5        |          |                  |
|                          | (processed |          |                  |
|                          | food) ^11^ |          |                  |
|                          |            |          |                  |
|                          | \[         |          |                  |
|                          | 185.1900\] |          |                  |
+--------------------------+------------+----------+------------------+
| \- Crack and Crevice     | None       | No ^16^  |                  |
| Treatments               | e          |          |                  |
|                          | stablished |          |                  |
+--------------------------+------------+----------+------------------+
| 860.1000: Reduction of   |            |          |                  |
| Residue                  |            |          |                  |
+--------------------------+------------+----------+------------------+
| \- Dried Beans           | N/A        | No       | 42910701 ^13^    |
+--------------------------+------------+----------+------------------+
| \- Cocoa Beans           | N/A        | No       | 42910701 ^13^    |
+--------------------------+------------+----------+------------------+
| \- Coffee Beans          | N/A        | No       | 42910701 ^13^    |
+--------------------------+------------+----------+------------------+
| \- Tomato                | N/A        | No       | 42910701 ^13^    |
+--------------------------+------------+----------+------------------+
| \- Meat, Eggs,           | N/A        | No       | 42910701 ^13^    |
| Pasteurized Milk         |            |          |                  |
+--------------------------+------------+----------+------------------+
| \- Degradation -         | N/A        | No ^17^  | 42858201 ^13^    |
| Packaged and Bagged Raw  |            |          |                  |
| and Processed            |            |          |                  |
| Commodities              |            |          |                  |
+--------------------------+------------+----------+------------------+
| \- Degradation - Bulk    | N/A        | No ^17^  | 42903801 ^7^     |
| Stored Raw and Processed |            |          |                  |
| Commodities              |            |          |                  |
+--------------------------+------------+----------+------------------+
| 860.1850: Confined       | N/A        | No ^8^   |                  |
| Rotational Crops         |            |          |                  |
+--------------------------+------------+----------+------------------+
| 860.1900: Field          | None       | No ^8^   |                  |
| Rotational Crops         |            |          |                  |
+--------------------------+------------+----------+------------------+

1 References without endnotes were reviewed in the Residue Chemistry
Chapter of the Dichlorvos Reregistration Standard dated 2/26/86. All
other references were reviewed as noted.

2\. Label amendments are required to incorporate the parameters of use
patterns reflected in the submitted data and to reflect the use patterns
that the registrant wishes to support which are supported by residue
data. Product labels with uses in mushroom houses must be amended to
reflect a 1-day PHI. All uses in greenhouses (food use only) and tobacco
warehouses must be deleted from product labels. Product labels which
allow uses in food-handling establishments must be amended to specify
that applications may only be made in: in warehouses, silos, bulk bins,
and food/feed processing, food/feed manufacturing, handling and storage
plants containing non-perishable, packaged or bagged raw or processed
food/feed commodities or bulk raw or processed food commodities; or in
non-food areas of food-handling establishments \[including garbage
rooms, lavatories, floor drains (sewers), entries and vestibules,
offices, locker rooms, machine rooms, boiler rooms, garages, mop
closets, and storage (after canning or bottling)\]. Use in food handling
establishments - food service areas must be canceled. There are no
tolerances or data supporting this use.

3 CB No. 11768, DP Barcode D190450, 7/21/93, D. McNeilly.

4\. CB No. 12766, DP Barcode D196572, 12/17/93, D. McNeilly.

5\. CB No. 11244, DP Barcode D187061, 9/29/93, D. McNeilly.

6\. Information pertaining to the storage intervals and conditions of
samples of the following commodities, from studies that were reviewed in
the Residue Chemistry Chapter of the Registration Standard (1987), must
be submitted: packaged and bagged raw agricultural commodities and
processed food; bulk stored raw agricultural commodities; milk; eggs;
and meat, fat, and meat byproducts of dairy cows and poultry.
Alternatively, the registrant may demonstrate that there are sufficient
residue data supported by storage stability data to support all
registered uses of dichlorvos.

7\. CB Nos. 12658, 13230, 13296, and 13297; DP Barcodes D195720 ,
D199212, D199977, and D199979; 6/2/94; S. Hummel.

8\. The registrant is not supporting any agricultural uses of
dichlorvos. Another registrant has indicated a willingness to support
dichlorvos use on tomatoes. If this use is to be supported, residue data
are required. We note that the tomato use is no longer on any dichlorvos
labels.

9\. Residues are expressed as naled.

10\. The registrant is not supporting use of dichlorvos in tobacco
warehouses.

11\. Resulting from application to packaged or bagged nonperishable
commodities.

12\. A dermal magnitude of the residue study must be submitted for
swine. Swine dermal use remains on dichlorvos labels.

