UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

MEMORANDUM 

Date: 1211 5/201 5 

SUBJECT : Uniconazole-P. Human Health Assessment Seeping Document in Support of 

Registration Review 

FROM: 

THROUGH: 

TO: 

PC Code: 138976 

Decision No.: 508172 

Petition No.: NA 

Risk Assessment Type: NA 

TXRNo.: NA 

MRID No.: NA 

DP Bar code: 0428794 

Registr ation No.: RegRev-7007-l 

Regulatory Action: Registration Review 

Case No.: 7007 

CAS No.: 83657- 17-4 

40 CFR: § 180.643 

Za

Jaim

ida 

e 

Figu

D' Agos

eroa

tin

, DrP

o, Ph

H, 

.D.

ndy

, Tox

~ie

icologist ~ 

t ...... --: !: " / / 

Ri

Wi

s

ll

k 

i

Assess

am Drew

me

, C

nt 

h

Branch 

emist 

II 

WI~ v 

...,. 

fiV ~ 

Health Effects Division (7509P) 

Office of Pesticide Programs - a \ A ~ 

Christina Swartz, Branch ~ ~ C"2.--

Risk Assessment Branch II \ ~ J 

Jess Rowland, Deputy Division Direc tor ~ ;:)A A ... J ___ Jeff Dawson, Acting Deputy Division DirectorTtf'lv--

Health Effects Division (7509P) 

Office of Pesticide Programs 

Susan Bartow, Chemical Review Manager 

Kevin Costello, Branch Chief 

Risk Management and Implementation Branch IV (RMIB IV) 

Pesticide Re-Evaluation Division (7508P) 

Office of Pesticide Programs 

Attached is the Health Effects Division's (HED) human health risk assessment seeping document for 

uniconazole-P to support registration review. 

Page 1 of 23 
Executive Summary 

The Health Effects Division (HEO) uniconazole-P Registration Review Team has evaluated the 

database and the most recent human health risk assessment for uniconazole-P. HED performed 

this evaluation in order to determine the scope of work necessary to support the established 

tolerances and existing registrations during registration review. The primary source of 

information for this evaluation was the most recent human health risk assessment (0 346558; E. 

Scollon; 3/3 1/2008). 

Uniconazole, (E)-(RS)- 1-( 4-chlorophenyl)-4,4-dimethyl-2-( lf/-1 ,2,4-triazol-1-yl)pent-l-en-3-ol, 

is a triazole Group 3 fungicide and plant growth regulator. The resolved S-isomer, identified as 

uniconazole-P, is the active pesticidal ingredient and is the active ingredient in registered end-use 

products. The technicaluniconazole-P product contains about 80% of the S-isomer and 20% of 

the R-isomer. Uniconazole-P reduces plant height by reducing internode elongation through 

inhibition of gibberellin biosynthesis. Uniconazole-P is registered for use in greenhouses on 

ornamental plants and fruiting vegetables (Crop Group 8) transplants, including eggplant, 

groundcherry, pepino, pepper, tomatillo, and tomato. Uniconazole-P is formulated as a 0.055% 

emulsifiable concentrate. The product is specified for use in commercial greenhouses, 

lathhouses, and shadehouses as a foliar spray or ground-directed applications using handheld 

equipment. 

The toxicology database for uniconazole-P is complete and no additional toxi city studies are 

required. HED's Hazard and Science Policy Council (HASPOC) determined that a subchronic 

inhalation study, acute neurotoxicity battery, and subchronic neurotoxicity battery are not 

required for uniconazole-P (U. Habiba; TXR#00572 12; 10/20/2015). Previously, an acute dietary 

risk assessment was conducted for the females 13-49 subpopulation onl y; however, further 

review of the toxicity database indicate that an acute dietary risk assessment for the general 

population should be conducted. 

The target organ for uniconazolc-P is the liver regardless of the route of exposure. There was no 

evidence of quantitative or qualitative susceptibility in the developmental rat/rabbit studies or the 

reproductive rat toxicity study. The only potential evidence of neurotoxicity was clinical signs 

that occurred at doses higher than those that caused liver toxicity. Therefore, based on the 

completeness of the database, the lack of susceptibility, the lack of concern for potential 

deve lopmental neurotoxicity, and the protective assumptions used in the exposure assessment, 

the required I Ox Food Quality Protection Act (FQPA) Safety Factor is reduced to I x. 

The residue chemistry database for uniconazole-P is complete. The metabolism of uniconazolep in crops is adequately understood. There are no significant livestock feedstuffs assoc iated with 

the use on fruiting vegetables (crop group 8). Therefore, no livestock metabolism data, 

enforcement methods, storage stability data, nor feeding studies were submitted. Adequate 

enforcement methods are available for determining residues in fruiting vegetable commodities. 

The tolerance expression (as stated in 40CFR § 180.643[a]) is not in accordance with cunent 

guidance, as it does not contain the appropriate coverage and compliance statements; it should be 

revised during registration review to comply with HED's interim guidance on tolerance 

expressions (S. Knizner, 5/27/2009). There are no Codex maximum residue limits (MRLs) 

Page 2 of 23 
established for uniconazole. Therefore, there are no harmonization issues with regard to Codex. 

The US tolerance in crop group 8 (0.0 l ppm) is harmonized with the Canadian MRL in the 

tomato subgroup 8-09A (0.0 1 mg/kg). 

HED will conduct a new dietary risk assessment during registration review, to incorporate a new 

acute endpoint and point of departure for the general US population. Any updated assessment 

will include the Environmental Fate and Effects Division (EFED) revised estimated drinking 

water concentrations (EDWCs), if applicable. 

There are no residential uses currently registered for uniconazole-P; therefore, a quantitative 

residential exposure/risk assessment will not be needed to support Registration Review. Based 

on the currently registered use pattern ofuniconazole-P (i.e., commercial greenhouses, 

lathhouses and shadehouses), the Agency is not expecting residential exposure from spray drift. 

The need for a volatilization risk assessment for uniconazole may be examined during 

Registration Review. 

The occupational exposure database is adequate to support the registration review process for 

uniconazole-P. The most recent occupational handler and post-application exposure assessments 

are not reflective of current exposure policies, but did not identify risks of concern. During 

registration review, updated occupational handler and post-application exposure assessments will 

be conducted to reflect all the registered uses using current occupational exposure policies. 

Introduction 

Uniconazole, (£)-(RS)-1-( 4-chlorophenyl)-4,4-dimethyl-2-( I H-l ,2,4-triazol-1-yl)pent-l-en-3-ol, 

is a triazole Group 3 fungicide and plant growth regul ator. The resolved S-isomer, identified as 

uniconazole-P, is the active pesticidal ingredient and is the acti ve ingredient in registered end-use 

products. The technical uniconazole-P product contains about 80% of the S-isomer and 20% of 

the R-isomer. 

