Document ID: EPA-HQ-OPP-2007-0968-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-11-28T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF

PREVENTION, PESTICIDES AND

TOXIC SUBSTANCES

June 12, 2007

				

Memorandum

SUBJECT:	Chlormequat Chloride: Occupational and Residential Exposure
Assessment for the Reregistration Eligibility Decision Document.

FROM:	Charles Smith, Environmental Scientist

		Reregistration Action Branch II/Health Effects Division (7509C)

THROUGH:	Alan Nielsen, Branch Senior Scientist

		Reregistration Action Branch II/Health Effects Division (7509C)

			

TO:		Donald Wilbur, Chemist/Risk Assessor

		Reregistration Action Branch II/Health Effects Division (7509C)

	

PC Code:	018101

DP Barcode:	D336714

The attached assessment contains the occupational and non-occupational
(residential) exposure and risk estimates for chlormequat chloride to
support HED’s reregistration eligibility decision (RED) document.

Table of Contents

  TOC \o "1-4" \h \z \u    HYPERLINK \l "_Toc168278212"  Executive
Summary	  PAGEREF _Toc168278212 \h  3  

  HYPERLINK \l "_Toc168278214"  1.0	Occupational and Residential
Exposure/Risk Assessment	  PAGEREF _Toc168278214 \h  5  

  HYPERLINK \l "_Toc168278215"  1.1	Purpose	  PAGEREF _Toc168278215 \h 
5  

  HYPERLINK \l "_Toc168278216"  1.2	Criteria for Conducting Exposure
Assessments	  PAGEREF _Toc168278216 \h  5  

  HYPERLINK \l "_Toc168278217"  1.3	Summary of Hazard Concerns for
Chlormequat Chloride	  PAGEREF _Toc168278217 \h  5  

  HYPERLINK \l "_Toc168278218"  1.4	Incident Reports	  PAGEREF
_Toc168278218 \h  8  

  HYPERLINK \l "_Toc168278220"  1.5	Summary of Physical and Chemical
Properties of Chlormequat Chloride	  PAGEREF _Toc168278220 \h  8  

  HYPERLINK \l "_Toc168278221"  1.5.1	Structure and Nomenclature	 
PAGEREF _Toc168278221 \h  8  

  HYPERLINK \l "_Toc168278222"  1.5.2	Physical and Chemical Properties	 
PAGEREF _Toc168278222 \h  9  

  HYPERLINK \l "_Toc168278223"  1.6	Summary of Use Patterns and
Formulations	  PAGEREF _Toc168278223 \h  9  

  HYPERLINK \l "_Toc168278224"  1.6.1	End-Use Products	  PAGEREF
_Toc168278224 \h  9  

  HYPERLINK \l "_Toc168278225"  1.6.2	Registered Use Categories and
Sites	  PAGEREF _Toc168278225 \h  9  

  HYPERLINK \l "_Toc168278226"  1.6.3	Application Methods and Rates	 
PAGEREF _Toc168278226 \h  10  

  HYPERLINK \l "_Toc168278227"  2.0	Occupational Exposures and Risks	 
PAGEREF _Toc168278227 \h  11  

  HYPERLINK \l "_Toc168278228"  2.1	Occupational Handler Exposures and
Risks	  PAGEREF _Toc168278228 \h  11  

  HYPERLINK \l "_Toc168278229"  2.1.1	Data and Assumptions for Handler
Exposure Scenarios	  PAGEREF _Toc168278229 \h  12  

  HYPERLINK \l "_Toc168278230"  2.1.1.1	Assumptions for Handler Exposure
Scenarios	  PAGEREF _Toc168278230 \h  12  

  HYPERLINK \l "_Toc168278231"  2.1.1.2	Exposure Data for Handler
Exposure Scenarios	  PAGEREF _Toc168278231 \h  13  

  HYPERLINK \l "_Toc168278232"  2.1.2	Chlormequat Chloride Handler
Exposure Scenarios	  PAGEREF _Toc168278232 \h  14  

  HYPERLINK \l "_Toc168278233"  2.1.3	Non-cancer Chlormequat Chloride
Handler Exposure and Assessment	  PAGEREF _Toc168278233 \h  15  

  HYPERLINK \l "_Toc168278234"  2.1.3.1	Non-cancer Chlormequat Chloride
Handler Exposure and Risk Calculations	  PAGEREF _Toc168278234 \h  15  

  HYPERLINK \l "_Toc168278235"  2.1.3.2	Chlormequat Chloride Non-cancer
Risk Summary (using    HYPERLINK \l "_Toc168278236"  PHED data)	 
PAGEREF _Toc168278236 \h  16  

  HYPERLINK \l "_Toc168278237"  2.1.4	Summary of Risk Concerns and Data
Gaps for Occupational Handlers	  PAGEREF _Toc168278237 \h  17  

  HYPERLINK \l "_Toc168278238"  2.1.4.1	Summary of Risk Concerns	 
PAGEREF _Toc168278238 \h  17  

  HYPERLINK \l "_Toc168278239"  2.1.4.2	Summary of Data Gaps	  PAGEREF
_Toc168278239 \h  17  

  HYPERLINK \l "_Toc168278240"  2.2	Occupational Postapplication
Exposures and Risks	  PAGEREF _Toc168278240 \h  17  

  HYPERLINK \l "_Toc168278242"  3.0	Residential and Other
Non-Occupational Exposures and Risks	  PAGEREF _Toc168278242 \h  17  

 

Executive Summary tc "Executive Summary" 

This document is the occupational and residential/non-occupational risk
assessment for chlormequat chloride from its use as a plant growth
regulator.  In this document, which is for use in EPA's development of
the Health Effects Division (HED) chapter of the chlormequat chloride
RED Document, EPA presents the results of its review of the potential
human health effects of occupational and residential/non-occupational
exposure to chlormequat chloride.

