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      UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
       	     WASHINGTON, D.C. 20460
      		
      
                         				OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION
                             OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION
       
   
                                         
   
   MEMORANDUM                                                                  September 19, 2012
   
SUBJECT:	Summary of Ecotoxicity Data for Methyl Nonyl Ketone Registration Review 
    
   
            Registration Review 
            Case #:		
            PC Code:	              44102			
            CAS Numbers:	       112-12-9		
            Chemical Class:		Aliphatic ketone	
               		
   
   FROM:	Miachel Rexrode, Ph.D., Senior Biologist          /s/             09/19/2012
               Biochemical Pesticides Branch
               Biopesticide & Pollution Prevention Division (7511P)
   
   TO:		Gina Burnett, Regulatory Action Leader   /s/                      09/19/2012
               Biochemical Pesticides Branch
               Biopesticide & Pollution Prevention Division (7511P)
   
         
         
         

ACTION REQUESTED

The following is the final ecotoxicity assessment for methyl nonyl ketone in support of the Registration Review Decision Document.   


RECOMMENDATIONS AND CONCLUSIONS

Executive Summary

Based on the available information for methyl nonyl ketone the Agency does not foresee the need for additional ecotoxicity data for a new risk assessment and has waived all hazard and exposure data on these chemicals. The unique characteristics of these products, there non-toxic mode of action, biodegradability (low to no persistence), and use patterns (non agricultural use, residential uses) should minimize the risks to all non-targets, including threatened and endangered species. Methyl nonyl ketone risk in the environment should be low because of a lack of potential exposure (residential and indoor use) suggesting minimal risk to terrestrial and aquatic organisms and a no effect (NE) to endangered/threatened species for registered uses.

Background

Methyl nonyl ketone, also known as 2-Undecanone and IBI-246, is an oily organic liquid manufactured synthetically, but which can also be extracted from oil of rue. It is found naturally in bananas, cloves, ginger, guava, strawberries, wild-grown tomatoes, and the perennial Houttuynia cordata. This compound is used in the perfumery and flavoring industries, but because of its strong odor it is primarily used as an insect repellent or dog and cat repellent/ training aid and iris borer deterrent. Typically, 1 - 2% concentrations of 2-undecanone are found in dog and cat repellents in the form of a liquid, aerosol spray, or gel. This pesticide is used in and around households, paths, patios, solid waste containers and ornamental plants. Methyl nonyl ketone is formulated as a pressurized liquid, granular, liquid ready-to-use (pump/sprayer), solid (crystalline), and liquid for reformulating use only. EPA assumes that the volume of use of this pesticide is relatively low. Methyl nonyl ketone was first registered in the United States in 1966 for use as a dog and cat repellant. Currently, there are 18 active products registered. The Agency does not foresee the need for additional ecotoxicity data for a new risk assessment.  Ecological effects data requirements were fulfilled. 

Toxicity to Terrestrial Animals

Birds: Acute and Subacute Toxicity

In order to establish the acute and subacute toxicity of methyl nonyl ketone to birds, the following tests were required using the technical grade of the active ingredient (a.i.): one avian single-dose oral (LD50) study on one species (preferably mallard or Bobwhite quail) and subacute dietary studies (LC50) on one species of waterfowl (preferably the mallard duck) and one species of upland game bird (preferably Bobwhite quail). The results of the studies summarized in Tables 1.0 and 2.0 show that methyl nonyl ketone is practically nontoxic to avian species on an acute oral and subacute dietary basis. The guideline requirements for both the avian acute oral LD50 and the avian subacute dietary LD50 studies have been met.

Table 1.0  Avian Acute Oral Toxicity for Methyl Nonyl Ketone
Species Tested
% AI
LD50 (mg/kg)
MRID
Conclusions
Northern  Bobwhite Quail
100
> 2,250
41986501
Practically nontoxic
Mallard
100
> 2,250
41986502
Practically
nontoxic





Table 2.0 Avian Subacute Dietary Toxicity for Methyl Nonyl Ketone
Species Tested
% AI
LD50 (mg/kg)
MRID
Conclusions
Northern  Bobwhite Quail
100
> 5,620
41947901
Practically
nontoxic
Mallard
100
> 5,620
41947902
Practically
nontoxic

 Mammals

Wild mammal testing is required on a case-by-case basis, depending on the results of the lower tier studies such as acute and subacute testing, intended use pattern, and pertinent environmental fate characteristics. Under the conditions of a range-finding and developmental toxicity study done for the Agency, as summarized in the Human Health Assessment, doses up to 1,000 mg/kg/day produced no apparent related maternal or developmental effects on rats. Based on these conclusions, wild animal testing was not required for methyl nonyl ketone. The rat oral LD50 > 5,000 mg/kg suggests that this compound is practically non-toxic to mammals (MRID 41904101).