HED evaluated the most recent human health risk assessment for uniconazole-P in association 

with updates to its toxicity, exposure, and usage databases to determine if sufficient data are 

avai lable, and if further updates are needed, to support registration review. The most recent 

human hea lth risk assessment was performed in 2008 when HED evaluated a request for a new 

use on Fruiting Vegetables Crop Group 8 (Except Cucurbits) (D346558; E. Scollon; 3/3112008). 

Tolerances for uniconazole-P are established in 40 CFR § 180.643. In fruiting vegetables, the 

tolerance is established, in terms of uni conazole-P, its R-enantiomer and its Z-isomer, at 0.01 

ppm. The tolerances were set based on the LOQ of the detection method since there were no 

quantifiable residues in peppers grown from treated transplants. 

The structure, the chemical names, and other identifiers can be found in the chemical identity 

table in Attachment l. 

Hazard ldentificationffoxicology 

Page 3 of23 
Uniconazole-P is a plant growth regulator and reduces plant height by reducing internode 

elongation through inhibition of gibbere llin biosynthesis. The toxicological mode of action in 

mammals is unknown. 

The toxicology database for uniconazole-P is complete and no additional toxicity studies are 

required. l-IED's HASPOC determined that a subchronic inhalation study, acute neurotoxicity 

battery, and subchronic neurotoxicity battery are not required for uniconazole-P (U. l-labiba; 

TXR#0057212; 10/20/2015). 

The target organ for uniconazole-P is the liver regardless of the route of exposure; liver effects 

were observed following oral, dermal, and inhalation (acute only) exposure. The effects 

observed were primarily increased liver weights, elevated liver enzymes (aspartate 

aminotransferase), and histopathological changes (vacuolation and hypertrophy). Effects on the 

liver were seen following even a single exposure; increased li ver weight and cytoplasmic 

vacuolation were observed at sacrifice (2 weeks post dose) in the acute lethality studies 

conducted by both oral and inhalation exposure. There appeared to be progression of the liver 

toxicity as effects were seen at lower doses as the duration of exposure increased. 

There was no evidence of quantitative or qualitative susceptibility in the developmental rat/rabbit 

studies or the reproducti ve rat toxicity study. Uni conazole-P was classified as a Group C 

chemical; Possible Human Carcinogen, based on the occurrence of liver tumors in male mice; 

there was no evidence of carcinogenicity in female mice or in male and female rats. There was 

no concern for mutagenicity. The chronic Reference Dose would adequately account for all 

chronic e ffects including carcinogenicity. 

In acute lethality studies, uniconazole-P has low or minimal toxicity via the dermal (Toxicity 

Category III) and inhalation (Toxicity Category Ill) routes of exposure; however, it has moderate 

oral toxicity (Toxicity Category II). It is minimally irritating to the eye (Toxicity Category Ill) 

and non-irritating to the skin (Toxicity Category IV). It is not a dermal sensitizer. 

In the most recent risk assessment, the required lOx FQPA Safety Factor was reduced to lx 

based on: I) the lack of increased pre- and post-natal susceptibility of rats and rabbits to in utero 

and/or post-natal exposure in the developmental and reproductive toxicity studies; 2) there is no 

frank evidence of neurotoxicity in the database (all clinical signs that could be related to a 

neurotoxic effect were seen at high doses above those that caused liver toxicity) and a 

developmental neurotoxicity study is not required; and 3) the risk assessment does not 

underestimate exposure because the dietary assessment is based on protecti ve assumptions such 

as tolerance-level residues in foods and upper-bound modeled estimates of residues in drinking 

water. 

In the previous risk assessment, an acute dietary endpoint for the general population was not 

identified due to the lack of an identifiable effect following a single exposure. However, 

uniconazole-P did result in non-lethal toxicity (decreased spontaneous activity and urinary 

incontinence) in the acute lethality studies. Therefore, an acute di etary endpoint will be chosen 

for uniconazole-P during registration review based on the acute lethality studies; no further data 

Page 4 of23 
are required. All other conclusions from the previous risk assessment are not expected to change 

during registration review. The toxicological endpoints and doses used in the most recent human 

health risk assessment are summarized in Attachment 2. The toxicity profile of uniconazole-P is 

summarized in Attachment 3. 

Conclusions for Hazard Identification/Toxicology 

The toxicity database is complete for the purpose of registration review, and is appropriate for 

assessment of potential carcinogenic, mutagenic, developmental, and reproductive effects. The 

FQPA Safety Factor was reduced to I x based on a number of factors including the lack of 

susceptibility in developmental and reproduction studies in rats and rabbits, the lack of frank 

evidence for neurotoxicity, and the protective assumptions used in the exposure assessments. No 

new toxicity data are required. However, during registration review, HED will consider the 

appropriateness of the existing endpoints based on current policies and risk assessment 

methodologies, including choosing an acute dietary endpoint and POD for the general US 

population from the currently available acute studies. 

Residue Chemistry 

The metabolism of uniconazole-P in crops is adequately understood. Metabolites of 

uniconazole-P include I ,2,4-triazole, triazolylalanine, triazolyacetic acid, and triazolylpyruvic 

acid. HED concluded that the toxicological effects resulting from exposure to 1 ,2,4-triazole, 

triazolylalanine, triazolyacetic acid, and triazolylpyruvic acid are different from that resulting 

from exposure to uniconazole-P and are addressed as a separate aggregate risk assessment 

(0426493, T. Morton, 4/9/20 15). Li vestock metabolism studies have not been conducted, as 

there are no significant feed items associated with fruiting vegetables. HED concluded that the 

residues of concern in plant commodities (for tolerance expression and risk assessment purposes) 

are defined as the parent compound, uni conazole-P (the resolved S-enantiomer, which is the 

pesticidal active enantiomer), along with its R-enantiomer and the Z-isomer. The residues of 

concern in drinking water (for risk assessment) are uniconazole-P and the R-enantiomer. 

The established tolerance for uniconazole in fruiting vegetables group 8 is supported by adequate 

data. Adequate analytical methods exist for data collection and tolerance enforcement in plant 

commodities. 

The tolerance expression for uniconazole-P (cited in 40CFR § 180. 643[a]) is not in accordance 

with current guidance as it does not contain the appropriate coverage and compliance statements. 

