![](media/image1.png){width="0.8541666666666666in"
height="0.9479166666666666in"}

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

> OFFICE OF PREVENTION, PESTICIDES
>
> AND TOXIC SUBSTANCES

**Date: 10/23/2007**

**[MEMORANDUM]{.underline}**

SUBJECT: Cyfluthrin/Beta-cyfluthrin -- Human Health Risk Assessment For
New Uses on Grasses, Alfalfa, and Sugar Beet Seed and Revised Tolerances
on Cereal Grain Commodities.

Regulatory Action: Section 3 Registration Action

Risk Assessment Type: Single Chemical Aggregate

> PC Codes: 128831 -- Cyfluthrin
>
> 118831 -- Beta-cyfluthrin
>
> Petitions 6E7058, 6F7160, 7F7226, and 7F7200.
>
> DP Barcode: D331951; D331952: D335486; D339095; D339413; D339414;
>
> D339415; D339445; D340710; D340711; D340712; D340713.

FROM: Christina Swartz, Branch Chief

> Kelly Schumacher, Toxicology

Douglas Dotson, Chemistry, Dietary Analysis

Suku Oonnithan, Occupational and Residential Exposure

Tom Moriarty, Risk Assessment

Registration Action Branch 2

Health Effects Division (7509P)

THROUGH: Christina Swartz, Branch Chief

Richard Loranger, Branch Senior Scientist

Registration Action Branch 2

Health Effects Division (7509P)

TO: Marion Johnson, Chief

Insecticide Branch

Registration Division (7505P)

And

Dan Rosenblatt, Chief

Risk Integration Minor Use, and Emergency Response Branch

Registration Division (7505P)

Summary: HED has completed a human health risk assessment for the
proposed uses of and tolerances for cyfluthrin/beta-cyfluthrin
associated with the subject petitions: 6E7058 -- use on grasses; 6F7160
-- new use on sugar beet seed; 7F7200 -crop group tolerances; and,
7F7226 -- increased application rate on alfalfa. The dietary assessment
reflects proposed new uses and tolerances, and includes an updated
drinking water assessment. While there are no residential exposures
associated with the subject petitions, an aggregate assessment was
conducted based on currently registered residential uses. An
occupational exposure assessment has also been performed for the
proposed uses on grasses, alfalfa, and sugar beet seed treatment.

**Table of Contents**

[**1.0 Executive Summary** 5](#__RefHeading___Toc179885342)

[**2.0 Ingredient Profile** 11](#__RefHeading___Toc179885343)

[**3.0 Hazard Characterization/Assessment**
12](#__RefHeading___Toc179885344)

[**3.1 Database Summary** 12](#__RefHeading___Toc179885345)

[**3.1.1 Studies Available and Considered**
12](#__RefHeading___Toc179885346)

[**3.1.2 Mode of Action, Metabolism, Toxicokinetic Data**
13](#__RefHeading___Toc179885347)

[**3.1.3 Sufficiency of Studies/Data** 14](#__RefHeading___Toc179885348)

[**3.2 Toxicological Effects** 14](#__RefHeading___Toc179885349)

[**3.3 FQPA Considerations** 16](#__RefHeading___Toc179885350)

[**3.4 Hazard Identification and Toxicity Endpoint Selection**
17](#__RefHeading___Toc179885351)

[**3.4.1 Acute Reference Dose (aRfD) -- General Population**
17](#__RefHeading___Toc179885352)

[**3.4.2 Chronic Reference Dose (cRfD)**
18](#__RefHeading___Toc179885353)

[**3.4.3** **Incidental Oral Exposure (Short- and Intermediate-Term)**
19](#__RefHeading___Toc179885354)

[**3.4.4 Dermal Absorption** 19](#__RefHeading___Toc179885355)

[**3.4.7 Inhalation Exposure (Short-Term)**
21](#__RefHeading___Toc179885356)

[**3.4.8 Inhalation Exposure (Intermediate- and Long-Term)**
21](#__RefHeading___Toc179885357)

[**3.4.9 Level of Concern for Margin of Exposure (MOE)**
22](#__RefHeading___Toc179885358)

[**3.4.10 Recommendation for Aggregate Exposure Risk Assessments**
22](#__RefHeading___Toc179885359)

[**3.4.11 Classification of Carcinogenic Potential**
23](#__RefHeading___Toc179885360)

[**3.4.12 Summary of Toxicological Doses and Endpoints for Cyfluthrin
and Beta-Cyfluthrin for Use in Human Health Risk Assessments**
23](#__RefHeading___Toc179885361)

[**3.5 Endocrine disruption** 24](#__RefHeading___Toc179885362)

[**4.0 Public Health and Pesticide Epidemiology Data**
25](#__RefHeading___Toc179885363)

[**5.0 Dietary Exposure/Risk Characterization**
25](#__RefHeading___Toc179885364)

[**5.1 Metabolism and Environmental Degradation**
25](#__RefHeading___Toc179885365)

[**5.1.1 Metabolism in Primary Crops** 25](#__RefHeading___Toc179885366)

[**5.1.2 Metabolism in Livestock** 25](#__RefHeading___Toc179885367)

[**5.1.4 Environmental Degradation** 26](#__RefHeading___Toc179885368)

[**5.1.5 Pesticide Metabolites and Degradates of Concern**
27](#__RefHeading___Toc179885369)

[**5.1.6 Drinking Water Residue Profile**
27](#__RefHeading___Toc179885370)

[**5.1.7 Food Residue Profile** 28](#__RefHeading___Toc179885371)

[**5.2 Dietary Exposure and Risk** 32](#__RefHeading___Toc179885372)

[**5.2.1 Dietary Exposure Refinements**
32](#__RefHeading___Toc179885373)

[**5.2.2 Acute and Chronic Dietary Exposure/Risk**
33](#__RefHeading___Toc179885374)

[**5.2.3 Cancer Dietary Risk** 34](#__RefHeading___Toc179885375)

[**6.0 Residential (Non-Occupational) Exposure/Risk Characterization**
34](#__RefHeading___Toc179885376)

[**6.1 Spray Drift** 35](#__RefHeading___Toc179885377)

[**7.0 Aggregate Risk Assessments and Risk Characterization**
35](#__RefHeading___Toc179885378)

[**7.1 Acute Aggregate Risk** 36](#__RefHeading___Toc179885379)

[**7.2 Short-Term and Intermediate-Term Aggregate Risk**
36](#__RefHeading___Toc179885380)

[**7.3 Chronic Aggregate Risk Assessment**
37](#__RefHeading___Toc179885381)

[**7.4 Cancer Aggregate Risk Assessment**
37](#__RefHeading___Toc179885382)

[**8.0 Cumulative Risk Characterization/Assessment**
37](#__RefHeading___Toc179885383)

[**9.0 Occupational Exposure/Risk Pathway**
38](#__RefHeading___Toc179885384)

[**9.1 Occupational/Non-Residential Toxicological Profile for
Cyfluthrin/Beta-cyfluthrin** 39](#__RefHeading___Toc179885385)

[**9.2 Occupational/Non-Residential Exposure Inputs**
40](#__RefHeading___Toc179885386)

[**9.3 Handler and Applicator Risks from Proposed Uses on Grasses and
Alfalfa** 41](#__RefHeading___Toc179885387)

[**9.4 Short-term and Intermediate-term Exposures and Risk from Proposed
Seed Treatment Use** 42](#__RefHeading___Toc179885388)

[**9.5 Post-application Exposure and Risk**
43](#__RefHeading___Toc179885389)

[**10.0 Data Needs and Label Recommendations**
44](#__RefHeading___Toc179885390)

[**References** 46](#__RefHeading___Toc179885391)

[**Appendix A. Occupational Exposure and Risk Tables**
47](#__RefHeading___Toc179885392)

[**Appendix B Toxicology Profile of Cyfluthrin and Beta-cyfluthrin**
51](#__RefHeading___Toc179885393)

[**Appendix C Summary of Cyfluthrin/Beta-cyfluthrin Tolerances**
65](#__RefHeading___Toc179885394)

[]{#__RefHeading___Toc179885342 .anchor}**1.0 Executive Summary**

Cyfluthrin and beta-cyfluthrin (an enriched isomer of cyfluthrin) are
non-systemic pyrethroid insecticides. Cyfluthrin was first registered in
1989, and currently there are approximately 145 active products
registered for use on a wide variety of sites including agricultural,
indoor/outdoor domestic dwellings, ant dens/mounds, and stored product
pests. Beta-cyfluthrin was first registered in 1995 and currently there
are approximately 27 active registrations. Permanent tolerances are
established for residues of cyfluthrin (40 CFR §180.436). Tolerances for
cyfluthrin also cover beta-cyfluthrin, provided that the use rates for
beta-cyfluthrin are ½ that of cyfluthrin. The current risk analysis on
cyfluthrin/beta-cyfluthrin was conducted to assess several petitions;
(i) an increase in the number of applications to alfalfa; (ii) expanded
geographical uses on grasses; (iii) request for crop group 15 (except
rice) and for crop group 16 tolerances; and, (iv) a new use for sugar
beet seed treatment. A summary of the subject petitions can be found in
Table 1. Several field trial studies were submitted in connection with
the subject petitions which were reviewed and incorporated into this
assessment.

Toxicologically, the primary target for cyfluthrin/beta-cyfluthrin is
the neuromuscular system; other non-specific effects include decreased
body weight gain, and decreased food consumption. The observed
neuromuscular effects (tremors, gait abnormities, abnormal postural
reactions, splaying of limbs and decreases in activity) occurred mainly
in oral studies in the dog and the rat. In general, the toxicity data
base does not indicate that any major differences in toxicity exist
between beta-cyfluthrin and cyfluthrin via the oral route. Data from the
inhalation toxicity study showed evidence of clinical signs as well as
hypothermia and decreased body weight gains. In a postnatal inhalation
study in mice, there were clinical signs of neurotoxicity in the pups as
well as increased spontaneous motor activity and paresthesia (tingling,
burning or prickling -- also seen in oral studies).

In oral developmental studies no increased susceptibility was observed
in the rat or rabbit; however, increased susceptibility was observed in
inhalation developmental studies. Increased susceptibility was also seen
in oral reproduction studies and in a developmental neurotoxicity study
on beta-cyfluthrin. The data also demonstrate increased susceptibility
of rats and mice to cyfluthrin postnatally. The FQPA Safety Factor was
reduced to 1x because the database is complete and the exposure database
is sufficient.

The database does not indicate that either cyfluthrin or beta-cyfluthrin
induces any endocrine disruption; and, there is no concern of
mutagenicity. HED has classified cyfluthrin/beta-cyfluthrin as "not
likely to be carcinogenic to humans."

The metabolism of cyfluthrin/beta-cyfluthrin is well understood in both
plant and animal matrices, and analytical methods for the currently
registered and proposed uses have been submitted and validated.

The dietary analysis is refined and includes processing factors, percent
crop treated estimates, and monitoring data. The dietary analysis also
includes secondary residues, and reflects revised tolerance values
associated with the subject petitions. The updated drinking water
analysis considers all currently registered and proposed uses.

Acute dietary risks for the general population and all population
subgroups were not of concern to HED, with children 1 -- 2 years old,
the highest exposed subpopulation, utilizing 53% of the acute population
adjusted dose (aPAD). Chronic dietary risks for the general population
and all population subgroups were also not of concern to HED, with
children 1 -- 2 years old, the highest exposed subpopulation, utilizing
17% of the chronic population adjusted dose (cPAD).

Aggregate assessments were also conducted for
cyfluthrin/beta-cyfluthrin. The acute aggregate assessment included food
and drinking water only, and therefore is equal to the acute dietary
risk (children 1 -- 2 years utilizing 53% of the aPAD). In the short-,
and intermediate-term assessments, HED combined the current chronic
dietary exposure estimates with (previously assessed) residential
exposures. (The current petitions do not indicate any potential
residential or non-occupational exposures). Aggregate assessments
indicated no risks of concern.

HED's occupational risk assessment examined risk to workers associated
with production of alfalfa, production of grasses, and for seed
treatment operations. HED's analysis indicates that handlers using
aerial or ground boom equipment for alfalfa or grass production are
required to wear base line protective equipment (PPE), chemical
resistant gloves, and a dust/mist respirator when handing liquid
formulations of cyfluthrin/beta-cyfluthrin; but, are adequately
protected with just base line PPE when handling water soluble bag
packaged wettable powder formulations. Applicators and flaggers involved
in alfalfa and grass production were also adequately protected with base
line PPE. Exposure to workers entering cyfluthrin and beta-cyfluthrin
treated fields to perform post-application activities is not of concern.

Risks to individuals associated with sugar beet seed treatment were also
assessed. Risks of concern existed for certain scenarios.
Intermediate-term exposure to loaders/treaters involved in sugar beet
seed treatment was a concern to HED (MOE = 81). Also, risks to an
individual performing all three seed treatment operations, (i.e.,
performing loading/treating, bagging, and sewing in one 8-hour work day)
was of concern to HED. Risks to other individuals involved in the seed
treatment operation were not of concern to HED. Also, risks to workers
who plant the Poncho Beta treated sugar beet seed are not a concern to
HED.

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, which comprise the Pesticide Handlers Exposure
Database (PHED), have been determined to require a review of their
ethical conduct, and have received that review. The studies in PHED were
considered appropriate (or ethically conducted) for use in risk
assessments.

Potential areas of environmental justice concerns, to the extent
possible, were considered for this human health risk assessment, in
accordance with US Executive Order 12898, Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations, <http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf>.

As a part of every pesticide risk assessment, OPP considers a large
variety of consumer subgroups according to well-established procedures.
In line with OPP policy, HED estimates risks to population subgroups
from pesticide exposures that are based on patterns of that subgroup's
food and water consumption, and activities in and around the home that
involve pesticide use in a residential setting. Extensive data on food
consumption patterns are compiled by USDA under the CSFII, and are used
in pesticide risk assessments for all registered food uses of a
pesticide. These data are analyzed and categorized by subgroups based on
age, season of the year, ethnic group, and region of the country.
Whenever appropriate, non-dietary exposures based on home use of
pesticide products, associated risks for adult applicators, and for
toddlers, youths, and adults entering or playing on treated areas
post-application are evaluated. Further considerations are currently in
development as OPP has committed resources and expertise to the
development of specialized software and models that consider exposure to
bystanders and farm workers as well as lifestyle and traditional dietary
patterns among specific subgroups.

A separate but related petition (6F7159) was also submitted regarding
the proposed (Poncho Beta®) use on sugar beet seed. The active
ingredient being addressed in Petition 6F7159 is clothianidin, which is
a co-active ingredient along with beta-cyfluthrin in Poncho Beta®. The
occupational risks associated with clothianidin are addressed in a
separate document (D340131). Together these two documents address the
occupational risks associated with the proposed use of Poncho Beta® for
sugar beet seed treatment.

*Summary of Recommendations*

-   HED recommends directions for use of Baythroid® 2, Renounce® 20WP,
    and Baythroid® XL, be amended to exclude ultra-low volume
    applications to grasses and alfalfa.

-   HED recommends the Addition of dust/mist respirators as a PPE
    requirement for all liquid formulations of Baythroid® 2, Renounce®
    20WP, and Baythroid® XL.

-   HED recommends the Registration Division consider the occupational
    risks associated with the proposed use of Poncho Beta® in light of
    the exposures from both beta-cyfluthrin and clothianidin prior to
    granting this sugar beet seed treatment use and its associated
    tolerances.

-   Pending amendments and changes suggested to the proposed Baythroid®
    2, Renounce® 20WP, and Baythroid® XL labels, HED recommends the
    registration of new uses and establishment of tolerances for
    cyfluthrin/beta-cyfluthrin.

-   HED recommends that the establishment of tolerances incorporates the
    correct commodity definitions for cyfluthrin (and beta-cyfluthrin)
    treated commodities as stated in Appendix C, Table 1 and in the
    table below in this section.

-   A revised Section F is required reflecting HED recommendations, and
    for the establishment of (separate) tolerances listed below for both
    cyfluthrin and beta-cyfluthrin. The cyfluthrin tolerances should be
    included in 40CFR§180.436(a)(1), while a separate section under
    180.436 should be established for tolerances for beta-cyfluthrin,
    analogous to the tolerances for lambda-cyhalothrin and
    gamma-cyhalothrin in §180.438. The section for beta-cyfluthrin needs
    to be established because registrations for cyfluthrin on these
    commodities might be cancelled at some point in the future. The
    tolerances for cyfluthrin and beta-cyfluthrin should be established
    at the same levels. The recommended wording for the beta-cyfluthrin
    tolerance expression is as follows: "Tolerances are established for
    residues of the insecticide beta-cyfluthrin \[mixture comprising the
    enantiomeric pair (R)-α-cyano-4-fluoro-3-phenoxybenzyl
    (1S,3S)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate
    and (S)-α-cyano-4-fluoro-3-phenoxybenzyl
    (1R,3R)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate
    with the enantiomeric pair (R)-α-cyano-4-fluoro-3-phenoxybenzyl
    (1S,3R)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate
    and (S)-α-cyano-4-fluoro-3-phenoxybenzyl
    (1R,3S)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate\]
    in or on the following commodities:"

-   HED also recommends that, at some point in the future, tolerances be
    established for all food uses of beta-cyfluthrin (i.e., on those
    commodities not included in the present actions) under the new
    section to be created under 40 CFR §180.436.

  -----------------------------------------------------------------------
  **Commodity**                                **Recommended Tolerance
                                               (ppm)**
  -------------------------------------------- --------------------------
  Grass, forage, fodder and hay, group 17,     12
  forage                                       

  Grass, forage, fodder and hay, group 17, hay 50

  Alfalfa, forage                              5.0

  Alfalfa, hay                                 13

  Beet, sugar, roots                           0.10

  Beet, sugar, dried pulp                      1.0

  Barley, grain                                0.15

  Buckwheat, grain                             0.15

  Millet, grain                                0.15

  Oat, grain                                   0.15

  Rye, grain                                   0.15

  Wheat, grain                                 0.15

  Corn, field, grain                           0.05

  Corn, sweet, kernel plus cob with husks      0.05
  removed                                      

  Sorghum, grain, grain                        3.5

  Wheat, bran                                  0.5

  Corn, field, refined oil                     None\*

  Rice, bran                                   None

  Rice, hulls                                  None

  Grain, cereal, forage, fodder and hay, group 25
  17, forage, except rice                      

  Grain, cereal, forage, fodder and hay, group 30
  17, stover, except rice                      

  Grain, cereal, forage, fodder and hay, group 7.0
  17, straw, except rice                       

  Grain, cereal, forage, fodder and hay, group 6.0
  17, hay except rice                          

  Wheat, forage                                None

  Corn, field, forage                          None

  Corn, sweet, forage                          None

  Sorghum, grain, forage                       None

  Corn, field, stover                          None

  Corn, pop, stover                            None

  Corn, sweet, stover                          None

  Sorghum, grain, stover                       None

  Wheat, hay                                   None

  Wheat, straw                                 None

  Cattle, fat                                  2.0

  Cattle, meat                                 0.10

  Cattle, meat byproducts                      0.10

  Goat, fat                                    2.0

  Goat, meat                                   0.05

  Goat, meat byproducts                        0.05

  Hog, fat                                     0.5

  Hog, meat                                    0.01

  Hog, meat byproducts                         0.01

  Horse, fat                                   2.0

  Horse, meat                                  0.05

  Horse, meat byproducts                       0.05

  Milk                                         0.2

  Milk, fat                                    5.0

  Sheep, fat                                   2.0

  Sheep, meat                                  0.05

  Sheep, meat byproducts                       0.05
  -----------------------------------------------------------------------

\*"None" indicates that an existing tolerance on that commodity should
be revoked.

+---+------------+---------+-----+----+-----+------+-----+--------+
| * |            |         |     |    |     |      |     |        |
| * |            |         |     |    |     |      |     |        |
| T |            |         |     |    |     |      |     |        |
| a |            |         |     |    |     |      |     |        |
| b |            |         |     |    |     |      |     |        |
| l |            |         |     |    |     |      |     |        |
| e |            |         |     |    |     |      |     |        |
|   |            |         |     |    |     |      |     |        |
| 1 |            |         |     |    |     |      |     |        |
| . |            |         |     |    |     |      |     |        |
| S |            |         |     |    |     |      |     |        |
| u |            |         |     |    |     |      |     |        |
| m |            |         |     |    |     |      |     |        |
| m |            |         |     |    |     |      |     |        |
| a |            |         |     |    |     |      |     |        |
| r |            |         |     |    |     |      |     |        |
| y |            |         |     |    |     |      |     |        |
| o |            |         |     |    |     |      |     |        |
| f |            |         |     |    |     |      |     |        |
| R |            |         |     |    |     |      |     |        |
| e |            |         |     |    |     |      |     |        |
| g |            |         |     |    |     |      |     |        |
| u |            |         |     |    |     |      |     |        |
| l |            |         |     |    |     |      |     |        |
| a |            |         |     |    |     |      |     |        |
| t |            |         |     |    |     |      |     |        |
| o |            |         |     |    |     |      |     |        |
| r |            |         |     |    |     |      |     |        |
| y |            |         |     |    |     |      |     |        |
| A |            |         |     |    |     |      |     |        |
| c |            |         |     |    |     |      |     |        |
| t |            |         |     |    |     |      |     |        |
| i |            |         |     |    |     |      |     |        |
| o |            |         |     |    |     |      |     |        |
| n |            |         |     |    |     |      |     |        |
| s |            |         |     |    |     |      |     |        |
| f |            |         |     |    |     |      |     |        |
| o |            |         |     |    |     |      |     |        |
| r |            |         |     |    |     |      |     |        |
| C |            |         |     |    |     |      |     |        |
| u |            |         |     |    |     |      |     |        |
| r |            |         |     |    |     |      |     |        |
| r |            |         |     |    |     |      |     |        |
| e |            |         |     |    |     |      |     |        |
| n |            |         |     |    |     |      |     |        |
| t |            |         |     |    |     |      |     |        |
| C |            |         |     |    |     |      |     |        |
| y |            |         |     |    |     |      |     |        |
| f |            |         |     |    |     |      |     |        |
| l |            |         |     |    |     |      |     |        |
| u |            |         |     |    |     |      |     |        |
| t |            |         |     |    |     |      |     |        |
| h |            |         |     |    |     |      |     |        |
| r |            |         |     |    |     |      |     |        |
| i |            |         |     |    |     |      |     |        |
| n |            |         |     |    |     |      |     |        |
| / |            |         |     |    |     |      |     |        |
| B |            |         |     |    |     |      |     |        |
| e |            |         |     |    |     |      |     |        |
| t |            |         |     |    |     |      |     |        |
| a |            |         |     |    |     |      |     |        |
| - |            |         |     |    |     |      |     |        |
| c |            |         |     |    |     |      |     |        |
| y |            |         |     |    |     |      |     |        |
| f |            |         |     |    |     |      |     |        |
| l |            |         |     |    |     |      |     |        |
| u |            |         |     |    |     |      |     |        |
| t |            |         |     |    |     |      |     |        |
| h |            |         |     |    |     |      |     |        |
| r |            |         |     |    |     |      |     |        |
| i |            |         |     |    |     |      |     |        |
| n |            |         |     |    |     |      |     |        |
| * |            |         |     |    |     |      |     |        |
| * |            |         |     |    |     |      |     |        |
+---+------------+---------+-----+----+-----+------+-----+--------+
| * | **Petition | **Label | **  | *  |     |      |     | **Asse |
| * | Request**  | Trade   | Pro | *L |     |      |     | ssment |
| P |            | Name/** | duc | ab |     |      |     | Condu  |
| e |            |         | t** | el |     |      |     | cted** |
| t |            | **EPA   |     | I  |     |      |     |        |
| i |            | Reg.    | **F | nf |     |      |     | **(Do  |
| t |            | Nu      | orm | or |     |      |     | cument |
| i |            | mber/** | ula | ma |     |      |     | B      |
| o |            |         | tio | ti |     |      |     | arcode |
| n |            | *       | n** | on |     |      |     | Ref    |
| / |            | *Active |     | ** |     |      |     | )**    |
| * |            | Ingre   |     |    |     |      |     |        |
| * |            | dient** |     |    |     |      |     |        |
|   |            |         |     |    |     |      |     |        |
| * |            |         |     |    |     |      |     |        |
| * |            |         |     |    |     |      |     |        |
| D |            |         |     |    |     |      |     |        |
| P |            |         |     |    |     |      |     |        |
| B |            |         |     |    |     |      |     |        |
| a |            |         |     |    |     |      |     |        |
| r |            |         |     |    |     |      |     |        |
| c |            |         |     |    |     |      |     |        |
| o |            |         |     |    |     |      |     |        |
| d |            |         |     |    |     |      |     |        |
| e |            |         |     |    |     |      |     |        |
| * |            |         |     |    |     |      |     |        |
| * |            |         |     |    |     |      |     |        |
+---+------------+---------+-----+----+-----+------+-----+--------+
|   |            |         |     | *  |     | **   |     |        |
|   |            |         |     | *C |     | Prop |     |        |
|   |            |         |     | ur |     | osed |     |        |
|   |            |         |     | re |     | L    |     |        |
|   |            |         |     | nt |     | abel |     |        |
|   |            |         |     | L  |     | Rat  |     |        |
|   |            |         |     | ab |     | es** |     |        |
|   |            |         |     | el |     |      |     |        |
|   |            |         |     | R  |     |      |     |        |
|   |            |         |     | at |     |      |     |        |
|   |            |         |     | es |     |      |     |        |
|   |            |         |     | ** |     |      |     |        |
+---+------------+---------+-----+----+-----+------+-----+--------+
|   |            |         |     | *  | **  | *    | **  |        |
|   |            |         |     | *M | No. | *Max | No. |        |
|   |            |         |     | ax | of  | Si   | of  |        |
|   |            |         |     | Si | App | ngle | Ap  |        |
|   |            |         |     | ng | .** | Ra   | p** |        |
|   |            |         |     | le |     | te** |     |        |
|   |            |         |     | Ra |     |      |     |        |
|   |            |         |     | te |     |      |     |        |
|   |            |         |     | ** |     |      |     |        |
+---+------------+---------+-----+----+-----+------+-----+--------+
|   |            |         |     |    |     |      |     |        |
+---+------------+---------+-----+----+-----+------+-----+--------+
| 6 | Request    | Bay     | EC  | 0  | 3   | 0    | 4   | R      |
| E | for use on | throid® |     | .0 |     | .044 |     | esidue |
| 7 | grasses    | 2       |     | 44 |     |      |     | che    |
| 0 | throughout | (2      |     |    |     |      |     | mistry |
| 5 | the U.S.   | 64-745) |     |    |     |      |     |        |
| 8 | (pas       |         |     |    |     |      |     | (D     |
|   | ture/range | *cyfl   |     |    |     |      |     | 3      |
| D | land/grass | uthrin* |     |    |     |      |     | 39413) |
| 3 | for        |         |     |    |     |      |     |        |
| 3 | seed/grass |         |     |    |     |      |     | D      |
| 9 | for        |         |     |    |     |      |     | ietary |
| 4 | hay/grass  |         |     |    |     |      |     |        |
| 4 | in mixed   |         |     |    |     |      |     | (D3    |
| 5 | stands     |         |     |    |     |      |     | 39414) |
|   | with       |         |     |    |     |      |     |        |
| D | alfalfa)   |         |     |    |     |      |     | Occupa |
| 3 |            |         |     |    |     |      |     | tional |
| 3 |            |         |     |    |     |      |     |        |
| 1 |            |         |     |    |     |      |     | (D3    |
| 9 |            |         |     |    |     |      |     | 39445) |
| 5 |            |         |     |    |     |      |     |        |
| 2 |            |         |     |    |     |      |     |        |
|   |            |         |     |    |     |      |     |        |
| D |            |         |     |    |     |      |     |        |
| 3 |            |         |     |    |     |      |     |        |
| 3 |            |         |     |    |     |      |     |        |
| 1 |            |         |     |    |     |      |     |        |
| 9 |            |         |     |    |     |      |     |        |
| 5 |            |         |     |    |     |      |     |        |
| 1 |            |         |     |    |     |      |     |        |
+---+------------+---------+-----+----+-----+------+-----+--------+
|   |            | Re      | WP/ | N  | Not | 0    | 4   |        |
|   |            | nounce® | WSP | ot | on  | .044 |     |        |
|   |            | 20WP    |     | on | la  |      |     |        |
|   |            |         |     | l  | bel |      |     |        |
|   |            | 264-784 |     | ab |     |      |     |        |
|   |            |         |     | el |     |      |     |        |
|   |            | *cyfl   |     |    |     |      |     |        |
|   |            | uthrin* |     |    |     |      |     |        |
+---+------------+---------+-----+----+-----+------+-----+--------+
|   |            | Bay     | EC  | 0  | 3   | 0    | 4   |        |
|   |            | throid® |     | .0 |     | .022 |     |        |
|   |            | XL      |     | 22 |     |      |     |        |
|   |            |         |     |    |     |      |     |        |
|   |            | 264-840 |     |    |     |      |     |        |
|   |            |         |     |    |     |      |     |        |
|   |            | *be     |     |    |     |      |     |        |
|   |            | ta-cyfl |     |    |     |      |     |        |
|   |            | uthrin* |     |    |     |      |     |        |
+---+------------+---------+-----+----+-----+------+-----+--------+
|   |            |         |     |    |     |      |     |        |
+---+------------+---------+-----+----+-----+------+-----+--------+
| 6 | Request    | Poncho  | Liq | No |     | 5.07 | 1   | R      |
| F | for new    | Beta    | uid | ex |     | fl.  |     | esidue |
| 7 | use on     | (26     |     | is |     | oz/  |     | che    |
| 1 | sugar beet | 4-RNLA) |     | ti |     | unit |     | mistry |
| 6 | seed       |         |     | ng |     | seed |     |        |
| 0 |            | 2       |     | us |     | (100 |     | (D     |
|   |            | 64-RNLA |     | e, |     | ,000 |     | 3      |
| D |            |         |     | n  |     | se   |     | 39413) |
| 3 |            | *be     |     | ew |     | eds) |     |        |
| 3 |            | ta-cyfl |     | u  |     |      |     | D      |
| 5 |            | uthrin* |     | se |     |      |     | ietary |
| 4 |            |         |     | is |     |      |     |        |
| 8 |            | *(      |     | b  |     |      |     | (D3    |
| 6 |            | clothia |     | ei |     |      |     | 39414) |
|   |            | nidin)* |     | ng |     |      |     |        |
| D |            |         |     | p  |     |      |     | Occupa |
| 3 |            |         |     | ro |     |      |     | tional |
| 3 |            |         |     | po |     |      |     |        |
| 9 |            |         |     | se |     |      |     | (D3    |
| 4 |            |         |     | d. |     |      |     | 39445) |
| 1 |            |         |     |    |     |      |     |        |
| 3 |            |         |     |    |     |      |     |        |
|   |            |         |     |    |     |      |     |        |
| D |            |         |     |    |     |      |     |        |
| 3 |            |         |     |    |     |      |     |        |
| 3 |            |         |     |    |     |      |     |        |
| 9 |            |         |     |    |     |      |     |        |
| 4 |            |         |     |    |     |      |     |        |
| 1 |            |         |     |    |     |      |     |        |
| 4 |            |         |     |    |     |      |     |        |
|   |            |         |     |    |     |      |     |        |
| D |            |         |     |    |     |      |     |        |
| 3 |            |         |     |    |     |      |     |        |
| 3 |            |         |     |    |     |      |     |        |
| 9 |            |         |     |    |     |      |     |        |
| 4 |            |         |     |    |     |      |     |        |
| 1 |            |         |     |    |     |      |     |        |
| 5 |            |         |     |    |     |      |     |        |
+---+------------+---------+-----+----+-----+------+-----+--------+
|   |            |         |     |    |     |      |     |        |
+---+------------+---------+-----+----+-----+------+-----+--------+
| 7 | Request to | Bay     | EC  | 0  | 2 - | No   |     | R      |
| F | amend      | throid® |     | .0 | 10  | prop |     | esidue |
| 7 | labels to  | XL      |     | 19 |     | osed |     | che    |
| 2 | include    |         |     | -- |     | ch   |     | mistry |
| 0 | Crop Group | 264-840 |     | 0  |     | ange |     |        |
| 0 | 15 (except |         |     | .0 |     | to   |     | (D     |
|   | rice) and  | *be     |     | 22 |     | this |     | 3      |
| D | Crop Group | ta-cyfl |     |    |     | l    |     | 39413) |
| 3 | 16;        | uthrin* |     |    |     | abel |     |        |
| 3 |            |         |     |    |     | in   |     | D      |
| 9 | Establish  |         |     |    |     | co   |     | ietary |
| 0 | tolerance  |         |     |    |     | nnec |     |        |
| 9 | for Crop   |         |     |    |     | tion |     | (D3    |
| 5 | Group 15   |         |     |    |     | to   |     | 39414) |
|   | (except    |         |     |    |     | this |     |        |
|   | rice) and  |         |     |    |     | p    |     |        |
|   | Crop Group |         |     |    |     | etit |     |        |
|   | 16         |         |     |    |     | ion. |     |        |
+---+------------+---------+-----+----+-----+------+-----+--------+
|   |            |         |     |    |     |      |     |        |
+---+------------+---------+-----+----+-----+------+-----+--------+
| 7 | Increased  | Bay     | EC  | 0  | \~5 | 0    | 8   | R      |
| F | seasonal   | throid® |     | .0 |     | .044 |     | esidue |
| 7 | rate on    | 2       |     | 44 |     |      |     | che    |
| 2 | alfalfa    |         |     |    |     |      |     | mistry |
| 2 | (increased | 2       |     |    |     |      |     |        |
| 6 | no. of     | 64-745; |     |    |     |      |     | (D     |
|   | appl       |         |     |    |     |      |     | 3      |
| D | ications); | *cyfl   |     |    |     |      |     | 39413) |
| 3 |            | uthrin* |     |    |     |      |     |        |
| 4 | Increased  |         |     |    |     |      |     | D      |
| 0 | tolerance  |         |     |    |     |      |     | ietary |
| 7 | on alfalfa |         |     |    |     |      |     |        |
| 1 |            |         |     |    |     |      |     | (D3    |
| 0 |            |         |     |    |     |      |     | 39414) |
|   |            |         |     |    |     |      |     |        |
| D |            |         |     |    |     |      |     | Occupa |
| 3 |            |         |     |    |     |      |     | tional |
| 4 |            |         |     |    |     |      |     |        |
| 0 |            |         |     |    |     |      |     | (D3    |
| 7 |            |         |     |    |     |      |     | 39445) |
| 1 |            |         |     |    |     |      |     |        |
| 1 |            |         |     |    |     |      |     |        |
|   |            |         |     |    |     |      |     |        |
| D |            |         |     |    |     |      |     |        |
| 3 |            |         |     |    |     |      |     |        |
| 4 |            |         |     |    |     |      |     |        |
| 0 |            |         |     |    |     |      |     |        |
| 7 |            |         |     |    |     |      |     |        |
| 1 |            |         |     |    |     |      |     |        |
| 2 |            |         |     |    |     |      |     |        |
|   |            |         |     |    |     |      |     |        |
| D |            |         |     |    |     |      |     |        |
| 3 |            |         |     |    |     |      |     |        |
| 4 |            |         |     |    |     |      |     |        |
| 0 |            |         |     |    |     |      |     |        |
| 7 |            |         |     |    |     |      |     |        |
| 1 |            |         |     |    |     |      |     |        |
| 3 |            |         |     |    |     |      |     |        |
+---+------------+---------+-----+----+-----+------+-----+--------+
|   |            | Re      | WP/ | 0  | \~5 | 0    | 8   |        |
|   |            | nounce® | WSP | .0 |     | .044 |     |        |
|   |            | 20WP    |     | 44 |     |      |     |        |
|   |            |         |     |    |     |      |     |        |
|   |            | 264-784 |     |    |     |      |     |        |
|   |            |         |     |    |     |      |     |        |
|   |            | *cyfl   |     |    |     |      |     |        |
|   |            | uthrin* |     |    |     |      |     |        |
+---+------------+---------+-----+----+-----+------+-----+--------+
|   |            | Bay     | EC  | 0  | 4   | 0    | 8   |        |
|   |            | throid® |     | .0 |     | .022 |     |        |
|   |            | XL      |     | 22 |     |      |     |        |
|   |            |         |     |    |     |      |     |        |
|   |            | 264-840 |     |    |     |      |     |        |
|   |            |         |     |    |     |      |     |        |
|   |            | *be     |     |    |     |      |     |        |
|   |            | ta-cyfl |     |    |     |      |     |        |
|   |            | uthrin* |     |    |     |      |     |        |
+---+------------+---------+-----+----+-----+------+-----+--------+

