UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION 

September 19, 2012 

MEMORANDUM 

SUBJECT: Ammonium Bromide: Human Health Registration Review Seeping Document 

PC Code: 000352 DP Barcode: 401466 

Decision No.: Registration No.: NA 

Petition No.: NA Regulatory Action: Registration Review 

Risk Assess Type: Single Chemical Case No.: 5002 

TXRNo.:NA 

MRIDNo.: NA 

FROM: 

THROUGH: 

TO: 

CAS No.: 12124-97-9 

40CFR: NA 

(}."'' Timothy C. Dole, CIH, Industnal Hygte~ 'l 1 ·~ Jenny Tao, Senior Toxicologist c)~ , . - / 

William Hazel, Ph. D., Senior Cliemist d:/"~ 

Risk Assessment and Science Support Branch (RASSB) 

Antimicrobials Division (751 OP) 

Timothy Leighton, Senior Scientist ---- { -

Risk Assessment and Science Support Branch (RA 

Antimicrobials Division (7510P) 

<'~I I~ Steve Weiss, Acting Branch Chief ~ {.;V.e 

Risk Assessment and Science Support Branch (RASSB) 

Antimicrobials Division (7 51 OP) 

Rebecca von dem Hagen, Chemical Review Manager 

Regulatory Management Branch II (RMBII) 

Antimicrobials Division (7 51 OP) 

Page 1 of 12 

~. ~ 
EXECUTIVE SUMMARY 

Ammonium bromide is registered for use in paper mills, recirculating cooling water systems 

and sewage systems. It is used in conjunction with a chlorine source (sodium hypochlorite or 

chlorine gas) in a closed system to produce bromide activated monochloramine. The specified 

dose on product labels is 1 to 5 ppm available chlorine for both initial and subsequent treatments. 

The toxicology database includes a 13 week oral study in rats with neurological observations, 

a 4 week oral range finding study in rats, a developmental oral study in rats, and a one generation 

reproductive toxicity study in rats. The most significant finding from these studies is a LOAEL 

of 100 mg/kg/day for displaced testes in male fetuses in the developmental study. As this was 

the lowest dose, the NOAEL could not be determined. The acute toxicity studies indicate that 

ammonium bromide is oflow acute oral, dermal, and inhalation toxicity (all are Toxicity 

Category III). It is irritating to the eyes (Toxicity Category II) but not to the skin (Toxicity 

Category IV) and is not a dermal sensitizer. The mutagenicity studies, which include the Ames 

test, the in vivo mouse micronucleus test and the mouse lymphoma mutation assay, indicate that 

ammonium bromide is not mutagenic. 

No dietary (food) or drinking water risks are expected to be associated with the existing uses 

of ammonium bromide. The only potentially toxic compound resulting in the water system from 

the ammonium bromide uses is monochloramine, however, any monochloramine not consumed 

in the water system is expected to degrade under the high temperature conditions of the paper 

drying process (11 0 °C) and it is not expected to remain in the paper to migrate to food. It is also 

highly unlikely that monochloramine drinking water exposures will result in risks of concern (i.e. 

exposures are not anticipated to exceed the maximum residual disinfectant level (MRDL) of 4.0 

ppm) because the maximum application rate is 5.0 ppm and most of the monochloramine will be 

consumed during the treatment process. 

Occupational exposures to the products formulated as liquids are not anticipated to result in 

risks of concern for ammonium bromide because the label requires that these products be 

handled in a closed system. Occupational exposures to the products formulated as solids, 

however, may result in risks of concern depending upon the physical properties of these products 

and how they are handled. Although information in the acute toxicity study for one of the 

products suggests that the product is not readily inhalable, specific product chemistry studies, 

such as particle size analysis or attrition testing, are needed to confirm this finding. Although the 

label specifies that the Fuzzicide feeder/delivery system, which is a closed system, is used to mix 

a solution of ammonium bromide with the oxidant to produce the biocide (i.e. bromine activated 

monochloramine) the label does not indicate how the ammonium bromide solution is mixed and 

the possibility exists that this process involves open pouring of ammonium bromide into a premix tank. Therefore, unless it can be proven that inhalation exposures will not occur, inhalation 

toxicity (Guideline #870.3465) and exposure (Guideline #875.1400) studies will be required. 

