formulations of paints, coatings, stucco, stains, and caulks containing 0.03-4% by 

weight in the final product. 

There are 38 end-use products (EP) formulated from these two MPs. Of the 

EPs, 30 are antifoulant boat paints containing Irgarol at 0.49-2.38% ai and eight, 

containing Irgarol at 3.5-32.5%, are used to manufacture paints (0.03-4% ai), 

coatings, stucco, stains, caulks, and building materials. Many of these treated 

materials are to be used outdoors only. Irgarol is used to prevent/control the 

growth of algae, slime, and plants on coated surfaces including fouling on 

submerged surfaces. To control other pests such as mussels and barnacles, 

many of the EPs also contain another pesticide, most frequently a coppercontaining compound. Some EPs also contain a fungicide or a bactericide. Most 

labels warn that neither treated materials nor coated surfaces are to come in 

contact with food, feed, livestock, dairy animals, potable water, or living plants. 

There are no EPA or FDA tolerances or tolerance exemptions associated with 

the use of Irgarol. 

Irgarol has low to moderate acute mammalian toxicity (Toxicity Category III or 

IV). It is a moderate dermal sensitizer. In a minimally-acceptable developmental 

toxicity study in rats, the maternal NOAEL was 50 mg/kg/day based on reduced 

mean daily food consumption and clinical signs at the LOAEL of 150 mg/kg/day 

(MRID 40684914). The developmental NOAEL was >300 mg/kg/day (HDT). It 

was the maternal NOAEL of 50 mg/kg/day from this study that was selected by 

the ADTC on 1/29/03 for use to calculate short- and intermediate-term oral and 

inhalation risks in the 5/13/03 occupational and residential assessment by D. 

Aviado (D286523). Note that a 2006 90-day dog oral toxicity study (MRID 

47042106) has been deemed to be unacceptable because the doses selected 

(0.8-38 mg/kg/day) were insufficiently high to elicit adverse effects. However, the 

maternal NOAEL from a 2006 rabbit developmental toxicity study was 15 

mg/kg/day based on decreased body weight, decreased body weight gain, and 

decreased food consumption at the LOAEL of 45 mg/kg/day (MRID 40684914). 

Based on a 21-day rat dermal toxicity study (MRID 40684912), short- and 

intermediate-term dermal risks are expected to be small as no adverse effects 

were incited by dermal doses up to the highest tested (1000 mg/kg/day). 

In the event long-term dermal exposure of workers is possible, e.g. military or 

professional boat/ship hull painters, the 90-day oral toxicity study in rats (MRID 

42239401) could be used for risk assessment. In this study, the NOAEL was 8.2 

mg/kg/day based on a number of adverse effects observed at the LOAEL of 59 

mg/kg/day. These adverse effects included: decreased red blood cells, 

hemoglobin (males), hematocrit, and bilirubin and increased MCH, MCHC, and 

cholesterol. Decreased testicular weight, testicle weight/body weight ratio, and 

ovary weight resulted as did a mammary carcinoma in one female at the LOAEL. 

Evidence was provided (MRID 42500001) to satisfy the Agency that the single 

mammary tumor was a spontaneous occurrence and that there were no Irgarolrelated morphological or histological effects on the epididymides (MRID 

42500002) (11/30/92 T. McMahon). 

2
In the minimally-acceptable developmental toxicity study in rats, the maternal 

NOAEL was 50 mg/kg/day based on reduced mean daily food consumption and 

clinical signs at the LOAEL of 150 mg/kg/day (MRID 40684914). The 

developmental NOAEL was >300 mg/kg/day (HDT). In the 2006 rabbit 

developmental toxicity study, the maternal NOAEL was 15 mg/kg/day based on 

decreased body weight, decreased body weight gain, and decreased food 

consumption at the LOAEL of 45 mg/kg/day (MRID 40684914). The 

developmental NOAEL was 15 mg/kg/day based on increased post-implantation 

loss, decreased fetal body weight, and delayed fetal development occurring at 

the LOAEL of 45 mg/kg/day. As developmental effects were not observed in rats 

at the HDT and as the developmental effects in rabbits were fairly generalized 

and occurred at the same dose eliciting maternal effects, there is no evidence of 

increased sensitivity of the developing fetus relative to adult animals. 

A two-generation rat reproductive toxicity study was conducted in 2006 (MRID 

46822901). It was screened 8/28/06 (S. Malish, D331274) and determined not to 

necessitate an expedited review under FIFRA 6(a)(2); therefore, it has not yet 

been thoroughly reviewed. Irgarol was administered to male and female rats in 

the diet over two generations at 0, 20, 120, and 720 ppm (mean doses of ♂ and 

♀ about 1.5, 9, and 55 mg/kg/day) for at least 70 days premating and during 

pairing and gestation. Females were also fed at about 2.8, 17, and 105 

mg/kg/day (mean of P and F1 generations) during the lactation period (days 1-14 

postpartum). The NOAEL for maternal effects (mean of P and F1) was 9.5 

mg/kg/day based on the following adverse effects occurring at the LOAEL of 58 

mg/kg/day: reduced food consumption, reduced body weight gain, increased 

kidney and liver weights, reduced uterus and ovary weights, and adverse 

histopathology in the kidney, ovary, uterus, and vagina. The NOAEL for 

reproductive effects was 55 mg/kg/day (HDT) due to the absence of adverse 

effects on any of the reproductive parameters evaluated. The NOAEL for pup 

developmental effects was 17 mg/kg/day based on reduced organ weight and 

decreased body weight of F1 and F2 pups during lactation at the LOAEL of 105 

mg/kg/day. The NOAEL for pup behavioral effects was 17 mg/kg/day based on 

reduced locomotor activity of F1 male pups at the LOAEL of 105 mg/kg/day. In 

summary, Irgarol induced no adverse effects on fertility/reproductive parameters 

even though histopathology and reduced organ weights were observed in organs 

and structures of the reproductive system of P and F1 animals. Any effects on 

pup behavior or pup development occurred at the same dose level causing 

maternal toxicity indicating that developing and young animals have no increased 

sensitivity to Irgarol compared to adults. 

To comply with FIFRA 6(a)(2) requirements, CIBA Corp. submitted two reports in 

2008 to address adverse ecological effects potentially due to endocrine 

disruption. Agency screening (N. Elkassabany, 11/25/08) determined that these 

studies need not receive an expedited review and, to date, have not been 

reviewed. Expert statements were submitted to refute the conclusion that Irgarol 

adversely affects reproduction of a snail and an isopod via an endocrinedisrupting mode of action in a freshwater indoor mesocosm study conducted by 

the German Federal Environment Agency (MRID 47569002). Also, a 

3
recombinant yeast screening study indicated that Irgarol did not exhibit 

estrogenic, androgenic, anti-estrogenic, or anti-androgenic activity (MRID 

47569001). 