Baythroid® 2 (264-745) contains cyfluthrin at 25%: Renounce® 20WP
(264-840) contains cyfluthrin at 20%

Baythroid® XL (264-840) contains beta-cyfluthrin at 12.7%; Poncho Beta®
contains beta-cyfluthrin at 4.6% and clothianidin at 34.3%.

[]{#__RefHeading___Toc179885343 .anchor}**2.0 Ingredient Profile**

Both cyfluthrin and beta-cyfluthrin are mixtures of the same four
diastereomers. Isomers I and II are in the *cis* configuration, and
Isomers III and IV are in the *trans* configuration. Cyfluthrin is
comprised of approximately equal parts: Isomer I is approximately 25%,
Isomer II is approximately 19%, Isomer III is approximately 34% and,
Isomer IV is approximately 23%. Beta-cyfluthrin on the other hand, is
enriched in Isomer II (approximately 35%) and Isomer IV (approximately
62%), and contains only minor amounts of Isomer I and Isomer III (less
than 3% of total). The nomenclature and physicochemical properties of
cyfluthrin and beta-cyfluthrin are presented below in Tables 2 and 3.

+--------------+---------------------------+---------------------------+
| **Table 2.   |                           |                           |
| Cyfluthrin   |                           |                           |
| and          |                           |                           |
| β-Cyfluthrin |                           |                           |
| Nom          |                           |                           |
| enclature.** |                           |                           |
+--------------+---------------------------+---------------------------+
|              | ![](media/image2.wmf){wi  |                           |
|              | dth="3.279861111111111in" |                           |
|              | height="0.99375in"}       |                           |
|              |                           |                           |
|              | Diastereomer I            |                           |
|              | (1R,3R,αR + 1S,3S,αS;     |                           |
|              | 1:1; cis)                 |                           |
|              |                           |                           |
|              | Diastereomer II           |                           |
|              | (1R,3R,αS + 1S,3S,αR;     |                           |
|              | 1:1; cis)                 |                           |
|              |                           |                           |
|              | Diastereomer III          |                           |
|              | (1R,3S,αR + 1S,3R,αS;     |                           |
|              | 1:1; trans)               |                           |
|              |                           |                           |
|              | Diastereomer IV           |                           |
|              | (1R,3S,αS + 1S,3R,αR;     |                           |
|              | 1:1; trans)               |                           |
+--------------+---------------------------+---------------------------+
|              | **Cyfluthrin**: Isomer I  | **beta-Cyfluthrin**:      |
|              | (23-27%), Isomer II       | Isomer I (\<2%), Isomer   |
|              | (17-21%), Isomer III      | II (30-40%), Isomer III   |
|              | (32-36%), and Isomer IV   | (\<3%), and Isomer IV     |
|              | (21-25%)                  | (57-60%)                  |
+--------------+---------------------------+---------------------------+
| Common names | Cyfluthrin and            |                           |
|              | beta-Cyfluthrin           |                           |
+--------------+---------------------------+---------------------------+
| Company      | Baythroid®, FCR1272       |                           |
| experimental |                           |                           |
| name         |                           |                           |
+--------------+---------------------------+---------------------------+
| IUPAC names  | **Cyfluthrin**:           |                           |
|              | (RS)-α-cyano              |                           |
|              | -4-fluoro-3-phenoxybenzyl |                           |
|              | (1RS,3RS;1RS,3SR)-3       |                           |
|              | -(2,2-dichlorovinyl)-2,2- |                           |
|              | dimeth                    |                           |
|              | ylcyclopropanecarboxylate |                           |
|              |                           |                           |
|              | **beta-Cyfluthrin**:      |                           |
|              | enantiomeric pair         |                           |
|              | (R)-α-cyano               |                           |
|              | -4-fluoro-3-phenoxybenzyl |                           |
|              | (1S,3S)-3-(2,2-           |                           |
|              | dichlorovinyl)-2,2-dimeth |                           |
|              | ylcyclopropanecarboxylate |                           |
|              | and                       |                           |
|              | (S)-α-cyano               |                           |
|              | -4-fluoro-3-phenoxybenzyl |                           |
|              | (1R,3R)-3-(2,2-           |                           |
|              | dichlorovinyl)-2,2-dimeth |                           |
|              | ylcyclopropanecarboxylate |                           |
|              | in ratio 1:2 with the     |                           |
|              | enantiomeric pair         |                           |
|              | (R)-α-cyano               |                           |
|              | -4-fluoro-3-phenoxybenzyl |                           |
|              | (1S,3R)-3-(2,2-           |                           |
|              | dichlorovinyl)-2,2-dimeth |                           |
|              | ylcyclopropanecarboxylate |                           |
|              | and                       |                           |
|              | (S)-α-cyano               |                           |
|              | -4-fluoro-3-phenoxybenzyl |                           |
|              | (1R,3S)-3-(2,2-           |                           |
|              | dichlorovinyl)-2,2-dimeth |                           |
|              | ylcyclopropanecarboxylate |                           |
+--------------+---------------------------+---------------------------+
| CAS name     | cyano(4-fluo              |                           |
|              | ro-3-phenoxyphenyl)methyl |                           |
|              | 3-(                       |                           |
|              | 2,2-dichloroethenyl)-2,2- |                           |
|              |                           |                           |
|              | dimeth                    |                           |
|              | ylcyclopropanecarboxylate |                           |
+--------------+---------------------------+---------------------------+
| CAS registry | 68359-37-5                |                           |
| number       |                           |                           |
+--------------+---------------------------+---------------------------+
| End-use      | Cyfluthrin: Baythroid^®^  |                           |
| products     | 2 (2 lb/gal EC; EPA Reg.  |                           |
| (EPs)        | No. 264-745)              |                           |
|              |                           |                           |
|              | Renounce^®^ 20WP (20% WP; |                           |
|              | EPA Reg. No. 264-784)     |                           |
|              |                           |                           |
|              | beta-Cyfluthrin:          |                           |
|              | Baythroid^®^ XL (1 lb/gal |                           |
|              | EC; EPA Reg. No. 264-840) |                           |
+--------------+---------------------------+---------------------------+

+-------------------------------+--------------------------------------+
| **Table 3. Physicochemical    |                                      |
| Properties of Technical Grade |                                      |
| Cyfluthrin**                  |                                      |
+-------------------------------+--------------------------------------+
| Parameter                     | Value                                |
+-------------------------------+--------------------------------------+
| Melting point/range (°C)      | Isomer I: 57 Isomer II: 73-74        |
|                               |                                      |
|                               | Isomer III: 65-66 Isomer IV: 101-102 |
+-------------------------------+--------------------------------------+
| pH                            | not measurable because of low        |
|                               | solubility in water                  |
+-------------------------------+--------------------------------------+
| Density (g/mL at 20ºC)        | 1.28                                 |
+-------------------------------+--------------------------------------+
| Water solubility (μg/L at     | Isomer I: 2.2 Isomer II: 1.9         |
| 20ºC)                         |                                      |
|                               | Isomer III: 2.2 Isomer IV: 2.9       |
+-------------------------------+--------------------------------------+
| Solvent solubility (g/L room  | Methylene chloride \>200 Toluene     |
| temperature)                  | \>200                                |
|                               |                                      |
|                               | Hexane 10-20 Isopropanol 20-50       |
+-------------------------------+--------------------------------------+
| Vapor pressure (20 or 25°C)   | 7.2 x 10^-9^ Pa                      |
+-------------------------------+--------------------------------------+
| Dissociation constant, pK~a~  | does not dissociate                  |
+-------------------------------+--------------------------------------+
| Octanol/water partition       | Isomer I: 6 Isomer II: 5.9           |
| coefficient, Log(K~OW~)       |                                      |
|                               | Isomer III: 6 Isomer IV: 5.9         |
+-------------------------------+--------------------------------------+
| UV/visible absorption         | Absorption maxima: primary: 196 nm,  |
| spectrum                      | secondary 275 nm                     |
+-------------------------------+--------------------------------------+

[]{#__RefHeading___Toc179885344 .anchor}**3.0 Hazard
Characterization/Assessment**

[]{#__RefHeading___Toc179885345 .anchor}**3.1 Database Summary**

[]{#__RefHeading___Toc179885346 .anchor}**3.1.1 Studies Available and
Considered**

Available mammalian toxicology studies considered in the hazard
characterization include:

-   Cyfluthrin

    -   acute oral, dermal, and inhalation toxicity; eye and dermal
        irritation; and dermal sensitization studies

    -   subchronic oral, dermal, and inhalation toxicity studies in rats

    -   prenatal developmental oral toxicity studies in rats and rabbits

    -   prenatal developmental inhalation toxicity studies in rats

    -   special postnatal inhalation study in mice

    -   multi-generation reproduction studies in rats

    -   chronic/carcinogenicity studies in rats and mice; chronic study
        in dogs

    -   a complete battery of mutagenicity studies

    -   delayed neurotoxicity oral and dermal studies in hens

    -   metabolism studies in rats

-   Beta-cyfluthrin

    -   acute oral, dermal, and inhalation toxicity; eye and dermal
        irritation; and dermal sensitization studies

    -   subchronic oral toxicity studies in rats and dogs

    -   subchronic inhalation toxicity study in rats

    -   prenatal developmental oral toxicity study in rats

    -   a complete battery of mutagenicity studies

    -   acute, subchronic, and developmental neurotoxicity studies in
        rats

        []{#__RefHeading___Toc179885347 .anchor}**3.1.2 Mode of Action,
        Metabolism, Toxicokinetic Data**

*Mode of Action*

Cyfluthrin is a type II pyrethroid (i.e., it has a cyano group at the α
carbon position of the alcohol moiety, and it is more effective when the
ambient temperature is raised); beta-cyfluthrin is an enriched isomer of
cyfluthrin. Pyrethroids initially stimulate nerve cells to produce
repetitive discharges which can eventually lead to paralysis. Such
effects are caused by their action on the sodium channel through which
sodium ions enter the axon to cause excitation. These effects are
produced in an insect's nerve cord, which contains ganglia and synapses,
as well as in giant nerve fiber axons.[^1] Type II pyrethroids give rise
to the C-S syndrome of clinical signs of toxicity. The C-S syndrome
consists of initial pawing and burrowing and later abnormal movements,
salivation, coarse tremors, and convulsions.

*Toxicokinetic Data*

Following oral administration, cyfluthrin is rapidly and nearly
completely absorbed. In radiolabeled studies, peak plasma levels
occurred at about 2 hours after dosing. Greater than 95% of the
administered radioactivity was excreted within 48 hours. Radioactivity
was excreted in the urine and feces with virtually none being excreted
in expired air. The ratio of radioactivity in urine/feces was higher in
males than in females. About 50% of the total urinary radioactivity was
recovered during the first 6-8 hours after dosing and about 90% within
the first 24 hours. At 48 hours, only the fat tissue (renal fat)
contained levels of radioactivity that clearly exceeded the overall mean
body level, being 6-11X higher. Different dose levels (0.5 or 10 mg/kg)
or pretreatment (14X) did not appreciably affect the above findings.
Results following intravenous dosing were quite similar to those
described for oral dosing. Studies in male rats with bile fistulas
indicated an enterohepatic circulation of test material. Parent
cyfluthrin is cleaved at the ester bond and then oxidized to yield
3-phenoxy-4-fluorobenzoic acid. This intermediate is then either
hydroxylated and subsequently conjugated and excreted, or first bound to
glycine and then hydroxylated, conjugated and excreted.

A comparative study in rats on the absorption of cyfluthrin after a
single dose indicates that when cremophor EL is used as the vehicle, the
concentration of cyfluthrin in the blood peaks after 1 hour and the rats
show signs of intoxication; whereas, when PEG 400 is used as the
vehicle, the blood level peaks at 6 hours after dosing and the maximum
blood level is about 1/5 of the level when the test substance is
administered with cremophor. There was more cyfluthrin in the stomachs
of the rats treated with PEG 400 than there was in the stomachs of those
treated with cremophor. Cyfluthrin appears to be absorbed more quickly
from the GI tract in the presence of cremophor than in the presence of
PEG 400.

[]{#__RefHeading___Toc179885348 .anchor}**3.1.3 Sufficiency of
Studies/Data**

Cyfluthrin toxicity data have been used as bridging data for
beta-cyfluthrin. The toxicology databases together are considered
complete and adequate for selecting toxicity endpoints for risk
assessment. The scientific quality is relatively high, and the toxicity
profiles of both cyfluthrin and beta-cyfluthrin can be characterized for
all effects, including potential developmental, reproductive, and
neurotoxic effects.

[]{#__RefHeading___Toc179885349 .anchor}**3.2 Toxicological Effects**

The HED risk assessment team has re-evaluated the
cyfluthrin/beta-cyfluthrin toxicological effects and endpoints for
assessing human health risk. For a complete discussion of the
toxicological effects of cyfluthrin and beta-cyfluthrin, excluding the
recently received developmental neurotoxicity study, refer to
"Toxicology Chapter for Cyfluthrin/Beta-Cyfluthrin" (D283924, V. Dobozy,
7/18/2002).

The acute toxicity of both cyfluthrin and beta-cyfluthrin is low to high
via the oral route of exposure (Categories I to III, depending on the
vehicle), moderate via the inhalation route (Categories II to III,
depending upon the vehicle), and low via the dermal route (Category IV).
Cyfluthrin and beta-cyfluthrin are slight eye and dermal irritants, but
neither is a dermal sensitizer.

The databases on cyfluthrin and beta-cyfluthrin indicate one major
target for these chemicals, the neuromuscular system, along with
non-specific effects such as decreased body weight gain and food
consumption. The neuromuscular effects (i.e., tremors, gait
abnormalities, abnormal postural reactions, splaying of limbs, and
decreases in activity) occurred mainly in oral studies in the dog and
the rat. In some studies in rats and mice, ear lesions were observed,
which appear to be related to a known pyrethroid effect, paresthesia
(tingling, burning or prickling), which caused the animals to scratch
excessively.

In oral studies with the rat, beta-cyfluthrin appeared more toxic than
cyfluthrin; however, in the oral studies with the dog (the most
sensitive species for clinical signs), beta-cyfluthrin did not appear to
be more toxic than cyfluthrin. Weight of the evidence from the
cyfluthrin rat studies (28-day feeding and gavage studies, subchronic
feeding study, 14-day and 5-month neurotoxicity studies (gavage),
chronic feeding studies and the reproduction studies) indicates that the
clinical signs of neurotoxicity in the rat may commence at a dose level
somewhere between 40 and 60 mg/kg/day. In the 90-day oral study with
beta-cyfluthrin, clinical signs of neurotoxicity were observed at
37.0/43.0 mg/kg/day (M/F), and in the 90-day subchronic neurotoxicity
study with beta-cyfluthrin, clinical signs of neurotoxicity were
observed at 27/30 mg/kg/day (M/F). Comparison of the developmental rat
studies indicates that the LOAEL for beta-cyfluthrin is 10 mg/kg/day
(decrease in body weights and food consumption); whereas, the LOAEL for
cyfluthrin is greater than 10 mg/kg/day (although some slight effects
were observed in the range-finding study at this dose level). In
contrast to the rat, when all of the available dog studies are
considered, gait abnormalities were observed at 13.9 mg/kg/day in the
90-day dog study with beta-cyfluthrin (NOAEL = 2.36 mg/kg/day), while
the LOAELs from three dog feeding studies on cyfluthrin (i.e., one
6-month and two 12-month studies) were based on similar effects and
occurred at similar doses of 15, 16, and 10.6 mg/kg/day (NOAELs = 5, 4,
and 2.4 mg/kg/day). A comparison of these NOAELs does not indicate any
major differences in toxicity between beta-cyfluthrin and cyfluthrin in
the oral studies. The studies also do not indicate any increase in the
severity of the effects over time (the NOAEL and LOAEL from the new dog
study is lower because of dose spread). In addition, the NOAELs for the
28-day dog study and the 90-day dog study conducted with beta-cyfluthrin
are similar. Therefore, it is unlikely that a NOAEL from a chronic dog
study conducted with beta-cyfluthrin would be less than the NOAEL for
the 90-day study conducted with beta-cyfluthrin. In the dog, the
neurological clinical signs induced by pyrethroids in general do not
appear to be cumulative but rather, are transient. In general, neither
sex appears to be more sensitive, for either dogs or rats.

The inhalation studies in the rat, cyfluthrin induced some clinical
signs, but these were not as severe as in the oral studies (e.g.,
reduced motility, dyspnea, piloerection, ungroomed coat, and eye
irritation). In addition to the clinical signs, hypothermia and
decreased body weight gains were also observed in the rat inhalation
studies. In a postnatal inhalation study in mice, there were clinical
signs of neurotoxicity in the pups as well as increased spontaneous
motor activity and paresthesia. The inhalation toxicity of
beta-cyfluthrin and cyfluthrin can be compared through examination of
the 4-week studies on each compound, both of which used a common
vehicle. A direct comparison is somewhat limited by the differences in
dose spacing; however, the studies show that the NOAELs and LOAELs are
not significantly different: the NOAEL and LOAEL for the study conducted
with cyfluthrin are 0.12 and 1.6 mg/kg/day, respectively and the NOAEL
and LOAEL for the study conducted with beta-cyfluthrin are 0.07 and 0.73
mg/kg/day, respectively. Both LOAELs are based on similar effects,
including body weight changes, with additional effects seen at the
higher dose of 1.6 mg/kg/day in the cyfluthrin study.

A number of the non-acute gavage studies conducted with cyfluthrin and
beta-cyfluthrin used cremophor as the vehicle. Therefore, the toxicity
of the two isomer mixtures is probably enhanced in these studies. The
repeated-dose dermal study conducted with cyfluthrin in the rat
validates this finding. In that study, the only systemic effects
observed were at the limit dose of 1077 mg/kg/day (decreased food
consumption, red nasal discharge and urine staining). All of the longer
term inhalation studies conducted with cyfluthrin and beta-cyfluthrin
use a PEG vehicle and it is likely that the same enhancement holds true
as well. These vehicles can cause damage to the lungs. The repeated dose
dermal study (18 applications) indicates that, with repeated dermal
exposure, significant dermal irritation will result. The NOAEL for skin
irritation in that study is 113 mg/kg/day and the LOAEL is 376
mg/kg/day.

Multiple hen studies by the oral, dermal and inhalation routes of
administration indicate that cyfluthrin is not a delayed neurotoxicant
and does not inhibit neurotoxic esterase.

Cyfluthrin has been classified as a Category E carcinogen (no evidence
of carcinogenicity) and, with the submission of new studies, is
reclassified as "not likely to be carcinogenic to humans" under the
Draft Proposed Guidelines for Carcinogen Risk Assessment (1999). No
increase in any type of tumors was found in rats or mice in the
available carcinogenicity studies, although structure-activity
comparisons reveal indications of lung tumors in mice with three other
pyrethroids. No evidence of mutagenicity was seen in any of the eight
acceptable studies on cyfluthrin or the five acceptable studies on
beta-cyfluthrin. The submitted studies on cyfluthrin satisfy the
pre-1991 mutagenicity test battery.

[]{#__RefHeading___Toc179885350 .anchor}**3.3 FQPA Considerations**

The cyfluthrin/beta-cyfluthrin risk assessment team has considered the
toxicity data regarding sensitivity of infants and children. For a more
in-depth description of the FQPA considerations associated with
cyfluthrin and beta-cyfluthrin, excluding the recently received
developmental neurotoxicity study, refer to "CYFLUTHRIN and
BETA-CYFLUTHRIN - 3rd Report of the Hazard Identification Assessment
Review Committee." (TXR 0050768, P. Hurley, 5/21/2002).

The mammalian toxicology database for cyfluthrin and beta-cyfluthrin is
complete and adequate for FQPA considerations. Studies available include
prenatal developmental oral toxicity studies with rats (cyfluthrin and
beta-cyfluthrin) and rabbits (cyfluthrin only); prenatal developmental
inhalation toxicity studies (cyfluthrin) in rats; a special postnatal
inhalation toxicity study (cyfluthrin) in mice; multi-generation
reproduction studies (cyfluthrin) in rats; delayed neurotoxicity oral
studies (cyfluthrin) in hens; and acute, subchronic, and developmental
neurotoxicity (DNT) studies (beta-cyfluthrin) in rats.

Evidence of neurotoxicity typical of the pyrethroids was observed
throughout the toxicology database. In the acute and subchronic
neurotoxicity studies, clinical signs of neurotoxicity, changes in
Functional Observational Battery (FOB) measurements, and decreased motor
activity were seen. In the DNT study, decreased brain weights were seen
in female offspring at study termination along with decreased body
weights and body weight gains in pups of both sexes. In the other
guideline studies on rats, dogs, and mice, neurotoxic effects including
clinical signs of neurotoxicity, gait abnormalities, changes in motor
activity, tremors, and abnormal postural reactions were seen following
oral and inhalation exposure.

There is a concern for pre- and/or postnatal toxicity resulting from
exposure to cyfluthrin and beta-cyfluthrin. In the prenatal
developmental studies, there was no evidence of increased susceptibility
of rats or rabbits to *in utero* exposure to either cyfluthrin or
beta-cyfluthrin via the oral route; however, there was evidence of
increased qualitative and quantitative susceptibility of rats to *in
utero* exposure to cyfluthrin via the inhalation route. A postnatal
inhalation study in mice demonstrates increased qualitative and
quantitative susceptibility of the offspring following exposure to
cyfluthrin. Increased susceptibility is also seen in rats in oral
reproduction studies on cyfluthrin and in a developmental neurotoxicity
study on beta-cyfluthrin.

The degree of concern for all of the prenatal developmental, special
postnatal, reproduction, and developmental neurotoxicity studies that
demonstrate increased susceptibility (quantitative and/or qualitative)
is low because the effects in each of these studies are well
characterized, with conservative NOAELs established for all
developmental and offspring effects. There are no residual uncertainties
because the points of departure (NOAELs) selected for risk assessment
are lower than the NOAELs from these studies and are, thus, protective
of any potential pre- and post-natal effects.

There are no residual uncertainties identified in the exposure
databases. The acute dietary exposure assessment is refined, and
drinking water estimates were derived from conservative screening
models. Although refined, HED believes that the dietary assessment is
based on reliable data and will not underestimate exposure/risk. The
residential exposure assessment utilizes reasonable high-end variables
set out in HED's Occupational/Residential Exposure SOPs. The aggregate
assessment is based upon reasonable worst-case residential assumptions,
and is also not likely to underestimate exposure/risk to any
subpopulation, including those comprised of infants and children.

Based on the data discussed above, the FQPA Safety Factor can be removed
(i.e., reduced to 1X) due to the completeness of the toxicology
database, the lack of residual concerns regarding pre- and post-natal
toxicity, and the reliance on exposure data that are unlikely to
underestimate exposure to the pesticide.

[]{#__RefHeading___Toc179885351 .anchor}**3.4 Hazard Identification and
Toxicity Endpoint Selection**

[]{#__RefHeading___Toc179885352 .anchor}**3.4.1 Acute Reference Dose
(aRfD) -- General Population**

***Study Selected***: Acute neurotoxicity study in rats
(beta-cyfluthrin)

***MRID Number***: 44401101

***Dose and Endpoint for Risk Assessment***: 2 mg/kg (NOAEL), based on
clinical signs, changes in FOB parameters, and decreases in motor
activity observed at 10 mg/kg (LOAEL)

***Uncertainty Factor(s)***: 100X (10X for interspecies variability, 10X
for intraspecies variability)

***Comments about Study/Endpoint/Uncertainty Factor***:

This endpoint for the general population is based on effects observed
after a single dose, which is the appropriate duration of exposure for
an acute endpoint, and the route of administration (oral) is appropriate
for dietary considerations. Selection of the acute dietary endpoint
based on the acute neurotoxicity (ACN) study is considered protective,
as the vehicle used in this study was cremophor, which has been shown to
enhance absorption of cyfluthrin, by increasing the amount of cyfluthrin
in the blood. However, the NOAEL of 2 mg/kg in the ACN study where
cremophor was the vehicle is supported by a NOAEL of 2.36 mg/kg in the
90-day dog feeding study where beta-cyfluthrin was mixed directly into
the feed (i.e., no vehicle was used). The LOAEL in this dog study was
based on gait abnormalities seen following 3 days of exposure to 13.9
mg/kg/day, similar to the effects seen after a single dose of 10 mg/kg
in the ACN study. Selection of an endpoint based on a beta-cyfluthrin
study is considered protective of effects from both beta-cyfluthrin and
cyfluthrin, as beta-cyfluthrin is an enriched isomer of cyfluthrin.

A separate endpoint for acute dietary exposure to females 13-49 was not
selected because the acute reference dose for the general population is
protective of any potential developmental effects. No developmental
effects are observed in any of the developmental studies at dose levels
in the 2 mg/kg range. In the rat developmental toxicity study with
beta-cyfluthrin, increases in skeletal variations were observed at 40
mg/kg/day (NOAEL = 10 mg/kg/day); however, these effects generally
consisted of changes in ossification rates likely to be connected with
an observed decrease in mean fetal body weights, which are not
considered to be single dose effects. Further, most of these differences
were seen in the number of fetuses affected and not in the number of
litters affected. The acute reference dose for the general population is
also protective of the offspring effects seen in the developmental
neurotoxicity study with beta-cyfluthrin, which included decreased brain
weights in females at study termination, at 17.8 mg/kg/day (NOAEL = 11
mg/kg/day). No other potential acute dietary endpoints for females 13-49
were found in the available database.

[]{#__RefHeading___Toc179885353 .anchor}**3.4.2 Chronic Reference Dose
(cRfD)**

***Study Selected:*** Chronic toxicity study in dogs (cyfluthrin)

***MRID Number:*** 44435401

***Dose and Endpoint for Risk Assessment***: 2.4 mg/kg/day (NOAEL),
based on clinical signs, gait abnormalities, and abnormal postural
reactions observed at 10.64 mg/kg (LOAEL)

***Uncertainty Factor(s):*** 100X (10X for interspecies variability, 10X
for intraspecies variability)

***Comments about Study/Endpoint/Uncertainty Factor***: This endpoint is
selected from a chronic feeding study, the appropriate length and route
of exposure for a chronic dietary endpoint. It is supported by the
chronic feeding study in the rat (NOAEL = 2.6 mg/kg/day) and the
multigeneration reproduction study in the rat (parental NOAEL = 3
mg/kg/day), where both LOAELs were based on decreased body weights.

