Page 2 of 39 

EXECUTIVE SUMMARY 

IPBC is registered for use as a wood preservative, an industrial preservative and as a dry film 

mildewcide. The wood preservative uses include dip, spray and pressure treatment applications 

for new lumber, millwork and joinery and brush and spray applications for existing above 

ground structures such as decks. The industrial preservation uses include metal working fluids, 

adhesives, caulks, sealants, plastics, textiles, paper coatings, canvas, cordage, and inks. 

Additional preservation uses include household, consumer, industrial, institutional and janitorial 

products such as air fresheners, dish detergents, laundry products, surface cleaners, floor care 

products and fabric care products. The RED for IPBC was completed in 1997 and most of the 

above uses were found to be eligible for registration. For the industrial wood treatment use, the 

HVAC use, the textile use and certain non-industrial wood treatment uses, the Agency was 

unable to make a registration eligibility decision due to a lack of exposure data. These data 

were required to be submitted as part of a generic antimicrobial exposure DCI. 

There is conflicting information regarding the use of IPBC for food contact surfaces. IPBC 

does not have any FDA approvals for food contact uses and most the labels restrict uses in 

adhesive, paper and paper board products and paper coating to non-food applications. The 

labels also have similar statements for plastics and surface cleaners that limit the use to non-food 

areas. There are several labels which were approved beginning in 2004, however, that allow use 

in dish detergent, which is considered to be a food contact surface. 

 Although the toxicological database for IPBC is fairly extensive, the following additional 

studies are needed for registration review: 

• Comparative Cholinesterase Assay with Thyroid Measurements 

• Dermal Sensitization Threshold Quantification 

Although some occupational and residential (ORE) exposures were assessed in the RED, 

they will need to be reassessed during registration review to account for the toxicology studies 

that were submitted after the RED or in response to the registration review needs listed above. 

The following exposure data will be needed to assess these exposures: 

• Indoor exposure studies (dermal and inhalation) during open pouring of liquids, open 

pouring of powders, sapstain treatment, pressure treatment of wood, use of metal working 

fluids, use of sponges and wipes and brush/roller application of preserved paints. 

• Outdoor exposure studies (dermal and inhalation) during airless sprayer application of 

wood preservative stains. 

• Leaching studies on plastics, leather and textiles preserved with IPBC 

• Surface residue dissipation studies on household floors cleaned with IPBC preserved 

floor cleaners. 

• Surface residue dissipation studies on IPBC treated wood. 

• Product use information

In addition, it will be necessary to assess dietary exposures from the dish detergent use and 

therefore a residue study on dishes will be needed for registration review.
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1.0 BACKGROUND 

1.1 Chemical Identity 

The chemical identity of IPBC listed in Table 1. 

Table 1 - Chemical Identity of IPBC 

Chemical Name 3-Iodo-2-propynyl butyl carbamate 

Common Name IPBC 

PC Code 107801 

CAS Registry Number 554-53-6 

Case No. 2725 

Empirical Formula C8H12INO2

Structure 

1.2 Chemical and Physical Properties 

The physical and chemical properties of IPBC that are relevant for human health risk assessment 

are listed in Table 2. It should be noted that IPBC has a very low vapor pressure. 

Table 2 - Physical and Chemical Properties of IPBC

Property Value Reference 

Molecular Weight 281 Based on formula 

Physical State Powder EPA, 1997 

Melting Point 66 C Toxnet HSDB 

Water Solubility 156 mg/l @ 20 C Toxnet HSDB 

Octanol/Water Partition Coefficient Log Kow = 2.4 EPI Suite Estimate 

Vapor Pressure <1.8 X 10-6 @ 20 C , 5 x 10-6 @ 30 C EPA, 1997 

Henry’s Law Constant 8.9 x 10-9 atm-m3/mole @ 25 C EPI Suite Estimate 

2.0 USE INFORMATION 

2.1 Formulation Types and Percent Active Ingredient

According to OPPIN, as of 03/21/2011, there are 106 products that contain IPBC (0.05% to 

99.5%) as the active ingredient (ai). The products are formulated as powders and liquids. 
Page 4 of 39 

2.2 Summary of Registered Uses 

IPBC is registered for use as a wood preservative, an industrial preservative and as a dry film 

mildewcide. The wood preservative uses include spray, dip and pressure treatment applications 

for new lumber, millwork and joinery and brush and spray applications for existing above 

ground structures such as decks. The industrial preservation uses include metal working fluids, 

adhesives, caulks, sealants, plastics, textiles, paper coatings, canvas, cordage, and inks. 

Additional preservation uses include household, consumer, industrial, institutional and janitorial 

products such as air fresheners, dish detergents, laundry products, surface cleaners, floor care 

products and fabric care products. IPBC is also registered for use as a dry film mildewcide in 

paints and stains. A summary listing of the application rates is included in Table 3. 

Table 3 – Application Rates for IPBC 

Use Application Rate Example Labels 

Sapstain and Mold Control 0.375% (Bulk Dip Tank) 

0.75% (Conventional Spray) 

43813-43 

Decay and Stain Protection 1.5% (Non – Pressure Treatment) 

0.0375 lb ai/ft3 (Pressure Treatment) 43813-43 

Wood Finish and Preservative – 

Homeowner Applied 

0.5 % 69857-4, 1022-540 

Mildew Inhibition for Paints and Stains 0.32 to 1.08% 5383-114 

Metal Working Fluids 0.03 - 0.53% 5383-77 

Adhesives, Caulks, Patching 

Compounds and Sealants 

0.004 to 0.6% 1258-1230 

Plastics and Plastic Coatings 0.45 to 1.2 % 1258-1230 

Textiles 0.23 to 0.98% 5383-91 

Paper Coatings 0.23 to 0.9% 1258-1230 

Canvas and Cordage 0.023 to 1.2% 5383-77 

Leather 0.20% 464-8125 

Inks 0.45 to 3.0% 1258-1222 

Household, Consumer, Industrial and 

Janitorial Products 

40 to 600 ppm 1258-1230 

Some of the IPBC labels have limitations for plastics (not to be used in plastics that will be in 

contact with food or medical applications), paper coatings (non-food contact packaging and nonfood contact paper tapes), textiles (not to be used on fabrics intended for human wear or direct 

skin contact) and surface cleaners (non-food contact). 

The RED for IPBC was completed in 1997 and most of the above uses were found to be 

eligible for registration. For the industrial wood treatment use, the HVAC use, the textile use 

and certain non-industrial wood treatment uses, the Agency was unable to make a registration 

eligibility decision due to a lack of exposure data. This data was required to be submitted as 

part of a generic antimicrobial exposure DCI. 

In 2004, the first label (5383-117) allowing the use of IPBC as a materials preservative in 

liquid detergents, soft soaps, and household cleaning products was approved. In 2005, the first 

label (67071-44) allowing the use of IPBC as a materials preservative in Household, Consumer, 
Page 5 of 39 

Industrial, Institutional and Janitorial products was approved. These products include liquid and 

solid soaps, cleaners, detergents, laundry products and dishwashing detergents. Since that time, 

several other labels have been approved for these uses. In 2009, the first label (464-8123) 

allowing the use on leather was approved. 

2.3 Summary of Use Data 

 

 According to the Specialty Biocides North America Report 2004-2005 (Kline, 2006), the total 

U.S. Consumption of IPBC was $48 million in 2004. The areas of consumption included paints 

and coatings (67% of total IPBC sales by value), wood preservation (25% of sales), metal 

working fluids (6% of sales), adhesives and sealants (2% of sales) and plastics and resins (<1% 

of sales). The market shares for IPBC were 56% for paints and coatings (as a fungicide), 2% for 

wood preservatives (water borne), 8% for metal working fluids (as a fungicide), 1% for plastics, 

and 4% for adhesives and sealants (fungicides and mildewcides). 

