OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION **UNITED ST AT**  **ES ENVIRONMENT AL**  **PROTECTION A GENCY** 

WA SHINGTON, D.C. 20460
Ju ly 2 5 , 2013 **MEMORANDUM SUBJECT:**  **Ammonium Carbamate**



### – Toxicology Review and Reponse s to Waiver

Requests to Support a New Active Ingredient to Be Used to Generate Monochloroamine t o Treat Pulp and Paper Mills and Recirculating Cooling Water System s PC Code: 000 374 DP Barcode: D 41 2666 Decision No.: 4 74 381 Registration No . : 74655 - GU Petition No(s).: N/A Regulatory Action: N ew active ingredient and new u se Risk Assess Ty

pe: 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:** Tim othy 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 a ctive i ngredient , ammonium c arbamate , to b e u sed to g enerate m onochloroamine for treating p ulp and p aper m ills and r ecirculating c ooling water s ys tems .Page **2** of **4**

**I. INTRODUCTION**  The registrant, Hercules Inc. , a Wholly Owned Subsidiary of Ashland Inc., submitted an application for SpectrumTM XD1878 (EPA Reg No. 74655 - GU ) , which contains 19.5% of ammonium c arbamate ( CAS No: 1111 - 78 - 0 ), a new active ingredient (a.i.). SpectrumTM XD1878 is intended to be used as bactericide, slimicide, and algaecide in control bacteria , fungi, and algae in water s ys tems of pulp and paper mills and recirculating cooling water s ys tems . According to the proposed label, SpectrumTM XD1878 is to be used in conjunction with an oxidant such as sodium hy pochlorite (12.5%) in specially designed SpectrumTM XD1878 feeder/delivery s ys tem, 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 s ys tem (MRI D 49042918) . The registrant submitted the acute 6 pack toxicity studies (except for acute inhalation toxicity) for ammonium c arbamate technical and requested waiver s for the following mammalian toxicology studies: 1. Acute Inhalation Toxicity Study (870.1 300) 2. 90 - Day

Oral Toxicity

Study

– Rodent (870.3100); 3. 90 - Day

Oral Toxicity

Study

– N on - Rodent (870.3150); 4. 90 - Day

Dermal Study

(870. 3 250); 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 Cy togenetics Test (870.53 80/5385/53 95); 11. Immunotoxicity

(870.7800). **II. DISCUSSION**  **1. A**  **cute T**  **oxicity** Ammonium c arbamate technical was found to be low toxic (Toxicity Category I II ) 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 c arbamate technical is severel y irritating to the e ye s ( Toxicity Category I) but is n ei ther 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 car bamate during an attempt to conduct an acute inhalation toxicity study , which made impossible to measure “either the chamber concentration or the aerodyn amic 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,Page **3** of **4**

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 LD 50 (fe ma le) = 1 080 mg/kg III 870.1200 Acute Dermal Toxicity 49042913 LD 50 (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 s ys tem 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 SpectrumTM XD1878 feeder/delivery sy stem was designed to generate monochloramine in a controlled optimal manner to limit its dietary /drinking water exposure s . The proposed use of Spectrum TM XD1878 for treating p ulp and p aper m ills and r ecirculating c ooling water s ys tems is essentiall y 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 abov e for ammonium carbamate as well but reserve the right to request specific toxicology studies on the active ingredient in the future , if s uch data are necessary

for refin ing the hazard identification and risk assessment. **I II.**  **CONCLUSION** The required toxicology stud ies are waived for the new a. i., ammonium carbamate, for the proposed use of treating p ulp and p aper m ills and r ecirculating c ooling water s ys tems , based on the fact that it’s operated in an enclosed system and there is minimum risk concern to exposure t o the active ingredient and its reacting agents .Page **4** of **4**

**IV. REFERENCES**  MRID 49042914 : Keenan, T. H. (2013). Technical Ammonium Carbamate, Request for Waiver o f 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 Paper

m ill Process Water and Recirculation Cooling water Treatment. U. S. Environmental Protection Agency (20 12 ). 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