Although the acute toxicity studies and the oral rat studies indicate
that beta-cyfluthrin is more toxic than cyfluthrin and the percentages
of the insecticidally active isomers in beta-cyfluthrin would indicate
that it could be up to twice as toxic as cyfluthrin, it is anticipated
that this endpoint would be protective for beta-cyfluthrin for the
following reasons. While the oral studies in rats indicate that
beta-cyfluthrin is more toxic than cyfluthrin, the oral studies in dogs
(the most sensitive species for clinical signs), do not show that
beta-cyfluthrin is more toxic than cyfluthrin. For example, the weight
of evidence from the cyfluthrin rat studies (28-day feeding and gavage
studies, subchronic feeding study, 14-day and 5-month neurotoxicity
studies (gavage), chronic feeding studies and the reproduction studies)
indicate that for cyfluthrin, it appears that the clinical signs of
neurotoxicity in the rat may commence at a dose level somewhere between
40 and 60 mg/kg/day; whereas, in the 90-day oral study with
beta-cyfluthrin, clinical signs of neurotoxicity were observed at
37.0/43.0 mg/kg/day (M/F) and in the 90-day subchronic neurotoxicity
study with beta-cyfluthrin, clinical signs of neurotoxicity were
observed at 27/30 mg/kg/day (M/F). In addition, examination of the
developmental rat studies indicates that while the LOAEL for
beta-cyfluthrin is 10 mg/kg/day (based on decreased body weights and
food consumption), the LOAEL for cyfluthrin is greater than 10 mg/kg/day
(although some slight effects were observed in the range-finding study
at this dose level). In contrast, when all of the available dog studies
are considered, the NOAEL for the 90-day dog study with beta-cyfluthrin
is 2.36 mg/kg/day with gait abnormalities observed at 13.9 mg/kg/day,
while the NOAELs and LOAELs from the 3 dog feeding studies conducted
with cyfluthrin (one 6-month and two 12- month studies are 5/4/2.4
(NOAELs) and 15/16/10.6 (LOAELs) mg/kg/day, respectively, based on
similar effects. A comparison of these NOAELs does not indicate any
major differences in toxicity between beta-cyfluthrin and cyfluthrin. A
comparison of these NOAELs also does not indicate any increase in the
severity of the effects over time (the NOAEL and LOAEL from the new dog
study is lower because of dose spread). In addition, the NOAELs for the
28-day dog study and the 90-day dog study conducted with beta-cyfluthrin
are similar. Therefore, it is unlikely that a NOAEL from a chronic dog
study conducted with beta-cyfluthrin would be less than the NOAEL for
the 90-day study conducted with beta-cyfluthrin. In general, the
neurological clinical signs induced by pyrethroids in dogs appear to be
transient, rather than cumulative.

The NOAEL selected for the chronic RfD would be protective of any
concerns to the offspring in the oral pre-and post-natal studies,
including the developmental neurotoxicity study, because the NOAELs for
the offspring are greater than the selected NOAEL from the chronic dog
study.

[]{#__RefHeading___Toc179885354 .anchor}**3.4.3** **Incidental Oral
Exposure (Short- and Intermediate-Term)**

***Study Selected:*** 90-Day feeding study in dogs (beta-cyfluthrin)

***MRID Number:*** 41267801

***Dose and Endpoint for Risk Assessment*:** 2.36 mg/kg/day (NOAEL),
based on gait abnormalities beginning in the first week, increased
incidence of vomiting, and suggestive decreased body weight gain
observed at 13.9 mg/kg/day (LOAEL)

***Uncertainty Factor(s)**:* 100X (10X for interspecies variability, 10X
for intraspecies variability)

***Comments about Study/Endpoint/Uncertainty Factor*:** For females, the
NOAEL/LOAEL in this study is 2.5/15.4 mg/kg/day. This study is
considered appropriate for short-term oral exposure (1-30 days) because
it is an oral study, and gait abnormalities were observed following 3
exposures. It is supported by the chronic feeding study in the dog with
cyfluthrin in which vomiting was considered to be related to treatment
and was observed starting on day 1 (NOAEL 2.4 mg/kg/day). The 90-day
feeding study in dogs is also supported by the acute neurotoxicity study
in rats conducted with beta-cyfluthrin, a single oral dose study with a
NOAEL of 2.0 mg/kg. This endpoint is also considered appropriate for
intermediate-term exposure (30 days to 6 months) because it is selected
from a subchronic feeding study, the appropriate length and route of
exposure for intermediate incidental oral exposure.

This endpoint would be protective of any concerns to developing fetuses
and/or offspring in the oral prenatal developmental, developmental
neurotoxicity, and reproduction studies. No developmental effects are
observed in any of these studies at dose levels in the 2.4 mg/kg/day
range.

[]{#__RefHeading___Toc179885355 .anchor}**3.4.4 Dermal Absorption**

***Dermal Absorption Factor:*** 5%

No dermal penetration/absorption studies are available for cyfluthrin or
beta-cyfluthrin. A conservative dermal absorption value of 5% was
calculated as a comparative ratio of toxicity between the oral LOAEL of
50 mg/kg/day from a 28-day feeding study on cyfluthrin in rats and the
dermal LOAEL of 1077 mg/kg/day from a 21-day (18 applications) dermal
study on cyfluthrin in rats. The basis for both LOAELs included
decreased food consumption; in addition, more severe toxic effects were
observed in the oral study (including gait abnormalities) at the LOAEL,
so the 5% dermal absorption factor is considered to be a conservative
estimate.

The dermal absorption factor is required for short-, intermediate- and
long-term dermal exposure assessments, since the endpoints for each of
these assessments are based on oral studies.

**3.4.5 Dermal Exposure (Short- and Intermediate-Term)**

***Study Selected:*** 90-Day feeding study in dogs (beta-cyfluthrin)

***MRID Number***: 41267801

***Dose and Endpoint for Risk Assessment***: 2.36 mg/kg/day (NOAEL),
based on gait abnormalities (both sexes), vomiting (both sexes), and
suggestive decreases in body weight gain observed in males at 13.9
mg/kg/day (LOAEL)

***Uncertainty Factor(s):*** 100X (10X for interspecies variability, 10X
for intraspecies variability)

***Comments about Study/Endpoint/Uncertainty Factor:*** For females, the
NOAEL/LOAEL in this study is 2.5/15.4 mg/kg/day. This endpoint is based
on an oral study and should be used in conjunction with a 5% dermal
absorption factor (section 3.3.4).

[]{.mark}

A 21-day dermal toxicity study in rats with a systemic NOAEL of 376
mg/kg/day and LOAEL of 1077 mg/kg/day was available. The LOAEL was based
on decreased food consumption, red nasal discharge and urine staining,
none of which are considered severely adverse, nor do they reflect the
major target for cyfluthrin (clinical signs of neurotoxicity). No
clinical signs of neurotoxicity were seen in this study, while such
signs were seen at comparable doses following a single oral dose in rats
as well as following repeated doses in dogs. Therefore, the HED did not
select this study for dermal exposure risk assessments.

Instead, the HED determined that an oral study is appropriate for both
short- and intermediate-term dermal exposure because the endpoints of
concern (clinical signs indicative of neurotoxicity) characteristic of
this compound, were seen in the most sensitive species (dog), starting
after 3 exposures. In addition, this dose and endpoint are supported by
similar findings in the acute neurotoxicity study with beta-cyfluthrin;
the NOAEL was 2 mg/kg/day, and the LOAEL was 10 mg/kg/day based on
clinical signs, changes in FOB parameters, and decreased motor activity.

This endpoint would be protective of any concerns to developing fetuses
and/or offspring in the oral prenatal developmental, developmental
neurotoxicity, and reproduction studies. No developmental effects are
observed in any of these studies at dose levels in the 2.4 mg/kg/day
range.

It was noted that following inhalation exposure, the developmental NOAEL
(0.00059 mg/L, which converts to 0.16 mg/kg/day) and LOAEL (0.0011 mg/L,
which converts to 0.3 mg/kg/day) are much lower than the dose (2.4
mg/kg/day) selected for this risk assessment. This would indicate that
the NOAEL from the dog study would not be specifically protective of
developmental effects observed in the inhalation studies. It is noted,
however, that due to the significantly higher potential for absorption
via the inhalation route (complete or 100%) when compared to the dermal
route (5%), a direct comparison of NOAELs from inhalation studies cannot
be made for dermal exposure.

**3.4.6 Dermal Exposure (Long-Term)**

***Study Selected***: Chronic toxicity study in dogs (cyfluthrin)

***MRID Number***: 44435401

***Dose and Endpoint for Risk Assessment*:** 2.4 mg/kg/day (NOAEL),
based on clinical signs, gait abnormalities, and abnormal postural
reactions observed at 10.64 mg/kg (LOAEL)

***Uncertainty Factor(s**):* 100X (10X for interspecies variability, 10X
for intraspecies variability)

***Comments about Study/Endpoint/Uncertainty Factor**:*

This endpoint is based on a chronic feeding study, which is the
appropriate length and route of exposure for a chronic endpoint. It
should be used in conjunction with a 5% dermal absorption factor
(Section 3.3.4).

[]{#__RefHeading___Toc179885356 .anchor}**3.4.7 Inhalation Exposure
(Short-Term)**

[]{.mark}

***Study Selected***: 4-Week inhalation study in rats (beta-cyfluthrin)

***MRID Number***: 41783001

***Dose and Endpoint for Risk Assessment***: 0.07 mg/kg/day (0.00026
mg/L; NOAEL), based on decreases in body weight in both sexes and
decreased urinary pH in males observed at 0.73 mg/kg/day (0.0027 mg/L;
LOAEL)

***Uncertainty Factor(s)*:** 100X (10X for interspecies variability, 10X
for intraspecies variability)

***Comments about Study/Endpoint/Uncertainty Factor***: This study is of
appropriate duration and route for a short-term endpoint. The 90-day
inhalation study of cyfluthrin in rats, which results in a lower
NOAEL/LOAEL was not selected because the duration of exposure is not
appropriate for a short-term endpoint. A 4-week inhalation study in rats
is also available for cyfluthrin; however, it was not selected for this
endpoint because the NOAEL and LOAEL in the 4-week beta-cyfluthrin
inhalation study are lower and protective of effects in both 4-week
studies. A 5-day inhalation study in rats with beta-cyfluthrin resulted
in the same NOAEL as the 4-week study that was ultimately selected for
this endpoint. Finally, there are four other inhalation studies which
could have been used for this endpoint: three developmental inhalation
studies and a 7-day postnatal inhalation mouse study. In all four
studies, qualitative and/or quantitative increased susceptibility was
observed in the offspring; however, all of the observed
developmental/offspring effects are well characterized and definitive
NOAELs can be established for these effects. Therefore, the degree of
concern for these studies is low. The developmental NOAELs for the three
developmental studies are 0.125 and 0.160 (two combined studies)
mg/kg/day. The NOAEL for the postnatal mouse study is 2.48 mg/kg/day.
The proposed endpoint of 0.07 mg/kg/day would be protective of these
developmental/offspring NOAELs, as well as of the toxicity seen in the
remainder of the toxicology database, including all oral studies.

[]{.mark}

[]{#__RefHeading___Toc179885357 .anchor}**3.4.8 Inhalation Exposure
(Intermediate- and Long-Term)**

[]{.mark}

***Study Selected*:** 13-Week inhalation study in rats (cyfluthrin)

***MRID Numbers*:** 00157793, 40082901, 40239301

***Dose and Endpoint for Risk Assessment*:** 0.02 mg/kg/day (0.00009
mg/L; NOAEL), based on decreased body weights and body weight gains in
males and clinical signs in females observed at 0.16 mg/kg/day (0.000071
mg/L; LOAEL)

***Uncertainty Factor(s)*:** 100X (10X for interspecies variability, 10X
for intraspecies variability)

***Comments about Study/Endpoint/Uncertainty Factor***: This is a
13-week inhalation study which is the appropriate route of exposure and
the appropriate time period for intermediate-term exposure. For long
term exposure, an uncertainty factor for extrapolating from a subchronic
study to a chronic study will not be applied because there is no
evidence to show that there will be greater toxicity following longer
exposure (see the chronic dietary section for a more complete
discussion). In addition, this study was conducted with cyfluthrin.
Although beta-cyfluthrin is more acutely toxic than cyfluthrin, an
uncertainty factor for extrapolating from cyfluthrin to beta-cyfluthrin
was not added. A comparison of 4-week inhalation data with cyfluthrin
and beta-cyfluthrin is somewhat limited by the differences in dose
spread; however, it does show that the NOAELs and LOAELs are not
significantly different: the NOAEL and LOAEL for the study conducted
with cyfluthrin are 0.12 and 1.6 mg/kg/day, respectively and the NOAEL
and LOAEL for the study conducted with beta-cyfluthrin are 0.07 and 0.73
mg/kg/day, respectively. Both 4-week study LOAELs are based on similar
effects, including body weight changes, with additional effects seen at
the higher dose of 1.6 mg/kg/day in the cyfluthrin study. For further
discussion on this point with the oral data, see the chronic dietary
section.

The discussion on comparison with studies for which there is increased
susceptibility follows the same logic as in Section 3.4.8. In addition,
the proposed endpoint of 0.02 mg/kg/day is protective of the toxicity
seen in the remainder of the toxicology database, including all oral
studies.

[]{#__RefHeading___Toc179885358 .anchor}**3.4.9 Level of Concern for
Margin of Exposure (MOE)**

+-------------------------+-----------+-----------------+--------------+
| **Table 4. Summary of   |           |                 |              |
| Levels of Concern for   |           |                 |              |
| Risk Assessment.**      |           |                 |              |
+-------------------------+-----------+-----------------+--------------+
| **Route**               | **Sho     | **Inte          | *            |
|                         | rt-Term** | rmediate-Term** | *Long-Term** |
|                         |           |                 |              |
|                         | **(1 - 30 | **(1 - 6        | **(\> 6      |
|                         | Days)**   | Months)**       | Months)**    |
+-------------------------+-----------+-----------------+--------------+
| **Occupational (Worker) |           |                 |              |
| Exposure**              |           |                 |              |
+-------------------------+-----------+-----------------+--------------+
| Dermal                  | 100       | 100             | N/A          |
+-------------------------+-----------+-----------------+--------------+
| Inhalation              | 100       | 100             | N/A          |
+-------------------------+-----------+-----------------+--------------+
| **Residential           |           |                 |              |
| Exposure**              |           |                 |              |
+-------------------------+-----------+-----------------+--------------+
| Dermal                  | 100       | 100             | N/A          |
+-------------------------+-----------+-----------------+--------------+
| Inhalation              | 100       | 100             | N/A          |
+-------------------------+-----------+-----------------+--------------+
| Incidental Oral         | 100       | 100             | N/A          |
+-------------------------+-----------+-----------------+--------------+

[]{#__RefHeading___Toc179885359 .anchor}**3.4.10 Recommendation for
Aggregate Exposure Risk Assessments**

Consistent with FQPA, 1996, HED considers an aggregate risk assessment
when there are potential residential exposures that may result in
exposure from three major pathways (oral, dermal, and inhalation). The
risks for the different routes of exposure may be aggregated due to the
presence of a common toxicity endpoint (clinical signs of neurotoxicity
and/or body weight effects).

Cyfluthrin/beta-cyfluthrin is currently registered for residential uses
including indoor (e.g. total release fogger and crack and crevice spray)
and outdoor uses (e.g. spray fogger, and lawn applications). Aggregate
risk assessments for acute, short-term, and intermediate-term durations
were conducted. In an acute aggregate risk assessment, HED combines
acute dietary exposures (food + water). For a short-term aggregate risk
assessment, HED combines the average dietary exposures (i.e., the
chronic dietary exposures from DEEM) with the short-term residential
exposure; and, for intermediate-term aggregate risk assessments, HED
combines average dietary exposures (food + water) with intermediate term
residential exposure. For the residential component of the cyfluthrin
aggregate risk assessment, HED combined exposures from indoor carpet use
and outdoor lawn use to present a conservative residential exposure
scenario. Exposure pathways from both indoor carpet use and outdoor lawn
use include dermal, inhalation, and oral routes for both short-term and
intermediate-term durations (see HED memo D283388; S. Tadayon; 7/31/03,
and HED memo; Y. Donovan; D290925; 7/15/05).

[]{#__RefHeading___Toc179885360 .anchor}**3.4.11 Classification of
Carcinogenic Potential**

On March 14, 1986, HED classified cyfluthrin as a Category E carcinogen
(no evidence of carcinogenicity) based on the two older rat and mouse
studies. Based on the new and old studies, cyfluthrin is classified as
"not likely to be carcinogenic to humans" (HIARC, 2001).

[]{#__RefHeading___Toc179885361 .anchor}**3.4.12 Summary of
Toxicological Doses and Endpoints for Cyfluthrin and Beta-Cyfluthrin for
Use in Human Health Risk Assessments**

A summary of toxicological endpoints and doses for use in the both the
dietary and non-occupational risk assessment as well as the occupational
assessment of cyfluthrin/beta-cyfluthrin is contained in Table 5, below.

+---------+--------+---------+-------------+------------------------+
| **Table |        |         |             |                        |
| 5.      |        |         |             |                        |
| Toxico  |        |         |             |                        |
| logical |        |         |             |                        |
| Doses   |        |         |             |                        |
| and     |        |         |             |                        |
| En      |        |         |             |                        |
| dpoints |        |         |             |                        |
| for     |        |         |             |                        |
| Cyf     |        |         |             |                        |
| luthrin |        |         |             |                        |
| and     |        |         |             |                        |
| B       |        |         |             |                        |
| eta-Cyf |        |         |             |                        |
| luthrin |        |         |             |                        |
| for Use |        |         |             |                        |
| in      |        |         |             |                        |
| No      |        |         |             |                        |
| n-Occup |        |         |             |                        |
| ational |        |         |             |                        |
| Human   |        |         |             |                        |
| Health  |        |         |             |                        |
| Risk    |        |         |             |                        |
| Assessm |        |         |             |                        |
| ents.** |        |         |             |                        |
+=========+========+=========+=============+========================+
| **Expo  | *      | **Unce  | **Level of  | **Study and            |
| sure/** | *Point | rtainty | Concern for | Toxicological          |
|         | of     | Fa      | Risk        | Effects**              |
| **Sce   | Depar  | ctors** | A           |                        |
| nario** | ture** |         | ssessment** |                        |
+---------+--------+---------+-------------+------------------------+
| **Acute | NOAEL= | UF~A~=  | Acute RfD = | Acute neurotoxicity in |
| Di      | 2      | 10x     |             | rats (beta-cyfluthrin) |
| etary** | mg/kg  |         | 0.02 mg/kg  |                        |
| (All    |        | UF~H~ = |             | LOAEL = 10 mg/kg based |
| Popul   |        | 10x     | aPAD =      | on clinical signs,     |
| ations) |        |         |             | changes in FOB         |
|         |        | FQPA    | 0.02 mg/kg  | parameters, and        |
|         |        | SF= 1x  |             | decreases in motor     |
|         |        |         |             | activity.              |
+---------+--------+---------+-------------+------------------------+
| **      | NOAEL= | UF~A~=  | Chronic RfD | Chronic toxicity in    |
| Chronic | 2.4    | 10x     | =           | dogs (cyfluthrin)      |
| Di      | mg/    |         |             |                        |
| etary** | kg/day | UF~H~ = | 0.024       | LOAEL = 10.64          |
|         |        | 10x     | mg/kg/day   | mg/kg/day based on     |
| (All    |        |         |             | clinical signs, gait   |
| Popul   |        | FQPA    | cPAD =      | abnormalities, and     |
| ations) |        | SF= 1x  |             | abnormal postural      |
|         |        |         | 0.024       | reactions.             |
|         |        |         | mg/kg/day   |                        |
+---------+--------+---------+-------------+------------------------+
| **Inc   | NOAEL= | UF~A~=  | Residential | 90-Day feeding study   |
| idental | 2.36   | 10x     | LOC for MOE | in dogs                |
| Oral**  | mg/    |         | = 100       | (beta-cyfluthrin)      |
|         | kg/day | UF~H~ = |             |                        |
| Short-  |        | 10x     |             | LOAEL = 13.9/15.4      |
| (1-30   |        |         |             | mg/kg/day (M/F) based  |
| Days)   |        | FQPA    |             | on gait abnormalities, |
| and     |        | SF= 1x  |             | increased incidence of |
| Interm  |        |         |             | vomiting, and          |
| ediate- |        |         |             | suggestive decreased   |
| Term    |        |         |             | body weight gain.      |
| (1 - 6  |        |         |             |                        |
| Months) |        |         |             |                        |
+---------+--------+---------+-------------+------------------------+
| **D     | NOAEL= | UF~A~=  | Residential | 90-Day dog feeding     |
| ermal** | 2.36   | 10x     | LOC for MOE | study                  |
|         | mg/    |         | = 100       | (beta-cyfluthrin)      |
| Short-  | kg/day | UF~H~ = |             |                        |
| (1-30   |        | 10x     |             | LOAEL = 13.9/15.4      |
| Days)   | Dermal |         |             | mg/kg/day (M/F) based  |
| and     | abso   | FQPA    |             | on gait abnormalities, |
| Interm  | rption | SF= 1x  |             | increased incidence of |
| ediate- | rate = |         |             | vomiting, and          |
| Term    | 5%     |         |             | suggestive decreased   |
| (1 - 6  |        |         |             | body weight gain.      |
| Months) |        |         |             |                        |
+---------+--------+---------+-------------+------------------------+
| **D     | NOAEL= | UF~A~=  | Residential | Chronic toxicity in    |
| ermal** | 2.4    | 10x     | LOC for MOE | dogs (cyfluthrin)      |
|         | mg/    |         | = 100       |                        |
| Lo      | kg/day | UF~H~ = |             | LOAEL = 10.64          |
| ng-Term |        | 10x     |             | mg/kg/day based on     |
| (\>6    | Dermal |         |             | clinical signs, gait   |
| Months) | abso   | FQPA    |             | abnormalities, and     |
|         | rption | SF= 1x  |             | abnormal postural      |
|         | rate = |         |             | reactions.             |
|         | 5%     |         |             |                        |
+---------+--------+---------+-------------+------------------------+
| **Inhal | NOAEL= | UF~A~=  | Residential | 28-Day rat inhalation  |
| ation** | 0      | 10x     | LOC for MOE | study                  |
|         | .00026 |         | = 100       | (beta-cyfluthrin)      |
| Sho     | mg/L   | UF~H~ = |             |                        |
| rt-Term |        | 10x     |             | LOAEL = 0.0027 mg/L    |
|         | (0.07  |         |             | (0.73 mg/kg/day) based |
| (1-30   | mg/k   | FQPA    |             | on decreases in body   |
| Days)   | g/day) | SF= 1x  |             | weight in both sexes   |
|         |        |         |             | and decreased urinary  |
|         |        |         |             | pH in males.           |
+---------+--------+---------+-------------+------------------------+
| **Inhal | NOAEL= | UF~A~=  | Residential | 13-Week rat inhalation |
| ation** | 0      | 10x     | LOC for MOE | study (cyfluthrin)     |
|         | .00009 |         | = 100       |                        |
| Interm  | mg/L   | UF~H~ = |             | LOAEL = 0.00071 mg/L   |
| ediate- |        | 10x     |             | (0.16 mg/kg/day) based |
| (1-6    | (0.02  |         |             | on decreases in body   |
| months) | mg/k   | FQPA    |             | weight and body weight |
| and     | g/day) | SF= 1x  |             | gain in males and      |
| Lo      |        |         |             | clinical signs in      |
| ng-Term |        |         |             | females.               |
| (\>6    |        |         |             |                        |
| months) |        |         |             |                        |
+---------+--------+---------+-------------+------------------------+
| **C     | Cla    |         |             |                        |
| ancer** | ssific |         |             |                        |
| (oral,  | ation: |         |             |                        |
| dermal, | "Not   |         |             |                        |
| inha    | likely |         |             |                        |
| lation) | to be  |         |             |                        |
|         | Carcin |         |             |                        |
|         | ogenic |         |             |                        |
|         | to     |         |             |                        |
|         | H      |         |             |                        |
|         | umans" |         |             |                        |
+---------+--------+---------+-------------+------------------------+

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 (interspecies). UF~H~ =
potential variation in sensitivity among members of the human population
(intraspecies). 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.

[]{#__RefHeading___Toc179885362 .anchor}**3.5 Endocrine Disruption**

EPA is required under the Federal Food Drug and Cosmetic Act (FFDCA), as
amended by FQPA, to develop a screening program to determine whether
certain substances (including all pesticide active and other
ingredients) \"may have an effect in humans that is similar to an effect
produced by a naturally occurring estrogen, or other such endocrine
effects as the Administrator may designate.\" Following the
recommendations of its Endocrine Disruptor Screening and Testing
Advisory Committee (EDSTAC), EPA determined that there was 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 has 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).

When the appropriate screening and/or testing protocols being considered
under the Agency's EDSP have been developed, beta-cyfluthrin may be
subjected to additional screening and/or testing to better characterize
effects related to endocrine disruption.

[]{#__RefHeading___Toc179885363 .anchor}**4.0 Public Health and
Pesticide Epidemiology Data**

No public health data are being considered at this time.

[]{#__RefHeading___Toc179885364 .anchor}**5.0 Dietary Exposure/Risk
Characterization**

[]{#__RefHeading___Toc179885365 .anchor}**5.1 Metabolism and
Environmental Degradation**

[]{#__RefHeading___Toc179885366 .anchor}**5.1.1 Metabolism in Primary
Crops**

HED has concluded that the nature of cyfluthrin/beta-cyfluthrin in
plants is adequately understood based on plant metabolism studies
conducted in cotton, soybeans, potatoes, apples, wheat, and tomatoes.
Data from those studies indicate that the nature of the residue is
similar in all plant matrices. The major detected residue is the parent
cyfluthrin which comprised between 38% -- 98% of the total radioactive
residues (TRR). In plants, cyfluthrin was seen to metabolize slowly with
little translocation. Other metabolites detected, including FPBalc,
FPBald, FPBacid, FPBamide, FPB methyl ester, and 4\'-OH-FPBacid,
generally comprised \<10% of the TRR. HED, therefore, has determined
that the residue of concern in plants is cyfluthrin *per se*. The nature
of cyfluthrin residues in plants is summarized in the HED memorandum
*Registration for Use on Grasses, Alfalfa, and Seed Treatment Use on
Sugar Beets,* (D. Dotson; D339413; 10/15/2007).

[]{#__RefHeading___Toc179885367 .anchor}**5.1.2 Metabolism in
Livestock**

The nature of cyfluthrin/beta-cyfluthrin is adequately understood in
livestock based upon metabolism data in cattle and poultry. In lactating
cows the parent comprised 56-100% of the TRR in tissues and milk. In
poultry, the parent comprised 28-56% of the TRR in muscle, fat, skin,
and eggs, (in poultry liver and kidney, the parent comprised 9-12% of
the TRR). Metabolites (FPBalc, FPBald, FPBacid, and 4\'-OH-FPBacid),
comprised 0-43% of the TRR in cow tissues and milk and 0-19% of the TRR
in poultry tissues and eggs. The residue of concern in animals is
cyfluthrin, *per se*.

**5.1.3 Analytical Methodology**

*Residue Analytical Method*

Adequate GC/ECD methods are available in PAM Vol. II for enforcing
tolerances for cyfluthrin/beta-cyfluthrin residues in/on plant
commodities (Method 85823) and animal commodities (Method 85883). The
limit of detection for cyfluthrin/beta-cyfluthrin in both methods is
0.01 ppm in the tested plant and animal commodities.

In the current grass, alfalfa, and sugar beet field trials, as well as
the sugar beet processing study, samples were analyzed for residues of
cyfluthrin using Bayer Method 108139-1 (GC/MS). This method was
previously reviewed by the Agency and deemed adequate for data
collection, and was adequately validated on grass, alfalfa, and sugar
beet commodities in conjunction with the analysis of field trial and
processing study samples.

The validated limit of quantitation (LOQ) for cyfluthrin residues in
grass forage and hay is 0.05 ppm, and the statistically calculated limit
of detection (LOD) is 0.014 ppm for forage, and 0.020 ppm for hay. The
validated LOQ for cyfluthrin residues is 0.01 ppm for all sugar beet
commodities, and the statistically calculated LODs are 0.003 ppm for
tops and roots, and 0.0011-0.0018 ppm for processed fractions.

*Multiresidue Method*

Data pertaining to the recovery of cyfluthrin using FDA\'s multiresidue
methods were submitted in 1998 (MRID 40355901), and forwarded to FDA.
The FDA Pestrak Data Base (PAM Vol. I, Appendix, dated 11/6/90)
indicates that complete recovery has been obtained for cyfluthrin using
FDA multiresidue methods.

[]{#__RefHeading___Toc179885368 .anchor}**5.1.4 Environmental
Degradation**

Cyfluthrin is moderately persistent in the environment and immobile.
Data suggest that the primary routes of dissipation include hydrolysis
in alkaline media (T½ = stable, essentially stable and 2.1 days at pH's
5, 7 and 9 respectively); aqueous photolysis (T½ = 0.7 - 4.5 days); and,
soil photolysis (T½ = 5.6 days). Data indicate that aerobic soil
metabolism plays a secondary role in the dissipation of cyfluthrin (T½ =
ranged from 73.5 and 94.8 days). Data show that cyfluthrin degrades
slowly under normal conditions of aerobicity and organic matter, but
degrades faster under anaerobic environments or in soils with higher
organic matter. While moisture level does not appear to have a
significant effect on cyfluthrin's rate of degradation, pH does
(degrading faster in conditions of higher pH).

Similar to other pyrethroids, cyfluthrin is hydrophobic, binding
strongly to soil surfaces. The moderate persistence of the chemical, its
high soil affinity and low solubility indicate (i) a low potential to
leach to subsurfaces and to contaminate groundwater; and, (ii) that the
chemical has a high potential to reach surface waters in runoff events
accompanied by erosion occurring during periods of weeks to months after
application. Once the chemical reaches surface waters, the potential
impact to water quality appears to be mostly due to parent compound.
Cyfluthrin residues could also reach surface waters via spray drift.

Once cyfluthrin reaches surface waters, the potential impact to water
quality appears to be mostly due to cyfluthrin, *per se*. Laboratory
studies predict that once the chemical reaches surface waters, it may
persist for moderate periods of time. Cyfluthrin's lipophilicity and
affinity to particulate make it unavailable to photolysis. In addition,
photolysis would be limited only to clear shallow waters or the upper
layers of the water column.

[]{#__RefHeading___Toc179885369 .anchor}**5.1.5 Pesticide Metabolites
and Degradates of Concern**

The HED previously determined that the residue of concern in all
matrices (plants, livestock, and drinking water) is cyfluthrin, per se
(MARC Decision Memorandum; 6/13/02; TXR 0050805). The cyfluthrin risk
assessment team is in agreement with this previous determination.

  ---------------------------- --------------------- -------------------- --------------------
  **Table 6. Summary of                                                   
  Metabolites and Degradates                                              
  to be included in the                                                   
  Cyfluthrin/Beta-cyfluthrin                                              
  Risk Assessment and                                                     
  Tolerance Expression\***                                                

  **Matrix**                                         **Residues included  **Residues included
                                                     in Risk Assessment** in Tolerance
                                                                          Expression**

                               Primary Crop          Cyfluthrin, *per se* Cyfluthrin, *per se*

                               Rotational Crop       N/A                  N/A

                               Ruminant              Cyfluthrin, *per se* Cyfluthrin, *per se*

                               Poultry               Cyfluthrin, *per se* Cyfluthrin, *per se*

                               Drinking Water        Cyfluthrin, *per se* Not Applicable
  ---------------------------- --------------------- -------------------- --------------------

\* Although most of the residue from for use of beta-cyfluthrin consists
of the enriched isomers of that active ingredient, low percentages of
the other isomers are present and the analytical method does not
distinguish between the isomers of cyfluthrin and beta-cyfluthrin.
Therefore, the residue of concern from use of beta-cyfluthrin for
practical purposes is cyfluthrin.

[]{#__RefHeading___Toc179885370 .anchor}**5.1.6 Drinking Water Residue
Profile**

Estimates of cyfluthrin residues in drinking water were provided by the
Environmental Fate and Effects Division (J.L. Melendez 9/6/2007;
D331952; D340739) and incorporated directly into the dietary assessment.
Acute and chronic screening level estimates of drinking water
concentrations (EDWCs) in surface water were generated using FIRST
v.1.1.0, (Dec. 12, 2005), and ground water concentration estimates were
generated using SCI-GROW v.2.3, (Jul 29, 2003).

