 

	UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

 		     WASHINGTON, D.C. 20460

 ADVANCE \d61 	OFF		ICE OF PREVENTION,

OFFICE OF PESTICIDES AND TOXIC SUBSTANCES        

MEMORANDUM

DATE:		03/04/2010

SUBJECT:	Final Non-Target Organism Hazard Assessment, Risk Assessment,
and Endangered Species Assessment for Menthol
(1R,2S,5R)-5-Methyl-2-(1-methylethyl)cyclohexanol) in Support of
Registration Review.    

			Case No.:			4063

			Chemical Class:		Biochemical

				PC Codes:			051601

CAS Nos.				2216-51-5 (L-Menthol); 153-56-60-2 (D-Menthol); 89-78-1
(D/L- 											racemic mixture) & 1490-04-6 (unspecified isomers)

			Tolerance Exemptions:	40 CFR 180.1092

FROM:			Russell S. Jones, Ph.D., Senior Biologist  /s/  03/04/2010

	Biochemical Pesticides Branch

	Biopesticides & Pollution Prevention Division (7511P)

TO:				Colin Walsh, Regulatory Action Leader

	Biochemical Pesticides Branch

	Biopesticides & Pollution Prevention Division (7511P)

EXECUTIVE SUMMARY

Menthol is a naturally-occurring organic compound found in many plants,
particularly in mint (Mentha arvensis), and it also is synthetically
manufactured.  It is found in foods derived from those plants, including
honey made from the pollen of those plants (EPA, 2004).  As an active
ingredient, it is used in two registered pesticide products intended for
use in beehives to control mites.  Two aquatic organism studies indicate
that Menthol is practically non-toxic to fish and marine invertebrates. 
However, based on the current registered uses, there will be no exposure
to any non-target animals or plants, except for honeybees.  The product
is used to protect honeybees from varroa  and tracheal mites and
treatments will not be applied at rates that would be harmful to
honeybees.  Therefore, there are no concerns for honeybees when the
product is used in accordance with EPA-approved product labeling.  

Based on the fact that Menthol is practically non-toxic to non-target
insects (honeybees) and on its use pattern and use instructions that
preclude exposure to other non-target terrestrial and aquatic organisms,
EPA has determined it will have "No Effect" on any currently listed
threatened or endangered species or any designated critical habitat. 

DESCRIPTION OF THE ACTIVE INGREDIENT

Menthol is a waxy, crystalline substance, clear or white in color, which
is solid at room temperature.  It is slightly soluble in water, a
melting point of 41-44 oC and a boiling point of 212 oC.  Menthol has a
vapor pressure of 0.8 mm Hg at 30 oC (see Memorandum from C. Swartz to
K. Davis, dated 10/26/92).  It is found in foods derived from those
plants, including honey made from the pollen of those plants (EPA,
2004).  Natural menthol exists as one pure stereoisomer, nearly always
the (1R,2S,5R) form (bottom left of diagram below) (L & A, 2010). The
other seven stereoisomers are

EPA-REGISTERED END-USE PRODUCTS

There are two registered end-use products containing Menthol as their
active ingredient (see Table 2 below).  

 Table 2.  EPA-registered Products Containing Menthol as Their Active
Ingredient

Product Name	EPA Reg. No.	Active Ingredient %	Label Use

Mite-A-Thol	61671-1	99.94   	For use in over-wintering honeybee hives
for the control of tracheal mites 2

Api Life Var	73291-1	3.373 1	For use in honeybee colonies for the
suppression of varroa mites 3

1	As L-menthol.  Product also contains 74.09% thymol and 16.00%
eucalyptus oil as active ingredients, which are subjects of a separate
Registration Review.  

2	From product label, dated 11/24/2004.  

3	From product label, dated 11/09/2006.  

EXPOSURE ASSESSMENT

The maximum use rate for Mite-A-Thol is 50 g product/hive/application,
equivalent to a Menthol application rate of 49.97 g.  The maximum use
rate for Api Life Var is 33 g product/hive/application, equivalent to a
Menthol application rate of 1.23 g.  The products are placed within
hives contained in bee-proof containers from which Menthol vapors will
diffuse into the hive.  Assuming a minimum population of 40,000 bees per
hive (UCBA, 2010) and a maximum application of 49.97 g
Menthol/hive/application, an individual bee would be exposed to no more
than approximately 1.25 mg Menthol over the diffusion time of the
product in the hive.

ENVIRONMENTAL FATE

According to the Hazardous Substance Data Base (HSDB) environmental fate
profile, volatilization from water surfaces is expected to be an
important fate process for menthol; estimated volatilization half-lives
for a model river are 2 days, and for a model lake 18 days.  In soils,
L-menthol is expected to have low mobility and will volatilize rapidly
under moist conditions" (EPA, 2004).  Due to the intended application of
Menthol-containing products within beehives, it is highly unlikely that
Menthol will enter aquatic systems when the products are used in
accordance with EPA-approved labeling.  