It is understood that the reaction of ammonium bromide with the chlorine source is controlled 

to enhance the production ofmonochloramine, which is non-volatile, while minimizing the 

production of trichloramine, which is volatile. It is recommended that the conditions needed to 

prevent the production of trichloramine be stated on the labels. 

Page 2 of 12 
1.0 BACKGROUND 

1.1 Chemical Identity 

The chemical identity of ammonium bromide is listed in Table 1. 

Table 1 - Chemical Identity of Ammonium Bromide 

Chemical Name Ammonium Bromide 

Common Name Ammonia Salt 

Synonym N/A 

PC Code 000352 

CAS Registry Number 12124-97-9 

Case No. N/A 

Empirical Formula (NH4)2 Br 

1.2 Chemical and Physical Properties 

The physical and chemical properties of ammonium bromide that are relevant for human health 

risk assessment are listed in Table 2. 

Table 2 - Physical and Chemical Properties of Ammonium Bromide 

Property Value Reference 

Molecular Weight 98 gm/mole Hazardous Substances Databank (HSDB) 

Physical State Solid HSDB 

Melting Point 452 C (sublimes) HSDB 

Boiling Point N/A N/A 

Water Solubility 764 gm/liter at 20 C HSDB 

Vapor Pressure 9.8 x 10-7 mm Hg PMRA,2007 

Henry's Law Constant 1.3 X 10-IO atm * m3

/mol PMRA,2007 

1.3 Use Information 

According to OPPIN, there are five products that contain ammonium bromide as an active 

ingredient (ai). These products are listed in Table 3. 

Table 3 -Ammonium Bromide Products 

EPA Reg. Year Product Name Percent Formulation 

Number Re2istered a.i. 

8622-58 2008 Fuzzicide-Comp. 99% EUP- Solid 

8622-76 2008 Fuzzicide SP 99% EUP- Solid 

8622-64 2003 Fuzzicide Solution 35% EUP- Liquid 

8622-59 2003 Ammonium Bromide - Comp. 99% MUP-Solid 

8622-75 2003 Ammonium Bromide -SP 99% MUP-Solid 

Page 3 of 12 
Ammonium bromide is registered for use in paper mills, recirculating cooling water systems 

and sewage systems. The paper mill uses include influent water systems, cooling water systems, 

waste water systems, mill water systems, non-potable water systems, starch slurries and process 

waters. The recirculating water uses include industrial cooling towers, evaporative condensers, 

industrial water scrubbing systems, brewery pasteurizers and industrial air washing systems and 

the sewage systems uses include septic tanks, leach fields, tank lines, sewers, lagoons and 

sewage effluent water. Ammonium bromide is used in conjunction with a chlorine source (12.5 

percent sodium hypochloride or 99 percent chlorine gas) in a closed metered chemical feed 

system to produce bromide activated monochloramine. The treatment can be administered using 

the slug, intermediate or continuous feed methods. The specified dose is 0.5 to 5 ppm residual 

biocide expressed as total chlorine. 

1.4 Previous Human Health Risk Assessments 

An occupational risk assessment (US EPA, 2002) was written to support the registration of 

ammonium bromide as a liquid product. The conclusions of this assessment were as follows: 

• No significant dermal or inhalation exposure potential exists during mixing and loading 

because closed systems are used. 

• Although dermal exposure to treated water can occur during application, these exposures are 

not expected to result in risks of concern because the application rate is very low and the rate 

of dermal absorption is also very low. 

• Inhalation exposures are negligible because the biocide is diluted in water and the exposure 

time is limited. 

A human health risk assessment was not written for the registration of ammonium bromide 

used as a solid in 2006. 

2.0 TOXICOLOGY 

At the time that ammonium bromide was registered, the toxicology databases were 

considered to be complete and no additional studies were required. 

2.1 Acute Toxicity 

A summary of the acute toxicity findings for ammonium bromide is included in Table 4. 

Ammonium bromide, when tested as the technical ingredient (99% of a.i.), is oflow acute oral, 

dermal, and inhalation toxicities (all are Toxicity Category III). It is irritating to the eyes 

(Toxicity Category II) but not to the skin (Toxicity Category IV) and is not a dermal sensitizer. 