3.0 TOXICOLOGY 

 

The toxicological database for the IPBC registration review case is comprised of studies that 

were available to the Agency when the RED was written in 1997 and additional studies that were 

submitted after the RED. The additional studies include the following: 

• Acute Neurotoxicity Study in Rats, MRID 455094-01 

• Subchronic Nuerotoxicity in Rats, MRID 455094-02 

• Subchronic Oral toxicity Study in Rats, MRID 458123-01 

• Subchronic Inhalation Toxicity Study in Rats, MRID 435302-03 

• Two-Generation Reproductive Toxicity Study in Rats, MRID 444788-01 

The acute neurotoxicity study is classified as Acceptable (Nonguideline) and does not 

satisfy the guideline requirement (870.6200; OECD 424) due to incomplete evaluations of 

neuropathology (lack of histopathology of nervous system tissue and brain weights). The 

subchronic neurotoxicity study, the subchronic oral study, the subchronic inhalation study and 

the two generation reproduction study are classified as Acceptable and fulfill the respective 

guideline requirements (870.6200, 82-1, 82-4, 870.3800). 

3.1 Acute Toxicity 

 A complete database of acute toxicity data was available to the Agency at the time the RED 

was written. A summary of the findings, which are detailed in the RED, is included in Table 4. 

IPBC is a severe eye irritant (i.e. Tox I) and is of low to moderate acute toxicity by the other 

routes of exposure. IPBC is not a dermal sensitizer at concentrations that do not exceed 0.32 

percent. However, incidence data and published literature suggest that IPBC may be a dermal 

sensitizer at either higher concentrations or following longer term exposures. Dermal exposure 

is the primary route of exposure for some residential use scenarios including textiles and treated 

wood. As suggested in the FIFRA Scientific Advisory Panel Meeting (SAP, 2004), it is 

important to evaluate the dermal sensitization concern if the dermal exposure is the primary 
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concern and there is no appropriate way to label the treated products. In order to conduct a 

quantitative risk assessment for dermal sensitization, a dermal sensitization study with different 

concentrations of the technical grade product will be required. 

Table 4 - Acute Toxicity Values for IPBC. 

Test (species) Result Toxicity Category 

81-1 Oral Toxicity (rat) LD50 = 1100 mg/kg (Females) 

LD50 = 1500 mg/kg (Males and Females) 

III 

81-2 Dermal Toxicity (rabbit) LD50 > 2000 mg/kg III 

81-3 Inhalation Toxicity (rat) LC50 = 0.68 mg/L III 

81-4 Eye Irritation (rabbit) Severely Irritating I 

81-5 Dermal Irritation (rabbit) Slightly Irritating IV 

81-6 Dermal sensitization (guinea pig) Non-sensitizer at 0.32% N/A 

3.2 Subchronic and Chronic Toxicity 

The following is a summary of the currently available toxicology studies for IPBC. 

a. Subchronic Toxicity 

Oral Studies

Subchronic Oral Toxicity in Rats, MRID 409474-01. IPBC was administered by gavage for 

13 weeks at doses of 0, 20, 50, and 125 mg/kg/day. An additional satellite group was dosed at 

125 mg/kg/day and held for a 28-day observation period following the 13-week dosing regimen. 

At 125 mg/kg/day, body weight gain was decreased (19% in males and 12% in females) and 

absolute liver weight was increased (20% in males and 31% in females). Liver to body weight 

ratio was significantly increased by approximately 31% in both males and females at 125 

mg/kg/day, while kidney to body weight ratio in females was increased 18% at 125 mg/kg/day. 

The systemic NOEL is 20 mg/kg/day, while the systemic LEL is 50 mg/kg/day, based on 

increased liver to body weight ratio. This study is classified as core supplementary data 

(guideline 82-1). Although this guideline is not satisfied, acceptable chronic toxicity data are 

available and therefore, additional oral subchronic data are not required. 

Subchronic Oral toxicity Study in Rats, MRID 458123-01. IPBC was administered by gavage 

at doses of 0, 10, 20, 35 and 80 mg/kg for 90 days. A Functional Observational Battery (FOB) 

was performed prior to the first exposure and then weekly. In the last week of the study, assessment of sensory reactivity to visual stimuli (visual placing) and motor activity was added. Food 

consumption for each rat was determined once a week. Hematology and clinical chemistry 

examinations were made at week 13, before the terminal sacrifice. Ophthalmoscopic 

examinations were made on all rats prior to the first administration of the test substance, in rats 

of the highest dose and on control rats at the termination. A gross necropsy and pathology 

examination was performed at the end of the study. 

 
Page 7 of 39 

There was no test article related findings with respect to food consumption ratio, assessment of 

hearing, righting reflex, grip strength, visual placing, motor activity, ophthalmoscopy, urinary 

parameters or macroscopic and microscopic findings. One male rat dosed at 35 mg/kg/day died 

on day 87 from a dosing accident. The most frequent clinical finding, observed during the daily 

post-treatment FOB observations was breathing sounds (slight to moderate in degree) seen in a 

dose-dependent manner. From day 19 of the study until the end of the treatment period, the main 

finding was a dose related incidence of slight salivation seen 25 minutes after dose 

administration. The effect may be due to be a local effect of the dosing solutions or to nonpalatability. Clinical observations included statistically significant decreases in body weight gain 

in males at 35 mg/kg/day (12%) and 80 mg/kg/day (17%). 

The NOAEL is 20 mg/kg/day based on decreased body weight in males, and salivation and 

breathing sounds in females with a LOAEL of 35 mg/kg/day.

The study is considered to be Acceptable and fulfils the guideline requirements §82-1. 

Dermal Studies

Subchronic Dermal Toxicity Study in Rats, MRID 421682-01, - During this study, rats 

(10/sex/dose) received dermal doses of 50, 200, and 500 mg/kg/day IPBC to the shaved skin for 

five days a week, six hours per day during a 91 day period. At 500 mg/kg/day, decreased body 

weight (4-6%) and weight gain (11%) were observed in males, but not in females. In females, 

significant increases in hemoglobin, hematocrit, and eosinophils were observed at 500 

mg/kg/day. Reticulocytes as a percentage of red cells were decreased at 50 and 200 mg/kg/day, 

but not at 500 mg/kg/day. Decreased serum glucose and decreased serum creatinine were 

observed in males at 500 mg/kg/day. Minimal to mild skin irritation (acanthosis and 

hyperkeratosis) was observed in both males and females. Increased serum gamma-glutamyl 

transpeptidase (24% increase) was observed in females. At 200 mg/kg/day, decreased serum 

glucose was observed in males, as was minimal to mild acanthosis and hyperkeratosis in males 

and females. Females showed inhibition of plasma ChE at 500 mg/kg/day, which may have been 

the result of either direct liver toxicity or inhibition of ChE itself. The systemic NOEL is 200 

mg/kg/day and the systemic LEL is 500 mg/kg/day. This study is classified as core minimum 

data (guideline 82-3) 

Inhalation Studies

In a subchronic inhalation toxicity study (MRID 43530203), Omacide (>97% ai) was 

administered to rats (15 rats/sex/dose) by whole-body exposure at nominal concentrations of 0, 

0.25, 1.25, or 6.25 mg/m3 (measured concentrations of 0, 0.3, 1.16, and 6.7 mg/m3) for 6 hours 

per day, 5 days per week, for 13 consecutive weeks. The 0.25 mg/m3 dose group was repeated 

based on exposure of the original 0.25 mg/m3 dose group to twice the nominal concentration 

during weeks 6-8 of the study. 

In the 6.25 mg/m3

 treatment group, plasma cholinesterase (ChE) activity was significantly 

reduced (approximately 20%) in males during weeks 2 and 13, and erythrocyte ChE was 

decreased in females at study week 2. Brain ChE activity was significantly reduced in males 
Page 8 of 39 

(17%) and females (25%), and hyperplasia or squamous metaplasia with necrosis of the ventral 

cartilage of the larynx was seen after 13 weeks of treatment. In the 1.25 mg/m3 treatment group, 

brain ChE levels were statistically significantly reduced in most of the females (25%; p<0.05). 

No effects were observed in the repeat 0.25 mg/m3

 treatment group. The LOEL for systemic 

toxicity is 1.25 mg/m3

, based on depressed brain ChE activity in females. The NOEL was 

0.25 mg/m3.

This study is acceptable and satisfies the guideline requirement for a subchronic inhalation study 

(82-4) in rats. 

b. Chronic Toxicity/Carcinogenicity 

Chronic Toxicity/Carcinogenicity Study in Rats, MRID 420082-06. IPBC was administered 

to Sprague-Dawley rats (50/sex/group) at doses of 0, 20, 40, and 80 mg/kg/day for two years. 

