Page 2 of 32 

EXECUTIVE SUMMARY

 The chemical 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride (CTAC) was first 

registered in 1964 and the Registration Eligibility Decision (RED) was completed in 1995. 

There are 2 end use products, DowicilR

 75 and DowicilR 150 that contain CTAC as the active 

ingredient (ai). Both of these products are formulated as water soluble powders and packaged in 

drums or water soluble packets. CTAC is registered for use as a materials preservative and for 

use in oil, pulp and paper, and textile production. CTAC is FDA approved for use as an indirect 

food additive in Adhesives and Components of Coatings, Paper and Paperboard Components and 

polyurethane resins. Both products are for industrial use only. 

 Several additional toxicity studies for CTAC were submitted after the RED. These studies 

include a set of acute toxicity studies for DowicilR

 75, an Unscheduled DNA Synthesis (UDS) 

Study and a Dermal Reproduction/Developmental Study in Rats. These studies were reviewed 

and found to be acceptable. 

Because CTAC releases formaldehyde it will also be necessary to assess formaldehyde 

inhalation exposures in addition to the CTAC oral, dermal and inhalation exposures from the 

parent compound. Based upon the use patterns, physical/chemical properties and hazard data, 

the following exposures to CTAC and formaldehyde will need to be assessed: 

• Dietary exposure from the use of CTAC in food packaging. 

• Incidental oral and dermal exposure from wearing clothing made from textiles treated with 

finishing fluids preserved with CTAC. 

• Occupational dermal and inhalation exposure to CTAC and inhalation exposure to 

formaldehyde during the open pour addition of CTAC powder for materials preservation, 

oil production, pulp and paper production and textile production. 

• Occupational dermal and inhalation exposures to CTAC and inhalation exposure to 

formaldehyde during the use of CTAC treated MWFs and paints. 

• Residential dermal and inhalation exposure to CTAC and inhalation exposure to 

formaldehyde during the use of treated paints and general purpose cleaners 

• Residential inhalation exposure to formaldehyde during the use of CTAC treated laundry 

detergents. 

To assess the above exposures the following toxicological and exposure data will be needed: 

• 90-day Oral Toxicity (rodent and non-rodent) – The existing studies are unacceptable 

because the data summary tables are illegible and will need to be repeated if legible copies 

cannot be obtained. 

• Developmental Toxicity (non-rodent) – Although a study has been done in rodents an 

additional study is needed for non-rodents because developmental effects can vary across 

species. 

• Reproductive Toxicity (Oral) – Although a dermal developmental/reproductive study has 

been done, an oral reproductive study is needed to assess the dietary exposures from the 

food packaging uses because reproductive effects can be route specific. 

• 90 Day Inhalation (rat) – This study is needed to assess exposures during open-pour 

addition of powders and the use of CTAC treated MWFs, paints and cleaners. 

• Chronic Oral (rodent) and carcinogenicity – This study is needed to assess long term 

dietary exposures from the FDA approved uses and long term occupational exposures from 

the MWF use.
• Dermal and Incidental Oral Exposure – Leaching studies are needed to assess exposures 

from wearing clothing made from textiles treated with finishing fluids preserved with 

CTAC. 

• Dermal and Inhalation Indoor Exposure – Studies are needed to assess the CTAC dermal 

and inhalation exposures and the formaldehyde inhalation exposures during the open 

pouring of powders and the use of CTAC treated MWFs, paints, general purpose cleaners 

and laundry detergents. 

1.0 BACKGROUND 

1.1 Chemical Identity 

The chemical name for CTAC is 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride and 

it can be in the form of a cis or trans isomer. DowicilR 75 is a racemic mixture of the cis and 

trans isomers of CTAC and DowicilR 150 contains primarily the cis isomer of CTAC. These 

chemicals were previously referred to as DowicilR

 100. 

Table 1 - Chemical Identity of CTAC 

Chemical Name 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride (CTAC) 

Trade Names Dowicil 75, Dowicil 150, Dowicil 100, Dowicil 200, Quaternium 15 

PC Codes 017901 (Cis/Trans CTAC, Dowicil 75) 

017902 (Cis CTAC, Dowicil 150) 

CAS Registry Number 4080-31-3 (Dowicil 75) 

51229-78-8 (Dowicil 150) 

Case No. 3069 

Empirical Formula C9H16N4Cl2

Structure 

trans - Form

1.2 Chemical and Physical Properties 

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

assessment are listed in Table 2. CTAC has a relatively low vapor pressure of 

<1.0 x 10-7 mm Hg at 25 C. 

Page 3 of 32 
Page 4 of 32 

Table 2 - Physical and Chemical Properties of CTAC 

Property Value Reference 

Molecular Weight 251.2 EPA, 1995 

Physical State Powder EPA, 1995 

Melting Point 178-210 C EPA, 1995 

Density 2.375 @ 21 C EPA, 1995 

Solubility (gms/100 gm solvent) Water = 127.2 EPA, 1995 

Octanol/Water Partition Coefficient Log p = -0.1 EPA, 1995 

Vapor Pressure <1.0 x 10-7 mm Hg @ 25 C EPA, 1995 

2.0 USE INFORMATION 

2.1 Formulation Types and Percent Active Ingredient

According to OPPIN, as of 01/07/2010, there are 2 end use products containing CTAC as the 

active ingredient (ai). These products include DowicilR

 75 (EPA Reg #464-403) and DowicilR

150 (EPA Reg #464-327) both of which are registered to the Dow Chemical Company. Both 

products are formulated as water soluble powders, and are packaged in drums or water soluble 

packets. 

