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


                                                            July 25, 2013


MEMORANDUM

SUBJECT:	Ammonium Carbamate  -  Toxicology Review and Reponses to Waiver Requests to Support a New Active Ingredient to Be Used to Generate Monochloroamine to Treat Pulp and Paper Mills and Recirculating Cooling Water Systems  

PC Code: 000374
DP Barcode:  D412666
Decision No.:  474381
Registration No.: 74655-GU
Petition No(s).:  N/A
Regulatory Action:  New active ingredient and new use 
Risk Assess Type: Single Chemical
Case No.:  N/A
TXR No.: N/A
CAS No: 1111-78-0
MRID No(s).: 49042914; 49042918
40 CFR:  N/A
  

FROM:	Jenny J. Tao, Toxicologist
	Risk Assessment and Science Support Branch
           Antimicrobials Division

THRU:        Timothy Leighton, Senior Scientist/Team Leader, Human Health
	Steven H. Weiss, Branch Chief
     Risk Assessment and Science Support Branch	
     Antimicrobials Division 
     
TO:	Bill Erickson, Biologist 
	Antimicrobials Division Toxicity Endpoint Selection Committee (ADTC)
           Risk Assessment and Science Support Branch (RASSB)
     Antimicrobials Division (AD) (7510P)

     
This memo includes the toxicology review and responses to the waiver requests to support a new active ingredient, ammonium carbamate, to be used to generate monochloroamine for treating pulp and paper mills and recirculating cooling water systems.

I.  INTRODUCTION

The registrant, Hercules Inc., a Wholly Owned Subsidiary of Ashland Inc., submitted an application for Spectrum[(TM)] XD1878 (EPA Reg No. 74655-GU), which contains 19.5% of ammonium carbamate (CAS No: 1111-78-0), a new active ingredient (a.i.).  Spectrum[(TM)] XD1878 is intended to be used as bactericide, slimicide, and algaecide in control bacteria, fungi, and algae in water systems of pulp and paper mills and recirculating cooling water systems.  According to the proposed label, Spectrum[(TM)] XD1878 is to be used in conjunction with an oxidant such as sodium hypochlorite (12.5%) in specially designed Spectrum[(TM)] XD1878 feeder/delivery system, which is "programmed to automatically and optimally produce a dilute solution of monochloramine", in situ. The registrant indicated that all feeding, reactions, and outputs are carried out in an enclosed system (MRID 49042918).  

The registrant submitted the acute 6 pack toxicity studies (except for acute inhalation toxicity) for ammonium carbamate technical and requested waivers for the following mammalian toxicology studies:

   1. Acute Inhalation Toxicity Study (870.1300)
   2. 90-Day Oral Toxicity Study  -  Rodent (870.3100);
   3. 90-Day Oral Toxicity Study  -  Non-Rodent (870.3150);
   4. 90-Day Dermal Study (870.3250);
   5. 90-Day Inhalation Study (870.3465);
   6. Developmental (Teratogenicity) Study  -  Rats and Rabbits (870.3700);
   7. Baterial Gene Mutation (870.5100);
   8. In Vitro Mammalian Cell Gene Mutation Test (870.5300);
   9. In Vitro Mammalian Chromosome Aberration Test (870.5375);
   10. In Vivo Mammalian Cytogenetics Test (870.5380/5385/5395);
   11. Immunotoxicity (870.7800).


II.  DISCUSSION

   1. Acute Toxicity
   
Ammonium carbamate technical was found to be low toxic (Toxicity Category III) with an observed lethal dose of 1080 mg/kg (female) for acute oral toxicity.  It is Toxicity Category IV for acute dermal toxicity with an LD50 greater than 5000 mg/kg (male and female combined).  Ammonium carbamate technical is severely irritating to the eyes (Toxicity Category I) but is neither a dermal irritant (Toxicity Category IV) nor a skin sensitizer (LLNA method).

The registrant requested a waiver for the acute inhalation toxicity, based on the fact that "a stable atmosphere of ammonium carbamate cannot be established and maintained for the purpose of an accurate acute inhalation toxicity study" due to the rapid evaporation of ammonium carbamate during an attempt to conduct an acute inhalation toxicity study, which made impossible to measure "either the chamber concentration or the aerodynamic particle size" (MRID 49042914).  Based on the Guideline requirements and the Office of Pesticide Programs (OPP) Guidance for Waiving or Bridging of Mammalian Acute Toxicity Tests for Pesticides and Pesticide Products (Acute Oral, Acute Dermal, Acute Inhalation, Primary Eye, Primary Dermal, and Dermal Sensitization) (EPA/OPP, 2012), an acute inhalation toxicity study is waived.  

The acute toxicity data are summarized below. 


                                   Guideline
                                      No.

                                  Study Type

                                   MRID No.

                                    Results

                               Toxicity Category

                                   870.1100

                              Acute Oral Toxicity

                                   49042912

                       LD50(female) = 1080 mg/kg       

                                      III

                                   870.1200

                             Acute Dermal Toxicity

                                   49042913

                      LD50(comb.) > 5000 mg/kg       

                                       IV

                                   870.1300

                           Acute Inhalation Toxicity

                                   49042914

                   waiver for technical material           

                                      N/A

                                   870.2400

                            Primary Eye Irritation

                                   49042915

                              Severe Eye Irritant

                                       I

                                   870.2500

                           Primary Dermal Irritation

                                   49042916

                             Not a Dermal Irritant

                                      IV

                                   870.2600

                             Dermal Sensitization
                                    (LLNA)

                                   49042917

                               Not a Sensitizer

                                      N/A
   
   
   2. Subchronic Toxicity

In the proposed label and the waiver request document (MRID 49042918), it is indicated that the proposed use will occur in an enclosed system for transportation, feeding, reactions, and outputs, which results in minimum workers' exposure, in addition to the required personal protective equipment (PPE).  It is also indicated that the Spectrum[(TM)] XD1878 feeder/delivery system was designed to generate monochloramine in a controlled optimal manner to limit its dietary/drinking water exposures.  The proposed use of Spectrum[(TM)] XD1878 for treating pulp and paper mills and recirculating cooling water systems is essentially the same as other existing registrations in which ammonium sulfate is the precursor chemical, and the Agency concluded that there is "no risk concern".   

Conclusively, RASSB will waive the data requirements listed above for ammonium carbamate as well but reserve the right to request specific toxicology studies on the active ingredient in the future, if such data are necessary for refining the hazard identification and risk assessment.  


III.	CONCLUSION	

The required toxicology studies are waived for the new a. i., ammonium carbamate, for the proposed use of treating pulp and paper mills and recirculating cooling water systems, based on the fact that it's operated in an enclosed system and there is minimum risk concern to exposure to the active ingredient and its reacting agents.



IV.	REFERENCES

MRID 49042914: Keenan, T. H. (2013).  Technical Ammonium Carbamate, Request for Waiver of Acute Inhalation, OCSPP Guideline No. 870.1300.

MRID 49042918: Keenan, T. H. (2013).  Discussion o f Toxicology and Occupational Exposure Data Requirements, Including Waiver Requests, For the Use of the Active Ingredient, Ammonium Carbamate, In Papermill Process Water and Recirculation Cooling water Treatment.

U. S. Environmental Protection Agency (2012). Office of Pesticide Programs (OPP): Guidance for Waiving or Bridging of Mammalian Acute Toxicity Tests for Pesticides and Pesticide Products (Acute Oral, Acute Dermal, Acute Inhalation, Primary Eye, Primary Dermal, and Dermal Sensitization).  http://www.epa.gov/pesticides/science/acute-data-waiver-guidance.pdf


