Toxicity to Aquatic Animals

Freshwater Fish

In order to establish the toxicity of methyl nonyl ketone to freshwater fish, the minimum data required on the technical grade of the active ingredient are two freshwater fish toxicity studies. One study should use a coldwater species (preferably the rainbow trout), and the other should use a warm water species (preferably the bluegill sunfish). The results of the acute toxicity studies summarized in Table 3.0 indicate that methyl nonyl ketone is moderately toxic to both cold and warm water fish. The guideline requirements for the freshwater fish toxicity studies have been met.

Table 3.0 Freshwater Fish Acute Toxicity to Methyl Nonyl Ketone
Species Tested
% AI
LC50 (ppm)
MRID
Conclusions
Rainbow Trout
100
3.0
41909603
Moderately toxic
Bluegill sunfish
100
2.1
41909602
Moderately toxic

Aquatic Invertebrates

The minimum testing required to assess the hazard of methyl nonyl ketone to freshwater invertebrates is a freshwater aquatic invertebrate toxicity test, preferably using first instar
Daphnia magna or early instar amphipods, stoneflies, mayflies, or midges. The results of the freshwater aquatic invertebrate toxicity study summarized in Table 4.0 indicate that there is sufficient information to characterize methyl nonyl ketone as highly toxic to aquatic invertebrates. The guideline requirement for the freshwater aquatic invertebrate toxicity study has been met.



Table 4.0 Freshwater Aquatic Invertebrates Acute Toxicity to Methyl Nonyl Ketone
Species Tested
% AI
EC50 (ppm)
MRID
Conclusions
Daphnia magna
97.9
0.54
41909604
Highly toxic


Ecological Effects and Endangered Species Risk Assessment

Terrestrial Species

The unique characteristics of this product, methyl nonyl ketone, the non-toxic mode of action, biodegradability (0.5 days aerobic and anaerobic degradation) and low potential for exposure will result in no risk to non-target organisms, including threatened and endangered species. Due to the non-toxic mode of action and/or lack of exposure to non-targets by this product, a Risk Quotient (RQ) is not typically calculated since the point estimates of either toxicity and/or exposure will be at or near zero. The product is not applied to agricultural plants or foliage. Label instructions specify that application is to the ground around bushes and plants (emulsifiable concentrate and granular product) and exposure is limited to residential areas.

The Agency, however, has estimated potential acute toxicity end points for avian and mammalian species (LD50 > 2,250 mg/kg) and calculated potential risk using the Terrestrial Residue Exposure Model (T-REX) Version 1.4.1 for granular formulations (Appendix A). The Agency estimated that if the granular formulation were used on one acre (1 lb product/250 sq ft or 174 lbs/A) the number of granular that would be required to achieve LC50 for terrestrial organisms (0.02 kg birds) would be about 274,884, suggesting an unlikely event. In addition, the product is a repellent, which lessens the likelihood for non-target exposure. The Agency also conducted a search (09/19/2012) of the Ecological Incident Information System version 2.1.1 (EIIS) and did not find any incidents to terrestrial species from exposure to methyl nonyl ketone. This low risk to non-target terrestrial species suggests that the potential for toxic exposure to endangered/ threatened species is also very low. The Agency calculated the chance of individual terrestrial exposure and risk by using the Individual Effects Chance Model (Version 1.1) which suggest that the chance of effects to a terrestrial species from methyl nonyl ketone exposure is about 1 in 418,000,000 (Appendix B) which may be considered as a highly unlikely event.  The low toxic risk of methyl nonyl ketone to terrestrial organisms, the short environmental half life (0.5 days), the low potential for exposure to non-target avian and mammalian species (residential application), the direct application to the ground (no contact with foliage), and an understanding of the repellent mode of action of this compound show that there is a very low potential for toxic risk to terrestrial species. Based on the proceeding information, methyl nonyl ketone presents a No Effect (NE) to threatened or endangered terrestrial species, if used in accordance with approved labeling.

Aquatic Species
 
It is difficult to assess the risks posed to aquatic species from the use of methyl nonyl ketone since uses are contained or indoors and the compound is non persistent (0.5 days) and relatively insoluble in water (18 ug/L). The potential for methyl nonyl ketone leaching into ground water or to moving offsite to surface water is unlikely. In a Leaching-Adsorption/Desorption study (MRID 42208301) methyl nonyl ketone was observed to be relatively immobile in soil (sodium azide-sterilized sandy loam, clay loam, sand, and silt loam soils). The Kads =18 and the Koc = 2,480. 