2.2 Summary of Registered Uses 

CTAC is registered for use as a preservative in pesticide formulations, adhesives, 

construction materials, latex emulsions, metal working fluids, paints, coatings and inks, and 

household, institutional and industrial cleaning and laundry products. Additional use sites 

include oil production (packer fluids, recirculated muds and underground strata), pulp and paper 

(coatings, finishes and printing colors) and textiles (finishing and spinning fluids). All of the 

above uses were included in the RED and were found to be eligible for reregistration (EPA, 

1995). 

CTAC is included in the listing of Inert Ingredients Permitted for Use in Non-food Use 

Pesticide Products which was last updated on January 27, 2009. The racemic mixture form (PC 

Code 817901) is a preservative in 63 end use products (EPs) and the cis form (PC Code 817902) 

is a preservative in 69 EPs. Most EPs are pet care and consumer products; most are insecticides 

but some are herbicides. 

2.3 Summary of Use Data 

 The Dow Chemical Company is the sole producer of CTAC and has extensive product 

information for DowicilR

 75 posted at www.dow.com/biocides. According to the DowicilR 75 

Preservative brochure (Dow, 2008), sales of DowicilR 75 were distributed as follows: Cleaners 

(52.0%), Paints (32.9%), Building Materials (10.9%), Adhesives (2.8%), Paper (1.0%) and 

Metal-working Fluids (0.4%). Although DowicilR

 150 is also mentioned on the Dow website, 

no product literature is provided, which suggests that CTAC is primarily marketed as DowicilR

75. DowicilR

 75 contains the racemic mixture whereas DowicilR 150 contains the cis isomer. 
Page 5 of 32 

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

DowicilR 75 is used for paints and coatings, adhesives and sealants and synthetic latex polymers. 

It is one of the top five preservatives used in paints and coating with an estimated U.S. 

consumption of 11% of the total category by volume and 5% of the total category by value. This 

report indicated that DowicilR

 75 is not used in metal working fluids or for petroleum production. 

CTAC is also used as a preservative in cosmetics and toiletry items as DowicilR 200. These 

uses are the purview of the FDA and DowicilR

 200 is not registered by the EPA. 

 

3.0 TOXICOLOGY 

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

were available to the Agency when the RED was written in 1994 and additional studies that were 

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

• A set of acute toxicity studies for DowicilR 75 (MRIDs 439564-08 to -12 and 439890-10) 

• An Unscheduled DNA Synthesis (UDS) Study for DowicilR 150 (MRID 457182-01) 

• A Dermal Reproduction/Developmental Study in Rats, MRID 472130-01 

The acute tox studies were reviewed by the Special Review and Reregistration Division 

(EPA, 1998) and were found to be acceptable for use in supporting the registration of DowicilR

75 (EPA reg. #464-403). The UDS study was reviewed by the Antimicrobials Division (EPA, 

2003) and classified as being acceptable and meeting the UDS assay guideline requirement 

(875.5500). The dermal reproduction/developmental study was reviewed by the Antimicrobials 

Division (EPA, 2010) and satisfies the guideline requirement for a combined repeated dose 

toxicity study with the reproduction/developmental toxicity screening test (OPPTS 870.3650; 

OECD-422) in the rat. 

3.1 Acute Toxicity 

 A complete database of acute toxicity data for CTAC as DowicilR 150 was available to the 

Agency at the time the RED was written and additional data for DowicilR

 75 was submitted after 

the RED. A summary of the findings is included in Table 3. 

Table 3 - Acute Toxicity Values for CTAC 

Test (species) Test 

Substance 

Result Toxicity 

Category 

81-1 Oral Toxicity (rat) LD50 - 2664 mg/kg III 

81-2 Dermal Toxicity (rabbit) LD50 – 923 mg/kg II 

81-3 Inhalation Toxicity (rat) LC50 - > 4.7 mg/L IV 

81-4 Eye Irritation (rabbit) Slight irritation III 

81-5 Skin Irritation (rabbit) Slight irritation IV 

81-6 Dermal sensitization (guinea pig) 

DowicilR

 150 

Non-sensitizer N/A 

81-1 Oral Toxicity (rat) LD50 - 1000 mg/kg III 

81-2 Dermal Toxicity (rabbit) LD50 >5000 mg/kg IV 

81-3 Inhalation Toxicity (rat) LC50 - > 5.2 mg/L IV 

81-4 Eye Irritation (rabbit) One animal had obvious swelling of the 

lids in the first hour, then cleared 

IV 

81-5 Skin Irritation (rabbit) Slight to well defined erythema and 

slight edema lasting through 72 hours 

IV 

81-6 Dermal sensitization (guinea pig) 

DowicilR

 75 

Not a dermal sensitizer N/A 
Page 6 of 32 

3.2 Subchronic and Chronic Toxicity 

Subchronic Dermal Toxicity

The RED included a 90 day dermal toxicity study (MRID #406502-01) during which doses 

of 0, 50, 200, or 1000 mg/kg/day of DowicilR

 75 were applied to the skin of rats (6 hrs/day; 5 

days/week) for 90 days. The only treatment related effect was a dose dependent increase in 

ulcerative dermatitis at the treatment site that was correlated with the abrasions from clipping. 

