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.
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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 carbamate (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 systems of pulp and 

paper mills and recirculating cooling water systems. According to the proposed label, SpectrumTM

XD1878 is to be used in conjunction with an oxidant such as sodium hypochlorite (12.5%) in specially

designed SpectrumTM 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, 
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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 SpectrumTM 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 SpectrumTM 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.
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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