UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: January 6, 2015 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Forchlorfenuron. Preliminary Human Health Risk Assessment for Registration 

Review. 

PC Code: 128819 

Decision No.: 494704 

Petition No.: NA 

Risk Assessment Type: Single Chemical 

TXRNo.: NA 

MRIDNo.: NA 

DP Barcode: 0422527 

Registration No.: NA 

Regulatory Action: Registration Review 

Case No.: 7057 

CAS No.: 68157-60-8 

40 CFR: 180.569 

FROM: 

t1 P_A 11 /../ 

Alexandra LaMay, Biologist . no.~ ...... ~ William Donovan, Chemist (;V/Jt'£ Matt Lloyd, Industrial Hygienist ~ I _,~ 

Linda Taylor, Ph.D. Toxicologist V~ 

Risk Assessment Branch VII 

Health Effects Division (7509P~ -(& 

THROUGH: Ronnie Bever, Toxicologist ~ f (AD \ry 

Michael Metzger, Chief ~ ~, I '-

Risk Assessment Branch VII 

Health Effects Division (7509P) 

TO: Wilhelmena Livingston, Chemical Review Manager 

Pesticide Re-evaluation Division (7508P) 
Forchlorfenuron Human Health Risk Assessment DP No. D422527 

1.0 Executive Summary .................... ........... ............ ................................................................ 4 

2.0 HED Recommendations .................................................................................................... 6 

2.1 Data Deficiencies ........ ..................................................... ......... ... ............. ......... ............ . 6 

2.2 Tolerance Considerations .................................... .......................................................... 7 

2.2.1 Enforcement Analytical Method ........ ............ ................................................. .......... 7 

2.2.2 Recommended Tolerances .......................................................... ............................... 7 

2.2.3 International Harmonization ..................................................................................... 8 

2.3 Label Recommendations ................................................................................................ 8 

3.0 Introduction ........ .............................................................................................................. .. 8 

3.1 Chemical Identity ........................................................................................ ........ .. ......... 8 

3.2 Physical/Chemical Characteristics .... .... ........................... ................. .... .... ......... .......... 9 

3.3 Pesticide Use Pattern .................................................................................................... .. 9 

3.4 Anticipated Exposure Pathways ........................... ..................................... ................. 10 

3.5 Consideration of Environmental Justice .................................................................... 11 

4.0 Hazard Characterization and Dose-Response Assessment. ......................................... 11 

4.1 Toxicology Studies Available for Analysis ...................................................................... 11 

4.2 Absorption, Distribution, Metabolism, & Excretion (ADME) ................................. 12 

4.2.1 Dermal Absorption .............................................. .... ................................................. 12 

4.3 Toxicological Effects .................................................................................................... 12 

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) .. ............................. 13 

4.4.1 Completeness of the Toxicology Database ............. ....... .... .................................. .... 13 

4.4.2 Evidence of Neurotoxicity ............................................... .................... ............. ........ 13 

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal. ....... 14 

4.4.4 Residual Uncertainty in the Exposure Database ................................................... 14 

4.5 Toxicity Endpoint and Point of Departure Selections .............................................. 14 

4.6 Endocrine Disruption ................................................................................................... 16 

5.0 Dietary Exposure and Risk Assessment ......................................................................... 17 

5.1 Residues of Concern Summary and Rationale ............. ............................................. 17 

5.2 Food Residue Profile ................................................................ .' ................................... 18 

5.3 Water Residue Profile ... .......... ........................... ... ..... .... .............................................. 18 

5.4 Dietary Risk Assessment.. ............................................................................................ 19 

5.4.1 Description of Residue Data Used in Dietary Assessment.. .................................. 19 

5.4.2 Percent Crop Treated Used in Dietary Assessment .............................................. 19 

5.4.3 Acute Dietary Risk Assessment ............................................................................... 19 

5.4.4 Chronic Dietary Risk Assessment ........................................................................... 20 

5.4.5 Cancer Dietary Risk Assessment.. ........................................................................... 20 

5.4.6 Summary Table ........................................................... .... .......................................... 20 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 20 

6.1 Residential Handler Exposure ... ... .... .................................................... ........ ..... .... .... . 21 

6.2 Post-Application Exposure ............................ .... ................................................. ......... 21 

6.3 Residential Bystander Post-application Inhalation Exposure ................................. 21 

6.4 Spray Drift ........................................................................................................... .... ..... 21 

7.0 Aggregate Exposure/Risk Characterization ................ ............................. : .................... 26 

7.1 Acute Aggregate Risk ................................................................................................... 26 

7.2 Short-Term Aggregate Risk ................................... .... .... .............................. ... ............. 26 

7.3 Intermediate-Term Aggregate Risk .................................................. ......................... 26 

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7.4 Chronic Aggregate Risk .............................................................................................. 26

7.5 Cancer Aggregate Risk ................................................................................................ 26

8.0 Cumulative Exposure/Risk Characterization ............................................................... 26

9.0 Occupational Exposure/Risk Characterization ............................................................ 27

9.1 Short-/Intermediate-Term Handler Risk................................................................... 27

9.2 Short-/Intermediate-Term Post-Application Risk .................................................... 30

9.2.1 Dermal Post-Application Risk................................................................................. 30

9.2.2 Inhalation Post-Application Risk............................................................................ 32

10.0 References......................................................................................................................... 32

Appendix A. Toxicology Profile and Executive Summaries .................................................. 34

A.1 Toxicology Data Requirements................................................................................... 34

A.2 Toxicity Profiles............................................................................................................ 35

Appendix B. Forchlorfenuron International Residue Limits Table ..................................... 39

Appendix C. Review of Human Research................................................................................ 40
Forchlorfenuron Human Health Risk Assessment DP No. D422527

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1.0 Executive Summary

HED has conducted a human health risk assessment to support registrations review for the active 

ingredient, forchlorfenuron, a plant growth regulator used to increase fruit set and size. 

Forchlorfenuron is registered for use on grapes, bushberries, blueberries, kiwi, almond, sweet 

cherry, fig, pear, pistachio, and plums/prunes. It is formulated as a soluble concentrate and a

wettable powder and applied via ground equipment. There are no non-agricultural uses 

registered for forchlorfenuron.

The toxicological database for forchlorfenuron is considered complete for characterization of 

potential developmental, reproductive, carcinogenetic, mutagenic, neurotoxic, and immunotoxic 

effects. Forchlorfenuron is rapidly absorbed following oral exposure, with the majority of the 

dose being recovered in the urine within 24 hours. Forchlorfenuron is not acutely toxic via the 

oral, dermal, and inhalation routes. It produces mild eye irritation, is not a dermal irritant, and is 

negative for dermal sensitization. Dose-related effects noted in the dog following subchronic 

and chronic exposure were generally limited to decreased body weight and body weight gain. In 

the rat, the only organ that appeared to be affected was the kidney, which showed suppurative 

inflammation, suppurative pyelonephritis, non-suppurative interstitial nephritis, and cortical 

cysts following chronic exposure. The prenatal developmental studies in rabbits and rats and the 

two-generation reproduction study in rats showed no indication of increased susceptibility to 

in utero and/or postnatal exposure to forchlorfenuron. Developmental toxicity occurred in the rat 

only at a maternally toxic dose level and was not observed in the rabbit. Reproductive toxicity 

was not observed. There is no concern for immunotoxicity or neurotoxicity following exposure 

to forchlorfenuron. Forchlorfenuron has been classified as not likely to be a human carcinogen, 

and there is no concern for mutagenicity. 

Based on the toxicity, duration of exposure, and uses of forchlorfenuron, the following toxicity 

endpoints were selected: 

Acute dietary (all populations): No appropriate toxicity endpoint attributable to a 

single dose (exposure) could be identified from the available toxicology data base.

Chronic dietary: cRfD = 0.07 mg/kg/day derived from a NOAEL of 7 mg/kg/day in a 

chronic oral toxicity study in the rat. LOAEL = 93 mg/kg/day based on decreased body 

weight parameters and kidney toxicity.

Dermal, inhalation, and incidental oral exposures (short-term): NOAEL = 100 

mg/kg/day from data of the main and range-finding developmental toxicity studies in the 

rabbit. LOAEL = 125 mg/kg/day based on body weight loss.

Dermal, inhalation, and incidental oral exposures (intermediate-term): NOAEL = 

87 mg/kg/day from a chronic oral toxicity in the dog. LOAEL = 195 mg/kg/day based on 

decreased body weight, body weight gain, and food consumption.

For dermal exposure and risk assessments, 100% absorption was assumed; inhalation toxicity 

was assumed to be equivalent to oral toxicity. For the occupational and residential risk 

assessments the level of concern (LOC) is for MOEs less than 100. The FQPA safety factor has 

been reduced to 1X since the database is complete, there is no evidence of pre- or post-natal 
Forchlorfenuron Human Health Risk Assessment DP No. D422527

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sensitivity/susceptibility, there is no evidence of neurotoxicity, and exposure estimates are not 

likely to underestimate risk.

The residue chemistry database for forchlorfenuron is complete. Validated analytical methods 

are available for both data collection and enforcement purposes. Sufficient storage stability data 

were submitted to support sample storage intervals in the magnitude of the residue studies, which 

supported the established tolerance levels in registered crops. The nature of the residue in plants 

is adequately understood, and the residue of concern in plants is forchlorfenuron only for both 

risk assessment and tolerance setting. As a 40 CFR §180.6(a)(3) situation exists, no residue 

definition is needed for livestock. The residue of concern in drinking water is forchlorfenuron

only. 

The Environmental Fate and Effects Division (EFED) has developed estimated drinking water 

concentration (EDWC) values for use in human health risk assessment using the PRZM/EXAMS 

and PRZM-GW models for surface and ground water, respectively. For the chronic dietary 

analysis, the maximum annual mean EDWC value of 7.3 μg/L, derived from the PRZM-GW 

model, was used as a point estimate to represent chronic drinking water concentration. The 

EDWC of 7.3 μg/L is a post-breakthrough mean that occurs after 88 years of annual use. The 

PRZM/EXAMS (surface water) EDWCs were considerably lower than the PRZM-GW EDWC 

(groundwater). No new drinking water assessment is required for this risk assessment.