Dermal absorption was studied in an in vivo rat study (2006; MRID 47042104) in 

which skin was treated with [14C]-Irgarol at 0.029 mg/cm2 applied in a ready-touse boat paint. Recovery of the administered radioactivity from skin plus 

adhered paint was 98.43% (±1.49%) after 10 hr, 94.61% (±2.02%) after 24 hr, 

and 87.63% (SD not given) after 72 hr. The maximum dermal absorption was 

4.9% which occurred at 72 hr. An in vitro comparison of rat skin and human skin 

was also conducted as part of this study. The [14C]-Irgarol at 0.029 mg/cm2 in a 

ready-to-use boat paint was also applied to 500-μ thick membranes mounted in 

diffusion cells. The receptor fluid was analyzed every 15-60 min for 24 hr after 

which time the membranes were rinsed. The mean absorbed dose was 12% 

through rat skin and 1.4% through human skin. It was estimated that, in vitro, rat 

skin is about 9.4 times more permeable to Irgarol than human skin. Although 

neither of these studies was deemed to be acceptable (S. Malish, 7/18/07, 

D338424), they indicate that there is a low rate of dermal absorption of Irgarol by 

human skin. This is consistent with the lack of adverse effects in the 21-day rat 

dermal toxicity study (MRID 40684912) at doses up to the highest tested (1000 

mg/kg/day). 

Irgarol is fairly rapidly metabolized and excreted by rats (MRID 47042103). 

Within 3-4 days of an oral dose of [14C]-Irgarol at 20 or 100 mg/kg, about 88 or 

94% of the administered 14C, respectively, was excreted. The bulk of this (65% 

of the low dose and 80% of the high dose) was biliary and thus was excreted in 

the feces. A lesser amount of the administered radioactivity was excreted in the 

urine: 23% of the low dose and 14% of the high dose. The principle rat 

metabolites were sulfur conjugates: M1 is the S-glucuronide, M2 is the Sglutamic acid, and M4 is the S-glycine conjugate; M4 accounted for 45% of the 

administered dose (S. Malish, 7/18/07, D338424). Note that all of these 

mammalian metabolites retain the cyclopropyl group and are conjugated – most 

likely to detoxify them and/or to facilitate excretion. However, several 

photodegradates identified in laboratory studies and natural waters (also named 

M1, M2, and M3) do not retain the intact cyclopropyl group and have not been 

conjugated [T. Arai, et al. (eds.) 2009]. 

Dietary (food) exposure to Irgarol is not expected to occur because all uses are 

outside and many of the use sites are inherently nonfood such as boat bottoms, 

stucco, and building materials. Although certain treated paints, coatings, stains, 

and caulks could be applied to surfaces having food contact, such as crop 

harvesting equipment or commodity shipping bins, four of eight EP labels prohibit 

use that may result in contact with food, feed, livestock, dairy animals, potable 

water, or living plants. The remaining four EP labels should be amended to bear 

this prohibition.

The registered uses of Irgarol could result in contamination of surface water and 

groundwater because the algaecide is expected to slowly leach from antifoulant4
painted boats or structures. Also, wastewater containing residues may be 

discharged from facilities manufacturing paints, coatings, stucco, stains, caulks, 

and building materials formulated with Irgarol. Finally, leaching of residues from 

outdoor surfaces covered with or comprised of Irgarol-treated materials may 

occur. Published literature indicates that abiotic hydrolysis, photolysis, and 

microbial metabolism will occur slowly in water. There is evidence that the 

degradates, which are closely related to Irgarol, are persistent in the aquatic 

environment. In fact, these degradates have been detected in coastal waters. 

Therefore, there is the potential for drinking water exposure to Irgarol residues to 

occur. The need for a drinking water exposure assessment will be revisited upon 

submission and review of the environmental fate data the Agency anticipates 

needing. These environmental fate data will be useful to determine if Irgarol can 

pass through wastewater treatment facilities into drinking water or migrate into 

residential groundwater wells as a result of its current use patterns. 

Manufactured materials formulated with Irgarol to protect the dry film (paints, 

coatings, stucco, stains, caulks, and building materials) from algal growth are 

permitted to be used outdoors only. They may generally be applied (including 

the boat paint ECs) by homeowners and other nonoccupational individuals thus 

resulting in residential exposure. Due to the nature of the treated materials and 

use sites as well as the low volatility of Irgarol, exposure of children is expected 

to be minimal. Data are needed to estimate residential or other nonoccupational 

exposure associated with application/use of Irgarol paints and coatings. A 

residential risk assessment will be needed. Provided that evidence is submitted 

to demonstrate that all preserved materials are labeled “For outdoor use only,” 

residential exposure data and risk assessment will be needed only for outdoor 

exposure scenarios. 

As dietary (food) human exposure is not expected to result from the currently 

registered Irgarol uses, aggregate risk is likely to consist of residential exposure 

and, possibly, drinking water exposure. However, the need for a drinking water 

exposure assessment (and inclusion in an aggregate assessment) will be 

determined upon submission and review of the environmental fate data the 

Agency anticipates needing. 

Occupational exposures fall into several general categories: (i) direct-pouring of 

Irgarol 1051 (EPA Reg. No. 40810-11) 98.1% MP to formulate antifoulant paint 

EPA-registered EPs; (ii) direct-pouring of 3.5-32.5% EPs or Irgarol 1071 (EPA 

Reg. No. 40810-15) 98.1% MP to preserve paints, coatings, stucco, stains, 

caulks, and building materials; (iii) construction workers/roofers/painters working 

with preserved building materials such as indoor latex paints, vinyl roofing, or 

elastomeric roofing; and (iv) painting boat hulls and other aquatic surfaces with 

EPA-registered EPs that serve as antifoulant coatings/paints. No chemicalspecific or site-specific exposure data are available to estimate Irgarol exposures 

to occupational handlers except several studies addressing residue migration 

from dried films of a number of EP antifoulant paints as well as three plastic 

polymers in association with the pending registration of EPA File No. 40810-RA 

in 2003 (this product is still pending). 

5
The primary sources of information for this assessment were the 6/2/03 Hazard 

Assessment by J. Chen (D286522) and the 5/13/03 occupational and residential 

assessment by D. Aviado (D286523). At that time, the lack of a developmental 

toxicity study in nonrodents and a reproductive toxicity study were cited as data 

deficiencies necessitating the application of an additional 10x database 

uncertainty factor. Six Irgarol toxicity studies were submitted by Ciba Specialty 

Chemicals Corp. in 2006 (90-day dog oral toxicity, rabbit developmental toxicity, 

rat two-generation reproductive toxicity, rat in vivo dermal penetration, in vitro

comparative rat vs. human skin penetration, and rat metabolism). These studies 

have been considered in this Human Health Scoping Document. The purpose of 

this document is to determine whether sufficient data are available to support 

registration review and whether new human health assessments are needed to 

reflect current use patterns, regulations, and policies. The Agency’s rationale for 

requiring additional data and/or conducting new risk assessments under the 

registration review process have been provided in Appendix A. 