It should be revised during registration review to compl y with HED's interim guidance on 

tolerance expressions. The tolerance expression for uniconazole in 40CFR § 180.643 [a] should 

be revised to state: 

Tolerances are established for residues of the fungicide/plant growth regulator 

uniconazole-P, including its metabolites and degradates, in or on the 

commodities listed in the table below. Compliance with the tolerance levels 

specified below is to be detennined by measuring only uniconazole-P [(E)-

(S)- 1-( 4-chlorophenyl)-4,4-dimethyl-2-(1 H- 1 ,2,4-tri azol-1-yl)penl-1-en-3-ol), 

its R-enantiomer and its Z-isomer. 

Page 5 of 23 
There are no Codex MRLs established for uniconazole. Therefore, there are no harmonization 

issues with regard to Codex. The US tolerance in crop group 8 (0.0 I ppm) is harmonized with 

the Canadian MRL in the tomato subgroup 8-09A (0.0 I mg/kg). 

Conclusions for Residue Chemistry 

The residue chemistry database for uniconazole-P is adequate to support current Registration 

Review data requirements. Adequate metabolism (crops, livestock, and rotational crops), storage 

stability, magnitude of the residue, and processing data are available to support the registered 

uses. Adequate methods are available for enforcement of the currently established tolerances. 

Dietary Exposure 

The Environmental Fate and Effects Division (EFED) is conducting a new drinking water 

assessment for uniconazole-P, in order to account for new modeling techniques introduced since 

the previous risk assessment. This new drinking water assessment will include the current 

residues of concern (uniconazole-P, its R-enantiomer and the Z-isomer). HED will conduct a 

new dietary risk assessment during registration review, to incorporate a new acute endpoint and 

point of departure for the general US population. Any updated assessment will include the 

Environmental Fate and Effects Division (EFED) revised estimated drinking water 

concentrations (EDWCs), if applicable.; This updated dietary exposure assessment would 

include updated consumption information and the latest version of the dietary model. 

In the most recent human health risk assessment (D346558; E. Scollon; 3/3 1/2008), there were 

no acute, chronic or cancer dietary (food+ water) risk estimates of concern. The dietary (food + 

water) estimates serve as the aggregate risk estimates. 

Conclusions for Dietary Exposure 

HED will conduct a new uniconazole-P dietary risk assessment during registration review using 

any revised EDWCs provided by EFED and incorporating changes in endpoint selection, 

particularly for acute dietary risk assessment. 

Residential Exposure 

The registered uses for uniconazole-P are not applied by homeowners to residential or 

recreational settings and are not expected to result in residential exposure. Therefore, a 

quantitative residential exposure assessment has not been conducted and will not be necessary 

for Registration Review. 

Spray Drift 

Residential exposures resulting from off-site transport (e.g., spray drift or volatilization) could 

conceivably occur as a result of applications of uniconazole-P. However, due to the currently 

registered use-pattern and application settings of uni conazole-P (i.e., commercial greenhouses, 

Page 6 of23 
lathhouses and shadehouses), indirect exposure from spray drift is expected to be negligible. 

Therefore, a quantitative spray drift assessment is not necessary for Registration Review. The 

need for a volatilization risk assessment for uniconazole-P may be examined during Registration 

Review. 

Conclusions for Residential Exposure 

There are no residential uses currently registered for uniconazole-P; therefore, a quantitative 

residential exposure/risk assessment is not necessary during Registration Review; exposure from 

drift is not expected, but HED may consider whether a volatilization risk assessment will be 

needed for uniconazole-P during registration review. 

Aggregate Risk Assessment 

The most recent aggregate risk assessment was perfonned in conjunction with the 2008 human 

health risk assessment. There arc no residential uses for uniconazole-P. As a result, aggregate 

exposure was comprised of exposures that occur through food and drinking water only and 

therefore, were equivalent to the acute and chronic dietary risk assessments. As indicated earlier, 

acute and chronic dietary risks were below HED's level of concern for the genera l U.S. 

population and aJ I population subgroups. 

Application of uniconazole-P also results in exposure to 1 ,2,4-triazole, triazolylalanine, 

triazolyacetic acid, and triazolylpyruvic acid. These compounds are considered to be 

toxicologically different from uni conazole-P. HED recently conducted an aggregate risk 

assessment for these compounds with the resulting exposure estimates less than HED's level of 

concern {0426493, T. Morton, 4/9/20 15). 

Conclusions for Aggregate Assessment 

The uniconazole-P acute and chronic dietary risk estimates were all below HED's level of 

concern. At the time of registration review, HED will conduct a new aggregate risk assessment 

that will be based on updated to points of departure and exposure estimates from food and 

drinking water. 

Occupational Exposure 

Uniconazole-P is formulated as a 0.055% (ofuniconazole-P) emulsifiable concentrate. The enduse product is specifically labeled for use in commercial greenhouses, lathhouses, and 

shadehouses as a foliar spray or ground-directed applications using handheld equipment. 

Application through any type of irrigation system is prohibited. As a result of the registered 

uses, there is a potential for short- and intermediate-term occupational exposure associated with 

handler activities (mixing, loading, and applying) as well as with post-application activities (i.e., 

re-entering treated areas). Long-term exposure is not expected for the registered use pattern. 

The personal protective equipment (PPE) listed on the registered label includes: baseline clothing 

(i.e., long-sleeved shirt and long pants, shoes and socks), chemical-resistant gloves and no 

respirator. The Restricted Entry [nterval (REI) on the registered label is 12 hours. 

Page 7 of23 
Occupational Handlers 

The previous exposure and risk assessment evaluated a number of occupational handler scenarios 

that represented the major uniconazole-P short- and intermediate-term occupational handler 

exposures based on application equipment and formulation type (0 347096; S. Wang; 

03112/2008). HED used surrogate data from the PHED Version 1.1 (PHED Surrogate Exposure 

Guide, 8/98) to assess exposures. Defaults established by the HED Science Advisory Council 

for Exposure were used for amounts treated per day and body weight. Occupational handler 

scenarios resulted in risk estimates that were not of concern at baseline/labeled level clothing 

(i.e., long-sleeved shirt and long pants, shoes and socks) and chemical-resistant gloves. 

In addition, HED previously assessed short- and intermediate-tem1 inhalation exposures for 

occupational handlers. The risk estimates were not of concern for all registered uses. In 

conjunction with determining data needs during registration review, uniconazole-P was reviewed 

by the HED HASPOC to evaluate the need for a route-specific inhalation study because the 

previous assessment was conducted using data from an oral study (0347096; S. Wang; 

03/12/2008). Revised inhalation risk estimates were calculated for occupational handlers using 

current policies and exposure assumptions. Short- and intermediate-term occupational handler 

inhalation MOEs ranged from 34,000 to 40,000,000 (LOC= 1 00) and are not of concern at 

baseline atlire with no respirator (U. Habiba; TXR#0057212; 10/20/2015). Since new exposure 

data (i.e., updated unit exposure values for occupational handlers) are available to assess 

exposure to occupational handlers, HED will reevaluate the occupational handler assessment for 

uniconazole-P to address updates to l-IED's exposure policies, including updates to default 

exposure data used for handler scenarios and assumptions for body weights. 