Table 4. Acute Toxicity Studies for Ammonium Bromide 

Test Guideline Guideline MRID Result Toxicity 

Numbers Category 

Acute Oral Toxicity (rat) 870.1100 44721303 LD50 (combined)= 2714 mg/kg III 

Acute Dermal Toxicity (rat) 870.1200 44721304 LD50 (combined) > 2000 mg!kg III 

Acute Inhalation Toxicity (rat) 870.1300 44721305 LC50 (combined)> 0.10 mg/1* III* 

Primary Eye Irritation (rabbit) 870.2400 44721306 Irritating II 

Primary Dermal Irritation (rabbit) 870.2500 44721307 Non Irritating IV 

Dermal Sensitization (guinea pig) 870.2600 44721308 Not a sensitizer N/A 

Page 4 of12 
* Maximum attainable concentration. Category III is assigned for regulatory purposes based on the National Library 

of Medicine's (NLM) Hazardous Substances Data Bank (HSDB) and the Vermont Safety Information Resources, 

Inc. (SIRI) MSDS Collection's description of ammonium bromide as moderately toxic. 

2.2 Repeat Dose Toxicity 

The following is a brief summary of the currently available repeat dose toxicology studies for 

ammonium bromide. All of these studies were done with technical a.i. containing at least 98.5% 

percent ammonium bromide. More detailed information is included in US EPA, 2012. 

MRID 45139301 - 4 Week Range Finding Study 

Ammonium bromide was administered via the diet to 4 groups of 5 male and 5 female rats at 

doses ofO, 100, 500, and 1000 mg/kg/day. Rats were monitored daily for clinical signs of 

toxicity, and weekly for body weight, and food and water consumption. 

There were no premature deaths. Mid and high dose animals of both sexes had agitated 

behavior, subdued behavior, a rolling gait, hunched posture and eyes partially closed. All other 

animals were normal throughout the study. Body weight gain and food consumption was 

decreased in the high dose males ( 49% and 24%, respectively). High dose females showed a 

body weight decrease of 31%. Water consumption was similar between all groups. 

Under the conditions of this study, the LOAEL for both sexes is 500 mg/kg/day, based on 

adverse clinical signs and decreased body weight/body weight gains and food consumption. A 

NOAEL of 100 mg/kg/day was observed for both males and females. 

This is an acceptable/non-guideline range-finding study for the subchronic toxicity study. 

MRID 45210801-13 Week Toxicity Study with Neurotoxicity Screening Battery 

Ammonium bromide was administered to rats in a powdered diet for 13 weeks. Control and 

high-dose groups included 25 rats per sex. Low- and mid-dose groups consisted of 15 rats per 

sex. The doses for the control, low, and mid dose groups were 0, 100, and 230 mg!kg/day, 

respectively. The dose for the high-dose group was 518 mg!kg/day for males and 785 mg/kg/day 

for females. Fifteen animals of each sex in the control and high-dose groups were sacrificed and 

necropsied at 13 weeks. Of these, 5 were examined for neurohistopathology. The other 10 

animals per sex were examined for gross pathology and histopathology. The additional10 

animals in the control and high-dose treatment groups (recovery group) were retained on study, 

without treatment, for an additional 4 weeks after which they were sacrificed for gross pathology 

only. 

Neurotoxicity parameters were measured during the pretrial week and in Weeks 4 and 8 on 5 

animals per sex in the control and high dose groups. At week 13, fifteen animals per sex in the 

control and high dose groups were evaluated for these parameters. These animals were then 

necropsied. At the end of the recovery period (week 17), the remaining 10 animals per sex in the 

control and high dose levels were evaluated. Ophthalmoscopic examinations, motor activity, and 

neurohistopathology were not remarkable in the treated animals vs. the controls. Organ weight 

Page 5 of 12 
changes were considered to be of no toxicological significance and histopathology of these 

organs was not remarkable. Gross and histopathology were not remarkable. Two males in the 

main study high-dose group (500 mg/kg/day), and a single male in the high dose recovery group 

were sacrificed in Weeks 6, 9, and 13, respectively, due to intractable conditions, not related to 

the administration of the test compound. 