Based on survey of all the currently registered and proposed uses of
cyfluthrin, it was determined that cyfluthrin use on alfalfa and cotton
would lead to the highest surface water and ground water drinking water
exposure estimates (EDWCs), respectively. Based upon the proposed use of
cyfluthrin on alfalfa (0.35 lb ai/acre/season), the acute drinking water
concentration in surface water is 3.677 ppb, and the chronic EDWC is
estimated to be 0.155 ppb. The SCI-GROW generated EDWC (in groundwater)
is 0.457 ppb of cyfluthrin, which is recommended for use both for acute
and chronic exposures. EDWCs are summarized in Table 7.

+-------------+--------------------+-----------------+-----------------+
| **Table 7.  |                    |                 |                 |
| Estimated   |                    |                 |                 |
| Drinking    |                    |                 |                 |
| Water       |                    |                 |                 |
| Con         |                    |                 |                 |
| centrations |                    |                 |                 |
| for         |                    |                 |                 |
| Cyflut      |                    |                 |                 |
| hrin/Beta-c |                    |                 |                 |
| yfluthrin** |                    |                 |                 |
+-------------+--------------------+-----------------+-----------------+
| *           | **Application      | **Surface Water | **Groundwater   |
| *Duration** | Rate**             | Concentration   | Concentration   |
|             |                    | (ppb)**         | (ppb)**         |
+-------------+--------------------+-----------------+-----------------+
| Acute       | 0.35 lb            | 3.677           | 0.457           |
|             | ai                 |                 |                 |
|             | /A/season(alfalfa) |                 |                 |
+-------------+--------------------+-----------------+-----------------+
| Chronic     | 0.50 lb.           | 0.155           | 0.457           |
|             | ai/A/season        |                 |                 |
| (           | (cotton)           |                 |                 |
| non-cancer) |                    |                 |                 |
+-------------+--------------------+-----------------+-----------------+

[]{#__RefHeading___Toc179885371 .anchor}**5.1.7 Food Residue Profile**

**5.1.7.1 Crop Field Trials**

*Grasses*

The available field trial data for grasses adequately reflect geographic
distribution, application rate, and proposed PHI. The data support the
use of cyfluthrin/beta-cyfluthrin on grasses at up to four broadcast
foliar applications at a maximum single application rate of 0.044 lb
ai/A, with a minimum RTI of 5 days, for a maximum use rate of 0.178 lb
ai/A/season. The data also support a 0-day PHI for cutting of both
forage and hay. The available data support proposed tolerances of 50 ppm
cyfluthrin/beta-cyfluthrin on grass hay and 12 ppm
cyfluthrin/beta-cyfluthrin on grass forage.

The field trial data using the emulsifiable concentrate (EC) formulation
of cyfluthrin on grasses also support the use of the WP formulation on
grass, since previous side-by-side tests on numerous crops using EC and
WP formulations of cyfluthrin have shown that the use of an EC
formulation typically results in higher crop residues than use of a WP.
Also, in accordance with an earlier HED decision the current field trial
data for cyfluthrin (conducted with cyfluthrin) also support the use of
beta-cyfluthrin at a maximum of 0.022 lb ai/A/application for a total
use rate of 0.089 lb ai/A/season.

*Alfalfa*

Crop field trial data was submitted to support the use of cyfluthrin on
alfalfa (EC). The highest average field trial (HAFT) value reported for
cyfluthrin residue in/on alfalfa forage was 5.65 ppm (max. individual
value 5.88 ppm). The HAFT value for cyfluthrin residue in/on alfalfa hay
was 15.27 ppm (max. individual value 16.49 ppm). HED used the recent
guidance for setting tolerances based on field trial data and determined
the appropriate tolerances for alfalfa forage to be 5.0 ppm, and for
alfalfa hay to be 13 ppm.

*Sugar Beets*

The available field trial data for sugar beet seed treatment was
conducted with cyfluthrin, and adequately support the use of cyfluthrin
on sugar beet seed at an application rate of 0.035 lb ai/100,000 seeds.
These data also support the use of beta/cyfluthrin at a maximum
application rate of 0.017 lb ai/100,000 seeds. These data adequately
reflect geographic distribution, and samples were collected at normal
crop maturity. The samples were analyzed using an adequate analytical
method and the sample storage durations are supported by the available
storage stability data. Field trial values for both sugar beet roots and
tops were below the LOQ, and as a result, HED's statistical tolerance
generator was not used to determine tolerances. Therefore, HED
recommends that the tolerance be set at 0.10 ppm.

*[Cereal Grains Except Rice (Crop Group 15)]{.underline}*

A tolerance of 4.0 ppm is currently in effect for residues of
cyfluthrin/beta-cyfluthrin in the Cereal Grain Crop Group (Group 15).
This tolerance covers residues resulting from stored grain uses as well
as from foliar applications. In 2004, HED recommended that the stored
grain uses be cancelled (Y. Donovan, 12/16/04, D290921), but noted that
cancellation of these uses should only occur after the product cleared
the channels of trade. Currently, HED has reviewed field trial data that
were originally reviewed between 1998 and 2004 regarding foliar
applications to wheat, field corn, sweet corn, and sorghum.

*Wheat*

Field trial data for foliar applications to wheat were submitted and
reviewed in 2004. In its 2004 review, HED recommended that the cereal
grain crop group tolerance of 4.0 ppm be revoked and that a tolerance of
0.2 ppm be established in wheat grain. However, the statistically
generated tolerance, which is currently required by HED policy, is 0.15
ppm. As a result, HED recommends that the wheat grain tolerance be
established at 0.15 ppm (rather than the 0.2 ppm tolerance proposed in
2002). This 0.15 ppm tolerance should be extended to the following
cereal grains: barley, buckwheat, millet, oats, and rye.

*Field Corn*

Field trial data for field corn have been submitted and reviewed. HED
previously concluded that the corn grain tolerance of 0.01 ppm was
adequate to cover the existing at-plant and foliar uses. However, the
0.01 ppm tolerance was not in harmonization with the Codex MRL (0.05
ppm). In 2002, HED did not recommend harmonizing the field corn grain
tolerance with the Codex MRL owing to a pending stored grain use
tolerance of 4.0 ppm. Since that time, the stored grain registrations
have been cancelled, and as a result, HED now recommends that the field
corn grain tolerance be harmonized with the Codex MRL. Therefore, HED
recommends in favor of a tolerance of 0.05 ppm in field corn grain. The
recommended tolerances for cyfluthrin resides on animal feed items
associated with field corn are discussed below, in the section entitled
*Forage, Fodder, and Straw of Cereal Grains Group Except Rice (Crop
Group 16)*.

*Corn*

Field trial data for sweet corn were evaluated by HED in 1989 and 1995.
A tolerance of 0.05 ppm was established for sweet corn, kernel plus cob
with husks removed. This tolerance is currently in effect and is
equivalent to the Codex MRL of 0.05 ppm in maize. HED recommends that
this tolerance remain in effect. Tolerances are also in effect in sweet
corn forage and stover. HED's recommendations concerning these
tolerances are discussed in the section below, entitled *Forage, Fodder,
and Straw of Cereal Grains Group Except Rice (Crop Group 16)*.

*Sorghum*

In 1996 HED recommended in favor of a 4.0 ppm tolerance for residues in
sorghum grain resulting from foliar applications. In 2004, HED
recommended that the sorghum grain tolerance be re-established based on
pre-harvest uses of cyfluthrin. This tolerance is equivalent to the
cereal grain crop group tolerance being cancelled, i.e., 4.0 ppm.
However, under current HED policy, the statistically generated tolerance
for sorghum grain is 3.5 ppm. The recommended tolerances for animal feed
items associated with sorghum are discussed in the section below.

*Rice*

Rice is a member of the cereal grains crop group, and therefore, was
covered by the 4.0 ppm tolerance set in that crop group. However, since
these uses have been cancelled the tolerance in rice should also be
removed. Since there are no further registrations for foliar application
of cyfluthrin to rice, HED recommends that no new tolerance in rice be
established.

*[Forage, Fodder, and Straw of Cereal Grains Group Except Rice (Crop
Group 16)]{.underline}*

Adequate field trial data have been submitted for wheat forage, fodder,
and straw, field corn forage and fodder, sweet corn forage and stover,
and sorghum forage and stover. Tolerances based upon these data are
currently in effect. The registrant has requested a tolerance in Crop
Group 16, the Forage, Fodder, and Hay of the Cereal Grains (Except Rice)
Group, and has proposed a tolerance of 7.0 ppm in the entire crop group.
Below is HED's current analysis of the data relevant to the petition for
a Crop Group 16 tolerance.

*Forage*

Forage field trial data are available for wheat, field corn, sweet corn,
and sorghum. The current tolerance in sweet corn forage is 15 ppm and is
based upon field trial data submitted in 1989 and 1990. Residue values
recorded in these data ranged from 2.97 ppm to 53.2 ppm. For statistical
reasons, HED believed that the 53.2 ppm value was aberrant, and so based
the existing 15 ppm tolerance on the next lowest value in that data set,
(13.6 ppm). For the current recommendation the same data set was
re-analyzed with HED's statistical tolerance generator. Based upon the
result of the tolerance generator, HED recommends that the tolerance in
the forage of the Cereal Grains Crop Group (Except Rice) be set at 25
ppm.

*Stover*

Stover field trial data are available for field corn, sweet corn, and
sorghum. The individual field trial values obtained for the stover of
each commodity were entered into HED's statistical tolerance generator
to determine the recommended tolerance for each. As a result, HED
recommends that the tolerance for the stover of the Cereal Grains Crop
Group (Except Rice) be set at 30 ppm, which is the highest value of the
three stover forms. A tolerance of 30 ppm is currently in effect for
sweet corn stover. HED recommends that this tolerance be extended to the
stover of the other cereal grains (except rice).

*Hay*

The only commodity for which hay field trial data are available is
wheat. Based upon the statistical tolerance generator, HED recommends
that this tolerance be set at 6.0 ppm and be applied to hay of the
Cereal Grains Crop Group (except rice).

*Straw*

The only commodity for which straw field trial data are available is
wheat. Based upon the statistical tolerance generator, HED recommends
that this tolerance be set at 7.0 ppm and be applied to straw of the
Cereal Grains Crop Group (except rice).

**5.1.7.2 Revocation of Certain Tolerances**

Since crop group tolerances are being established in the forage, stover,
hay, and straw of the cereal grains commodities, the individual
tolerances that are currently in effect should be revoked. These
tolerances include the following: wheat forage (5.0 ppm), wheat hay (6.0
ppm), wheat straw (6.0 ppm), field corn forage (3.0 ppm), field corn
stover (6.0 ppm), popcorn stover (6.0 ppm), sweet corn forage (15 ppm),
sweet corn stover (30 ppm), sorghum grain forage (2.0 ppm), and sorghum
grain stover (5.0 ppm). A Tolerance Summary table for
cyfluthrin/beta-cyfluthrin can be found in Appendix C.

**5.1.7.3 Processed Food and Feed**

*Grass*

There are no regulated processed commodities associated with grass.

*Sugar Beets*

The available sugar beet processing study (MRID 47007810) is adequate.
Using all values ≥LOD for each commodity, the processing factors were
calculated to be \<0.3x for refined sugar, \<0.2x for molasses, and 12x
for dried pulp.

*[Cereal Grains Crop Group Except Rice]{.underline}*

*Wheat*

In 2004, HED recommended in favor of a 0.5 ppm tolerance in wheat bran.
However, at that time a 6.5 ppm tolerance was established based upon the
stored grains use. Since the stored grains use has been cancelled, HED
recommends that the current 6.5 ppm tolerance in wheat bran be decreased
to 0.5 ppm.

*Corn*\
An acceptable field corn processing study was submitted in 2002. Even
though the residues in processed commodities were not measured, HED
concluded that residues would not exceed 0.01 ppm. There is a current
corn oil tolerance of 30 ppm, which was established in conjunction with
the stored grain uses; however, this use is being cancelled. Therefore,
HED recommends that the 30 ppm tolerance be revoked. The recommended
corn grain tolerance of 0.05 ppm will be adequate to cover residues in
field corn, refined oil.

*Rice*

The current tolerances in effect for rice bran (6.0 ppm) and hulls (18.0
ppm) are derived from rice as a component of the cereal grains crop
group. As mentioned above, the cereal grains group tolerance is being
cancelled. Therefore, since there are no other registrations for foliar
application of cyfluthrin/beta-cyfluthrin to rice, the current
tolerances for rice bran and hulls should be revoked.

**5.1.7.4 International Residue Limits**

Whenever possible, HED attempts to harmonize with Codex MRLs. As stated
above, HED currently recommends that the field corn grain tolerance be
harmonized with the Codex MRL, and set at 0.05 ppm. The current 0.05 ppm
tolerance in sweet corn, kernel plus cob with husks removed is
harmonized with the Codex MRL for maize. Regarding international
harmonization of the proposed tolerances associated with the subject
petitions (grasses, and sugar beet), there are no established or
proposed Canadian, Mexican or Codex MRLs for cyfluthrin residues.

[]{#__RefHeading___Toc179885372 .anchor}**5.2 Dietary Exposure and
Risk**

Acute and chronic dietary exposures via food and drinking water result
from the currently registered and proposed uses of
cyfluthrin/beta-cyfluthrin. A full discussion of the refined dietary
exposure from the registered and proposed uses of
cyfluthrin/beta-cyfluthrin can be found in the HED memorandum
*Cyfluthrin and Beta-Cyfluthrin Acute Probabilistic and Chronic Dietary
Exposure Assessments for the Section 3 Registration Actions*, (D.
Dotson; 10/15/07; D339414).

Permanent tolerances are established for residues of cyfluthrin in/on a
wide variety of plant commodities at levels ranging from 0.01 ppm in/on
peanuts, tree nuts, and tuberous and corm vegetables to 600 ppm in/on
aspirated grain fractions (40CFR §180.436). Tolerances are also
established on animal commodities at levels ranging from 0.01 ppm in
eggs and poultry fat, meat, and meat byproducts to 30 ppm in milk fat;
as well as a tolerance for the use of cyfluthrin in food and feed
handling establishments. The Agency previously concluded that tolerances
for cyfluthrin will also cover beta-cyfluthrin provided that the use
rates for beta-cyfluthrin are ½ the use rates of cyfluthrin*.*

The current dietary analyses are refined, incorporating the most
appropriate factor(s) to estimate residues of cyfluthrin/beta-cyfluthrin
in/on agricultural commodities or animal commodities. Dietary residue
estimates were refined using: (i) empirical and default processing
factors; (ii) percent crop treated estimates and projected percent crop
treated estimates; and, (iii) monitoring data. The dietary exposure
estimates reflect: (i) currently registered and proposed agricultural
crops; (ii) residues resulting from animal feed treatment; (iii)
secondary residues from use of cyfluthrin/beta-cyfluthrin as a direct
animal treatment; and, (iv) for the chronic analysis, residues resulting
from treatment of food handling establishments.

[]{#__RefHeading___Toc179885373 .anchor}**5.2.1 Dietary Exposure
Refinements**

Processing factors were available for many of the commodities in the
analysis. Various studies provided by the registrant characterize the
effect (reduction or concentration) of the pesticide on a commodity as a
result of various processing or preparation procedures such as washing,
juicing, drying, peeling, trimming, oil extraction, etc. When empirical
processing factors were not available, default processing factors were
used. Where appropriate, HED translated a processing factor from one
commodity to another, and when two processing factors were available
(e.g., a processing factor for washing leaf lettuce and one for washing
mustard greens), HED chose the more conservative value. HED does not
apply a processing factor to a commodity where monitoring data is
available, since monitored commodities already reflect food preparation
practices which processing factors aim to characterize. Processing
factors are applicable when estimating both acute and chronic dietary
exposures.

Percent crop treated values were applied to further refine residue
estimates. For crops which are currently registered, percent crop
treated values are taken from the USDA's National Agricultural
Statistics Service. HED used projected percent crop treated values where
tolerances are being proposed or where usage information is not yet
available. In the acute dietary analysis, the maximum percent crop
treated value is applied, whereas in the chronic analysis the average
percent crop treated value is used.

Tolerances for cyfluthrin/beta-cyfluthrin exist in animal (cattle, goat,
hog, poultry, and sheep) meat, meat byproducts and fat, as well as in
milk and eggs. Residue values for these commodities were entered either
as the established tolerance value, or refined by deriving a secondary
residue estimate (which incorporates refined residue estimates on animal
feed items). The current secondary residue estimates for
cyfluthrin/beta-cyfluthrin also reflect updated guidance, and therefore,
differs from secondary residue estimates contained in previous
cyfluthrin/beta-cyfluthrin risk assessments. The secondary residue
estimates from cattle (residues in tissues and in milk) reflected not
only exposure to the animal via the diet but also exposure from a direct
"pour-on" treatment (currently registered for application to beef and
dairy cattle only). Residues resulting from both these pathways were
added together in order to determine the total secondary residues in
cattle commodities.

The current dietary risk assessment also reflects proposed changes to
the cyfluthrin/beta-cyfluthrin tolerance expression resulting from
current petitions and changes to guidance regarding livestock diets as
discussed above.

[]{#__RefHeading___Toc179885374 .anchor}**5.2.2 Acute and Chronic
Dietary Exposure/Risk**

To calculate dietary exposure, residue estimates are coupled with
consumption information. The Dietary Exposure Evaluation Model software
with the Food Commodity Intake Database (DEEM-FCID, V. 2.03) integrates
consumption data from USDA's Continuing Surveys of Food Intakes by
Individuals (CSFII), 1994-1996, and 1998. Based upon the 1994-1996, and
1998 CSFII consumption data, HED concluded that is appropriate to report
risk for the following population subgroups: the general U.S.
population; all infants (\< 1); children 1-2; children 3-5; children
6-12; youth 13-19 adults 20-49; females 13-49; and, adults 50+ yrs old.
For acute dietary scenarios, consumption data are retained as individual
components whereas for chronic dietary scenarios, consumption data are
averaged for the entire US population and within population subgroups.
Estimated concentrations of cyfluthrin/beta-cyfluthrin in drinking
water, Sec. 5.1.6, are incorporated directly into the dietary analysis.
Finally, dietary exposure estimates are compared to either the acute
population adjusted dose (aPAD), or the chronic population adjusted dose
(cPAD). (The aPAD and cPAD are arrived at by dividing the endpoint/dose
by the appropriate uncertainty factors and FQPA factor.) Exposures that
exceed 100% of the aPAD or cPAD are a risk concern to HED.

Estimated acute dietary risks for the U.S population and all population
subgroups are not of concern to HED at the 99.9^th^ percentile.
Estimated chronic dietary risks for the U.S. population and all
population subgroups are also not of concern to HED. The results of the
chronic dietary exposure analysis are reported in Table 8.

+------------------+------------+---------------+------------+-------+
| **Table 8.       |            |               |            |       |
| Summary of       |            |               |            |       |
| Dietary Exposure |            |               |            |       |
| and Risk for     |            |               |            |       |
| Cyfluthrin**     |            |               |            |       |
+------------------+------------+---------------+------------+-------+
| **Population     | **Acute    | **% aPAD**    | **Chronic  | **%   |
| Subgroup**       | Dietary    |               | Dietary    | c     |
|                  | Exposure** | **(99.9^th^   | Exposure** | PAD** |
|                  |            | Percentile)** |            |       |
+------------------+------------+---------------+------------+-------+
| General U.S.     | 0.006378   | 32            | 0.001195   | 5     |
| Population       |            |               |            |       |
+------------------+------------+---------------+------------+-------+
| All Infants \< 1 | 0.007614   | 38            | 0.002075   | 8.6   |
| yr old           |            |               |            |       |
+------------------+------------+---------------+------------+-------+
| Children 1-2 yrs | 0.010536   | 53            | 0.004084   | 17    |
| old              |            |               |            |       |
+------------------+------------+---------------+------------+-------+
| Children 3-5 yrs | 0.009869   | 49            | 0.002951   | 12    |
| old              |            |               |            |       |
+------------------+------------+---------------+------------+-------+
| Children 6-12    | 0.004907   | 25            | 0.001750   | 7.3   |
| yrs old          |            |               |            |       |
+------------------+------------+---------------+------------+-------+
| Youth 13-19 yrs  | 0.005287   | 26            | 0.000973   | 4.1   |
| old              |            |               |            |       |
+------------------+------------+---------------+------------+-------+
| Adults 20-40 yrs | 0.005390   | 27            | 0.000865   | 3.6   |
| old              |            |               |            |       |
+------------------+------------+---------------+------------+-------+
| Adults 50+ yrs   | 0.006398   | 32            | 0.000909   | 3.8   |
| old              |            |               |            |       |
+------------------+------------+---------------+------------+-------+
| Females 13-49    | 0.004788   | 24            | 0.000855   | 3.6   |
| yrs old          |            |               |            |       |
+------------------+------------+---------------+------------+-------+

[]{#__RefHeading___Toc179885375 .anchor}**5.2.3 Cancer Dietary Risk**

HED has classified cyfluthrin as "not likely to be carcinogenic to
humans." Based upon this classification, HED has determined there is
insufficient hazard to warrant a cancer dietary risk assessment.

[]{#__RefHeading___Toc179885376 .anchor}**6.0 Residential
(Non-Occupational) Exposure/Risk Characterization**

The current petitions do not involve any residential/non-occupational
uses. However, several active cyfluthrin products are registered for use
at residential sites including indoor (e.g. total release fogger, and
crack and crevice spray) and outdoor uses (e.g. spray fogger, and lawn
applications). In 2002, HED completed an updated
residential/non-occupational assessment of these uses (D283388; S.
Tadayon; 7/31/02). Estimated risks from the residential/non-occupational
uses were not of concern to HED. The 2002 assessment was considered
screening level since it did not reflect applicable revisions to the HED
Residential Exposure SOPs. Incorporation of the updated SOPs would have
refined the exposure estimates and likely would have resulted in higher
MOEs. Risks for the population subgroups at greatest risk, from both
indoor and outdoor residential uses of cyfluthrin are summarized below
in Table 9.

  ------------------------------ ----------------- ----------------- ---------------------
  **Table 9. Selected MOEs for                                       
  Residential/Non-Occupational                                       
  Uses of Cyfluthrin**                                               

  **Scenario**                   **Population      **Duration**      
                                 Subgroup**                          

                                                   **Short-term      **Intermediate-term
                                                   duration**        duration**

  Indoor Uses (carpet use)       All infants \<    1300              490
                                 1year                               

  Outdoor Uses (lawn use)        All infants \< 1  1400              920
                                 year                                

                                 Adults            1600              540
  ------------------------------ ----------------- ----------------- ---------------------

[]{#__RefHeading___Toc179885377 .anchor}**6.1 Spray Drift**

Spray drift is always a potential source of exposure to residents near
spraying operations. This is particularly the case with aerial
application but, to a lesser extent, could also be a potential source of
exposure from the ground application method. 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 database 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.

HED notes that 0.14 lb ai/acre was the application rate use to estimate
non-occupational/residential exposure from cyfluthrin/beta-cyfluthrin
use on lawns. Since this rate is equal to or higher than many of the
agricultural application rates, the scenario is protective of any
exposure of farm children, including toddlers, via spray drift from
agricultural cyfluthrin/beta-cyfluthrin applications.

[]{#__RefHeading___Toc179885378 .anchor}**7.0 Aggregate Risk Assessments
and Risk Characterization**

Consistent with FQPA, HED considers aggregate risk to pesticide
exposures that come from three major sources: food, drinking water, and
residential uses. In an aggregate assessment, exposures from relevant
sources are added together and compared to quantitative estimates of
hazard (e.g., a NOAEL or PAD), or the risks themselves can be
aggregated. When aggregating exposures and risks from various sources,
HED considers both the route (oral, dermal, and inhalation) and duration
of exposure.

Based upon the non-occupational/residential uses of cyfluthrin, HED has
determined that acute, short-term, intermediate-term, and chronic
aggregate risk assessments are appropriate. For the short-term and
intermediate-term aggregate assessments, HED combined the two potential
residential exposure scenarios (indoor carpet, and outdoor lawn) for a
single worst-case residential exposure component. (Estimates of exposure
and risk from residential uses of cyfluthrin/beta-cyfluthrin can be
found in HED document D283388; S. Tadayon; 7/31/03). For both short-term
and intermediate-term scenarios, HED estimated aggregate risk to the
general U.S. population, infants (\< 1 year), and children (1 -- 2
years).

[]{#__RefHeading___Toc179885379 .anchor}**7.1 Acute Aggregate Risk**

The acute aggregate risk is equal to dietary exposure via food and
drinking water, and is identical to the exposure and risk characterized
in Section 5.2.2. Acute aggregate risks for cyfluthrin/beta-cyfluthrin
are less than 100% of the aPAD and therefore, do not present a risk
concern to HED.

[]{#__RefHeading___Toc179885380 .anchor}**7.2 Short-Term and
Intermediate-Term Aggregate Risk**

To estimate short-term aggregate risk, HED combined the chronic dietary
(food + water) exposures (as a measure of average dietary exposure) with
the short-term residential exposure. To estimate intermediate-term
aggregate risk HED combined chronic dietary (food + water) exposures
with intermediate term residential exposure. Short-term and
intermediate-term aggregate risks are summarized in Tables 10 and 11
below.

<table style="width:100%;">
<colgroup>
<col style="width: 11%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 10%" />
<col style="width: 10%" />
<col style="width: 10%" />
<col style="width: 8%" />
<col style="width: 10%" />
</colgroup>
<tbody>
<tr class="odd">
<td colspan="10"><strong>Table 10. Short-Term Aggregate Risk
Calculations for Cyfluthrin</strong></td>
</tr>
<tr class="even">
<td rowspan="3"><p><strong>Population</strong></p>
<p><strong>Subgroup</strong></p></td>
<td colspan="2"><strong>Average Dietary</strong></td>
<td colspan="6"><strong>Residential (indoor carpet + outdoor
lawn)<sup>1</sup></strong></td>
<td rowspan="3"><strong>Aggregate MOE<sup>6</sup></strong></td>
</tr>
<tr class="odd">
<td colspan="2"><p><strong>Dietary</strong></p>
<p><strong>(food + water)</strong></p></td>
<td colspan="2"><p><strong>Residential</strong></p>
<p><strong>Inhalation</strong></p></td>
<td colspan="2"><p><strong>Residential</strong></p>
<p><strong>Dermal</strong></p></td>
<td colspan="2"><p><strong>Residential</strong></p>
<p><strong>Incidental Oral</strong></p></td>
</tr>
<tr class="even">
<td>Exposure</td>
<td>MOE<sub>f+w</sub><sup>2</sup></td>
<td>Exposure</td>
<td>MOE<sub>I</sub><sup>3</sup></td>
<td>Exposure</td>
<td>MOE<sub>D</sub><sup>4</sup></td>
<td>Exposure</td>
<td>MOE<sub>O</sub><sup>5</sup></td>
</tr>
<tr class="odd">
<td>U.S population</td>
<td>0.001195</td>
<td>2000</td>
<td>5.7E<sup>-5</sup></td>
<td>1200</td>
<td>2.5E<sup>-3</sup></td>
<td>940</td>
<td>Not assessed</td>
<td>Not assessed</td>
<td>420</td>
</tr>
<tr class="even">
<td><p>Infant</p>
<p>(&lt;1 yr)</p></td>
<td>0.002075</td>
<td>1100</td>
<td>4.6E<sup>-5</sup></td>
<td>1500</td>
<td>1.5E<sup>-3</sup></td>
<td>1600</td>
<td>6.9E<sup>-4</sup></td>
<td>3400</td>
<td>400</td>
</tr>
<tr class="odd">
<td><p>Child</p>
<p>(1-2 yrs)</p></td>
<td>0.004084</td>
<td>580</td>
<td>3.6E<sup>-5</sup></td>
<td>1900</td>
<td>1.4E<sup>-3</sup></td>
<td>1700</td>
<td>6.4E<sup>-4</sup></td>
<td>3700</td>
<td>320</td>
</tr>
</tbody>
</table>

1 Individual exposure values for residential uses can be found in HED
Memo; S. Tadayon; 6/31/0; D28338. Exposure values and MOEs for combined
residential exposures can be found in HED Memo; Y. Donovan; 7/15/05;
D290925.

2 MOE ~food\ +\ water~ : short-term oral NOAEL = (2.36 mg/kg/day) /
chronic dietary exposure from DEEM.

3 MOE inhalation = short-term inhalation NOAEL (0.07
mg/kg/day)/residential inhalation exposure

4 MOE dermal = short-term dermal NOAEL (2.36 mg/kg/day)/dermal
residential exposure. Dermal exposure adjusted with 5% dermal absorption
factor.

5 MOE oral = short-term incidental oral NOAEL (2.36
mg/kg/day)/hand-to-mouth residential exposure.

6 Aggregate MOE (food + water + residential) =

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_1\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

1/MOE ~f+w~ + 1/MOE~I~ + 1/MOE~D~ + 1/MOE~O~

<table>
<colgroup>
<col style="width: 11%" />
<col style="width: 10%" />
<col style="width: 8%" />
<col style="width: 10%" />
<col style="width: 9%" />
<col style="width: 10%" />
<col style="width: 10%" />
<col style="width: 10%" />
<col style="width: 8%" />
<col style="width: 10%" />
</colgroup>
<tbody>
<tr class="odd">
<td colspan="10"><strong>Table 11. Intermediate-Term Aggregate Risk
Calculations for Cyfluthrin/Beta-Cyfluthrin</strong></td>
</tr>
<tr class="even">
<td rowspan="3"><strong>Population Subgroup</strong></td>
<td colspan="2"><strong>Average Dietary</strong></td>
<td colspan="6"><strong>Residential (indoor carpet + outdoor
lawn)<sup>1</sup></strong></td>
<td rowspan="3"><strong>Aggregate MOE<sup>6</sup></strong></td>
</tr>
<tr class="odd">
<td colspan="2"><p><strong>Dietary</strong></p>
<p><strong>(food + water)</strong></p></td>
<td colspan="2"><p><strong>Residential</strong></p>
<p><strong>Inhalation</strong></p></td>
<td colspan="2"><p><strong>Residential</strong></p>
<p><strong>Dermal</strong></p></td>
<td colspan="2"><p><strong>Residential</strong></p>
<p><strong>Incidental Oral</strong></p></td>
</tr>
<tr class="even">
<td><strong>Exposure</strong></td>
<td><strong>MOE<sup>2</sup><sub>f+w</sub></strong></td>
<td><strong>Exposure</strong></td>
<td><strong>MOE<sup>3</sup><sub>I</sub></strong></td>
<td><strong>Exposure</strong></td>
<td><strong>MOE<sup>4</sup><sub>D</sub></strong></td>
<td><strong>Exposure</strong></td>
<td><strong>MOE<sup>5</sup><sub>O</sub></strong></td>
</tr>
<tr class="odd">
<td><p>U.S.</p>
<p>Population</p></td>
<td>0.001195</td>
<td>2000</td>
<td>5.7E<sup>-5</sup></td>
<td>350</td>
<td>2.5E<sup>-3</sup></td>
<td>940</td>
<td>Not assessed</td>
<td>Not assessed</td>
<td>220</td>
</tr>
<tr class="even">
<td><p>Infant</p>
<p>(&lt;1 yr)</p></td>
<td>0.002075</td>
<td>1100</td>
<td>4.6E<sup>-5</sup></td>
<td>430</td>
<td>1.5E<sup>-3</sup></td>
<td>1600</td>
<td>6.9E<sup>-4</sup></td>
<td>3400</td>
<td>240</td>
</tr>
<tr class="odd">
<td><p>Child</p>
<p>(1-2 yrs)</p></td>
<td>0.004084</td>
<td>580</td>
<td>3.6E<sup>-5</sup></td>
<td>560</td>
<td>1.4E<sup>-3</sup></td>
<td>1700</td>
<td>6.4E<sup>-4</sup></td>
<td>3700</td>
<td>230</td>
</tr>
</tbody>
</table>

1: Individual exposure values for residential uses can be found in HED
Memo; S. Tadayon; 6/31/0; D28338. Exposure values and MOEs for combined
residential exposures can be found in HED Memo; Y. Donovan;
7/15/05;D290925.

