Document ID: EPA-HQ-OPP-2012-0125-0009
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2018-05-24T04:00Z

--------------------------------------------------------------------------------

--------------------------------------------------------------------------------

--------------------------------------------------------------------------------

--------------------------------------------------------------------------------

OFFICE OF CHEMICAL SAFETY
AND POLLUTION PREVENTION
                 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                            WASHINGTON, D.C.  20460

      	
      
      
                                                                               

MEMORANDUM

DATE:		February 7, 2012

SUBJECT:	Toxicology Scoping Document for the Registration Review of Methyl Nonyl Ketone

				Registration Review Case #: 	3094
				PC Code: 					044102				
				CAS #:						112-12-9
				Chemical Class: 				Biochemical

FROM:		Angela L. Gonzales, Biologist 	/s/
            Biochemical Pesticides Branch
            Biopesticides & Pollution Prevention Division (7511P)
            				
TO:			Leonard Cole, Senior Regulatory Specialist
				Biochemical Pesticides Branch
            Biopesticides & Pollution Prevention Division (7511P)

                                       

ACTION REQUESTED

The following scoping document contains the human health assessment for the biopesticide methyl nonyl ketone (2-undecanone) in support of the development of the Registration Review Work Plan.  
 

Executive Summary

Based on the available data and information, the Agency may need to reevaluate the current human health risk assessments for methyl nonyl ketone.  Although all human health assessment data requirements under 40 CFR 158.2050 have been fulfilled, a substantial amount of incident reports have been submitted to the Agency which will need to be reviewed.  During the course of registration review, the Agency will determine if the information in the incident reports warrants a reevaluation of the current risk assessments.  
  
I. Background

Methyl nonyl ketone is used as a dog and cat repellent in indoor and outdoor residential settings.  Products are applied on objects and around the borders of areas to be protected from dogs and cats.  The active ingredient is also employed in a pesticide product as an insect repellent which is applied to skin and clothing.  This product is primarily for use as a mosquito and tick repellent.    

The ingredient was first registered by the Agency in 1966 for use as a dog and cat repellent (Methyl Nonyl Ketone RED, 1995).  There are currently 18 registered products containing the active ingredient.  Three of these products are manufacturing-use products (MPs); the remaining 15 are end-use products (EPs).  Methyl nonyl ketone is the sole active ingredient in these products. 

The chemical is currently approved for use as an inert ingredient in pesticide products when used at 0.02% w/w or less in residential use pesticide bait products containing metaldehyde. 
        
II. Tolerances

There are no approved food uses associated with methyl nonyl ketone when used in pesticide formulations; consequently, there are no tolerances or tolerance exemptions for this active ingredient.

III. Incidents

According to the Incident Data System, there have been 452 reports of incidents occurring between January 1, 1992 and October 27, 2011 from use of products containing methyl nonyl ketone as the active ingredient.  A summary of the classification of these incidents is provided in table 1 below.  
      Table 1. Incident Data Summary for Methyl Nonyl Ketone (1992-2011)
                            Description of Incident
                               Number of Reports
                         Domestic Animal  -  Fatality
                                      11
                           Domestic Animal  -  Major
                                       7
                         Domestic Animal  -  Moderate
                                      34
                Domestic Animal  -  Moderate, Minor and Unknown
                                      170
                        Domestic Animal  -  Unspecified
                                       9
                                Human  -  Minor
                                      180
                            Human  -  Unspecified 
                                       3
                             Plant Damage - Minor
                                       1

Incidents have been reported from the use of cat and dog repellent products in the form of emulsifiable concentrates, pressurized liquids and granular formulations.  As of the date of the report, no incidents have been reported for the insect repellent product.  Based on the information presented above, the Agency will need to conduct an in-depth assessment of the incident data to determine if the current risk assessments will need to be reevaluated. 

IV. Toxicity Profile

Sufficient data have been provided to fulfill the biochemical pesticide data requirements under 40 CFR 158.2050 for the current use patterns for this active ingredient.  The data available to the Agency are summarized in Table 2 below.