Body weight gain in males showed a decrease in the high (23%) and mid (10.5%) dose by the 

end of the study. Females showed a decrease in the high (22.2%) dose by the end of the study. 

During the 4 week recovery period, although a 45% increase in the rate of weight gain occurred, 

body weight still showed a significant decrease of 11% and 8% in males and females, 

respectively. Food consumption in males was generally decreased starting on day 28 in the high 

dose and day 42 in the intermediate dose when compared to the controls. No change was seen in 

the food consumption during the 4 week recovery period in males and in females at all dose 

levels during the main and the recovery study. 

After 12 weeks exposure at the high dose, there were minor, but statistically significant 

increases in hemoglobin and hematocrit for both sexes. In the high dose female, increases in 

neutrophils and monocytes were noted. After the 4-week recovery period, total and differential 

white cell counts in males showed a significantly, although slight decrease vs. the controls. 

Mean phosphate levels in the blood increased 15% and 10% in males exposed at 225 (P<0.01) 

and 500 (P<0.05) mg/kg/day, respectively, relative to controls. In the high dose females at the 

recovery period, clinical chemistry changes were noted, but were slight and not considered of 

any toxicological importance. During the recovery period, the high dose females showed a 62% 

increase in alkaline phosphatase values vs. the control, but such change was probably of little 

toxicological importance. 

At the high dose, clinical observations included nasal bleeding, claws longer than normal, 

rolling gait, staggering, subdued behavior, reduced activity and hind limp splaying in both male 

and female animals. The functional neurobehavioral findings (FOB) recorded a high incidence of 

decreases in both fore and hindlimb grip strength, limpness and postural/rolling gait 

abnormalities. A slight increase in the incidence of decreased alertness, and increased landing 

foot splay was also seen. The reduced hindlimb grip strength of the high-dose females (but not 

high-dose males) remained through the 4-week recovery period. 

Males at the mid dose exhibited the clinical observations similar to the high dose, except for 

reduced activity. Correlation was afforded in the FOB tests and included limpness, decreased 

hindlimb grip strength, postural/rolling gait abnormalities and slight increases in the incidence of 

increased landing foot splay. At the low dose, limpness was observed in 3/10 males, but only 

1110 showed limpness on more than one occasion. Females exhibited a very low incidence of 

general clinical observations. The FOB findings included limpness and a slight increase in 

increased landing foot splay. At the low dose, generally no clinical observations or abnormalities 

in the FOB were noted. 

The LOAEL for both sexes is 225 mg/kg/day, based on decrease in body weight gain and 

food consumption in males, neurobehavioral findings of limpness, reduced hindlimb grip 

Page 6 of 12 
strength, and increased landing foot splay, which was more pronounced in the males. A NOAEL 

of 100 mg/kg/day was observed for both males and females. 

This study is classified as ACCEP ABLE for a 90-day subchronic study. However, the 

neurotoxicity screening assessment portion of the study is UNACCEPTABLE, but upgradable. 

This assessment can be upgraded if the following data are submitted and found to be acceptable: 

1. Additional details on how individual neurobehavioral parameters were evaluated (e.g. 

criteria used to score the different endpoints and description of methods of statistical 

analysis). 

2. A description of the neurotoxicity screening battery positive control or some other 

demonstration of the laboratory's experience with these tests. 

MRID 45139302- Developmental Toxicity Study in Rats 

Ammonium bromide was administered by oral gavage to 4 groups of 24 mated female rats at 

doses of 0, 100, 300, and 1000 mg/kg/day from days 6 - 19 inclusive of gestation where Day 0 

was the day of detection of mating. 

One high dose level female was sacrificed on day 1 0 of gestation because of severe clinical 

signs. Maternal toxicity at 1000 mg/kg/day included abnormal clinical observations such as 

rolling gait, animal limp when handled, piloerection, subdued behavior, hunched posture, eyes 

dark and slow respiration which were generally noted throughout the treatment period. Virtually 

no effects were seen at the lower dose levels compared to the controls. 