2: MOE food + water = intermediate-term oral NOAEL (2.36
mg/kg/day)/chronic dietary exposure from DEEM.

3: MOE inhalation = intermediate-term inhalation NOAEL (0.02
mg/kg/day)/residential inhalation exposure

4: MOE dermal = intermediate-term dermal NOAEL (2.36 mg/kg/day)/dermal
residential exposure. Dermal exposure adjusted with 5% dermal absorption
factor.

5: MOE oral = intermediate-term incidental oral NOAEL (2.36 mg/kg/day
)/hand-to-mouth residential exposure.

6: Aggregate MOE (food + water + residential) =

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_1\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

1/MOE ~f+w~ + 1/MOE~I~ + 1/MOE~D~ + 1/MOE~O~

[]{#__RefHeading___Toc179885381 .anchor}**7.3 Chronic Aggregate Risk
Assessment**

The dietary exposure pathway (food and drinking water) is the only
source of chronic exposure to cyfluthrin (i.e., 180 consecutive days or
more). Therefore, the long-term aggregate exposure and risk estimates
are equivalent to the chronic dietary exposure and risk estimates
discussed in Section 5.2.2 above. The chronic aggregate risks for
cyfluthrin are less than 100% of the cPAD for all population subgroups,
and therefore, do not pose a risk concern for HED.

[]{#__RefHeading___Toc179885382 .anchor}**7.4 Cancer Aggregate Risk
Assessment**

Based upon HED's cancer classification of cyfluthrin and consequently
the lack of hazard to warrant a cancer dietary risk assessment, a cancer
aggregate risk assessment was not conducted.

[]{#__RefHeading___Toc179885383 .anchor}**8.0 Cumulative Risk
Characterization/Assessment**

Cyfluthrin and beta-cyfluthrin are members of the pyrethroid class of
pesticides. Although all pyrethroids alter nerve function by modifying
the normal biochemistry and physiology of nerve membrane sodium
channels, EPA is not currently following a cumulative risk approach
based on a common mechanism of toxicity for the pyrethroids. Although
all pyrethroids interact with sodium channels, there are multiple types
of sodium channels and it is currently unknown whether the pyrethroids
have similar effects on all channels. The Agency does not have a clear
understanding of effects on key downstream neuronal function e.g., nerve
excitability, nor do we understand how these key events interact to
produce their compound specific patterns of neurotoxicity. There is
ongoing research by the EPA's Office of Research and Development and
pyrethroid registrants to evaluate the differential biochemical and
physiological actions of pyrethroids in mammals. When the results of the
research become available, the Agency will consider the findings and
make a determination of common mechanism as a basis for assessing
cumulative risk. Information regarding EPA's procedures for cumulating
effects from substances found to have a common mechanism can be found on
EPA's website at <http://www.epa.gov/pesticides/cumulative/>.

[]{#__RefHeading___Toc179885384 .anchor}**9.0 Occupational Exposure/Risk
Pathway**

A full analysis of the occupational exposure and risks associated with
the proposed uses of cyfluthrin/beta-cyfluthrin can be found in the HED
memorandum, *Cyfluthrin and Beta-cyfluthrin: Occupational Risk
Assessment to Support the Uses o Alfalfa and Grasses and the Use of
Beta-Cyfluthrin on Sugar Beet*, (September 7, 2007; D339445).

To assess occupational risks, HED compares estimated exposure to the
appropriate toxicological endpoint dose. The ratio of exposure to
endpoint is expressed as a margin of exposure (MOE). If the
toxicological endpoint dose is equal to or greater than 100x the
estimated exposure, (i.e., MOE ≥ 100) then the risk is not of concern to
HED. To estimate exposure to handlers (mixers, loaders, and
applicators), HED begins by assuming baseline personal protective
equipment (PPE) which is defined as long sleeve shirt, long pants, socks
and shoes. If risks are of concern with baseline PPE (i.e., MOE \< 100),
then HED recalculates exposure and risk by increasing levels of PPE
until the risks are not of concern to HED (i.e., MOE ≥ 100). When
estimating risk to workers who reenter treated areas, HED considers the
post-application activities for a given crop, and the expected exposure
from each activity to estimate risk. For handlers as well as workers who
reenter fields treated with cyfluthrin/beta-cyfluthrin, HED's level of
concern (LOC) is 100.

Application methods associated with the proposed uses on alfalfa and
grasses include aerial/aerial ULV (by fixed wing or by helicopter), and
groundboom/chemigation (sprinkler irrigation system only). Application
for commercial seed treatment is with a slurry or liquid with a slurry
treater or a direct treater. Commercial seed treatment also involves
individuals who bag the treated seed and/or sew the bag shut. Table 12
lists the occupational exposures associated with each petition.

+-----------------------------+------+--------------------------------+
| **Table 12. Summary of      |      |                                |
| Petitions and Occupational  |      |                                |
| Assessments for             |      |                                |
| C                           |      |                                |
| yfluthrin/Beta-cyfluthrin** |      |                                |
+-----------------------------+------+--------------------------------+
| **Petition Description**    | **   | **Occupational Exposures       |
|                             | Peti | Assessed**                     |
|                             | tion |                                |
|                             | N    |                                |
|                             | o.** |                                |
+-----------------------------+------+--------------------------------+
| Petition for use of         | 6E   | Exposure to handlers (mixers,  |
| cyfluthrin/beta-cyfluthrin  | 7058 | loaders, applicators,          |
| on grasses throughout the   |      | flaggers)                      |
| U.S. including mixed stands |      |                                |
| with alfalfa                |      | Exposure to post application   |
|                             |      | workers                        |
+-----------------------------+------+--------------------------------+
| Petition for new use as     | 6F   | Exposure to loader, and seed   |
| sugar beet seed treatment   | 7160 | treater;                       |
|                             |      |                                |
|                             |      | Exposure to the bagger of      |
|                             |      | treated seeds                  |
|                             |      |                                |
|                             |      | Exposure to the sewer of bags  |
|                             |      | filled with treated seed       |
|                             |      |                                |
|                             |      | Exposure to post treatment     |
|                             |      | workers (planters)             |
+-----------------------------+------+--------------------------------+
| Petition for increased      | 7F   | Exposure to handlers (mixers,  |
| number of applications to   | 7226 | loaders, applicators,          |
| alfalfa (increased seasonal |      | flaggers)                      |
| application rate)           |      |                                |
|                             |      | Exposure to post application   |
|                             |      | workers                        |
+-----------------------------+------+--------------------------------+
| Request to amend labels to  | 7F   | No occupational exposure       |
| include Crop Group 15       | 7200 | assessments associated with    |
| (except rice) and Crop      |      | this petition.                 |
| Group 16                    |      |                                |
+-----------------------------+------+--------------------------------+

[]{#__RefHeading___Toc179885385 .anchor}**9.1
Occupational/Non-Residential Toxicological Profile for
Cyfluthrin/Beta-cyfluthrin**

The cyfluthrin risk assessment team has re-evaluated the cyfluthrin
toxicological database and believes it continues to be sufficient to
assess the occupational risks associated with the subject petitions. The
cyfluthrin risk assessment team remains in agreement with the previous
conclusions drawn by HED regarding the hazard of cyfluthrin. A full
characterization of the hazard of cyfluthrin and beta-cyfluthrin can be
found in the HED memorandum *Cyfluthrin and Beta-cyfluthrin -- 3^rd^
Report of the Hazard Identification Assessment Review Committee* (P.
Hurley, TXR 0050768, 05/21/2002). Based upon the proposed uses and
information regarding the production of grasses, sugar beet seed
treatment, and alfalfa production, HED has determined that exposure
duration for occupational handlers and applicators is short-term (1 --
30 days), and intermediate-term (1 -- 6 months). Therefore, both the
short-term and intermediate-term toxicity endpoints were applied in this
cyfluthrin/beta-cyfluthrin occupational assessment. Table 13 summarizes
the toxicological endpoints for assessing occupational/non-residential
risks from cyfluthrin/beta-cyfluthrin.

+---------+---------+---------+-------------+------------------------+
| **Table |         |         |             |                        |
| 13.     |         |         |             |                        |
| Summary |         |         |             |                        |
| of      |         |         |             |                        |
| Toxico  |         |         |             |                        |
| logical |         |         |             |                        |
| Doses   |         |         |             |                        |
| and     |         |         |             |                        |
| En      |         |         |             |                        |
| dpoints |         |         |             |                        |
| for     |         |         |             |                        |
| Cyf     |         |         |             |                        |
| luthrin |         |         |             |                        |
| and     |         |         |             |                        |
| B       |         |         |             |                        |
| eta-Cyf |         |         |             |                        |
| luthrin |         |         |             |                        |
| for Use |         |         |             |                        |
| in      |         |         |             |                        |
| Occup   |         |         |             |                        |
| ational |         |         |             |                        |
| Human   |         |         |             |                        |
| Health  |         |         |             |                        |
| Risk    |         |         |             |                        |
| Assessm |         |         |             |                        |
| ents.** |         |         |             |                        |
+=========+=========+=========+=============+========================+
| **Expo  | **Point | **Unce  | **Level of  | **Study and            |
| sure/** | of      | rtainty | Concern for | Toxicological          |
|         | Depa    | Fa      | Risk        | Effects**              |
| **Sce   | rture** | ctors** | A           |                        |
| nario** |         |         | ssessment** |                        |
+---------+---------+---------+-------------+------------------------+
| **D     | NOAEL=  | UF~A~=  | O           | 90-Day dog feeding     |
| ermal** | 2.36    | 10x     | ccupational | study                  |
|         | mg      |         | LOC for MOE | (beta-cyfluthrin)      |
| Short-  | /kg/day | UF~H~ = | = 100       |                        |
| (1-30   |         | 10x     |             | LOAEL = 13.9/15.4      |
| Days)   | Dermal  |         |             | mg/kg/day (M/F) based  |
| and     | abs     |         |             | on gait abnormalities, |
| Interm  | orption |         |             | increased incidence of |
| ediate- | rate =  |         |             | vomiting, and          |
| Term    | 5%      |         |             | suggestive decreased   |
| (1 - 6  |         |         |             | body weight gain.      |
| Months) |         |         |             |                        |
+---------+---------+---------+-------------+------------------------+
| **D     | NOAEL=  | UF~A~=  | O           | Chronic toxicity in    |
| ermal** | 2.4     | 10x     | ccupational | dogs (cyfluthrin)      |
|         | mg      |         | LOC for MOE |                        |
| Lo      | /kg/day | UF~H~ = | = 100       | LOAEL = 10.64          |
| ng-Term |         | 10x     |             | mg/kg/day based on     |
| (\>6    | Dermal  |         |             | clinical signs, gait   |
| Months) | abs     |         |             | abnormalities, and     |
|         | orption |         |             | abnormal postural      |
|         | rate =  |         |             | reactions.             |
|         | 5%      |         |             |                        |
+---------+---------+---------+-------------+------------------------+
| **Inhal | NOAEL=  | UF~A~=  | O           | 28-Day rat inhalation  |
| ation** | 0.00026 | 10x     | ccupational | study                  |
|         | mg/L    |         | LOC for MOE | (beta-cyfluthrin)      |
| Sho     |         | UF~H~ = | = 100       |                        |
| rt-Term | (0.07   | 10x     |             | LOAEL = 0.0027 mg/L    |
|         | mg/     |         |             | (0.73 mg/kg/day) based |
| (1-30   | kg/day) |         |             | on decreases in body   |
| Days)   |         |         |             | weight in both sexes   |
|         |         |         |             | and decreased urinary  |
|         |         |         |             | pH in males.           |
+---------+---------+---------+-------------+------------------------+
| **Inhal | NOAEL=  | UF~A~=  | O           | 13-Week rat inhalation |
| ation** | 0.00009 | 10x     | ccupational | study (cyfluthrin)     |
|         | mg/L    |         | LOC for MOE |                        |
| Interm  |         | UF~H~ = | = 100       | LOAEL = 0.00071 mg/L   |
| ediate- | (0.02   | 10x     |             | (0.16 mg/kg/day) based |
| (1-6    | mg/     |         |             | on decreases in body   |
| months) | kg/day) |         |             | weight and body weight |
| and     |         |         |             | gain in males and      |
| Lo      |         |         |             | clinical signs in      |
| ng-Term |         |         |             | females.               |
| (\>6    |         |         |             |                        |
| months) |         |         |             |                        |
+---------+---------+---------+-------------+------------------------+
| **C     | C       |         |             |                        |
| ancer** | lassifi |         |             |                        |
| (oral,  | cation: |         |             |                        |
| dermal, | "Not    |         |             |                        |
| inha    | likely  |         |             |                        |
| lation) | to be   |         |             |                        |
|         | Carci   |         |             |                        |
|         | nogenic |         |             |                        |
|         | to      |         |             |                        |
|         | Humans" |         |             |                        |
+---------+---------+---------+-------------+------------------------+

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 (interspecies). UF~H~ =
potential variation in sensitivity among members of the human population
(intraspecies). MOE = margin of exposure. LOC = level of concern. N/A =
not applicable.

[]{#__RefHeading___Toc179885386 .anchor}**9.2
Occupational/Non-Residential Exposure Inputs**

No chemical specific exposure data were submitted with the subject
petition for grasses, or with the petition for the increased number of
applications to alfalfa. Therefore, when estimating exposure from the
proposed uses on grasses, and increased rate for alfalfa, HED used
surrogate data from the Pesticide Handlers Exposure Data Base (PHED)
Version 1.1, and standard assessment variables established by the Health
Effects Division Science Advisory Council for Exposure.

With regard to the subject petition for new use on sugar beet seed, no
chemical specific data were submitted with this petition either.
However, the petitioner did submit an occupational risk assessment
summary (MRID 47007811) with the subject petition for sugar beet seed
treatment. A data evaluation record for this MRID was not prepared
because it did not contain any original field data. Table 14 identifies
the specific occupational exposure scenario combinations, including the
worker population, the product formulation and equipment variations.

+----+--------------------------------------------------+-------------+
| *  |                                                  |             |
| *T |                                                  |             |
| ab |                                                  |             |
| le |                                                  |             |
| 1  |                                                  |             |
| 4. |                                                  |             |
| ** |                                                  |             |
|    |                                                  |             |
| ** |                                                  |             |
| Sh |                                                  |             |
| or |                                                  |             |
| t- |                                                  |             |
| a  |                                                  |             |
| nd |                                                  |             |
| I  |                                                  |             |
| nt |                                                  |             |
| er |                                                  |             |
| me |                                                  |             |
| di |                                                  |             |
| at |                                                  |             |
| e- |                                                  |             |
| te |                                                  |             |
| rm |                                                  |             |
| Oc |                                                  |             |
| cu |                                                  |             |
| pa |                                                  |             |
| ti |                                                  |             |
| on |                                                  |             |
| al |                                                  |             |
| Ex |                                                  |             |
| po |                                                  |             |
| su |                                                  |             |
| re |                                                  |             |
| S  |                                                  |             |
| ce |                                                  |             |
| na |                                                  |             |
| ri |                                                  |             |
| os |                                                  |             |
| Ap |                                                  |             |
| pl |                                                  |             |
| ic |                                                  |             |
| ab |                                                  |             |
| le |                                                  |             |
| f  |                                                  |             |
| or |                                                  |             |
| t  |                                                  |             |
| he |                                                  |             |
| Pr |                                                  |             |
| op |                                                  |             |
| os |                                                  |             |
| ed |                                                  |             |
| Us |                                                  |             |
| es |                                                  |             |
| of |                                                  |             |
| Cy |                                                  |             |
| fl |                                                  |             |
| ut |                                                  |             |
| hr |                                                  |             |
| in |                                                  |             |
| a  |                                                  |             |
| nd |                                                  |             |
| b  |                                                  |             |
| et |                                                  |             |
| a- |                                                  |             |
| Cy |                                                  |             |
| fl |                                                  |             |
| ut |                                                  |             |
| hr |                                                  |             |
| in |                                                  |             |
| on |                                                  |             |
| A  |                                                  |             |
| lf |                                                  |             |
| al |                                                  |             |
| fa |                                                  |             |
| a  |                                                  |             |
| nd |                                                  |             |
| Gr |                                                  |             |
| as |                                                  |             |
| se |                                                  |             |
| s. |                                                  |             |
| ** |                                                  |             |
+----+--------------------------------------------------+-------------+
| *  | **Exposure Scenario**                            | **Active    |
| *N |                                                  | I           |
| o. |                                                  | ngredient** |
| ** |                                                  |             |
+----+--------------------------------------------------+-------------+
| Mi |                                                  |             |
| xi |                                                  |             |
| ng |                                                  |             |
| /L |                                                  |             |
| oa |                                                  |             |
| di |                                                  |             |
| ng |                                                  |             |
+----+--------------------------------------------------+-------------+
| 1  | liquid, open mixing/loading for aerial, fixed    | Cyfluthrin  |
|    | wing and rotary equipment                        |             |
+----+--------------------------------------------------+-------------+
| 2  | liquid, open mixing/loading for ground boom      | Cyfluthrin  |
|    | equipment                                        |             |
+----+--------------------------------------------------+-------------+
| 3  | liquid, open mixing/loading for chemigation      | Cyfluthrin  |
+----+--------------------------------------------------+-------------+
| 4  | WP/WSB, open mixing/loading for aerial equipment | Cyfluthrin  |
+----+--------------------------------------------------+-------------+
| 5  | WP/WSB, open mixing/loading for ground boom      | Cyfluthrin  |
|    | equipment                                        |             |
+----+--------------------------------------------------+-------------+
| 6  | WP/WSB, open mixing/loading for chemigation      | Cyfluthrin  |
+----+--------------------------------------------------+-------------+
| 7  | liquid, open mixing/loading for aerial equipment | beta        |
|    |                                                  | -Cyfluthrin |
+----+--------------------------------------------------+-------------+
| 8  | liquid, open mixing/loading for ground boom      | beta        |
|    | equipment                                        | -Cyfluthrin |
+----+--------------------------------------------------+-------------+
| 9  | liquid, open mixing/loading for chemigation      | beta        |
|    |                                                  | -Cyfluthrin |
+----+--------------------------------------------------+-------------+
| A  |                                                  |             |
| pp |                                                  |             |
| ly |                                                  |             |
| in |                                                  |             |
| g/ |                                                  |             |
| Fl |                                                  |             |
| ag |                                                  |             |
| gi |                                                  |             |
| ng |                                                  |             |
+----+--------------------------------------------------+-------------+
| 10 | liquid and WP, applying by aerial fixed wing     | Cyfluthrin  |
|    | equipment, enclosed cab                          |             |
+----+--------------------------------------------------+-------------+
| 11 | liquid and WP, applying by aerial rotary         | Cyfluthrin  |
|    | equipment, enclosed cab                          |             |
+----+--------------------------------------------------+-------------+
| 12 | liquid and WP, applying by ground boom           | Cyfluthrin  |
|    | equipment, open cab                              |             |
+----+--------------------------------------------------+-------------+
| 13 | liquid and WP, flagging, aerial applications     | Cyfluthrin  |
+----+--------------------------------------------------+-------------+
| 14 | liquid, applying by aerial fixed wing equipment, | beta        |
|    | enclosed cab                                     | -Cyfluthrin |
+----+--------------------------------------------------+-------------+
| 15 | liquid, applying by aerial rotary equipment,     | beta        |
|    | enclosed cab                                     | -Cyfluthrin |
+----+--------------------------------------------------+-------------+
| 16 | liquid, applying by ground boom equipment, open  | beta        |
|    | cab                                              | -Cyfluthrin |
+----+--------------------------------------------------+-------------+
| 17 | liquid, flagging, aerial application             | beta        |
|    |                                                  | -Cyfluthrin |
+----+--------------------------------------------------+-------------+

1: scenario numbers listed in Table 14 correspond with scenario numbers
found in Table 1, and Table 2 in Appendix A.

[]{#__RefHeading___Toc179885387 .anchor}**9.3 Handler and Applicator
Risks from Proposed Uses on Grasses and Alfalfa**

The proposed labels for grasses and alfalfa specify baseline PPE
(long-sleeved shirt and long pants, socks, and shoes), chemical
resistant gloves, and protective eye-wear for handlers; and, specify a
restricted entry interval of (REI) of 12-hours. Dermal and inhalation
exposures can be combined for short and intermediate-term scenarios
respectively, due to the common endpoints between these exposure routes.

Estimated risk to handlers of wettable powder/water soluble bag
formulation, when using either aerial, ground boom, or chemigation
equipment are not a risk concern to HED when baseline PPE is assumed.
Estimated risk to handlers of liquid formulations, when using ground
boom equipment, are not a risk concern to HED when baseline PPE is
assumed. However, risks associated with liquid formulations when using
either aerial or chemigation equipment are a concern to HED when only
baseline PPE is assumed. However, when HED assumes baseline PPE,
chemical resistant gloves, and a dust/mist respirator, risks were not of
concern. As can be seen in Table 15, five of six handler exposure
scenarios involving liquid formulations require a dust/mist respirator,
(which is not indicated on the petition labels), to reach a MOE ≥ 100.
Addition of a dust/mist respirator was required to bring
intermediate-term inhalation exposure risks above HED's LOC of 100.

Regarding applicators and flaggers for the proposed use on grasses and
on alfalfa, the short-term and intermediate-term risks are not a concern
to HED when liquid or wettable powder formulations are applied via
aerial, groundboom, or chemigation equipment when baseline PPE is
assumed. HED notes that the proposed use directions for grasses and
alfalfa require gloves which will provide additional protection to
applicators and flaggers. Conclusions of handler and applicator risks
and required PPE are presented in Table 15. Appendix A contains expanded
tables of handler and applicator exposure and risk.

+------+---------+--------+-----------+------------------------------+
| **T  |         |        |           |                              |
| able |         |        |           |                              |
| 1    |         |        |           |                              |
| 5.** |         |        |           |                              |
|      |         |        |           |                              |
| **   |         |        |           |                              |
| Hand |         |        |           |                              |
| lers |         |        |           |                              |
| and  |         |        |           |                              |
| App  |         |        |           |                              |
| lica |         |        |           |                              |
| tors |         |        |           |                              |
| for  |         |        |           |                              |
| Prop |         |        |           |                              |
| osed |         |        |           |                              |
| Use  |         |        |           |                              |
| on   |         |        |           |                              |
| Gra  |         |        |           |                              |
| sses |         |        |           |                              |
| and  |         |        |           |                              |
| Use  |         |        |           |                              |
| on   |         |        |           |                              |
| Alfa |         |        |           |                              |
| lfa: |         |        |           |                              |
| Sum  |         |        |           |                              |
| mary |         |        |           |                              |
| of   |         |        |           |                              |
| PPE  |         |        |           |                              |
| W    |         |        |           |                              |
| here |         |        |           |                              |
| MOE  |         |        |           |                              |
| ≥    |         |        |           |                              |
| 1    |         |        |           |                              |
| 00** |         |        |           |                              |
+------+---------+--------+-----------+------------------------------+
| *    | *       | **P    | **Ap      | **PPE Required to Reach MOE≥ |
| *Ope | *Active | roduct | plication | 100**                        |
| rati | Ingre   | F      | Method**  |                              |
| on** | dient** | ormula |           |                              |
|      |         | tion** |           |                              |
+------+---------+--------+-----------+------------------------------+
|      |         |        |           |                              |
+------+---------+--------+-----------+------------------------------+
| >    | Cyf     | Liquid | Aerial    | PPE stated on proposed       |
| Hand | luthrin |        |           | label + dust/mist respirator |
| lers |         |        |           |                              |
+------+---------+--------+-----------+------------------------------+
|      |         |        | Ground    | PPE stated on proposed       |
|      |         |        | boom      | label + dust/mist respirator |
+------+---------+--------+-----------+------------------------------+
|      |         |        | Ch        | PPE stated on proposed       |
|      |         |        | emigation | label + dust/mist respirator |
+------+---------+--------+-----------+------------------------------+
|      |         | WP/WSB | Aerial    | PPE stated on proposed label |
+------+---------+--------+-----------+------------------------------+
|      |         |        | Ch        | PPE stated on proposed label |
|      |         |        | emigation |                              |
+------+---------+--------+-----------+------------------------------+
|      |         |        | Ground    | PPE stated on proposed label |
|      |         |        | boom      |                              |
+------+---------+--------+-----------+------------------------------+
|      | B       | Liquid | Aerial    | PPE stated on proposed       |
|      | eta-cyf |        |           | label + dust/mist respirator |
|      | luthrin |        |           |                              |
+------+---------+--------+-----------+------------------------------+
|      |         |        | Ground    | PPE stated on proposed label |
|      |         |        | boom      |                              |
+------+---------+--------+-----------+------------------------------+
|      |         |        | Ch        | PPE stated on proposed       |
|      |         |        | emigation | label + dust/mist respirator |
+------+---------+--------+-----------+------------------------------+
|      |         |        |           |                              |
+------+---------+--------+-----------+------------------------------+
| >    | Cyf     | All    | All       | PPE stated on proposed label |
|  App | luthrin | formul | ap        |                              |
| lica |         | ations | plication |                              |
| tors | and     |        | methods   |                              |
|      |         |        |           |                              |
|      | B       |        |           |                              |
|      | eta-cyf |        |           |                              |
|      | luthrin |        |           |                              |
+------+---------+--------+-----------+------------------------------+

[]{#__RefHeading___Toc179885388 .anchor}**9.4 Short-term and
Intermediate-term Exposures and Risk from Proposed Seed Treatment Use**

The proposed use pattern for sugar beet seed treatment indicates that
during the seed treatment season, workers may be treating several
batches of seeds per day for several weeks resulting in both short-term
(1-30 days) and intermediate-term (1-6 months) exposure durations.
Dermal and inhalation exposures can be combined for short and
intermediate-term scenarios respectively, due to the common endpoints
between these exposure routes.

The Poncho Beta® label specifies the following PPE: (i) loaders/treaters
must wear long sleeved shirt and long pants, shoes with socks, chemical
resistant gloves, and dust/mist respirator, (ii) baggers and sewers must
wear long sleeved shirt and long pants, shoes with socks, and a
dust/mist respirator. HED assessed the risk to loaders, to baggers, and
to sewers separately (i.e., an individual who only loads, or only bags,
or only sews), and also assessed risks to an individual who would
perform all three tasks involved in seed treatment.

*Risks to Individuals Performing One Discrete Task*

-   Short-term MOEs for all three operations do not represent a risk
    concern to HED.

-   Intermediate-term MOEs to baggers and sewers do not represent a risk
    concern to HED.

-   Intermediate-term MOE to loader/treaters does represent a risk
    concern to HED (MOE = 81).

*Risks to Individuals Performing All Three Discrete Tasks*

-   Short-term and intermediate-term MOEs for individuals who perform
    all three tasks represent a risk concern to HED, (short-term MOE =
    58, intermediate-term MOE = 19).

HED notes that the estimated risks to an "multiple operator" may be an
overestimation because HED does not have data that accurately represents
exposures from a single-person operation (including representative
equipment, and/or the amount of seed that can be treated by a single
person). Additional information regarding seed treatment run by a single
person would be necessary to better estimate exposure and risk from this
scenario. However, in the absence of more specific data, HED must rely
on the data in hand which indicates that the risk to a multiple operator
is a concern to HED. Conclusions of seed treatment risks and required
PPE are presented in Table 16.

+-----------------+----------------------------------------------------+
| **Table 16.     |                                                    |
| Seed Treatment  |                                                    |
| Operations for  |                                                    |
| Proposed Use on |                                                    |
| Sugar beet      |                                                    |
| Seed:**         |                                                    |
|                 |                                                    |
| **Summary of    |                                                    |
| Risks and PPE   |                                                    |
| Where MOE ≥     |                                                    |
| 100**           |                                                    |
+-----------------+----------------------------------------------------+
| **Operation**   | **PPE Required to Reach MOE≥ 100**                 |
+-----------------+----------------------------------------------------+
| Loading,        | *Intermediate-term MOE = 81 and represents a risk  |
| treating        | concern to HED*                                    |
|                 |                                                    |
|                 | *Assumes PPE stated on the proposed label*         |
+-----------------+----------------------------------------------------+
| Bagging         | PPE stated on the proposed label                   |
+-----------------+----------------------------------------------------+
| Sewing          | PPE stated on the proposed label                   |
+-----------------+----------------------------------------------------+
| Multiple        | *Risks are above HED's level of concern*           |
| operations      |                                                    |
|                 | *Short-term MOE = 58*                              |
|                 |                                                    |
|                 | *Intermediate-term MOE = 19*                       |
|                 |                                                    |
|                 | *Assumes PPE stated on the proposed label +        |
|                 | chemical resistant gloves*                         |
+-----------------+----------------------------------------------------+

[]{#__RefHeading___Toc179885389 .anchor}**9.5 Post-application Exposure
and Risk**

Post-application exposure from the proposed uses of
cyfluthrin/beta-cyfluthrin on grasses and alfalfa occurs when workers
enter treated fields to conduct irrigation, scouting, harvesting, or
other operations. Most of these post-application operations are
performed using mechanical equipment, thus reducing worker exposure.
Nonetheless, other post-application activities, such as scouting, are
not mechanized and are expected to result in measurable exposures. HED
estimated short-term and intermediate-term dermal exposure to workers
who may enter cyfluthrin and beta-cyfluthrin treated fields of alfalfa
and grasses and determined that risks are not of concern (MOEs ≥ 100).

Post-application exposure from the proposed seed treatment use is likely
when workers (planters) transfer the treated seeds from bags to
planter-hoppers and/or while planting/drilling the seed. The estimated
post-application exposures and risks (short- and intermediate-term) to
planters of Poncho Beta® treated sugar beet seed are not of concern.
While no PPE is required for planters while seeding/planting, HED does
not anticipate direct contact with treated seed since the planting
machinery places/drills the seed and covers it in one operation. Treated
seeds once covered with soil are protective of workers who may reenter
the field soon after planting for irrigation. No other post-application
activity is performed in a freshly seeded sugar beet field. There is no
restricted entry interval (REI) for the treating and planting of
pre-treated seeds.

[]{#__RefHeading___Toc179885390 .anchor}**10.0 Data Needs and Label
Recommendations**

No data gaps were identified in the process of conducting the above
analysis for the subject petitions. Based upon HED's analysis, the
following label amendments are recommended to the proposed
cyfluthrin/beta-cyfluthrin labels submitted in connection with the
subject petitions.

*Directions for Use:*

-   Proposed labels for use on grasses and alfalfa must be amended to
    exclude ultra-low volume aerial application (using a minimum of 1
    qt./A of vegetable oil). No data were submitted to support this type
    of application, and therefore, should be removed from the proposed
    label.

*Occupational Personal Protective Equipment:*

-   Addition of dust/mist respirators as a PPE requirement for all
    liquid formulations of Baythroid® 2, Renounce® 20WP, and Baythroid®
    XL.

-   The intermediate-term MOE for loaders involved in the sugar beet
    seed treatment process is of concern to HED (intermediate-term MOE
    for loader/treater = 81), additional PPE may be warranted for this
    scenario (such as double layer clothing, or a respirator with
    protection factor of 10). As earlier, additional risk considerations
    regarding sugar beet seed treatment with Poncho Beta®, are also
    being addressed through a separate HED document (D340131). Together,
    this document and D340131 address the occupational risks associated
    with the proposed use of Poncho Beta® on sugar beet seed. Therefore,
    HED recommends the Registration Division consider the occupational
    risks associated with the proposed use of Poncho Beta® in light of
    the exposures and risks from both beta-cyfluthrin and clothianidin
    prior to granting the proposed use and/or tolerances associated with
    the proposed sugar beet seed treatment use (sugar beet roots, and
    sugar beet dried pulp).