There were no systemic effects observed and the systemic NOAEL was 1000 mg/kg/day. This 

study was rated as acceptable.

Subchronic Oral Toxicity

The RED included a 90 day oral toxicity study in rats (MRID #111075) during which 

DowicilR

 75 was administered in the diet at doses of 0, 7.5, 15, or 30 mg/kg/day. A NOAEL 

could not be derived from this study because some of the data summary tables in the study 

report were illegible. These tables were requested in the RED; however, there is no indication 

that they have been received. 

The RED included a 90 day oral toxicity study in dogs (MRID #127915) during which 

DowicilR

 75 was administered in gelatin capsules to dose levels of 0, 7.5, 15 and 30 mg/kg/day. 

One female in the 30 mg/kg/day group was sacrificed due to general deterioration on the 84th day 

of the study; necropsy revealed ascites with evidence of liver toxicity. The only other 

toxicologically significant findings during the study included a significant decrease in the 

hemocrit, hemoglobin and white blood counts in the 30 mg/kg/day males and histopathological 

changes, especially in the liver, in 30 mg/kg/day males and females. The incidence and/or 

severity of several findings in the liver were increased in the 30 mg/kg/day males and females. 

These findings included obliterative vasculitis and perivasculitis of hepatic blood vessels, 

perivascular and pericholangiolar infiltration of mononuclear cells; and hyperplasia of the 

reticuloendothelial cells lining the hepatic sinusoid. The study was classified as supplementary 

due to absence of legible summary tables for hematology and organ weights. 

Developmental Toxicity

The RED included a dermal developmental toxicity study (MRID#403497-01) during which 

rats were administered DowicilR

 75 at doses of 0, 250 or 500 mg/kg/day. These doses were 

applied as a 50 percent aqueous solution to skin daily on gestation days 6 through 15. No 

significant adverse effects were observed and the study was considered to be adequate. 

Subsequent to the RED, a combined reproduction/developmental dermal toxicity repeated 

dose screening test (MRID 472130-01) was submitted. During this study Cis/Trans-CTAC 

(DowicilR 75) was applied to the skin of groups of 10 rats/sex/dose at dose levels of 0 (wrapped 

vehicle control), 0 (unwrapped, untreated control), 75, 225, or 750 mg/kg/day. Females were 

treated four weeks prior to breeding, during breeding (two weeks), gestation (three weeks), and 

lactation (three weeks). The adult males were dosed for 10 weeks. F1 offspring were dosed for 

one week after weaning. The additional control group was included to evaluate the impact of 

dermal wrapping. 
Page 7 of 32 

In the adult female and male rats, exposure to 750/mg/kg/day of DowicilR

 75 caused 

excessive dermal irritation and reduced body weight and feed consumption. This dose group was 

sacrificed on day 17 for humane reasons. Adult rats dosed with 225 mg/kg/day experienced less 

severe, though still apparent dermal effect. Treatment with 75 mg/kg/day resulted in minor, 

transient skin effects in two male rats and one female. 

There were no reproductive effects in adult animals. The offspring of the 225 mg/kg/day 

group showed slight decreases in pup and weanling body weights and slightly decreased food 

consumption. There was slight scaling of the skin in one male weanling, but this was the only 

dermal effect in the offspring. The NOAEL for general system toxicity and reproductive 

toxicity were both 75 mg/kg/day. A NOAEL for dermal effects could not be established due 

to the mild severity of skin effects at 75 mg/kg/day. 

The reproductive/developmental toxicity study in the rat is classified acceptable - guideline

and satisfies the guideline requirement for a combined repeated dose toxicity study with the 

reproduction/developmental toxicity screening test (OPPTS 870.3650; OECD-422) in the rat. 

Reproductive Toxicity

Although a dermal developmental/reproductive study has been done as discussed above, this 

study cannot be used to assess the reproductive effects from oral exposures because these effects 

could be route specific. 

Mutagenicity

There were three mutagenicity studies for DowicilR 75 reported in the RED. In the Chinese 

hamster ovary (CHO) cell assay (MRID#405451-01) DowicilR 75 was mutagenic with metabolic 

activation and non-mutagenic without metabolic activation. DowicilR

 75 was negative in the rat 

hepatocyte unscheduled DNA synthesis (UDS) assay (MRID#405451-03) and in the mouse 

micronucleus assay (MRID 405451-02). Based on the results of CHO assay, the HED RfD/Peer 

Review Committee recommended in their memo of 2/9/1995 that follow-up testing be conducted 

to evaluate the interaction of DowicilR 75 with gonadal DNA. In 2002, a UDS Study in Rat 

Heptocytes (MRID #457182-01) using Cis-CTAC (i.e. DowicilR

 150) was submitted and this 

study indicated that Cis-CTAC did not cause UDS. 