There were no statistically significant increases in tumor incidences in males. The incidence of 

mammary gland fibroadenoma and combined fibroadenoma/carcinoma in females was 

significantly increased at 20 mg/kg/day vs. control by pair wise comparison (p < 0.01), but there 

was no dose-related trend. Except at 20 mg/kg/day, the incidence of this tumor type was within 

historical control range for Sprague-Dawley rats. Since the mammary tumor incidence at 80 

mg/kg/day was almost equal to control, the Agency’s (OPP) Health Effects Division 

Carcinogenicity Peer Review Committee concluded that the mammary fibroadenomas were not 

related to treatment with IPBC. At 80 mg/kg/day, body weight gain decrements of 20% and 15% 

were observed in males and females, respectively, during the first 13 weeks of the study. At 

study termination, body weight gain in males at 80 mg/kg/day was decreased to 71% of control, 

and in females, to 76% of control. Significant changes in serum chemistry were observed in 

males at 80 mg/kg/day, as were significant non-neoplastic changes in the stomach in both sexes. 

The non-neoplastic changes in the stomach were considered the result of chronic irritation, and 

were not considered indicative of a neoplastic response. The systemic LEL is 20 mg/kg/day, 

which is the lowest dose tested, and it is based on decreased body weight gain in male rats.

The 80 mg/kg/day dose was considered adequate for testing of carcinogenic potential of IPBC, 

based upon decreased body weight gain in male and female rats. This study is classified as core 

minimum data (guideline 83-5). 

Carcinogenicity Study in Mice, MRID 420082-02. CD-1 mice (50 mice/sex/dose) were 

administered IPBC in the diet at 0, 20, 50, and 150 mg/kg/day for 78 weeks. In males, a 

statistically significant trend was observed for hepatocellular adenoma and hepatocellular 

adenoma/ carcinoma combined (p< 0.01). A statistically significant pair-wise comparison was 

also observed for the incidence of hepatocellular adenoma and adenoma/carcinoma combined at 

150 mg/kg/day vs. control (p< 0.05). At 150 mg/kg/day, the incidence of hepatocellular adenoma 

(24%) and combined adenoma/carcinoma (33%) exceeded the historical control range for CD-1 

mice provided by the registrant (average benign hepatocellular tumor incidence 11%, malignant 

tumor incidence 7%). There was no increase in hepatocellular tumor incidence in female mice. 

There was a significant dose-related positive trend in pulmonary carcinoma for females, but no 

significant pair-wise comparison at any dose level tested in this study. Since the formation of 

pulmonary carcinomas in mice is considered part of a continuum from pulmonary adenomas, the 
Page 9 of 39 

positive trend in carcinomas was not considered biologically significant. At the highest dose (150 

mg/kg/day), body weight gain in males was decreased to 73% of control for weeks 0-13 of the 

study, and to 77% of control at study termination. In females, body weight gain for weeks 0-13 at 

the high dose was decreased to 70% of control, and to 80% of control at study termination. No 

significant effects on food consumption were observed in this study. In addition, no statistically 

significant effects on survival were seen in this study. The systemic LEL is 20 mg/kg/day, 

which is the lowest dose tested, and is based on the increased incidence of non-neoplastic 

pathology of the thyroid in both sexes (atrophic vacuolation, follicular coalescence, and 

general follicular enlargement). This study is classified as core minimum data (guideline 83-2). 

c. Developmental Toxicity 

Developmental Toxicity Study in Rats, MRID 409904-01, Rats were dosed by oral 

administration of IPBC at 0, 20, 50, and 125 mg/kg/day on gestation days six through 15. 

Maternal toxicity as reduced body weight gain during dosing was observed at 125 mg/kg/day. 

Developmental toxicity consisted of an increased incidence of skeletal abnormalities at 125 

mg/kg/day. The maternal toxicity NOEL is 50 mg/kg/day, and the maternal toxicity LEL is 125 

mg/kg/day, based on reduced body weight gain. The developmental toxicity NOEL is 50 

mg/kg/day, and the developmental toxicity LEL is 125 mg/kg/day, based on incompletely 

ossified frontal skull bones and pelvic girdles. This study is classified as core minimum data 

(guideline 83-3). 

Developmental Toxicity Study in Rabbits, MRID 424816-04. This study was conducted in 

female New Zealand white rabbits, which received oral doses of 0, 2, 20, and 50 mg/kg/day 

IPBC on gestation days 6 through 19. At 50 mg/kg/day, maternal toxicity in the form of 

increased mortality and abortion was observed. Although changes in cesarean section 

observations were reported at 50 mg/kg/day, these changes are likely a secondary effect of 

maternal toxicity. The maternal toxicity NOEL is 20mg/kg/day, and the LEL is 50 

mg/kg/day, based on increased mortality, clinical signs, and decreased body weight gain. 

The developmental toxicity NOEL is 50 mg/kg/day which was the highest dose tested. This 

study is classified as core minimum data (guideline 83-3). 

d. Mutagenicity 

Ames Test, MRID 419752-06. IPBC was tested for the ability to cause mutations in Salmonella 

typhimurium strains TA 1535, TA 1537, TA 1538, TA 98, and TA 100. IPBC was found to be 

non-mutagenic in all five strains with and without metabolic activation at all concentrations 

tested (1-1000 ug/plate). 

Micronucleus Assay in Mice, MRID 409904-04. IPBC at doses of 200, 600, and 2000 mg/kg 

did not induce any significant increase of the PCE containing micronuclei from the treated mice 

when compared to that of the vehicle control mice. 

Unscheduled DNA Synthesis Assays, MRID 409904-03. In primary rat hepatocytes, eight 

doses of IPBC ranging from 3.0 to 13.5 ug/ml did not cause an appreciable increase in mean net 
Page 10 of 39 

nuclear grain counts. Doses >13.5 ug/ml were cytotoxic, supporting the conclusion that IPBC 

induced cytotoxicity but not genotoxicity in this assay (guideline 84-2). 

e. Metabolism 

Rat Metabolism Study, MRID #409474-04. Disposition of C14 IPBC was examined in male 

and female rats at single oral doses of 20 and 125 mg/kg, at 20 mg/kg x 14 days, and as a single 

intravenous dose of 0.5 mg/kg. The time course of tissue distribution, conducted in 5 rats of each 

sex administered 7 daily doses of 20 mg/kg/day, was also performed. Several deficiencies were 

noted in the original review of this study, including an inadequate number of rats per dose group, 

inadequate design of the repeat dose study, no justification for dose levels used in the study, and 

no identification of major metabolites. 

In another rat metabolism study (MRID #435707-01), IBPC was administered orally in 0.5% 

carboxymethylcellulose in the following manner: Groups of 5 male and 5 female rats (groups A 

and B) received either a single oral high dose of radiolabelled IPBC (125mg/kg) or a repeated 

low oral dose of non-radiolabelled IPBC followed by a single radio-labeled dose (20 mg/kg). 

Separate groups of rats (9/sex/group, groups C and D) received single oral doses (20 and 125 

mg/kg) of radiolabelled IPBC, and 3 rats/sex were sacrificed at 2, 4, and 120 hours post-dose for 

determination of tissue distribution of radioactivity. Urine, feces and expired air were collected 

at 24 hour intervals for groups A and B, while urine and feces were collected from groups C and 

D. Absorption of test chemical at the low and high dose was between 80-90% for all dose 

groups, as suggested by excretion data showing the majority of a dose eliminated through urine 

or exhaled air. 

Excretion of IPBC-derived radioactivity was mainly via the urine, with between 50-70% 

of an administered dose excreted by this route at 168 hours post-dose. Feces was a minor route 

of excretion in all dose groups (4-7% of the administered dose), while radiolabelled CO2 

constituted between 18-24% of the administered dose. Repeated low oral dosing or a single high 

oral dose appeared to result in a decrease in the percentage of radioactivity excreted as 14-CO2 

compared to a single low dose (38.22% in MRID # 409474-04). 

Based on the metabolite identification data, a scheme for metabolism of IPBC was proposed. 