An acute dietary endpoint was not selected since there were no effects seen in the toxicological 

database that were attributable to a single dose of forchlorfenuron; therefore, quantification of

acute dietary exposure and risk assessment is not required. A highly conservative chronic 

dietary risk assessment was conducted using tolerance level residues, assuming 100% crop 

treated for all commodities, and using default concentration values (or actual processing study 

information when available) for processed commodities. For the U.S. general population and for 

all subpopulations, risks were <1% of the cPAD, and are, therefore, not of concern. Since 

forchlorfenuron has been classified as not likely to be carcinogenic, quantification of dietary 

cancer risk assessment is not required. 

Quantification of acute aggregate risk assessment is not required since forchlorfenuron does not 

pose an acute hazard. Since there are no uses of forchlorfenuron existing that would result in 

residential (non-occupational) exposure to the pesticide, short- and intermediate-term aggregate 

risk assessment are not required. 

The chronic aggregate risk assessment includes only food and drinking water exposure, and is 

equivalent to the chronic dietary (food and water) risk assessment. The chronic dietary risk 

estimates are not of concern for the general population and all population subgroups. 

Quantification of aggregate cancer risk assessment is not required.

A spray drift assessment was completed for forchlorfenuron. The spray drift risk estimates are 

based on an estimated deposited residue concentration as a result of the screening level 

agricultural application scenarios. Children’s (1 to < 2 year old) dermal and incidental oral risk 

estimates from indirect exposure to forchlorfenuron, related to spray drift, result in no buffers for 
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groundboom or airblast applications. Risk estimates from ground boom and airblast applications 

are not of concern at the field edge for all situations considered. 

EPA has not assumed that forchlorfenuron has a common mechanism of toxicity with other 

substances, and thus cumulative risk characterization is not required

HED conducted occupational handler and post-application exposure and risk assessments for all 

registered uses. Short- and intermediate-term MOEs for handlers (mixers/loaders and 

applicators) were not of concern to HED as they significantly exceeded the target MOE of 100. 

Total MOEs for the occupational handler assessment range from 3,300 to 180,000. The 

occupational post-application exposure and risk estimates indicate that short- and intermediateterm MOEs are not of concern to HED, also significantly exceeding the target MOE of 100. 

MOEs for the occupational post-application assessment range from 720 to 200,000, depending 

on the crop/activity combination.

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human-health risk assessment, in accordance with U.S. Executive Order 12898, “Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations.1” 

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide to determine their exposure. Appendix C provides additional 

information on the review of human research used to complete the risk assessment. There is no 

regulatory barrier to continued reliance on these studies, and all applicable requirements of 

EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been 

satisfied.

2.0 HED Recommendations

During the conduct of the forchlorfenuron PRA, HED did not identify any data deficiencies or 

label recommendations.

2.1 Data Deficiencies

The toxicity, exposure and residue chemistry data bases are considered complete for the purpose 

of registration review. No additional data are required to support the registration review of 

forchlorfenuron. 

Although HED would typically require dislodgeable foliar residue (DFR) studies based on the 

existing use pattern, no studies are required due to forchlorfenuron’s risk estimates exceeding the 

criteria laid out in HED’s guidance on waiving DFR data2.

 

1 http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf.

2 Guidance for Requiring/Waiving Turf Transferrable Residue (TTR) and Dislodgeable Foliar Residue (DFR) 

Studies. 10/23/2014, Exposure Science Advisory Council 
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2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

HPLC/UV method CCRL-MTH-029, Analytical Method for the Determination of 

Forchlorfenuron In/On Grapes, Grape Juice and Raisins, (D344334, D. Davis, 2/13/08) is 

available for enforcing the tolerances for forchlorfenuron on plant commodities. For this 

method, residues are extracted with methanol or acetone, diluted with water, and partitioned 

against hexane. Residues remaining in the aqueous fraction are then partitioned into 

dichloromethane (DCM), and if necessary, further purified using a silica SPE cartridge. 

Residues are determined by HPLC/UV using external standards, and residues are confirmed by 

LC/MS/MS analysis. This method has been adequately validated by the registrant and the 

Agency. The validated limit of quantitation (LOQ) is 0.01 ppm for forchlorfenuron in fruit and 

nut crops, and the reported limits of detection (LOD) are 0.002-0.003 ppm. 

Validated analytical methods are available for both data collection and enforcement purposes. 

Tolerances are not required for livestock commodities; therefore, an enforcement analytical 

method in livestock commodities is not required.

2.2.2 Recommended Tolerances

Permanent and temporary tolerances are currently established under 40 CFR §180.569(a)(1) and 

180.569(a)(2) for residues of forchlorfenuron in or on several commodities. HED recommends 

that the residue definition for the forchlorfenuron tolerance expression retain its current wording 

as:

“Tolerances are established for residues of the plant growth regulator forchlorfenuron, 

including its metabolites and degradates, in or on the commodities listed below. 

Compliance with the tolerance levels specified below is to be determined by measuring 

only forchlorfenuron (N-(2-chloro-4-pyridinyl)-N’-phenylurea), in or on the commodity”.

The expiration date of the temporary tolerances is 12/31/2015. Upon expiration, section 

§180.569(a)(2) may be removed from the CFR, as all the commodities with temporary tolerances 

also have permanent tolerances listed in §180.569(a)(1).

Table 2.2.2. Tolerance Summary for Forchlorfenuron.

Commodity Established Tolerance 

(ppm)

HED-Recommended 

Tolerance (ppm)

Comments 

(Correct Commodity Definition)

Almond 0.01 0.01 Almond

Almond, hulls 

(processed commodity)

0.15 0.15 Almond, hulls

Bushberry subgroup 

13-07B

0.01 0.01 Bushberry subgroup 13-07B

Cherry, sweet 0.01 0.01 Cherry, sweet

Fig 0.01 0.01 Fig

Grape 0.03 0.03 Grape

Grape, raisin 0.06 0.06 Grape, raisin
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Kiwifruit 0.04 0.04 Kiwifruit

Pear 0.01 0.01 Pear

Pistachio 0.01 0.01 Pistachio

Plum, prune, fresh 0.01 0.01 Plum, prune, fresh

2.2.3 International Harmonization

No Codex or Canadian Maximum Residue Limits (MRLs) have been established for 

forchlorfenuron. At this time, there are no international harmonization issues for 

forchlorfenuron. 

2.3 Label Recommendations

No revisions to the labels are required. 

3.0 Introduction

Forchlorfenuron (N-(2-chloro-4-pyrindinyl)-N-phenyl urea) is a plant growth regulator used to 

increase fruit set and size. Forchlorfenuron is registered for use on almonds, sweet cherries, figs, 

pears, pistachios, kiwifruit, grapes, bushberries, and plums/prunes. The agricultural products are 

generally formulated as wettable powder and soluble concentrates. There are no forchlorfenuron 

products registered for residential use sites (e.g., lawns or turf).

The most recent risk assessment was performed for the then-proposed uses of forchlorfenuron on 

almonds, sweet cherries, figs, pears, pistachios, and plums/prunes (A. LaMay, D407226; 2/6/14). 

3.1 Chemical Identity

Table 3.1 Forchlorfenuron Nomenclature

Chemical Structure

Empirical Formula C12H10ClN3O

Common Name Forchlorfenuron

Company experimental name CPPU

IUPAC name 1-(2-chloro-4-pyridyl)-3-phenylurea

CAS Name N-(2-chloro-4-pyridinyl)-N’-phenylurea

CAS Registry Number 68157-60-8

N

N

O

Cl N
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3.2 Physical/Chemical Characteristics

Forchlorfenuron is a lipophilic compound with a low vapor pressure (not volatile) and has low 

water solubility. The physicochemical properties for forchlorfenuron are summarized in Table 

3.2, below. 

Table 3.2 Physicochemical Properties of Forchlorfenuron Technical. 

Parameter Value Reference

State Crystalline solid

D309772, L. Kutney, 

12/20/2004

Color Off white

Melting point/range 165-170°C

Molecular Weight 247.67

pH 6.7

Density 1.44 g/cm3at 21 °C

Water solubility 39 mg/L

Solvent solubility 17g/100 mL in acetone

Vapor pressure (25°C) 3.5 x10-10 torr

Dissociation constant, pKa pKa1 = 2.5; pKa2 = 12.3

Octanol/water partition coefficient, 

Log(KOW)

3.2 @ 20°C

UV/visible absorption spectrum pH < 2: A1 = 2.18 × 104 @ 202 nm; A2

= 1.47 × 104 @ 279 nm

pH =7: A1 = 1.93 × 104 @ 205 nm; A2

= 1.51 × 104 @ 261 nm

pH >10: A1 = 2.24 × 104 @ 207 nm; A2

= 1.89 × 104 @ 261 nm

3.3 Pesticide Use Pattern

The registered use directions for forchlorfenuron are summarized in Table 3.3 below.

Table 3.3. Summary of Directions for Use of Forchlorfenuron

Application 

Timing, 

Type, and 

Equip.

Formulation

[EPA Reg. 

No.]

Applic. 

Rate 

(lb ai/A)

Max. No. 

Applic. 

per Season

Max. 

Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Almond

Ground 

application 

CPPUTM 

Plant Growth 

Regulator 

[71049-4]

0.011 –

0.022 1 0.022 NS

Apply during early nut 

development.

Apply in 100 – 200 

gallons spray/acre.

Sweet Cherry

Ground 

application

CPPUTM 

Plant Growth 

Regulator 

[71049-4]

0.011 –

0.022 1 0.022 7

Apply in 100 – 200 

gallons spray/acre.

Fig

Ground 

application

CPPUTM 

Plant Growth 

Regulator 

[71049-4]

0.011 –

0.022 1 0.022 NS

Apply during early fig 

development. Apply in

100 – 200 gallons 

spray/acre.

Pear
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Table 3.3. Summary of Directions for Use of Forchlorfenuron

Application 

Timing, 

Type, and 

Equip.

Formulation

[EPA Reg. 

No.]

Applic. 

Rate 

(lb ai/A)

Max. No. 

Applic. 

per Season

Max. 

Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Ground 

application

CPPUTM 

Plant Growth 

Regulator 

[71049-4]

0.011 –

0.022 1 0.022 NS

Apply 25-days postpetal fall. Apply in 100 

– 200 gallons spray/acre.