Hazard Concerns:  The toxicological endpoints used to complete the
occupational risk assessments have been selected by HED and are
summarized below.  Adverse effects were identified at durations of
exposure ranging from short-term (up to 30 days) to intermediate-term
durations (> 30 days up to 6 months) durations.  No cancer endpoint was
identified; therefore cancer risks are not assessed.  There are no
residential uses for chlormequat chloride so residential exposures are
not expected.

No dermal endpoint was selected for chlormequat chloride because the
21-day dermal rat study for chlormequat chloride did not result in
systemic toxicity up to the limit dose of 1000 mg/kg/day.  Therefore, a
quantitative dermal assessment is not appropriate for chlormequat
chloride.  The short- and intermediate-term (non-cancer) inhalation risk
assessment for chlormequat chloride is based on a NOAEL of 30 mg/kg/day
from an oral developmental toxicity study in rats.  Absorption via the
inhalation route is presumed to be equivalent to oral absorption
therefore; a default inhalation factor of 100% was applied to inhalation
exposures.  Long-term exposures to chlormequat chloride (i.e., greater
than 6 months) are not expected for current registered uses.    HED’s
level of concern (LOC) for chlormequat chloride inhalation exposures is
100 (i.e., a margin of exposure (MOE) less than 100 exceeds HED’s
level of concern) for all scenarios.  The level of concern is based on
10x for interspecies extrapolation and 10x for intraspecies
extrapolation.

Use Patterns:  Chlormequat chloride is a plant growth regulator that
belongs to the quaternary ammonium class of chemicals.   tc "1.6.2
Registered Use Categories and Sites " \l 3 Chlormequat chloride
(formulated as an emulsifiable concentrate) is currently registered for
use on ornamentals grown in greenhouses, shadehouses, and nurseries. 
Use is restricted to containerized ornamentals in situations where
production areas are not under cover.  Chlormequat chloride applications
are applied using several types of application equipment – including
groundbooms, low pressure handwands, backpack sprayers, and high
pressure handwands.

Occupational Handler Risks:  It has been determined that exposure to
pesticide handlers is likely during the occupational use of chlormequat
chloride.  The anticipated use patterns and current labeling indicate
several dermal and inhalation occupational exposure scenarios based on
the types of equipment and techniques that can potentially be used for
chlormequat chloride applications.  No dermal occupational
postapplication risk assessment was performed because a dermal endpoint
was not selected for chlormequat chloride due to its lack of systemic
toxicity via the dermal route.  Results indicate that all of the
inhalation occupational handler risks for chlormequat chloride do not
exceed HED’s level of concern [i.e., MOEs are greater than 100].

Occupational Postapplication Risks:  No dermal occupational
postapplication risk assessment was performed because a dermal endpoint
was not selected for chlormequat chloride due to its lack of systemic
toxicity via the dermal route.  When there is no dermal occupational
postapplication risk assessment the restricted entry interval (REI) is
based on the acute toxicity of the chemical.  The current chlormequat
chloride label requires a 12-hour REI but chlormequat chloride has been
classified as Category II for acute dermal toxicity.  In accordance with
the requirements in the Worker Protection Standards (WPS) - 40CFR170,
ingredients classified as Category II are assigned a 24-hour REI.  The
Health Effects Division (HED) recommends that the Registration Division
(RD) ensure that the proper REI for ornamental plants grown in
containers in greenhouses, nurseries, and shadehouses be included on the
chlormequat chloride labels.

An inhalation occupational postapplication assessment was not performed
for chlormequat chloride due to its low vapor pressure.  However, in
nurseries and greenhouses, the WPS prohibits workers from entering the
treated area for the first four hours after an application is completed
to allow time for sprays and dusts to settle out of the air to protect
workers against postapplication inhalation exposures.

Residential Risks:  Chlormequat chloride does not currently have any
registrations for residential use nor is it registered for use in any
residential settings.  As a result, no residential chlormequat chloride
handler or postapplication assessments are required at this time.

Review of Human Research:  This assessment relies in part on data from
studies in which adult human subjects were intentionally exposed to a
pesticide.  These studies, listed below, have been determined to require
a review of their ethical conduct.  The listed studies have either
received the appropriate review or are in the process of being ethically
reviewed.

The PHED Task Force, 1995.  The Pesticide Handler Exposure Database
(PHED), Version 1.1.  Task Force members Health Canada, U.S.
Environmental Protection Agency, and the National Agricultural Chemicals
Association, released February 1995.

1.0	Occupational and Residential Exposure/Risk Assessment tc "1.0
Occupational and Residential Exposure/Risk Assessment" 

	1.1	Purpose tc "1.1	Purpose " \l 2 

This document is the occupational and residential/non-occupational risk
assessment for chlormequat chloride from its use as a plant growth
regulator.  In this document, which is for use in EPA's development of
the Health Effects Division (HED) chapter of the chlormequat chloride
RED Document, EPA presents the results of its review of the potential
human health effects of occupational and residential/non-occupational
exposure to chlormequat chloride.