Section 1. Chemical Identity

Table 1.1 Chemical Identity 

Common Name Irgarol, cybutryn 

Chemical Name 1,3,5-Triazine-2,4-diamine, N-cyclopropyl-N’-(1,1-

dimethylethyl)-6-(methylthio)- 

Synonyms s-Triazine, 2-(tert-butylamino)-4-(cyclopropylamino)-6-

(methylthio)- 

Molecular Formula C11H19N5S 

Molecular Weight 253.4 

PC Code 128996 

CAS Registry Number 28159-98-0 

Registration Review Case No. 5031 

Chemical Structure 

Irgarol is an odorless, whitish-yellow solid at room temperature (25 C) that melts 

at 127-130 °C. It has low solubility in water (7 ppm) and an octanol/water 

partition coefficient (log KO/W) of 3.95 at 25 °C. Irgarol does not dissociate and 

has very low tendency to volatilize (vapor pressure = 6.6 x 10-7 mmHg at 25 °C). 

Irgarol is fairly stable to hydrolysis (at pHs of 5-9), microbial metabolism, and 

photodegradation. 

6
Section 2. Toxicology 

The Irgarol toxicology database is considered adequate to permit the registration 

review process to continue. Summarized below are the toxicology studies 

available at the time of the 5/13/03 assessment as well as the six toxicity studies 

submitted since that time. 

a. Acute Toxicity 

Irgarol poses mild acute toxicity to rats (Toxicity Category III) via the oral route 

(LD50 ≥200 mg/kg), the dermal route (LD50 ≥200 mg/kg), and the inhalation route 

(LC50 ≥4.09 mg/L) and is a slight eye irritant to rabbit (Toxicity Category III). It is 

a moderate skin sensitizer to guinea pigs and does not induce dermal irritation in 

the rabbit (Toxicity Category IV). [MRIDs 00160084, 40684907-40684909, 

41099401, and 41891405] 

b. Subchronic Toxicity 

In a 21-day rat dermal study (MRID 40684912), five albino rats, Tif:RAIF (SPF) 

per sex per group received repeated dermal dosing of test compound at 0, 10, 

100, or 1000 mg/kg/day for 6 hours/day, 5 days/week for 3 weeks. All rats 

survived during the course of this study. No signs or symptoms were observed in 

any of the dose groups. No erythema or edema reactions occurred either in the 

animals of the control or the treated groups. The systemic NOAEL is greater 

than 1000 mg/kg/day (highest dose tested). 

In a subchronic (90-day) rat toxicity study, Irgarol (99% ai) was administered to 

groups of male and female albino rats (20/sex/dose) by dietary admix (MRID 

42239401). Doses were 0 ppm, 20 ppm (0.89 and 0.90 mg/kg/day [M/F]), 150 

ppm (8.37 and 8.20 mg/kg/day [M/F]), and 1000 ppm (58.63 and 59.32 

mg/kg/day [M/F]). Toxicity was observed at the 1000-ppm LOAEL in male and 

female rats. Decreases in red cell count, hemoglobin, and hematocrit were 

observed, as were decreases in total bilirubin. Increased mean corpuscular 

hemoglobin, mean corpuscular hemoglobin concentration, and increased 

cholesterol were observed at the LOAEL. Decreased testicular weight and 

testicular/body weight ratio was observed in male rats at the LOAEL as was 

decreased ovarian weight in females. A spermatocele and a mammary 

carcinoma were observed at the LOAEL in one of 20 males and one of 20 

females, respectively. Evidence was provided (MRID 42500001) to satisfy the 

Agency that the mammary tumor in the female at the LOAEL was a spontaneous 

occurrence and that there were no Irgarol-related morphological or histological 

effects on the epididymides (MRID 42500002) (11/30/92 T. McMahon). Based 

on the results of this study, the systemic NOAEL was determined to be 8.2 

mg/kg/day, and the systemic LOAEL was 59 mg/kg/day for both sexes. 

In the 2006 90-day dog oral toxicity study (MRID 47042106), Irgarol (98% ai) was 

administered to four groups of beagle dogs/sex/dose in the diet at dose levels of 

0, 25, 100, 250, or 1000 ppm (equivalent in the male to 0, 0.8, 3, 8, or 32 mg/kg/ 

7
day and in the female to 0, 0.9, 4, 9, or 38 mg/kg/day). A satellite recovery group 

of four animals/sex/dose was maintained for 4 weeks on an Irgarol-free diet 

following dosing at 0, 250, or 1000 ppm. No treatment-related effects were seen 

including survival, body weight, food consumption, appearance and behavior, 

hematology, urinalysis, gross pathology, organ weight (absolute and relative), 

and histopathology. Increased cholesterol values were seen at the mid- and 

high-dose levels. Cholesterol values in the recovery group were still mildly 

elevated at the mid- and high-dose levels vs. the control group. Neither a 

NOAEL nor a LOAEL could be calculated. This 90-day oral toxicity study in the 

dog was considered not to be an acceptable study (OPPTS GLN 870.3150) due 

to the lack of overt toxicity at any dose (S. Malish, 7/18/07, D338424). Higher 

doses should have been used. 

The subchronic inhalation toxicity of Irgarol is not understood. Although this 

chemical is only mildly irritating via the inhalation route of exposure and it has a 

low vapor pressure (6.6 x 10-7 mmHg at 25 °C), exposure of residential and 

occupational antifoulant painters is likely via inhalation of aerosols. The Agency 

is concerned that one of the available oral-dosing toxicity studies will not be 

protective of the toxicity incited via the inhalation route of exposure. Therefore, 

an inhalation toxicity study is expected to be needed at this time to assess the 

risks associated with this major route of exposure. The Agency also anticipates 

that a quantitative assessment of inhalation risks posed by Irgarol should be 

conducted, especially reflecting application of Irgarol-preserved paint/antifoulant 

coatings. 

c. Developmental Toxicity 

In a developmental toxicity study in rats (MRIDs 40684913 and 40684914), 

naturally inseminated female Sprague-Dawley rats (25-31/group) were 

administered Irgarol (97.6% a.i.) by arachis oil gavage at doses of 0, 50, 150, 

and 300 mg/kg/day on gestation days 6 through 15. Pushing of the nose through 

the sawdust bedding after dosing and decreased body weight gain on days 6-15 

were observed at the 300 mg/kg/day dose level. Reduced food consumption 

was also observed at the high dose on days 6-10. There were no significant 

Cesarean section observations at any dose level in this study. The increased 

post-implantation loss observed at the high dose (two-fold higher than control) 

was not treatment-related as the data were derived from only one dam. No 

abnormal external or skeletal observations were noted in this study from 

examination of fetuses. The Maternal toxicity LOAEL was determined to be 150 

mg/kg/day (decreased body weight gain and clinical signs) and the Maternal 

toxicity NOAEL was determined to be 50 mg/kg/day. The Developmental toxicity 

NOAEL was determined to be >300 mg/kg/day (HDT), and the Developmental 

toxicity LOAEL was not established. The ADTC considered this study to be 

minimally acceptable, and recommended that the study be repeated using a 

higher top dose. The animals could have tolerated higher doses and the effects 

observed at 300 mg/kg/day were not toxicologically significant. 