3.4 Toxicology of Formaldehyde 

 As the release of formaldehyde is associated with the use of CTAC, the exposure and risk 

associated with the formaldehyde released as a result of registered CTAC uses must be assessed. 

The characterization of formaldehyde toxicity and the selection of endpoints for risk assessment 

was included in the Formaldehyde RED (EPA, 2008) and the following endpoints were selected 

for the purposes of the RED: 

• To assess non-cancer risks, a NOAEL of 0.1 ppm for peak exposures was selected from 

literature studies where respiratory irritation was observed in workers exposed to 

formaldehyde. To account for the variability in human sensitivity in the general 

population an uncertainty factor of 10 was added for residential exposures. 
Page 8 of 32 

• To assess cancer risks a unit risk of 1.3 x 10-5 per ug/m3

 from IRIS and the results of CIIT 

model runs as presented in Conolly et. al. 2004 were used. 

At the time of the RED, there was uncertainty regarding the approach for the assessment of 

the cancer risks and it was anticipated that these uncertainties would be resolved upon 

completion of the IRIS update for formaldehyde. As an interim measure, the cancer risks were 

presented as range based on the existing IRIS unit risk and the results of CIIT model runs. 

There were also uncertainties regarding the selection of the non-cancer endpoint because an 

evaluation of formaldehyde was also being conducted by OPPT and NCEA to evaluate a petition 

regarding formaldehyde emissions from pressed wood. As discussed in the Response to Public 

Comments on the Formaldehyde Preliminary Risk Assessment (EPA, 2009) the following 

disclaimer was provided for the non-cancer formaldehyde inhalation endpoint that was selected 

by OPP for use in the RED: 

OPP developed the formaldehyde inhalation noncancer toxicological endpoint used in this 

RED through the established reregistration process, which includes stakeholder consultation 

and public comment. However, the result has not been subjected to an interagency review or 

external peer review. Because of time constraints imposed by statutory deadline, OPP could 

not consider all available peer-reviewed science (for example, the intentional human dosing 

toxicity studies). Thus, this value should be considered an interim value, developed solely for 

the purposes of this determination and subject to future revision and subsequent peer review 

and should not be used in other contexts as EPA's opinion of the best available science on 

the non-cancer effects of formaldehyde. 

 3.5 Toxicological Endpoints Used for Risk Assessment 

In the human health risk assessment that supported the CTAC RED, dietary and residential 

exposures to CTAC were considered not likely due to the use pattern and were not assessed. 

The risk assessment did indicate that formaldehyde exposures could be of concern for 

occupational populations; however it did not evaluate these exposures. The risk assessment also 

considered the residential exposure of formaldehyde in treated materials such as paints, 

adhesives and cleaners to be minimal because an emission study on carpet adhesives indicated 

“formaldehyde does not present an exposure hazard.” 

Toxicity Data Needs

Six toxicology studies will be needed to complete registration review. These studies are listed in 

Section 10. 
Page 9 of 32 

4.0 DIETARY ASSESSMENT 

Dietary Exposure

CTAC is FDA approved for use as an indirect food additive as listed in Table 4. Use of 

CTAC in food contact articles is interpreted as a food use. These uses were not assessed during 

the RED; therefore, a dietary risk assessment will be needed to determine if there are any 

potential dietary concerns from indirect food exposures to CTAC. 

Table 4 – FDA Approved Uses of CTAC in Food

CFR Use Limitations 

Part 175 – Indirect Food Additives: Adhesives and Components of Coatings

21 CFR 175.105 Adhesives For use as a preservative only. 

Part 176 – Indirect Food Additives: Paper and Paperboard Components 

21 CFR 176.170 Components of paper and 

paperboard in contact 

with aqueous and fatty 

foods 

For use only: 

1. As a preservative at a level of 0.3 weight percent in latexes 

used as pigment binders in paper and paperboard intended for 

use in contact with nonacidic, nonalcoholic food. 

2. As a preservative at a level not to exceed 0.07 weight 

percent in latexes and 0.05 percent in pigment slurries used as 

components of coatings for paper and paperboard intended for 

use in contact with food 

21 CFR 176.180 Components of paper and 

paperboard in contact 

with dry food 

Same as above. 

Part 177 – Polyurethane resins in contact with bulk quantities of dry foods 

21 CFR 177.1680 As a preservative. 

Drinking Water Exposure

The registered uses of CTAC are not likely to result in contamination of surface water and 

ground water and as a result drinking water exposure is not expected. However, the need for a 

dietary drinking water exposure assessment for CTAC will be determined upon review of 

environmental fate data, which the Agency anticipates requiring. The Agency anticipates that 

environmental fate data will be useful to determine if CTAC can pass through waste-water 

treatment facilities into drinking water or migrate into residential groundwater wells as a result of 

its current use patterns. Therefore, the need for a dietary drinking water assessment will be 

revisited upon submission and review of the environmental fate data that are anticipated as being 

required. 