Assuming that 174 lbs. of methyl nonyl ketone product was applied to 1 acre, the Agency conducted a worst case scenario using the Generic Estimated Environmental Concentration Model (GENEEC) to assess potential exposure of the granular formulation (Appendix C). The expected peak estimated environmental concentration was calculated at 18 ppb. Using this value, a risk quotient (RQ) was calculated at (0.0) showing no toxic risk to aquatic species.
The Agency conducted a search (09/19/2012) of the Ecological Incident Information System (EIIS, version 2.1), the `Aggregate Incident Reports' (v. 1.0) database, for ecological incidents involving methyl nonyl ketone and no aquatic incidents were reported. The Agency also calculated the chance of individual fish and aquatic invertebrate exposure and risk by using the Individual Effects Chance Model (Version 1.1). These calculations suggest that the chance of effects to aquatic invertebrates (food source) or to fish from methyl nonyl ketone exposure is about 1 in 418,000,000 (Appendix B), which may be considered as a highly unlikely event. Therefore, the Agency concludes a no effect (NE) to aquatic endangered/ threatened species because of the lack of potential toxic risk to aquatic ecological systems from exposure to methyl nonyl ketone. 

Conclusion

The low toxic risk of methyl nonyl ketone to aquatic and terrestrial organisms, the short environmental half life (0.5 days), the low potential for exposure to non-target aquatic and terrestrial species (residential application), the direct application to the ground (no contact with foliage), the immobility in soil (Koc = 2,480), low water solubility (18 ug/L),  and an understanding of the repellent mode of action of this compound show that there is a very low potential for toxic risk to terrestrial and aquatic species. Based on the proceeding information, methyl nonyl ketone presents a No Effect (NE) to threatened or endangered terrestrial or aquatic species, if used in accordance with approved labeling.
















References


Beavers, J.; Grimes, J.; Smith, G. (1991) Methyl Nonyl Ketone (MGK Dog and
Cat Repellent): A Dietary LC50 Study with the Northern Bobwhite: Lab Project
Number: 163-114. Unpublished study prepared by Wildlife International Ltd.
24 p. (MRID 41947901)

Beavers, J.; Grimes, J.; Smith, G. (1991) Methyl Nonyl Ketone (MGK Dog and
Cat Repellent): A Dietary LC50 Study with the Mallard: Lab Project Number:
163-115. Unpublished study prepared by Wildlife International Ltd. 24 p. (MRID 41947902)

Campbell, S.; Lynn, S.; Smith, G. (1991) Methyl Nonyl Ketone (MGK Dog and
Cat Repellent): An Acute Oral Toxicity Study with the Northern Bobwhite: Lab
Project Number: 163-116. Unpublished study prepared by Wildlife International
Ltd. 29 p. (MRID 41986501)

Campbell, S.; Lynn, S.; Smith, G. (1991) Methyl Nonyl Ketone (MGK Dog and
Cat Repellent): An Acute Oral Toxicity Study with the Mallard: Lab Project
Number: 163-117. Unpublished study prepared by Wildlife International Ltd.
28 p. (MRID 41986502).

EPA (1993) Reregistration Eligibility Decision (RED) Methyl Nonyl Ketone. Washington, DC, US Environmental Protection Agency, EPA 738-R-95-038, 63 pp.

Gabriel, D. (1991) MGK Dog and Cat Repellent (Methyl Nonyl Ketone Acute Oral Toxicity, Single Level-Rats: Lab Project Number: 91-7236A. Unpublished study prepared by Biosearch Inc. 10 p. (MRID 41904101)

Pesselman, R. (1991) Water Solubility Determination of Methyl Nonyl Ketone:
Final Report: Lab Project Number: HWI 6001-709. Unpublished study prepared
by Hazleton Wisc. Inc. 33 p. (MRID 41986503)

Williams, M. (1992) Soil/Sediment Adsorption-Desorption of Methyl Nonyl
Ketone: Lab Project Number: 39436. Unpublished study prepared by ABC
Labs., Inc. 51 p. (MRID 42208301)










