UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: JO June 2015 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Ipconazole - Health Effects Draft Risk Assessment in Support of Registration 

Review 

PC Code: 125618 

Decision No.: NA 

Petition No.: NA 

Risk Assessment Type: Single-Chemical Aggregate 

TXR No.: None 

MRIDNo.: NA 

FROM: Michael A. Doherty, Ph.D., Senior Chemist 

Risk Assessment Branch 11 

Health Effects Division (7509P) 

THROUGH: Christina Swartz, Branch Chief 

Risk Assessment Branch II 

Health Effects Division (7509P) 

TO: Brittany Pruitt/Tracy Perry/Kelly Sherman 

DP Barcode: D427364 

Registration No.: Multiple 

Regulatory Action: Registration Review 

Case No.: 7041 

CAS No.: 125225-28-7 

40 CFR: 180.646 

~~ 

Risk Management and Implementation Branch 3 

Pesticide Reevaluation Division (7508P) 

Page I of5 
Executive Summary 

lpconazole is a triazole-derivative fungicide and is currently registered only for seed-treatment 

use on numerous crops. These uses are considered to be "non-food uses" for root and tuber 

vegetables (Crop Group 1 ), leafy vegetables (non-Brassica and Brassica; Crop Groups 4 and 5), 

cucurbit vegetables (Crop Group 9), sorghum, sunflower, canola, rape, mustard, and corn (field, 

pop and sweet). Tolerances at the limit of quantitation (LOQ, 0.0 l ppm) have been established to 

support food uses on cotton, cereal grains (Crop Group 15) except rice, peanuts, and legume 

vegetables (Crop Group 6). 

The Health Effects Division has conducted three risk assessments for ipconazole. The most 

recent assessment was conducted in 2013 [M. Doherty, 0413830, 8 August 2013; with an 

addendum dated 16 January 201 4 (M. Doherty, 0417425)). 

The toxicology and residue chemistry databases for ipconazole are complete for purposes of 

assessing risk under the Food Quality Protection Act of 1996 (FQPA). Although the toxicology 

database lacks an immunotoxicity study, this is not considered to be a data gap because the 

Office's Hazard and Science Policy Council (HASPOC) waived the requirement for this study 

for all conazole compounds (U. Habiba, TXR No. 56730, 8 January 2014). All residue chemistry 

data gaps identified in previous assessments have been fulfilled (M. Doherty, D369458, 31 

March 2011 ). 

Ipconazole shows low acute toxicity via the oral, dermal, and inhalation routes of exposure, and 

causes low to mild irritation to the eyes and skin. Subchronic and chronic studi es show the liver 

to be the primary target organ for ipconazole. For risk assessment, acute dietary exposures to 

women of child-bearing age have been assessed based on visceral and skeletal variations 

observed in rats and skeletal variations and malformations observed in rabbits. Acute dietary 

assessments for other population groups have not been conducted due to the Jack of an 

appropriate endpoint. Chronic dietary assessments have been based on skin reddening and 

decreased body weight gain (females only) observed in dogs. Dermal and inhalation risk 

assessments have been based on route-specific studies. In the case of dermal exposure, the 

endpoints have been decreased body weight, body weight gain, and food consumption as well as 

increased dermal irritation. Inhalation exposure endpoints are portal-of-entry specific and include 

hyperplasia in the hard palate and larynx mucosa, and mixed inflammatory cells in the trachea. 

The 2013 dietary exposure and risk estimates were derived using screening-level assumptions 

(tolerance-level residues, I 00% crop treated) and 2003-2008 food consumption data. The dietary 

risk estimates were less than I% of the population-adjusted dose (PAD) for both acute and 

chronic exposures for all population groups. Therefore, HED confirms its previous conclusion 

that dietary risk estimates for ipconazole are below our level of concern. 

HED has not assessed residential exposure and risk for ipconazole. Although ipconazole is 

registered for use on turf, it is as a seed-treatment use and is not expected to result in residential 

exposures. Consequently, aggregate exposure and risk estimates are equivalent to the dietary 

estimates and are below HED's level of concern for all population groups and scenarios. 