13\. CB Nos. 13006, 13294, 13295, 13296, and 13427; DP Barcodes D197522
, D199975, D199976, D199979, and D200905; 7/18/94; S. Hummel.
Non-detectable residues were reported from direct dermal uses and from
secondary residues in livestock feeds.

14\. Resulting from application to bulk stored nonperishable
commodities, regardless of fat content.

15\. See also \"860.1520: Processed Food/Feed.\"

16\. Data had been required reflecting crack and crevice treatment of
food handling establishments; however, because this use is more
restrictive than the registered use on bulk stored and packaged and
bagged commodities, these data are no longer required.

17\. Although no additional data are required concerning this guideline
topic for the purposes of reregistration, the Agency's risk assessment
could be better refined if the registrant provides information
concerning the typical length of time commodities remain in storage
following treatment. This information would include typical total
storage times, frequency of applications, and rates of application
(g/1000 cu. ft.).

**4.0 Tolerance Reassessment**

Table C. Tolerance Reassessment Summary for Dichlorvos.

+---------------------+-----------+-------------+----------------------+
| Commodity           | Current   | Tolerance   | Comment/             |
|                     | T         | Re          |                      |
|                     | olerance, | assessment, | *\[Correct Commodity |
|                     | ppm       | ppm         | Definition\]*        |
+=====================+===========+=============+======================+
| Tolerances Listed   |           |             |                      |
| Under 40 CFR        |           |             |                      |
| §180.235(a)(1)\*    |           |             |                      |
+---------------------+-----------+-------------+----------------------+
| Cattle, fat         | 0.02(N)   | 0.05        | Harmonize with       |
|                     |           |             | CODEX.               |
+---------------------+-----------+-------------+----------------------+
| Cattle, meat        | 0.02(N)   | 0.05        | Harmonize with       |
|                     |           |             | CODEX.               |
+---------------------+-----------+-------------+----------------------+
| Cattle, mbyp        | 0.02(N)   | 0.05        | Harmonize with       |
|                     |           |             | CODEX.               |
+---------------------+-----------+-------------+----------------------+
| Cucumbers           | 0.5 ^1^   | Revoke      | The registrant is    |
|                     |           |             | not supporting use   |
|                     |           |             | of dichlorvos on     |
|                     |           |             | this commodity.      |
|                     |           |             | Tolerance has been   |
|                     |           |             | revoked.             |
+---------------------+-----------+-------------+----------------------+
| Eggs                | 0.05(N)   | 0.05        |                      |
+---------------------+-----------+-------------+----------------------+
| Goats, fat          | 0.02(N)   | 0.05        | Harmonize with       |
|                     |           |             | CODEX.               |
+---------------------+-----------+-------------+----------------------+
| Goats, meat         | 0.02(N)   | 0.05        | Harmonize with       |
|                     |           |             | CODEX.               |
+---------------------+-----------+-------------+----------------------+
| Goats, mbyp         | 0.02(N)   | 0.05        | Harmonize with       |
|                     |           |             | CODEX.               |
+---------------------+-----------+-------------+----------------------+
| Horses, fat         | 0.02(N)   | 0.05        | Harmonize with       |
|                     |           |             | CODEX.               |
+---------------------+-----------+-------------+----------------------+
| Horses, meat        | 0.02(N)   | 0.05        | Harmonize with       |
|                     |           |             | CODEX.               |
+---------------------+-----------+-------------+----------------------+
| Horses, mbyp        | 0.02(N)   | 0.05        | Harmonize with       |
|                     |           |             | CODEX.               |
+---------------------+-----------+-------------+----------------------+
| Lettuce             | 1 ^1^     | Revoke      | The registrant is    |
|                     |           |             | not supporting use   |
|                     |           |             | of dichlorvos on     |
|                     |           |             | this commodity.      |
|                     |           |             | Tolerance has been   |
|                     |           |             | revoked.             |
+---------------------+-----------+-------------+----------------------+
| Milk                | 0.02(N)   | 0.05        | Harmonize with       |
|                     |           |             | CODEX.               |
+---------------------+-----------+-------------+----------------------+
| Mushrooms           | 0.5 ^1^   | 0.5         | The tolerance should |
|                     |           |             | be revised to be     |
|                     |           |             | expressed in terms   |
|                     |           |             | of dichlorvos.       |
+---------------------+-----------+-------------+----------------------+
| Poultry, fat        | 0.05(N)   | 0.05        |                      |
+---------------------+-----------+-------------+----------------------+
| Poultry, meat       | 0.05(N)   | 0.05        |                      |
+---------------------+-----------+-------------+----------------------+
| Poultry, mbyp       | 0.05(N)   | 0.05        |                      |
+---------------------+-----------+-------------+----------------------+
| Radishes            | 0.5       | Revoke      | The registrant is    |
|                     |           |             | not supporting use   |
|                     |           |             | of dichlorvos on     |
|                     |           |             | this commodity.      |
+---------------------+-----------+-------------+----------------------+

