Menthol Registration Review Case No. 4063

PC Code: 051601

**UNITED STATES ENVIRONM ENTAL PROTECTION AGENCY** 
**WASHINGTON, D.C. 20460**

**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 isMenthol Registration Review Case No. 4063

PC Code: 051601

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 o C and a boiling point of

212 o C. Menthol has a vapor pressure of 0.8 mm Hg at 30 o C (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 areMenthol Registration Review Case No. 4063

PC Code: 051601

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 o il 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 ASSESSMENTMenthol Registration Review Case No. 4063

PC Code: 051601

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 LD 50 = 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 LC 50 = 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 LC 50 for the mites was approximately 19x lower (approximately 0.26 ppm) than the LC 50 for honey bees. Therefore, good control of tracheal mites could be obtained

at Menthol concentrations well below the LC 50 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.Menthol Registration Review Case No. 4063

PC Code: 051601

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. 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. Wals h, BPPD Subject File/IHAD R. S. Jones, Sr. Biologi st, FT, OPY: 03/04/2010