According to this scheme, IPBC undergoes reductive dehalogenation followed by dealkylation to 

form the URM-9 and URM-10 metabolites. In addition, de-carboxylation following reductive 

dehalogenation yields carbon dioxide. Various other metabolites formed from dehalogenation are 

glucuronidated and constitute minor metabolites of IPBC. This study was submitted in order to 

address deficiencies from review of a previous metabolism study (MRID # 409474-04). The data 

provided in this study in conjunction with MRID #409474-04, satisfy the data requirement for a 

metabolism study in rats under Subdivision F guideline 85-1. 

f. Reproductive Toxicity 

Two-Generation Reproductive Toxicity Study in Rats, MRID 409904-02. This study was 

conducted in rats where IPBC was administered over two generations at doses of 0, 6, 15, and 

37.5 mg/kg/day. Reduced body weight and food consumption was observed for P and F males 
Page 11 of 39 

during the premating period at 37.5 mg/kg/day. A decreased mean live birth index was reported 

for P and F generations without an effect on viability and development of pups. No adverse 

effects on reproductive indices or mating performance were observed at any dose level. The 

parental toxicity NOEL is 15 mg/kg/day, and the parental toxicity LEL is 37.5 mg/kg/day, 

based on decreased body weight and food consumption during premating for P and F 

males, and decreased mean live birth index for the P and F generations. The reproductive 

toxicity NOEL is 37.5 mg/kg/day which was the highest dose tested. This study is classified 

as core minimum data (guideline 83-4). 

Two-Generation Reproductive Toxicity Study in Rats, MRID 444788-01. Omacide® (>97% 

IPBC) was administered to groups of 25 male and 25 female rats by gavage at doses of 0, 10, 30, 

or 100 mg/kg/day for two generations. Clinical signs of toxicity observed in the mid- and high 

dose levels included salivation, paddling with both forepaws, and hunched posture. No 

treatment-related gross findings were observed at necropsy of the F0 or F1 females. Microscopic 

examination of the F0 adults was unremarkable. In the F1 adults, diffuse acanthosis with 

hyperkeratosis was observed in the stomach of 10/10 males and 7/10 females from the 30 

mg/kg/day groups. Therefore, the LOAEL for systemic toxicity is 30 mg/kg/day based on 

clinical signs of toxicity in the F0 and F1 males and females and on microscopic lesions in 

the stomach of F1 males and females. The systemic toxicity NOAEL is 10 mg/kg/day.

Fertility indices for the 100 mg/kg/day F0 males and females were significantly (p ≤ 0.05) less 

than the controls. No treatment-related effects were observed on copulation or fertility of the F1

rats. The live birth indices for the F1 litters in the 0, 10, 30, and 100 mg/kg/day groups were 

98%, 98%, 90%, and 80% (p ≤ 0.001). The live birth index was ≥98% for all groups of F2 litters. 

For the F1 pups, the viability indices on lactation day 4 (precull) were 92%, 96%, 72% (p ≤

0.01), and 30% (p ≤ 0.001), respectively, and the cumulative survival indices were 88%, 94%, 

67% (p ≤ 0.01), and 28% (p ≤ 0.001), respectively. For the F2 pups in the 0, 10, and 30 

mg/kg/day groups the viability indices on lactation day 4 (precull) were 92%, 97%, and 87%, 

respectively, and the cumulative survival indices were 85%, 93%, and 83%, respectively. Whole 

litter losses occurred for three mid-dose and six high-dose F0 females and for two mid-dose F1

females. Clinical signs of toxicity in the pups associated with whole litter losses were indicative 

of lack of maternal care. 

Body weights of the 100 mg/kg/day F1 male pups were significantly (79-86% of controls) less 

than the controls beginning on lactation day 4 (precull) and continuing throughout lactation. 

Body weights of the 100 mg/kg/day F1 female pups were significantly (81-93% of controls) less 

than the controls throughout lactation. Body weight gains by the 100 mg/kg/day F1 male and 

female pups were 79% and 82%, respectively, of the control level during lactation days 0-14 and 

were 93% and 91%, respectively, for lactation days 14-21. Body weights of the 30 mg/kg/day 

male and female F1 pups during lactation were slightly but non-significantly lower than the 

controls. No statistical differences in body weights of the F2 male pups were observed between 

the treated and control groups at any time during lactation. F2 female pups in the 30 mg/kg/day 

group had significantly lower body weights than the controls on lactation days 14 (93% of 

controls) and 21 (91% of control). Body weight gains by the 30 mg/kg/ F2 female pups for 

lactation days 0-14 and 14-21 were 92% and 87%, respectively, of the control level. Pup body 

weights in the low-dose group were similar to the controls in both generations. Because dosing 
Page 12 of 39 

of the pups did not begin until after weaning at 25 days of age, the only exposure of the pups to 

the test article was through the milk. 

Treatment with the test article resulted in developmental delays of the offspring including a 

significantly (p ≤ 0.01) greater anogenital distance in the 30 mg/kg/day F2 females as compared 

to the controls (1.1 mm vs 1.0 mm), delayed eye opening for the 100 mg/kg/day F1 pups (79% vs 

85% of the controls on day 15) and for the 30 mg/kg/day F2 pups (85% vs 97% of the controls on 

day 15). 

Therefore, the LOAEL for reproductive toxicity is 30 mg/kg/day based on reduced pup 

survival, lower pup body weights, and developmental delays during lactation. The 

reproductive toxicity NOAEL is 10 mg/kg/day.

This study is classified as Acceptable (guideline) and satisfies the guideline requirement for a 

reproduction study (OPPTS 870.3800; 40 CFR §83-4) in rats. 

g. Neurotoxicity 

Acute Neurotoxicity Study (MRID 455094-01). Rats were given a single gavage oral dose of 

IPBC at doses of 0, 100, 300, or 1000 mg/kg/day and observed twice daily for 15 days. Control 

and treatment groups were divided into the following 3 sets for neurobehavioral assessment and 

ChE activity evaluations: 

• Set 1 (12/sex/group) was evaluated for FOB (functional observational battery), MA 

(motor activity), and blood, plasma and brain ChE at pretest and on Day 1. 

• Set 2 (12/sex/group) was evaluated for FOB, MA, blood, plasma ChE at pretest, Days 1, 

8, and 15, and brain ChE on Day 15. 

• Set 3 (6/sex/group) was evaluated for neuropathology on Day 15 at study termination, 

these animals were euthanized and perfused in situ for neuropathological examination. 

A statistically significant decreased mean body weight gain was observed for males at 300 and 

1000 mg/kg/day. In the females, body weight and body weight gain showed no change at any 

dose level. FOB observations (Incidences) included a statistically significant lower number of 

rears in females treated at 1,000 mg/kg/day. This effect was not seen in males. A dose 

relationship was seen on Day 1 (Sets 1 and 2) and Day 8 (Set 2). Low Locomotor (Open field) 

activity was seen at 1000 mg/kg/day on Day 1 in Sets 1 and 2 in both sexes. This effect was still 

evident to a lesser degree in both sexes on day 8. 

The number of approaches (open field) showed a dose related decrease in sets 1 and 2 in males 

which was statistically significant at 1000 mg/kg/day. In females decreases were noted at 1000 

mg/kg/day but they were not statistically significant. Rats of both sexes in all treatment groups 

had an overall lower incidence of motor activity than their control counterparts. Females treated 

with 300 and 1,000 mg/kg had decreased plasma ChE activity on Days 8 and 15. No significant 

changes were observed in erythrocyte and brain ChE activity in both sexes. Macroscopic 

evaluation revealed no evidence of lesion formation due to treatment. 
Page 13 of 39 

Based on the effects seen in this study, the LOAEL was 100 mg/kg bw (LDT) based on 

changes in motor activity. A NOAEL could not be determined. 

This study is classified as Acceptable (Nonguideline) and does not satisfy the guideline 

requirement for an acute neurotoxicity study in rats (870.6200; OECD 424) due to incomplete 

evaluations of neuropathology (lack of histopathology of nervous system tissue and brain 

weights). It should be noted; however, that no changes were seen in a companion subchronic 

neurotoxicity study MRID 455094-02. 

Subchronic Neurotoxicity Study (MRID 45509402) IPBC was administered to rats at dose 

levels of 0, 10, 50, or 120 mg/kg/day for 13 weeks. Control and treatment groups were divided 

into 4 sets for neurobehavioral assessment (FOB, MA), ChE activity, and neuropathology 

evaluations. Neurobehavioral assessment was performed in animals (12/sex/dose) before the 

initiation of the study and at Weeks 4, 8, and 13. ChE activity was determined by a 

spectrophotometeric assay in plasma and erythrocytes prestudy and at Weeks 4, 8, and 13, and in 

3 regions of the brain during Weeks 4, 8, and 17. At study termination (week 13) and at 

recovery (week 17), 6/sex/dose were euthanized and perfused for neuropathological examination. 

