Document ID: EPA-HQ-OPP-2007-1039-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-12-12T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

 OFFICE OF

                                                                        
                                    PREVENTION, PESTICIDES AND 

         TOXIC SUBSTANCES

November 29, 2007

MEMORANDUM

SUBJECT:	Summary of Human Health Effects Data for Alkyl Amine
Hydrochloride (Coco Alkyl Amine Registration Review Case) Decision
Document.

	DP #:	342138		Case No.:  3051

			PC Code:  069152		CAS#:  91745-52-7

FROM:		Nathan Mottl, Biologist    

Risk Assessment and Science Support Branch (RASSB)

Antimicrobials Division (7510P)

TO:			Heather Garvie, Chemical Review Manager

Regulatory Management Branch II

Antimicrobials Division (7510P)

THRU:	Norm Cook, Branch Chief

Risk Assessment and Science Support Branch (RASSB)

Antimicrobials Division (7510P)

Introduction

	The AD Alkyl Amine Hydrochloride Registration Review Team has evaluated
the status of the human health assessments for alkyl amine
hydrochloride, which is an antimicrobial pesticide used for material
preservative use sites (resins, paints, adhesives, printing inks and
dispersed colors, caulks, spackling, joint cements, sealants, grouts,
and wallboard compounds).  Alkyl amine hydrochloride (derived from fatty
acids of coconut oil) acts as a bacteriostat and fungicide. The team
looked at the hazard and exposure databases for alkyl amine
hydrochloride to determine whether changes in science policy or
deficiencies in the databases materially affected the overall risk
picture.  Alkyl amine hydrochloride (a.k.a, alkyl amine hydrochloride)
was first registered in 1971. A Reregistration Eligibility Decision
(RED) document was prepared for alkyl amine hydrochloride in 1992.  

	Alkyl amine hydrochloride products are formulated as liquid or soluble
concentrate.  Coco alky amine is soluble in water (44.5 gm/100mL) and
has a log Kow of 11± 3.  It has a low vapor pressure (1E-5 torr) and it
is stable to hydrolysis over the short term.  Alkyl amine hydrochloride
is registered as a formulation intermediate on labels and is a non-food
use chemical in material preservatives such as resins, paints,
adhesives, printing inks and colors, caulks, spackling, grouts and ready
mix wallboard compounds. Therefore, a dietary assessment is not
required.  The occupational uses of alkyl amine hydrochloride were
qualitatively assessed in the 1992 RED. Since this RED was performed
before FQPA, the residential uses were not assessed. 

	The primary source of information was the most recent alkyl amine
hydrochloride RED (1992).  No new toxicity data for alkyl amine
hydrochloride have been submitted to the Agency since registration.  The
purpose of this screen is to determine whether sufficient data are
available to support registration review, whether new human health
assessments are needed to support registration review, and to report why
the Agency feels it may be appropriate to conduct a new risk assessment
under the registration review process.  

	There are no direct food or feed uses of alkyl amine hydrochloride;
therefore, EPA has not established tolerances or exemptions from
tolerances in raw agricultural commodities or processed food and feed
products under the Federal Food, Drug and Cosmetic Act (FFDCA).

 

Section 1.  Chemical Identity

	Alkyl amine hydrochloride is a liquid at room temperature which is
soluble in water (44.5 gm/100mL) and an octanol/water partition
coefficient of 11± 3. It has a low vapor pressure (1E-5 torr), a
boiling point of 101.4° C, density of 0.975 g/cm3 and it is stable to
hydrolysis over the short term.  

Section 2.  Toxicology

	This health assessment addresses the toxicity of alkyl amine
hydrochloride. Alkyl amine hydrochloride is a liquid under room
temperature and is miscible in water and is stable to hydrolysis. 
Therefore, based on current use patterns only the parent compound is
likely a concern for handlers for liquids, and post-application in
material preservatives. 

	When alkyl amine hydrochloride was initially registered, the registrant
submitted a toxicity data set which consisted mainly of acute toxicity
data requirements, both 21-day and 90-day rat dermal toxicity studies, a
rat developmental toxicity study, and various mutagenicity studies.
Alkyl amine hydrochloride was classified as toxicity category III for
acute oral and dermal (rats), was a severe irritant in two rabbit
studies, and was also corrosive to the skin of rabbits.  It was also a
mild to strong dermal sensitizer in guinea pigs.

	The acute inhalation toxicity test and eye effects test in rats was
waived, but the categories for these tests were both category I based on
the evidence of dermal irritation.  A 1-hr inhalation limit dose test
identified an LC50 of 1.3 mg/L.  However, a 90-day inhalation study was
not submitted.  This study will be essential in order to characterize
the risks of the short- and intermediate inhalation exposure route for
uses of alkyl amine hydrochloride to paints. 