+---------------------+-----------+-------------+----------------------+
| Commodity           | Current   | Tolerance   | Comment/             |
|                     | T         | Re          |                      |
|                     | olerance, | assessment, | *\[Correct Commodity |
|                     | ppm       | ppm         | Definition\]*        |
+---------------------+-----------+-------------+----------------------+
| Raw agricultural    | 0.5       | 4.0         | *\[Raw agricultural  |
| commodities,        |           |             | commodities,         |
| nonperishable, bulk |           |             | nonperishable, bulk  |
| stored regardless   |           |             | stored\]*            |
| of fat content      |           |             |                      |
| (post-H)            |           |             |                      |
+---------------------+-----------+-------------+----------------------+
| Raw agricultural    | 0.5       | 4.0         | *\[Raw agricultural  |
| commodities,        |           |             | commodities,         |
| nonperishable,      |           |             | nonperishable,       |
| packaged or bagged, |           |             | packaged and         |
| containing 6        |           |             | bagged\]*            |
| percent fat or less |           |             |                      |
| (post-H)            |           |             |                      |
+---------------------+-----------+-------------+----------------------+
| Raw agricultural    | 2.0       |             |                      |
| commodities,        |           |             |                      |
| nonperishable,      |           |             |                      |
| packaged or bagged, |           |             |                      |
| containing more     |           |             |                      |
| than 6 percent fat  |           |             |                      |
| (post-H)            |           |             |                      |
+---------------------+-----------+-------------+----------------------+
| Sheep, fat          | 0.02(N)   | 0.05        | Harmonize with       |
|                     |           |             | CODEX.               |
+---------------------+-----------+-------------+----------------------+
| Sheep, meat         | 0.02(N)   | 0.05        | Harmonize with       |
|                     |           |             | CODEX.               |
+---------------------+-----------+-------------+----------------------+
| Sheep, mbyp         | 0.02(N)   | 0.05        | Harmonize with       |
|                     |           |             | CODEX.               |
+---------------------+-----------+-------------+----------------------+
| Tomatoes (pre- and  | 0.05 ^1^  | Revoke      | The registrant is    |
| post-H)             |           |             | not supporting use   |
|                     |           |             | of dichlorvos on     |
|                     |           |             | this commodity.      |
+---------------------+-----------+-------------+----------------------+
| Tolerances Listed   |           |             |                      |
| Under 40 CFR        |           |             |                      |
| §180.235(a)(2)      |           |             |                      |
+---------------------+-----------+-------------+----------------------+
| Edible swine tissue | 0.1       | Revoke      | Residue data have    |
| ^2^                 |           |             | been required and    |
|                     |           |             | not submitted.       |
+---------------------+-----------+-------------+----------------------+
| Tolerances Listed   |           |             |                      |
| Under 40 CFR        |           |             |                      |
| §180.235(a)(3)      |           |             |                      |
+---------------------+-----------+-------------+----------------------+
| Packaged or bagged  | 0.5       | 4.0         | The tolerance should |
| nonperishable       |           |             | be moved to          |
| processed food      |           |             | §180.235(a)(1).      |
|                     |           |             |                      |
|                     |           |             | *\[Processed food,   |
|                     |           |             | nonperishable,       |
|                     |           |             | packaged or          |
|                     |           |             | bagged\]*            |
+---------------------+-----------+-------------+----------------------+
| Tolerances to be    |           |             |                      |
| Proposed Under 40   |           |             |                      |
| CFR §180.235(a)     |           |             |                      |
+---------------------+-----------+-------------+----------------------+
| Soybean, hulls      | \--       | 15.0        |                      |
+---------------------+-----------+-------------+----------------------+
| Aspirated grain     | \--       | 20.0        |                      |
| fractions           |           |             |                      |
+---------------------+-----------+-------------+----------------------+

**\* Concurrently with the revocation of the tolerance for edible swine
tissue in §180.235(a)(2) and the moving of the tolerance for packaged or
bagged nonperishable processed food in §180.235(a)(3), §180.235(a)(1)
should be redesignated §180.235(a).**

**^1^ Residues expressed as naled. Another registrant has expressed
interest in supporting the tolerance on tomato. However, data have been
required and not submitted.**

**^2^ Resulting both from its use as an anthelmintic in swine feed and
as an insecticide applied directly to swine; prescribed by 21 CFR
558.205 as a feed additive in swine, with a tolerance of 0.1 ppm for
residues of dichlorvos in edible swine tissue listed in 21 CFR
556.180.**