	1.2	Criteria for Conducting Exposure Assessments  tc "1.2	Criteria for
Conducting Exposure Assessments " \l 2 

An occupational and/or residential exposure assessment is required for
an active ingredient if (1) certain toxicological criteria are triggered
and (2) there is a potential for exposure to handlers (mixers, loaders,
applicators) during use or to persons entering treated sites or exposed
to vapors after application is complete.  Toxicological endpoints were
selected for short- and intermediate-term inhalation exposures to
chlormequat chloride.  No dermal endpoint was selected for chlormequat
chloride because the 21-day dermal rat study for chlormequat chloride
did not result in systemic toxicity up to the limit dose of 1000
mg/kg/day.  Therefore, a quantitative dermal assessment is not
appropriate.  There is a potential for chlormequat chloride inhalation
exposure from mixing/loading, applying, and other handling tasks
involved in applications to ornamentals and from postapplication
activities after applications to ornamentals.  Therefore, short- and
intermeditate-term inhalation risk assessments are required for
occupational handlers that can occur as a result of chlormequat chloride
use.  No long-term occupational handler assessment was performed for
chlormequat chloride because long-term exposure is not expected based on
the current use profile.  Chlormequat chloride is likely used in
greenhouses and nurseries throughout the year on various ornamental
species.  These uses would likely result in a series of short-term
exposures as opposed to 6 months of consecutive daily exposure (i.e.,
long-term exposure).

	1.3	Summary of Hazard Concerns for Chlormequat Chloride  tc "1.3    
Summary of Hazard Concerns for MGK-264 " \l 2 

The toxicological endpoints used to complete the occupational risk
assessments have been selected by HED and are summarized below.  Adverse
effects were identified at durations of exposure ranging from short-term
(up to 30 days) to intermediate-term durations (> 30 days up to 6
months) durations.  No cancer endpoint was identified; therefore cancer
risks are not assessed.  There are no residential uses for chlormequat
chloride so residential exposures are not expected.

	

	Dermal Route (non-cancer)

No dermal endpoint was selected for chlormequat chloride because the
21-day dermal rat study for chlormequat chloride did not result in
systemic toxicity up to the limit dose of 1000 mg/kg/day.  Therefore, a
quantitative dermal assessment is not appropriate for chlormequat
chloride.

Although no systemic toxicity was observed in the 21-day dermal toxicity
rabbit study when tested higher than the limit dose (1035 mg/kg/day), a
review of the dermal toxicology data for chlormequat chloride suggests
the potential for significant dermal irritation.  Localized dermal
toxicity was observed (days 10-21) in the 21-day dermal rabbit study at
345 mg/kg/day in the form of dermal irritation (erythema, edema, and
fissuring), gross lesion of treated skin (foci), and histopathological
lesions in the treated skin (acanthosis, subacute inflammation and
edema), in females only.  The test substance was in contact with the
skin of the rabbit by a secured gauze dressing for 6 hours/day and 5
days/week.  The primary dermal irritation study with rabbits also
applied the pesticide to secured gauze for 4 hours.  This single
exposure produced slight irritation that was resolved by 48 hours
post-exposure.  In contrast, the pesticide was applied directly to the
skin of the rabbits for 24 hours in the acute LD50 dermal toxicity
rabbit study.  Mortality (1/10) was observed at the lowest dose of 312
mg/kg.  This increased toxicity was likely due to the direct application
and occlusion of the pesticide to the skin of the animal.  As protection
against dermal irritation from occupational handler exposures is
addressed through proper labeling and protection against dermal
irritation from occupational worker exposures is addressed by the worker
protection standard, and as dermal irritation cannot be quantified for
dermal risk assessments, it is concluded that if adequate measures are
in place to protect against dermal irritancy, (through proper labeling
language and/or worker protection standard), then quantitative risk
assessment is not necessary for pesticide chemicals meeting the above
criteria.

	Inhalation Route (non-cancer)

The short- and intermediate-term (non-cancer) inhalation risk assessment
for chlormequat chloride is based on a NOAEL of 30 mg/kg/day from an
oral developmental toxicity study in rats.  Long-term exposures to
chlormequat chloride (i.e., greater than 6 months) are not expected for
current registered uses.  Absorption via the inhalation route is
presumed to be equivalent to oral absorption therefore; a default
inhalation factor of 100% was applied to inhalation exposures.    

	Non-cancer Level of Concern (LOC)

HED’s level of concern (LOC) for chlormequat chloride inhalation
exposures is 100 (i.e., a margin of exposure (MOE) less than 100 exceeds
HED’s level of concern) for occupational and residential scenarios. 
The level of concern is based on 10x for interspecies extrapolation and
10x for intraspecies extrapolation.

	Cancer

No cancer endpoint was identified for chlormequat chloride.             
                       

	Acute Toxicity 

The acute toxicity data indicate that chlormequat chloride is moderately
toxic (Category II) via oral and dermal routes of exposure, and
minimally toxic via acute inhalation exposure (Category IV).  It is
slightly irritating to the skin and moderately irritating to the eye
(Category IV and III, respectively).  Chlormequat chloride did not
produce sensitization in test with guinea pigs.		

	Body Weight

The adverse effects for the inhalation endpoint are based on a
reproductive study; however, the effects were seen in both males and
females.  Therefore, the body weight of an average adult (i.e., 70 kg)
was used to estimate inhalation exposure.  