	The Agency has received a 21-day dermal study (MRID 41671708) on rats. 
This study indicated dermal irritation effects for rats at all test
doses tested (0, 100, 500, or 1000 mg/kg/day).  In addition, a 90-day
dermal study (MRID 41735501) was conducted on rats. In this study, doses
were administered at 0, 50, 125, and 250 mg/kg/day.  A LOAEL of 125
mg/kg/day was assigned based on dermal inflammatory responses and
increased adrenal weight.  Both a NOAEL of < 50 mg/kg/day was assigned
for dermal effects and a NOAEL of 50 mg/kg/day was evident for systemic
effects.  In addition, a rat developmental study (MRID
41537601/41537602) was submitted.  In this study, a maternal NOAEL of 25
mg/kg/day was identified.  The LOAEL of 75 mg/kg/day was based on
reduced body weight gain and food consumption in female rats. In
addition, a developmental NOAEL of 75 mg/kg/day was also identified. The
LOAEL of 150 mg/kg/day was based on increased post-implantation loss and
reduced fetal weight.         

Section 3. Dietary Assessment

A dietary risk assessment is not needed for alkyl amine hydrochloride
because it has no registered uses where it will come in direct contact
with food.  In addition, alkyl amine hydrochloride has no tolerances or
exemptions from tolerance in raw agricultural commodities or processed
food and feed products. Because there is an adhesive use for alkyl amine
hydrochloride and there are no use limitations stated on either of the
labels, there may be potential for indirect food contact.  During the
public comment period, the Agency may receive additional information
clarifying use patterns for alkyl amine hydrochloride.  Therefore, the
Agency may conduct a dietary risk assessment in the future.

Section 4.  Aggregate and Cumulative Exposure

	In examining aggregate exposure, EPA takes into account the available
and reliable information concerning exposures to pesticide residues in
food and drinking water, and non-occupational pesticide exposures. Alkyl
amine hydrochloride has no food registrations and is therefore is not
subject to FQPA which requires the Agency to consider aggregate and
cumulative exposures.  However, there is the potential of
non-occupational (i.e., residential) exposures from this use.  EPA has
not yet determined whether alkyl amine hydrochloride has a common
mechanism with other compounds, consequently a cumulative assessment
will not be performed.



Section 5.  Occupational/Residential Exposure

	The Agency conducted an occupational assessment of alkyl amine
hydrochloride for the Alkyl Amine Hydrochloride RED. However, the Agency
must conduct risk assessments to ensure that alkyl amine hydrochloride
meet the safety standards established by FFDCA, as amended by FQPA. 
Because the Alkyl Amine RED occurred in 1992 before the advent of FQPA,
a quantitative occupational and residential exposure assessment was not
performed.

	In manufacturing situations, handlers would be expected to be exposed
via the dermal and inhalation exposure route to alkyl amine
hydrochloride liquid.  The acute toxicity of the technical product
indicates that alkyl amine hydrochloride is category I for inhalation,
category III for acute dermal and oral toxicity. However, alkyl amine
hydrochloride is corrosive to skin (Category I) and causes eye and
dermal irritation and may cause allergic skin reactions.  The existing
label requires users to wear chemical spray goggles and eye shields,
protective clothing, respirators and rubber gloves to protect handlers. 
In the previous RED, the Agency has concluded that when used as with PPE
directed by the label, the occupational risks to alkyl amine
hydrochloride would be minimal.  However, the Agency now will require a
quantitative risk assessment.  Since the 1992 RED, the Agency has
identified new exposure databases (e.g., PHED and CMA) that have more
adequately characterized specific antimicrobial exposures (e.g. paint)
and the Agency have found for certain antimicrobial chemicals that
exposures to products such as paints, etc. may potentially lead to risk
concerns to both occupational and residential handlers even when PPE
label restrictions are imposed.  Therefore, the Agency needs to
quantitatively assess risk.   

	 

	The Agency anticipates that for registration review both short- and
intermediate-term dermal occupational quantitative assessments will be
required to assess exposure to alkyl amine hydrochloride for open
situations in manufacturing settings for all material preservative uses
(e.g., during the manufacturing of resins, paints, adhesives, printing
inks and colors, and caulks, spackling, grouts and ready mix wallboard
compounds) and short-term residential assessments will be required for
paint. These risk assessments were not conducted in the original alkyl
amine hydrochloride RED. In addition, the Agency will also examine alkyl
amine hydrochloride inhalation occupational and residential assessments
for the material preservative applications (e.g. painting). The
inhalation exposure assessment can also not be assessed at this time due
to a lack of 90-day inhalation toxicity data (see Appendix A for
justification).   When a toxicological inhalation endpoint is
established, the Agency will likely use task force submitted data to
conduct the inhalation handler occupational and residential assessments.
 A dermal handler assessment for alkyl amine hydrochloride will be
assessed later during registration review once the toxicological
endpoints are selected from a more complete toxicity database. 
Toxicological endpoints for quantitative risk assessment were not
originally selected in the original alkyl amine hydrochloride RED.
Occupational and residential post-application dermal and inhalation
exposures are expected to be minimal based on the use patterns and low
volatility of the chemical and an assessment will not be required. 