Page 2 of 5 
The 2013 occupational exposure and risk estimates were based on a personal protective 

equipment (PPE) level of baseline clothing (long sleeve shirt, pants, socks and shoes)+ gloves. 

Furthermore, the 2013 assessment used the most current transfer coefficients and policies with 

respect to seed-treatment assessment. Occupational margins of exposure ranged from 41 ,000 to 

140,000 for dermal exposure and from 2,000 to 20,000 for inhalation exposure. The levels of 

concern for occupational exposure are I 00 for dermal exposure and 300 for inhalation exposure; 

therefore, HED confirms its previous conclusion that all occupational risk estimates are not of 

concern. The restricted entry interval (REI) on the labels for ipconazole is supported by the acute 

toxicity categories. 

Given that the most recent risk assessment for ipconazole reflects current risk assessment 

policies and methodologies, there are no data gaps for the chemical, and there are no risks of 

concern or incident data that would warrant the need for mitigation, HED is principally relying 

on its 2013 assessment in making its findings for ipconazole under registration review. 

Endocrine disruption, which was not addressed in the 2013 assessment, and spray 

drift/volatilization, which is somewhat revised, are presented below. 

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 

taxonomic groups. As part of its most recent registration decision for ipconazole, 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), ipconazole 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 I 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, 

Page 3 of5 
which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals 

identified for EDSP screening was published on June 14, 2013 1 and includes some pesticides 

scheduled for Registration Review and chemicals found in water. 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 website.2 

Spray Drift and Volatilization 

All of the currently registered uses of ipconazole are as a seed treatment; therefore, spray drift is 

not a concern. Similarly, post-application inhalation exposure due to volatilization is expected to 

be negligible. Seed treatment assessments provide quantitative inhalation exposure assessments 

for seed treaters and secondary handlers (i.e., planters). It is expected that those exposure 

estimates are protective of any potential low-level post-application inhalation exposure that 

could result from these types of applications. 

Review of Human Incident Data 

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

Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event 

Notification System for Occupational Risk-Pesticides (SENSOR) database, and by the National 

Pesticide Information Center (NPIC) database were consulted for pesticide incident data on the 

active ingredient ipconazole (pc code: 125618). The purpose of the database search is to identify 

potential patterns in the frequency and severity of the health effects attributed to ipconazole 

exposure. lpconazole is not included in the AHS, and therefore this study does not provide 

information for this report. 

Based on the low frequency and low severity of incident cases reported for ipconazole in IDS, 

SENSOR-Pesticides, and NPIC, 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. 

References 

Doherty, M. D369458. 3 1 March 2011. Ipconazole - Evaluation of Conditional Residue 

Chemistry Data Submitted in Support of New Seed Treatment Uses on Cotton, Peanut, 

Soybean, Cereal Grains (Except Rice), and Dry Shelled Pea and Bean. 

Doherty, M. D413830. 8 August 2013. Revised lpconazole Human Health Risk Assessment of 

the Proposed Use on Legume Vegetables (Crop Group 6) 

Doherty, M. D417425. 16 January 2014. Addendum to the Revised Ipconazole Human Health 

Risk Assessment of the Proposed Use on Legume Vegetables (Crop Group 6) 

1 See h11p://\\\\ w.regula1ions.gov/#!documentDe1ail;D=EPA-HQ-OPPT-2009-0-l77-0074 for the final second list of 

chemicals. 2 http://w"" .epa.gov cndo1 

Page 4 of5 
Habiba, U. TXR No. 56730. 8 January 2014. CONAZOLE FUNGICIDES: Summary of Hazard 

and Science Policy Council (HASPOC) Meeting on July 25, 2013: Recommendations on 

Data Requirement for lmmunotoxicity Studies for Conazole Pesticides. 

Recore, S. D427368. June 2015. Ipconazole: Tier I (Scoping) Review of Human Incidents 

Page 5 of5