*New Uses:*

-   Pending amendments and changes HED has suggested to the proposed
    Baythroid® 2, Renounce® 20WP, and Baythroid® XL labels, HED
    recommends the registration of new uses and establishment of
    tolerances for cyfluthrin/beta-cyfluthrin.

*Revised Tolerances for Cyfluthrin:*

-   HED recommends that the establishment of tolerances incorporates the
    correct commodity definitions for cyfluthrin (and beta-cyfluthrin)
    treated commodities as stated in Appendix C, Table 1 and in the
    *Summary of Recommendations*.

*Revised Section F:*

-   A revised Section F is required reflecting HED recommendations, and
    for the establishment of (separate) tolerances listed below for both
    cyfluthrin and beta-cyfluthrin. The cyfluthrin tolerances should be
    included in 40 CFR §180.436(a)(1), while a separate section under
    180.436 should be established for tolerances for beta-cyfluthrin,
    analogous to the tolerances for lambda-cyhalothrin and
    gamma-cyhalothrin in §180.438. The section for beta-cyfluthrin needs
    to be established because registrations for cyfluthrin on these
    commodities might be cancelled at some point in the future. The
    tolerances for cyfluthrin and beta-cyfluthrin should be established
    at the same levels. The recommended wording for the beta-cyfluthrin
    tolerance expression is as follows: "Tolerances are established for
    residues of the insecticide beta-cyfluthrin \[mixture comprising the
    enantiomeric pair (R)-α-cyano-4-fluoro-3-phenoxybenzyl
    (1S,3S)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate
    and (S)-α-cyano-4-fluoro-3-phenoxybenzyl
    (1R,3R)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate
    with the enantiomeric pair (R)-α-cyano-4-fluoro-3-phenoxybenzyl
    (1S,3R)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate
    and (S)-α-cyano-4-fluoro-3-phenoxybenzyl
    (1R,3S)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate\]
    in or on the following commodities:"

-   HED also recommends that, at some point in the future, tolerances be
    established for all food uses of beta-cyfluthrin (i.e., on those
    commodities not included in the present actions) under the new
    section to be created under 40 CFR §180.436.

    []{#__RefHeading___Toc179885391 .anchor}**References**

Cyfluthrin and Beta-Cyfluthrin: Occupational Risk Assessment to Support
the Uses on Alfalfa and Grasses and the Use of Beta-Cyfluthrin on Sugar
Beet. Petition Nos. 6E7058 (Grasses), 6F7160 (Sugar Beet), and 7F7226
(Alfalfa). Sep. 28, 2007; S.Oonnithan; D339445.

Tier I Drinking Water Assessment for the Registration for the New Uses
of Cyfluthrin and Beta-cyfluthrin on Alfalfa (Increased Application
Rate, Section 3), Grasses (Pasture, Rangeland, Grass for Seed, Grass for
Hay, Grass in Mixed Stands with Alfalfa, IR-4 Tolerance Petition),
Cereals Crop Group 15 (Beta-cyfluthrin), Cereals Crop Group 16 except
rice (Beta-cyfluthrin), and sugar beets (Beta-cyfluthrin). Sep. 24,
2007; J.L. Meléndez; D331952, and D340739.

Cyfluthrin and Beta-Cyfluthrin Acute Probabilistic and Chronic Dietary
Exposure Assessments for the Section 3 Registration Actions. 10/15/2007;
D.Dotson; D339414.

Cyfluthrin and beta-Cyfluthrin. Registration for Uses on Grasses,
Alfalfa, and Seed Treatment Use on Sugar Beets. Request for Replacement
of Individual Cereal Grain Tolerances with Crop Group Tolerance for
Cereal Grains (Except Rice), Crop Group 15, and Replacement of
Individual Tolerances on Forage and Stover/Straw of Wheat, Corn, and
Sorghum with Crop Group Tolerance for Forage, Fodder, and Straw of
Cereal Grains, Crop Group 16 (Except Rice). Summary of Analytical
Chemistry and Residue Data. 10/15/2007; D.Dotson; D339413.

Beta-Cyfluthrin: Developmental Neurotoxicity Study in Rats. September 6,
2007; A.Levy; D293830.

Cyfluthrin: Occupational and Residential Exposure Assessment (Section 3)
for the Registration of Brassica Vegetables, Garbanzo Beans, Head
Lettuce, Peas, Soybeans, Corn and Stored Grain. July 31, 2002;
S.Tadayon; D283388.

PP# 2F6445, 2F6479, 1F6290, 1E6318, 3E6583, and 3D6776. FQPA Human
Health Risk Assessment for Cyfluthrin -- Proposal for Tolerances of
Residues in/on numerous vegetable crops, fruit crops, tree nuts,
peanuts, wheat, grass, and dried peas and beans. 07/15/05; Y.Donovan;
D290925.

Cyfluthrin and Beta-Cyfluthrin -- Report of the Hazard Identification
Assessment Review Committee. April 11, 2001; P.Hurley; HED Doc. No.
014535.

[]{#__RefHeading___Toc179885392 .anchor}**Appendix A. Occupational
Exposure and Risk Tables**

  -------------------------------------------------------------------------------------------------------------------------
  **Table 6. Short-                                                                                              
  and                                                                                                            
  Intermediate-term                                                                                              
  Occupational Risks                                                                                             
  to Mixers/Loaders                                                                                              
  From the Use of                                                                                                
  Cyfluthrin and                                                                                                 
  *beta-*Cyfluthrin                                                                                              
  on Alfalfa and                                                                                                 
  Grasses**                                                                                                      
  ------------------- ---------------- -------- ---------- ------------ ------------- ------------- ------------ ----------
  Chemical            Mixing/Loading   PPE ^1^  Dermal     Inhalation   Dermal Dose   Inhal. Dose   Total        Total
                      Exposure                  Unit       Unit         (mg/kg/day)   (mg/kg/day)   Short-term   Interm.-
                      Scenario \#               Exposure   Exposure     ^2^           ^3^           MOE ^4^      term MOE
                                                (mg/lb ai) (µg/lb ai)                                            ^4^

  Cyfluthrin          1\. Liquid,      BL       2.9        1.2          0.109371      0.000905      17           11
                      Open, Aerial                                                                               

  \" \"               1a. \" \"        BL+G+R   0.023      0.24\*       0.000867      0.000181      340          110

  \" \"               2\. Liquid,      BL       2.9        1.2          0.018229      0.000151      100          66
                      Open, Ground                                                                               
                      boom                                                                                       

  \" \"               2a. \" \"        BL+G+R   2.9        0.24\*       0.018229      0.000030      120          110

  \" \"               3\. Liquid,      BL       2.9        1.2          0.031900      0.000264      58           37
                      Open,                                                                                      
                      Chemigation                                                                                

  \" \"               3a. \" \"        BL+G+R   0.023      0.24\*       0.000253      0.000053      1,200        360

  \" \"               4\. WP/WSB,      BL       0.021      0.24         0.000792      0.000181      340          110
                      Open, Aerial                                                                               

  \" \"               5\. WP/WSB,      BL       0.021      0.24         0.000132      0.000030      2,100        640
                      Open, Ground                                                                               
                      boom                                                                                       

  \" \"               6\. WP/WSB,      BL       0.021      0.24         0.000231      0.000053      1,200        370
                      Open,                                                                                      
                      Chemigation                                                                                

  *Beta*-cyfluthrin   7\. Liquid,      BL       2.9        1.2          0.054686      0.000453      34           22
                      Open, Aerial                                                                               

  \" \"               7a. \" \"        BL+G+R   0.023      0.24\*       0.000434      0.000091      680          210

  \" \"               8\. Liquid,      BL       2.9        1.2          0.009114      0.000075      200          130
                      Open, Ground                                                                               
                      boom                                                                                       

  \" \"               9\. Liquid,      BL       2.9        1.2          0.015950      0.000132      120          75
                      Open,                                                                                      
                      Chemigation                                                                                

  \" \"               9a. \" \"        BL+G+R   2.9        0.24\*       0.015950      0.000026      140          120
  -------------------------------------------------------------------------------------------------------------------------

> 1\. BL = baseline PPE (long-sleeve shirt, long pants, shoes with
> socks, and no respirator), G = Gloves, R = dust-mist respirator.
>
> 2\. Dermal dose/day = (app. rate)(area treated/day)(dermal unit
> exposure)(dermal absorption factor)(conversion factor \[0.01\]) ÷ body
> weight
>
> 3\. Inhalation dose/day = (app. rate)(area treated/day)(inhalation
> unit exposure)(conversion factor \[0.01\]) ÷ body weight
>
> 4\. Total Short-term or Total Intermediate-term MOE: 1 ÷ 1/dermal
> MOE + 1/ inhalation MOE
>
> \*. Applied an 80% reduction factor to the inhalation unit exposures
> for the use of dust/mist respirator as a mitigation measure. Ref:
> Exposure mitigating Table (PHED).

  -----------------------------------------------------------------------------------------------------------------------
  **Table 7. Short-                                                                                            
  and                                                                                                          
  Intermediate-term                                                                                            
  Occupational Risks                                                                                           
  to Applicators From                                                                                          
  the Use of                                                                                                   
  Cyfluthrin and                                                                                               
  *beta-*Cyfluthrin                                                                                            
  on Alfalfa and                                                                                               
  Grasses**                                                                                                    
  ------------------- ---------------- ------ ---------- ------------ ------------- ------------- ------------ ----------
  Chemical            Mixing/Loading   PPE    Dermal     Inhalation   Dermal Dose   Inhal. Dose   Total        Total
                      Exposure         ^1^    Unit       Unit Exp.    (mg/kg/day)   (mg/kg/day)   Short-term   Interm.-
                      Scenario \#             Exposure   (µg/lb ai)   ^2^           ^3^           MOE ^4^      term MOE
                                              (mg/lb ai)                                                       ^4^

  Cyfluthrin          10\. Liquid &    BL     0.005      0.068        0.000189      0.000051      1,200        380
                      WP, Aerial,                                                                              
                      Fixed wing,                                                                              
                      Enclosed cab                                                                             

  \" \"               11\. Liquid &    BL     0.0019     0.0018       0.000072      0.0000014     20,000       10,000
                      WP, Aerial,                                                                              
                      Rotary, Enclosed                                                                         
                      cab                                                                                      

  \" \"               12\. Liquid &    BL     0.014      0.74         0.000088      0.000093      730          210
                      WP, Gr. boom,                                                                            
                      Open cab                                                                                 

  \" \"               13\. Liquid &    BL     0.011      0.35         0.000121      0.000077      870          260
                      WP, Aerial,                                                                              
                      Flagger                                                                                  

  *Beta*-cyfluthrin   14\. Liquid &    BL     0.005      0.068        0.000094      0.000026      2,500        760
                      WP, Aerial,                                                                              
                      Fixed Wing,                                                                              
                      Enclosed cab                                                                             

  \" \"               15\. Liquid &    BL     0.0019     0.0018       0.000036      0.000001      40,000       20,000
                      WP, Aerial,                                                                              
                      Rotary, Enclosed                                                                         
                      cab                                                                                      

  \" \"               16\. Liquid &    BL     0.014      0.74         0.000044      0.000047      1,500        430
                      WP, Gr. boom,                                                                            
                      Open cab                                                                                 

  \" \"               17\. Liquid &    BL     0.011      0.35         0.000061      0.000039      1,700        510
                      WP, Aerial,                                                                              
                      Flagger                                                                                  
  -----------------------------------------------------------------------------------------------------------------------

> 1\. BL = baseline PPE, G = Gloves, R = dust/mist respirator; baseline
> PPE consists of long-sleeve shirt, long pants, shoes with socks and no
> respirator.
>
> 2\. Dermal dose/day = (app. rate)(area treated/day)(dermal unit
> exposure)(dermal absorption factor)(conversion factor \[0.01\]) ÷ body
> weight
>
> 3\. Inhalation dose/day = (app. rate)(area treated/day)(inhalation
> unit exposure)(conversion factor \[0.01\]) ÷ body weight
>
> 4\. Total Short-term or Total Intermediate-term MOE: 1 ÷ 1/dermal
> MOE + 1/ inhalation MOE

  ---------------------- ------------------- ---------- ---------- ------------- ------------- --------------
  **Table 10. Short-and                                                                        
  Intermediate-Term                                                                            
  Postapplication Risks                                                                        
  to Workers Who Enter                                                                         
  Alfalfa and Grass                                                                            
  Fields Treated with                                                                          
  Cyfluthrin and                                                                               
  *beta*-Cyfluthrin.**                                                                         

  Crops ^1^              Chemical            Max.       DFR        Transfer      Dermal Dose   Short &
                                             Single     µg/cm^2^   Coefficient   (mg/kg/day)   Inter.-term
                                             Appl. Rate            ^3^           ^4^           MOE ^5^
                                             (lb ai/A)                                         

  Alfalfa and Grass      cyfluthrin          0.044      0.099      1500 scouting 0.00085       2,800
  grown for seed                                                                               

                         *beta*-cyfluthrin   0.022      0.049      1500 scouting 0.00042       5,600
  ---------------------- ------------------- ---------- ---------- ------------- ------------- --------------

1\. Among the grass crop sites (pasture, rangeland, grasses grown for
hay and seed, grass mixed-stands with alfalfa), grass grown for seed is
expected to have the maximum postapplication activities.

2\. DFR :

(app. rate)(fraction of ai retained on foliage \[20%\])(fraction of
residue that dissipates daily \[10%\])(conversion factor \[4.54
E+8\]\[2.47E-8\])

3\. Transfer coefficient (TC) is for alfalfa (surrogate crop) with
medium exposure potential.

4\. Dermal Dose: (dislodgeable foliar residue on designated
day)(conversion factor \[10E-3\])(transfer coefficient)(dermal
absorption factor)(exposure time \[8 hrs\]) ÷ body weight

5\. Dermal MOE: NOAEL/dermal dose

<table>
<colgroup>
<col style="width: 15%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 9%" />
</colgroup>
<tbody>
<tr class="odd">
<td colspan="10"><strong>Table 9. Short- and Intermediate-Term Risks to
Seed Treatment Workers and Planters From the Use of
<em>beta</em>-Cyfluthrin Containing Poncho Beta on Sugar Beet.</strong>
<sup>1</sup></td>
</tr>
<tr class="even">
<td><p>Exposure</p>
<p>Scenarios</p></td>
<td><p>Worker</p>
<p>Type</p></td>
<td>PPE <sup>2</sup></td>
<td>Qty Treated / Planted/day (lbs)</td>
<td><p>Unit Exp. Dermal/day</p>
<p>(mg/lb ai)</p></td>
<td><p>Unit Exp. Inhal./day</p>
<p>(µg/lb ai)</p></td>
<td><p>Dermal</p>
<p>Dose/day</p>
<p>(mg/kg) <sup>3</sup></p></td>
<td><p>Inhalation</p>
<p>Dose/day</p>
<p>(mg/kg) <sup>4</sup></p></td>
<td>Total Short-term MOE <sup>5</sup></td>
<td>Total Interm.- term MOE <sup>5</sup></td>
</tr>
<tr class="odd">
<td>Loading/Treating</td>
<td>L/T</td>
<td>S, G</td>
<td>52,000</td>
<td>0.023</td>
<td>0.34</td>
<td>0.00365</td>
<td>0.00108</td>
<td>59</td>
<td>18</td>
</tr>
<tr class="even">
<td>Loading/Treating</td>
<td>L/T</td>
<td>S, G, R</td>
<td>52,000</td>
<td>0.023</td>
<td>0.068 *</td>
<td>0.00365</td>
<td>0.00022</td>
<td>220</td>
<td>81</td>
</tr>
<tr class="odd">
<td>Bagging, treated seed</td>
<td>Bagger</td>
<td>S</td>
<td>52,000</td>
<td>0.0091</td>
<td>0.16</td>
<td>0.00144</td>
<td>0.00051</td>
<td>130</td>
<td>38</td>
</tr>
<tr class="even">
<td>Bagging, treated seed</td>
<td>Bagger</td>
<td>S, R</td>
<td>52,000</td>
<td>0.0091</td>
<td>0.032 *</td>
<td>0.00144</td>
<td>0.00010</td>
<td>490</td>
<td>180</td>
</tr>
<tr class="odd">
<td>Sewing, bagged seed</td>
<td>Sewer</td>
<td>S</td>
<td>52,000</td>
<td>0.0062</td>
<td>0.23</td>
<td>0.00098</td>
<td>0.00073</td>
<td>92</td>
<td>27</td>
</tr>
<tr class="even">
<td>Sewing, bagged seed</td>
<td>Sewer</td>
<td>S, R</td>
<td>52,000</td>
<td>0.0062</td>
<td>0.046 *</td>
<td>0.00098</td>
<td>0.00015</td>
<td>400</td>
<td>130</td>
</tr>
<tr class="odd">
<td>Doing multiple jobs</td>
<td>Multiple</td>
<td>S, G</td>
<td>52,000</td>
<td>0.0420</td>
<td>1.6</td>
<td>0.00666</td>
<td>0.00508</td>
<td>13</td>
<td>4</td>
</tr>
<tr class="even">
<td>Doing multiple jobs</td>
<td>Multiple</td>
<td>S, G, R</td>
<td>52,000</td>
<td>0.0420</td>
<td>0.32 *</td>
<td>0.00666</td>
<td>0.00102</td>
<td>58</td>
<td>19</td>
</tr>
<tr class="odd">
<td>Handling/ Planting <sup>6</sup></td>
<td>Farmer, Postappl.</td>
<td>S, #</td>
<td>640</td>
<td>0.25</td>
<td>3.4</td>
<td>0.00049</td>
<td>0.00013</td>
<td>470</td>
<td>150</td>
</tr>
</tbody>
</table>

2\. S = Single layer (long sleeve shirt and long pants) and no gloves, G
= chemical resistant gloves, R = dust/mist respirator

3\. Dermal dose = (app. rate)(area treated/day)(dermal unit
exposure)(dermal absorption factor)(conversion factor \[0.01\]) ÷ body
weight

4\. Inhalation dose = (app. rate)(area treated/day)(inhalation unit
exposure)(conversion factor \[0.01\]) ÷ body weight

5\. Total Short-term or Total Intermediate-term MOE: 1 ÷ 1/dermal MOE +
1/ inhalation MOE

6\. Postapplication exposure.

\* Applied an 80% reduction factor to the inhalation unit exposure for
the use of dust/mist respirator, which is a PPE requirement on the label
for all seed treatment workers. Ref: Exposure Mitigating Table (PHED).

#\. For handlers/planters, label specifies gloves for loading only.

[]{#__RefHeading___Toc179885393 .anchor}**Appendix B. Toxicology Profile
of Cyfluthrin and Beta-cyfluthrin**

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

+-----------------------------------------+-------------+-------------+
| **Appendix B, Table 1**                 |             |             |
|                                         |             |             |
| **Toxicology Data Requirements --       |             |             |
| cyfluthrin/beta-cyfluthrin**            |             |             |
+=========================================+=============+=============+
| **Test**                                | **          |             |
|                                         | Technical** |             |
+-----------------------------------------+-------------+-------------+
|                                         | *           | **          |
|                                         | *Required** | Satisfied** |
+-----------------------------------------+-------------+-------------+
| 870.1100 Acute Oral Toxicity            | yes         | yes         |
|                                         |             |             |
| 870.1200 Acute Dermal Toxicity          | yes         | yes         |
|                                         |             |             |
| 870.1300 Acute 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         |
|                                         |             |             |
| 870.3200 21-Day Dermal                  | yes         | yes         |
|                                         |             |             |
| 870.3250 90-Day Dermal                  | no          | \-          |
|                                         |             |             |
| 870.3465 90-Day Inhalation              | no          | 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^1^      |
|                                         |             |             |
| 870.4100b Chronic Toxicity (nonrodent)  | yes         | yes         |
|                                         |             |             |
| 870.4200a Oncogenicity (rat)            | yes         | yes         |
|                                         |             |             |
| 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         |
|                                         |             |             |
| 870.5375 Mutagenicity---Structural      | yes         | yes         |
| Chromosomal Aberrations                 |             |             |
|                                         |             |             |
| 870.5550 Mutagenicity---Other Genotoxic |             |             |
| Effects                                 |             |             |
+-----------------------------------------+-------------+-------------+
| 870.6100a Acute Delayed Neurotox. (hen) | yes         | yes         |
|                                         |             |             |
| 870.6100b 90-Day Neurotoxicity (hen)    | no          | \-          |
|                                         |             |             |
| 870.6200a Acute Neurotox. Screening     | yes         | yes         |
| Battery (rat)                           |             |             |
|                                         | yes         | yes         |
| 870.6200b 90-Day Neurotox. Screening    |             |             |
| Battery (rat)                           | yes         | yes         |
|                                         |             |             |
| 870.6300 Developmental Neurotoxicity    |             |             |
+-----------------------------------------+-------------+-------------+
| 870.7485 General Metabolism             | yes         | yes         |
|                                         |             |             |
| 870.7600 Dermal Penetration             | no          | \-          |
+-----------------------------------------+-------------+-------------+

^1^ Satisfied with combined chronic toxicity/carcinogenicity study

**Appendix B Toxicology Profile of Cyfluthrin and Beta-cyfluthrin**

+--------+----------------------+-------+------------------+----------+
| **Ap   |                      |       |                  |          |
| pendix |                      |       |                  |          |
| B,     |                      |       |                  |          |
| Table  |                      |       |                  |          |
| 2**    |                      |       |                  |          |
|        |                      |       |                  |          |
| *      |                      |       |                  |          |
| *Acute |                      |       |                  |          |
| To     |                      |       |                  |          |
| xicity |                      |       |                  |          |
| P      |                      |       |                  |          |
| rofile |                      |       |                  |          |
| --     |                      |       |                  |          |
| Cyflut |                      |       |                  |          |
| hrin** |                      |       |                  |          |
+--------+----------------------+-------+------------------+----------+
| **Gui  | **Study Type**       | *     | **Results**      | **       |
| deline |                      | *MRID |                  | Toxicity |
| No.**  |                      | (s)** |                  | Ca       |
|        |                      |       |                  | tegory** |
+--------+----------------------+-------+------------------+----------+
| 87     | Acute oral -- rat    | 001   | **In cremophor** | I        |
| 0.1100 |                      | 31499 |                  |          |
|        |                      |       | LD~50~ = 16.2    | II       |
|        |                      | 001   | mg/kg (♂)        |          |
|        |                      | 31518 |                  | III      |
|        |                      |       | **In acetone**   |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ = 254     |          |
|        |                      |       | mg/kg (♂)        |          |
|        |                      |       |                  |          |
|        |                      |       | **In N-methyl    |          |
|        |                      |       | pyrollidone**    |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ = 500     |          |
|        |                      |       | -1000 mg/kg (♂)  |          |
+--------+----------------------+-------+------------------+----------+
| 87     | Acute dermal -- rat  | 001   | **In cremophor** | IV       |
| 0.1200 |                      | 31499 |                  |          |
|        |                      |       | LD~50~ \> 5000   |          |
|        |                      | 001   | mg/kg (♂+♀)      |          |
|        |                      | 31518 |                  |          |
|        |                      |       | **In 0.9% NaCl** |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ \> 5000   |          |
|        |                      |       | mg/kg (♂+♀)      |          |
|        |                      |       |                  |          |
|        |                      |       | **Undiluted**    |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ \> 5000   |          |
|        |                      |       | mg/kg (♂+♀)      |          |
+--------+----------------------+-------+------------------+----------+
| 87     | Acute inhalation --  | 001   | **Aqueous        | II       |
| 0.1300 | rat                  | 31509 | cremophor**      |          |
|        |                      |       |                  |          |
|        |                      |       | LC~50~ \> 0.735  |          |
|        |                      |       | mg/L (♂)         |          |
|        |                      |       |                  |          |
|        |                      |       | LC~50~ = 0.468   |          |
|        |                      |       | mg/L (♀)         |          |
|        |                      |       |                  |          |
|        |                      |       | **D              |          |
|        |                      |       | MSO/polyethylene |          |
|        |                      |       | glycol** LC~50~  |          |
|        |                      |       | = 0.575 mg/L (♂) |          |
|        |                      |       |                  |          |
|        |                      |       | LC~50~ = 0.490   |          |
|        |                      |       | mg/L (♀)         |          |
+--------+----------------------+-------+------------------+----------+
| 87     | Acute eye irritation | 001   | No corneal       | III      |
| 0.2400 | -- rabbit            | 31499 | opacity;         |          |
|        |                      |       | transient        |          |
|        |                      |       | irritation for 3 |          |
|        |                      |       | days             |          |
+--------+----------------------+-------+------------------+----------+
| 87     | Acute dermal         | 001   | Non-irritating.  | IV       |
| 0.2500 | irritation -- rabbit | 31499 | Primary          |          |
|        |                      |       | irritation score |          |
|        |                      |       | = 0              |          |
+--------+----------------------+-------+------------------+----------+
| 87     | Skin sensitization   | 001   | Not a sensitizer | N/A      |
| 0.2600 | -- guinea pig        | 31512 | (Draize test)    |          |
|        |                      |       |                  |          |
|        |                      | 001   | Not a sensitizer |          |
|        |                      | 31513 |                  |          |
|        |                      |       | (Maximization    |          |
|        |                      |       | test)            |          |
+--------+----------------------+-------+------------------+----------+

**Appendix B Toxicology Profile of Cyfluthrin and Beta-cyfluthrin**

+--------+----------------------+-------+------------------+----------+
| **Ap   |                      |       |                  |          |
| pendix |                      |       |                  |          |
| B,     |                      |       |                  |          |
| Table  |                      |       |                  |          |
| 3**    |                      |       |                  |          |
|        |                      |       |                  |          |
| *      |                      |       |                  |          |
| *Acute |                      |       |                  |          |
| To     |                      |       |                  |          |
| xicity |                      |       |                  |          |
| P      |                      |       |                  |          |
| rofile |                      |       |                  |          |
| --     |                      |       |                  |          |
| Beta-  |                      |       |                  |          |
| Cyflut |                      |       |                  |          |
| hrin** |                      |       |                  |          |
+--------+----------------------+-------+------------------+----------+
| **Gui  | **Study Type**       | *     | **Results**      | **       |
| deline |                      | *MRID |                  | Toxicity |
| No.**  |                      | (s)** |                  | Ca       |
|        |                      |       |                  | tegory** |
+--------+----------------------+-------+------------------+----------+
| 87     | Acute oral -- rat    | 412   | **In xylene**    | II       |
| 0.1100 |                      | 44101 |                  |          |
|        |                      |       | Fasted:          |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ = 211     |          |
|        |                      |       | mg/kg (♂)        |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ = 336     |          |
|        |                      |       | mg/kg (♀)        |          |
|        |                      |       |                  |          |
|        |                      |       | Fed:             |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ = 307     |          |
|        |                      |       | mg/kg (♂)        |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ = 343     |          |
|        |                      |       | mg/kg (♀)        |          |
+--------+----------------------+-------+------------------+----------+
| 87     | Acute oral -- rat    | 412   | **In PEG 400**   | II (♂)   |
| 0.1100 |                      | 44102 |                  |          |
|        |                      |       | Fasted:          | III (♀)  |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ = 380     |          |
|        |                      |       | mg/kg (♂)        |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ = 651     |          |
|        |                      |       | mg/kg (♀)        |          |
|        |                      |       |                  |          |
|        |                      |       | Fed:             |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ = 655     |          |
|        |                      |       | mg/kg (♂)        |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ = 1369    |          |
|        |                      |       | mg/kg (♀)        |          |
+--------+----------------------+-------+------------------+----------+
| 87     | Acute oral -- rat    | 412   | **In             | II       |
| 0.1100 |                      | 44104 | acetone/peanut   |          |
|        |                      |       | oil**            |          |
|        |                      |       |                  |          |
|        |                      |       | Fasted:          |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ = 84      |          |
|        |                      |       | mg/kg (♂)        |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ = 77      |          |
|        |                      |       | mg/kg (♀)        |          |
|        |                      |       |                  |          |
|        |                      |       | Fed:             |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ = 141     |          |
|        |                      |       | mg/kg (♂)        |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ = 108     |          |
|        |                      |       | mg/kg (♀)        |          |
+--------+----------------------+-------+------------------+----------+
| 87     | Acute oral -- mouse  | 412   | **In PEG 400**   | II       |
| 0.1100 |                      | 44103 |                  |          |
|        |                      |       | Fasted:          |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ = 91      |          |
|        |                      |       | mg/kg (♂)        |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ = 165     |          |
|        |                      |       | mg/kg (♀)        |          |
+--------+----------------------+-------+------------------+----------+
| 87     | Acute dermal -- rat  | 412   | **In xylene**    | IV       |
| 0.1200 |                      | 44105 |                  |          |
|        |                      |       | LD~50~ \> 5000   |          |
|        |                      |       | mg/kg (♂)        |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ \> 5000   |          |
|        |                      |       | mg/kg (♀)        |          |
+--------+----------------------+-------+------------------+----------+
| 87     | Acute dermal -- rat  | 412   | **In PEG 400**   | IV       |
| 0.1200 |                      | 44106 |                  |          |
|        |                      |       | LD~50~ \> 5000   |          |
|        |                      |       | mg/kg (♂)        |          |
|        |                      |       |                  |          |
|        |                      |       | LD~50~ \> 5000   |          |
|        |                      |       | mg/kg (♀)        |          |
+--------+----------------------+-------+------------------+----------+
| 87     | Acute inhalation --  | 412   | **Aerosol**      | II       |
| 0.1300 | rat                  | 05701 |                  |          |
|        |                      |       | LC~50~ =         | III      |
|        |                      |       | 0.081-0.082 mg/L |          |
|        |                      |       | (♂+♀)            |          |
|        |                      |       |                  |          |
|        |                      |       | **Dust**         |          |
|        |                      |       |                  |          |
|        |                      |       | LC~50~ = 0.532   |          |
|        |                      |       | mg/L (♂+♀)       |          |
+--------+----------------------+-------+------------------+----------+
| 87     | Acute eye irritation | 412   | Slight ocular    | III      |
| 0.2400 | -- rabbit            | 05702 | irritant         |          |
+--------+----------------------+-------+------------------+----------+
| 87     | Acute dermal         | 412   | Very slight      | IV       |
| 0.2500 | irritation -- rabbit | 05702 | dermal irritant  |          |
+--------+----------------------+-------+------------------+----------+
| 87     | Skin sensitization   | 436   | Not a            | N/A      |
| 0.2600 | -- guinea pig        | 11601 | sensitizer;      |          |
|        |                      |       | however,         |          |
|        |                      |       | positive control |          |
|        |                      |       | data not         |          |
|        |                      |       | available        |          |
+--------+----------------------+-------+------------------+----------+