Pistachio

Ground 

application

CPPUTM 

Plant Growth 

Regulator 

[71049-4]

0.011 –

0.022 1 0.022 NS

Apply at beginning of 

kernel formation. Apply 

in 100 – 200 gallons 

spray/acre.

Plum/Prune

Ground 

application

CPPUTM 

Plant Growth 

Regulator 

[71049-4]

0.011 –

0.022 1 0.022 NS

Apply during bloom. 

Apply in 100 – 200 

gallons spray/acre.

Bushberry subgroup 13-07B

Ground 

application

98% SC/S

[71049-1]

0.07 lb/gal 

SC/L 

[71049-3]

0.0044-

0.022 1 0.022 NS

Apply from early 

flowering to 14 days 

after petal fall. Apply in 

a minimum of 50 gal/A.

Grape

Ground 

application

98% SC/S

[71049-1]

0.07 lb/gal 

SC/L 

[71049-3]

0.0044-

0.022 1 0.022 NS

Apply early post-bloom, 

or at bloom for grapes 

grown for raisins. 

Apply in a minimum of 

200 gallons of water/A.

Kiwifruit

Ground 

application

98% SC/S

[71049-1]

0.07 lb/gal 

SC/L 

[71049-3]

0.0044-

0.018 1 0.018 NS

Apply 2-3 weeks post 

bloom. Apply in a 

minimum of 200 gallons 

of water/A.

For all labeled crops except sweet cherry, the directions permit a single application at specific 

fruit and nut formation stages in lieu of specifying a PHI. Since the Agency recognizes that 

different varieties mature at different rates, HED considers it appropriate to specify timing based 

on growth stage instead of specific PHI for these crops. 

3.4 Anticipated Exposure Pathways

PRD has requested an assessment of human health risk to support Registration Review of all 

existing registered uses of forchlorfenuron. Humans may be exposed to forchlorfenuron in food 

and drinking water, since forchlorfenuron may be applied directly to growing crops and 

application may result in forchlorfenuron reaching surface and ground water sources of drinking 

water. There are no residential uses of forchlorfenuron, so there is not likely to be exposure in 

residential or non-occupational settings. In an occupational setting, applicators may be exposed 

while handling the pesticide prior to application, as well as during application. There is a 
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potential for post-application exposure for workers re-entering treated fields. 

This risk assessment considers all of the aforementioned exposure pathways based on the 

existing uses of forchlorfenuron. 

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. 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 the USDA under the National 

Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA) 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. Additionally, OPP is able to assess dietary exposure to smaller, 

specialized subgroups, and exposure assessments are performed when conditions or 

circumstances warrant. Whenever appropriate, non-dietary exposures based on home use of 

pesticide products and associated risks for adult applicators and for toddlers, youths, and adults 

entering or playing on treated areas postapplication 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.

4.0 Hazard Characterization and Dose-Response Assessment

No new toxicity and/or rat metabolism data have been received since the last risk assessment, 

which did not identify any data deficiencies with respect to toxicology. Based on the current 40 

CFR Part 158 data requirements, an immunotoxicity study, subchronic dermal and inhalation 

toxicity studies, and acute and subchronic neurotoxicity studies are required for forchlorfenuron. 

However, the Hazard and Science Policy Council (HASPOC) concluded that these studies 

should be waived for forchlorfenuron (TXR Nos. 0056596 and 0056795). This assessment 

includes summaries of prior assessments (D341628, 3/11/08).

4.1 Toxicology Studies Available for Analysis

The toxicology database for forchlorfenuron is complete for risk assessment. There are 

acceptable studies available for toxicity endpoint selection; they include: 

 subchronic oral toxicity studies in rats and dogs 

 chronic oral toxicity studies in rats and dogs 

 carcinogenicity studies in rats and mice 
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 developmental studies in rats and rabbits 

 reproduction study in rats 

 complete mutagenicity study battery 

 metabolism study in rats 

4.2 Absorption, Distribution, Metabolism, & Excretion (ADME)

Metabolism studies in rats indicate that forchlorfenuron is rapidly and almost entirely absorbed 

and metabolized, tissue residues are minimal, and excretion is almost complete. Overall recovery 

of the radioactive dose was 97%. The majority of the dose was recovered in the urine within 24 

hours (62-74% dose). Fecal excretion accounted for 16-28% dose, and 20-23% of the dose was 

found in the bile. At 168 hours post-dose, excluding the GI contents and the carcass, the highest 

concentrations of radioactivity were found in the kidney and liver in both sexes. The elimination 

half-life was 13.1-16.2 hours. There were no sex-related differences.

The metabolism of forchlorfenuron in rats includes conjugation with sulfate at the phenyl ring 

(major pathway) before or after hydroxylation of the phenyl ring, hydroxylation of the phenyl 

ring (major pathway), conjugation with glucuronide at the phenyl ring, methylation of the 

hydroxy group of hydroxyl CPPU-sulfate, and hydroxylation of both the chloropyridinyl and 

phenyl rings.

4.2.1 Dermal Absorption

A dermal absorption study is not available for forchlorfenuron, and 100% dermal absorption is 

used for risk assessment.

4.3 Toxicological Effects

Forchlorfenuron is a plant growth regulator that is absorbed by leaves, stem, cotyledon, and 

germinated seeds. It promotes cell division, differentiation, and development; induces budding of 

callus; controls apical dominance; breaks dormancy of lateral buds; promotes germination; 

delays the aging process; maintains chlorophyll in excised leaves; regulates the transport of 

nutrients; and promotes fruit formation. In the submitted studies, there were no apparent effects 

observed consistent with this mode of action.

Dose-related effects noted in the dog following subchronic and chronic exposure were generally 

limited to decreased body weight and body weight gain. In the rat, the only organ that appeared 

to be affected was the kidney, which showed suppurative inflammation, suppurative 

pyelonephritis, non-suppurative interstitial nephritis, and cortical cysts following chronic 

exposure. 

Developmental toxicity was not observed in the rabbit but was observed in the rat (decreased 

fetal body weight and delayed ossification of the sternebrae) only at a maternally-toxic dose level 

(decreased body weight and death). Forchlorfenuron did not induce any signs of reproductive 

toxicity or neurotoxic potential. The developmental toxicity studies in rats and rabbits, as well as 

the reproductive toxicity study in rats, did not demonstrate any pre- or postnatal sensitivity. 
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There is no evidence of immunotoxicity, and the requirement for an immunotoxicity study has 

been waived (TXR No. 0056795).

A repeated exposure study via either the dermal or inhalation routes of exposure is not available 

for forchlorfenuron; however, these studies have been waived by HASPOC (TXR No. 0056596). 

No neurotoxicity studies are available on forchlorfenuron, but there was no evidence of 

neurotoxicity in any of the submitted studies and these studies have been waived by HASPOC 

(TXR No. 0056596). 

The database for carcinogenicity is complete, and forchlorfenuron is classified as not likely to be 

a human carcinogen. The mutagenicity/genetic toxicity database is considered complete, and 

there is no concern for mutagenicity. 

Forchlorfenuron is not acutely toxic via the oral, dermal, and inhalation routes. It is not a dermal 

sensitizer or dermal irritant, but it is a mild eye irritant. 

4.4 Safety Factor for Infants and Children (FQPA Safety Factor)

The Food Quality Protection Act (FQPA) safety factor for the protection of infants and children 

has been reduced to 1X. There are no concerns and no residual uncertainties with regard to preand/or postnatal toxicity. An FQPA Safety Factor of 1X is appropriate for the following reasons:

The database for prenatal developmental and reproductive toxicity is considered adequate to 

assess safety for infants and children. There is no evidence of increased qualitative or 

quantitative susceptibility in the developmental rat and rabbit studies or in the rat 2-generation 

reproduction study. These studies have clearly defined NOAEL/LOAELs. There is a lack of 

evidence of neurotoxicity in any study on forchlorfenuron. 

Exposure estimates (food and water) are not likely to underestimate risk.

Further details may be found in the following sections.

4.4.1 Completeness of the Toxicology Database

The toxicology database for forchlorfenuron is complete. Acceptable rat and rabbit 

developmental toxicity studies and a rat 2-generation reproduction study are available. The 

HASPOC determined that the acute and subchronic neurotoxicity studies and the 

immunotoxicity study may be waived (TXR Nos. 0056596 and 0056795). All other required 

toxicology studies have been submitted and are considered acceptable. 

4.4.2 Evidence of Neurotoxicity

There is no concern for neurotoxicity resulting from exposure to forchlorfenuron based on a lack 

of evidence of neurotoxicity in any study on forchlorfenuron. There is not a concern for 

developmental neurotoxicity.
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4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

There is no evidence of increased susceptibility (qualitative or quantitative) following in utero

exposure to forchlorfenuron in either the rat or rabbit developmental toxicity study, and there is 

no evidence of increased susceptibility (qualitative or quantitative) following in utero and/or pre-

/post-natal exposure in the 2-generation reproduction study in rats. 

Forchlorfenuron has been evaluated for potential developmental effects in the rat and rabbit 

(gavage administration). Maternal toxicity included death of one dam and significantly decreased 

body weight in the rat and was not observed in the rabbit. Decreased fetal body weight and a 

slight increase in the incidence of delayed ossification were observed in the rat at the same dose 

level at which the maternal effects were seen, whereas there were no developmental effects in the 

rabbit. Retarded growth was observed in the F1 and F2 offspring in the 2-generation 

reproduction study at a dose level where clinical signs of toxicity and decreased body weight 

occurred in the parental rats. 

4.4.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the exposure database. The dietary exposure estimates are 

unrefined and reflect tolerance-level residue in food, 100% crop treated, and upper-bound 

drinking water estimates based on modeling. These assumptions and refinements are detailed in 

the Section 5.4.1. There are no non-occupational exposures for forchlorfenuron. 

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment

There have been no changes, except as noted below, to the prior dose-response assessment, 

recommendations for combining routes of exposure, and/or cancer classification. Incidental oral 

exposure endpoints and points of departure have been added.

Refer to Table 4.5.1 for the summary of the toxicological doses and endpoints for 

forchlorfenuron.

