Document ID: EPA-HQ-OPP-2006-0108-0019
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-03-28T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF           

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date:		January 30, 2003

Subject:	Occupational and Residential Risk Assessment to Support Request
for a Section 3 Registration of Cyromazine on Brassica (Cole) Leafy
Vegetables Group 5, and Turnip Greens.

 

DP Barcode:	

PC Code:	

Trade Name:	

EPA Reg#	

MRID#	

PRAT Case	

Class	

Caswell#	

40 CFR

D285851	

121301	

Trigard ®	

100-654	

N/A	

295479	

Insecticide	

N/A	

N/A

 

From:		Jack Arthur, Environmental Scientist

Registration Action Branch 3

Health Effects Division (7509C)

To:		William Wassell, Risk Assessor

Registration Action Branch 3

Health Effects Division (7509C)

Thru:		Stephen Dapson, Ph.D., Branch Senior Scientist

Registration Action Branch 3

Health Effects Division (7509C)

Introduction

The Interregional Research Project Number 4 (IR-4) requests the
establishment of tolerances for residues of the insecticide cyromazine
on brassica (cole) leafy vegetables group 5 (including: abyssinian
cabbage; bok choy; broccoli; broccoli, Chinese; broccoli raab; Brussels
sprouts; cabbage; cabbage, Chinese; cabbage, Chinese mustard; cabbage,
seakale; cauliflower; cavalo broccolo; collards; Hanover salad; kale,
common; kohlrabi; mustard, wild; mustard, Chinese; mustard greens;
mustard spinach; and rape greens) and turnip greens .  This memorandum
addresses risk from occupational and residential exposure only.  An
aggregate human risk assessment for cyromazine will be included as a
separate HED memorandum.

1.0  Executive Summary

Cyromazine is currently registered for a number of uses including, on
mango, onion (green and dry bulb), potato, head lettuce, celery, leafy
vegetables (except Brassica) crop group, cucurbit vegetables crop group,
tomato, mushroom and pepper.  The formulated end use product evaluated
in this assessment is labeled under the trade name Trigard®.  In this
memorandum, the name cyromazine will be used for the active ingredient
(ai) in this product.

Cyromazine is an insecticide for the control of leafminers.  The
formulation of cyromazine evaluated in this assessment is a wettable
powder, packaged in water-soluble packets (i.e., Trigard® 75% ai).  The
petitioner proposes multiple foliar sprays at a rate of 0.125 lb ai/A,
using ground or aerial equipment.  Applications are proposed to begin
when leafminers first appear and continue throughout the season at 7-day
intervals to maintain control.  

There are no residential use sites associated with current or proposed
uses of cyromazine.  Therefore, a residential risk assessment was not
conducted.

There is a potential for occupational exposure to cyromazine during
mixing, loading, application, and postapplication activities.  The
Health Effects Division's Hazard Identification Assessment Review
Committee (HIARC) did not select any dermal endpoints for cyromazine,
because no hazard was identified via the dermal route (i.e., no toxicity
was observed at the limit dose of 1,000 mg/kg/day; there are no concerns
for pre/postnatal toxicity; and dermal absorption is relatively low
[13%]).  Therefore, the occupational risk assessment was based on
inhalation exposure only.  For handlers, daily inhalation doses were
compared to the oral NOAELs of 10 mg/kg/day (based on decreases in
maternal body weight gain and food consumption in the developmental oral
study in the rabbit) and 7.5 mg/kg/day (based on alterations in
hematological parameters, body weight and body weight gain decreases and
increase in several organ weights in the 6-month feeding study in the
dog) to estimate the risk from short- and intermediate-term inhalation
exposures, respectively.  Chronic exposures are not expected for
handlers of cyromazine for the proposed use patterns.

No chemical-specific handler exposure data were submitted in support of
this Section 3 registration.  It is the policy of the HED to use data
from the Pesticide Handlers Exposure Database (PHED) Version 1.1 as
presented in PHED Surrogate Exposure Guide (8/98) to assess handler
exposures for regulatory actions when chemical-specific monitoring data
are not available (HED Science Advisory Council for Exposure Draft
Policy # 7, dated 1/28/99). 

Occupational handlers’ inhalation MOEs range from 34,000 for
intermediate-term flagging sprays for aerial operations to 290,000 for
short-term mixing/loading wettable powder packaged in water-soluble
packets for groundboom application.  These MOEs are greater than HED’s
target MOE of 100, and therefore, are not of concern.