5.0 OCCUPATIONAL AND RESIDENTIAL EXPOSURE 

Occupational Handler Exposures 

CTAC is formulated as a soluble powder and is packaged in drums or in 2.5 pound water 

soluble packets. Occupational handler dermal and inhalation exposures to CTAC and inhalation 

exposures to formaldehyde can occur when manually transferring the powder from the drums to 

day tanks or mixing vessels during material preservation operations, oil production, paper 

production or textile production operations. These exposures were not evaluated in the RED 
Page 10 of 32 

and need to be assessed during registration review unless the use is restricted to powder 

packaged in water soluble packets in which case the exposure potential is greatly reduced and no 

assessment would be needed. 

 Occupational handler dermal and inhalation exposures to CTAC and inhalation exposure to 

formaldehyde can occur for machinists and painters using metal working fluids (MWFs) or 

paints treated with CTAC. These exposures were not evaluated in the RED and will need to be 

assessed during registration review. 

Occupational Handler Exposure Data for Formaldehyde 

There are some exposure data for formaldehyde available from studies that the Dow 

Chemical Company has conducted of operations such as paint production where DowicilR 75 

was added as a preservative to day tanks. The Agency has several of these studies on file that 

date back to 1984 and a more recent study from 2004 is available from the Dow Biocides 

Website. In 1991, two studies were conducted at latex plant where formaldehyde worker 

exposures were measured during the use of DowicilR

 75 in day tank operations. During the first 

study, two workers were sampled and average daily exposure was 0.009 and 0.010 ppm and 

excursion exposure was 0.006 and 0.120 ppm. During the second study, three workers were 

sampled for approximately three hours each and the results ranged from 0.02 to 0.05 ppm. In 

the 2004 study, Dow collected area samples for 240 minutes at breathing height in areas of 

highest expected levels which were the make-up room and the loading filter. The results were all 

non-detect with a limit of detection of 0.04 mg/m3. Direct read measurements were also taken 

with a Lion Formaldemeter Mark II and no formaldehyde was detected with an instrument 

sensitivity of 0.1 ppm. 

Chamber Emission Testing of Formaldehyde Emissions from Paint 

As a result of formaldehyde exposure concerns highlighted in the RED, the Dow Chemical 

Company completed small chamber emission testing of DowicilR

 treated paints. Initially the 

testing was done on steel plates according to an ASTM protocol, but when data from other 

studies indicated that wall board was a more appropriate substrate, the testing was repeated on 

wallboard. The testing on wallboard was done using paints formulated in the Dow Laboratory 

and paints formulated by a manufacturer, both of which were treated with 1500 ppm DowicilR

75. A brief summary of the data is included in Table 5 and a more detailed listing is included in 

MRID 448957-01. 

Table 5 - Release Rate of Formaldehyde from Paints Treated with 1500 ppm DowicilR 75 

(ug/m2 per hour) 

Dow Laboratory Formulations of 

Vinyl Acrylic Paints 

Manufacturer Vinyl Acrylic Paint 

Products 

Time 

(hours) 

Control Paint Treated Paint Control Paint Treated Paint 

Wallboard Control – 

No Paint Application 

0 27.3 138 38.9 271 8.5 

2 35.4 95.4 36.6 211 12.4 

4 27.8 75.3 31.2 147 16.4 

8 22.4 59.3 25.6 108 19.2 

16 16.2 48.3 18 65.1 20.3 

24 14.1 45.2 14.9 56.9 18.9 

168 3.3 26.5 3.9 29.2 6.6 
Page 11 of 32 

The Dow Chemical Company used the release rate data along with some assumptions (area 

painted per day, room ventilation rate, days of painting per year, years painting per lifetime etc.) 

and the IRIS unit risk of 1.3 x 10-5 per ug/m3 (EPA, 1991) to write a cancer risk assessment of 

occupational painter exposure to formaldehyde when applying a finish coat to six rooms (MRID 

448957-01) and when applying a primer and finish coat to three rooms (MRID 449947-01). The 

assessment for the finish coat application concluded that the cancer risk was 3.1 x 10-5 when 

using laboratory formulated paint and 3.7 x 10-5 when using manufacturer formulated paint. The 

assessment for the finish and primer coat application concluded that the cancer risk was 

8.6 x 10-5 when using laboratory formulated paint. Dow also used the release rate data to assess 

a cancer risk of 2.6 x 10-6 for janitors exposed to formaldehyde when mopping with cleaning 

solutions that contain 25 ppm DowicilR (Dow, 2000). It should be noted that these assessments 

are not human exposure studies not did they rely on data from human exposure studies. 

In a review of the Dow assessments (EPA, 2003), AD agreed with most of the assumptions 

used, but had some questions regarding the algorithm and the release rate. In particular, it was 

not clear if the release rate was based on the 0 hr timepoint as described in the middle of the 

paragraph that begins with the phrase “The three options for a weighted average are” or if was 

based on an average of the time 0 to the time 168 hours data as suggested by the last sentence of 

this same paragraph. There was also a discrepancy between formula 4-35 as cited by Dow 

Chemical in the report and as presented in EPA Volume 7 which may have involved the 

substitution of the term “mQ/v” for “k”. 