Occupational Post-application 

The previous risk assessment evaluated a number of occupational post-application scenarios that 

represented the major uniconazole-P occupational post-application exposure scenarios based on 

the registered uses. HED has determined that there are potential dennal exposures to persons 

entering treated sites (e.g., harvesters) after application. Sources of generic post-application data, 

used as surrogate data in the absence of chemical-specific data, are derived from Agricultural 

Reentry Task Force (ARTF) exposure monitoring studies. HED used standard values 

recommended for use in predicting post-application exposure in the 2008 risk assessment, known 

as " transfer coefficients" or TCs. The TC values are presented in the ExpoSAC Policy 3 which, 

along with additional inforn1ation about the ARTF data, can be found at the Agency website 1• 

The 2008 risk assessment indicated that occupational post-application scenarios resulted in risk 

estimates not of concern for workers conducting activities on treated areas. 

In addition, the REI specified on the registered label is based on the acute toxicity of 

uniconazole-P. It is classified as Toxicity Category III via the dermal route and Toxicity 

Category IV for skin irritation potential. It is not a skin sensiti zer. Short- and intermediate-term 

1 A vai lab le at: http://www2.epa.gov/pesticide-scicnce-and-assessing-pesticide-risks/occupat ional-pestic ide-postapplication-exposure. 

Page 8 of 23 
post-application risk estimates were not a concern on day 0 (i.e., 12 hours following appli cation) 

for all post-application activities (0347096; S. Wang; 03112/2008). 

Under 40 CFR 156.208 (c) (2) (iii), ai's classified as Acute III or TV for acute dermal, eye 

irritation and primary skin irritation are assigned a 12-hour REI. Therefore, the [ 156 subpart K] 

Worker Protection Statement REI of 12 hours appearing on the registered label is adequate to 

protect agricultural workers from post-application exposure to uni conazole-P. 

In accordance with the updated 40 CFR Part 158 data requirements (2007), one or more 

Dislodgeabl e Foli ar Residue (OFR) studies are required when a pesticide has residential or 

occupational uses that could result in post-application dermal exposure. Since the highest 

estimated occupational post-application exposure using default DFR values for uniconazole-P is 

minimal in comparison to the level of concern (i. e., the calculated MOE is greater than 2 times 

higher than the level of concern, MOE = 450 compared to the LOC of I 00 using the updated 

science policies); H ED has determined that the DFR data are not needed. In this instance, it is 

unlikely that chemical-specific DFR data would be needed to furthe r refine exposure assessments 

or would add appreciably to our overall understanding of the availability of dislodgeable foliar 

pesticide residues for uniconazole-P. 

There are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated fields. These potential sources 

include volati I ization 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, 20 I 02 . The Agency 

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

subsequent Volatilization Screening Analysis3 . During registration review, the Agency wi ll 

utili ze this analysis to determine if data (i.e., flux studies, route-specific inhalation toxicological 

studies) or further analysis are required for uni conazole-P. 

Although a quantitati ve occupational post-application inhalation exposure assessment was not 

previously performed, an inhalation exposure assessment was performed for occupational 

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. The Worker Protection Standard (WPS) for Agricultural 

Pestic ides also contains requirements for protecting workers from inhalation exposures during 

and after greenhouse applications through the use of ventilation requirements [ 40 CFR 170.110, 

(3) (Restrictions associated with pesticide applications)]. 

Conc lusions for Occupational Exposure and Risks 

2 A vai I able at: http://www.cpa.gov/scipoly/SA P/meetings/2009/ 120 I 09meeting.html. 3 A vailablc at: http://www.rcgulations.gov/#!docketDetaii;D=EPA-HQ-OPP-20 14-0219. 

Page 9 of 23 
The occupational exposure database is adequate to support the registration review process for 

uniconazole-P. The previous assessment addressed the occupational handler scenarios 

anticipated for all registered uses. Updated occupational handler and post-application (dermal) 

exposure assessments may be required under Registration Review based upon revisions to the 

Agency's scenario-specific surrogate exposure data and assumptions for body weights. Any 

changes related to toxicological POD will also be incorporated. The Agency may also revisit the 

need for a quantitative occupational post-application (inhalation) exposure assessment for 

uniconazole-P during Registration Review. 

Risk Assessment Updates, Data Deficiencies, and Label Revisions 

No data deficiencies were identified for uniconazole-P. 

EPA anticipates conducting the following risk assessment updates during registration review: 

Toxicology: 

• HED will consider the appropriateness of the existing endpoints and PODs based on 

current policies and risk assessment methodologies; HED expects to select an acute 

dietary endpoint and dose for the general US population. 

Dietary Exposure: 

• A revised dietary exposure analysis will be required to reflect the new acute dietary 

endpoint and dose for risk assessment, as well as potential revised drinking water 

estimates. 

Occupational/Residential Exposure: 

• HED anticipates conducting a revised occupational exposure assessment to reflect the use 

of the most recent handler exposure data and updated body weights. 

Public Health and Pesticide Epidemiology Data 

For this evaluation, the Agency consulted the OPP Incident Data System (IDS), the Centers for 

Disease Control and Prevention/Nationallnstitute for Occupational Safety and Health 

(CDCINIOSH) Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR), 

and the National Pesticide Information Center (NPIC) databases for pesticide incident data on 

the active ingredient uniconazole-P (D428899; S. Recore; 911 2115). Uniconazole-P is not 

included in the Agricultural Health Study (AHS); therefore, that study does not provide 

information for this document. 

There were no incident cases reported, involving uniconazole-P, to either IDS or SENSORPesticides. There does not appear to be a concern at this time that would wanant 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. 

Tolerance Assessment and International Harmonization 

Page 10 of23 
Tolerances for uniconazole are established under 40CFR § 180.643 for residues resulting from 

applications of the fungicide/plant growth regulator to frui ting vegetables. The tolerance 

expression is not in accordance with current guidance, as it does not contain the appropriate 

coverage and compliance statements. It should be revised during registration review to comply 

with HED's interim guidance on tolerance expressions, as stated above in the residue chemistry 

section. 

There are no Codex MRLs established for residues ofuniconazole at this time. A Canadi an 

MRL exists for uniconazole in the tomato subgroup 8-09A; the residue definitions are not the 

same for the US and Canada. The US tolerance in crop group 8 (0.01 ppm) is ham1onized with 

the Canadian MRL in the tomato subgroup 8-09A (0.0 1 mg/kg). An International Residue Limit 

Status sheet is attached to this document as Attachment 4. 