There were no treatment-related effects on mortality, clinical signs, neurobehavioral activity, and 

erythrocyte and brain ChE activity. Treatment-related effects included lower mean body 

weight/body weight gain and decreased food consumption at 50- and 120-mg/kg/day. 

Decreased food efficiency at 120 mg/kg/day correlated with the decrease in food consumption, 

contributing to the lower body weights of treated animals. 

Plasma ChE inhibition was observed at 50- and 120-mg/kg/day in females only. Erythrocyte and 

brain ChE activity was not affected in either sex at any dose or time point. Macroscopic 

examination indicated that the cervical and lumbar dorsal root ganglion might be potential target 

tissues of the test article. Microscopic examination reported neuronal vacuolation, satellite cell 

hypertrophy/hyperplasia, and neuronal degeneration in these tissues; however, these effects were 

determined not to be treatment-related. No other gross, histo-pathological, or neuro-pathological 

effects were observed. All the noted effects in body weight, food consumption, food efficiency, 

and plasma ChE activity were reversed during the recovery period, indicating that the effects of 

the test article were not permanent. No frank neurotoxicity was observed. 

Based on the effects seen in this study, the LOAEL is 50 mg/kg/day (based on body weight, 

food consumption, and ChE activity data), with a NOAEL of 10 mg/kg/day. 

The study is classified as Acceptable-Guideline and satisfies the guideline requirement for a 

subchronic neurotoxicity study in rats (870.6200). 

3.3 Toxicology Endpoints 

 The most recent hazard assessment for IPBC is included in D354908 (EPA, 2009) which was 

prepared to evaluate a proposed new use of IPBC on leather. This assessment included a 

selection of endpoints to be used for risk assessment; however, these endpoints will need to be 
Page 14 of 39 

reevaluated during registration review because additional toxicology studies have subsequently 

become available. 

4.0 DIETARY ASSESSMENT 

Dietary Exposure

There is conflicting information regarding the use of IPBC for food contact surfaces. IPBC 

does not have any FDA approvals for food contact uses and most the labels restrict uses in 

adhesive, paper and paper board products and paper coating to non-food applications. The 

labels also have similar statements for plastics and surface cleaners that limit the use to non-food 

areas. There are several labels such as #1258-1230, #1529-51, #67071-44, however, that allow 

use in dish detergent, which is considered to be a food contact surface. If it is determined that 

the registrants intend to support the dish detergent use, then dietary exposures from this use will 

need to be assessed during registration review. 

Drinking Water Exposure

There is a potential for drinking water exposure from the material preservative uses. The 

Agency expects that the environmental fate data that are being required will be useful to evaluate 

this potential. Therefore, the need for a drinking water assessment will be determined after the 

environmental fate data are received and reviewed. 

5.0 OCCUPATIONAL/RESIDENTIAL EXPOSURE 

Occupational Exposures Assessed in the RED 

Occupational handler exposures were assessed in the RED for the mixing and loading for the 

following uses: general preservatives, the metal working fluids, oil production and pulp and 

paper. The MOEs were calculated for “total exposures” based on the addition of the dermal and 

inhalation exposures and were assessed using the dermal endpoint of 200 mg/kg/day for 

short/intermediate term exposures and the oral endpoint of 20 mg/kg/day for long term exposures 

(in conjunction with a dermal absorption factor of 10 percent). All of the MOEs exceeded the 

target MOE of 100 and were not considered to be of concern. Occupational handler risks were 

also assessed for the application of paints or stains using brushes or air less sprayers and one of 

these MOEs (airless sprayer application of wood preserving stain, MOE = 71) was of concern. 

Based on these assessments, the RED required that products intended primarily for occupational 

use specify that applicators and other handlers must wear long-sleeve short and long pants, 

chemical resistant gloves and shoe plus socks. The RED did not require respiratory protection. 

Occupational Exposures That Need to be Assessed

Occupational exposures were not assessed in the RED for the handlers applying wood 

preservatives to lumber using the dip or spray treatment nor were exposures assessed for 
Page 15 of 39 

machinists using IPBC preserved metal working fluids. In addition, the inhalation exposures for 

all of the scenarios were not assessed separately, nor were they compared to an inhalation 

specific endpoint. Given these deficiencies, it will be necessary to reassess all of the exposure 

scenarios during registration review. 

Residential Exposures Assessed in the RED

Residential handler exposures were assessed in the RED for home owner application of 

paints and stains containing IPBC using brushes and rollers. The MOEs were calculated as 

discussed above for occupational exposures they exceeded the target MOE of 100 and were not 

considered to be of concern. Based on these assessments the RED did not require any label 

changes. No other residential exposures were assessed. 

Residential Exposures That Need to be Assessed

As is the case for occupational applicators, the inhalation exposures for residential 

applicators of paints or stains containing IPBC will need to be re-assessed separately using an 

inhalation specific endpoint. It will also be necessary to assess incidental oral exposures to 

household items and toys made of plastics preserved with IPBC, incidental oral and dermal 

exposures to floors cleaned with IPBC treated household cleaners and incidental oral and dermal 

exposures to textile and leather products treated with IPDB. 

A listing of the exposure studies that will be needed for registration review is included in 

Section 10 and detailed justifications are included in Appendix A. 

 

6.0 AGGREGATE AND CUMULATIVE EXPOSURE 

 In examining aggregate exposure, EPA takes into account the available and reliable 

information concerning exposures to pesticide residues in food and drinking water, as well as 

non-occupational (i.e. residential) pesticide exposures. An aggregate risk assessment may be 

needed for IPBC if it is determined that a drinking water exposure could occur based on the 

environmental fate data. This assessment might also need to include dietary exposures from the 

dishwashing detergent use and residential exposures from the wood treatment, floor cleaners, 

plastics, paints, leathers and textile uses. 

 Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, 

modify, or revoke a tolerance, the Agency consider "available information” concerning the 

cumulative effects of a particular pesticide's residues and "other substances that have a common 

mechanism of toxicity.” IPBC (3-Iodo-2-propynyl butyl carbamate) it an iodo-carbamate. 

Iodo-carbamates are not part of the N-methyl carbamate (NMC) class of pesticides and should 

not be included as part of the NMC cumulative risk assessment as supported by the SAP (2004). 
Page 16 of 39 

7.0 INCIDENTS 

There are 27 human incidents reported in the OPP incident database that are associated with 

IPBC exposure. Both local skin irritation and systemic effects were reported in these incidents. 

Skin irritation and skin sensitization-like symptoms are the primary effects that have been 

reported, and these effects include rash, swelling, itching, burning and/or tingling sensation, 

blister, erythema/flushing, and hives. In some cases, chest tightness and respiratory problems 

were reported. Other reported systemic effects include nausea/vomit, headache, fatigue, vertigo, 

and fever. 

There are also reports of skin sensitization in the literature. The most recent of these is a 

report by the North American American Contact Dermatitis Group of the results of IPBC patch 

testing (Warshaw, 2010). This testing was done on 25,321 patients between 1998 and 2008 

using 0.1 or 0.5 percent IPBC in petrolatum. There were 226 weak reactors and 67 strong 

reactors. The majority of the reactions were to personal care products and most reactions were 

not related to occupation. Only four of the strong reactors had definite clinical relevance with a 

positive use-test reaction or positive patch-test reaction to a product containing IPBC. The 

frequency of positive reactions increased from 0.2 percent to 1.5 percent when the higher 

concentration of IPBC was utilized, but most were weak reactions of which some were likely 

irritant. 

8.0 TOLERANCES 

There are no tolerances or exemptions from tolerances for IPBC. As mentioned in Section 

4.0, IPBC is not approved for use as an indirect food additive. 

9.0 ENDOCRINE DISRUPTION EFFECTS 

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor 

Screening Program (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. 

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. 