 At the time that the DowicilR

 assessments were prepared, formula 4-35 was used because it 

was believed to be the most representative of the exposure scenario and because it accounted for 

the fact that paint is applied a few square feet at time rather than all at once as implied by the 

chamber testing protocol. Since that time, the Wall Paint Exposure Model (WPEM) and the 

Indoor Air Quality Model (IAQX) have become available. These models were used in a recent 

assessment of a proposed formaldehyde releaser (EPA, 2009) and could be used to assess the 

exposures from CTAC. There are, however, uncertainties associated with estimating whole 

house air concentrations using small chamber test data and models and it may be necessary to 

conduct whole house or large chamber studies to resolve these uncertainties. 

 

Residential Exposures

Residential inhalation and dermal exposures to CTAC and/or inhalation exposure to 

formaldehyde can occur during the use of treated paints, general purpose cleaners and laundry 

detergents. These exposures were not evaluated in the RED and will need to be assessed during 

registration review. 

Exposure Studies Needed for Registration Review

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. 

 
Page 12 of 32 

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 pesticide exposures. An aggregate risk assessment may be needed for CTAC if 

it is determined that a drinking water exposure could occur based on the environmental fate data. 

This assessment would consist of the aggregation of the dietary food exposure from CTAC 

residues in treated food packaging and the exposure that would occur from CTAC residues in 

drinking water. The need for including residential incidental oral, dermal and inhalation 

exposures in the aggregate will be determined when the required toxicology studies are 

completed and added to the database for use in endpoint selection. 

 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.” EPA has not yet determined whether CTAC has a common mechanism 

with other compounds; consequently, a cumulative assessment will not be performed at this time. 

 With respect to formaldehyde, the assessment of aggregate risk is complicated by the fact 

that formaldehyde is released from a variety of non-biocidal sources such as pressed wood (EPA, 

2007a) and oxygenated fuels (ASTDR, 1999). A summary of formaldehyde air concentrations 

measured at outdoor sites and inside office buildings and homes is included in Table 6. 

Table 6 – Formaldehyde Ambient Air Concentrations 

Location Formaldehyde Air Concentrations (ppb) 

Median Mean High End 

Source 

Urban Air Toxics Monitoring Program 

(33 sites, 1828 samples) 

2.0 3.4 135 (maximum) EPA, 2008 

Office Buildings (n=100) 12 13 26 (95th percentile) EPA, 2007b 

Homes in Three US Cities (n=234) 16 18 26 (95th percentile) Lui et al, 2007 

 

7.0 INCIDENTS 

No CTAC specific incidents have been reported in the OPP Incident Data System (IDS). 

CTAC (as Quaternium-15) has been used as a preservative in cosmetics and it has been reported 

as one of the potential causes of allergic contact dermatitis in consumers of cosmetics. (Groot,et 

al, 1988; Storrs, et al. 1989; and O'Reilly and Murphy, 1996). Formaldehyde has also been 

identified as one of the major allergens in the cosmetic related allergic contact dermatitis 

(Groot,et al, 1988 and Storrs, et al. 1989). Although the individuals involved in these incidents 

may have been exposed to different type of allergens, Agency cannot rule out the possibility 

CATC may be related to the cosmetic related allergic contact dermatitis. It is also not known if 

the contact dermatitis is due to exposure to the CTAC parent or if it is due to exposure to the 

formaldehyde released by the parent. In a patch test study (Zug et. al., 2009) of 4,454 patients 

who had suspected contact dermatitis, 10.3% had positive reactions to Quaternium 15 and 9% 

had positive reactions to formaldehyde. Quaternium 15 was the among the 4 most positive 
Page 13 of 32 

allergens with the top three being nickel sulfate (19.0%), balsam of Peru (11.9%) and fragrance 

mix (11.5%). 

 

8.0 TOLERANCES 

As listed in 40 CFR §180.920 (growing crops), residues of the cis-isomer of 1-(3-

chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride (CAS Reg. No. 51229-78-8) are exempted 

from the requirement of a tolerance when used as an inert ingredient as a preservative at 0.14% 

by weight or less of pesticide formulations. This listing is based on a decision document that is 

available at ww.regulations.gov under docket number EPA-HQ-OPP-2007-0220. 

As mentioned in Section 4.0, CTAC is FDA approved for use as an indirect food additive in 

adhesives and components of coatings, paper and paperboard components and polyurethane 

resins in contact with bulk quantities of dry foods. 