Table 1:  Acute Toxicity Data on Chlormequat Chloride

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

870.1100

81-1	Acute oral [rat]	41721604	LD50 Males = 487 mg/kg 

(95% C.I.= 369-643)

Females = 560 mg/kg

(95% C.I.= 399-786)

Combined = 522 mg/kg (95% C.I.= 423-646)	II

870.1200

81-2	Acute dermal [rabbit]	41721605	LD50 Males = 964 mg/kg (95% C.I.=
509-1825)

Females = 1621 mg/kg (95% C.I.= 856-3069)

Combined = 1250 mg/kg (95% C.I.= 647-2414)	II

870.1300

81-3	Acute inhalation [rat]	41721606	LC50 => 4.57 mg/L  

(males, females combined)	IV

870.2400

81-4	Acute eye irritation [rabbit]	41721607	Slight irritation.  No
positive signs at 48 hours.	III

870.2500.

81-5	Acute dermal irritation [rabbit]	41721608	Mildly irritating	IV

870.2600

81-6	Skin sensitization [guinea pig]	41721609	Not a sensitizer	N/A

Table 2.  Summary of Toxicological Doses and Endpoints for Chlormequat
Chloride for Use in Human Risk Assessments

Exposure

Scenario	Dose Used in Risk Assessment, UF	Special FQPA SF* and Level of
Concern for Risk Assessment	Study and Toxicological Effects

Short-Term (1 to 30 days) Dermal

Intermediate-Term 

(1 to 6 months) Dermal	No dermal endpoint was selected for chlormequat
chloride because the 21-day dermal rat study for chlormequat chloride
did not result in systemic toxicity up to the limit dose of 1000
mg/kg/day.

Short-Term (1 to 30 days) Inhalation

Intermediate-Term (1 to 6 months) Inhalation	NOAEL (oral study) = 30
mg/kg/day

(Inhalation Absorption Factor = 100%)	Occupational LOC for MOE = 100
Developmental toxicity-rat (MRID 42246604)

LOAEL= 90 mg/kg/day, based on decreased body weight gain (38-112%-GD
6-9; 21-67% GD 6-12) and food consumption and greater incidences of
increased salivation and chromorrhinorrhea

Cancer (oral, dermal, inhalation)	Classification: “Not likely to be
Carcinogenic to Humans” based on the no carcinogenic potential was
noted in the available studies.

UF = uncertainty factor, NOAEL = no observed adverse effect level, LOAEL
= lowest observed adverse effect level, MOE = margin of exposure, LOC =
level of concern

	1.4	Incident Reports  tc "1.4	Incident Reports " \l 2 

Public health/epidemiology data were not available for the development
of this assessment.									

 	1.5	Summary of Physical and Chemical Properties of Chlormequat
Chloride  tc "1.5	Summary of Physical and Chemical Properties of MGK-264
" \l 2 

		1.5.1	Structure and Nomenclature tc "2.2	Structure and Nomenclature "
\l 2 

Table 3.  Test Compound Nomenclature

Chemical Structure	

Empirical Formula	C5H13Cl2 N

Common Name	Chlormequat chloride

Company Experimental Name	N/A

IUPAC Name	2-chloroethyl trimethyl ammonium chloride

CAS Name	2-chloro-N,N,N-trimethylethanaminium chloride

CAS Registry Number	999-81-5

End-use Product/EP	CYCOCEL® Plant Growth Regulator

Chemical Class	quaternary ammonium compound 

Use Type	plant growth regulator

Known Impurities of Concern	N/A

		1.5.2	Physical and Chemical Properties tc "2.3	Physical and Chemical
Properties " \l 2 

Table 4.    SEQ CHAPTER \h \r 1 The Physicochemical Properties of
Chlormequat Chloride

Parameter	Value	Reference

Molecular Weight	158.1	MSDS CYCOCEL® Plant Growth Regulator by BASF
Canada, 08/15/2000

Melting Point	245ºC	MSDS CYCOCEL® Plant Growth Regulator by BASF
Canada, 08/15/2000

pH	5.14 	MSDS CYCOCEL® Plant Growth Regulator by BASF Canada,
08/15/2000

Density	1.241 g/ml	Study: Surface Tension, Density and Vapour Pressure
of Chlormequat-Chloride (PAI) by BASF Germany, 03/27/2001

Water Solubility (20° C)	74 g/100 ml	MSDS CYCOCEL® Plant Growth
Regulator by BASF Canada, 08/15/2000

Surface Tension 	70.3 mN/m	Study: Surface Tension, Density and Vapour
Pressure of Chlormequat-Chloride (PAI) by BASF Germany, 03/27/2001

Vapor Pressure ( 20°C)	 <1.0 x 10-8 mbar	Study: Surface Tension,
Density and Vapour Pressure of Chlormequat-Chloride (PAI) by BASF
Germany, 03/27/2001

Octanol/water partition coefficient,

log KOW (25°C)	Not Applicable 	MSDS CYCOCEL® Plant Growth Regulator by
BASF Canada, 08/15/2000

	1.6	Summary of Use Patterns and Formulations  tc "1.6	Summary of Use
Patterns and Formulations " \l 2 

		1.6.1	End-Use Products  tc "1.6.1	End-Use Products " \l 3 

Chlormequat chloride is a plant growth regulator that belongs to the
quaternary ammonium class of chemicals.  Chlormequat chloride works
through inhibition of gibberellin biosynthesis in the early stages of
the pathway.  This early blockage prevents the synthesis of numerous
gibberellins needed for normal plant growth and development.  It is
formulated as an soluble concentrate/liquid (SC/L).

Registered Use Categories and Sites

  tc "1.6.2	Registered Use Categories and Sites " \l 3 

Chlormequat chloride is currently registered for use on a wide variety
of ornamentals grown in greenhouses, shadehouses, and nurseries.  Crops
include herbaceous and woody annual and perennial plants such as
begonias, vincas, azaleas, and poinsettias.  Use is restricted to
containerized ornamentals in situations where production areas are not
under cover.