**Appendix B Toxicology Profile of Cyfluthrin and Beta-cyfluthrin**

+-------+------------+-----------------+------------------------------+
| **App |            |                 |                              |
| endix |            |                 |                              |
| B,    |            |                 |                              |
| Table |            |                 |                              |
| 4**   |            |                 |                              |
|       |            |                 |                              |
| **S   |            |                 |                              |
| ubchr |            |                 |                              |
| onic, |            |                 |                              |
| Ch    |            |                 |                              |
| ronic |            |                 |                              |
| and   |            |                 |                              |
| Other |            |                 |                              |
| Tox   |            |                 |                              |
| icity |            |                 |                              |
| Pr    |            |                 |                              |
| ofile |            |                 |                              |
| --    |            |                 |                              |
| Cyflu |            |                 |                              |
| thrin |            |                 |                              |
| and   |            |                 |                              |
| Be    |            |                 |                              |
| ta-Cy |            |                 |                              |
| fluth |            |                 |                              |
| rin** |            |                 |                              |
+=======+============+=================+==============================+
| *     | **Study    | **MRID No.      | **Results**                  |
| *Guid | Type**     | (year)/         |                              |
| eline |            | Classification  |                              |
| No.** |            | /Doses**        |                              |
+-------+------------+-----------------+------------------------------+
| 870   | 90-Day     | 41244108 (1986) | **NOAEL** = 9.5/10.9         |
| .3100 | oral       |                 | mg/kg/day (M/F)              |
|       | toxicity   | Accep           |                              |
|       | (rat)      | table/guideline | **LOAEL** = 37.0/43.0        |
|       |            |                 | mg/kg/day (M/F) based on     |
|       | **Beta-cy  | M: 0, 2.3, 9.5, | gait abnormalities, necrosis |
|       | fluthrin** | 18.9 mg/kg/day  | in head and neck region,     |
|       | (99.7%     |                 | mortality (2), decreased     |
|       | a.i.)      | F: 0, 2.5,      | body weight gain.            |
|       |            | 10.9, 42.4      |                              |
|       |            | mg/kg/day       |                              |
|       |            |                 |                              |
|       |            | M: 0, 37.0      |                              |
|       |            | mg/kg/day       |                              |
|       |            |                 |                              |
|       |            | F: 0, 43.0      |                              |
|       |            | mg/kg/day       |                              |
+-------+------------+-----------------+------------------------------+
| 870   | 90-Day     | 00131524 (1980) | **NOAEL** = 22.3/28.0        |
| .3100 | oral       |                 | mg/kg/day (M/F)              |
|       | toxicity   | **Unaccepta     |                              |
|       | (rat)      | ble**/guideline | **LOAEL** = not observed     |
|       |            |                 |                              |
|       | **Cy       | M: 0, 2.2, 7.4, |                              |
|       | fluthrin** | 22.3 mg/kg/day  |                              |
|       | (84.2%     |                 |                              |
|       | a.i.)      | F: 0, 2.7, 8.8, |                              |
|       |            | 28.0 mg/kg/day  |                              |
+-------+------------+-----------------+------------------------------+
| 870   | 90-Day     | 41267801 (1987) | **NOAEL** = 2.36/2.5         |
| .3150 | oral       |                 | mg/kg/day (M/F)              |
|       | toxicity   | Accep           |                              |
|       | (dog)      | table/guideline | **LOAEL** = 13.9/15.4        |
|       |            |                 | mg/kg/day (M/F) based on     |
|       | **Beta-cy  | M: 0, 0.39,     | gait abnormalities (both     |
|       | fluthrin** | 2.36, 13.9      | sexes), vomiting (both       |
|       | (99% a.i.) | mg/kg/day       | sexes) and suggestive        |
|       |            |                 | decrease in body weight      |
|       |            | F: 0, 0.39,     | gain.                        |
|       |            | 2.5, 15.4       |                              |
|       |            | mg/kg/day       |                              |
+-------+------------+-----------------+------------------------------+
| 870   | 21/28-Day  | 44066001 (1996) | **Dermal NOAEL** = 113       |
| .3200 | dermal     |                 | mg/kg/day                    |
|       | toxicity   | Accep           |                              |
|       | (rat)      | table/guideline | **Dermal LOAEL** = 376       |
|       |            |                 | mg/kg/day based on gross and |
|       | **Cy       | 0, 113, 376,    | histological skin lesions.   |
|       | fluthrin** | 1077 mg/kg/day  |                              |
|       | (95.5%)    |                 | **Systemic NOAEL** = 376     |
|       |            | In acetone, 6   | mg/kg/day                    |
|       |            | hrs/day, for 18 |                              |
|       |            | applications    | **Systemic LOAEL** = 1077    |
|       |            | within 23 days  | mg/kg/day based on decreased |
|       |            | (♂) or 17       | food consumption, red nasal  |
|       |            | applications    | discharge and urine          |
|       |            | within 22 days  | staining.                    |
|       |            | (♀)             |                              |
+-------+------------+-----------------+------------------------------+
| Non   | 28-Day     | 00131525 (1983) | **NOAEL** = 15 mg/kg/day     |
| -guid | oral       |                 |                              |
| eline | toxicity   | Supplementary   | **LOAEL** = 50 mg/kg/day     |
|       | (rat)      |                 | based on gait abnormalities, |
|       |            | 0, 5, 15, 50    | salivation, nervousness,     |
|       | **Cy       | mg/kg/day       | decrease in body weight,     |
|       | fluthrin** |                 | food consumption, changes in |
|       |            |                 | hematological, clinical      |
|       |            |                 | chem. & urinalysis           |
|       |            |                 | parameters, increases in     |
|       |            |                 | selected organ wts.,         |
|       |            |                 | cytoplasmic swelling of      |
|       |            |                 | glandular epithelium of      |
|       |            |                 | submaxillary gland, minimal  |
|       |            |                 | degrees of fiber             |
|       |            |                 | degeneration in sciatic      |
|       |            |                 | nerve (# not reported) which |
|       |            |                 | disappeared after recovery   |
|       |            |                 | period.                      |
|       |            |                 |                              |
|       |            |                 | *Note: The NOAEL was changed |
|       |            |                 | to 15 mg/kg/day and the      |
|       |            |                 | LOAEL to 50 mg/kg/day by the |
|       |            |                 | HIARC (May 21, 2002          |
|       |            |                 | report).*                    |
+-------+------------+-----------------+------------------------------+
| 870   | 90-Day     | 00157793        | **NOAEL** = 0.00009 mg/L     |
| .3465 | inhalation | (1984),         | (0.02 mg/kg/day)             |
|       | toxicity   | 40082901,       |                              |
|       | (rat)      | 40239301        | **LOAEL** = 0.00071 mg/L     |
|       |            |                 | (0.16 mg/kg/day) based on    |
|       | **Cy       | Accep           | decreased body weights and   |
|       | fluthrin** | table/guideline | body weight gains in males   |
|       | (94.9%     |                 | and clinical signs in        |
|       | a.i.)      | 0, 0.00009,     | females.                     |
|       |            | 0.00071,        |                              |
|       |            | 0.00451 mg/L    |                              |
|       |            |                 |                              |
|       |            | (0, 0.02, 0.16, |                              |
|       |            | 0.91 mg/kg/day) |                              |
|       |            |                 |                              |
|       |            | In ethanol/PEG  |                              |
|       |            | 400 (1:1),      |                              |
|       |            |                 |                              |
|       |            | 6 hrs/day, 5    |                              |
|       |            | consecutive     |                              |
|       |            | days/week       |                              |
+-------+------------+-----------------+------------------------------+
| Non   | 4-Week     | 41842601 (1989) | **NOAEL** = 0.00044 mg/L     |
| -guid | inhalation |                 | (0.12 mg/kg/day)             |
| eline | toxicity   | Acceptabl       |                              |
|       | (rat)      | e/non-guideline | **LOAEL** = 0.006 mg/L (1.6  |
|       |            |                 | mg/kg/day) based on          |
|       | **Cy       | 0, 0.00044,     | decreases in body weight and |
|       | fluthrin** | 0.006, 0.047    | body weight gain in males,   |
|       | (93.8%     | mg/L            | hypothermia, reduction in    |
|       | a.i.)      |                 | leukocyte counts (F) and low |
|       |            | (0, 0.12, 1.6,  | serum protein.               |
|       |            | 12.8 mg/kg/day) |                              |
|       |            |                 |                              |
|       |            | In ethanol/PEG  |                              |
|       |            | 400 (1:1),      |                              |
|       |            |                 |                              |
|       |            | 6 hrs/day, 5    |                              |
|       |            | consecutive     |                              |
|       |            | days/week       |                              |
+-------+------------+-----------------+------------------------------+
| Non   | 4-Week     | 41783001 (1989) | **NOAEL** = 0.00026 mg/L     |
| -guid | inhalation |                 | (0.07 mg/kg/day)             |
| eline | toxicity   | Acceptabl       |                              |
|       | (rat)      | e/non-guideline | **LOAEL** = 0.0027 mg/L      |
|       |            |                 | (0.73 mg/kg/day) based on    |
|       | **Beta-cy  | 0, 0.00026,     | decreased body weights,      |
|       | fluthrin** | 0.0027, 0.023   | urine pH in males.           |
|       | (97.9%     | mg/L            |                              |
|       | a.i.)      |                 |                              |
|       |            | (0, 0.07, 0.73, |                              |
|       |            | 6.3 mg/kg/day)  |                              |
|       |            |                 |                              |
|       |            | In ethanol/PEG  |                              |
|       |            | 400 (1:1),      |                              |
|       |            |                 |                              |
|       |            | 6 hrs/day, 5    |                              |
|       |            | consecutive     |                              |
|       |            | days/week       |                              |
+-------+------------+-----------------+------------------------------+
| Non   | 5-Day      | 41205708 (1988) | **NOAEL** = 0.00025 mg/L     |
| -guid | inhalation |                 | (0.07 mg/kg/day)             |
| eline | study      | Acceptabl       |                              |
|       | (rat)      | e/non-guideline | **LOAEL** = 0.0038 mg/L      |
|       |            |                 | (1.03 mg/kg/day) based on    |
|       | **Beta-cy  | 0, 0.00025,     | unpreened hair coat,         |
|       | fluthrin** | 0.0038, 0.028   | piloerection, hepatoid foci  |
|       | (98% a.i.) | mg/L            | in lungs.                    |
|       |            |                 |                              |
|       |            | (0, 0.07, 1.03, |                              |
|       |            | 7.6 mg/kg/day)  |                              |
|       |            |                 |                              |
|       |            | In ethanol/PEG  |                              |
|       |            | 400 (1:1),      |                              |
|       |            |                 |                              |
|       |            | 6 hrs/day       |                              |
+-------+------------+-----------------+------------------------------+
| Non   | 28-Day     | 41244109 (1986) | **NOAEL** = 2.0 mg/kg/day    |
| -guid | oral       |                 | (both sexes)                 |
| eline | toxicity   | Acceptabl       |                              |
|       | (dog)      | e/non-guideline | **LOAEL** = 8.0 mg/kg/day    |
|       |            |                 | based on impaired movement   |
|       | **Beta-cy  | 0, 0.25, 2.0,   | and conjunctival irritation. |
|       | fluthrin** | 16.0/8.0        |                              |
|       |            | mg/kg/day       |                              |
|       |            |                 |                              |
|       |            | (2              |                              |
|       |            | dogs/sex/dose)  |                              |
+-------+------------+-----------------+------------------------------+
| 870.  | Prenatal   | 44116501 (1996) | **Maternal** **NOAEL** = 3   |
| 3700a | oral       |                 | mg/kg/day                    |
|       | dev        | Accep           |                              |
|       | elopmental | table/guideline | **Maternal LOAEL** = 10      |
|       | toxicity   |                 | mg/kg/day based on reduced   |
|       | in rodents | 0, 3, 10, 40    | body weight gain and reduced |
|       | (rat)      | mg/kg/day       | food consumption with        |
|       |            |                 | post-treatment recovery.     |
|       | **Beta-cy  | 1% Cremophor in |                              |
|       | fluthrin** | municipal tap   | **Developmental NOAEL** = 10 |
|       | (          | water           | mg/kg/day                    |
|       | 96.5-97.3% |                 |                              |
|       | a.i.)      |                 | **Developmental LOAEL** = 40 |
|       |            |                 | mg/kg/day based on reduced   |
|       |            |                 | fetal body weights and       |
|       |            |                 | increased skeletal           |
|       |            |                 | variations.                  |
+-------+------------+-----------------+------------------------------+
| 870.  | Prenatal   | 00157794 (1983) | **Maternal** **NOAEL** = 10  |
| 3700a | oral       |                 | mg/kg/day                    |
|       | dev        | **Unaccepta     |                              |
|       | elopmental | ble**/guideline | **Maternal LOAEL** = not     |
|       | toxicity   |                 | observed                     |
|       | in rodents | 0, 1, 3, 10     |                              |
|       | (rat)      | mg/kg/day       | **Developmental NOAEL** = 10 |
|       |            |                 | mg/kg/day                    |
|       | **Cy       | 1% Cremophor EL |                              |
|       | fluthrin** | in distilled    | **Developmental LOAEL** =    |
|       | (93.4%)    | water           | not observed                 |
+-------+------------+-----------------+------------------------------+
| 870.  | Prenatal   | 42675401 (1992) | **Maternal** **NOAEL** = 20  |
| 3700b | oral       |                 | mg/kg/day                    |
|       | dev        | Accep           |                              |
|       | elopmental | table/guideline | **Maternal LOAEL** = 60      |
|       | toxicity   |                 | mg/kg/day based on decreased |
|       | in         | 0, 20, 60, 180  | body weight gain and food    |
|       | n          | mg/kg/day       | consumption during the       |
|       | on-rodents |                 | dosing period.               |
|       | (rabbit)   | In corn oil, by |                              |
|       |            | gavage          | **Developmental NOAEL** =    |
|       | **Cy       |                 | 180 mg/kg/day                |
|       | fluthrin** |                 |                              |
|       |            |                 | **Developmental LOAEL** =    |
|       | (96% a.i.) |                 | not observed                 |
+-------+------------+-----------------+------------------------------+
| 870.  | Prenatal   | 43393401        | **Maternal** **NOAEL** = not |
| 3700a | inhalation | (1991-1994)     | determined                   |
|       | dev        |                 |                              |
|       | elopmental | Accep           | **Maternal LOAEL** = 0.00046 |
|       | toxicity   | table/guideline | mg/L (0.125 mg/kg/day) based |
|       | in rodents |                 | on decreased body weight     |
|       | (rat )     | 0, 0.00046,     | gain and relative food       |
|       |            | 0.00255,        | efficiency.                  |
|       | **Cy       | 0.0119, 0.0128  |                              |
|       | fluthrin** | mg/L/day        | **Developmental NOAEL** =    |
|       | (96.2%     | (0.125, 0.692,  | 0.00046 mg/L (0.125          |
|       | a.i.)      | 3.234, 3.478    | mg/kg/day)                   |
|       |            | mg/kg/day)      |                              |
|       |            |                 | **Developmental LOAEL** =    |
|       |            | In              | 0.00255 mg/L (0.692          |
|       |            | PEG-400:ethanol | mg/kg/day) based on reduced  |
|       |            | for 6 hrs/day   | fetal and placental weights  |
|       |            |                 | and reduced ossification in  |
|       |            |                 | phalanx, metacarpals,        |
|       |            |                 | vertebrae.                   |
+-------+------------+-----------------+------------------------------+
| 870.  | Prenatal   | 40780401 (1988) | **Maternal** **NOAEL** =     |
| 3700a | inhalation |                 | 0.0011 mg/L (0.299           |
|       | dev        | Accep           | mg/kg/day)                   |
|       | elopmental | table/guideline |                              |
|       | toxicity   |                 | **Maternal LOAEL** = 0.0047  |
|       | in rodents | **1.** 0,       | mg/L (1.277 mg/kg/day) based |
|       | (rat )     | 0.0011, 0.0047, | on reduced motility,         |
|       |            | 0.0237 mg/L/day | dyspnea, piloerection,       |
|       | **Cy       |                 | ungroomed coats, eye         |
|       | fluthrin** | (0, 0.299,      | irritation.                  |
|       | (92.9% and | 1.277, 6.44     |                              |
|       | 93%)       | mg/kg/day)      | **Developmental NOAEL** =    |
|       |            |                 | 0.00059 mg/L (0.160          |
|       |            | **2.** 0,       | mg/kg/day)                   |
|       |            | 0.00009,        |                              |
|       |            | 0.00025,        | **Developmental LOAEL** =    |
|       |            | 0.00059, 0.0042 | 0.0011 mg/L (0.299           |
|       |            | mg/L/day        | mg/kg/day) based on          |
|       |            |                 | increased incidence of runts |
|       |            | (0, 0.0245,     | and skeletal anomalies in    |
|       |            | 0.0679, 0.160,  | sternum.                     |
|       |            | 1.141           |                              |
|       |            | mg/kg/day)      |                              |
|       |            |                 |                              |
|       |            | Dissolved in a  |                              |
|       |            | 1:1 mixture of  |                              |
|       |            | Lutrol and      |                              |
|       |            | ethanol for 6   |                              |
|       |            | hrs/day.        |                              |
+-------+------------+-----------------+------------------------------+
| Non   | 7-Day      | 44373401 (1997) | **Maternal** **NOAEL** =     |
| -guid | postnatal  |                 | 0.058 mg/L (24.0 mg/kg/day)  |
| eline | inhalation | Acceptabl       |                              |
|       | study      | e/non-guideline | **Maternal LOAEL** = not     |
|       | (pups &    |                 | determined                   |
|       | dams) in   | 0, 0.006,       |                              |
|       | mice with  | 0.015, 0.058    | **Offspring NOAEL** = 0.006  |
|       | s          | mg/L            | mg/L (2.48 mg/kg/day)        |
|       | pontaneous |                 |                              |
|       | motor      | (0, 2.48, 6.21, | **Offspring LOAEL** = 0.015  |
|       | activity   | 24.0 mg/kg/day) | mg/L (6.21 mg/kg/day) based  |
|       | me         |                 | on clinical signs of         |
|       | asurements | In PEG 400, 6   | toxicity and spontaneous     |
|       |            | hrs/day, for 7  | motor activity observed in   |
|       | **Cy       | consecutive     | females 4 months after       |
|       | fluthrin** | days            | exposure.                    |
|       | (96.8%     |                 |                              |
|       | a.i.)      |                 |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Re         | 44371401 (1996) | **Parental/Systemic NOAEL**  |
| .3800 | production |                 | = 3/4 mg/kg/day (M/F)        |
|       | and        | Accep           |                              |
|       | fertility  | table/guideline | **Parental/Systemic LOAEL**  |
|       | effects    |                 | = 9/10 mg/kg/day (M/F) based |
|       |            | **Premating and | on reductions in body        |
|       | (rat)      | gestation:**    | weights and food             |
|       |            |                 | consumption.                 |
|       | **Cy       | M: 0, 3, 9, 29  |                              |
|       | fluthrin** | mg/kg/day       | **Offspring NOAEL** = 7      |
|       | (95.4%     |                 | mg/kg/day (M/F)              |
|       | a.i.),     | F: 0, 4, 10, 33 |                              |
|       | corn       | mg/kg/day       | **Offspring LOAEL** = 19     |
|       | o          |                 | mg/kg/day based on coarse    |
|       | il/acetone | **First 2 weeks | tremors in pups during       |
|       | premix     | of lactation:** | lactation and decreases in   |
|       |            |                 | mean litter weight.          |
|       |            | 0, 7, 19, 59    |                              |
|       |            | mg/kg/day       |                              |
+-------+------------+-----------------+------------------------------+
| Non   | "Sup       | 44371402 (1997) | **Parental/Systemic NOAEL**  |
| -guid | plemental" |                 | = 3.8/4.2 mg/kg/day (M/F)    |
| eline | 2-         | Acceptabl       |                              |
|       | generation | e/non-guideline | **Parental/Systemic LOAEL**  |
|       | re         |                 | = not determined             |
|       | production | M: 0, 1.9, 3.8  |                              |
|       | study      | mg/kg/day       | **Offspring NOAEL** =        |
|       | (rat)      |                 | 3.8/4.2 mg/kg/day (M/F)      |
|       |            | F: 0, 2.1, 4.2  |                              |
|       | **Cy       | mg/kg/day       | **Offspring LOAEL** = not    |
|       | fluthrin** |                 | determined                   |
|       | (95.5%     | Corn            |                              |
|       | a.i.)      | oil/acetone     |                              |
|       |            | premix          |                              |
+-------+------------+-----------------+------------------------------+
| Non   | Pilot      | 43792901 (1995) | **Parental/Systemic NOAEL**  |
| -guid | one-       |                 | = 22.9 mg/kg/day             |
| eline | generation | Acceptabl       |                              |
|       | re         | e/non-guideline | **Parental/Systemic LOAEL**  |
|       | production |                 | = 59.6 mg/kg/day based on    |
|       | study      | M: 0, 3.4, 9.3, | hind leg splay, ataxia,      |
|       | (rat)      | 24.2, 38.9      | reduction in body weight     |
|       |            | mg/kg/day       | gain.                        |
|       | **         |                 |                              |
|       | Cyfluthrin | F: 0, 4.1,      | **Offspring NOAEL** = 7.8    |
|       | (          | 10.5, 27.2,     | mg/kg/day                    |
|       | 95.7-96.2% | 43.9 mg/kg/day  |                              |
|       | a.i.),     |                 | **Offspring LOAEL** = 22.9   |
|       | corn       | **Gestation:**  | mg/kg/day based on tremors   |
|       | o          |                 | during lactation and pup     |
|       | il/acetone | 0, 3.9, 10.1,   | weight decreases.            |
|       | premix**   | 27.2, 45.0      |                              |
|       |            | mg/kg/day       | Dosages for the NOAEL and    |
|       |            |                 | LOAEL calculated from weekly |
|       |            | **Lactation:**  | mean test material           |
|       |            |                 | consumption during lactation |
|       |            | 0, 7.8, 22.9,   | because both the large       |
|       |            | 59.6, 95.9      | variation in consumption     |
|       |            | mg/kg/day       | values and the increased     |
|       |            |                 | test material consumption    |
|       |            |                 | during the time that the     |
|       |            |                 | effects were noted.          |
+-------+------------+-----------------+------------------------------+
| 870   | Re         | 00131532 (1983) | **Parental/Systemic NOAEL**  |
| .3800 | production |                 | = 12.3/15.1 mg/kg/day (M/F)  |
|       | and        | Acceptable      |                              |
|       | fertility  |                 | **Parental/Systemic LOAEL**  |
|       | effects    | M: 0, 3.8,      | = 37.2/48.5 mg/kg/day (M/F)  |
|       | (rat)      | 12.3, 37.2      | based on decreased body      |
|       |            | mg/kg/day       | weight gain.                 |
|       | \(1983\)   |                 |                              |
|       |            | F: 0, 5.4,      | **Offspring NOAEL** = 5.4    |
|       | **Cy       | 15.1, 48.5      | mg/kg/day                    |
|       | fluthrin** | mg/kg/day       |                              |
|       |            |                 | **Offspring LOAEL** = 15.1   |
|       |            | This study was  | mg/kg/day based on decreased |
|       |            | classified core | viability during lactation   |
|       |            | minimum,        | period and decreased body    |
|       |            | although it had | weight gains.                |
|       |            | a number of     |                              |
|       |            | deficiencies:   |                              |
|       |            | test article    |                              |
|       |            | 50% premix with |                              |
|       |            | Wessalon S, no  |                              |
|       |            | individual      |                              |
|       |            | litter          |                              |
|       |            | observations,   |                              |
|       |            | limited         |                              |
|       |            | necropsy &      |                              |
|       |            | histopathology, |                              |
|       |            | other reporting |                              |
|       |            | deficiencies.   |                              |
+-------+------------+-----------------+------------------------------+
| 870.  | Chronic    | 44435401 (1997) | **NOAEL** = 2.43/3.61        |
| 4100b | toxicity   |                 | mg/kg/day (M/F)              |
|       | (dog)      | Accep           |                              |
|       |            | table/guideline | **LOAEL** = 10.64/10.74      |
|       | **Cy       |                 | mg/kg/day (M/F) based on     |
|       | fluthrin** | M: 0, 1.36,     | clinical signs, gait         |
|       |            | 2.43, 10.64,    | abnormalities, and abnormal  |
|       | (          | 15.47 mg/kg/day | postural reactions in males  |
|       | 94.9-95.1% |                 | and females.                 |
|       | a.i.)      | F: 0, 1.46,     |                              |
|       |            | 3.61, 10.74,    |                              |
|       |            | 17.99 mg/kg/day |                              |
|       |            |                 |                              |
|       |            | Corn oil premix |                              |
+-------+------------+-----------------+------------------------------+
| 870.  | Chronic    | 00151358 (1983) | **NOAEL** = 4.0 mg/kg/day    |
| 4100b | toxicity   |                 |                              |
|       | (dog)      | Core minimum    | **LOAEL** = 16.0 mg/kg/day   |
|       |            |                 | based on gait abnormalities, |
|       | **Cy       | 0, 1, 4, 16     | vomiting, liquid feces,      |
|       | fluthrin** | mg/kg/day       | decreased body weights       |
|       |            |                 | (males).                     |
|       |            | 50% premix with |                              |
|       |            | Wessalon S      |                              |
+-------+------------+-----------------+------------------------------+
| 870.  | 6-Month    | 00131530 (1981) | **NOAEL** = 5.0 mg/kg/day    |
| 4100b | oral       |                 |                              |
|       | toxicity   | Core minimum    | **LOAEL** = 15.0 mg/kg/day   |
|       | (dog)      |                 | based on gait abnormalities, |
|       |            | 0, 1.62, 5, 15  | arching backs, vomiting,     |
|       | **Cy       | mg/kg/day       | diarrhea.                    |
|       | fluthrin** |                 |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Carci      | 44589701 (1998) | **NOAEL** = 31.9/140.6       |
| .4200 | nogenicity |                 | mg/kg/day (M/F)              |
|       | (mouse)    | Accep           |                              |
|       |            | table/guideline | **LOAEL** = 114.8 mg/kg/day  |
|       | **Cy       |                 | (M) based on ear skin        |
|       | fluthrin** | M: 0, 31.9,     | lesions and reduced body     |
|       | (93.9%     | 114.8, 232.7    | weight gains. 309.7          |
|       | a.i.)      | mg/kg/day       | mg/kg/day (F) based on       |
|       |            |                 | clinical signs, macroscopic  |
|       |            | F: 0, 38.4,     | and microscopic pathology    |
|       |            | 140.6, 309.7    | findings, and reduced body   |
|       |            | mg/kg/day       | weights, body weight gains,  |
|       |            |                 | and food consumption.        |
|       |            | Corn oil premix |                              |
|       |            |                 | ***No evidence of            |
|       |            |                 | carcinogenicity***           |
+-------+------------+-----------------+------------------------------+
| 870   | Carci      | 00137304 (1983) | Study not acceptable for     |
| .4200 | nogenicity |                 | chronic toxicity.            |
|       | (mouse)    | Accep           |                              |
|       |            | table/guideline | ***No evidence of            |
|       | **Cy       |                 | carcinogenicity***           |
|       | fluthrin** | M: 0, 11.6,     |                              |
|       |            | 45.8, 194.5     |                              |
|       | (          | mg/kg/day       |                              |
|       | 49.7-51.0% |                 |                              |
|       | a.i.)      | F: 0, 15.3,     |                              |
|       |            | 63.0, 259.9     |                              |
|       |            | mg/kg/day       |                              |
|       |            |                 |                              |
|       |            | Premix in       |                              |
|       |            | Wessalon S      |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Combined   | 44459301 (1997) | **NOAEL** = 2.6/3.3          |
| .4300 | chronic    |                 | mg/kg/day (M/F)              |
|       | feeding/   | Accep           |                              |
|       | carci      | table/guideline | **LOAEL** = 11.6/14.4        |
|       | nogenicity |                 | mg/kg/day (M/F) based on     |
|       | (rat)      | M: 0, 2.6,      | overall declines in body     |
|       |            | 11.6, 22.8      | weight gain by 12 and 10% in |
|       | **Cy       | mg/kg/day       | males and females,           |
|       | fluthrin** |                 | respectively.                |
|       | (94.7%     | F: 0, 3.3,      |                              |
|       | a.i.),     | 14.4, 28.3      | ***No evidence of            |
|       |            | mg/kg/day       | carcinogenicity***           |
|       |            |                 |                              |
|       |            | Acetone/corn    |                              |
|       |            | oil pre-mix     |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Combined   | 00137303 (1983) | **NOAEL** = 6.19/8.15        |
| .4300 | chronic    |                 | mg/kg/day (M/F)              |
|       | feeding/   | Accep           |                              |
|       | carci      | table/guideline | **LOAEL** = 19.20/25.47      |
|       | nogenicity |                 | mg/kg/day (M/F) based on     |
|       | (rat)      | M: 0, 2.02,     | decreased body weights and   |
|       |            | 6.19, 19.20     | body weight gains.           |
|       | **Cy       | mg/kg/day       |                              |
|       | fluthrin** |                 | ***No evidence of            |
|       |            | F: 0, 2.71,     | carcinogenicity***           |
|       | (          | 8.15, 25.47     |                              |
|       | 49.7-51.0% | mg/kg/day       |                              |
|       | purity as  |                 |                              |
|       | a premix   |                 |                              |
|       | c          |                 |                              |
|       | oncentrate |                 |                              |
|       | in         |                 |                              |
|       | Wessalon   |                 |                              |
|       | S)         |                 |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Gene       | 00131539 (1982) | Negative.                    |
| .5100 | mutation   |                 |                              |
|       | --         | Accep           | No increases in reverse      |
|       | bacterial  | table/guideline | mutations with and without   |
|       | reverse    |                 | activation.                  |
|       | mutation   | 5-5000 ug/plate |                              |
|       | assay      |                 |                              |
|       |            |                 |                              |
|       | **Cy       |                 |                              |
|       | fluthrin** |                 |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Gene       | 00131541,       | Negative.                    |
| .5100 | mutation   | 00144017 (1982) |                              |
|       | -- yeast   |                 | No increase in number of     |
|       | reverse    | Accep           | revertants with S138         |
|       | mutation   | table/guideline | cultures. Increase in number |
|       | assay      |                 | of revertants with S211      |
|       |            | 312.5-1000      | culture but not              |
|       | **Cy       | ug/mL           | dose-related; no increase in |
|       | fluthrin** |                 | number of revertants when    |
|       |            |                 | assay repeated.              |
+-------+------------+-----------------+------------------------------+
| 870   | Gene       | 00131540 (1982) | Negative.                    |
| .5100 | mutation   |                 |                              |
|       | --         | Accep           | No increases in reverse      |
|       | bacterial  | table/guideline | mutations with and without   |
|       | reverse    |                 | activation.                  |
|       | mutation   |                 |                              |
|       | assay      |                 |                              |
|       |            |                 |                              |
|       | **Cy       |                 |                              |
|       | fluthrin** |                 |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Gene       | 41244110 (1986) | Negative.                    |
| .5100 | mutation   |                 |                              |
|       | --         | Accep           | No increases in reverse      |
|       | bacterial  | table/guideline | mutations in *S.             |
|       | reverse    |                 | typhimurium* strains TA      |
|       | mutation   | Initial assay:  | 1535, TA 1537, TA 98 or TA   |
|       | assay      |                 | 100 with and without         |
|       |            | 20-12500        | activation.                  |
|       | **Beta-cy  | ug/plate        |                              |
|       | fluthrin** |                 |                              |
|       |            | Confirmatory    |                              |
|       |            | assay:          |                              |
|       |            |                 |                              |
|       |            | 500-8000        |                              |
|       |            | ug/plate        |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Gene       | 00157796 (1985) | Negative.                    |
| .5300 | mutation   |                 |                              |
|       | --         | Accep           | Cyfluthrin did not induce    |
|       |            | table/guideline | forward mutations under      |
|       | *in vitro* |                 | conditions of assay          |
|       | mammalian  | 3, 5, 7, 9, 10  |                              |
|       | cell gene  | ul/ml           |                              |
|       | forward    |                 |                              |
|       | mutation   |                 |                              |
|       | assay      |                 |                              |
|       |            |                 |                              |
|       | **Cy       |                 |                              |
|       | fluthrin** |                 |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Gene       | 41244112 (1989) | Negative.                    |
| .5300 | mutation   |                 |                              |
|       | --         | Accep           | No mutagenic response in CHO |
|       |            | table/guideline | cells HGPRT assay with and   |
|       | *in vitro* |                 | without activation.          |
|       | mammalian  | 50-100 ug/mL    |                              |
|       | cell gene  | (insoluble),    |                              |
|       | forward    | 20-40 ug/mL     |                              |
|       | mutation   | (soluble)       |                              |
|       | assay      |                 |                              |
|       |            |                 |                              |
|       | **Beta-cy  |                 |                              |
|       | fluthrin** |                 |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Cyto       | 41205703 (1988) | Negative.                    |
| .5375 | genetics - |                 |                              |
|       | *in vitro* | Accep           | Not clastogenic in human     |
|       | mammalian  | table/guideline | lymphocytes.                 |
|       | cell       |                 |                              |
|       | chromosome | 500, 1000, 5000 |                              |
|       | aberration | ug/mL           |                              |
|       | test       |                 |                              |
|       |            |                 |                              |
|       | **Beta-cy  |                 |                              |
|       | fluthrin** |                 |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Cy         | 4124411 (1988)  | Negative.                    |
| .5395 | togenetics |                 |                              |
|       | --         | Accep           | No increased frequency of    |
|       |            | table/guideline | micronucleated polychromatic |
|       | mammalian  |                 | erythrocytes in mice bone    |
|       | e          | 80 mg/kg        | marrow cells.                |
|       | rythrocyte |                 |                              |
|       | mi         |                 |                              |
|       | cronucleus |                 |                              |
|       | test       |                 |                              |
|       |            |                 |                              |
|       | **Beta-cy  |                 |                              |
|       | fluthrin** |                 |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Other      | 00131540 (1982) | Negative.                    |
| .5500 | effects -- |                 |                              |
|       | bacterial  | Accep           | In rec^-^ assay, no          |
|       | DNA damage | table/guideline | inhibition at doses of       |
|       |            |                 | 100-10000 ug/disk.           |
|       | **Cy       |                 |                              |
|       | fluthrin** |                 |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Other      | 00131538 (1981) | Negative.                    |
| .5550 | effects -- |                 |                              |
|       | bacterial  | Accep           | No induction of inhibition,  |
|       | DNA damage | table/guideline | both with and without        |
|       | and repair |                 | activation.                  |
|       | in *E.     | 62.5-1000       |                              |
|       | coli*      | ug/plate        |                              |
|       |            |                 |                              |
|       | **Cy       |                 |                              |
|       | fluthrin** |                 |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Other      | 00157798 (1985) | Negative.                    |
| .5550 | effects -- |                 |                              |
|       |            | Accep           |                              |
|       | u          | table/guideline |                              |
|       | nscheduled |                 |                              |
|       | DNA        | 17, 50, 167,    |                              |
|       | synthesis  | 500, 1667, 5000 |                              |
|       | in         | ug/ml           |                              |
|       | cultured   |                 |                              |
|       | rat        |                 |                              |
|       | h          |                 |                              |
|       | epatocytes |                 |                              |
|       |            |                 |                              |
|       | **Cy       |                 |                              |
|       | fluthrin** |                 |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Other      | 41205704 (1987) | Negative.                    |
| .5550 | effects -- |                 |                              |
|       |            | Accep           |                              |
|       | u          | table/guideline |                              |
|       | nscheduled |                 |                              |
|       | DNA        | 1.01-1010 ug/mL |                              |
|       | synthesis  |                 |                              |
|       | in         |                 |                              |
|       | mammalian  |                 |                              |
|       | cells in   |                 |                              |
|       | culture    |                 |                              |
|       |            |                 |                              |
|       | **Beta-cy  |                 |                              |
|       | fluthrin** |                 |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Other      | 00131542 (1982) | Negative.                    |
| .5575 | effects -- |                 |                              |
|       |            | Accep           |                              |
|       | mitotic    | table/guideline |                              |
|       | gene       |                 |                              |
|       | conversion | 625-10000 ug/ml |                              |
|       | in         |                 |                              |
|       | *Sac       |                 |                              |
|       | charomyces |                 |                              |
|       | c          |                 |                              |
|       | erevisiae* |                 |                              |
|       |            |                 |                              |
|       | **Cy       |                 |                              |
|       | fluthrin** |                 |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Other      | 00157795 (1985) | Negative.                    |
| .5915 | effects -- |                 |                              |
|       | *in vivo*  | Accep           | no increase in SCE frequency |
|       | sister     | table/guideline | in treated cells             |
|       | chromatid  |                 |                              |
|       | exchange   | Non-activated   |                              |
|       | assay in   | assays: 3, 5,   |                              |
|       | Chinese    | 10, 20 ug/ml    |                              |
|       | hamster    |                 |                              |
|       | ovary      | Activated       |                              |
|       | cells      | assays: 125,    |                              |
|       |            | 250, 500, 1000  |                              |
|       | **Cy       | ug/ml           |                              |
|       | fluthrin** |                 |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Delayed    | 00156585 (1985) | All hens died within 3 days; |
| .6100 | neu        |                 | NTE activity was not         |
|       | rotoxicity | Supplementary   | inhibited                    |
|       | (hen)      |                 |                              |
|       |            | 0 and 5000      |                              |
|       | **Cy       | mg/kg/day for 3 |                              |
|       | fluthrin** | days            |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Oral       | 00131543 (1981) | **In the single dose         |
| .6100 | delayed    |                 | study**, at 5000 mg/kg, five |
|       | neu        | Supplementary   | of the ten hens died.        |
|       | rotoxicity |                 | Moderate fiber alterations   |
|       | (hen)      | 10 hens: 1000   | (axon fragmentation,         |
|       |            | (1x), 2500      | occasional swelling and      |
|       | **Cy       | (1x), 5000 (1x) | eosinophilia of the axon     |
|       | fluthrin** | mg/kg;          | fragments and vacuolation of |
|       |            |                 | the myelin sheaths) in the   |
|       |            | 30 hens: 5000   | sciatic nerve were observed  |
|       |            | mg/kg (2x, 21   | in 2 hens. Six hens at 2500  |
|       |            | days apart);    | mg/kg showed signs of        |
|       |            |                 | excitation during the first  |
|       |            | 10 hens: 5000   | 3 days following treatment.  |
|       |            | mg/kg (5x daily | **In the two dose study**,   |
|       |            | for 1 week)     | hens showed initial signs of |
|       |            |                 | intoxication during the      |
|       |            |                 | first 3 days but were normal |
|       |            |                 | until the second dose was    |
|       |            |                 | administered when 4 hens     |
|       |            |                 | died. Symptoms following the |
|       |            |                 | second treatment subsided;   |
|       |            |                 | however, a second set of     |
|       |            |                 | symptoms developed in 4/30   |
|       |            |                 | hens. These symptoms         |
|       |            |                 | resembled delayed type       |
|       |            |                 | neurotoxicity. Nerve fiber   |
|       |            |                 | degeneration was present in  |
|       |            |                 | the majority of the hens.    |
|       |            |                 | The myelin sheath was        |
|       |            |                 | distended and the myelin     |
|       |            |                 | sheath was described as      |
|       |            |                 | being optically void or      |
|       |            |                 | granularly disintegrated.    |
|       |            |                 | The axons were described as  |
|       |            |                 | swollen or fragmented and in |
|       |            |                 | some areas activated or      |
|       |            |                 | proliferated Schwann's cells |
|       |            |                 | were noted. The nerves also  |
|       |            |                 | contained macrophages in     |
|       |            |                 | which cytoplasm contained    |
|       |            |                 | granular material. **In the  |
|       |            |                 | 5-day study**, 4/10 hens     |
|       |            |                 | died. All hens showed        |
|       |            |                 | initial toxic responses      |
|       |            |                 | which eventually             |
|       |            |                 | disappeared. Behavioral      |
|       |            |                 | disorders accompanied by     |
|       |            |                 | drowsiness and a cramped     |
|       |            |                 | gait were observed in 3 of   |
|       |            |                 | the 6 survivors. Mottled     |
|       |            |                 | kidneys and brittle livers   |
|       |            |                 | were noted at necropsy.      |
|       |            |                 | Treatment-related fiber      |
|       |            |                 | degeneration (distension or  |
|       |            |                 | granular disintegration of   |
|       |            |                 | the medullary sheath,        |
|       |            |                 | swollen or fragmented axis   |
|       |            |                 | cylinders and proliferated   |
|       |            |                 | Schwann's cell in the        |
|       |            |                 | sciatic nerve were reported. |
|       |            |                 | One hen had similar lesions  |
|       |            |                 | in the spinal marrow.        |
+-------+------------+-----------------+------------------------------+
| 870   | Oral       | 00131544 (1982) | In the single dose study,    |
| .6100 | delayed    |                 | the hens showed an initial   |
|       | neu        | 10 hens: (5000  | weight loss but recovered.   |
|       | rotoxicity | mg/kg, 1 x) or  | No other treatment-related   |
|       | (hen)      | 20 hens: (5000  | effects were observed. In    |
|       |            | mg/kg, 2 x, 7   | the two-dose study, 1 hen    |
|       | **Cy       | days apart).    | showed some signs of         |
|       | fluthrin** | The first study | neurotoxicity on day 30.     |
|       |            | was classified  | There were no microscopic    |
|       |            | as Core         | lesions in the nervous       |
|       |            | supplementary - | system.                      |
|       |            | no              |                              |
|       |            | histopathology  |                              |
|       |            | conducted) and  |                              |
|       |            | the second      |                              |
|       |            | study was       |                              |
|       |            | classified as   |                              |
|       |            | Core minimum.   |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Dermal     | 00131545 (1982) | In the first study there     |
| .6100 | delayed    |                 | were 2 deaths on the 3^rd^   |
|       | neu        | Minimum         | and 10^th^ day. All other    |
|       | rotoxicity |                 | hens had symptoms (apathy    |
|       | (hen)      | 5000 mg/kg      | and disturbed behavior) but  |
|       |            | (paste with     | recovered. Local irritation  |
|       | **Cy       | cellulose       | and weight loss were also    |
|       | fluthrin** | powder); in the | noted. Two hens had minimal  |
|       |            | first study, 10 | segment-like nerve fiber     |
|       |            | hens were       | degeneration (sciatic        |
|       |            | exposed for 5   | nerve), but this type is     |
|       |            | days for 23     | often found in hens. In the  |
|       |            | hours/day. In   | second study, the hens were  |
|       |            | the second      | apathetic. These symptoms    |
|       |            | study, 10 hens  | disappeared after the first  |
|       |            | were exposed    | week in all hens except 2,   |
|       |            | for 3 weeks, 5  | in which they persisted      |
|       |            | days/week, 6    | until the 38^th^ and 51^st^  |
|       |            | hours/day.      | day after the start of the   |
|       |            |                 | treatment, respectively.     |
|       |            |                 | Local irritation and body    |
|       |            |                 | weight loss were also        |
|       |            |                 | observed. No other           |
|       |            |                 | neurologic effects were      |
|       |            |                 | observed, including          |
|       |            |                 | microscopic.                 |
+-------+------------+-----------------+------------------------------+
| 870   | Acute      | 00131510 (1983) | Nine of 10 hens died at      |
| .6100 | delayed    |                 | 0.596 mg/L and none died in  |
|       | neu        | Core minimum    | any of the lower             |
|       | rotoxicity |                 | concentrations. These had    |
|       | (hen)      | single 4-hour   | some nonspecific symptoms    |
|       |            | exposure or to  | (behavior disturbances,      |
|       | **Cy       | 15 six-hour     | sedation, eye irritancy),    |
|       | fluthrin** | exposures over  | which disappeared after 2    |
|       |            | a 3-week period | days. Some initial weight    |
|       |            | at              | loss was also noted. In the  |
|       |            | concentrations  | 3-week study, one hen died.  |
|       |            | of 0.285, 0.445 | Nonspecific symptoms were    |
|       |            | or 0.596 mg/L   | again observed. Nothing      |
|       |            | in the single   | remarkable was noted at      |
|       |            | dose study and  | necropsy.                    |
|       |            | 0.614 mg/L in   |                              |
|       |            | the 3 week      |                              |
|       |            | study           |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Acute      | 00163040 (1986) | 4300, 1500: mortality,       |
| .6100 | delayed    |                 | aggression, somnolence,      |
|       | neu        | Core Minimum    | cyanosis of crest. Sl.       |
|       | rotoxicity |                 | axonal degeneration of       |
|       | (hen)      | 4300 (1x), 4300 | sciatic nerve in 1 hen given |
|       |            | (2x: days 1 &   | a single dose; sl. axonal    |
|       | **Cy       | 21), 1500 (5    | degeneration of spinal cord  |
|       | fluthrin** | consecutive     | in 1 hen given 2 doses. No   |
|       |            | days).          | treatment-related changes in |
|       |            |                 | NTE activity.                |
+-------+------------+-----------------+------------------------------+
| 870.  | Acute      | 44401101 (1997) | **NOAEL** = 2 mg/kg          |
| 6200a | neu        | Accep           |                              |
|       | rotoxicity | table/guideline | **LOAEL** = 10 mg/kg based   |
|       | (rat)      |                 | on clinical signs, changes   |
|       |            | 0, 0.5, 2, 10   | in FOB parameters, and       |
|       | **Beta-cy  | mg/kg           | decreases in motor activity. |
|       | fluthrin** |                 |                              |
|       |            | In 1% Cremophor |                              |
|       | (96.9%     | EL in deionized |                              |
|       | a.i.)      | water           |                              |
+-------+------------+-----------------+------------------------------+
| 870.  | Subchronic | 44296001 (1997) | **NOAEL** = 7.99/9.40        |
| 6200b | neu        | Accep           | mg/kg/day (M/F)              |
|       | rotoxicity | table/guideline |                              |
|       | (rat)      |                 | **LOAEL** = 26.81/30.83      |
|       |            | M: 0, 2.02,     | mg/kg/day (M/F) based on     |
|       | **Beta-cy  | 7.99, 26.81     | clinical signs, changes in   |
|       | fluthrin** | mg/kg/day       | FOB measurements and         |
|       | (96.5%     |                 | possibly decreased body      |
|       | a.i.)      | F: 0, 2.34,     | weights, body weight gains,  |
|       |            | 9.40, 30.83     | and food consumption         |
|       |            | mg/kg/day       |                              |
|       |            |                 |                              |
|       |            | In corn oil, 1% |                              |
|       |            | by weight in    |                              |
|       |            | diet            |                              |
+-------+------------+-----------------+------------------------------+
| 870   | Dev        | 46054101 (2003) | **Maternal NOAEL** = 17.8    |
| .6300 | elopmental |                 | mg/kg/day                    |
|       | neu        | Acceptabl       |                              |
|       | rotoxicity | e/non-guideline | **Maternal LOAEL** = not     |
|       | (rat)      |                 | observed                     |
|       |            | 0, 30, 125, 200 |                              |
|       | **Beta-cy  | ppm             | **Offspring NOAEL** = 11.0   |
|       | fluthrin** |                 | mg/kg/day                    |
|       | (          | (Gestation: 0,  |                              |
|       | 95.1-97.6% | 2.4, 11.0, 17.8 | **Offspring LOAEL** = 17.8   |
|       | a.i.)      | mg/kg/day)      | mg/kg/day based on decreased |
|       |            |                 | body weight and body weight  |
|       |            |                 | gain and decreased brain     |
|       |            |                 | weights in females at        |
|       |            |                 | termination.                 |
+-------+------------+-----------------+------------------------------+
| 870   | Metabolism | 00072007 (1983) | Following oral               |
| .7485 | and        |                 | administration, the test     |
|       | Pharma     | Core Minimum    | material was rapidly and     |
|       | cokinetics | when considered | nearly completely absorbed.  |
|       |            | together with   | Peak plasma levels of        |
|       | **Cy       | metabolism part | radioactivity were observed  |
|       | fluthrin** | of study        | at about 2 hours after       |
|       |            |                 | dosing. Greater than 95% of  |
|       | (98%       | **Single oral   | the administered             |
|       | purity in  | dose:**         | radioactivity was excreted   |
|       | 5%         |                 | within 48 hours.             |
|       | Cremophor  | 0.5 and 10      | Radioactivity was excreted   |
|       | EL)        | mg/kg           | in the urine and feces with  |
|       |            |                 | virtually none being         |
|       |            | **Single i.v.** | excreted in expired air. By  |
|       |            | dose:           | 48 hours after dosing, \>98% |
|       |            |                 | of the total retrieved       |
|       |            | 0.5 and 10      | radioactivity was recovered  |
|       |            | mg/kg           | in the urine and feces. The  |
|       |            |                 | ratio of radioactivity in    |
|       |            | **Repeated oral | urine/feces was higher in    |
|       |            | dose:**         | males than in females. About |
|       |            |                 | 50% of the total urinary     |
|       |            | 0.5 mg/kg/day   | radioactivity was recovered  |
|       |            | unlabeled for   | during the first 6-8 hours   |
|       |            | 14 days, then   | after dosing and about 90%   |
|       |            | single dose     | within the first 24 hours.   |
|       |            | labeled         | At 48 hours, only the fat    |
|       |            |                 | tissue (renal fat) contained |
|       |            |                 | levels of radioactivity that |
|       |            |                 | clearly exceeded the overall |
|       |            |                 | mean body level, being 6-11X |
|       |            |                 | higher. Levels of            |
|       |            |                 | radioactivity in brain were  |
|       |            |                 | quite low, being 15-20X      |
|       |            |                 | lower than the overall mean  |
|       |            |                 | body level. Different dose   |
|       |            |                 | levels (0.5 or 10 mg/kg) or  |
|       |            |                 | pretreatment (14X) did not   |
|       |            |                 | appreciably affect the above |
|       |            |                 | findings. Some sex           |
|       |            |                 | differences, however, were   |
|       |            |                 | observed as indicated by     |
|       |            |                 | higher urine/feces ratios in |
|       |            |                 | males and slightly higher    |
|       |            |                 | organ/tissue levels of       |
|       |            |                 | radioactivity in females     |
|       |            |                 | (except for fat tissue).     |
|       |            |                 |                              |
|       |            |                 | Following intravenous        |
|       |            |                 | administration, a 2 phase    |
|       |            |                 | plasma elimination pattern   |
|       |            |                 | was observed with plasma     |
|       |            |                 | half-lives of about 2.1 and  |
|       |            |                 | 20 hours. The apparent       |
|       |            |                 | volume of distribution (Vd)  |
|       |            |                 | was about 17% of the total   |
|       |            |                 | body volume, corresponding   |
|       |            |                 | to the "readily diffusable   |
|       |            |                 | part of the extracellular    |
|       |            |                 | fluid". Greater than 90% of  |
|       |            |                 | the administered             |
|       |            |                 | radioactivity was excreted   |
|       |            |                 | within 48 hours. By 48 hours |
|       |            |                 | after dosing, about 93-94%   |
|       |            |                 | of the total retrieved       |
|       |            |                 | radioactivity was recovered  |
|       |            |                 | in the urine and feces.      |
|       |            |                 | Residual levels of           |
|       |            |                 | radioactivity in the body    |
|       |            |                 | and in individual            |
|       |            |                 | organs/tissues were higher   |
|       |            |                 | than after oral              |
|       |            |                 | administration. In other     |
|       |            |                 | respects, the results        |
|       |            |                 | following intravenous dosing |
|       |            |                 | were quite similar to those  |
|       |            |                 | described for oral dosing.   |
|       |            |                 | Studies in male rats with    |
|       |            |                 | bile fistulas indicated an   |
|       |            |                 | enterohepatic circulation of |
|       |            |                 | test material.               |
+-------+------------+-----------------+------------------------------+
| 870   | Metabolism | 00072007 (1983) | Excretion of radioactivity   |
| .7485 | and        |                 | was rapid. Following oral    |
|       | Pharma     | Core Minimum    | administration, \>95% of the |
|       | cokinetics | when considered | administered radioactivity   |
|       |            | together with   | was excreted within 48       |
|       | **Cy       | biokinetic part | hours, and following         |
|       | fluthrin** | of study        | intravenous injection, \>90% |
|       |            |                 | within 48 hours. Most of the |
|       | (98%       | **Single oral   | radioactivity was excreted   |
|       | purity in  | dose:**         | in urine, the urine/fecal    |
|       | 5%         |                 | ratio being about 2-3X in    |
|       | Cremophor  | 0.5 and 10      | males and about 1.6-1.8X in  |
|       | EL)        | mg/kg           | females following oral       |
|       |            |                 | administration and about     |
|       |            | **Single i.v.** | 2.5X in males and about 2.6X |
|       |            | dose:           | in females following         |
|       |            |                 | intravenous injection.       |
|       |            | 0.5 and 10      | Parent cyfluthrin is cleaved |
|       |            | mg/kg           | at the ester bond and then   |
|       |            |                 | oxidized to yield            |
|       |            | **Repeated oral | 3-phenoxy-4-fluorobenzoic    |
|       |            | dose:**         | acid. This intermediate is   |
|       |            |                 | then either hydroxylated and |
|       |            | 0.5 mg/kg/day   | subsequently conjugated and  |
|       |            | unlabeled for   | excreted or first bound to   |
|       |            | 14 days, then   | glycine and then             |
|       |            | single dose     | hydroxylated, conjugated and |
|       |            | labeled         | excreted. Identified         |
|       |            |                 | metabolites and parent       |
|       |            |                 | cyfluthrin (in urine, feces  |
|       |            |                 | and body) accounted for      |
|       |            |                 | 65-73% of the recovered      |
|       |            |                 | radioactivity after a single |
|       |            |                 | oral or intravenous dose of  |
|       |            |                 | 0.5 mg/kg and about 82-83%   |
|       |            |                 | of the recovered             |
|       |            |                 | radioactivity after a single |
|       |            |                 | oral dose of 10 mg/kg or     |
|       |            |                 | after 14 daily oral doses.   |
+-------+------------+-----------------+------------------------------+