	

Section 6.  Anticipated Data Needs

The Antimicrobial Division (AD) anticipates the need for the following
studies to complete the registration review for this chemical.  These
studies were not required in the original 1992 RED data callin (DCI),
but this data are now anticipated (refer to Appendix A for
justifications):

Human Health Toxicity Data Needs 

(GLN 870.3465) 90-Day Inhalation Toxicity Study

Residential Applicator Exposure Data Needs

(GLN 875.1100) Dermal Outdoor Exposure

(GLN 875.1200) Dermal Indoor Exposure

(GLN 875.1300) Inhalation Outdoor Exposure

(GLN 875.1400) Inhalation Indoor Exposure

(GLN 875.1600) Data Reporting and Calculations

(GLN 875.1700) Product Use Information

Occupational Applicator Exposure Data Needs

(GLN 875.1100) Dermal Outdoor Exposure

(GLN 875.1200) Dermal Indoor Exposure

(GLN 875.1300) Inhalation Outdoor Exposure

(GLN 875.1400) Inhalation Indoor Exposure

(GLN 875.1600) Data Reporting and Calculations

(GLN 875.1700) Product Use Information

Appendix A and B provide detailed justifications why these studies are
required.

Section 7.  Tolerances

There are no tolerances for alkyl amine hydrochloride.

Section 8.  Overall Conclusions

	The Agency reviewed the hazard and exposure databases for alkyl amine
hydrochloride and anticipates that additional toxicity and exposure data
will be needed (see section 6 for specific studies) for registration
review.  In addition, the EPA anticipates that an occupational and
residential handler assessment will need to be conducted for the dermal
and inhalation exposure route, since no specific quantitative
occupational or residential risk assessments are currently available in
the current database for alkyl amine hydrochloride.  The Agency feels
that they need to conduct risk assessments to ensure that alkyl amine
hydrochloride registration review case meets the safety standards
established by FFDCA, as amended by FQPA. 

Section 9.  Reference 

The  August, 1992 Alkyl Amine Hydrochloride RED was considered in the
development of this document.  The full RED and Fact Sheet are available
on EPA’s Pesticide Reregistration Status web site.    HYPERLINK
"http://www.epa.gov/pesticides/reregistration/status.htm" 
http://www.epa.gov/pesticides/reregistration/status.htm 

Appendix A. Toxicity Guideline Study Justifications

Guideline	Study Title	Practical Utility of the Data

870.3465	90-Day Inhalation Toxicity Study

(Rat)	1)  What is the value of the study?

The Agency does not have a full picture of the potential effects which
alkyl amine hydrochloride could occur as a result of exposure via the
inhalation route.  The needed study would provide insight into concerns
regarding toxicity via the inhalation route.  It may also provide a
toxicity endpoint applicable to risk assessment.

2)  How would the data be used?

The study may result in a change in how risks are quantified.  The data
would allow the Agency to conclude more definitively whether or not
there would be any concerns for inhalation toxicity in the rat.  This
would provide a more complete hazard characterization of alkyl amine
hydrochloride in regards to the potential risks to the U.S. general
population.

3)  How could the data affect the risk assessment?

The study may result in a change in how risks are quantified.  It is
possible that the database uncertainty factor be reduced or removed,
resulting in different magnitude of the value of the endpoint used for
regulation.

4)  What is triggering the need for this data?

The difficulty of predicting real world human inhalation exposure with
limited data and no inhalation data or other alternative information,
such as SAR (structure-activity-relationship), surrogate data, and/or
weight-of-evidence to the Agency triggered the need for a 90-day
(guideline) Inhalation toxicity study, in order to adequately evaluate
real world human exposure to alkyl amine hydrochloride particles based
on how it is used (The OPPTS Guidelines require an MMAD of 1-3 (m in
inhalation toxicity studies of aerosols so that a portion of the test
article will reach the lungs). The exposure to paints from sprays and
mists are triggering the need for toxicological data in order to conduct
a risk assessment. 



Appendix B: Exposure Guideline Study Justifications 

Guideline	Study Title	Practical Utility of the Data

875.1100 and 875.1200

(Applicator)

	Dermal Outdoor Exposure and Dermal Indoor Exposure	Note:  Dermal
exposure data are needed for both residential and occupational uses. 
The selection of an outdoor versus an indoor site is based on the high
end exposure scenario.  In almost all cases, repeating an exposure study
for the same scenario outdoors and indoors is not necessary.

