Document ID: EPA-HQ-OPP-2011-1033-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-03-14T04:00Z

EPA ANTIMICROBIALS DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

EPA Antimicrobials Division contact: Tom Luminello, 703-308-8075, Luminello.tom@epa.gov

INSTRUCTIONS:  Please utilize this outline in preparing the pesticide petition.  In cases where the outline element does not apply, please insert "NA-Remove" and maintain the outline. Please do not change the margins, font, or format in your pesticide petition. Simply replace the instructions that appear in green, i.e., "[insert company name]," with the information specific to your action.

TEMPLATE:

Albemarle Corporation

Petition number to be assigned

	EPA has received a pesticide petition (1F7914 and 1F7914.02) from Albemarle Corporation, 451 Florida Street, Baton Rouge, LA  70801 requesting, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180

(Options (pick one)
   
   NA  -  Remove 1. by establishing a tolerance for residues of
   
   2. to amend 40 CFR 180.940(a) to establish a tolerance exemption for active and inert ingredients for use in antimicrobial formulations (Food-contact surface sanitizing solutions).  May be applied to: Food-contact surfaces in public eating places, dairy processing equipment, and food-processing equipment and utensils
   
Pesticide Chemical
CAS Reg. No.
Limits
1,3-dibromo-5,5-dimethylhydantoin
CAS Reg. No. 77-48-5
When ready for use, end-use concentration of all bromine-producing chemicals in solution is not to exceed 500 parts per million (ppm) of total bromine.
   
   3. to establish an exemption from the requirements of a tolerance in 40 CFR 180.____ for residues of 1,3-Dibromo-5,5-Dimethylhydantoin in or on all raw agricultural commodities, when such residues result from the use of 1,3-Dibromo-5,5-Dimethylhydantoin as an antimicrobial treatment in solutions containing a diluted end-use concentration of all bromide-producing chemicals in the solution not to exceed 900 ppm of total bromine.

EPA has determined that the petition contains data and information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

	1. Plant metabolism.  
NA

	2. Analytical method. 
Analytical method is not necessary since 1,3-dibromo-5,5-dimethylhydantoin residues are exempted from the requirements of a tolerance.

	3. Magnitude of residues. 
NA

B. Toxicological Profile

DBDMH is stable in its solid form.  It must be diluted in water in an appropriate feeder before it can be used in any application.  Upon dilution in water, DBDMH rapidly hydrolyzes to release bromine in the form of hypobromous acid, which functions as the active antimicrobial agent.  Accordingly, 1,3-Dibromo-5,5-Dimethylhydantoin is essentially a delivery system for the hypobromous acid.
DMDMH is considered a halohydantoin.  The halohydantoins include a group of chemicals composed of several halogenated and non-halogenated compounds.  
As indicated in the September 2007 Halohydantoins RED, generic data have been developed on the breakdown products, dimethylhydantoin (DMH) and ethylmethylhydantoin (EMH).  The primary reason for developing generic data on DMH and EMH rather than the entire halohydantoin molecule is that these ring structures represent the persistent component of the halohydantoins.  A secondary reason for evaluating the halohydantoin moieties is that the corrosive properties of the released halogens would limit the amount of chemical that could be administered laboratory animals; thereby, precluding a meaningful evaluation of the halohydantoin moieties.  The Agency also determined that data developed on DMH was applicable to EMH and vice versa.  The basis for this decision was the similarity of the chemical structure of these two chemicals and the similarity of results from  studies conducted on both the DMH and EMH compounds.
Non-acute toxicity testing of dimethylhydantoins (including subchronic, developmental, reproductive, and chronic toxicity testing) all show the presence of non-specific toxicity only at relatively high doses of the test chemical.

      1. Acute toxicity.  
Albemarle has submitted acute toxicity data on the undiluted product which contains 99.4% by weight 1,3-Dibromo-5,5-Dimethylhydantoin.  The results of this testing follow:

                                     Test
                                    Result
                               Toxicity Category
Acute Oral Toxicity
50 mg/kg < LD50 <= 500 mg/kg
II
Acute Dermal Toxicity
LD50 >= 2000 mg/kg
III
Acute Inhalation Toxicity
0.5 mg/liter < LC50 <= 2 mg/liter
III
Primary Eye Irritation
Study was waived due to the corrosiveness of the test material
II
Primary Dermal Irritation
Corrosive
I
Dermal Sensitization
Not a sensitizer
NA

	2. Genotoxicity. 
A battery of mutagenicity assays were performed including reverse mutation, mammalian cell gene mutation, chromosome aberration and  unscheduled DNA damage.  In most assays, no mutagenicity was observed; however, two in vitro mammalian cytogenetics assays in Chinese Hamster Ovary cells indicated positive results.

