UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

MEMORANDUM 

Date: September 15, 20 15 

SUB.JECT: Difenoconazolc: Tier I (Scoping) Review of Human Incidents and Epidemiology 

PC Code: 128847 DP Ba r codc: 04290&1 

Decisio n No.: 50897 1 

Petition No.: NA 

Ris k Assessment Type: A 

T XR No.: 'A 

HUD No.: , A 

Registration 'o.: NA 

Regulatory Action: NA 

Case No.: NA 

CAS o.: I 19 .. 46-68-3 

-'O CFR: t A 

Vcr.Apr.08 

FROM: Shanna Recore, industrial Hygienist O " °' f\, , 

Toxicol

Health Effec

ogy and 

t Divi

Ep

s

id

ion 

emio

(7509P) 

logy Branch ~ ~ 

, 

El izabeth 

and 

Evans, Environmental Protection Specialist <"'~~~ ~ 

Toxicology and Epidemiology Branch ,, U --- - Health Effects Division (7509P) 

THROUGH: David Miller, Acting Branch hi ~,_//t;!l.l_ )<J'J '1.ai~tkj Toxicology and Epidemiology Branch /-17 () /) 

TO: 

Health Effects Division (7509P) 

lvan Nieves. Risk Assessor 

Risk Assessment Branch IV 

Health Effects Division (7509P) 

and 

Ke ll y Ballard, Chemical Review Manager 

Risk Management & Implementation Branch 1 

Pesticide Re-evaluation Division (7508P) 

Summary and Conclusio ns 

Based on the low frequency and severity of incident cases reported for di fenoconazole in both 

I OS and SE SOR-Pesticides there does not appear to be a concern at this time that would 

warrant further in vestigatio n. The Agency will continue to monitor the incident inforn1ation and 

if a concern is triggered, additio nal analysis will be included in the risk assessment. 

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Detailed Review 

I. ACTION REQUESTED 

This review is intended to fulfill our requirement to docket summaries of incident data that were 

reported to the Agency, as we ll as to ensure human incident data and the Agricultural Health 

Study (A HS) are part of the problem formulation phase of registration review. Reports of 

adverse health effects allegedly due to a specific pesticide exposure (i.e .. an " incident") arc 

largely sci f-reported and therefore, generally speaking, neither exposure to a pesticide or 

reported symptom (or the connection between the t\·VO) is validated or otherwise confirmed. 

Typically, causation cannot be determined based on incident data. However, incident 

information can be an important source of feedback to the Agency: incidents of severe outcome, 

or a suggested pattern or trend among less severe incidents, can signal the Agency to further 

investigate a particular chemical or product. Observational epidemiology studies relate the risk 

of disease, e.g. , cancer, and exposure to an agent such as a pesticide product in the general 

population or specific sub-groups like pesticide applicators. 

II. BACKGROUN D 

Difenoconazole is a broad spectrum fungicide belonging to the triazolc group of fungicides. ll is 

currently registered for use as a seed treatment on a number of cereal grain crops, cotton, potato 

seed pieces and canola and for foliar application to numerous food crops and ornamentals and for 

post-harvest use on tuberous and corm vegetables subgroup IC. Difenoconazole acts by 

blocking demethylation during sterol biosynthesis which, in turn, disrupts membrane synthesis. 

Difenoconazole is available as emulsifiable concentrate, soluble concentrate, emulsion [oil) in 

water, flowable suspension, and ready-to-use formulations. As a seed treatment, it is applied 

with commercial grade seed treatment equipment. As a foliar treatment, it is applied to field and 

vegetable crops, landscape ornamentals and golf course turf by commercial applicators using 

aerial and ground application methods and equipment. It is applied to ornamentals by residential 

applicators using hand held sprayers. 

For this evaluation, both the OPP Incident Data System (IDS) and the Centers for Disease 

Control and Prevention/National Institute for Occupational Safety and Health (CDC IOSH) 

Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR) databases were 

consulted for pesticide incident data on the active ingredient difenoconazole (pc code: 128847). 