There are no pending requests for the establishment of new tolerances for uniconazole. 

Environmental Justice 

Potential areas of environmental j ustice concerns, to the extent possible, will be considered in 

Registration Review, in accordance with U.S. Executive Order 12898, "Federal Actions to 

Address Environmental Justice in Minority Populations and Low-Income Populations," 

(http://www.hss.energy .gov/nuclearsafety/env/guidance/justice/eo 12898. pd 1). The OPP 

typically considers the highest potential exposures from the legal use of a pesticide when 

conducting human-health risk assessments, including, but not limited to, people who obtain 

drinking water from sources near agricultural areas, the variability of diets within the U.S., and 

people who might be exposed when harvesting crops. Should these highest exposures indicate 

potential risks of concern, OPP further refines the risk assessments to ensure that the risk 

estimates are based on the best available information. 

Cumulative Risk Assessments 

Section 408(b)(2)(D)(v) of the FFDCA requires that, when considering whether to establish, 

modify, or revoke a tolerance, the Agency consider "available information concerning the 

cumulative effects" of a particular pesticide's residues and "other substances that have a common 

mechanism oftoxicity." 

Uniconazole is a member of the triazole-containing class of pesticides. Although these 

conazoles act similarl y in plants by inhibiting ergosterol biosynthesis, there is not necessarily a 

relationship between their pesticidal activity and their mechanism of toxicity in mammals. 

Structural similarities do not constitute a common mechanism of toxicity. Evidence is needed to 

establish that the chemicals operate by the same, or essenti ally the same, sequence of major 

biochemical events (EPA, 2002). In conazoles, however, a variable pattern of toxicological 

responses is found. Responses include hepatotoxicity and hepatocarcinogenicity in mice, thyroid 

tumors in rats, and developmental, reproductive, and neurological effects in rodents. 

Furthermore, the conazoles produce a diverse range of biochemical events including altered 

cholesterol levels, stress responses, and altered DNA methylation. It is not clearly understood 

whether these biochemical events are directly connected to their toxicological outcomes. Thus, 

Page 11 of 23 
there is currently no evidence to indicate that conazoles share common mechanisms of toxicity, 

and EPA is not following a cumulative risk approach based on a common mechanism of toxicity 

for the conazoles. For information regarding EPA's procedures for cumulating effects from 

substances found to have a common mechanism of toxicity, see EPA's website at 

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

Human Studies 

The 2008 risk assessment relied 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 

Pesticide Handler Exposure Database (PHED) 1.1 and the Agricultural Reentry Task Force 

(ARTF) database, are: (I) 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 website". 

References 

Author Barcode Date Title 

S. Wang 0347096 3/ 12/2008 Occupational and Residential Exposure/Risk Assessment of 

Uniconazole for New Use on Fruiting Vegetables (Pepper, Tomato, 

Eggplant, etc.). 

E.Scollon 0346558 3/31/2008 Uniconazolc-P Human Health Risk Assessment for Proposed Uses 

on Fruiting Vegetables (Except Cucurbits), Crop Group 8 

U. Habiba TX R#0057212 10/20/2015 Uniconazole: Summary of Hazard and Science Policy Council 

(HASPOC) Meeting of July 23, 20 15: Recommendation on the 

Requirement for a Subchronic Inhalation Study, Acute 

Neurotoxicity Battery and Subchronic Neurotoxicity Battery. 

S. Recore 0428899 9112/15 Uniconazole: Tier I (Scoping) Review of Human Incidents and 

Epidemiology 

T. Morton 0426493 4/09/ 15 Common Triazolc Mctabolih:s: Updated Aggregate Human Health Risk 

Assessment to Address The New Section 3 Registrations For Usc of 

Propiconazole on Tea, Dill. Mustard Greens. Radish. and Watercress: Usc 

of Difenoconazole on Globe Artichoke. Ginseng and Greenhouse Grown 

Cucumbers and Conversion of the Established Foliar Uses/Tolerances for 

Stone Fruit and Tree Nut Crop Groups to Fruit. Stone. Group 12-12 and the 

Nut, Tree. Group 14-1 2.; and Use of f'lutriafol on Hops. 

Attachments 

Attachment I. Chemical Identity Table for Uniconazole 

Attachment 2. Uniconazole-P Endpoint Selection Tables 

Attachment 3. Summary of Acute, Subchronic and Chronic Toxicity Profile, Toxicological 

Doses for Uniconazole-P for Use in Human Health Risk Assessments 

4 Ava i I able at: http://www2.epa.gov/pesticide-scicnce-and-assessing-pest icide-risks/occupational-pest icidehand ler-ex pos ure-data and http ://www2. epa. go v /pest ic ide-sc ie nee-and -assessing -pesticide-risks/ occupation a)-

pesticide-post-application-exposure. 

Page 12 of 23 
Attachment 4 . International Residue Limit Status 

Attachment 5. Summary of End-Use Products Containing Uniconazole-P. 

Page 13 of 23 
Attachment 1. Uniconazole Chemical identity. 

Table ALI. Uniconazole Nomenclature. 

Chemical structure Cl 

Common name 

Company experimental 

name 

IUPAC name 

CAS name 

CAS registry number 

End-use product (EP) 

Uniconazole (unresolved mixture) 

None 

(£)-(RS)-1-(4-chlorophenyl)-4,4-dimethyl2-( I H- 1 ,2,4-triazol- 1-yl)pent-l-cn-3-ol 

CP£)-P-[ ( 4-chlorophenyl)methylene ]-a-

( I, I-dimcthylethyl)-1 H-1 ,2,4-triazole-1-

ethanol 

83657-22- 1 

None 

Table Al.2. Physicochemical Properties of Uniconazole. 

Cl 

Uniconazole-P (S-isomer) 

XE-10 19D 

(£)-(S)-1 -(4-chlorophenyl)-4,4-dimethyl2-( I H-1 ,2,4-triazol-l-yl)pcnt-1-en-3-ol 

( aS,p£)-p-[( 4-chlorophenyl)methylene ]-a-

( I, 1-dimethylethyl)-l//-l ,2,4-triazole-1-

ethanol 

83657-17-4 

Various 

Parameter Value Reference 

Melting point/range 150°C MRID #46424905 

pH 6.54 (I% suspension of uniconazole) 

Density 1.256 g/mL em 20°C 

Water solubil ity I 1.1 mg/L at 20°C 

Solvent solubility Not Submitted 

Vapor pressure 1.0 x 10·8 Pa @ 20°C MRID #46424907 

2.3 X I 0'8 Pa @ 25°C 

Dissociation constant, pK. Does not dissociate MRID #46424905 

Octanol/water partition coefficient, Log(Kow) Log(Kow) = 3.67 @l 25°C 

UV/visible absorption spectrum No significant differences were observed 

between the spectra obtained for the 

acidic, alkaline, and neutral samples. 