	3. Reproductive and developmental toxicity. 
Developmental and reproductive toxicity data demonstrate no increase in the susceptibility to the toxic effects of DMH with the exception of one study.  In this one study, fetal and litter effects (increased incidence of 27[th] presacral vertebrae) in rabbits were observed at a lower does level than that which resulted in material toxicity (decreased body weight and food consumption during the dosing period) following treatment.  The increase of the 27[th] presacral vertebrae is a common variation found in rabbit development toxicity studies and was not considered an adverse effect.  In a prenatal developmental toxicity study conducted with EMH, there was not increased susceptibility of the fetuses observed..

	4. Subchronic toxicity. 
Subchronic testing all show the presence of non-specific toxicity only at relatively high dose levels of the test chemical.

                                     Test
                                    Result
                                Test Substance
90-Day Oral Toxicity - Rat
NOAEL >= 1000 mg/kg/day (highest dose tested)

LOAEL > 1000 mg/kg/day
Dimethylhydantoin (>99.5% a.i.)
28-Day Oral Toxicity - Mouse
NOAEL >= 50,000 ppm [males: 10,057 mg/kg/day, females: 14,972 mg/kg/day] (highest dose tested)

LOAEL > 50,000 ppm [males: 10,057 mg/kg/day, females: 14,972 mg/kg/day] (highest dose tested)
Dimethylhydantoin (100% a.i.)
90-Day Dermal Toxicity - Rat
NOAEL = 390 mg/kg/day (highest dose tested)

LOAEL > 390 mg/kg/day
5,5-Dimethylhydantoin

	5. Chronic toxicity. 
The combined chronic/carcinogenicity testing of dimethylhydantoins in rats showed a decrement in body weight and body weight gain in females and increased mortality, particularly in females.  Males showed increase incidences of hyperplasia of submandibular lymph nodes, and testicular fibroid vascular degeneration in early decedents.  Both sexes increased mammary galactoceles in early decedents and enlarged pituitary glands.  In two chronic toxicity studies conducted in dogs, dimethylhydantoin produced slight (enlarged pituitary glands) to no toxicity at or above the limit dose of 1000 mg/kg/day.

	6. Animal metabolism. 
Available metabolism data indicate that DMH and EMH are excreted unchanged in the rat.

	7. Metabolite toxicology. 
NA

	8. Endocrine disruption. 
When the appropriate screening and/or testing protocols being considered under the Agency's Endocrine Disruptor Screening Program have been developed, the Halohydantoins may be subjected to additional screening and/or testing to better characterized effects related to endocrine disruption.

C. Aggregate Exposure

	1. Dietary exposure. 
The halohydantoins are currently used for microbial control in water and water systems.  The only current pesticide food use (indirect) for 1,3-Dibromo-5,5-Dimethylhydantoin is as a slimicide in the manufacture of food contact paper and paperboard.  In addition, there are five effective Food Contact Substance Notifications (FCNs) for 1,3-Dibromo-5,5-Dimethylhydantoin and one FCN that is the substance of an FDA Acknowledgement letter.  On August 1, 2011, Albemarle submitted a FCN to address some of the pesticide uses proposed in this application.

The proposed uses for 1,3-Dibromo-5,5-Dimethylhydantoin are:
   1.    To control the growth of spoilage and decay causing non-public health organisms in wash and process water and on the surface of processed fruits and vegetables.  (Note: This use will be covered by the August 1, 2011 Food Contact Notification).
   2.    To control the growth of spoilage and decay causing non-public health organisms in wash and process water and on the surface of raw, unprocessed fruits and vegetables.
   3.    For use as a terminal sanitizing rinse on hard surfaces and food processing equipment.
   4.    For use as a continuous sanitizing rinse on conveyor belts.
   5.    To sanitize shell eggs intended for food.  (Note: This use will be covered by the August 1, 2011 Food Contact Notification).

         i. Food. 
Generally, a dietary risk estimate that is less than 100% from the acute or chronic PAD does not exceed the Agency's risk concern.  