8
In a second developmental toxicity study (MRID 47042105) TK 13079, Irgarol 

(98% a.i., Batch No. 34076FC4) was administered to 20 female Himalayan 

rabbits/dose by gavage at dose levels of 0, 5, 15, or 45 mg/kg/day (in 0.5% 

aqueous methyl-cellulose) from days 6 through 27 of gestation. Maternal toxicity 

was observed at 45 mg/kg/day and included decreased body weight, decreased 

body weight gain, and decreased food consumption. There were no treatmentrelated effects on maternal survival or clinical signs. The maternal NOAEL is 15 

mg/kg/day based on decreased body weight, decreased body weight gain, and 

decreased food consumption at the maternal LOAEL of 45 mg/kg/day. 

Treatment-related effects on developmental parameters observed at 45 

mg/kg/day included increased post-implantation loss, decreased fetal body 

weights, and increased incidences of delayed ossification. The decreased fetal 

body weights were attributed to maternal toxicity. The delayed ossification was 

attributed to delayed fetal development, as evidenced by decreased fetal body 

weight in this group. The developmental LOAEL is 45 mg/kg/day, based on 

increased post-implantation loss, decreased fetal body weight, and delayed fetal 

development. The developmental NOAEL is 15 mg/kg/day. 

As developmental effects were not observed in rats at the HDT and as the 

developmental effects in rabbits were fairly generalized and occurred only at the 

same dose eliciting maternal effects, there is no evidence of increased sensitivity 

of the developing fetus relative to adult animals. 

d. Reproductive Toxicity 

A two-generation rat reproductive toxicity study was conducted in 2006 (MRID 

46822901). It was screened 8/28/06 (S. Malish, D331274) and determined not to 

necessitate an expedited review under FIFRA 6(a)(2); therefore, it has not yet 

been thoroughly reviewed. Irgarol was administered to male and female rats in 

the diet over two generations at 0, 20, 120, and 720 ppm (mean doses of ♂ and 

♀ about 1.5, 9, and 55 mg/kg/day) for at least 70 days premating and during 

pairing and gestation. Females were also fed at about 2.8, 17, and 105 

mg/kg/day (mean of P and F1 generations) during the lactation period (days 1-14 

postpartum). The NOAEL for maternal effects (mean of P and F1) was 9.5 

mg/kg/day based on the following adverse effects occurring at the LOAEL of 58 

mg/kg/day: reduced food consumption, reduced body weight gain, increased 

kidney and liver weights, reduced uterus and ovary weights, and adverse 

histopathology in the kidney, ovary, uterus, and vagina. The NOAEL for 

reproductive effects was 55 mg/kg/day (HDT) due to the absence of adverse 

effects on any of the reproductive parameters evaluated. The NOAEL for pup 

developmental effects was 17 mg/kg/day based on reduced organ weight and 

decreased body weight of F1 and F2 pups during lactation at the LOAEL of 105 

mg/kg/day. The NOAEL for pup behavioral effects was 17 mg/kg/day based on 

reduced locomotor activity of F1 male pups at the LOAEL of 105 mg/kg/day. In 

summary, Irgarol induced no adverse effects on fertility/reproductive parameters 

even though histopathology and reduced organ weights were observed in organs 

and structures of the reproductive system of P and F1 animals. Any effects on 

pup behavior or pup development occurred at the same dose level causing 

9
maternal toxicity indicating that developing and young animals have no increased 

sensitivity to Irgarol compared to adults. 

e. Chronic Toxicity 

A chronic toxicity study is not available for Irgarol. In the 6/2/03 Toxicology 

Review (J. Chen, D286522) and the 5/13/03 risk assessment (D. Aviado, 

D286523), this antimicrobial was considered to be a nonfood chemical; the 

registered uses are still considered to be nonfood. Upon receipt and review of 

the environmental fate data considered to be needed, a determination of the 

extent of Irgarol exposure via drinking water will be made. Drinking water risks 

and long-term dermal and inhalation risks may be calculated using the 90-day rat 

oral subchronic toxicity endpoint. As a result, a chronic toxicity study has been 

determined not to be needed at this time. The available toxicity database is 

adequate for the conduct of any needed human health risk assessments. 

f. Carcinogenicity 

A carcinogenicity study for Irgarol is not available. The absence of positive 

results in the available mutagenicity studies (below) provide some evidence that 

Irgarol is not a mutagen with the potential to be a mammalian carcinogen. The 

available toxicity database is adequate for the conduct of any needed human 

health risk assessments. 

g. Mutagenicity 

In the Ames Salmonella test (MRID # 40684915), Irgarol was nonmutagenic to 

TA 98, TA100, TA100, TA102, TA1535 and TA1537 strains of Salmonella 

typhimurium either with or without metabolic activation at tested concentrations of 

20, 78, 313, 1250, & 5000 μg/plate (0.1ml). Irgarol was nonmutagenic in the in 

vitro Chinese hamster (CCL61) forward mutation assay and Chinese Hamster 

(V79) with or without metabolic activation at the tested concentrations (MRID 

40684916 and 41578303). Irgarol did not cause DNA damage or inducible repair 

in rat hepatocytes in the DNA repair assay (MRID 40684918). The tested 

concentrations were 0.3, 3, 5, 15, 20, and 30 μg/ml. Irgarol had a negative effect 

in the in vivo Chinese hamster micronucleus test (MRID 40684917) at all the 

three sampling times (16, 24, & 48 hrs posttreatment) at the dose level tested 

(3334 mg/kg). The results of these tests indicate that Irgarol is not likely to be 

mutagenic. 

h. Potential Endocrine Effects 

To comply with FIFRA 6(a)(2) requirements, CIBA Corp. submitted two reports in 

2008 to address adverse ecological effects potentially due to endocrine 

disruption. Agency screening (N. Elkassabany, 11/25/08) determined that these 

studies need not receive an expedited review and, to date, have not been 

reviewed. Expert statements were submitted to refute the conclusion that Irgarol 

adversely affects reproduction of a snail and an isopod via an endocrine10
disrupting mode of action in a freshwater indoor mesocosm study conducted by 

the German Federal Environment Agency (MRID 47569002). Also, a 

recombinant yeast screening study indicated that Irgarol did not exhibit 

estrogenic, androgenic, anti-estrogenic, or anti-androgenic activity (MRID 

47569001). 

Irgarol is a member of a class of pesticides collectively referred to as “triazine” 

pesticides. The triazines are derivatives of the s-triazine moiety, manufactured by 

the reaction of trichlorocyanuric acid with appropriate intermediates. Several 

classes of compounds result from these reactions, and include the s-triazine 

herbicides, the sulfonyl urea herbicides with an s-triazine moiety, and 

miscellaneous s-triazines. 