Table 4.5.1 Summary of Toxicological Doses and Endpoints for Forchlorfenuron for Use in Dietary and 

Occupational Human Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/FQP

A Safety Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(All 

Populations)

No appropriate endpoint attributable to a single exposure (dose) was identified from oral 

toxicity studies, including the developmental studies; therefore an acute endpoint was not 

selected and an acute dietary risk assessment is not required. 
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Table 4.5.1 Summary of Toxicological Doses and Endpoints for Forchlorfenuron for Use in Dietary and 

Occupational Human Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/FQP

A Safety Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Chronic 

Dietary (All 

Populations)

NOAEL = 

7 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

chronic RfD 

= 0.07 

mg/kg/day

cPAD = 0.07 

mg/kg/day

Chronic oral toxicity study – rat

LOAEL = 93 mg/kg/day, based on 

decreased body weight, body weight 

gain, and food consumption, and kidney 

toxicity (suppurative inflammation in 

males; nonsuppurative interstitial 

nephritis in females)

Dermal ShortTerm (1-30 

days)

oral 

NOAEL = 

100 

mg/kg/day

(dermal 

absorption 

rate = 

100%)

UFA= 10x

UFH=10x

FQPA SF= 1x

Residential 

LOC for 

MOE = 100

Occupational 

LOC for 

MOE = 100

Developmental toxicity study – rabbit

LOAEL = 125 mg/kg/day, based on body

weight loss during dosing period in the 

range-finding study

Dermal 

IntermediateTerm (1-6 

months)

oral 

NOAEL = 

87 

mg/kg/day

(dermal 

absorption

rate = 

100%)

UFA= 10x

UFH=10x

FQPA SF= 1x

Residential 

LOC for 

MOE = 100

Occupational 

LOC for 

MOE = 100

Chronic oral toxicity study - dog 

LOAEL = 195 mg/kg/day based on 

decreased body weight, body weight 

gain, and food consumption

Inhalation 

Short-Term 

(1-30 days)

oral 

NOAEL= 

100 

mg/kg/day

(inhalation 

toxicity 

assumed to 

be 

equivalent 

to oral )

UFA= 10x

UFH=10x

FQPA SF= 1x

Residential 

LOC for 

MOE = 100 

Occupational 

LOC for 

MOE = 100

Developmental toxicity study – rabbit

LOAEL = 125 mg/kg/day based on body

weight loss during dosing period in the 

range-finding study

Inhalation 

IntermediateTerm (1-6 

months)

oral 

NOAEL = 

87 

mg/kg/day

(inhalation 

toxicity 

assumed to 

be 

equivalent 

to oral)

UFA= 10x

UFH=10x

FQPA SF= 1x

Residential 

LOC for 

MOE = 100 

Occupational 

LOC for 

MOE = 100

Chronic oral toxicity study - dog 

LOAEL = 195 mg/kg/day based on 

decreased body weight, body weight 

gain, and food consumption
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Table 4.5.1 Summary of Toxicological Doses and Endpoints for Forchlorfenuron for Use in Dietary and 

Occupational Human Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/FQP

A Safety Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Incidental 

Oral ShortTerm (1-30 

days)

oral 

NOAEL= 

100 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Residential 

LOC for 

MOE = 100 

Occupational 

LOC for 

MOE = 100

Developmental toxicity study – rabbit

LOAEL = 125 mg/kg/day based on body

weight loss during dosing period in the 

range-finding study

Incidental 

Oral 

IntermediateTerm (1-6 

months)

oral 

NOAEL = 

87 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Residential 

LOC for 

MOE = 100 

Occupational 

LOC for 

MOE = 100

Chronic oral toxicity study - dog 

LOAEL = 195 mg/kg/day based on 

decreased body weight, body weight 

gain, and food consumption

Cancer (oral, 

dermal, 

inhalation)

Classification: not likely to be a human carcinogen, based on two adequate rodent 

carcinogenicity studies.

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. UFA = extrapolation from animal to human (interspecies). UFH = 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. 

4.5.2 Recommendation for Combining Routes of Exposure for Risk Assessment

The toxicity endpoints (based on body weight effects) for the incidental oral, inhalation, and 

dermal routes are similar and need to be combined. 

4.5.3 Cancer Classification and Risk Assessment Recommendation

The database for carcinogenicity is complete, and forchlorfenuron is classified as “not likely to 

be carcinogenic to humans”, based on the lack of evidence of tumors in two animal species. The 

mutagenicity database is considered complete, and there is no concern for mutagenicity.

4.6 Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental,

reproductive, and general or systemic toxicity. These studies include endpoints which may be

susceptible to endocrine influence, including effects on endocrine target organ histopathology,

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss,

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and

chronic studies that assess growth, developmental and reproductive effects in different
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taxonomic groups. As part of its preliminary re-registration decision for forchlorfenuron, EPA 

reviewed these data and selected the most sensitive endpoints for relevant risk assessment 

scenarios from the existing hazard database. However, as required by FFDCA section 408(p), 

forchlorfenuron is subject to the endocrine screening part of the Endocrine Disruptor Screening 

Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal

systems. Chemicals that go through Tier 1 screening and are found to have the potential to

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2

testing is designed to identify any adverse endocrine-related effects caused by the substance, and

establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list

of chemicals identified for EDSP screening was published on June 14, 20133and includes some

pesticides scheduled for registration review and chemicals found in water. Neither of these lists 

should be construed as a list of known or likely endocrine disruptors. List 2 represents the next 

set of chemicals for which EPA intends to issue test orders/data call-ins in the near future. For 

further information on the status of the EDSP, the policies and procedures, the lists of chemicals, 

future lists, the test guidelines and the Tier 1 screening battery, please visit our website4.

5.0 Dietary Exposure and Risk Assessment 

For this risk assessment, a new drinking water and dietary exposure assessments were not 

required. The most recent dietary assessment is summarized below.

5.1 Residues of Concern Summary and Rationale

The qualitative nature of the residue in plants is understood, based on acceptable apple and 

kiwifruit metabolism studies and supportive grape metabolism data. The residue of concern for 

both tolerance expression and risk assessment is parent forchlorfenuron.

The nature of the residue in livestock and rotational crops has not been determined. Since there 

is no reasonable expectation of finite residues in livestock and there are no rotational crop uses 

since all registered crops are perennials, no additional data are required at this time. However, if 

 

3

See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of chemicals.

4

http://www.epa.gov/endo/
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any future uses are proposed for annual crops or result in significant residues in feedstuffs, 

additional data may be required to determine the residue definition in these matrices. 

HED has determined that the residue of concern in drinking water is parent forchlorfenuron only. 

Table 5.1. Summary of Metabolites and Degradates to be included in the Risk 

Assessment and Tolerance Expression

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Plants

Primary Crop Forchlorfenuron Forchlorfenuron

Rotational Crop Not Determined Not Determined

Livestock

Ruminant Not Determined Not Determined

Poultry Not Determined Not Determined

Drinking Water Forchlorfenuron Not Applicable

5.2 Food Residue Profile

Based on acceptable apple and kiwifruit metabolism studies and supportive grape metabolism 

data, the nature of the residue in plants is adequately understood, and the residue of concern is 

forchlorfenuron. Available metabolism data shows that forchlorfenuron does not significantly 

translocate; therefore, residues from foliar application are likely to be surface residues. 

However, as forchlorfenuron is used at relatively low application rates, the submitted field trial 

studies demonstrate that, among registered crops, quantifiable residues are expected only in the 

following commodities: almond hulls, grape, raisin, and kiwifruit. Sufficient storage stability 

data are available to support the sample storage intervals reported in the magnitude of the residue 

studies. Further, validated analytical methods were used for data collection purposes. As 

forchlorfenuron has been registered for use only on perennial crops, no rotational crop studies 

have been submitted. The only animal feedstuff associated with forchlorfenuron is almond hulls. 

Due to the low dietary burden and limited residue transfer to livestock commodities, there is no 

reasonable expectation of finite residues to livestock (40 CFR §180.6(a)(3)).

5.3 Water Residue Profile

For the chronic dietary analysis, the maximum annual mean chronic estimated drinking water 

concentration (EDWC) value (7.3 μg/L) derived from the PRZM-GW model was used as a point 

estimate to represent chronic drinking water concentration. The EDWC of 7.3 μg/L is a postbreakthrough mean that occurs after 88 years of annual use. This maximum post-breakthrough 

average value was from the WI corn modeled scenario. The PRZM/EXAMS (surface water) 

EDWCs were considerably lower than the PRZM-GW EDWC (groundwater). 
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Table 5.3. Summary of Estimated Surface Water and Groundwater Concentrations for 

Forchlorfenuron.

Scenario Surface Water Conc., ppb a Groundwater Conc., ppb b

Acute 0.6 8.8

Chronic (non-cancer) 0.21 7.3

a From the Tier II PRZM-EXAMS - Index Reservoir model; 34% PCA

b From the Tier I PRZM-GW model.

Source: G. Orrick, D407227, 3/11/13.

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

Tolerances are established for residues of forchlorfenuron in/on grapes at 0.03 ppm; raisins at 

0.06 ppm; kiwifruit at 0.04 ppm; the bushberry subgroup 13-07B at 0.01 ppm; and on almonds, 

sweet cherries, figs, pears, plums and pistachios at 0.01 ppm [40 CFR §180.569(a)]. There are 

no forchlorfenuron tolerances established for animal commodities.

HED has determined that the residues of concern in plants include only the parent compound for 

purposes of both the tolerance expression and risk assessment. No animal commodity tolerances 

are required to support the existing uses for forchlorfenuron.

Tolerance level residues and 100% crop treated was assumed for all existing uses. HED notes 

that the temporary tolerances in or on olive and apple have expired; thus, these commodities 

were not included in the assessment. DEEM (Version 7.81) default processing factors were used 

for dried pears, prune juice, cranberry juice and grape juice. A processing factor was not used 

for raisins because a separate tolerance has been established for that commodity. In addition, a 

processing factor was not used for prunes (dried plums), because data show that residues of 

forchlorfenuron in prunes are not likely to exceed 0.01 ppm, the tolerance established for fresh 

plums. A processing factor was also not used for dried figs, because data show that residues of 

forchlorfenuron in dried figs are not likely to exceed the tolerance for fresh figs (D414083, D. 

Davis, 9/12/13). Lastly, the maximum annual mean groundwater concentration from the PRZMGW model was incorporated into the assessment.

5.4.2 Percent Crop Treated Used in Dietary Assessment

Percent crop treated (%CT) data were not applied to the chronic assessment; 100% CT was 

assumed for all commodities. 