1.6.3	Label Personal Protective Equipment (PPE) Requirments

 

The current chlormequat chloride labels require that applicators and
other handlers wear the following personal protective equipment (PPE):

Long-sleeved shirt and long pants.

Chemical resistant gloves, such as butyl rubber ≥ 14 mils, natural
rubber ≥ 14 mils, neoprene rubber ≥ 14 mils, or nitrile rubber ≥
14 mils.

Shoes plus socks.

1.6.4	Application Methods and Rates tc "1.6.3	Application Methods " \l 3

 

Chlormequat chloride applications are applied using several types of
application equipment – including groundbooms, low pressure handwands,
backpack sprayers, and high pressure handwands.  Table 5 includes a
description of application methods and rates that are currently
registered for chlormequat chloride.

Table 5. Chlormequat Chloride Use Patterns and Formulations

Formulation	Use Site	Method of Application 	Use Sites	Application Rate
Label Restrictions

CYCOCEL® Plant Growth Regulator - liquid

(11.8% a.i.)

For Commercial Use

EPA Reg #241-74 	Shadehouses and nurseries	foliar spray by low pressure
handwand, backpack sprayer, or groundboom	Ornamentals	0.017 lb ai/gal

(at 2,000 ppm)

3.7 lb ai/A

(at 2,000 ppm and 

1 gal/200 ft2) or 5.5 lb ai/A (at 2,000 ppm and 1.5 gal/200 ft2 – only
for larger plants with well defined canopies)	Do not apply through any
type of irrigation equipment.  Apply only to containerized plants.  Do
not apply as a soil drench.

	Greenhouse	foliar spray by low pressure handwand, backpack sprayer
Ornamentals	0.013 lb ai/gal (at 1,500 ppm)	Do not apply through any type
of irrigation equipment.

	Greenhouse	drench by high pressure handwand	Ornamentals	0.025 lb ai/gal
(at 3,000 ppm)	Do not apply through any type of irrigation equipment.

  HYPERLINK "http://www.etigra.com/product_chlormequat.php"  Chlormequat
E-Pro Plant Growth Regulator  - liquid

(11.8% a.i.)

For Commercial Use

EPA Reg #   HYPERLINK "http://ppis.ceris.purdue.edu/htbin/prodset.com"
\l "#"  81959-12  	Greenhouse	foliar spray by low pressure handwand,
backpack sprayer	Ornamentals	0.034 lb ai/gal

(at 4,000 ppm)

Greenhouse	drench by high pressure handwand	Ornamentals	0.034 lb ai/gal

(at 4,000 ppm)

	

2.0	Occupational Exposures and Risks tc "2.0	Occupational Exposures and
Risks" 

There is a potential for exposure to chlormequat chloride in
occupational settings from handling chlormequat chloride products during
the application process (i.e., mixer/loaders, applicators, and
mixer/loader/applicators) and during postapplication activities.  As a
result, short- and intermediate-term risk assessments have been
completed for a number of occupational handler and postapplication
scenarios.

	

2.1	Occupational Handler Exposures and Risks  tc "2.1	Occupational
Handler Exposures and Risks " \l 2 

HED uses the term “handlers” to describe those individuals who are
involved in the pesticide application process.  HED believes that there
are distinct job functions or tasks related to applications and that
exposures can vary depending on the specifics of each task. Job
requirements (e.g., amount of chemical to be used in an application),
the kinds of equipment used, the target being treated, and the level of
protection used by a handler can cause exposure levels to differ in a
manner specific to each application event. 

HED uses exposure scenarios to describe the various types of handler
exposures that may occur for a specific active ingredient. The use of
scenarios as a basis for exposure assessment is very common as described
in the U.S. EPA Guidelines for Exposure Assessment (U.S. EPA; Federal
Register Volume 57, Number 104; May 29, 1992).  Information from the
current labels, use and usage information, toxicology data, and exposure
data were all key components in the development of the exposure
scenarios.  HED has developed a series of general descriptions for tasks
that are associated with pesticide applications.  Tasks associated with
occupational pesticide handlers are categorized using one of the
following terms:

Mixers and/or Loaders: These individuals perform tasks in preparation
for an application.  These individuals would mix the chlormequat
chloride and transfer it into the application equipment.

Applicators: These individuals operate application equipment during the
release of a pesticide product into the environment.  These individuals
would apply the chlormequat chloride.

Mixer/Loader/Applicators and or Loader/Applicators: These individuals
are involved in the entire pesticide application process (i.e., they do
all job functions related to a pesticide application event).  These
individuals would transfer chlormequat chloride into the application
equipment and then also apply it.

A chemical can produce different effects based on how long a person is
exposed, how frequently exposures occur, and the level of exposure.  HED
classifies exposures up to 30 days as short-term and exposures greater
than 30 days up to several months as intermediate-term.  HED completes
both short- and intermediate-term assessments for occupational scenarios
in essentially all cases, because these kinds of exposures are likely
and acceptable use/usage data are not available to justify deleting
intermediate-term scenarios.  Based on use data and label instructions,
HED believes that occupational chlormequat chloride exposures may occur
over a few days for many use-patterns and that intermittent exposure
over several weeks also may occur.  Long-term handler exposures are not
expected to occur for chlormequat chloride based on the current use
profile.  Chlormequat chloride is likely used in greenhouses and
nurseries throughout the year on various ornamental species.  These uses
would likely result in a series of short-term exposures as opposed to 6
months of consecutive daily exposure (i.e., long-term exposure).  Note
that the same toxicological endpoint of concern (from the same
developmental study) has been selected for short- and intermediate-term
inhalation exposures to chlormequat chloride, therefore, the risk
results for these inhalation durations of exposure also are numerically
identical.