At 1000 mg/kg/day, a statistically significant depression in body weight gain was seen from 

gestational days 6- 12 (57%) and 6- 20 (18%) were noted. The lower dose levels were not 

remarkable compared to the controls. Food consumption at all dose levels was equivalent to the 

control group. 

Interuterine mortality was unaffected at 1000 mg/kg/day. A reduction (14.5%; p<0.001) in 

mean fetal weight of males and females combined was noted. At 1000 mg/kg/day fetal 

abnormalities included reduced/absent left kidney, often associated with absences of the left 

adrenal and/or ureter. Many animals also showed narrowing of the left uterine hom and 

abnormalities of the spleen. 

There was a dose-related increase in the incidence of fetuses and litters with kinked ribs, 

often associated with incomplete ossification of the ribs at all dose levels vs. the control. These 

animals also showed an increased incidence of curved scapula at 1000 mg/kg/day. The incidence 

of animals with slightly kinked ribs was also increased at 300 and 1000 mg/kg/day. There was a 

slight increase in the incidence of fetuses with reduction in the size of the 13th rib(s) at 1000 

mg/kg/day with a marginal increase occurring at 300 mg/kg/day. 

An increase incidence of dilated renal pelvis, dilated ureter was seen at 1000 mg/kg/day. A 

displacement of the testes was seen at all dose levels, and was in a dose-related trend (low: 11 

Page 7 of 12 
fetuses of 7 litters, mid: 15 fetuses of 10 litters, high: 20 fetuses of 10 litters vs. the control: 3 

fetuses of 3 litters). A dose-related increase in the incidence of subcutaneous hemorrhage 

affecting the limbs and the cranium also occurred. Hemorrhage affecting the brain ventricles and 

the surrounding tissues was also seen in a dose-related manner. The number of small fetuses was 

increased at 1 000 mglkg/ day. 

The maternal LOAEL was 1000 mglkg/day based on abnormal clinical observations, 

including rolling gait, animal limp when handled, piloerection, subdued behavior, hunched 

posture, eyes dark and slow respiration, and a decrease in weight gain during the first 6 days of 

the study. The maternal NOAEL was 300 mg!kg/day. The developmental LOAEL was 100 

mglkg/day based on displaced testes in the male fetuses. The developmental NOAEL could not 

be determined. 

The developmental toxicity study with ammonium bromide in the rat is classified as 

Acceptable/Guideline. 

MRID 45579201 -Range Finding Reproduction Study in Rats 

Ammonium bromide was administered via the diet to 4 groups of 1 0 rats/sex randomly 

selected at doses at 0, 1600, 3200, and 6400 ppm for the premating interval. The low dose of 

1600 ppm is equivalent to 151/176 mglkg/day for males/females, the mid dose of3200 ppm is 

equivalent to 277/34 7 mg/kg/day for males/females, and the high dose of 6400 ppm is equivalent 

to 591/717 mglkg/day for males/females. The parent (PO) animals received treated diet for 2 

weeks prior to mating and throughout the mating, gestation and lactation periods for both sexes 

until termination after the first generation (F 1) had been weaned. 

At the high dose (5911717 mglkg/day) parental toxicity was demonstrated by reduced body 

weight gain over the treatment period and reduced food consumption after cohabitation. Clinical 

signs included rolling gait, piloerection, hunched posture and unkempt coat. In addition, females 

showed hyperactive behavior. Reduced body weight gain (16%) in males over the treatment 

period was noted. For the one female that produced a litter; the litter died before Day 4 of 

lactation. The high dose, therefore, produced both mating performance and fertility effects. 

At the mid dose (277/347 mglkg/day), clinical signs for both sexes were similar to, but less 

severe than those described for animals at the high dose. Unkempt coat was not noted. Reduced 

body weight gain (13%) in males over the treatment period was noted. Body weight gain in the 

female was not affected. There was an increased incidence oftotallitter loss and a slight 

increase in pup mortality for surviving litters. Mean litter and pup weights were reduced 

throughout the Day 21 of lactation, except on day 4 when compared to the Control. 

The parental toxicity LOAEL is 277/347 mg!kg!day for males/females based on clinical 

signs in both sexes and reduced body weight gain (13%) in males. The NOAEL is 1511176 

mg!kg!day. 