5.4.3 Acute Dietary Risk Assessment

An acute dietary endpoint was not selected, since there were no effects seen in the toxicological 

database that were attributable to a single dose of forchlorfenuron; therefore, quantification of 

acute dietary exposure and risk assessment is not required.
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5.4.4 Chronic Dietary Risk Assessment

HED conducted a Tier 1, screening level chronic dietary (food and drinking water) risk 

assessment. The assessment assumed that all commodities will contain residues of 

forchlorfenuron at the tolerance level. When available, data from processing studies were used 

to estimate residue in processed commodities; however, in the absence of data, DEEM default 

processing factors were incorporated into the assessment. Lastly, the highest modeled estimate 

of the exposure to drinking water concentrations was used in this assessment. Based on the 

conservative inputs into the analysis, it is unlikely that the assessment will underestimate chronic 

dietary risks from the existing uses of forchlorfenuron. 

HED is concerned when dietary risk exceeds 100% of the PAD. The dietary analysis estimates 

the dietary exposure of the U.S. population and various population subgroups. The results are 

reported for the general U.S. Population, all infants (<1 year old), children 1-2, children 3-5, 

children 6-12, youth 13-19, females 13-49, adults 20-49, and adults 50-99 years. 

For forchlorfenuron, the U.S. population and all population subgroups had dietary risk (food and 

drinking water) estimates that were below 1% of the cPAD. The general population had an 

exposure of 0.000175 mg/kg/day. The most highly exposed subpopulation, all infants, had an 

exposure of 0.000447 mg/kg/day. The results of the chronic dietary exposure analysis for all 

subpopulations are summarized in Table 5.4.6. 

5.4.5 Cancer Dietary Risk Assessment

Forchlorfenuron has been classified as not likely to be carcinogenic; therefore, quantification of

cancer dietary exposure and risk assessment is not required.

5.4.6 Summary Table

Table 5.4.6. Summary of Dietary (Food and Drinking Water) Exposure and 

Risk for Forchlorfenuron.

Population Subgroup

Chronic Dietary

Dietary Exposure

(mg/kg/day) % cPAD*

General U.S. Population 0.000175 <1

All Infants (<1 year old)* 0.000447 <1

Children 1-2 years old 0.000346 <1

Children 3-5 years old 0.000261 <1

Children 6-12 years old 0.000165 <1

Youth 13-19 years old 0.000122 <1

Adults 20-49 years old 0.000167 <1

Adults 50-99 years old 0.000168 <1

Females 13-49 years old 0.000167 <1

*The subpopulation(s) with the highest risk estimates. 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization
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6.1 Residential Handler Exposure

There are no registered, non-occupational uses for forchlorfenuron; therefore, a residential 

handler exposure and risk assessment is not required.

6.2 Post-Application Exposure

There are no registered uses for forchlorfenuron which would result in residential (nonoccupational) post-application exposures; therefore, a post-application exposure and risk 

assessment is not required.

6.3 Residential Bystander Post-application Inhalation Exposure

Volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby pesticide applications. The agency sought expert advice and input on issues 

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on 

March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The 

agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). 

During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux 

studies and route-specific inhalation toxicological studies) or further analysis is required for 

forchlorfenuron.

6.4 Spray Drift

Off-target movement of pesticides can occur via many types of pathways, and it is governed by a 

variety of factors. Sprays that are released and do not deposit in the application area end up offtarget and can lead to exposures to those it may directly contact. They can also deposit on 

surfaces where contact with residues can eventually lead to indirect exposures (e.g., children 

playing on lawns where residues have deposited next to treated fields). The potential risk 

estimates from these residues can be calculated using drift modeling onto 50-feet wide lawns 

coupled with methods employed for residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment is based 

on a premise of compliant applications which, by definition, should not result in direct exposures 

to individuals because of existing label language and other regulatory requirements intended to 

prevent them.5 Direct exposures would include inhalation of the spray plume or being sprayed 

directly. Rather, the exposures addressed here are thought to occur indirectly through contact 

with impacted areas, such as residential lawns, when compliant applications are conducted. 

Given this premise, exposures for children (1 to 2 years old) and adults who have contact with 

turf where residues are assumed to have deposited via spray drift, thus resulting in an indirect 

 

5 This approach is consistent with the requirements of the EPA’s Worker Protection Standard.
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exposure, are the focus of this analysis analogous to how exposures to turf products are 

considered in risk assessment. 

In order to evaluate the drift potential and associated risks, an approach based on drift modeling 

coupled with techniques used to evaluate residential uses of pesticides was utilized. Essentially, a 

residential turf assessment based on exposure to deposited residues has been completed to 

address drift from the agricultural applications of forchlorfenuron. In the spray drift scenario, the 

deposited residue value was determined based on the amount of spray drift that may occur at 

varying distances from the edge of the treated field using the AgDrift (v2.1.1) model and the

Residential Exposure Assessment Standard Operating Procedures Addenda 1: Consideration of 

Spray Drift Policy. Once the deposited residue values were determined, the remainder of the 

spray drift assessment was based on the algorithms and input values specified in the recently 

revised (2012) Standard Operating Procedures For Residential Risk Assessment (SOPs). 

A screening approach was developed based on the use of the AgDrift model in situations where 

specific label guidance that defines application parameters is not available.6,7 AgDrift is 

appropriate for use only when applications are made by aircraft, airblast orchard sprayers, and 

groundboom sprayers. When AgDrift was developed, a series of screening values (i.e., the Tier 

1 option) were incorporated into the model and represent each equipment type and use under 

varied conditions. The screening options specifically recommended in this methodology were 

selected because they are plausible and represent a reasonable upper bound level of drift for 

common application methods in agriculture. These screening options are consistent with how 

spray drift is considered in a number of ecological risk assessments and in the process used to 

develop drinking water concentrations used for risk assessment. In all cases, each scenario is to 

be evaluated unless it is not plausible based on the anticipated use pattern (e.g., herbicides are 

not typically applied to tree canopies) or specific label prohibitions (e.g., aerial applications are 

not allowed). Section 6.4.1 provides the screening level drift-related risk estimates. 

In many cases, risks are of concern when the screening level estimates for spray drift are used as 

the basis for the analysis. In order to account for this issue and to provide additional risk 

management options, additional spray drift deposition fractions were also considered. These 

drift estimates represent plausible options for pesticide labels.

6.4.1 Combined Risk Estimates From Lawn Deposition Adjacent to Applications

The spray drift risk estimates are based on an estimated deposited residue concentration, as a 

result of the screening level agricultural application scenarios. Forchlorfenuron is used on 

orchard and field crops and can be applied via groundboom and airblast equipment. The 

recommended drift scenario screening level options are listed below: 

 Groundboom applications are based on the AgDrift option for high boom height and 

using very fine to fine spray type using the 90th percentile results. 

 Orchard airblast applications are based on the AgDrift option for Sparse 

(Young/Dormant) tree canopies.

 

6http://www.agdrift.com/ 

7 Note that for many cases the scenarios outlined in the screening approach represent actual use practice so risk assessors should 

be aware and characterize these appropriately.
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In addition to the screening level spray drift scenarios described above, results are provided 

which represent viable drift reduction technologies (DRTs) that represent potential risk 

management options. In particular, different spray qualities have been considered, as well as the 

impact of other application conditions (e.g., boom height and crop canopy conditions). 

Dermal and incidental oral risk estimates were combined, because the toxicity endpoint for each 

route of exposure is the same. The total applicable Level of Concern is 100, so MOEs < 100 

would be of concern. Children’s (1 to < 2 year old) dermal and incidental oral risk estimates 

from indirect exposure to forchlorfenuron, related to spray drift, result in no buffers for

groundboom or airblast applications.

Exposures were considered for 50 feet wide lawns where the nearest side of the property was 

directly adjoining the treated field (at field edge) and at varied distances up to 300 feet 

downwind of a treated field. Results are presented in Tables 6.4.1 and 6.4.2; no risk estimates of 

concern were identified at field edge or any distance downwind of the treated field. The spray

drift assessment presented below is protective of the use on kiwifruit, which is registered at a 

lower application rate than the scenarios assessed.

Risk estimates from ground boom and airblast applications are not of concern at the field edge 

for all situations considered. Using coarser sprays and lowering boom height for groundboom 

sprayers or applications to denser crop canopies with airblast sprayers lowers risk estimates.
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Table 6.4.1 Adult Risk Estimates (MOEs) Related to Indirect Exposure to Spray Drift for Forchlorfenuron for the Dermal Route of Exposure

Crop/Rate 

Group

Spray Type/ 

Nozzle 

Configuration

Appl. 

Rate 

(lb 

ai/A)

TTR 

(ug/cm2) At Edge 10 Feet 25 Feet 50 Feet 75 Feet 100 Feet 125 Feet 150 Feet 200 Feet 250 Feet 300 Feet

Almond, Cherry, Fig, Pear, Pistachio, Plum/Prune, Grape, Bushberry (Covers use on Kiwifruit)

Groundboom

High Boom Very 

fine to Fine

0.022 0.00245

 

56,000 

 

110,000 

 

190,000 

 

300,000 

 

420,000 

 

520,000 

 

610,000 

 

750,000 

 

950,000 

 

1,300,000 

 

1,500,000 

Low Boom Very fine 

to Fine

 

120,000 

 

330,000 

 

520,000 

 

800,000 

 

1,000,000 

 

1,300,000 

 

1,500,000 

 

1,700,000 

 

2,100,000 

 

2,600,000 

 

3,500,000 

High Boom Fine to 

Medium/Coarse

 

210,000 

 

550,000 

 

800,000 

 

1,200,000 

 

1,500,000 

 

1,700,000 

 

2,100,000 

 

2,100,000 

 

2,600,000 

 

3,500,000 

 

3,500,000 

Low Boom Fine to 

Medium/Coarse

 

320,000 

 

870,000 

 

1,300,000 

 

1,700,000 

 

2,100,000 

 

2,600,000 

 

3,500,000 

 

3,500,000 

 

5,200,000 5,200,000 5,200,000 

Airblast

Sparse 

73,000 

 

130,000 

 

240,000 

 

520,000 

 

950,000 

 

1,500,000 

 

2,300,000 

 

3,300,000 

 

5,800,000 

 

9,500,000 

 

13,000,000 

Normal 

3,500,000 

 

5,200,000 

 

8,000,000 

 

12,000,000 

 

17,000,000 

 

21,000,000 

 

26,000,000 

 

35,000,000 

 

35,000,000 

 

52,000,000 

 

52,000,000 

Dense 

250,000 

 

370,000 

 

600,000 

 

1,000,000 

 

1,600,000 

 

2,100,000 

 

2,700,000 

 

3,300,000 

 

4,500,000 

 

5,800,000 

 

7,000,000 

Vineyard 

1,300,000 

 

2,500,000 

 

4,800,000 

 

8,700,000 

 

13,000,000 

 

17,000,000 

 

21,000,000 

 

26,000,000 

 

35,000,000 

 

52,000,000 

 

52,000,000 
Forchlorfenuron Human Health Risk Assessment DP No. D422527

Page 25 of 40

Table 6.4.2 Children (1<2 years old) Risk Estimates (MOEs) Related to Indirect Exposure to Spray Drift for Forchlorfenuron for the Combined Dermal and Oral Routes of Exposure

Crop/Rate 

Group

Spray Type/ 

Nozzle 

Configuration

Appl. 

