**UNITED STATES ENVIRONMENTAL PROTECTION
AGENCY**![](media/image1.png){width="1.6243055555555554in"
height="1.5416666666666667in"}

**WASHINGTON, D.C. 20460**

**OFFICE OF**

**PREVENTION, PESTICIDES AND**

**TOXIC SUBSTANCES**

> November 29, 2007

**[MEMORANDUM]{.underline}**

**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 K~ow~ 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**

  ------------------ ----------------------------------------------------
  **Table 1.1        
  Chemical           
  Identity**         

  Common Name        Alkyl amine hydrochloride

  CAS name           p-alkyl amine hydrochloride, 1-Dodecanamine
                     hydrochloride; Dodecylamine hydrochloride;
                     n-Dodecylamine Hydrochloride

  PC Code            069152

  CAS registry       929-73-7
  number             

  Registration       3051
  Review Case No.    

  Chemical Structure ![](media/image2.png){width="2.9902777777777776in"
                     height="1.3020833333333333in"}
  ------------------ ----------------------------------------------------

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/cm^3^ 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 LC~50~ 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]{.underline}

-   (GLN 870.3465) 90-Day Inhalation Toxicity Study

[Residential Applicator Exposure Data Needs]{.underline}

-   (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]{.underline}

-   (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.
<http://www.epa.gov/pesticides/reregistration/status.htm>

+------+--------+-----------------------------------------------------+
| #    |        |                                                     |
|  App |        |                                                     |
| endi |        |                                                     |
| x A. |        |                                                     |
|  Tox |        |                                                     |
| icit |        |                                                     |
| y Gu |        |                                                     |
| idel |        |                                                     |
| ine  |        |                                                     |
| Stud |        |                                                     |
| y Ju |        |                                                     |
| stif |        |                                                     |
| icat |        |                                                     |
| ions |        |                                                     |
+======+========+=====================================================+
| G    | Study  | Practical Utility of the Data                       |
| uide | Title  |                                                     |
| line |        |                                                     |
+------+--------+-----------------------------------------------------+
| 870. | 90-Day | **1) What is the value of the study?**              |
| 3465 | Inha   |                                                     |
|      | lation | The Agency does not have a full picture of the      |
|      | To     | potential effects which alkyl amine hydrochloride   |
|      | xicity | could occur as a result of exposure via the         |
|      | Study  | inhalation route. The needed study would provide    |
|      |        | insight into concerns regarding toxicity via the    |
|      | (Rat)  | 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.         |
+------+--------+-----------------------------------------------------+

+------+-------+------------------------------------------------------+
| #    |       |                                                      |
| Appe |       |                                                      |
| ndix |       |                                                      |
|  B:  |       |                                                      |
| Expo |       |                                                      |
| sure |       |                                                      |
|  Gui |       |                                                      |
| deli |       |                                                      |
| ne S |       |                                                      |
| tudy |       |                                                      |
|  Jus |       |                                                      |
| tifi |       |                                                      |
| cati |       |                                                      |
| ons  |       |                                                      |
+======+=======+======================================================+
| G    | Study | Practical Utility of the Data                        |
| uide | Title |                                                      |
| line |       |                                                      |
+------+-------+------------------------------------------------------+
| 875. | D     | *Note: Dermal exposure data are needed for both      |
| 1100 | ermal | residential and occupational uses. The selection of  |
| and  | Ou    | an outdoor versus an indoor site is based on the     |
| 875. | tdoor | high end exposure scenario. In almost all cases,     |
| 1200 | Exp   | repeating an exposure study for the same scenario    |
|      | osure | outdoors and indoors is not necessary.*              |
| (App | and   |                                                      |
| lica | D     | **1) What is the value of the study?**               |
| tor) | ermal |                                                      |
|      | I     | The potential for dermal exposure is very likely for |
|      | ndoor | exposure scenarios such as paint rollers, airless    |
|      | Exp   | sprayers, and liquid pouring. The existing CMA data  |
|      | osure | 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. | Inhal | *Note: Inhalation exposure data are needed for both  |
| 1300 | ation | residential and occupational uses. The selection of  |
| and  | Ou    | an outdoor versus an indoor site is based on the     |
|      | tdoor | high end exposure scenario (for inhalation the       |
| 875. | Exp   | selection is typically indoors). In almost all       |
| 1400 | osure | cases, repeating an exposure study for the same      |
|      | and   | scenario outdoors and indoors is not necessary.*     |
| (App | Inhal |                                                      |
| lica | ation | **1) What is the value of the study?**               |
| tor) | I     |                                                      |
|      | ndoor | The inhalation exposure route is very important for  |
|      | Exp   | exposure scenarios such as paint rollers and airless |
|      | osure | 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.                                 |
|      |       |                                                      |
|      |       | 4)  **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. | Data  | **1) What is the value of the study?**               |
| 1600 | Repo  |                                                      |
|      | rting | For all exposure studies this data need is needed to |
| (App | and   | facilitate the review of the data.                   |
| lica | Ca    |                                                      |
| tor) | lcula | **2) How would the data be used?**                   |
|      | tions |                                                      |
|      |       | 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. | Pr    | **1) What is the value of the study?**               |
| 1700 | oduct |                                                      |
|      | Use   | Product use information is a description of how the  |
| (App | I     | product is actually applied; it is not a field       |
| lica | nform | study. A description of how this product is used     |
| tor) | ation | 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.                                    |
|      |       |                                                      |
|      |       | 4)  **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.     |
+------+-------+------------------------------------------------------+