Page 14 of23 
Attachment 2. Uniconazole-P Endpoint Selection Tables. 

Table A2.1. Summary of Toxicological Doses and Endpoints for Uniconazolc-P for Use in Dietary a nd NonOccupational Human Health Risk Assessments. 

RID, PAD, 

Exposure/ Point of Uncertainty/FQPA Level of Study and Toxicological Effects 

Scen Concern for ario Departure Safety Factors Risk 

Assessment 

UFA= lOx Acute RID = 

Acute Dietary NOAEL = UFH=IOx 

0.05 mglkg/day Prenatal Developmental Toxicity- rat 

(Females 13-49 5 FQPA SF= lx LOAEL = 25 mglkg/day based on years of age) mg!kg/day aPAD = 0.05 increased incidence of 14111 rib 

mg/kglday 

Chronic RID = Chronic Oral (Capsule) Toxicity- dog 

NOAEL= UF,,= lOx 0.02 LOAEL = 20 mglkg/day based on the 

Chronic Dietary 2 UFu= lOx mg/kglday increased absolute and relative liver (All Populations) mglkg/day FQPA SF= lx weight changes in males supported by 

cPAD = 0.02 histological and enzyme changes in the 

mglkg/day liver 

Incidental Oral 

Short- ( 1-30 days) NOAEL = UFA= lOx 

R Prenatal Developmental Toxicity- rat esidential LOC 

and Intermediate5 UFH= lOx for MOE= 100 LOAEL = 25 rnglkglday based on 

Tenn ( 1-6 months) mg/kg/day FQPASF= lx decreased maternal body weight gain 

Dermal Short- ( 1- NOAEL = UF"= lOx Residential LOC Subchronic Dermal Toxicity - rat 30 days) and 5 UFH= lOx for MOE= 100 LOAEL = 25 mglkg!day based on Intermediate-Term mglkg!day FQPA SF= lx increased liver weight and ( 1-6 months) hi stopatholog~ of the liver 

Inhalation Short-

( 1-30 days) and NOAEL = UFA= lOx Residential LOC Prenatal Developmental Toxicity- rat 

I ntenned iate-Term 5 UFH= lOx for MOE = 100 LOAEL = 25 mglkg/day based on 

( 1-6 months) mg!kg/day FQPA SF= lx increased incidence of 14th rib 

Uniconazole was classified by the HED Carcinogenicity Peer Review Comminee as a Group C, Cancer (oral, possible human carcinogen. The CARC recommended the reference dose (RID) approach for risk 

dem1al, inhalation) assessment and concluded that the chronic RID would be protective of all chronic effects 

including carcinogenicity (TXR No.0052723). 

Pomt of Departure (POD)= A data pomt or an estimated pomt that 1s dcnved 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 (interspccies). UF11 = potential variation in sensiti vity among members of the human population 

(intr8$pecies). UFL = usc of a LOAEL to extrapolate a NOAEL. UFs =use of a short-term study for long-term risk assessment. 

UFoo = to account for the absence of key data (i.e .. lack of a critical study}. FQPA SF = FQPA Safety Factor. PAD = population 

adjusted dose (a = acute, c = chronic). RID = reference dose. MOE= margin of exposure. LOC = level of concern. N/A = not 

applicable. 

Page 15 of23 
Table A2.2. Summary of Toxicological Doses and Endpoints for Uniconazole-P for Use in Occupational 

Human Hea lth Risk Assessments. 

Exposure/ Point of Uncertainty 

Level of Concern 

for Risk Study a nd Toxicological Effects 

Scenario Departure Factors Assessment 

Dermal Short- Subchronic Dermal Toxicity- rat 

and Occupational 

Intermediate 

NOAEL = 5 UFA= IOx LOC for MOE= LOAEL = 25 mglkglday based on 

Term (0-6 mglkglday UFu= IOx 100 increased liver weight and histopathology 

months) 

ofthe liver 

Inhalation 

Short- and NOAEL = 5 UFA= IOx 

Occupational Prenatal Developmental Toxiciry - rat 

Intermediate- mglkglday UFu= IOx LOC for MOE= LOAEL = 25 mglkg/day based on 

term (0-6 100 increased incidence of 14'h rib 

months) 

Cancer (oral, Uniconazole was classified by the HED Carcinogenicity Peer Review Committee as a Group C, 

possible human carcinogen. The CPRC recommended the reference dose (RID) approach for 

dermal, risk assessment and concluded that the chronic RID would be protective of all chronic effects 

inhalation) including carcinogenicity (TXR No.0052723). 

Pomt of Departure (POD)= A data pomt or an estimated pomt that IS dcnved from observ..:d 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). UFL = use of a LOAEL to extrapolate a NOAEL. UFs = use of a shon-tenn study for long-tenn risk 

assessment. UFos = to account for the absence of key data (i.e .. lack of a critical study). MOE= margin of exposure. LOC = 

level of concern. N/1\ "" not applicable. 

Attachment 3. Summary of Acute, Subchronic and Chronic Toxicity Profile, Toxicological 

Doses for Uniconazole-P for Use in Human Health Risk Assessments. 

Table A3.1. Acute Toxicity Profile - Uniconazolc-P. 

Guideline Study Type MRID(s) Results Toxicity 

No. Category 

870.1100 Acute oral - rat 40345405 LDso II 

S-33070, Lot PY-84013, M = 460 mg/kg 

Purity 97.2%, E/Z = 

96.2/3.8, RJS = 20.8/79.2 F = 430 mg/kg 

870.1 200 Acute dermal - rat 40345408 LDso > 2000 Ill 

S-33070, Lot No. PY- mg/kg 

84013, Purity 97.2% E/Z96.2/3 .8; RJS = 20.8/79.2 

870.1 300 Acute inhalation - rat 40345409 LCso > 2.75 Ill 

S-33070, Lot PYG-86047. mg/L 

Purity 97.6%, E2 = 96.9/3.1, 

ES/ER = 80.6/19.4 

870.2400 Acute eye irritation - rabbit 40345411 Minimally Ill 

S-33070 , Lot PY -84013, irritating 

Purity 97.2%, E/Z = 

96.2/3 .8; RJS = 20.8/79.2 

Page 16 of 23 
Table A3.1. Acute Toxicity Profile- Uniconazole-P. 