Rate 

(lb 

ai/A)

TTR 

(ug/cm2) At Edge 10 Feet 25 Feet 50 Feet 75 Feet 100 Feet 125 Feet 150 Feet 200 Feet 250 Feet 300 Feet

Almond, Cherry, Fig, Pear, Pistachio, Plum/Prune, Grape, Bushberry (Covers use on Kiwifruit)

Groundboom

High Boom 

Very fine to 

Fine

0.022 0.00244

 

32,000 

 

64,000 

 

110,000 

 

170,000 

 

240,000 

 

300,000 

 

350,000 

 

430,000 

 

550,000 

 

750,000 

 

860,000 

Low Boom Very 

fine to Fine

 

71,000 

 

190,000 

 

300,000 

 

460,000 

 

600,000 

 

750,000 

 

860,000 

 

1,000,000 

 

1,200,000 

 

1,500,000 

 

2,000,000 

High Boom Fine 

to 

Medium/Coarse

 

120,000 

 

320,000 

 

460,000 

 

670,000 

 

860,000 

 

1,000,000 

 

1,200,000 

 

1,200,000 

 

1,500,000 

 

2,000,000 

 

2,000,000 

Low Boom Fine 

to 

Medium/Coarse

 

180,000 

 

500,000 

 

750,000 

 

1,000,000 

 

1,200,000 

 

1,500,000 

 

2,000,000 

 

2,000,000 

 

3,000,000 

 

3,000,000 

 

3,000,000 

Airblast

Sparse 

42,000 

 

72,000 

 

140,000 

 

300,000 

 

550,000 

 

880,000 

 

1,300,000 

 

1,900,000 

 

3,300,000 

 

5,500,000 

 

7,500,000 

Normal 

2,000,000 

 

3,000,000 

 

4,600,000 

 

6,700,000 

 

10,000,000 

 

12,000,000 

 

15,000,000 

 

20,000,000 

 

20,000,000 

 

30,000,000 

 

30,000,000 

Dense 

140,000 

 

210,000 

 

340,000 

 

600,000 

 

900,000 

 

1,200,000 

 

1,500,000 

 

1,900,000 

 

2,600,000 

 

3,300,000 

 

4,000,000 

Vineyard 

750,000 

 

1,500,000 

 

2,700,000 

 

5,000,000 

 

7,500,000 

 

10,000,000 

 

12,000,000 

 

15,000,000 

 

20,000,000 

 

30,000,000 

 

30,000,000 
Forchlorfenuron Human Health Risk Assessment DP No. D422527

Page 26 of 40

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (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 and 

duration of exposure.

7.1 Acute Aggregate Risk

An acute endpoint was not selected; therefore, quantification of acute aggregate risk is not 

required.

7.2 Short-Term Aggregate Risk

Since there are no uses for forchlorfenuron that would result in residential (non-occupational) 

exposure, a short-term aggregate risk assessment is not required. 

7.3 Intermediate-Term Aggregate Risk

Since there are no uses for forchlorfenuron that would result in residential (non-occupational) 

exposure, an intermediate-term aggregate risk assessment is not required. 

7.4 Chronic Aggregate Risk

The chronic aggregate risk assessment includes food and water exposure only. The chronic food 

plus drinking water risk estimates are not of concern to HED for the general population and all 

population subgroups. Refer to section 5.4.4 for a detailed discussion of the chronic dietary risk

assessment.

7.5 Cancer Aggregate Risk

Since forchlorfenuron has been classified as not likely to be carcinogenic, quantification of

aggregate cancer risk is not required.

8.0 Cumulative Exposure/Risk Characterization

EPA has followed a cumulative risk approach for other pesticides based on a common 

mechanism of toxicity. EPA has not made a common mechanism of toxicity finding as to 

forchlorfenuron and any other substances. Forchlorfenuron does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed that forchlorfenuron has a common mechanism of toxicity with other 

substances, and a cumulative risk approach is unnecessary. For information regarding EPA’s 

efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the 

cumulative effects of such chemicals, see the policy statements released by EPA’s Office of 
Forchlorfenuron Human Health Risk Assessment DP No. D422527

Page 27 of 40

Pesticide Programs concerning common mechanism determinations and procedures for 

cumulating effects from substances found to have a common mechanism on EPA’s website at 

http://www.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposure/Risk Characterization

An occupational exposure and risk assessment was completed to include all registered uses of 

forchlorfenuron.

9.1 Short-/Intermediate-Term Handler Risk

HED uses the term “handlers” to describe those individuals who are involved in the pesticide 

application process. HED has determined that there are potential exposures to handlers during 

application of forchlorfenuron. Scenarios assessed include mixing/loading wettable powders and 

soluble concentrate formulations for groundboom and airblast applications and applying sprays 

with groundboom and airblast equipment. No chemical-specific data for assessing human 

exposures during pesticide handling activities were submitted to the Agency; therefore, handler 

exposure was assessed using the Pesticide Handlers Exposure Database version 1.1 (PHED 

V.1.1). The forchlorfenuron product labels direct mixers, loaders, applicators and other handlers 

to wear baseline PPE plus chemical-resistant gloves. The occupational handler exposure and risk 

estimates indicate that short- and intermediate-term MOEs are not of concern to HED (i.e., 

MOEs > 100) with label-specified PPE. Total MOEs for the occupational handler assessment 

range from 3,300 to 180,000. While the assessment has been completed for both the short- and 

intermediate-term exposure durations, the 1 application per season make the short-term exposure 

duration risk estimates more probable from a risk management perspective.
Forchlorfenuron Human Health Risk Assessment DP No. D422527

Page 28 of 40

Table 9.1.1. Occupational Handler Short-Term Non-Cancer Exposure and Risk Estimates for Forchlorfenuron. 

Exposure Scenario Crop or 

Target

Dermal Unit 

Exposure (μg/lb 

ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Mitigation Level Mitigation Level Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

Mixer/Loader

SC - Airblast applications Orchard 37.6 – SL/G 0.219 0.03 40 0.000564 180,000 0.00000329 30,000,000 180,000

WP - Airblast applications Orchard 170 – SL/G 43 0.03 40 0.0026 39,000 0.000645 160,000 31,000

SC - Groundboom 

applications Field Crops 37.6 – SL/G 0.219 0.03 80 0.00113 88,000 0.00000658 15,000,000 87,000

WP - Groundboom 

applications Field Crops 170 – SL/G 43 0.03 80 0.005 20,000 0.00129 78,000 16,000

Applicator

Liquid - Airblast 

applications

Orchard 1770 – SL/no G 4.71 – no-R

0.03 40 0.0265 3,300 0.0000706 1,200,000 3,300

Liquid - Groundboom 

applications

Field Crops 78.6 – SL/no-G 0.34 – no-R

0.03 80 0.00236 37,000 0.0000102 8,500,000 37,000

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2012); Level of mitigation: Baseline, PPE, Eng. Controls.

2 Based on registered labels.

3 Exposure Science Advisory Council Policy #9.1.

4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) × DAF (%) ÷ BW (kg).

5 Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW (kg).

7 Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

8 Total MOE = NOAEL (mg/kg/day) ÷ Dermal Dose + Inhalation Dose OR Total MOE = 1 ÷ (1/Dermal MOE + 1/Inhalation MOE).
Forchlorfenuron Human Health Risk Assessment DP No. D422527

Page 29 of 40

Table 9.1.2. Occupational Handler Intermediate-Term Non-Cancer Exposure and Risk Estimates for Forchlorfenuron. 

Exposure Scenario Crop or 

Target

Dermal Unit 

Exposure (μg/lb 

ai)1

Inhalation Unit 

Exposure (μg/lb 

ai)1

Maximum 

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Mitigation Level Mitigation Level Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7 MOE8

Mixer/Loader

SC - Airblast applications Orchard 37.6 – SL/G 0.219 0.03 40 0.000564 150,000 0.00000329 26,000,000 150,000

WP - Airblast applications Orchard 170 – SL/G 43 0.03 40 0.0026 34,000 0.000645 130,000 27,000

SC - Groundboom 

applications

Field Crops 37.6 – SL/G 0.219 0.03 80 0.00113 77,000 0.00000658 13,000,000 77,000

WP - Groundboom 

applications

Field Crops 170 – SL/G 43 0.03 80 0.005 17,000 0.00129 67,000 14,000

Applicator

Spray - Airblast 

applications

Orchard 1770 – SL/no G 4.71 – no-R

0.03 40 0.0265 3,300 0.0000706 1,200,000 3,300

Spray - Groundboom 

applications

Field Crops 78.6 – SL/no-G 0.34 – no-R

0.03 80 0.00236 37,000 0.0000102 8,500,000 37,000

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2012); Level of mitigation: Baseline, PPE, Eng. Controls.

2 Based on registered labels.

3 Exposure Science Advisory Council Policy #9.1.

4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) × DAF (%) ÷ BW (kg).

5 Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW (kg).

7 Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

8 Total MOE = NOAEL (mg/kg/day) ÷ Dermal Dose + Inhalation Dose OR Total MOE = 1 ÷ (1/Dermal MOE + 1/Inhalation MOE).
Forchlorfenuron Human Health Risk Assessment DP No. D422527

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9.2 Short-/Intermediate-Term Post-Application Risk

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.