The Agency has examined the triazine class of pesticides with respect to a 

potential common mechanism of toxicity. This examination may be found at 

http://www.epa.gov/oppsrrd1/cumulative/triazines/triazinescommonmech.pdf. 

Several members of this class have been identified as causing toxicity through a 

similar mechanism of action. Specifically, atrazine, simazine, propazine, and 

certain degradates are considered to act through disruption of the hypothalamicpituitary-gonadal axis to attenuate the luteinizing hormone surge. As a result of 

this attenuation, exposure of the animal to estrogen is continuous, providing an 

environment conducive to the development of mammary gland tumors. 

Mammary gland tumors have been observed in female rats after administration 

of these chemicals, and the postulated mode of action of the triazine pesticide 

atrazine has been reviewed by the FIFRA Scientific Advisory Panel and has been 

found to be plausible (U.S. EPA, 2000). 

In the case of Irgarol, structural similarity exists with at least one member of the 

triazine class, namely Terbutryn. In the subchronic toxicity study conducted 

using Irgarol, the induction of mammary carcinoma at 1000 ppm occurred. This 

is similar to mammary tumors being induced by the close structural analog 

Terbutryn at 3000 ppm although other triazine pesticides induce mammary 

tumors after chronic administration. The induction of a mammary tumor in a rat 

dosed with Irgarol at 1000 ppm for only 90 days as opposed to chronic dosing 

raises concern and suggests that Irgarol shares a similar mechanism of 

mammary tumor production to other triazine pesticides. However, there are no 

mechanistic data specific to Irgarol that have been generated to determine if it 

causes any disruption of the hypothalamic-pituitary-gonadal axis. Pharmacokinetic data for Irgarol have also not been generated to permit comparison with 

those of other structurally-similar triazine pesticides. Without additional data 

such as the above, neither can it be determined whether Irgarol shares a 

common mechanism of toxicity with other triazine pesticides nor can it be 

completely ruled out. 

i. Dermal absorption 

Dermal absorption was studied in an in vivo rat study (2006; MRID 47042104) in 

which skin was treated with [14C]-Irgarol at 0.029 mg/cm2

 applied in a ready-to11
use boat paint. Recovery of the administered radioactivity from skin plus 

adhered paint was 98.43% (±1.49%) after 10 hr, 94.61% (±2.02%) after 24 hr, 

and 87.63% (SD not given) after 72 hr. The maximum dermal absorption was 

4.9% which occurred at 72 hr. An in vitro comparison of rat skin and human skin 

was also conducted as part of this study. The [14C]-Irgarol at 0.029 mg/cm2 in a 

ready-to-use boat paint was also applied to 500-μ thick membranes mounted in 

diffusion cells. The receptor fluid was analyzed every 15-60 min for 24 hr after 

which time the membranes were rinsed. The mean absorbed dose was 12% 

through rat skin and 1.4% through human skin. It was estimated that, in vitro, rat 

skin is about 9.4 times more permeable to Irgarol than human skin. Although 

neither of these studies was deemed to be acceptable (S. Malish, 7/18/07, 

D338424), they indicate that there is a low rate of dermal absorption of Irgarol by 

human skin. This is consistent with the lack of adverse effects in the 21-day rat 

dermal toxicity study (MRID 40684912) at doses up to the highest dose tested 

(1000 mg/kg/day). 

j. Rat Metabolism 

Irgarol is fairly rapidly metabolized and excreted by rats (MRID 47042103). 

Within 3-4 days of an oral dose of [14C]-Irgarol at 20 or 100 mg/kg, about 88 or 

94% of the administered 14C, respectively, was excreted. The bulk of this (65% 

of the low dose and 80% of the high dose) was biliary and thus was excreted in 

the feces. A lesser amount of the administered radioactivity was excreted in the 

urine: 23% of the low dose and 14% of the high dose. The principle rat 

metabolites were Sulfur conjugates: M1 is the S-glucuronide, M2 is the Sglutamic acid, and M4 is the S-glycine conjugate; M4 accounted for 45% of the 

administered dose (S. Malish, 7/18/07, D338424). Note that all of these 

mammalian metabolites retain the cyclopropyl group and are conjugated – most 

likely to detoxify them and/or to facilitate excretion. However, several 

photodegradates identified in laboratory studies and natural waters (also named 

M1, M2, and M3) do not retain the intact cyclopropyl group and have not been 

conjugated [T. Arai, et al. (eds.) 2009]. 

k. Toxicology Data Needs

The Agency anticipates the need for a 90-day rat inhalation toxicity study testing 

Irgarol.

Section 3. Dietary Exposure 

a. Food Exposure 

Dietary (food) exposure to Irgarol is not expected to occur because all uses are 

outside and many of the use sites are inherently nonfood such as boat bottoms, 

stucco, and building materials. Although certain treated paints, coatings, stains, 

and caulks could be applied to surfaces having food contact, such as picnic 

tables, crop harvesting equipment, or commodity shipping bins, product labels 

12
prohibit use that may result in contact with food, feed, livestock, dairy animals, 

potable water, or living plants. The label for the MP (Irgarol 1071; EPA Reg. No. 

40810-15) from which these EPs are formulated clearly specifies that 

manufactured (treated) products are not to be used where they can contact food; 

therefore, all EP labels should clearly limit use of preserved materials to nonfood 

areas. 

b. Drinking Water Exposure 

The registered uses of Irgarol could result in contamination of surface water and 

groundwater because the algaecide is expected to slowly leach from antifoulantpainted boats. Also, wastewater containing residues may be discharged from 

facilities manufacturing paints, coatings, stucco, stains, caulks, and building 

materials formulated with Irgarol. Finally, leaching of residues from outdoor 

surfaces covered with Irgarol-treated materials may occur. Published literature 

indicates that abiotic hydrolysis, photolysis, and microbial metabolism will occur 

slowly in water. There is evidence that the degradates, which are closely related 

to Irgarol, are persistent in the aquatic environment. In fact, these degradates 

have been detected in a number of coastal waterways. Therefore, there is the 

potential for human exposure to Irgarol residues in drinking water to occur. The 

need for a drinking water exposure assessment will be revisited upon submission 

and review of the environmental fate data the Agency anticipates needing. 

These environmental fate data will be useful to determine if Irgarol can pass 

through wastewater treatment facilities into drinking water or migrate into 

residential groundwater wells as a result of its current use patterns. 

Section 4. Residential Exposure

The dry film of paints, coatings, stucco, stains, and caulks and finished building 

materials are protected from algal growth by formulating with one of eight Irgarol 

EPs. These treated materials may be used in residential and public settings thus 

resulting in residential and other nonoccupational exposures. Three of the eight 

EPs specifically limit use to outdoor products such as exterior paints, two labels 

limit a few materials to outdoor use, whereas three EPs are silent on the final use 

site of the preserved materials. The label for the MP (Irgarol 1071; EPA Reg. No. 