The purpose of the database search is to identify potential patterns in the frequency and severity 

of the health effects attributed to difenoconazole exposure. Difenoconazole is not included in the 

AHS, and therefore this study does not provide information for this report. 

III. RESULTS/DISCUSSION 

a. IDS (Incident Data System) 

OPP's IDS includes reports of alleged human health incidents from various sources, including 

mandatory Federal Insecticide, f-ungicide and Rodenticide Act (FIFRA) Section 6(a)(2) reports 

from registrants, other federal and state health and environmental agencies, and individual 

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consumers. Since 1992, OPP has compiled these reports in IDS. IDS contains reports from 

across the U.S. and most incidents have all relevant product information recorded. Reports 

submitted to the IDS represent anecdotal reports or allegations only, unless otherwise stated in 

the report. 

IDS records incidents in one of two modules: Main IDS and Aggregate IDS: 

o Main IDS contains incidents resulting in higher severity outcomes and provides 

more deta il with regard to case specifics. This system stores incident data for 

death, major and moderate incidents, and it includes informat ion about the 

location, date and nature of the incident. Main IDS incidents involving only one 

active ingredient (as opposed to pesticide products with multiple active 

ingredients) are considered to provide more certain information about the 

potential effects of exposure from the pesticide. 

o Aggregate IDS contains incidents resulting in less severe human incidents (minor. 

unknown. or no effects outcomes). These are reported by registrants only as 

counts in what are aggregate summaries. 

For the Main IDS, from January 1, 2010 to May 27, 2015, there were 0 incidents reported for the 

single chemical difenoconazole only in the database. There were 6 incidents reported involving 

more than one chemical. Five of these incidents were classified as moderate severity and one 

was classified as minor severity. 

In Aggregate IDS. from .J anuary 1, 2010 to May 27, 20 15, there were 14 incidents reported 

involving difenoconazole. These incidents were classified as minor severity. Overall. there arc 

few incidents reported to IDS involving difenoconazole. 

b. SENSOR-Pesticides 

The SENSOR-Pesticides database covers 12 states from 1998-20 11 , although reporting varies 

from state to state. Cases of pesticide-related i II nesses are ascertained from a vari ety of sources, 

including: reports from local Poison Control Centers, state Department of Labor workers' 

compensation claims when reported by physicians, reports from State Departments of 

Agriculture, and physician reports to state Departments of Health. Although both occupational 

and non-occupational incidents are included in the database, SENSOR-Pesticides focuses on 

occupational pesticide incidents, and is of particular value in providing that infom1ation. The 

state coordinator at each of the 12 respective state Departments of Health conducts case followup activities such as obta ining medical records to verify symptoms and severity. Using 

standardized protocol and case definitions derived from poison center reporting, the state 

SENSOR-Pesticide coordinator enters the incident information into the state-based system which 

is sent to N IOSH annually to be aggregated. 

A query of SENSOR-Pesticides 1998-2011 identifies one case involving difenoconazole ~ 

code 12884 7). This case involved multipl e active ingredients and was low in severity. This case 

was reported in 1999. 

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c. Agricultural Health Study (AHS) 

The AHS is a high quality, prospective epidemiology study evaluating the link between pesticide 

use and various health outcomes including cancer. The AHS includes private and commercial 

pesti cide applicators and their spouses. If there are AH S findings relevant to a particular 

pesticide going through registration review, the Agency will ensure they are considered in the 

problem formulation/scoping phase of the process and, if appropriate. fully reviewed in the risk 

assessment phase of the process. The Al IS includes information on use of 80 different pesticide 

acti ve ingredients commonly used in agriculture. Difenoconazole is not included in the Al IS, 

and therefore this study docs not provide information for this report. 

IV. CONCLUSION 

Based on the low frequency and severity of incident cases reported for difenoconazole in both 

IDS and SENSOR-Pesticides there does not appear to be a concern at this time that would 

warrant further investigation. The Agency will continue to monitor the incident information and 

if a concern is triggered, additional analysis will be included in the risk assessment. 

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