IPBC is not among this group of chemicals. This list of chemicals was selected based on the 

potential for human exposure through pathways such as food and water, residential activity, and 

certain post-application agricultural scenarios. This list should not be construed as a list of 

known or likely endocrine disruptors. For further information on the status of the EDSP, the 
Page 17 of 39 

policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening 

battery, please visit our website: http://www.epa.gov/endo/. 

Endocrine related effects were observed for IPBC in some of the available toxicity studies. 

For example, in the carcinogenicity study (MRID 420082-02), thyroid gland atrophic 

vacuolation, follicular coalescence, and general follicular enlargement were noticed in both 

sexes. In the rat reproductive study, the F2 females had a greater anogenital distance as 

compared to the controls. 

10.0 ANTICIPATED DATA NEEDS 

10.1 Toxicology Studies 

 

1. Comparative Cholinesterase Assay with Thyroid Measurements

 

Toxicity studies with IPBC suggest it is an acetyl cholinesterase (AChE) inhibitor. AChE 

inhibition is observed in toxicity studies of different routes of administration from the acute oral 

neurotoxicity study (MRID 455094-01), subchronic inhalation study (MRID 435302-03), 

subchronic dermal toxicity study (MRID 421682-01), and subchronic oral neurotoxicity study 

(MRID 455094-02). These various toxicity studies support the finding that IPBC inhibits AChE. 

According to the studies submitted to the agency for the n-methyl carbamates (NMCs), the 

Comparative Cholinesterase Assay (CCA) study results have shown juveniles to be more 

sensitive to AChE inhibition than adults. Therefore, a CCA, which includes both adult and 

PND11 juvenile rats is needed, to address potential life stage sensitivity. In addition, the existing 

database for IPBC does not address the time to peak ACHE inhibition, which might under 

predict the true AChE inhibition. Therefore, the CCA study for IPBC should include sufficient 

measurements so that the time to peak inhibition can be determined. 

Current toxicity studies have also demonstrated that IPBC affects the thyroid. In the chronic 

mouse study, IPBC increased the incidence of non-neoplastic pathology of the thyroid in both 

sexes (atrophic vacuolation, follicular coalescence, and general follicular enlargement). 

Furthermore, iodine uptake in the developing fetus is a critical developmental life stage. 

Therefore, the Agency requires comparative thyroid measurements in the pregnant females and 

the developing fetus to determine potential susceptibility. 

The AChE and thyroid measurements may be sampled from the same sets of animals in the 

CCA study. The thyroid parameters should include triiodothyronine (T3), thyroid stimulating 

hormone (TSH), and thyroxine (T4) hormone measurements as well as thyroid weight and 

histopathological examination of both the adult and young animals. This is consistent with 

Agency policy to reduce the number of animals and to refine the measurements taken in the 

study. Fetal thyroid evaluations are conducted at GD 20 in order to determine whether the test 

chemical alters fetal hormones or thyroid structure during this critical period of brain 

development. 
Page 18 of 39 

The CCA with Thyroid Measurement Study should include the following components: 

1) Acute study: measure AChE inhibition in direct dosing to post-natal day 11 and young 

adult rats. The acute study should be accompanied by a range-finding and time to peak 

effect study; 

2) Eleven (11) day repeated, direct dosing to juvenile rats (PND 11-21) and young adult 

rats; and 

3) Gestational exposures to pregnant dams followed by sacrifice at gestational day 20 

(measuring brain and blood AChE activity in dams and fetuses). 

Each component study should include a control group and at least 3 treatment groups. The 

AChE measurements should include both RBC and brain AChE. The studies should be 

performed in order, since the results of the first study impact the design of subsequent studies. 

Protocols should be submitted to the Agency for review before onset of testing. 

2. Dermal Sensitization Study

In order to conduct a quantitative risk assessment for dermal sensitization, a dermal sensitization 

study with different concentrations of the technical grade product is needed. 

10.2 Exposure Studies 

There are 15 exposures studies that are needed to assess dietary and occupational/residential 

exposures. These studies are listed in Table 5 with brief rationales as to why they are needed and 

more detailed justifications are provided in Appendix A. 
Page 19 of 39 

Table 5 –Exposure Studies Needed for IPBC Registration Review

Study Needed Guideline Rationale 

Residues from Dish 

Detergent 

No Guideline Dishes washed with IPBC preserved dishwashing 

detergents may become contaminated with IPBC. 

Indoor Exposure 

(Open Pour PowdersA,B) 

875.1100 (Dermal) 

875.1300 (Inhalation) 

875.1600 (Data Reporting) 

Exposure may occur during open pour addition of IPBC 

powder products during material preservation. 

Indoor Exposure 

(Open Pour LiquidsA,B) 

875.1100 (Dermal) 

875.1300 (Inhalation) 

875.1600 (Data Reporting) 

Exposure may occur during open pour addition of IPBC 

liquid products during material preservation. 

Indoor Exposure 

(Spray and Dip TreatmentB) 

875.1100 (Dermal) 

875.1300 (Inhalation) 

875.1600 (Data Reporting) 

Exposure may occur during in-plant spray and dip 

treatment of lumber using IPBC. 

Indoor Exposure 

(Pressure TreatmentB

) 

875.1100 (Dermal) 

875.1300 (Inhalation) 

875.1600 (Data Reporting) 

Exposure may occur during pressure treatment of lumber 

using IPBC. 

Indoor Exposure 

(Brush/Roller PaintingB

) 

875.1100 (Dermal) 

875.1300 (Inhalation) 

875.1600 (Data Reporting) 

Exposures may occur during brush roller application of 

paints preserved with IPBC. 

Indoor Exposure 

(Metal Working FluidsB) 

875.1100 (Dermal) 

875.1300 (Inhalation) 

875.1600 (Data Reporting) 

Exposure may occur during use of metal working fluids 

preserved with IPBC. 

Indoor Exposure 

(Sponges and WipesB

) 

875.1100 (Dermal) 

875.1300 (Inhalation) 

875.1600 (Data Reporting) 

Exposure may occur during use of sponges and wipes 

preserved with IPBC. 

Outdoor Exposure 

(Airless Sprayer PaintingB

) 

875.1200 (Dermal) 

875.1400 (Inhalation) 

875.1600 (Data Reporting) 

Exposures to paint aerosols containing IPBC. 

Leaching Study on Plastics No Guideline Incidental oral exposures may occur from mouthing 

household items and toys made from IPBC preserved 

plastics. 

Leaching Study on Leather No Guideline Dermal and incidental oral exposures may occur from 

leather articles made from IPBC preserved leather. 

Leaching Study on Textiles No Guideline Dermal and incidental oral exposures may occur from 

clothing made from textiles treated with IPBC preserved 

spin finish solutions. 

Surface Residue Dissipation 

(Household Floors) 

875.2300 Dermal and incidental oral exposures may occur from 

contact with floors cleaned with IPBC treated household 

cleaning products. 

Surface Residue Dissipation 

(Treated Wood) 

875.2300 Dermal and incidental oral exposures may occur from 

contact with IPBC treated wood. 

Product Use Information 875.1700 Use information can be used to evaluate exposures and 

assist in the planning of exposure studies. 

A. If the labels are amended to require closed mixing and loading for liquid products and water soluble packaging 

for powder products, then the exposure studies will not be needed for the open loading/mixing scenarios. 

B. It may be possible to use proprietary surrogate exposure data if data compensation issues can be addressed. 
Page 20 of 39 

11.0 REFERENCES 

EPA, 1997. Reregistration Eligibility Decision (RED) for 3-Iodo-2-propynyl butylcarbamate 

(IPBC), March 1997, http://www.epa.gov/pesticides/reregistration/status.htm

EPA, 2009. Toxicology Endpoints for Risk Assessment for a Proposed New Use of 3-Iodo-2-

propynyl butyl carbamate in/on Leather. D354908, January 5, 2009 

Kline, 2006. Specialty Biocides North America 2004-2005, Kline and Company, Inc. 

Warshaw et al., 2010. Positive Patch-Test Reactions to Iodopropynl Butylcarbamate: 

Retrospective Analysis of North American Contact Dermatitis Group Data from 1998 to 2008. 