The reproductive toxicity LOAEL is 277/347 mg!kg!day for females/males based on an 

increased incidence of total litter loss and a slight increase in pup mortality for surviving litters. 

Page 8 of 12 
Mean litter and pup weights were reduced throughout the Day 21 lactation period (except on day 

4) when compared to the control. The NOAEL is 1511176 mg/Jiglday. 

This study is an acceptable/non-guideline range finding study for reproduction toxicity. 

2.3 Mutagenicity 

Three mutagenicity studies are available. Ammonium bromide was found to be negative in 

all three studies. The study results are summarized in Table 5. 

Table 5 -Ammonium Bromide Mutagenicity Studies 

MRID Test Results 

44721309 Ames Test Not mutagenic with Salmonella typhimurium strains TA1535, TA1537, TA98, 

and TAIOO and E. coli strain WP2uvrA, when tested up to viability limits of 

5000 Jlg/plate with and without S9 activation. 

44721310 in vivo mouse Not mutagenic in micronucleus test in bone marrow of CD-I mice when tested 

micronucleus test at the concentrations ofO, 400, 800, and 1600 (maximum tolerated dose) 

mg/kg/day. 

44721311 mouse lymphoma Not mutagenic in mouse lymphoma (L5178Y) mutation assay at maximum 

mutation assay concentration (induced partial cytotoxicity) of 5000 Jlg/ml with and without S9 

activation. 

2.4 Chronic Toxicity/Carcinogenicity 

There are no chronic toxicity or carcinogenicity studies in the Agency's hazard database for 

ammonium bromide. 

2.5 Toxicology Endpoints 

When ammonium bromide was initially registered as a liquid product in 2003, toxicity endpoints 

for inhalation exposure were not selected and quantitative risk assessments were not warranted 

because of the limited use pattern that did not involve human exposure. While this rationale was 

valid for the liquid product it may not be valid for the solid products that were subsequently 

registered in 2006. Depending upon the physical properties of the solid products and how they are 

handled it may be necessary to select endpoints to evaluate occupational inhalation exposure. 

3.0 DIETARY ASSESSMENT 

3.1 Dietary Exposure 

No residues of potential toxicological concern are expected to survive the paper or 

paperboard manufacturing processes. Any monochloramine not consumed in the water system is 

expected to degrade under the high temperature conditions ofthe paper drying process (110 °C). 

Of course, any remaining ammonium bromide will exist as the dissociated ions. The chemical 

species likely to remain to be incorporated into the dried/finished paper and paperboard are 

ammonium ion, bromide ion, nitrate ion, and chloride ion for which there are no dietary toxicity 

Page 9 of12 
concerns. It is only these benign compounds that could potentially migrate into food from foodcontact paper or paperboard. Therefore, dietary (food) risks need not be calculated. 

3.2 Drinking Water Exposure 

No drinking water risks are expected from the existing uses of ammonium bromide. Very 

low levels of monochloramine may survive to the point of discharge. EPA has established a 

maximum residual disinfectant level (MRDL) of 4.0 ppm and water utilities are required to 

maintain total chloramines at or below this MRDL. Given this limits, the fact that the maximum 

application rate is 5.0 ppm and the fact that most of the monochloramine will be consumed 

during the treatment process, it is highly unlikely that drinking exposures to monochloramine 

will result in risks of concern. 

4.0 OCCUPATIONAL AND RESIDENTIAL EXPOSURES 

Occupational exposures to the liquid product are not anticipated to result in any risks of 

concern for ammonium bromide because the label requires that this product be handled in a 

closed system. 

Occupational exposures to the solid products may result in risks of concern depending upon 

the physical properties of the products and how the products are handled. Although the label 

specifies that the Fuzzicide feeder/delivery system, which is a closed system, is used to mix a 

solution of ammonium bromide with the oxidant to produce the biocide (i.e. bromine activated 

monochloramine) the label does not indicate how the ammonium bromide solution is mixed and 

the possibility exists that this process involves open pouring of ammonium bromide into a mix 

tank. It is also not known exactly how the product is formulated (i.e. powder or granule) and if 

it will release inhalable particles when handled. Although information in the acute toxicity 

study suggests that the product is not readily inhalable, specific product chemistry studies, such 

as particle size analysis (Guideline #830.7520) or attrition testing, are needed to confirm this 

finding. 