Occupational postapplication dermal exposure is possible following
treatment of crops with cyromazine.  However, because no appropriate
dermal endpoints were identified for this exposure potential, and
inhalation exposure is expected to be negligible for reentry activities,
a postapplication risk assessment based foliar treatment was not
conducted.

The current label for  Trigard® has a 12-hour restricted entry interval
(REI).  The cyromazine technical material has been classified in
Toxicity Category III for acute dermal, and Toxicity Category IV for
primary eye irritation and primary skin irritation.  Per the Worker
Protection Standard(WPS), a 12-hour restricted entry interval (REI) is
required for chemicals classified under Toxicity Category III or IV. 
Therefore, the REI of 12 hours is in compliance with the WPS.

2.0  Hazard Profile

On April 4, 2002, the Health Effects Division (HED) Hazard
Identification Assessment Review Committee (HIARC) reviewed the
recommendations of the toxicology reviewer for cyromazine with regard to
the acute and chronic Reference Doses (RfDs) and the toxicological
endpoint selection for use as appropriate in occupational/residential
exposure risk assessments.  The potential for increased susceptibility
of infants and children from exposure to cyromazine was also evaluated
as required by the Food Quality Protection Act (FQPA) of 1996 according
to the 2002 OPP 10x guidance document.  HED’s FQPA Safety Factor
Committee met on August 12, 2002 and confirmed that the 10-fold safety
factor for increased susceptibility of infants and children should be
removed (i.e., reduced to 1x) for cyromazine for the U.S. population and
all population subgroups and for all exposure scenarios.  The acute
toxicity and endpoint selection for cyromazine are in Tables 1 and 2,
respectively. 

Table 1.  Acute Toxicity Data on Cyromazine Technical

Guideline

 No.	

Study Type	

MRID #	

Results	

Toxicity Category

81-1	

Acute Oral	

00082836	

LD50 = > 3387 mg/kg	

III

81-2	

Acute Dermal-Rat	

00082839	

LD50 = > 3100 g/kg	

III

81-3	

Acute Inhalation	

43799901	

LC50 > 0.744 mg/L	

III

81-4	

Primary Eye Irritation	

00082841	

no irritation	

IV

81-5 	

Primary Skin Irritation	

00082842	

mild irritant	

IV

81-6	

Dermal Sensitization	

00082843	

non-sensitizing	



Table 2.  Summary of Toxicological Doses and Endpoints for Cyromazine
for Use in Human Risk Assessment 

Exposure

Scenario	

Dose (mg/kg/day) 

UF /MOE	

Hazard Based Special FQPA Safety Factor	

Endpoint for Risk Assessment

Dietary Risk Assessments

Acute Dietary

	

NA	

NA	

An appropriate end point attributable to a single dose (exposure) was
not observed in oral toxicity studies.

Chronic Dietary

all populations	

NOAEL = 7.5

UF =100

Chronic RfD =  0.075 

	

1x	

6-Month Feeding-Dog

LOAEL = 75 mg/kg/day based on  alterations in hematological parameters
[hematocrit,  and hemoglobin (males)], body weight and body weight gain
decreases and increase in several organ weights

Incidental Oral

Short-Term 

(1 - 30 Days)

Residential Only	

NOAEL= 10 

MOE= 100	

1x	

Developmental Toxicity-Rabbit

LOAEL=30 mg/kg/day based on decreases in body weight gain and food
consumption

Incidental Oral

Intermediate-Term

(1 - 6 Months)

Residential Only	

NOAEL= 7.5 

MOE = 100	

1x	

6-Month Feeding-Dog

LOAEL = 75 mg/kg/day based on  alterations in hematological parameters
[hematocrit,  and hemoglobin (males)], body weight and body weight gain
decreases and increase in several organ weights

Non-Dietary Risk Assessments

Dermal 

Short-Term 

(1 - 30 days)	

NA	

	

No hazard was identified via the dermal route. Quantification of risk is
not required.  There are no concerns for pre/post natal toxicity.

Residential 	

 MOE = NA	

NA

	

Occupational	

 MOE = NA	

NA

	

Dermal 

Intermediate-Term 

(1 - 6 Months)	

NA	

	

No hazard was identified via the dermal route. Quantification of risk is
not required.  There are no concerns for pre/post natal toxicity.

Residential 	

 MOE = NA	

NA

	

Occupational	

 MOE = NA	

NA

	

Dermal 

Long-Term 

(> 6 Months)	

NA	

	

No hazard was identified via the dermal route. Quantification of risk is
not required.  There are no concerns for pre/post natal toxicity.