40810-15) from which these EPs are formulated clearly specifies that 

manufactured (treated) products are to be used outdoors only; therefore, all EP 

labels should clearly limit use of preserved materials to the outdoors. Residential 

exposure of children to Irgarol is expected to be minimal due to the nature of the 

treated materials and use sites as well as the low volatility of Irgarol. Adults in 

residential settings are expected to be exposed to Irgarol via both the inhalation 

and dermal routes while painting or applying coatings or stains. Adult applicator 

and children’s postapplication exposure studies will be needed to permit the 

needed assessment of residential risk. Provided that evidence is submitted to 

demonstrate that all preserved materials are labeled “For outdoor use only,” 

residential exposure data and risk assessment will be needed only for outdoor 

exposure scenarios. 

13
Also, the boat antifouling paint EPs may be applied by homeowners and other 

private boat-owners. Data are needed to estimate residential exposure 

associated with brush/roller and spray-application of Irgarol-treated paints or 

coatings. A residential risk assessment will be needed reflecting this boat 

antifoulant paint application scenario. 

Section 5. Aggregate Risk 

As dietary (food) human exposure is not expected to result from the currently 

registered Irgarol uses, aggregate risk is likely to consist of residential exposure 

and, possibly, drinking water exposure. However, the need for a drinking water 

exposure assessment (and inclusion in an aggregate assessment) will be 

determined upon submission and review of the environmental fate data the 

Agency anticipates needing. 

Section 6. Occupational Exposure 

Occupational exposures fall into several general categories: (i) direct-pouring of 

Irgarol 1051 (EPA Reg. No. 40810-11) 98.1% MP to formulate EPA-registered 

antifoulant paint EPs; (ii) direct-pouring of 3.5-32.5% EPs or Irgarol 1071 (EPA 

Reg. No. 40810-15) 98.1% MP to preserve paints, coatings, stucco, stains, 

caulks, and building materials; (iii) construction workers/roofers/painters using or 

applying preserved building materials such as latex paints, vinyl roofing, or 

elastomeric roofing; and (iv) painting boat hulls and other aquatic surfaces, using 

paint rollers and airless sprayers with EPA-registered EPs that serve as 

antifoulant coatings/paints. No chemical-specific or site-specific exposure data 

are available to estimate Irgarol exposures to occupational handlers except a 

preliminary study of three TBT alternative antifoulants including Irgarol which was 

determined to be insufficient (D. Aviado, 3/31/98, D243433 and D243434); the 

full spectrum of worker exposure studies were recommended. Studies are also 

available addressing residue migration from dried films of a number of EP 

antifoulant paints as well as from three plastic polymers (MRID 45753201) in 

association with the pending registration of EPA File No. 40810-RA in 2003 (this 

product is still pending). Data are needed to estimate occupational exposures 

reflecting the four general categories listed above. These exposure estimates 

will be used to calculate occupational risks which also need to be assessed. 

Section 7. Cumulative Risk 

EPA does not have, at this time, available data to determine whether Irgarol has 

a common mechanism of toxicity with other substances or how to include this 

pesticide in a cumulative risk assessment. At this stage of this Registration 

Review, EPA has assumed that Irgarol does not have a common mechanism of 

toxicity with other substances. During the risk assessment stage, however, the 

14
Agency will address the possibility that Irgarol shares a common mechanism of 

toxicity with other substances including members of the Triazine Common 

Mechanism Group (CMG). Note that Irgarol (cybutryn) was neither included in 

the Triazine Cumulative Assessment Group (CAG) nor a member of the Triazine 

CMG associated with the 3/28/06 Triazine Cumulative Risk Assessment. 

Section 8. Endocrine Disruption 

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. 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. 

Irgarol is not among the group of 58 pesticide active ingredients on the initial list 

to be screened under the EDSP. Under FFDCA sec. 408(p) the Agency must 

screen all pesticide chemicals. Accordingly, EPA anticipates issuing future 

EDSP test orders/data call-ins for all pesticide active ingredients. 

For further information on the status of the EDSP, the 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/. 

Section 9. Human Incident Data 

There have been no human incidents reported in any of the OPP databases 

associated with exposure to Irgarol.

15
Section 10. Overall Conclusions 

There is no reasonable expectation of human dietary exposure to residues of 

Irgarol via food. No EPA or FDA regulations (tolerances or tolerance exemption) 

have been established for Irgarol. There are use patterns of Irgarol that could 

result in contamination of drinking water. However, environmental fate data 

anticipated to be needed concerning Irgarol passage through wastewater 

treatment plants will be used to determine the likelihood of human drinking water 

exposure. 

The dry film of paints, coatings, stucco, stains, and caulks and finished building 

materials are protected from algal growth by formulating with one of eight Irgarol 

EPs. These treated materials may be used in residential and public settings thus 

resulting in residential and other nonoccupational exposures. Also, the boat 

antifouling paint EPs may be applied by homeowners and other private boatowners thus resulting in residential exposure. Studies are expected to be 

needed to estimate exposures reflecting these residential scenarios. A 

residential risk assessment is recommended. Aggregate assessment of 

residential exposure and, possibly, drinking water exposure, will then need to be 

conducted. 

Exposure studies are needed for the following scenarios to estimate inhalation 

and dermal exposures to occupational handlers: (i) direct-pouring of Irgarol 1051 

(98.1% MP) to formulate EPA-registered antifoulant paint EPs; (ii) direct-pouring 

of 3.5-32.5% EPs or Irgarol 1071 (98.1% MP) to preserve paints, coatings, 

stucco, stains, caulks, and building materials; (iii) construction workers, roofers, 

and painters using or applying preserved building materials such as latex paints, 

vinyl roofing, or elastomeric roofing; and (iv) painting boat hulls and other aquatic 

surfaces with EPA-registered EPs that serve as antifoulant coatings/paints. Each 

of these scenarios will need to be assessed to estimate the risks to workers. 

a. Data Needs

The Agency anticipates that the following toxicology study (utility and rationale 

provided in Appendix A) is needed: 

Toxicology Data

• 90-day rat inhalation toxicity study (GLN 870.3465)

In addition, the nondietary exposure studies listed below (utility and rationale 

provided in Appendix A) are anticipated to be needed to permit assessment of 

several residential and occupational handler scenarios.

Residential/Occupational Exposure Data

• Outdoor Dermal Exposure (GLN 875.1100) 

• Indoor Dermal Exposure (GLN 875.1200) 

16
• Outdoor Inhalation Exposure (GLN 875.1300) 

• Indoor Inhalation Exposure (GLN 875.1400) 

• Applicator Exposure Monitoring Data Reporting for Dermal and Inhalation 

Data (GLN 875.1600) 

• Product Use Information (GLN 875.1700) 

b. Risk Assessments Needed

• A dietary (drinking water) exposure assessment may be needed to 

estimate any risk associated with leaching of Irgarol residues into 

water from antifoulants, paints, coatings, stucco, stains, caulks, and 

building materials formulated with Irgarol. The need for this 

assessment will depend on the outcome of the environmental fate data 

anticipated to be needed. 