Other parameters are also defined from use and usage data such as
application rates and application frequency.  HED always completes
non-cancer risk assessments using maximum application rates for each in
order to ensure there are no concerns for each specific use.

  

Occupational handler exposure assessments are completed by HED using
different levels of risk mitigation.  Typically, HED uses a tiered
approach.  The lowest tier is designated as the baseline exposure
scenario (i.e., long-sleeve shirt, long pants, shoes, socks, and no
respirator).  If risks are of concern at baseline attire, then
increasing levels of personal protective equipment or PPE (e.g., gloves,
double-layer body protection, and respirators) are evaluated.  If risks
remain a concern with maximum PPE, then engineering controls (e.g.,
enclosed cabs or cockpits, water-soluble packaging, and closed
mixing/loading systems) are evaluated.  This approach is used to ensure
that the lowest level of risk mitigation that provides adequate
protection is selected, since the addition of PPE and engineering
controls involves an additional expense to the user and – in the case
of PPE – also involves an additional burden to the user due to
decreased comfort and dexterity and increased heat stress and
respiratory stress.

		2.1.1	Data and Assumptions for Handler Exposure Scenarios  tc "2.1.1
Data and Assumptions For Handler Exposure Scenarios " \l 3 

2.1.1.1	Assumptions for Handler Exposure Scenarios  tc "2.1.1.1
Assumptions for Handler Exposure Scenarios " \l 4 

A series of assumptions and exposure factors served as the basis for
completing the occupational handler risk assessments.  Each assumption
and factor is detailed below on an individual basis. The assumptions and
factors used in the risk calculations include:

HED has patterned this risk assessment on a series of likely
representative scenarios that are believed by HED to represent the vast
majority of chlormequat chloride uses.

Occupational handler exposure estimates were based on surrogate data
from the Pesticide Handlers Exposure Database (PHED).

Average body weight of an adult handler is 70 kg because the toxicity
endpoint values used for the assessments are appropriate for average
adult body weight representing the general population

Generic protection factors (PFs) were used to calculate exposures when
data were not available.  For example, an 80 percent protection factor
was assumed for the use of a respirator equipped with a dust/mist
filter.

For non-cancer assessments, HED assumes the maximum application rates
allowed by labels in its risk assessments (see Table 5).

The average occupational workday is assumed to be 8 hours.

The daily areas treated were defined for each handler scenario (in
appropriate units) by determining the amount that can be reasonably
treated in a single day (e.g. acres, square feet, cubic feet, or gallons
per day).  When possible, the assumptions for daily areas treated are
taken from the HED ExpoSAC SOP #9: Standard Values for Daily Acres
Treated in Agriculture which was completed on July 5, 2000.

Groundboom: 1 acre (based on label requirements);

Low Pressure Handwand Sprayer: 40 gallons per day;

Backpack Sprayer: 40 gallons per day; and

High Pressure/Volume Handwand: 1,000 gallons per day.

2.1.1.2	Exposure Data for Handler Exposure Scenarios  tc "2.1.1.2
Exposure Data for Handler Exposure Scenarios " \l 4 

HED uses unit exposure to assess handler exposures to pesticides.  Unit
exposures are estimates of the amount of exposure to an active
ingredient a handler receives while performing various handler tasks and
are expressed in terms of micrograms or milligrams of active ingredient
per pounds of active ingredient handled.  HED has developed a series of
unit exposures that are unique for each scenario typically considered in
our assessments (i.e., there are different unit exposures for different
types of application equipment, job functions, and levels of
protection).  The unit exposure concept has been established in the
scientific literature and also through various exposure monitoring
guidelines published by the U.S. EPA and international organizations
such as Health Canada and OECD (Organization for Economic Cooperation
and Development).

Pesticide Handler Exposure Database (PHED) Version 1.1 (August 1998):
PHED was designed by a task force of representatives from the U.S. EPA,
Health Canada, the California Department of Pesticide regulation, and
member companies of the American Crop Protection Association.  PHED is a
software system consisting of two parts – a database of measured
exposures for workers involved in the handling of pesticides under
actual field conditions and a set of computer algorithms used to subset
and statistically summarize the selected data.  Currently, the database
contains values for over 1,700 monitored individuals (i.e., replicates).

Users select criteria to subset the PHED database to reflect the
exposure scenario being evaluated.   The subsetting algorithms in PHED
are based on the central assumption that the magnitude of handler
exposures to pesticides are primarily a function of activity (e.g.,
mixing/loading, applying), formulation type (e.g., liquids, granulars),
application method (e.g., aerial, groundboom), and clothing scenarios
(e.g., gloves, double layer clothing).

Once the data for a given exposure scenario have been selected, the data
are normalized (i.e., divided by) by the amount of pesticide handled
resulting in standard unit exposures (milligrams of exposure per pound
of active ingredient handled).  Following normalization, the data are
statistically summarized.  The distribution of exposure for each body
part (e.g., chest, upper arm) is categorized as normal, lognormal, or
“other” (i.e., neither normal nor lognormal).  A central tendency
value is then selected from the distribution of the exposure for each
body part.  These values are the arithmetic mean for normal
distributions, the geometric mean for lognormal distributions, and the
median for all “other” distributions.  Once selected, the central
tendency values for each body part are combined into a “best fit”
exposure value representing the entire body.