Residential 	

 MOE = NA	

NA

	

Occupational	

 MOE = NA	

NA

	

Inhalation

Short-Term 

(1 - 30 days)	

Oral NOAEL = 10	

	

Developmental Toxicity-Rabbit

LOAEL=30 mg/kg/day based on decreases in body weight gain and food
consumption

Residential 	

 MOE = 100	

1x

	

Occupational	

 MOE = 100	

NA

	

Inhalation

Intermediate-Term  

(1 - 6 Months)	

Oral NOAEL = 7.5	

	

6-Month Feeding-Dog

LOAEL = 75 mg/kg/day based on  alterations in hematological parameters
[hematocrit,  and hemoglobin (males)], body weight and body weight gain
decreases and increase in several organ weights

Residential	

 MOE = 100	

1x

	

Occupational	

 MOE = 100	

NA

	

Inhalation

Long-Term 

(>6 Months)	

Oral NOAEL = 7.5	

	

6-Month Feeding-Dog

LOAEL = 75 mg/kg/day based on  alterations in hematological parameters
[hematocrit,  and hemoglobin (males)], body weight and body weight gain
decreases and increase in several organ weights

Residential 	

  MOE = 100	

1x

	

Occupational	

  MOE = 100	

NA

	

Cancer 	

Classification: E

NA = Not Applicable; MOE = Margin of Exposure.

3.0  Use Profile

The proposed uses for this Section 3 petition are summarized in Table 3.

Table 3.  Summary of Use Patterns/Formulation Information

Formulation Type (% ai)	

Application Method	

Use Site	

Application Rate 

(lb ai/A)	

Frequency of Application (interval)

Wettable Powder in Water-Soluble Packet

(75% ai)	

Groundboom and Aerial Sprayer	

brassica (cole) leafy vegetables group 5 (including: abyssinian cabbage;
bok choy; broccoli; broccoli, Chinese; broccoli raab; Brussels sprouts;
cabbage; cabbage, Chinese; cabbage Chinese mustard; cabbage, seakale;
cauliflower; cavalo broccolo; collards; Hanover salad; kale, common;
kohlrabi; mustard, wild; mustard, Chinese; mustard greens; mustard
spinach; and rape greens) and turnip greens

	

0.125	

6 apps

 (7 days)

PHI = 7 days

4.0  Occupational Exposure

4.1   Handler Exposure and Risk			

There is a potential for exposure to cyromazine during mixing, loading,
and application  activities.  An exposure/risk assessment using
applicable endpoints selected by the HIARC was performed.  No
chemical-specific handler exposure data were submitted in support of
this Section 3 registration.  In accordance with HED’s Exposure
Science Advisory Council (SAC) policy, exposure data from the Pesticide
Handlers Exposure Database (PHED) Version 1.1 as presented in PHED
Surrogate Exposure Guide (8/98) were used with other HED default values
for acres treated per day, body weight, and the level of personal
protective equipment to assess handler exposures.

Handler’s exposure and risk were estimated for the following
scenarios:  (1) mixing/loading wettable powder packaged in water-soluble
packets for aerial application, (2) mixing/loading wettable powder
packaged in water-soluble packets for groundboom application, (3)
applying sprays with fixed-wing aircraft, (4) applying sprays with a
groundboom sprayer, and (5) flagging sprays for aerial operations. 

The minimum level of PPE for handlers is based on acute toxicity for the
end-use products.  The Registration Division (RD) is responsible for
ensuring that PPE listed on the label is in compliance with the Worker
Protection Standard (WPS).

As mentioned previously, no dermal endpoint was selected for cyromazine
by the HIARC, because no hazard was identified via the dermal route
(i.e., no toxicity was observed at the limit dose of 1,000 mg/kg/day;
there are no concerns for pre/postnatal toxicity; and dermal absorption
is relatively low [13%]).  Therefore, the occupational risk assessment
was based on inhalation exposure only.  The daily inhalation doses were
compared to the oral NOAELs of 10 mg/kg/day (based on decreases in
maternal body weight gain and food consumption in the developmental oral
study in the rabbit) and 7.5 mg/kg/day (based on alterations in
hematological parameters, body weight and body weight gain decreases and
increase in several organ weights in the 6-month feeding study in the
dog) to estimate the risk from short- and intermediate-term inhalation
exposures, respectively.  Chronic exposures are not expected for
handlers of cyromazine for the proposed use patterns.  