It is noted that exemptions and regulations for food additives under Section 409 of the 

Federal Food, Drug, and Cosmetic Act (FFDCA) do not relieve the registrant of meeting the 

standard under Section 408 as amended by the Food Quality Protection Act (FQPA), when the 

active ingredient is subject to regulation as a food-use pesticide under the Federal Insecticide, 

Fungicide, and Rodenticide Act (FIFRA). Under Section 408, a determination of safety for 

residues of a pesticide that may be in food is required, and as defined in Section 408(b)(2)(ii), 

“that there is a reasonable certainty that no harm will result from aggregate exposure to the 

pesticide chemical residue, including all anticipated dietary exposures and all other exposures for 

which there is reliable information.” EPA will be performing risk assessments to determine if 

tolerances or exemptions from tolerances will be needed to support the existing registered uses of 

CTAC. 

9.0 ENDOCRINE DISRUPTION 

EPA is required under FFDCA, as amended by FQPA, to develop a screening program to 

determine whether certain substances (including all pesticide active ingredients) "may have an 

effect in humans that is similar to an effect produced by naturally occurring estrogen, or other 

such endocrine effects as the Administrator may designate." Following recommendations of its 

Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), EPA determined 

that there was a scientific basis for including, as part of the program, the androgen and thyroid 

hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC's 

recommendation that the Program include evaluations of potential effects in wildlife. For 

pesticide chemicals, EPA will use FIFRA and, to the extent that effects in wildlife may help 

determine whether a substance may have an effect in humans, FFDCA authority to require the 

wildlife evaluations. As the science develops and resources allow, screening of additional 

hormone systems may be added to the Endocrine Disruptor Screening Program (EDSP). 

When additional appropriate screening and/or testing protocols being considered under the 

Agency’s EDSP have been developed, CTAC may be subjected to further screening and/or 

testing to better characterize effects related to endocrine disruption. 
Page 14 of 32 

10.0 ANTICIPATED DATA NEEDS 

Based upon the use patterns, physical/chemical properties and hazard data for CTAC, the 

following exposures will need to be assessed: 

• Dietary exposure from the use of CTAC in food packaging. 

• Incidental oral and dermal exposure from wearing clothing made from textiles treated 

 with finishing fluids preserved with CTAC. 

• Occupational dermal and inhalation exposure to CTAC and inhalation exposure to 

formaldehyde during the open pour addition of CTAC powder during materials 

preservation, oil production, paper production and textile production. 

• Occupational dermal and inhalation exposures to CTAC and inhalation exposure to 

formaldehyde during the use of CTAC treated metal working fluids. 

• Occupational and residential dermal and inhalation exposure to CTAC aerosols and 

inhalation exposure to formaldehyde vapors during the use of treated paints. 

• Occupational and residential dermal and inhalation exposures to CTAC and inhalation 

exposure to formaldehyde during the use of cleaning solutions preserved with CTAC. 

• Residential inhalation exposures to formaldehyde during the use of laundry detergents 

treated with CTAC. 

To assess the above exposures the toxicological and exposure studies listed in Tables 7 and 8 

will be needed. Detailed justifications for these studies are provided in Appendix A. 

Table 7 – Human Toxicology Studies Needed for CTAC Registration Review

Study Needed Guideline Rationale 

90 Day Oral Toxicity – 

rodent and non-rodent 

870.3250 The existing studies are unacceptable because the data summary tables are 

illegible and will need to be repeated if legible copies cannot be obtained. 

Developmental Toxicity –

Non-Rodent 

870.3700 Although studies have been done in rodents an additional study is needed for 

non-rodents because developmental effects can vary across species. 

90 Day Inhalation - rat 870.3465 Potential occupational inhalation exposures during open-pour addition of 

powders during material preservation and the use of CTAC treated MWFs and 

paints. Potential residential exposure during the use of CTAC treated paints. 

Reproductive Study (Oral) 870.3800 Although a dermal developmental/reproductive study has been done, an oral 

reproductive study is needed to assess the dietary exposures from the food 

packaging uses because reproductive effects can be route specific. 

Chronic Oral – Rodent* 870.4100 

Carcinogenicity* 870.4200 

Long term dietary exposures from the food contact paper use, and long term 

occupational exposures from the MWF use. 

*A combined chronic toxicity/carcinogenicity study (OPPT 870.4300) can fulfill both the chronic oral and 

carcinogenicity data requirements. 
Page 15 of 32 

Table 8 –Exposure Studies Needed for CTAC Registration Review

Study Needed Guideline Rationale 

Dermal and Inhalation 

Indoor Exposure 

(Open Mixing/Loading Powders) 

875.1200 (Dermal) 

875.1400 (Inhalation) 

875.1600 (Data Reporting/Calculations) 

Exposure to CTAC aerosols and residues 

and formaldehyde vapors may occur 

during open pour addition of CTAC 

products*. 

Dermal and Inhalation 

Indoor Exposure 

(Metal Working Fluids) 

875.1200 (Dermal) 

875.1400 (Inhalation 

875.1600 (Data Reporting/Calculations) 

Exposure to CTAC aerosols and residues 

and formaldehyde vapors may occur 

during the use of metal working fluids 

treated with CTAC 

Dermal and Inhalation 

Outdoor Exposure 

(Airless Sprayer Painting) 

875.1100 (Dermal) 

875.1300 (Inhalation) 

875.1600 (Data Reporting/Calculations) 

Exposures to CTAC paint aerosols and 

residues may occur during exterior airless 

sprayer application of CTAC preserved 

paints. 