The unit exposures calculated by PHED generally range from the geometric
mean to the median of the selected data set.  To add consistency and
quality control to the values produced from this system, the PHED Task
Force has evaluated all data within the system and has developed a set
of grading criteria to characterize the quality of the original study
data.  The assessment of data quality is based on the number of
observations and the available quality control data.  While data from
PHED provide the best available information on handler exposures, it
should be noted that some aspects of the included studies (e.g.,
duration, acres treated, pounds of active ingredient handled) may not
accurately represent labeled uses in all cases.  HED has developed a
series of tables of standard unit exposure for many occupational
scenarios that can be utilized to ensure consistency in exposure
assessments.  Unit exposures are used which represent different levels
of personal protection as described above.  Protection factors were used
to calculate unit exposures for varying levels of personal protection if
data were not available.

		2.1.2	Chlormequat Chloride Handler Exposure Scenarios  tc "2.1.2
MGK-264 Handler Exposure Scenarios " \l 3 

It has been determined that exposure to pesticide handlers is likely
during the occupational use of chlormequat chloride in greenhouse,
nurseries, and shadehouses.  The anticipated use patterns and current
labeling indicate several occupational exposure scenarios based on the
types of equipment and techniques that can potentially be used for
chlormequat chloride applications. The quantitative exposure/risk
assessment developed for occupational handlers is based on the following
scenarios. [Note: The scenario numbers correspond to the tables of risk
calculations included in the occupational risk calculation aspects of
the appendices.]

Mixer/Loaders:

	(1) Liquid Formulations for Groundboom Applications

	Applicators:

(2) Groundboom Spray Applications

	

	Mixer/Loader/Applicators:

(3) Liquid Formulations: Low Pressure Handwand/HandwandBackpack Sprayer
(using PHED liquid low pressure handwand data)

(4) Liquid Formulations: High Pressure Handwand

	2.1.3	Non-cancer Chlormequat Chloride Handler Exposure and 			
Assessment tc "2.1.3	Non-cancer MGK-264 Handler Exposure and Assessment
" \l 3 

2.1.3.1	Non-cancer Chlormequat Chloride Handler Exposure and 			Risk
Calculations  tc "2.1.3.1	Non-cancer MGK-264 Handler Exposure and Risk
Calculations " \l 4 

Daily Exposure: Daily inhalation handler exposures are estimated for
each applicable handler task with the application rate, the area treated
in a day, and the applicable inhalation unit exposure using the
following formula:

Daily Exposure (mg ai/day) = Unit Exposure * Application Rate * Daily
Area Treated

Where:  

μg ai/day) inhaled that is available for 				inhalation absorption;

Unit Exposure 		=	Unit exposure value (mg or μg ai/day) derived from
August 1998 			PHED data;

Application Rate		=	Normalized application rate based on a logical unit
treatment, such as 			acre or gallon; and

Daily Area Treated	=	Normalized application area based on a logical unit
treatment such as 	acres/day (A/day) or gallons/day (gal/day).

Daily Dose:  The daily inhalation dose is calculated by normalizing the
daily exposure by body weight and adjusting, if necessary, with an
appropriate inhalation absorption factor.  For all inhalation exposure
scenarios for chlormequat chloride, an average adult body weight of 70
kilograms was used, since the toxicological endpoint of concern was not
gender-specific.  Since the inhalation toxicological endpoint of concern
is based on an oral study, an inhalation absorption rate of 100% was
used to estimate the amount of chlormequat chloride likely to be
absorbed through the lungs following inhalation exposures.

Daily dose was calculated using the following formula:

Average Daily Dose (mg/kg/day) = Daily Exposure * Absorption Factor /
Body Weight

Where:

Average Daily Dose	= 	Absorbed dose received from exposure to a
pesticide in a given 	scenario (mg pesticide active ingredient/kg body
weight/day);

	Daily Exposure		=	Amount (mg ai/day) inhaled that is available for
inhalation absorption;

Absorption Factor	= 	A measure of the amount of chemical that crosses a
biological 							boundary such as the lungs (% of the total available
absorbed); and

Body Weight		= 	Body weight determined to represent the population of
interest in a risk 

	assessment (kg).

Margins of Exposure:  Non-cancer inhalation risks for each applicable
handler scenario are calculated using a Margin of Exposure (MOE), which
is a ratio of the daily dose to the toxicological endpoint of concern. 
All MOE values were calculated using the formula below:

MOE = NOAEL or LOAEL (mg/kg/day) / Average Daily Dose (mg/kg/day)

Where:

MOE 	= 	Margin of Exposure, value used by HED to represent risk or how
close 	a chemical exposure is to being a concern (unitless);

Average Daily Dose	= 	Average Daily Dose or the absorbed dose received
from exposure to a 						pesticide in a given scenario (mg pesticide
active ingredient/kg body 						weight/day); and

NOAEL or LOAEL	= 	Dose level in a toxicity study, where no observed
adverse effects 						(NOAEL) or where the lowest observed adverse
effects (LOAEL) 						occurred in the study.

Risk values are presented below for each scenario.

Chlormequat Chloride Non-cancer Risk Summary (using 	

	PHED data)

 tc "2.1.3.2	MGK-264 Non-cancer Risk Summary (using PHED, ORETF, and
proprietary data) " \l 4 

The results indicate that all of the occupational handler risks do not
exceed HED’s level of concern [i.e., MOEs are greater than 100].  A
summary of the short- and intermediate-term risks for each exposure
scenario are presented below in Table 6.