It is understood that the reaction of ammonium bromide with the chlorine source is controlled 

to enhance the production of monochloramine, which is non-volatile, while minimizing the 

production of trichloramine, which is volatile. It is recommended that the conditions needed to 

prevent the production of trichloramine be stated on the label. 

Residential exposures are not anticipated for ammonium bromide and monochloramine 

because these products are only used in industrial areas. 

5.0 AGGREGATE AND CUMULATIVE EXPOSURE 

As there are no dietary (food or drinking water) or residential exposures associated with the 

currently registered uses of ammonium bromide there is no need to estimate aggregate or 

cumulative risks. 

Page 10 of 12 
6.0 INCIDENTS 

There are no hwnan incidents reported in the OPP incident database that are associated with 

ammoniwn bromide exposure. 

7.0 TOLERANCES 

There are no tolerances for ammoniwn bromide. 

8.0 ENDOCRINE DISRUPTION EFFECTS 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential 

adverse outcomes from exposure to chemicals. Collectively, these studies include acute, 

subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, 

developmental, reproductive, and general or systemic toxicity. These studies include endpoints 

which may be susceptible to endocrine influence, including effects on endocrine target organ 

histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, 

reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates 

acute tests and chronic studies that assess growth, developmental and reproductive effects in 

different taxonomic groups. As part of its most recent registration decision, EPA reviewed these 

data and selected the most sensitive endpoints for relevant risk assessment scenarios from the 

existing hazard database. However, as required by FFDCA section 408(p ), ammonium bromide 

is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a "naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate." The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p ), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Ammoniwn 

bromide is not among the group of 58 pesticide active ingredients on the initial list to be 

screened under the EDSP. Accordingly, as part of registration review, EPA will issue future 

EDSP orders/data call-ins, requiring the submission ofEDSP screening assays for ammoniwn 

bromide. For further information on the status of the EDSP, the policies and procedures, the list 

of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website at: http://www.epa.gov/endo/. 

Page 11 of 12 
9.0 ANTICIPATED DATA NEEDS 

A listing of the studies required for the human health registration review of ammonium 

bromide is included in Table 6. The inhalation toxicity and exposure studies are needed to 

evaluate inhalation exposures to ammonium bromide that occur during the open pour addition of 

products that are formulated as solids. These studies can be waived if it can be proven that no 

exposure occurs due to the nature of the product (i.e. granules that are not inhalable based on 

particle size data) or the manner in which it is handled (i.e. closed system addition to the premix 

tank used to make the ammonium bromide solution). No additional studies are needed to assess 

the hazards of bromine activated monochloramine. 

Table 6 -Studies Needed for the Registration Review of Ammonium Bromide 

Study Needed Guideline Applicable Exposure Scenarios 

90 Day Inhalation Toxicity 870.3465 Open pour solid formulations into premix tankA 

Indoor Exposure, Inhalation 875.1300 Open pour solid formulations into premix t:ank"B 

Data Reporting/Calculations 875.1600 

Particle Size 875.7520 Open pour solid formulations into premix tank 

A. These studies can be waived if it can be proven that no exposure occurs due to the nature of the product (i.e. granules 

that are not inhalable based on particle size data) or the manner in which it is handled (i.e. closed system addition to the 

premix tank used to make the ammonium bromide solution) 

B. It may be possible to use proprietary surrogate exposure data if data compensation issues can be addressed. 

10.0 REFERENCES 

PMRA, 2007. Evaluation Report ERC2007-09 Ammonium Bromide Fuzzicide, H113-26/2007-

9E-PDF, Pest Management Regulatory Agency, Health Canada, 13 November 2007. 

U.S. EPA, 2002. Review ofthe Evaluation ofthe Potential Exposure and Human Health Risks 

for Fuzzicide (Ammonium Bromide) When Used in Cooling Water Systems and Pulp and Paper 

Mills, D282465. June 6, 2002 

U.S. EPA, 2012. Ammonium Bromide: Summary of Mammalian Toxicology Data for the 

Registration Review Scoping Document. D401624. 

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