• Assessment of residential handler risks reflecting exposures 

associated with use of preserved materials and antifoulant paint 

(brush/roller and airless sprayer) are expected to be needed. 

• Residential (and possibly drinking water) sources of exposure will be 

aggregated to estimate aggregate risks. 

• Risks to occupational handlers: (i) direct-pouring of Irgarol 1051 (EPA 

Reg. No. 40810-11) 98.1% MP to formulate EPA-registered antifoulant 

paint EPs; (ii) direct-pouring of 3.5-32.5% EPs or Irgarol 1071 (EPA 

Reg. No. 40810-15) 98.1% MP to preserve paints, coatings, stucco, 

stains, caulks, and building materials; (iii) using or applying preserved 

building materials such as latex paints, vinyl roofing, or elastomeric 

roofing (construction workers/roofers/painters); and (iv) painting boat 

hulls and other aquatic surfaces with EPA-registered EPs that serve as 

antifoulant coatings/paints using brush/roller and airless sprayer. 

c. Recommended Label Changes 

• Three of the eight EPs specifically limit use to outdoor products such as 

exterior paints, two labels limit a few materials to outdoor use, whereas 

three EPs are silent on the final disposition (indoors vs. outdoors) of the 

preserved materials. The label for the MP (Irgarol 1071; EPA Reg. No. 

40810-15) from which these EPs are formulated clearly specifies that 

manufactured (treated) products are to be used outdoors only; therefore, 

all EP labels should clearly limit use of preserved materials to the 

outdoors. Confirmation is needed that all preserved materials treated with 

Irgarol to protect the film from algal growth are labeled to restrict their use 

to outdoors only. 

• The Irgarol 1071 MP also directs that treated materials may not be used in 

such a way as to contact food, feed, drinking water, livestock, or living 

plants. Of the eight EPs, four state the same whereas four are silent on 

this topic. The remaining four EP labels should be amended to also bear 

this prohibition 

17
Appendix A. Need for, and Uses of, the Data 

Guideline Number: 870.3465 

Study Title: 90-Day Inhalation Toxicity (Rat) 

Rationale for Requiring the Data 

This study is required under the updated data requirements at 40 CFR 158.500 because, 

although Irgarol has very low vapor pressure, inhalable aerosols are created during application 

of preserved materials (especially airless paint spraying). The length of the study is important 

because human handlers of Irgarol-treated materials will often be repeatedly exposed for weeks 

or months at a stretch. A 90-day inhalation toxicity study has not been conducted and is 

required. The inhalation route is expected to be a major route of human exposure to Irgarol for 

several occupational and residential handler scenarios. 

Practical Utility of the Data 

1. How did the Agency make its earlier regulatory decisions without these data? 

Earlier regulatory decisions were made having only oral toxicity studies and a 21-day dermal 

toxicity study. Route-to-route extrapolation of both dose and effect cannot be done with any 

confidence. As a major exposure route for several scenarios is inhalation, there is no toxicity 

study to demonstrate the types of adverse effects that may be manifested via the inhalation route 

of exposure or expressed at the lung-specific adverse effect dose. A dose and effect from this 

90-day inhalation toxicity study are the most appropriate to be used as the hazard components 

of a quantitative inhalation risk assessment. 

2. How will the data be used? 

The data will be used to properly characterize and quantify the hazard and risks to occupational 

and residential handlers exposed to Irgarol associated with its use in such a way that a spray or 

aerosol is generated. This study will allow the selection of a dose and endpoint and the conduct 

of a risk assessment that is duration- and route-appropriate. 

3. How could the data impact the Agency’s future decision-making? 

In the absence of inhalation toxicity data, the Agency would have to estimate inhalation risks 

using an oral toxicity study and rely on the assumption that effects, absorption, distribution, and 

toxicity of Irgarol are the same via the oral and inhalation routes of exposure. The 90-day 

inhalation toxicity study will allow the Agency to refine its estimates of inhalation risks which 

allows greater confidence that risks from Irgarol will not be over- or underestimated. This study 

will permit appropriate label warnings, PPE, and any necessary risk mitigation. 

18
Guideline Number: 875.1100

Study Title: Outdoor Dermal Exposure 

Guideline Number: 875.1200 

Study Title: Indoor Dermal Exposure 

Rationale for Requiring the Data 

The dermal exposure route is very important for exposure scenarios such as painting with 

antifoulants, caulking, or applying roofing shingles. However, very limited worker exposure 

monitoring data are available for antimicrobial pesticides, including materials preservatives used 

in paint and other consumer products. EPA would be forced to use these limited data to perform 

screening level risk assessments if it did not now require these studies. The existing data in the 

Chemical Manufacturers Association (CMA) database and Pesticide Handlers Exposure 

Database (PHED) for worker exposure scenarios are limited in scope and quality. The CMA 

data also has QA/QC problems, including the lack of field fortification, laboratory recoveries, 

and/or storage stability information. In addition, the CMA data have an insufficient number of 

replicates. EPA presented the need for additional handler exposure data to the January 2007 

Science Advisory Panel (SAP) as well as to the April 2007 Human Studies Review Board 

(HSRB) and both groups agreed that additional data are warranted. To protect workers from 

dermal exposures to pesticides, EPA requires dermal exposure monitoring data. Chemicalspecific dermal exposure data are needed to estimate handler exposures for the occupational 

and residential uses. 

Practical Utility of the Data 

1. How did the Agency make its earlier regulatory decisions without these data? 

The Agency conducted a risk assessment in 1998 using limited, preliminary exposure data 

concerning antifoulant application. No other quantitative assessments of registered uses have 

been conducted. Significant dermal exposure is associated with registered Irgarol uses. This 

triggers the need for chemical- and use pattern-specific occupational and residential exposure 

data upon which to base a quantitative risk assessment. 

2. How will the data be used? 

The dermal exposure data will be used to quantitatively assess the occupational and residential 

exposure of handlers applying antifoulant paints using sprayers and brush/rollers, handlers 

direct-pouring the preservative during the manufacturing of paint, coatings, stains, caulk, stucco, 

and building materials. These data will be used to assess Irgarol exposure of residential and 

professional handlers in a chemical- and use pattern-specific way.

3. How could the data impact the Agency’s future decision-making?

The dermal exposure data will be used to quantify dermal risks to occupational and residential 

handlers using the registered antifoulant paint products and materials preserved with Irgarol. 

These data will be used to accurately quantify exposures for the first time. 