[]{#__RefHeading___Toc179885394 .anchor}**Appendix C Summary of
Cyfluthrin/Beta-cyfluthrin Tolerances**

+-----------------+-------+--------+----------+-----------------------+
| **Appendix C;   |       |        |          |                       |
| Table 1**       |       |        |          |                       |
|                 |       |        |          |                       |
| **Tolerance     |       |        |          |                       |
| Summary Table   |       |        |          |                       |
| for             |       |        |          |                       |
| Cyfluthrin/Be   |       |        |          |                       |
| ta-cyfluthrin** |       |        |          |                       |
+=================+=======+========+==========+=======================+
| **Commodity**   | **E   | **Pr   | **Rec    | **Comments; Correct   |
|                 | stabl | oposed | ommended | Commodity             |
|                 | ished | Tol    | T        | Definition**          |
|                 | Tole  | erance | olerance |                       |
|                 | rance | (      | (ppm)**  |                       |
|                 | (p    | ppm)** |          |                       |
|                 | pm)** |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Grass, forage,  | 6.0   | 13.0   | 12       | Adequate grass field  |
| fodder and hay, | ^1^   |        |          | trial data are        |
| group 17,       |       |        |          | available.            |
| forage          |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Grass, forage,  | 8.0   | 40.0   | 50       |                       |
| fodder and hay, | ^1^   |        |          |                       |
| group 17, hay   |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Alfalfa, forage | \-    | 5.0    | 5.0      | Adequate alfalfa      |
|                 |       |        |          | field trial data are  |
|                 |       |        |          | available.            |
+-----------------+-------+--------+----------+-----------------------+
| Alfalfa, hay    | 10.0  | 15.0   | 13       |                       |
+-----------------+-------+--------+----------+-----------------------+
| Beet, sugar,    | \-    | 0.09   | 0.10     | Adequate field trial  |
| roots           |       |        |          | data are available    |
+-----------------+-------+--------+----------+-----------------------+
| Beet, sugar,    | \-    | 11     | 1.0      | Maximum expected      |
| dried pulp      |       |        |          | residues are 0.59 ppm |
|                 |       |        |          | based on HAFT         |
|                 |       |        |          | residues of 0.049 ppm |
|                 |       |        |          | and a 12x processing  |
|                 |       |        |          | factor for dried      |
|                 |       |        |          | pulp.                 |
+-----------------+-------+--------+----------+-----------------------+
| Grain, cereal;  | 4.0   | 4.0    | 0.15     | Wheat grain, barley   |
| Crop Group 15   |       |        |          | grain, buckwheat      |
| (except Rice)   |       |        |          | grain, millet grain,  |
|                 |       |        |          | oat grain, rye grain, |
|                 |       |        |          | triticale grain       |
+-----------------+-------+--------+----------+-----------------------+
| Grain, cereal;  | 4.0   | 4.0    | 0.05     | Corn, field, grain    |
| Crop Group 15   |       |        |          |                       |
| (except Rice)   |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Grain, cereal;  | 4.0   | 4.0    | 0.05     | Corn, sweet, kernel   |
| Crop Group 15   |       |        |          | plus cob with husks   |
| (except Rice)   |       |        |          | removed               |
+-----------------+-------+--------+----------+-----------------------+
| Grain, cereal;  | 4.0   | 4.0    | 3.5      | Sorghum, grain, grain |
| Crop Group 15   |       |        |          |                       |
| (except Rice)   |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Wheat, bran     | 6.5   | \-     | 0.5      | Stored grain uses     |
|                 |       |        |          | have been revoked     |
+-----------------+-------+--------+----------+-----------------------+
| Corn, field,    | 30.0  | \-     | \-       | The field corn, grain |
| refined oil     |       |        |          | tolerance will cover  |
|                 |       |        |          | residues in corn oil  |
+-----------------+-------+--------+----------+-----------------------+
| Rice, bran      | 6.0   | \-     | \-       | Stored grain uses     |
|                 |       |        |          | have been revoked     |
+-----------------+-------+--------+----------+-----------------------+
| Rice, hulls     | 18.0  | \-     | \-       | Stored grain uses     |
|                 |       |        |          | have been revoked     |
+-----------------+-------+--------+----------+-----------------------+
| Grain, cereal,  | \-^2^ | 7.0    | 25       | Grain, cereal,        |
| forage, fodder  |       |        |          | forage, fodder and    |
| and straw, Crop |       |        |          | hay, group 17,        |
| Group 16        |       |        |          | forage, except rice   |
| (except Rice)   |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Grain, cereal,  | \-    | 7.0    | 30       | Grain, cereal,        |
| forage, fodder  | ^3^   |        |          | forage, fodder and    |
| and straw, Crop |       |        |          | hay, group 17,        |
| Group 16        |       |        |          | stover, except rice   |
| (except Rice)   |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Grain, cereal,  | \-    | 7.0    | 7.0      | Grain, cereal,        |
| forage, fodder  | ^4^   |        |          | forage, fodder, and   |
| and straw, Crop |       |        |          | hay, group 17, straw, |
| Group 16        |       |        |          | except rice           |
| (except Rice)   |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Grain, cereal,  | \-    | 7.0    | 6.0      | Grain, cereal,        |
| forage, fodder  | ^5^   |        |          | forage, fodder and    |
| and straw, Crop |       |        |          | hay, group 17, hay,   |
| Group 16        |       |        |          | except rice           |
| (except Rice)   |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Wheat, forage   | 5.0   | \-     | \-       | Crop group tolerance  |
|                 |       |        |          | is being established  |
|                 |       |        |          | for Forage of Grain,  |
|                 |       |        |          | Cereal, except Rice   |
|                 |       |        |          | (Crop Group 16)       |
+-----------------+-------+--------+----------+-----------------------+
| Corn, field,    | 3.0   | \-     | \-       |                       |
| forage          |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Corn, sweet,    | 15    | \-     | \-       |                       |
| forage          |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Sorghum, grain, | 2.0   | \-     | \-       |                       |
| forage          |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Corn, field,    | 6.0   | \-     | \-       | Crop group tolerance  |
| stover          |       |        |          | is being established  |
|                 |       |        |          | for Stover of Grain,  |
|                 |       |        |          | Cereal, except Rice   |
|                 |       |        |          | (Crop Group 16)       |
+-----------------+-------+--------+----------+-----------------------+
| Corn, pop,      | 6.0   | \-     | \-       |                       |
| stover          |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Corn, sweet,    | 30.0  | \-     | \-       |                       |
| stover          |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Sorghum, grain, | 5.0   | \-     | \-       |                       |
| stover          |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Wheat, hay      | 6.0   | \-     | \-       | Crop group tolerance  |
|                 |       |        |          | is being established  |
|                 |       |        |          | for Hay of Grain,     |
|                 |       |        |          | Cereal, except Rice   |
|                 |       |        |          | (Crop Group 16)       |
+-----------------+-------+--------+----------+-----------------------+
| Wheat, straw    | 6.0   | \-     | \-       | Crop group tolerance  |
|                 |       |        |          | is being established  |
|                 |       |        |          | for Straw of Grain,   |
|                 |       |        |          | Cereal, except Rice   |
|                 |       |        |          | (Crop Group 16)       |
+-----------------+-------+--------+----------+-----------------------+
| Cattle, fat     | 10    | NA     | 2.0      | Based on the          |
|                 |       |        |          | recalculated maximum  |
|                 |       |        |          | dietary burdens       |
|                 |       |        |          | (MDBs) for beef       |
|                 |       |        |          | cattle (20.9 ppm),    |
|                 |       |        |          | dairy cattle (27.1    |
|                 |       |        |          | ppm) and swine (3.21  |
|                 |       |        |          | ppm) and the residue  |
|                 |       |        |          | data from the         |
|                 |       |        |          | available cattle      |
|                 |       |        |          | feeding study,        |
|                 |       |        |          | tolerances for        |
|                 |       |        |          | livestock commodities |
|                 |       |        |          | can be substantially  |
|                 |       |        |          | reduced.              |
+-----------------+-------+--------+----------+-----------------------+
| Cattle, meat    | 0.4   | NA     | 0.10     |                       |
+-----------------+-------+--------+----------+-----------------------+
| Cattle, meat    | 0.4   | NA     | 0.10     |                       |
| byproducts      |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Goat, fat       | 10    | NA     | 2.0      |                       |
+-----------------+-------+--------+----------+-----------------------+
| Goat, meat      | 0.4   | NA     | 0.05     |                       |
+-----------------+-------+--------+----------+-----------------------+
| Goat, meat      | 0.4   | NA     | 0.05     |                       |
| byproducts      |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Hog, fat        | 10    | NA     | 0.5      |                       |
+-----------------+-------+--------+----------+-----------------------+
| Hog, meat       | 0.4   | NA     | 0.01     |                       |
+-----------------+-------+--------+----------+-----------------------+
| Hog, meat       | 0.4   | NA     | 0.01     |                       |
| byproducts      |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Horse, fat      | 10    | NA     | 2.0      |                       |
+-----------------+-------+--------+----------+-----------------------+
| Horse, meat     | 0.4   | NA     | 0.05     |                       |
+-----------------+-------+--------+----------+-----------------------+
| Horse, meat     | 0.4   | NA     | 0.05     |                       |
| byproducts      |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+
| Milk            | 1.0   | NA     | 0.2      |                       |
+-----------------+-------+--------+----------+-----------------------+
| Milk, fat       | 30    | NA     | 5.0      |                       |
+-----------------+-------+--------+----------+-----------------------+
| Sheep, fat      | 10    | NA     | 2.0      |                       |
+-----------------+-------+--------+----------+-----------------------+
| Sheep, meat     | 0.4   | NA     | 0.05     |                       |
+-----------------+-------+--------+----------+-----------------------+
| Sheep, meat     | 0.4   | NA     | 0.05     |                       |
| byproducts      |       |        |          |                       |
+-----------------+-------+--------+----------+-----------------------+

NA = not applicable

^1^ Regionally restricted tolerances for grass grown in CA, OR, ID and
WA.

^2^ Forage tolerances are established for wheat (5.0 ppm), field corn
(3.0 ppm), sweet corn (15 ppm), and sorghum (2.0 ppm)

^3^ Stover tolerances are established for field corn (6.0 ppm), popcorn
(6.0 ppm), sweet corn (30 ppm), and sorghum (5.0 ppm)

^4^ A Straw tolerance is established for wheat (6.0 ppm)

^5^ A hay tolerance is established for wheat (6.0 ppm)

[^1]: Ware, G.W. *The Pesticide Book*. Fresno, CA, Thomson Publications,
    1994, pgs 171-172.