None of these proposed food contact scenarios (either direct or indirect) exceed the Agency's level of concern.

	ii. Drinking water. 
All uses of 1,3-Dibromo-5,5-Dimethylhydantoin will be indoor.  When compared to the proposed uses, an existing use (once-through cooling tower water system) is expected to have the greatest impact on water, since the scenario has the greatest quantity of effluent being produced and has the greatest chance of bacterial fouling, needing a pesticide application.  For this cooling tower use, EPA calculated that the short-term Estimated Environmental concentration (EEC) in surface water use was estimated to be 36 ug/L.  The chronic maximum EEC was determined to be 313 ug./L.

	2. Non-dietary exposure. 
Since the proposed uses will be non-residential, the only non-dietary exposures from pesticide uses will be occupational (i.e., commercial applicator).  Occupational exposures are not included under the Federal Food, Drug and Cosmetic Act (FFDCA) in the assessment of aggregate exposures for the purposes of establishing tolerances and exemptions from tolerances.

D. Cumulative Effects

The petitioner is not aware of any data regarding adverse cumulative effects from exposure of this chemical from its current food uses.  

E. Safety Determination

	1. U.S. population. This active ingredient has been approved for pesticide use since 1976.  As indicated in the Aggregate Exposure section above, 1,3-Dibromo-5,5-Dimethylhydantoin is currently approved as a slimicide in the manufacture of food-contact paper and paperboard under 21 C.F.R. Part 176.300.  Additionally, there are currently six Food Contact Notifications for this material.  These include:

                                    FCN No.
                                 Intended Use
                          Limitations/Specifications
334
As an antimicrobial in chiller water used during poultry processing
The Food Contact Substance (FCS) will be used at a level not to exceed that needed to provide the equivalent of 100 parts per million (ppm) of available bromine in the chiller water.
357
As an antimicrobial in water applied via an Inside-Outside Bird Washer (IOBW) and in water used for Off-Line Preprocessing (OLR) of poultry.
The FCS will be used at a level not to exceed that needed to provide the equivalent of 100 parts per million (ppm) of available bromine in the IOBW and OLR water.
453
For general use an as antimicrobial agent in water used in poultry processing for disinfecting poultry carcasses and their parts and organs
The FCS will be used at a level not to exceed that needed to provide the equivalent of 100 parts per million (ppm) of available bromine (90 mg DBDMH/kg water) in poultry process water.
775
For use as an antimicrobial in water supplied to ice machines intended for general use in the poultry processing industry
The FCS will be used at a level not to exceed that needed to provide the equivalent of 100 ppm of available bromine (corresponding to a maximum level of 90 mg DBDMH/kg water) in the water supplied to ice machines.
792
For use as an antimicrobial in water applied to beef hides, carcasses, heads, trim, parts, and organs
The FCS will be used at a level not to exceed that needed to provide the equivalent of 300 parts per million (ppm) of available bromine in the water.
1102
Effective date October 20, 2011
For use as an antimicrobial agent in water used in meat processing for disinfecting pig, goat, and sheep carcasses and their parts and organs
The FCS may be used at levels up to 500 parts per million (ppm) available bromine in  process water for pork, sheep carcasses and their parts and organs.

On August 1, 2011, Albemarle submitted one additional FCN.  Information on this follows:

                                    FCN No.
                                 Intended Use
                          Limitations/Specifications
Pending
For use as an antimicrobial agent in process water for fruits and vegetables, and as a component of a sanitizing solution for shell eggs
The FCS will be used at a level not to exceed that needed to provide the equivalent of 500 parts per million of available bromine for shell eggs and 900 parts per million of available bromine for fruits and vegetables.  When used in water to process fruits and vegetables, treatment shall be followed by a potable water rinse.

Albemarle is not aware of any detrimental information regarding the use of this active ingredient that would bring into question the safety of this chemical.  

	2. Infants and children. Albemarle is not aware of any specific safety concerns for infants and children, including any specific susceptibilities and exposure patterns.

F. International Tolerances.  None