19
Guideline Number: 875.1300 Study Title: Outdoor Inhalation Exposure

Guideline Number: 875.1400 Study Title: Indoor Inhalation Exposure 

Rationale for Requiring the Data 

The inhalation exposure route is likely to be the most important for exposure scenarios such as 

application of antifoulant paint using paint rollers/airless sprayers where aerosols will be 

generated. However, very limited worker exposure monitoring data are available for 

antimicrobial pesticides, including antifoulants and material preservatives used in paint, caulk, 

and other building products. EPA would be forced to use these limited data to perform screening 

level risk assessments for Irgarol if it did not now require these studies. The existing data in the 

Chemical Manufacturers Association (CMA) database and Pesticide Handlers Exposure 

Database (PHED) for worker exposure scenarios are limited in scope and quality. For the CMA 

data, inhalation concentrations were typically below the detection limits, so the unit exposures for 

the inhalation exposure could not be accurately calculated. The CMA data also has QA/QC 

problems, including the lack of field fortification, laboratory recoveries, and/or storage stability 

information. In addition, the CMA data have an insufficient number of replicates. EPA presented 

the need for additional handler exposure data to the January 2007 Science Advisory Panel 

(SAP) as well as to the April 2007 Human Studies Review Board (HSRB) and both groups 

agreed that additional data are warranted. To protect workers from inhalation exposure to 

pesticides, EPA requires inhalation exposure monitoring data. The data are required to support 

handler exposures for the industrial and residential uses. 

Practical Utility of the Data 

1. How did the Agency make its earlier regulatory decisions without these data? 

The Agency conducted a risk assessment in 1998 using limited, preliminary exposure data 

concerning antifoulant application; there was low confidence in the risk estimates resulting. No 

quantitative assessments of other registered uses have been conducted. Significant inhalation 

exposure is associated with registered Irgarol uses. This triggers the need for chemical- and 

use pattern-specific occupational and residential exposure data upon which to base a 

quantitative risk assessment. 

2. How will the data be used? 

The inhalation exposure data will be used to quantitatively assess the occupational and 

residential exposure of handlers applying antifoulant paints using sprayers and brush/rollers, 

handlers direct-pouring the preservative during the manufacturing of paint, coatings, stains, 

caulk, stucco, and building materials. These data will be used to assess Irgarol exposure of 

residential and professional handlers in a chemical- and use pattern-specific way. 

3. How could the data impact the Agency’s future decision-making?

The inhalation exposure data will be used to reliably estimate inhalation risks to occupational and 

residential handlers using Irgarol-treated antifoulant paints and building materials. If future risk 

assessments are performed without these data, the Agency will have to assume a significant 

degree of uncertainty in its regulatory decision-making process. The lack of these data could 

result in underestimation or overestimation of handler risks. The former would result in the 

Agency not protecting human health whereas the latter could greatly limit the flexibility of the 

Agency and registrants with respect to decisions made from high-end screening level 

assessments. If risks warrant mitigation, the inhalation exposure data will provide the types of 

mitigation necessary, such as closed systems for commercial uses and/or potential removal of 

uses from the label. 

20
Guideline Number: 875.1600 

Study Title: Applicator Exposure Monitoring Data Reporting for Dermal and Inhalation 

Data 

Rationale for Requiring the Data 

This data requirement is linked to the dermal and inhalation exposure data also being required. 

The submission of these exposure monitoring data serves as quality assurance and control 

(QA/QC) for the dermal and inhalation data. These data are intended to ensure that the product 

manufacturer and registrant conducting the study adhere to a defined set of quality criteria and 

meet the study requirements of the Agency. These data allow the Agency to determine if the 

quality of data provided will serve the risk assessment needs of the Agency and support the 

registrant’s goal for registration review. Submission of exposure monitoring data reporting 

increases the Agency’s confidence in the data submitted. 

Practical Utility of the Data 

1. How did the Agency make its earlier regulatory decisions without these data? 

There are currently only very limited, preliminary exposure data that permitted an assessment of 

risk to only one Irgarol use scenario. As the study was unsatisfactory, the reporting data were 

likewise unsatisfactory. As a result, earlier regulatory decisions were based on an incomplete 

and low-confidence assessment of risk. 

2. How will the data be used? 

These studies will be used to validate the data generated in the indoor and outdoor dermal and 

inhalation applicator exposure studies. These data are important because it allows EPA to 

assess the quality of each exposure study and thus the accuracy of the exposure calculations 

derived from that study. Information that must be submitted includes a description of the 

purpose of the study and what requirement(s) it is intended to satisfy, a summary of the study, a 

comprehensive section on materials, methods, and calculations, a section interpreting the 

scientific results of the study, a discussion of quality assurance, identification of the location of 

the raw data, and any references, communications, and protocols relevant to the conduct of the 

study. 

3. How could the data impact the Agency’s future decision-making? 

If the exposure monitoring data reporting is not submitted in conjunction with the indoor and 

outdoor dermal and inhalation applicator exposure studies, the Agency may not be able to utilize 

the studies to the fullest extent to conduct its human health exposure and risk assessments. The 

lack of such data could cause the Agency to use inadequate surrogate data, resulting in a highend screening level risk assessment and a potential overestimation of exposures.

21
22

Guideline Number: 875.1700 

Study Title: Product Use Information 

Rationale for Requiring the Data 

Product use information is a narrative description of which, when, and how materials are 

preserved when the product is actually applied; it is not a field study. A description of how 

products containing Irgarol are used will provide a comprehensive, realistic assessment of its 

potential applications and resulting handler exposure. Descriptions are needed of: (i) what 

specific types of materials are treated; (ii) what stage in the manufacturing process each material 

is treated; (iii) the conditions to which the Irgarol will be exposed (temperatures, pH’s, etc.); (iv) 

the rate of degradation of Irgarol; etc. These will provide a comprehensive, realistic assessment 

of potential residential and occupational exposures. Therefore, these data are required. 

Product use information permits EPA to more accurately assess pesticide exposure to 

applicators by describing how the pesticide is actually used and applied. EPA requires this 

information because differences in use can translate to significant differences in exposure and 

thus risk. 

The guideline for postapplication product use information was presented to the FIFRA Science 

Advisory Panel (SAP) in March 1998. (The draft guideline is available at 

http://www.epa.gov/scipoly/sap/meetings/1998/march/contents.htm.). The guideline for 

applicator product use information should be substantially similar to the one for postapplication. 

Practical Utility of the Data 

1. How did the Agency make its earlier regulatory decisions without these data? 

The Agency used its best professional judgment based on its years of experience and general 

use information from the registered product labels as well as product chemistry data. 

2. How will the data be used? 

The description of the materials preserved, application techniques, and physicochemical 

disposition will be used to determine the exposure scenarios for which exposure studies will be 

required for use in risk assessment and for the Agency to determine how representative the 

exposure data are of the “real-world” use scenarios. 

3. How could the data impact the Agency’s future decision-making? 

These data will enable the Agency to understand how the registered products are applied and to 

ensure that the risk assessment is inclusive of the types of exposures occurring during pesticide 

use and from any potential postapplication contact. This information will permit a determination 

of which use patterns are expected to result in exposures less than the Agency’s level of 

concern, which ones must be supported by additional data, and which ones are likely to have 

risks of concern and, therefore, must be mitigated.