The MOEs range from 34,000 for intermediate-term flagging sprays for
aerial operations to 290,000 for short-term mixing/loading wettable
powder packaged in water-soluble packets for groundboom application. 
These MOEs are above HED’s target of 100, and therefore, are not of
concern.  Exposure assumptions and estimates for occupational handlers
are summarized in Table 4.  

    				

Table 4.  Inhalation Exposure and Risk Assessment for Occupational
Handlers

PHED Scenario

Selected from PSEG (8/98)	

PHED Unit Exposure 1

(mg/lb ai) 	

Application Rate 2

(lb ai/A)	

Area Treated 3

(A/day)	

Daily 

Dose 4

(mg/kg/day)	

Short- Term Inhalation

MOE 5	

Intermed- Term Inhalation 

MOE 5

1. Mixing/Loading Wettable Powder packaged in Water-Soluble Packets for
Aerial Application	

0.00024	

0.125	

350	

0.00015	

67,000	

50,000

2. Mixing/Loading Wettable Powder packaged in Water-Soluble Packets for
Groundboom Application

0.125	

80	

0.000034	

290,000	

220,000

3. Applying Sprays with Fixed-wing Aircraft (enclosed cockpit)	

0.000068	

0.125	

350	

0.000043	

240,000	

180,000

4. Applying Sprays with a Groundboom Sprayer (open cab)	

0.00074	

0.125	

80	

0.00011	

95,000	

71,000

5. Flagging (Sprays) for Aerial Operations	

0.00035	

0.125	

350	

0.00022	

46,000	

34,000

1Unit Exposure values are based on exposure without a respirator.  There
is low confidence in values used for M/L wettable powder in
water-soluble packets, high confidence in the values for groundboom
application and flagging for aerial operations, and medium confidence in
values used for aerial application with an enclosed-cockpit aircraft.

2 Maximum application rate of 0.125 lb ai/acre was used as a screening
value.

3Standard values for acres treated in a day were used. 

4 Daily Dose = [Unit Exposure (mg/lb ai handled) x Application Rate (lb
ai/A) x Acres Treated (A/day)] / Body Weight (70 kg used because
endpoint effects were not considered gender-specific)

5 MOE = NOAEL/ Daily Inhalation Dose.  Short-term Inhalation NOAEL = 10
mg/kg/day.  Intermediate-term Inhalation  NOAEL = 7.5 mg/kg/day.

4.2   Postapplication Exposure and Risk

This action on cyromazine involves foliar applications.  Therefore,
there is a potential for postapplication exposure to scouts, harvesters
and other field workers.  However, because no appropriate dermal
endpoints were identified for this exposure potential, and 
postapplication inhalation exposure is expected to be negligible, an
occupational postapplication risk assessment was not conducted. 
Non-occupational postapplication risk in residential settings is covered
in Section 5.0. 

The current label for  Trigard® has a 12-hour restricted entry interval
(REI).  The cyromazine technical material has been classified in
Toxicity Category III for acute dermal, and Toxicity Category IV for
primary eye irritation and primary skin irritation.  Per the Worker
Protection Standard(WPS), a 12-hour restricted entry interval (REI) is
required for chemicals classified under Toxicity Category III or IV. 
Therefore, the REI of 12 hours is in compliance with the WPS.

5.0  Non-Occupational/Residential Exposure

There are no residential use sites associated with current or proposed
uses of cyromazine.  Therefore, a residential risk assessment was not
conducted.

Off Target Non-Occupational Exposure

Spray drift is always a potential source of exposure to residents nearby
to spraying operations.  This is particularly the case with aerial
application, but, to a lesser extent, could also be a potential source
of exposure from the ground application method employed for cyromazine. 
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.  The
Agency is now requiring interim mitigation measures for aerial
applications that must be placed on product labels/labeling.  The Agency
has completed its evaluation of the new data base submitted by the Spray
Drift Task Force, a membership of U.S. pesticide registrants, and is
developing a policy on how to appropriately apply the data and the
AgDRIFT computer model to its risk assessments for pesticides applied by
air, orchard airblast and ground hydraulic methods.  After the policy is
in place, the Agency may impose further refinements in spray drift
management practices to reduce off-target drift and risks associated
with aerial as well as other application types where appropriate.  

CC:     RAB3 RF

SignOff Date: January 2003

DP Barcode:  D285851

 PAGE  9