Table 6.  Chlormequat Chloride Inhalation Occupational Handler Risks

Exposure Scenario	Crop or Target	Application Rate a	Area Treated Daily 
Baseline Inhalation Unit Exposure (ug/lb ai)	Baseline Inhalation Dose
(mg/gk/day)  b	Baseline Inhalation MOE c

Mixer/Loader

Mixing/Loading Liquids Concentrates for Groundboom Applications (1)
ornamentals: shadehouses and nurseries	5.5 lb ai/A	1 A d	1.2	0.000094
320000

3.7 lb ai/A

	0.000063	470000

Applicator

Applying Sprays via Groundboom Equipment (2)	ornamentals: shadehouses
and nurseries	5.5 lb ai/A	1 A d	0.74	0.000058	520000

3.7 lb ai/A

	0.000039	770000

Mixer/Loader/Applicator

Mixing/Loading/Applying Liquid Concentrates with Low Pressure Handwand
(PHED) (3) 	ornamentals: shadehouses and nurseries	0.017 lb ai/gal	40
gals	30	0.00029	100000

	ornamentals: greenhouse	0.034 lb ai/gal

	0.00058	51000

	ornamentals: greenhouse	0.013 lb ai/gal

	0.00022	130000

Mixing/Loading/Applying Liquid Concentrates with a High Pressure
Handwand (only study is for greenhouse use) (4)	ornamentals: greenhouse
0.025 lb ai/gal	1000 gals	120	0.043	700

	ornamentals: greenhouse	0.034 lb ai/gal

	0.058	510

a	Application rates are the maximum application rates determined from
EPA registered labels for chlormequat chloride

b	Average Daily Dose (mg/kg/day) = Daily Exposure * Absorption Factor /
Body Weight

c	MOE = NOAEL / Average Daily Dose (mg/kg/day)

d	Maximum area treated per day of 1 acre for groundboom applications is
based on label restrictions.

2.1.4	Summary of Risk Concerns and Data Gaps for Occupational 			
Handlers  tc "2.1.5 	Summary of Risk Concerns and Data Gaps for
Occupational Handlers " \l 3 

			2.1.4.1	Summary of Risk Concerns 

All of the chlormequat chloride occupational handler risks do not exceed
HED’s level of concern [i.e., MOEs are greater than 100].

			2.1.4.2	Summary of Data Gaps  tc "2.1.5.2	Summary of Data Gaps " \l 4

There are currently no specific data gaps for chlormequat chloride.

2.2	Occupational Postapplication Exposures and Risks

No dermal occupational postapplication risk assessment was performed
because a dermal endpoint was not selected for chlormequat chloride due
to its lack of systemic toxicity via the dermal route.  When there is no
dermal occupational postapplication risk assessment the restricted entry
interval (REI) is based on the acute toxicity of the chemical.  The
current chlormequat chloride label requires a 12-hour REI but
chlormequat chloride has been classified as Category II for acute dermal
toxicity.  In accordance with the requirements in the Worker Protection
Standards (WPS) - 40CFR170, ingredients classified as Category II are
assigned a 24-hour REI.  HED recommends that RD ensure that the proper
REI for ornamental plants grown in greenhouses, nurseries, and
shadehouses be included on the chlormequat chloride labels.

An inhalation occupational postapplication assessment was not performed
for chlormequat chloride due to its low vapor pressure.  However, in
nurseries and greenhouses, the WPS prohibits workers from entering the
treated area for the first four hours after an application is completed
to allow time for sprays and dusts to settle out of the air to protect
workers against postapplication inhalation exposures.

3.0	Residential and Other Non-Occupational Exposures and Risks tc "3.0
Residential and Other Non-Occupational Exposures and Risks" 

n

‚

ï

,

¦

ý

	o

	n

n

 

(

P

m

o

€

‚

ƒ

š

›

-›

œ

¹

º

»

¼

Í

Î

Ï

é

ê

ë

ì

í

î

ï

ð

ñ

jJ

jÇ



&

'

(

)

*

+

,

-

.

J

K

L

M

P

Q

„

…

†

 

 

¡

¢

£

¤

¥

¦

§

¨

Ä

Å

Æ

Ç

Ê

Ë

Û

Ü

Ý

÷

ø

ù

ú

û

ü

ý

þ

ÿ

 h:

h:

h:

h:

 h:

h:

h€

Å

&

¶

\

혈F娃똀損㘔$将

혈F娃똀損㘔$将

혈F娃똀損㘔$将

혈F娃똀損㘔$将

혈F娃똀損㘔$将

혈F娃똀損㘔$将

혈F娃똀損㘔$将

鐇Ė혈F娃똀損㘔$将

摧墂I

摧猷	

葞ￂ摧猷	

摧猷	

摧猷	

摧绁~

摧绁~

摧妭Ô

h€

„@

÷^„@

„@

÷^„@

„@

÷^„@

옍)

옍)

		

Chlormequat chloride does not currently have any registrations for
residential use nor is it registered for use in any residential
settings.  As a result, no residential chlormequat chloride handler or
postapplication assessments are required at this time.

References tc \l1 "References 

U.S. Environmental Protection Agency.  (1992).  U.S. EPA Guidelines For
Exposure Assessment (Federal Register Volume 57, Number 104; May 29,
1992).  National Center for Environmental Assessment.

U.S. Environmental Protection Agency.  Pesticide Handler Exposure
Database (PHED) Version 1.1.  Office of Pesticide Programs.  August
1998.

U.S. Environmental Protection Agency.  Health Effects Division, ExpoSAC
SOP #9: Standard Values for Daily Acres Treated in Agriculture.  July 5,
2000.

Page   PAGE  10  of   NUMPAGES  18