Table 2. Human Health Assessment Data Requirements for Methyl Nonyl Ketone (40 CFR § 158.2050)
                           Study/OCSPP Guideline No.
                                    Results
                         Toxicity Category/Description
                                     MRID
                           Acute oral toxicity (rat)
                                  (870.1100)
                                       
                  LD50 > 5,000 mg/kg for males and females
                                       
                                      IV
                                   41904101
                        Acute dermal toxicity (rabbit)
                                  (870.1200)
                                       
       LD50 > 2,000 mg/kg (single dose tested) for males and females
                                       
                                      III
                                   41904102
                                   43163801
                       Acute inhalation toxicity	 (rat)
                                  (870.1300)
                                       
                   LC50 > 5.43 mg/L for males and females
                                       
                                      IV
                                   41904103
                        Primary eye irritation (rabbit)
                                  (870.2400)
Mildly irritating. Conjunctival irritation was cleared in all rabbits by day 7 in the study.  No corneal opacity or iritis was reported.
                                      III
                                   41904104
                      Primary dermal irritation (rabbit)
                                  (870.2500)
Moderately irritating.  Erythema and eschar formation was observed in all rabbits through 72 hours post-application.  Edema was reported in 2/6 rabbits at 72 hours post-application.
                                      III
                                   41904105
                  Dermal sensitization  (Buehler-guinea pig)
                                  (870.2600)
                                Weak sensitizer
                                       
                                   41904106
                             90-Day oral toxicity
                                  (870.3100)
Registered products are nonfood-use.  Repeated oral exposure to humans is not expected based on the use patterns of registered products.
                                       
                                      N/A
                            90-Day dermal toxicity
                                  (870.3250)
The active ingredient was administered to young adult female and male white New Zealand rabbits in a 21-day dermal toxicity study.  The doses were 0, 30, 100, or 300 mg/kg/day.  There were no systemic effects reported.  The systemic NOEL was >= 300 mg/kg/day and the LOEL was > 300 mg/kg/day. The NOEL for dermal irritation was 100 mg/kg/day and the LOEL was 300 mg/kg/day based on moderate to severe dermal irritation. 
                                       
                                   43110301
                          90-Day inhalation toxicity
                                  (870.3465)
Significant repeated inhalation exposure as a gas, vapor or aerosol is not expected based on the low vapor pressure of the chemical (4.49 X 10[-2] Torr)
                                       
                        Methyl Nonyl Ketone RED, 1995)
                                 Mutagenicity
                           (870.5100, 5300 and 5375)
Not mutagenic. 

In a mouse lymphoma cell forward mutation study, there was no evidence of induced forward mutation at the TK locus at any dose tested with or without S9 activation.  Ten doses were tested which ranged from 0 to 0.042 uL/mL in the absence of S9 activation and 0 to 0.13 uL/mL with S9 activation.

In a Chinese hamster ovary study, there was no evidence of induced chromosomal aberrations over the control values at any dose tested with or without S9 activation.  Five doses were tested which ranged from 0 to 0.10 uL/mL.   

In an unscheduled DNA synthesis (UDS) assay using primary rat hepatocytes, there was no evidence of UDS induction as measured by the incorporation of tritiated thymidine into DNA.  Five doses were tested which ranged from 0.003 to 0.3 uL/mL.  Cells were exposed for 18 to 20 hours in the presence of tritiated thymidine.  

In a bacterial reverse mutation (Ames) assay, there was no increase in reversion frequency with or without S9 activation.  Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 were exposed for 48 hours to doses ranging from 3.3, 10, 33, 100, 333, and 1000 ug/plate. 
                                       
                                   41740001
                                       
                                       
                                       
                                       
                                       
                                       
                                   41783101
                                       
                                       
                                       
                                       
                                   41774401
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                       
                                   41774402
                            Developmental toxicity
                                  (870.3700)
The active ingredient was administered by gavage to albino rats on gestation days 6 through 15 in a developmental toxicity study.  The doses were 0, 100, 300, or 1,000 mg/kg/day.  No maternal toxicity or developmental toxicity was observed.  The maternal and developmental NOELs were > 1,000 mg/kg/day.  
                                       
                                   42225901
                                   42225902

VI. References

U.S. EPA Reregistration Eligibility Decision (RED) for Methyl Nonyl Ketone.  Issued July, 1995. <http://www.epa.gov/oppsrrd1/REDs/3094.pdf>

cc:  A. L. Gonzales, L. Cole, BPPD Science Review File, IHAD/ARS
 	  A. L. Gonzales, FT, PY-S: 02/07/12