9.2.1 Dermal Post-Application Risk

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). HED has determined that there are potential exposures to persons entering 

treated sites (e.g., harvesters) after application of forchlorfenuron is complete. Since no postapplication data were submitted in support of this registration action, dermal exposures during 

post-application activities were estimated using (1) dermal transfer coefficients from the Science 

Advisory Council for Exposure Standard Operating Procedure (SOP) Number 3: Agricultural 

Transfer Coefficients, March 2013; (2) the standard assumption that 25 percent of the 

application rate is initially available to dislodge from foliar surfaces; and (3) the standard 

assumption that residues dissipate at a rate of 10 percent per day. The application rate is 0.022 lb 

ai/acre. The results of the post-application occupational exposure and risk assessment indicate 

that risk estimates are not a concern on the day of application (12 hours following the end of the 

application). HED concurs with a 12-hour REI for all crops.

The table below summarizes the occupational post-application risk estimates for the registered

applications of forchlorfenuron. The occupational post-application exposure and risk estimates 

indicate that short- and intermediate-term MOEs are not of concern to HED (i.e., MOEs > 100). 

MOEs for the occupational post-application assessment range from 720 to 200,000. The crops

assessed cover the use on kiwifruit, which has a lower application rate.

Table 9.2.1. Occupational Post-Application Non-Cancer Exposure and Risk Estimates for Forchlorfenuron.

Crop/Site Activities Transfer Coefficient 

(cm2/hr) DFR/TTR1 Dermal Dose (mg/kg/day)2 MOE3

Short-term

Grape Turning/ Girdling 19,300

0.06

0.13807 720

Grape

Tying/ Training / 

Hand harvesting/ 

Leaf pulling

10,100 0.07226 1,400

Grape

Tying/ Training/ 

Hand harvesting/ 

Leaf pulling

5,500 0.03935 2,500

Cherry/ pear/ plum Thinning fruit 3,600 0.02575 3,900

Blueberry/ grape Irrigation 1,900 0.01359 7,400
Forchlorfenuron Human Health Risk Assessment DP No. D422527

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Table 9.2.1. Occupational Post-Application Non-Cancer Exposure and Risk Estimates for Forchlorfenuron.

Crop/Site Activities Transfer Coefficient 

(cm2/hr) DFR/TTR1 Dermal Dose (mg/kg/day)2 MOE3

Short-term

Cherry/plum/pear/fig/ 

blueberry/ pistachio

Hand harvesting/ 

Pollination 1,400 0.01 10,000

Blueberry Hand harvesting/ 

Scouting 1,100 0.00787 13,000

Blueberry/ grape

Scouting/ Hand 

pruning/ Hand 

weeding

640 0.00458 22,000

Cherry/plum/pear/fig/ 

almond/ pistachio

Hand pruning/ 

Scouting/ Training 580 0.00415 24,000

Fig/ almond/ pear/ 

blueberry/ cherry/ 

grape/ pistachio

Transplanting 230 0.00165 61,000

Almond/pistachio Mechanical 

Harvesting 190 0.00136 74,000

Almond/pistachio/ 

cherry/ fig/ pear/ plum 

Orchard 

maintenance/ Hand 

weeding/ Propping

100 0.00072 140,000

Blueberry Hand Weeding/ 

Hand Pruning 70 0.0005 200,000

Intermediate-term

Grape Turning/ Girdling 19,300

0.06

0.12 730

Grape

Tying/ Training / 

Hand harvesting/ 

Leaf pulling

10,100 0.062 1,400

Grape

Tying/ Training/ 

Hand harvesting/ 

Leaf pulling

5,500 0.033 2,500

Cherry/ pear/ plum Thinning fruit 3,600 0.022 3,900

Blueberry/ grape Irrigation 1,900 0.011 7,400

Cherry/plum/pear/fig/ 

blueberry/ pistachio

Hand harvesting/ 

Pollination 1,400 0.008 10,000

Blueberry Hand harvesting/ 

Scouting 1,100 0.00679 13,000

Blueberry/ grape

Scouting/ Hand 

pruning/ Hand 

weeding

640 0.00395 22,000

Cherry/plum/pear/fig/ 

almond/ pistachio

Hand pruning/ 

Scouting/ Training 580 0.00358 24,000

Fig/ almond/ pear/ 

blueberry/ cherry/ 

grape/ pistachio

Transplanting 230 0.00142 61,000

Almond/pistachio Mechanical 

Harvesting 190 0.0012 74,000

Almond/pistachio/ 

cherry/ fig/ pear/ plum 

Orchard 

maintenance/ Hand 

weeding/ Propping

100 0.00062 140,000

Blueberry Hand Weeding/ 

Hand Pruning 70 0.00043 200,000

1 DFR = Application Rate × F × (1-D)t × 4.54E8 μg/lb × 2.47E-8 acre/cm2; where F = 0.25

2 Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (%)]  BW (kg).

3 MOE = POD (mg/kg/day) / Daily Dermal Dose. Daily Dermal Dose = [DFR/TTR (μg/cm2) × TC × 0.001 mg/μg × 8 hrs/day × dermal 

absorption factor (%)]  BW (kg).
Forchlorfenuron Human Health Risk Assessment DP No. D422527

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Restricted Entry Interval

The REI specified on the labels is based on the acute toxicity of forchlorfenuron.

Forchlorfenuron is classified as Toxicity Category III via the dermal route and Toxicity Category 

IV for skin irritation potential. It is not a skin sensitizer. Short- and intermediate-term postapplication risk estimates were not a concern on day 0 (12 hours following application) for all 

post-application activities. Under 40 CFR 156.208 (c) (2) (iii), active ingredient’s classified as 

Acute III or IV for acute dermal, eye irritation and primary skin irritation are assigned a 12-hour 

REI. Therefore, the [156 subpart K] Worker Protection Statement interim REI of 12 hours is 

adequate to protect agricultural workers from post-application exposures to forchlorfenuron. 

9.2.2 Inhalation Post-Application Risk

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for forchlorfenuron at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV), low vapor pressure (3.5 x 10-5torr (25°C)), and the 

low use rate (0.025 lb ai/A). However, there are multiple potential sources of post-application 

inhalation exposure to individuals performing post-application activities in previously treated 

fields. These potential sources include volatilization of pesticides and resuspension of dusts 

and/or particulates that contain pesticides. The Agency sought expert advice and input on issues 

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

Scientific Advisory Panel (SAP) in December 2009 and received the SAP’s final report on 

March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The 

Agency is in the process of evaluating the SAP report, as well as available post-application 

inhalation exposure data generated by the Agricultural Reentry Task Force and may, as 

appropriate, develop policies and procedures to identify the need for and, subsequently, the way 

to incorporate occupational post-application inhalation exposure into the Agency's risk 

assessments. If new policies or procedures are put into place, the Agency may revisit the need 

for a quantitative occupational post-application inhalation exposure assessment for 

forchlorfenuron.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.

10.0 References

Davis, D. 3/11/08. D341628. Forchlorfenuron: Human Health Risk Assessment for Proposed 

Uses on the Bushberry Subgroup 13 B and to Support a Requested Experimental Use Permit on 

Almonds, Sweet Cherries, Figs, Pears, Pistachios and Plums/Prunes. PC Code: 128819, Petition 

No: 7E7228, DP Barcode: D341628.
Forchlorfenuron Human Health Risk Assessment DP No. D422527

Page 33 of 40

Davis, D. 9/12/13. D414083. Forchlorfenuron (CPPU). Petition for the Establishment of 

Permanent Tolerances and Registration for Use on Almond, Cherry (Sweet), Fig, Pear, Pistachio, 

Plum/Prune. Summary of Analytical Chemistry and Residue Data.

Orrick, G. 3/11/13. D407227. Forchlorfenuron: Drinking Water Exposure Assessment for 

Proposed New Uses on Almonds, Sweet Cherries, Figs, Pears, Pistachios, and Plums Including 

Prunes

Lloyd, M. 1/23/13. D407548. Forchlorfenuron (CCPU) - Occupational/Residential 

Exposure/Risk Assessment for the Use of Forchlorfenuron on Figs, Plums, Pears, Sweet 

Cherries, Almonds and Pistachios.

LaMay, A. 2/6/14. D414331. Forchlorfenuron - Chronic Aggregate Dietary (Food and Drinking 

Water) Exposure and Risk Assessment for the Section 3 Registration Action on Almonds, Sweet 

Cherries, Figs, Pears, Pistachios and Plums/Prunes

LaMay, A. 2/6/14. D407226. Forchlorfenuron. Human Health Risk Assessment for Proposed 

Uses on Almond, Sweet Cherry, Fig, Pear, Pistachio and Plum/Prune.
Forchlorfenuron Human Health Risk Assessment DP No. D422527

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Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for food use for forchlorfenuron are in Table 1. Use of the 

new guideline numbers does not imply that the new (1998) guideline protocols were used.

Study Technical

Required Satisfied

870.1100 Acute Oral Toxicity................................................................

870.1200 Acute Dermal Toxicity...........................................................

870.1300 Acute Inhalation Toxicity.......................................................

870.2400 Primary Eye Irritation.............................................................

870.2500 Primary Dermal Irritation.......................................................

870.2600 Dermal Sensitization ..............................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)........................................................

870.3150 Oral Subchronic (nonrodent)..................................................

870.3200 21/28-Day Dermal..................................................................

870.3250 90-Day Dermal.......................................................................

870.3465 90-Day Inhalation...................................................................

yes

yes

yes

no

CR

yes

yes

---

A

---

---

A

870.3700a Developmental Toxicity (rodent) ............................................

870.3700b Developmental Toxicity (nonrodent) ......................................

870.3800 Reproduction...........................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)........................................................

870.4100b Chronic Toxicity (nonrodent)..................................................

870.4200a Oncogenicity (rat)....................................................................

870.4200b Oncogenicity (mouse) .............................................................

870.4300 Chronic/Oncogenicity .............................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial..............................

870.5300 Mutagenicity—Gene Mutation - mammalian.........................

870.5375 Mutagenicity—Structural Chromosomal Aberrations............

870.5395 Mutagenicity—Other Genotoxic Effects................................

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotox. (hen)...............................................

870.6100b 90-Day Neurotoxicity (hen) ....................................................

870.6200a Acute Neurotox. Screening Battery (rat) .................................