Warshaw E.M. et al., Dermatitis, Volume 21, Issue 6, pp 303-310, November – December, 2010. 
Page 21 of 39 

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Page 22 of 39 

Appendix A – Justification for the 

Studies Needed for the Human Health 

Registration Review of IPBC 
Page 23 of 39 

Appendix A, Table 1 - Toxicology Study Justifications for IPBC Registration R

Guideline Study Title Practical Utility of the Data 

N/A Comparative 

Cholinesterase Assay (CCA) with Thyroid Measurements 

1) What is the value of the study?The existing toxicity studies for IPBC indicate that it inhibits AChE. Accosubmitted for the NMCs, the Comparative Cholinesterase Assay (CCA) resjuveniles to be more sensitive to AChE inhibition than adults. Therefore, a is needed to address potential life stage sensitivity by including both adult a

rats. It also is not known the time to peak AChE inhibition, such that the exIPBC may be under predicting the true AChE inhibition. Therefore, the CCshould include sufficient measurements so that the time to peak inhibition c

addition, current toxicity studies have demonstrated that IPBC affects the thmouse study, IPBC increased the incidence of non-neoplastic pathology of 

sexes. Furthermore, iodine uptake in the developing fetus is critical. There

should include comparative thyroid measurements in the pregnant females fetus to determine potential susceptibility. 2) How would the data be used?The data would be used to identify endpoints for risk assessment to be used exposures of adults and children to products preserved with IPBC. 3) How could the data affect the risk assessment?The data might indicate that existing endpoints are not sufficiently protectivor thyroid effects. 4) What is triggering the need for this data? The fact that IPBC causes AChE inhibition and affects the thyroid. 
Page 24 of 39 

Appendix A, Table 1 - Toxicology Study Justifications for IPBC Registration R

Guideline Study Title Practical Utility of the Data 

N/A Dermal 

Sensitization Threshold Quantification 

1) What is the value of the study?This study is needed to quantify the dermal sensitization effects that have bliterature. 2) How would the data be used?The data would be used to identify a threshold for the dermal sensitization 

the data would be used to identify a safe threshold level for the elicitation p

which is protective of induction as recommended by the FIFRA SAP (See nwould then be used to assess the risk of dermal sensitization from exposure 3) How could the data affect the risk assessment?Currently it is not possible to assess the risks of sensitization from exposure 

some of the use rates are higher than the rate tested in the submitted study. 4) What is triggering the need for this data? The need for this data is triggered by occupational dermal exposures from t

fluid use and the residential dermal exposures from the wood and textiles u

Note 1 - Transmittal of Minutes of the FIFRA Scientific Advisory Panel Meeting Held May 4-6, 2004: A Consul

Sensitization Issues for Exposures to Pesticides, Memorandum of 1 July 2004.
Page 25 of 39 

Appendix A- Table 2 - Exposure Study Justifications for IPBC Registration R

Guideline Study Title Practical Utility of the Data 

N/A Residue 

Dissipation(Dishwashing Detergents) 

1) What is the value of the study? Dietary exposures to IPBC are expected during the use of dish detergents that are This residue data from this study could be used in place of default assumptions to exposures and risks resulting from the dish detergent use. 2) How would the data be used? The data would be used to assess the risks of dietary exposures that result from thdetergents preserved with IPBC. 3) How could the data affect the risk assessment? The residue data would be used to assess the dietary risks from the IPBC dish dedetermine if mitigation measures, such as rate reductions are needed to reduce th4) What is triggering the need for this data? IPBC is labeled for use as a preservative in “Household, consumer, industrial, an

such as liquid and solid air fresheners, dish detergents, laundry products, soaps food contact surface cleaners, floor care products, bathroom cleaners, window clproducts, automotive care products and furniture care products”. 
Page 26 of 39 

Appendix A- Table 2 - Exposure Study Justifications for IPBC Registration R

Guideline Study Title Practical Utility of the Data 

875.1100 875.1300 875.1600 

Applicator Indoor Exposure (Open Pour Powders) Dermal Inhalation Data Reporting 

1) What is the value of the study? Dermal and inhalation exposures to IPBC are expected during the o

powders such as product #1529-40 during materials preservation. Iinhalation exposures from open pouring of powders are evident in ePesticide Handlers Exposure Database (PHED). The existing ChemAssociation (CMA) data base and PHED for these scenarios are limQA/QC and the number of replicates (i.e., number of times a workespecific activity). EPA presented the need for additional handler exJanuary 2007 Science Advisory Panel (SAP) as well as to the April Review Board (HSRB) and both groups agreed that additional data 2) How would the data be used? The data would be used to assess dermal and inhalation exposures topen pour addition of powders during materials preservation. 3) How could the data affect the risk assessment? The exposure data would be used to assess the risks to occupational determine if mitigation measures, such as water soluble packaging, these risks. 5) What is triggering the need for this data? The need for the exposure study is based on the potential for exposuaddition of liquids during the materials preservation uses listed on t
Page 27 of 39 

Appendix A- Table 2 - Exposure Study Justifications for IPBC Registration R

Guideline Study Title Practical Utility of the Data 

875.1100 875.1300 875.1600 

Applicator Indoor Exposure (Open Pour Liquids) Dermal Inhalation Data Reporting 

1) What is the value of the study? Dermal and inhalation exposures to IPBC are expected during the o

liquids during materials preservation. In addition, dermal and inhalopen pouring of liquids are evident in exposure studies in the PesticDatabase (PHED). The existing Chemical Manufacturer Associatioand PHED for these scenarios are limited in scope for QA/QC and treplicates (i.e., number of times a worker is monitored for a specific presented the need for additional handler exposure data to the JanuaAdvisory Panel (SAP) as well as to the April 2007 Human Studies R

and both groups agreed that additional data are warranted. 2) How would the data be used? The data would be used to assess dermal and inhalation exposures topen pour addition of liquids during materials preservation. 3) How could the data affect the risk assessment? The exposure data would be used to assess the risks to occupational determine if mitigation measures, such as closed system loading, arthese risks. 6) What is triggering the need for this data? The need for the exposure study is based on the potential for exposuaddition of liquids during the materials preservation uses listed on t
Page 28 of 39 

Appendix A- Exposure Study Justifications for IPBC Registration Review 

Guideline Study Title Practical Utility of the Data 875.1100 875.1300 875.1600 

Applicator Indoor Exposure (Spray and Dip Treatment) Dermal Inhalation Data Reporting 

1) What is the value of the study? Dermal and inhalation exposures to IPBC are expected during the sapplications IPBC containing sapstain treatments for treating fresh cno open literature studies available to assess these exposures*. 2) How would the data be used? The exposure data would be used to assess IPBC exposures that resdip applications of IPBC Sapstain treatments. 3) How could the data affect the risk assessment? Current there are no open literature data available to assess the expouse of IPBC in Sapstain treatment and therefore the risks from this uexposure data would be used to assess these risks and determine if mreduce these risks. 4) What is triggering the need for this data? IPBC is labeled for use as a sapstain dip and spray treatment in fres

*There are proprietary studies, such as the Sapstain Industry Group Study (MRID 476183-01), that can be used a

this exposure scenario if data compensation issues can be addressed. 
Page 29 of 39 

Appendix A- Exposure Study Justifications for IPBC Registration Review 

Guideline Study Title Practical Utility of the Data 875.1100 875.1300 875.1600 

Applicator Indoor Exposure (Pressure Treatment) Dermal Inhalation Data Reporting 

1) What is the value of the study? Dermal and inhalation exposures to IPBC are expected during the papplications of IPBC containing sapstain treatments to fresh cut lumopen literature studies available to assess these exposures*. 2) How would the data be used? The exposure data would be used to assess IPBC exposures that res

treatment applications of IPBC sapstain treatments. 3) How could the data affect the risk assessment? Current there are no open literature data available to assess the expouse of IPBC in sapstain pressure treatment and therefore the risks frunknown. The exposure data would be used to assess these risks anmitigation is needed to reduce these risks. 4) What is triggering the need for this data? IPBC is labeled for use as a sapstain pressure treatment in fresh cut 

*There are proprietary studies, such as the CCA Pressure Treatment Worker Exposure Study (MRID 455021-01) surrogate data for this exposure scenario if data compensation issues are addressed. 
Page 30 of 39 

Appendix A- Exposure Study Justifications for IPBC Registration Review 

Guideline Study Title Practical Utility of the Data 875.1100 875.1300 875.1600 

Applicator Indoor Exposure (Brush/Roller Painting) Dermal Inhalation Data Reporting 