Appendix A.  T-REX Output for Methyl Nonyl Ketone Granular Formulation



Estimation of the number of granules needed to achieve toxicity thresholds
Step 1.  Estimate mass of a.i. consumed for the assessed species weight to achieve the desired toxicity threshold
Weight of assessed bird (kg)
                                     0.02
INPUT (0.02 kg is typically used for general assessments)
Adjusted LD50, mg/kg-bw
                                    1168.26
Calculated from the body weight entered in B13 and the LD50 entered in the "Inputs" sheet.
Mg a.i. needed to achieve the adjusted LD50 for bird of assessed weight
                                     23.37
mg a.i./kg-bw * kg-bw = mg a.i.
Mg a.i. needed to achieve acute LOC exceedance (1/2 adjusted LD50) for bird of assessed weight
                                     11.68

Mg a.i. needed to achieve endangered species LOC exceedance (1/10th adjusted LD50) for bird of assessed weight
                                     2.34

Step 2.  Determine the mass of a.i. per granule
Percent of a.i. in formulated product
                                     2.00%
Must enter percent a.i. specified on the label
Weight of 1 granule (mg, obtained from registrant)
                                     0.43%
INPUT (Note: Be sure to enter units in mg!)
mg a.i./granule
                                    0.0001
weight of granule (mg) x fraction of a.i. = mg a.i./granule 
Step 3.  Calculate number of granules with mass of a.i. equivalent to adjusted LD50 for bird of assessed weight
No. of granules needed to achieve adjusted LD50 
                                   274884.04
mg a.i. needed to achieve adjusted LD50 (B14) / mg a.i. per granule (B20)
No. of granules needed to achieve acute LOC exceedance (1/2 adjusted LD50) 
                                   137442.02
mg a.i. needed to achieve 1/2 adjusted LD50 (B15) / mg a.i. per granule (B20)
No. of granules needed to achieve endangered species LOC exceedance (1/10 adjusted LD50) 
                                   27488.40
mg a.i. needed to achieve 1/10 adjusted LD50 (B16) / mg a.i. per granule (B20)




















Appendix B. Individual Effects Chance Model Version 1.1 for Methyl Nonyl Ketone Exposure to Endangered/Threatened Species

Terrestrial
IEC V1.1 - Individual Effect Chance Model Version 1.1
Predictor of chance of individual effect using probit dose-response curve slope and median lethal estimate 
Enter LC50 or LD50
                                                                           5620
Enter desired threshold 
                                                                            0.1
Enter slope of dose-response
                                                                            4.5
z score result
                                                                           -4.5
Probability associated with z
                                                                       3.40E-06
Chance of individual effect,                  ~1 in .  .  .
                                                                       2.94E+05
 
 





Aquatic
IEC V1.1 - Individual Effect Chance Model Version 1.1
Predictor of chance of individual effect using probit dose-response curve slope and median lethal estimate 
Enter LC50 or LD50
                                                                           0.54
Enter desired threshold 
                                                                           0.05
Enter slope of dose-response
                                                                            4.5
z score result
                                                                    -5.85463498
Probability associated with z
                                                                       2.39E-09
Chance of individual effect,                  ~1 in .  .  .
                                                                       4.18E+08














Appendix C. GENEEC Run for Methyl Nonyl Ketone (Granular)



   Methyl Nonyl Ketone Potential Aquatic Exposure: GENEEC version 2.1
  ________________________________________________________________________________
   RATE (#/AC)   No.APPS &   SOIL    SOLUBIL    APPL TYPE   NO-SPRAY INCORP
    ONE(MULT)    INTERVAL    Koc    (PPB )         (%DRIFT)           (FT)          (IN)
 ----------------------------------------------------------------------------------------------------------------------------
74.000(*******)       12 / 30        2480.0   18.0          GRANUL        ( .0)                .0                             

  FIELD AND STANDARD POND HALFLIFE VALUES (DAYS)
 -----------------------------------------------------------------------------------------------------------------------------
  
 METABOLIC   DAYS  UNTIL   HYDROLYSIS    PHOTOLYSIS          METABOLIC  COMBINED
   (FIELD)           RAIN/RUNOFF   (POND)     (POND-EFF)    (POND)       (POND)
   -----------------------------------------------------------------------------------------------------------------------------
      .00                    2          N/A         .00-                 .00                    .50               .50


  GENERIC EECs (IN MICROGRAMS/LITER (PPB))     Version 2.0 Aug 1, 2001
  --------------------------------------------------------------------
      PEAK      MAX 4 DAY      MAX 21 DAY    MAX 60 DAY   MAX 90 DAY
      GEEC      AVG GEEC        AVG GEEC        AVG GEEC       AVG GEEC
  ------------------------------------------------------------------------------------------------------------------------------
      18.00           18.00                    18.00                18.00                        18.00

  