Guideline Study Type MRID(s) Results Toxicity 

No. Category 

870.2500 Acute derma l irritation - 40345411 Not irritating IV 

rabbit 

S-33070, Lot PY -8401 3, 

Purity 97.2%, E/Z = 

96.2/3.8; R/S = 20.8/79.2 

870.2600 Skin sensitization - guinea 4034541 2 Not a skin NA 

pig sensitizer 

S-3307-0, Lot PY-8401 3, 

Purity 97.2%, E/Z = 

96.2/3.8; R/S 20.8/79.2 

There are several versions of the technical grade active ingredient that were tested in the acute 

battery. The teclmical uniconazole can contain various quantities of related isomers which can 

a lter the chemistry and toxicology of the test substance. The studi es listed above that were 

performed with the technical grade active ingredient are the studies that provide the most 

protective toxicity categories. 

Page 17 of23 
Table A3.2. Toxicity Studies Profile. 

Guideline No. MRID No. (year)/ Results 

Classification /Doses 

870.3 100 40462605 ( 1986) NOAEL = 7.5 mg/kg/day 

Subchronic Acceptable/guideline LOAEL = 73.0 mg/kg/day based on based on 

oral toxicity 0, 30, 100, l 000, 3000 ppm changes in body weights, hematology, lipid 

(rat) M: 0, 23, 7.5, 73.0, 228.0 metabolism and effects on liver and thyroid. 

mg/kg/day 

F: 0, 2.4, 8.4, 79.4, 229.0 

mg/kg/day 

870.3150 40462606 ( 1986) NOAEL = 20 mg/kg/day 

Subchronic Acceptable/guideline LOAEL = 80 mg/kg/day based on increased 

oral (capsule) 0, 5, 20, 80, 320 mg/kg/day alkaline phosphatase activity (males and 

toxicity (dog) in gelatin capsules females) and increased liver weights (males). 

870.3100 4144240 I (1986) NOAEL = 58 mg/kg/day 

Subchronic Acceptable-Nonguideline LOAEL = 193 mglkg/day based on the body 

Oral (Feeding) 0, 100, 300, 1000, 3000, weight changes, clinical chemistry changes, 

Toxicity Study 10000 ppm 

hematology changes and liver effects. 

(Mouse) M: 0,20, 58, 193,622, 

5 weeks 2673 mg/kg/day 

F: 0,27, 77,274, 849, 3758 

mg/kg/day 

870.3200 40462607 ( 1987) Systemic Toxicity NOAEL = 5 mg/kg/day 

Subchronic Acceptable/guideline Systemic Toxicity LOAEL = 25 mg/kg/day 

dermal toxicity 0, 5,25,50, 200,500 based on increased liver weight and 

- 28 day (rat) mg/kg/day 

histopathology of the liver. 

Dem1al Toxicity NOAEL < 5 mg/kg/day 

Dermal Toxicity LOAEL :S 5 mglkg/day based 

on dermal irritation at all dose levels tested. 

870.3200 41162003 (1989) Systemic Toxicity NOAEL 2': I 000 mg/kg/day. 

Subchronic Acceptable/guideline Systemic Toxicity LOAEL was not achieved. 

dermal toxicity 0, 100,500, 1000 Dermal Toxicity NOAEL 2: I 000 mg/kg/day. 

- 28 days (rat) mglkg/day Dermal Toxicity LOAEL was not achieved. 

Formulation However, the irritation noted at all dose levels 

2.66% a.i. was slight. 

Page 18 of23 
Table A3.2. Toxicity Studies Profile. 

Guideline No. MRID No. (year)/ Results 

Classification /Doses 

870.3200 41162002 ( 1987) Only a single dose tested. 

Subchronic Acceptable/guideli ne Denn al Toxicity LOAEL ~ l 000 mg/kg/day 

dern1al toxicity 0, 1 000 mg/kg/day 

based on acanthosis noted. 

- 28 days (rat) No systemic toxicity was noted. 

Formulation 

0.05% a.i. 

870.3700 40462609 ( 1987) Materna l Toxic ity NOAEL = 5 mg/kg/day 

Prenatal 42123201 (1991) Maternal Toxicity LOAEL = 25 mg/kg/day 

deve lopmental Acceptable/guide! ine 

based o n decreased body weight. 

toxi city (rat) Developmental Toxicity NOAEL = 5 

0, 1, 5, 25, 50 mg/kg/day in mg/kg/day 

0.5%CMC Developmental Toxicity LOAEL = 25 

mg/kg/day based on increased incidence of 14111 

rib. 

870.3700 40462610 ( 1987) Maternal Toxicity NOAEL = l 0 mg/kg/day 

Acceptable/ guide! i ne Maternal Toxicity LOAEL = 20 mg/kg/day 

Prenatal 0, 1, 3, l 0, 20 mg/kg/day in based on statistically significant reduced food 

developmental 0.5%CMC consumption and marginally reduced body 

toxicity weight gains. 

(rabbit) Developmental Toxicity NOAEL ~ 20 

mg/kg/day (HDT). 

Developmental Toxicity LOAEL was not 

achieved. 

Page 19 of 23 
Table A3.2. Toxicity Studies Profile. 

Guideline No. MRID No. (year)/ Results 

Classification /Doses 

870.3800 41162004 (1989) Parental Systemic Toxicity NOAEL = 7.5 

Reproduction Acceptable/guide! ine 

mg/kg/day 

Parental Systemic Toxicity LOAEL = 75 

and fertility 0, 15, 150, 1500 ppm 

effects 

mg/kg/day based on reduced body weight and 

(rat) 0, 0.75, 7.5, 75 mg/kg/day food intake, increased liver weight, and 

by standard conversion hepatocellular enlargement and vacuolization. 

factor for older rats 

Reproductive Toxicity NOAEL ~ 75 

mg/kg/day 

Reproducti ve Toxicity LOAEL > 75 

mg/kg/day 

Offspring Systemi c/Developmental Toxicity 

NOAEL = 7.5 mg/kg/day 

Offspring Systemic/Developmental Toxicity 

LOAEL = 75 mg/kg/day based on reduced pup 

growth (reduced body weight during lactation). 

870.4100 See 4 1 162006 below N/A 

Chronic 

toxicity 

870.4100 41162001 ( 1988) Systemic Toxicity NOAEL = 2 mg/kg/day 

Chronic Oral Acceptable/guide line 

Systemic Toxicity LOAEL = 20 mg/kg/day 

based on the increased absolute and re lati ve 

Toxicity (dog) 0, 2, 20, 200 mg/kg/day in liver weight changes in males supported by 

Capsule gelatin capsules histological and enzyme changes in the liver. 

administration 

52 weeks 

870.4200 4 1 162005 ( 1988) Systemic Toxicity NOAEL = 30 mg/kg/day 

Carcino- Acceptable/guideline 

Systemic Toxicity LOAEL = 225 mg/kg/day 

based on liver lesions observed in high-dose 

genic ity 0, I 0, 40, 200, 1500 ppm male and female mice. 