870.6200b 90 Day Neurotox. Screening Battery (rat)...............................

870.6300 Develop. Neurotoxicity ...........................................................

no

no

yes

yes

CR

---

---

---

A

---

A

---

870.7485 General Metabolism ...............................................................

870.7600 Dermal Penetration.................................................................

870.7800 Immunotoxicity......................................................

yes

CR

yes

yes

---

---

B

Non guideline Thyroid MOA Investigation Study no ---

A Waived by HASPOC (TXR# 0056596)

B Waived by HASPOC (TXR# 0056795)
Forchlorfenuron Human Health Risk Assessment DP No. D422527

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A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Profile - Forchlorfenuron

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral [rat] 44394609 LD50 (mg/kg) = 

M = 4904

F = 4899

III

870.1200 Acute dermal [rabbit] 44394611 LD50 (mg/kg) = 

>2000

III

870.1300 Acute inhalation [rat] 44394608 LC50 (mg/L) = 

>3.0

IV

870.2400 Acute eye irritation [rabbit] 44394607 Mild eye irritant III

870.2500 Acute dermal irritation [rabbit] 44394610 Non-irritant IV

870.2600 Skin sensitization [guinea pig] 44394606 Non-sensitizer -

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – Forchlorfenuron

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3100 90-Day oral 

toxicity (Fischer

344 rats)

44394614 (1987)

Acceptable/Guideline

0, 200, 1000, 5000 ppm

M: 0, 16, 79, 400

mg/kg/day

F: 0, 17, 84, 428 mg/kg/day

NOAEL =  400 (male)

LOAEL = no adverse effects observed (male)

NOAEL = 84 mg/kg/day (female)

LOAEL = 428 mg/kg/day (female), based on 

decreased body weight, body weight gain, and

food efficiency

870.3150 Subchronic oral

toxicity 

(Beagle dog)

44394615 (1987/1993)

Acceptable/Guideline

0, 50, 500, 5000 ppm

M: 0, 1.8, 16.8, 162.4 

mg/kg/day

F: 0, 1.8, 19.1, 188.7 

mg/kg/day

NOAEL = 16.8/19.1 mg/kg/day (male/female)

LOAEL = 162.4/188.7 mg/kg/day 

(male/female), based on decreases ( 10%) in 

body weight gain, food consumption, and food 

efficiency

870.3700a Developmental 

toxicity

(Sprague Dawley 

Crl:CD®BR rat)

(GD 6-15)

44394612 (1986)

45840123 (2002)

Acceptable/Guideline

0, 100, 200, 400 mg/kg/day

45840113 (2002)

analytical information

Maternal NOAEL = 200 mg/kg/day

Maternal LOAEL = 400 mg/kg/day, based on 

death of one dam, increased incidence of 

alopecia; significantly decreased body weight

(BW) and body weight gains

Developmental NOAEL = 200 mg/kg/day

Developmental LOAEL = 400 mg/kg/day, 

based on decreased mean fetal BW and a slight 

increase in the incidence of delayed ossification 

of the sternebrae
Forchlorfenuron Human Health Risk Assessment DP No. D422527

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – Forchlorfenuron

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3700b Prenatal 

developmental in 

(New Zealand 

White rabbit)

GD 6-18

44394613 (1986)

45840122 (2002)

Acceptable/Guideline

0, 25, 50, 100 mg/kg/day

44359526 (1985) - range 

finding

0, 125, 250, 500, 1000 

mg/kg/day

45840113 (2002)

analytical information

Maternal NOAEL = 100 mg/kg/day

Maternal LOAEL not determined

Developmental NOAEL = 100 mg/kg/day

Developmental LOAEL not determined

870.3800 Reproduction and 

fertility effects

(Sprague Dawley 

Crl:CD®BR rat)

44394616 (1997)

Acceptable/Guideline

0, 150, 2000, 7500 ppm

F0M: 0, 11, 144, 544 

mg/kg/day

F0F: 0, 13, 169, 701 

mg/kg/day

F1M: 0, 13, 168, 829 

mg/kg/day 

F1F: 0, 15, 202, 926 

mg/kg/day

Parental NOAEL = 11 mg/kg/day.

Parental LOAEL = 144 mg/kg/day, based on 

decreased food consumption (F0 & F1 males), 

clinical signs of toxicity [dried tan or yellow 

staining around the anogenital, urogenital, and 

abdominal areas; brown staining the entire 

length of the tail (both sexes); an unkempt 

appearance and pale extremities (F0 females), 

and dried red material around the nose (F0 and 

F1 females)], and lower BW in F1 males and 

females

At highest dose tested (HDT), decreased body 

weight and kidney lesions (suppurative 

inflammation in F0 rats; suppurative 

pyelonephritis in F1 rats)

Reproductive NOAEL = 7500 ppm (544/701 

mg/kg/day (HDT).

Reproductive LOAEL not determined.

Offspring NOAEL = 11 mg/kg/day

Offspring LOAEL = 144 mg/kg/day based on

growth retardation in F1 and F2 pups.

At HDT, increased pup mortality (F1a, F1b & 

F2a), growth retardation in F1b, and decrease in 

F2 pups/litter

870.4100b Chronic toxicity 

(dog)

45840105 (1998)

Acceptable/Guideline

0, 150, 3000, 7500 ppm

M: 0, 5, 87, 195 mg/kg/day

F: 0, 5, 91, 246 mg/kg/day

NOAEL = 87/91 mg/kg/day (male/female)

LOAEL = 195/246 mg/kg/day (male/female), 

based on decreases in BW, BW gains, and FC
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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – Forchlorfenuron

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.4200 Carcinogenicity 

(Crl:CD-1®(ICR) 

BR mouse)

45840106 (2002)

Acceptable/Guideline

M: 0, 10, 991.4 mg/kg/day 

F: 0, 9.9, 1001.8 mg/kg/day 

NOAEL = 10.0/9.9 mg/kg/day (male/female)

LOAEL = 991.4/1001.8 mg/kg/day 

(male/female), based on decreases in body 

weight and body weight gains (both sexes)

no evidence of carcinogenicity

870.4300 Combined 

Chronic Toxicity/

Carcinogenicity

(Crl:CD®BR rats)

44394617 (1996)

Acceptable/Guideline

0, 150, 2000, 7500 ppm

M: 0, 7, 93, 352 mg/kg/day

F: 0, 9, 122, 518 mg/kg/day

NOAEL= 7/9 mg/kg/day (male/female)

LOAEL= 93/122 mg/kg/day (male/female), 

based on reduced BW, BW gain, and food 

consumption; kidney toxicity (suppurative 

inflammation in males; non-suppurative 

interstitial nephritis in females)

no evidence of carcinogenicity

870.5100 Salmonella/

mammalian 

activation gene 

mutation assay

44394621 (1985)

Acceptable/Guideline

10-1000 g/plate +S9

2-200 g/plate -S9

Evidence of induced mutant colonies over 

background in tester strain TA1535 in absence 

of S9 (repeat of MRID 44394620).

There is no evidence of reproductive effects (no 

decrease in fertility; no increase in dead 

implants/fetuses) to suggest a genetic 

component

870.5100 Salmonella/

mammalian 

activation gene 

mutation assay

44394620 (1985)

Acceptable/Guideline

10-1000 g/plate +S9

2-200 g/plate -S9

Evidence of a positive response in tester strain 

TA1535 in absence of S9 at 50, 100, and 200 

g/plate; negative ± S9 at all other doses and 

strains (see above)

870.5375 In vitro 

mammalian 

chromosome 

aberration test in 

Chinese Hamster 

CHO-KI cells

44394618 (1985)

Acceptable/Guideline

10, 20, 40, and 80 g/mL ± 

S9 activation

No increase in chromosomal aberrations over 

background ± S9

870.5550 Unscheduled DNA 

synthesis in 

mammalian cell 

cultures (primary 

rat hepatocytes)

44394619 (1985)

Acceptable/Guideline

0.1 to 60 g/mL

Negative for induction of unscheduled DNA 

synthesis
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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile – Forchlorfenuron

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.7485 Metabolism and 

pharmacokinetics

(Sprague Dawley 

rat)

MRID 45840107 (2002)

Acceptable/Guideline

100 mg/kg (acute)

Forchlorfenuron is rapidly and almost entirely 

absorbed and metabolized, tissue residues are 

minimal, and excretion is almost complete. 

Overall recovery was 97%. The majority of the 

dose was recovered in the urine within 24 hours 

(62-74% dose). Fecal excretion accounted for 

16-28% dose, and 20-23% of the dose was 

found in the bile. At 168 hours post-dose, the 

highest concentrations of radioactivity were 

found in the kidney and liver. The elimination 

half-life was 13.1-16.2 hours. There were no 

sex-related differences.

The metabolism of forchlorfenuron in rats 

includes conjugation with sulfate at the phenyl 

ring (major pathway) before or after 

hydroxylation of the phenyl ring, hydroxylation 

of the phenyl ring (major pathway), 

conjugation with glucuronide at the phenyl 

ring, methylation of the hydroxy group of 

hydroxyl CPPU-sulfate, and hydroxylation of 

both the chloropyridinyl and phenyl rings. 
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Appendix B. Forchlorfenuron International Residue Limits Table

Table B.1 Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

40 CFR 180.569:

Plant: forchlorfenuron (N-(2-chloro-4-

pyridinyl)-N'-phenylurea)

None None

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex

Almond 0.01

Almond, hulls 0.15

Bushberry subgroup 13-07B 0.01

Cherry, sweet 0.01

Fig 0.01

Grape 0.03

Grape, raisin 0.06

Kiwifruit 0.04

Pear 0.01

Pistachio 0.01

Plum, prune, fresh 0.01

Completed: M. Negussie; 11/17/14

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.
Forchlorfenuron Human Health Risk Assessment DP No. D422527

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Appendix C. Review of Human Research

Human Studies Review

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 data, which include studies from 

PHED 1.1; the AHETF database; the Outdoor Residential Exposure Task Force (ORETF) 

database; and the ARTF database; are (1) subject to ethics review pursuant to 40 CFR 26, (2) 

have received that review, and (3) are compliant with applicable ethics requirements. For certain 

studies, the ethics review may have included review by the Human Studies Review Board. 

Descriptions of data sources, as well as guidance on their use, can be found at the Agency 

website8. 

 

8 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html