1)  What is the value of the study?

The potential for dermal exposure is very likely for exposure scenarios
such as paint rollers, airless sprayers, and liquid pouring. The
existing CMA data base and PHED for these scenarios are limited in scope
for QA/QC and number of monitoring units.  EPA presented the need for
additional handler exposure data to the January 2007 Science Advisory
Panel (SAP) as well as to the April 2007 Human Studies Review Board
(HSRB) and both groups agreed that additional data are warranted. 

2)  How will the data be used?

The dermal exposure data will be used to assess the residential
short-term duration of painting with a paint brush/roller and an airless
sprayer.  For occupational uses, the dermal exposure data will be used
to assess the short- and intermediate-term commercial painters
(brush/roller and airless sprayer), as well as open pouring of the
product (e.g., poured into paint as a preservative in manufacturing
settings, adhesives, etc).  

3)  How could the data affect the risk assessment?

The dermal exposure data will be used to determine the accuracy of the
dermal risks to both residence and occupational workers.  If risks
warrant mitigation, the dermal exposure data will provide the types of
mitigation necessary such as chemical resistant gloves or closed systems
for commercial uses to potential removal of uses from the label.

4)  What is triggering the need for this data?

The criteria for the dermal exposure data are based on the potential for
dermal exposure from the labeled uses (e.g., airless sprayers, etc.) and
evidence of toxicity.  If the toxicological endpoints from alkyl amine
hydrochloride are used to assess the risks, there is an endpoint
selected for the dermal route.  

875.1300 and

875.1400

(Applicator)	Inhalation Outdoor Exposure and Inhalation Indoor Exposure
Note:  Inhalation exposure data are needed for both residential and
occupational uses.  The selection of an outdoor versus an indoor site is
based on the high end exposure scenario (for inhalation the selection is
typically indoors).  In almost all cases, repeating an exposure study
for the same scenario outdoors and indoors is not necessary.

1) What is the value of the study?

The inhalation exposure route is very important for exposure scenarios
such as paint rollers and airless sprayers where aerosols would be
generated.  In addition, inhalation exposures from liquid pouring are
evident in exposure studies in the Pesticide Handlers Exposure Database
(PHED).  The significance of these exposures is directly affected by the
severity of the inhalation toxicological endpoint of concern.  At this
point in time, no toxicological data are available to assess the
inhalation risk. The existing Chemical Manufacturer Association (CMA)
data base and PHED for these scenarios are limited in scope for QA/QC
and number of monitoring units.  EPA presented the need for additional
handler exposure data to the January 2007 Science Advisory Panel (SAP)
as well as to the April 2007 Human Studies Review Board (HSRB) and both
groups agreed that additional data are warranted. 

2) How would the data be used?

The inhalation exposure data would be used to assess the residential
short-term duration of painting with a paint brush/roller and an airless
sprayer.  For occupational uses, the inhalation exposure data would be
used to assess the short- and intermediate-term as well as pouring zinc
borate powders (e.g., poured into paint as a preservative in
manufacturing settings for rubber, plastic, wood composite, etc). 

3) How could the data affect the risk assessment?

The inhalation exposure data would be used to determine the accuracy of
the inhalation risks to both residence and occupational workers.  If
risks warrant mitigation, the inhalation exposure data would provide the
types of mitigation necessary such as respiratory protection from
respirators or closed systems for commercial uses to potential removal
of uses from the label.

What is triggering the need for this data?

The criteria for the inhalation exposure data are based on the potential
for respiratory exposure from the labeled uses (e.g., airless sprayers)
and evidence of toxicity.  If no toxicological endpoints of concern were
identified, then the inhalation exposure data would not be needed.

875.1600

(Applicator)	Data Reporting and Calculations 	1) What is the value of
the study?

For all exposure studies this data need is needed to facilitate the
review of the data.

2) How would the data be used?

The study report and all raw data/calculations would be reviewed for the
adequacy of the data.

3) How could the data affect the risk assessment?

The data are needed to interpret the inhalation exposure data collected.

4) What is triggering the need for this data?

This data need is triggered if an exposure study is conducted.

875.1700

(Applicator)	Product Use Information	1) What is the value of the study?

Product use information is a description of how the product is actually
applied; it is not a field study.  A description of how this product is
used would provide for a comprehensive realistic assessment of its
potential applications.

2) How would the data be used?

The description of the application techniques would be used to define
the exposure scenarios to be assessed in the risk assessment.

3) How could the data affect the risk assessment?

A complete description of product use would ensure that the risk
assessment is inclusive of the types of exposures occurring during
residential and occupational use.

What is triggering the need for this data?

The need for a risk assessment as needed under Registration Review would
require that the risk assessor understands how the product is applied.

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