(mouse) Mean of both sexes evidence of carcinogenicity 

78 weeks 0, 1.5, 6, 30, 225 

Based on the increased incidence of 

hepatocellul ar neoplasms observed in highmg/kg/day dose male mice, the chemical was reviewed by 

the HED Cancer Peer Review Committee 

(CPRC document dated 1 0/ll/1990). 

Page 20 of 23 
Table A3.2. Toxicity Studies Profile. 

Guideline No. MRID No. (year)/ Results 

Classification /Doses 

870.4300 41 162006 ( 1989) Systemic Toxicity NOAEL = 7.78 mg/kg/day 

Combined Acceptable/guide! ine Systemic Toxicity LOAEL = 39.41 mg/kg/day 

based on reduced body weight gain and/or an Chronic 0, I 0, 40, 200, l 000 ppm increased incidence of centrilobular Toxicity/ M: 0, 0.36, 1.48, 7,78, hepatocell ular enlargement and vacuolization 

Carcino- 39.41 mg/kg/day in male and female rats, and decreased 

genicity F: 0, 0.43, 1.81, 9.37, 47.85 cholesterol levels in female rats. 

(rat) mg/kg/day no evidence of carcinogenicity 

104 weeks 

870.5 100 40462612 ( 1987) No evidence of mutagenicity at concentrations 

Bacterial Acceptable up to the limit of solubility with or without 

Reverse metabolic acti vitation in S. typhimurium 

Mutation Test I to 500 ~t plate without TAI535, TAI537, TAI538, TA98, and TAtOO 

S9 activation; 5 to 1000 and in E. coli WP2, uvrA 

ug/plate vvith S9 activation 

870.5375 404626 13 ( 1987) The nonactivated test material was not 

In vitro Acceptable 

clastogenic; however, in the presence of S9 

mammalian activation, S-33070 induced a clear dosechromosome 2 X 1 o·S to 2 X l O"" M dependent clastogenic response. S9-activated 

aberration test without S9 acti vation; 5 x S-3307D is a clastogcn in this test system. 

(CHO) I 0"5 to 3 X I O"" M with S9 

activation 

870.5385 40462615 ( 1987) Negative for in vivo micronuclei induction Mammalian Acceptable when combined bone marrow 

chromosomal with 42123203 (below) 

aberration test 

870.5385 42123203 ( 1989) Negative for in vivo mi cronuclei induction Mammalian Acceptable when combined bone marrow 

chromosomal with 404626 15 (above) 

aberration test 

870.5550 40936004 ( 1988) Conduct and reporting deficiencies Unscheduled Unacceptable DNA Synthesis 

in Mammalian 

Cells in 

Culture 

Page 21 of 23 
Table A3.2. Toxicity Studies Profile. 

Guideline No. MRID No. (year)/ Results 

Classification /Doses 

870.5900 404626 14 (1987) Negative for inducing sister-chromatid 

In vitro sister Unacceptable exchanges (SCEs) in Chinese hamster ovary 

chromatid cells treated up to the cytotoxic concentration 

exchange assay range. Top doses demonstrated weak 

(CHO) gcnotoxic activity in the presence of activation. 

870.7485 40496701 (1987) Uniconazole was rapidly absorbed, extensively 

Metabolism Acceptable metabolized, and rapidly excreted. Over a 3-

and pharmacoday period, most (96-99 percent) of the test 

kinetics compound administered was excreted from the 

(rat) animals. The radioactivity recovered in the 

urine, feces, and C02 in the exhaled air was 

40-66, 33-59 and 0. 1 percent of the 

administered dose, respectively. Peak tissue 

(including plasma) concentration of 

radioactivity occurred 1 to 8 hours after the 

administration of the test compound. Three 

major metabolites were identified in the urine 

and feces. These represent 83-91 percent of the 

administered dose. The metabolites of 

uniconazole were two oxidation products (58-

75 percent of the dose) of the methyl moiety of 

the tert-butyl group and a free triazole (3-15 

percent of the dose) liberated from 

uniconazole. 

870.7600 40462616 ( 1987) The 10 hour absorption value is 7.2% 

Dermal Acceptable 

penetration 0.05, 0.5, 5.0 mg/rat 

(rat) 

Page 22 of 23 
Attachment 4. Uniconazole International Residue Limit Status. 

Table A.2. Summary of US Tolerances a nd International MRLs. 

Uniconazole (Uniconazole-P); PC Code 128976; 40CFR §I80.643(a) 

Residue Definitions 

us Canada Mexico• Codex2 

Uniconazolc-P [(E)-(RS)-(4- (13E)-13-(( 4-chlorophenyl)methylene ]-a-( I, 1- None 

chlorophenyl)-4,4-dimethyl-2-( I H- dimethylethyl)-1 H-1 ,2,4-triazole-1-ethanol, 

I ,2,4-triazol-1-yl)pent-1-en-3-ol], its including the Z-isomer [(13Z)-13-[( 4-

R-enantiomer and Z-isomer. chlorophenyl)methylene]-a-(1 , 1-

dimethylethyl)-1 H-1 ,2,4-rriazole-1 -ethanol] 

Commodity Tolerance (ppm)!MRL (mg/k2) 

us Ca nada 

40CFR §I80.643(a) General 

Vegetable, fruiting, group 8 0.01 Tomato crop subgroup 8-09A (0.0 I) 

Completed: 12 August 20 15 

I. Mextco adopts US tolerances and/or Codex MRLs for tts export purposes. 

2. There are no Codex MRLs established for uniconazole. 

Mexico• Codex2 

Attachment 5. Summary of End-Use Products Containing Uniconazole-P. 

Reg

N

istration Accepted %AI Formulation Product Home- Application Method Type 

umber Date Name owner 

Use 

59639-37 5 December 0.055 SL Sumagic Plant No Foliar spray, drench, bulb or 

2011 Growth cutting dip, pre-plant 

Regulator application to soil surface 

59639-38 5 December 78. 1 Technical Valent No For further preparation and 

2011 Uniconazole-P manufacture of plant growth 

Technical regulator formulations 

62097-15 7 October 79.7 Technical Uniconazole-P No For further preparation and 

20 10 Technical manufacture of plant growth 

regulator formulations 

62097- 18 3 August 2006 0.055 SL Concise No Foliar spray, drench, bulb or 

cutting dip, pre-plant 

application to soil surface 

AL080004 Not available 0.055 SL Sumagic Plant No Foliar spray, drench, bulb or 

Growth cuning dip, pre-plant 

Regulator application to soil surface 

Page 23 of 23