1) What is the value of the study? Dermal and inhalation exposures to IPBC are expected during interapplication of IPBC preserved paints. There are no studies availabexposures. 2) How would the data be used? The exposure data would be used to assess IPBC exposures that resapplication of IPBC preserved paints. 3) How could the data affect the risk assessment? Current there are no data available to assess the exposure of IPBC f

in paints and therefore the risks from this use are unknown. The exused to assess these risks and determine if mitigation is needed to re4) What is triggering the need for this data? IPBC is labeled for use as a preservative in “Paints”.
Page 31 of 39 

Appendix A- Exposure Study Justifications for IPBC Registration Review 

Guideline Study Title Practical Utility of the Data 875.1100 875.1300 875.1600 

Applicator Indoor Exposure (Metal Working Fluids) Dermal Inhalation Data Reporting 

1) What is the value of the study? Dermal and inhalation exposures to IPBC are expected use of metal preserved with IPBC. There are no studies available to assess thes2) How would the data be used? The exposure data would be used to assess IPBC exposures that resIPBC preserved metal working fluids. 3) How could the data affect the risk assessment? Current there are no data available to assess the exposure of IPBC f

in metal working fluids and therefore the risks from this use are unkdata would be used to assess these risks and determine if mitigation these risks. 4) What is triggering the need for this data? IPBC is labeled for use as a preservative in “Metal Working Fluids”
Page 32 of 39 

Appendix A- Exposure Study Justifications for IPBC Registration Review 

Guideline Study Title Practical Utility of the Data 875.1100 875.1300 875.1600 

Applicator Indoor Exposure (Sponges and Wipes) Dermal Inhalation Data Reporting 

1) What is the value of the study? Dermal and inhalation exposures to IPBC are expected during the usponges and wipes. There are no studies available to assess these e2) How would the data be used? The exposure data would be used to assess IPBC exposures that resIPBC preserved sponges and wipes. 3) How could the data affect the risk assessment? Current there are no data available to assess the exposure of IPBC f

preserved sponges and wipes and therefore the risks from this use aexposure data would be used to assess these risks and determine if mreduce these risks. 4) What is triggering the need for this data? IPBC is labeled for use as a preservative in sponges and wipes.

*There are proprietary studies, such as the AEATF II Wipe Study (MRID 483756-01), that can be used as surrogexposure scenario if data compensation issues are addressed 
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Appendix A- Exposure Study Justifications for IPBC Registration Review 

Guideline Study Title Practical Utility of the Data 875.1200 875.1400 875.1600 

Applicator Outdoor Exposure (Airless Sprayer Painting) Dermal Inhalation Data Reporting 

1) What is the value of the study? Dermal and inhalation exposures to IPBC are expected during outdoapplication of IPBC containing wood preservatives. There are no s

assess these exposures. 2) How would the data be used? The exposure data would be used to assess IPBC exposures that resapplication of IPBC containing wood preservatives. 3) How could the data affect the risk assessment? Current there are no data available to assess the exposure of IPBC fin airless sprayer applied wood preservatives and therefore the risks unknown. The exposure data would be used to assess these risks anmitigation is needed to reduce these risks. 4) What is triggering the need for this data? IPBC is labeled for use as a water repellant wood preservative that can exterior coating (see label 1022-540 which indicates that desirabshould be covered to prevent injury). 
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Appendix A- Exposure Study Justifications for IPBC Registration Review 

Guideline Study Title Practical Utility of the Data N/A Plastics Leaching Study 1) What is the value of the study? 

Incidental oral exposures to IPBC are expected during use of housemade from plastics that are preserved with IPBC. There are no leato assess these exposures. 2) How would the data be used? The leaching data would be used to assess IPBC exposures that resuhousehold items and toys made from plastics that have been preserv3) How could the data affect the risk assessment? The IPBC specific leaching data would refine the risk assessment bof default assumptions of the amount that could be leached. 4) What is triggering the need for this data? IPBC is labeled for use as a preservative in plastics. Although somDisclaimer: “Product is not intended for use in food-contact articlesother materials used in prolonged direct dermal contact with the humdo not have this disclaimer. 
Page 35 of 39 

Appendix A- Exposure Study Justifications for IPBC Registration Review 

Guideline Study Title Practical Utility of the Data N/A Leather Leaching Study 1) What is the value of the study? 

Dermal and incidental oral exposures to IPBC are expected during umade from leather that is processed with leather processing liquors IPBC. There are no leaching studies available to assess these expo2) How would the data be used? The leaching data would be used to assess IPBC exposures that resuleather processed with leather processing liquors that are preserved 3) How could the data affect the risk assessment? The IPBC specific leaching data would refine the risk assessment bof default assumptions of the amount that could be leached. 4) What is triggering the need for this data? IPBC is labeled for use as a preservative in “Leather” on label #4644/28/10) and there are no human contact restrictions listed on the la
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Appendix A- Exposure Study Justifications for IPBC Registration Review 

Guideline Study Title Practical Utility of the Data N/A Textiles Leaching Study 1) What is the value of the study? 

Dermal and incidental oral exposures to IPBC are expected during usuch as clothing, towels and blankets made from textiles that are tre

that are preserved with IPBC. There are no leaching studies availaexposures. 2) How would the data be used? The leaching data would be used to assess IPBC exposures that resu

clothing, towels and blankets made from textiles that are treated witpreserved with IPBC. 3) How could the data affect the risk assessment? The IPBC specwould refine the risk assessment by eliminating the use of default aamount that could be leached. 4) What is triggering the need for this data? IPBC is labeled for use as a preservative in “Spin-finish solution in on label # 67071-44 (approved 3/31/10) and there are no human con

on the label for this use. 
Page 37 of 39 

Appendix A- Exposure Study Justifications for IPBC Registration Review 

Guideline Study Title Practical Utility of the Data 875.2300 Surface Residue 

Dissipation (Household Floors) 

1) What is the value of the study? Dermal and incidental oral exposures to IPBC are expected for toddhousehold floors after they are cleaned with floor cleaners that are p

Surface residue dissipation data are needed to accurately assess thes2) How would the data be used? The surface residue data would be used to assess IPBC exposures thof floor cleaners preserved with IPBC. 3) How could the data affect the risk assessment?The surface residue data will be used during registration review to dand incidental oral exposures to toddlers playing on floors treated w

risk of concern that requires mitigation. This mitigation could incluapplication rate or elimination of the use. If surface residue data arthe standard assumption of 100 percent transferable surface residue might overestimate the risk and require excessive mitigation. 4) What is triggering the need for this data? IPBC is labeled for use as a preservative in “Household, consumer, janitorial products such as liquid and solid air fresheners, dish deterproducts, soaps and detergents, non-food contact surface cleaners, fbathroom cleaners, window cleaners, fabric care products, automoti

furniture care products”. 
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Appendix A- Exposure Study Justifications for IPBC Registration Review 

Guideline Study Title Practical Utility of the Data 875.2300 Surface Residue 

Dissipation (Treated Wood) 

1) What is the value of the study? Dermal and incidental oral exposures to IPBC are expected for toddIPBC treated wood surfaces. Surface residue dissipation data are nassess these exposures. 2) How would the data be used? The surface residue data would be used to assess IPBC exposures th

with wood treated with IPBC. 3) How could the data affect the risk assessment?The surface residue data will be used during registration review to dand incidental oral exposures to toddlers playing on wood surfaces IPBC generates a risk of concern that requires mitigation. This miti

reduction of the application rate or elimination of the use. If surfacavailable, then the standard assumption of 1.0 ug/cm2 transferable s

used which might overestimate the risk and require excessive mitig4) What is triggering the need for this data? IPBC is labeled for use as a wood preservative applied to fresh cut l
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Appendix A- Exposure Study Justifications for IPBC Registration Review

Guideline Study Title Practical Utility of the Data 875.1700 Product Use Information 1) What is the value of the study? 

Product use information is a description of how the product is actuafield study. A description of how this product is used would providrealistic assessment of its potential applications. 2) How would the data be used? The product use information will be used to define and characterize scenarios that will be assessed in the risk assessment. 3) How could the data affect the risk assessment? A complete description of product use would ensure that the risk asof the types of exposures occurring during use and that these exposu

assessed. 4) What is triggering the need for this data? The need for a risk assessment under Registration Review in turn neassessor understand how the product is used.