HAZARD ASSESSMENT

An ECOTOX search did not reveal any available study data for birds, or
any toxic endpoints for other non-target terrestrial organisms.   One
study in fish and one study in a marine aquatic invertebrate indicated
that there would be no adverse effects on aquatic organisms.  Fathead
minnows (Pimephales promelas) exhibited a 96-hr LD50 = 189 ppm
(practically non-toxic) when exposed to 99% Menthol in solution (Geiger,
Call, & Brooke, 1988).  In a non-guideline aquatic organism study, no
mortality was observed in Pink or Queen conch (Strombus gigas) exposed
to 250 ppm Menthol (practically non-toxic) for 24 hours (Acosta-Salmon &
Davis, 2007).  

A non-guideline laboratory bioassay with worker honey bees infested with
tracheal mites reported an LC50 = 5 ppm (Ellis and Baxendale, 1997). 
The bees were contained within a wire cage that was suspended within a
glass container whose inner walls were coated with crystallized Menthol.
 The study authors noted that the Menthol had a high margin of safety
(MOS) for honey bees in that the LC50 for the mites was approximately
19x lower (approximately 0.26 ppm) than the LC50 for honey bees. 
Therefore, good control of tracheal mites could be obtained at Menthol
concentrations well below the LC50 for honey bees.   No honey bee adult
or brood mortalities were reported in a series of efficacy studies
conducted in Nebraska, Oklahoma, Texas, and Mexico at Menthol
application rates ranging from 25 to 90 g per hive (EPA, 1988).  

A recent science review in support of the registration of Api Live Var
(EPA Reg. No. 73291-1), containing 3.73% Menthol as its active
ingredient, waived all non-target organism data requirements due to an
expected lack of exposure resulting from the intended use site (see
Memorandum from R. Sjoblad to A. Bryceland, dated 06/28/2006).  An
Aggregate Incident Summary Report for Menthol for the time period
01/01/1992 through 10/02/2009 did not list any non-target organism or
environmental effects incidents resulting from the use of products
containing Menthol as their active ingredient.  In a report from the
OECD (2003), it was noted that although Menthol "may possess a hazard to
the environment," no further testing was needed because "acute toxicity
is only evident at very high doses."  

RISK ASSESSMENT

Based on the application method of end-use products containing Menthol
as their active ingredient in beehives, there is no exposure of Menthol
to non-target terrestrial and aquatic organisms, except for honeybees. 
There are no concerns for honeybees because the product is used to
protect honeybees from varroa  and tracheal mites and treatments will
not be applied at rates that would be harmful to honeybees.  The end-use
products containing Menthol as their active ingredient are not intended
for any terrestrial or aquatic applications, except for application
within beehives.  

Based on the fact that is practically non-toxic to non-target insects
(honeybees) and aquatic organisms, and on its use pattern and use
instructions, EPA has determined it will have "No Effect" on any
currently listed threatened or endangered species or any designated
critical habitat. 

REFERENCES

Acosta-Salmon, H. and M. Davis.   2007.   Inducing Relaxation in the
Queen Conch Strombus gigas (L.) for Cultured Pearl Production. 
Aquaculture 262(1):73-77.

Ellis, M. D. and F. P. Baxendale.  1997.  Toxicity of seven
monoterpenoids to tracheal mites (Acari:  Tarsonemidae) and their honey
bee (Hymenoptera:  Apidae) hosts when applied as fumigants.  Journal of
Economic Entomology 90(5):  1087-1091.  

EPA.  1988.  Memorandum from V. F. Boyd to H. L. Jamerson, dated
09/30/1988.  

EPA.  2004.  Report on of the Food Quality Protection Act (FQPA)
Tolerance Reassessment Progress and Risk Management Decision (TRED) for
Menthol.  

Geiger, D.L., D.J. Call, and L.T. Brooke.  1988.  Acute Toxicities of
Organic Chemicals to Fathead Minnows (Pimephales promelas) Volume IV. 
Ctr. for Lake Superior Environ. Stud., Volume 4, Univ.of 
Wisconsin-Superior, Superior, WI :355.  

Leffingwell & Associates (L & A).  2010.  Menthol and Menthol Enatiomers
- Organoleptic Properties. 
http://www.leffingwell.com/menthol1/menthinfo.htm  

Organization for Economic Cooperation and Development (OECD).  2003. 
Screening Information Data Set (SIDS)  Initial Assessment Report.   
HYPERLINK "http://www.chem.unep.ch/irptc/sids/OECDSIDS/MENTHOLS.PDF" 
http://www.chem.unep.ch/irptc/sids/OECDSIDS/MENTHOLS.PDF 

Utah County Beekeepers Association (UCBA).  2010.  Fun facts about
honey, and beehives. February 20, 2010 Update. 
http://www.utahcountybeekeepers.org/Fun%20Facts.html

cc:	R. S. Jones, C. Walsh, BPPD Subject File/IHAD

	R. S. Jones, Sr. Biologist, FT, OPY:  03/04/2010

	 

Menthol	           	Registration Review Case No. 4063

PC Code:   051601		    	    