Dermal and Inhalation 

Indoor Exposure 

(Brush/Roller Painting) 

875.1200 (Dermal) 

875.1400 (Inhalation) 

875.1600 (Data Reporting/Calculations) 

Exposures to CTAC paint aerosols and 

residues and formaldehyde vapors** may 

occur during interior brush/roller 

applications of CTAC preserved paints. 

Dermal and Inhalation 

Indoor Exposure 

(Laundry Detergent) 

875.1200 (Dermal) 

875.1400 (Inhalation) 

875.1600 (Data Reporting/Calculations) 

Exposures to formaldehyde vapors** may 

occur during use of CTAC preserved 

laundry detergents. 

Dermal and Inhalation 

Indoor Exposure 

(General Purpose Cleaners) 

875.1200 (Dermal) 

875.1400 (Inhalation 

875.1600 (Data Reporting/Calculations) 

Exposure to CTAC aerosols and residues 

and formaldehyde vapors** may occur 

during the use of CTAC preserved general 

purpose cleaners. 

Textile Leaching Study None Established Need to determine leaching rate to assess 

incidental oral and dermal exposure from 

wearing clothing made from textiles 

treated with finishing fluids preserved with 

CTAC. 

Product Use Information 875.1700 Use information can be used to evaluate 

exposures and assist in the planning of 

exposure studies. 

*If the labels are amended to require water soluble packets, then the exposure studies will not be needed for the 

open loading/mixing scenario. 

**As discussed in Section 5.0, it may be possible to assess the formaldehyde exposures using chamber emission 

data and appropriate models.
Page 16 of 32 

11.0 REFERENCES 

ATSDR, 1999. Toxicological Profile for Formaldehyde, U.S. Department of Health and Human 

Services, Public Health Service, Agency for Toxic Substances and Disease Registry, July 1999 

Conolly, 2004. Human Respiratory Tract Cancer Risks of Inhaled Formaldehyde: Dose Response 

Predictions Derived from Biologically-Motivated Computational Modeling of a Combined Rodent and 

Human Dataset, CIIT, Toxicological Sciences Volume 82, pages 279-296, 2004. 

De Groot et. al., 1988. The Allergens in Cosmetics, Archives of Dermatology Volume 124, 

Pages 1525-1529, October 1988. 

Dow, 1999a. Methodology and Screening Risk Assessment for Latex Paint Formulations 

containing DowicilR 75 and Trace Quantities of Formaldehyde as a Hydrolysis Degradation 

Product (MRID 449957-01), Bryce D. Landenberger, Dow Chemical Company, August 6, 1999. 

Dow, 1999b. Methodology and Screening Risk Assessment for Vinyl Acrylic Paint/Primer 

Formulations containing DowicilR

 75 and Trace Quantities of Formaldehyde as a Hydrolysis 

Degradation Product (MRID 449947-01), Bryce D. Landenberger, Dow Chemical Company, 

December 9, 1999. 

Dow, 2000. Screening Risk Assessment: DOWFAXR 2A1 Product Containing DowicilR 75 and 

Trace Quantities of Formaldehyde as a Hydrolysis Degradation Product (MRID 451078-01). 

Bryce D. Landenberger, Dow Chemical Company, April 24, 2000. 

EPA, 1991. Integrated Risk Assessment Information System (IRIS) assessment for formaldehyde, Last 

Revised 5/1/1991. Accessed 3/18/2008. 

EPA, 1995. DowicilR CTAC Reregistration Eligibility Decision (RED), April 1995, 

http://www.epa.gov/pesticides/reregistration/status.htm

EPA, 1995b. RfD/Peer Review Report of Dowicil: cis/trans [1- (3- chloroallyl) -3,5,7-triaza-1-

azonia-adamantane chloride] Health Effects Division, February 9, 1995. 

EPA, 1995c. The HED Chapter of the Registration Eligibility Decision Document (RED) for 

Dowicil, Health Effects Division, January 27, 1995. 

EPA, 1998. Memorandum from Marianne Lewis to Steve Morrill, Subject: EPA Reg. No: 464-

403/Dowicil 75, Product Reregistration Branch of the Special Review and Reregistration 

Division. D240925 of January 27, 1998. 

EPA, 2003. Memorandum from S. L. Malish to Adam Heyward, Subject: Toxicity Review on 

Cis-CTAC (MRID 457182-01). Antimicrobials Division. D285704 of January 2, 2003. 

EPA, 2003. Memorandum from Siroos Mostaghimi to Adam Heyward, Subject: Review of 

Screening Risk Assessments for Latex Paint Formulations and Cleaning Solutions Containing 

Dowicil 75, D285124 of January 2, 2003. 
Page 17 of 32 

EPA, 2007a. Indoor Air Quality, Basic Information, Formaldehyde, 

http://www.epa.gov/iaq/formalde.html, updated 10/27/2009, Accessed 1/29/2010 

EPA, 2007b. Building and Assessment Survey and Evaluation (BASE) Study. 

http://www.epa.gov/iaq/base/voc_master_list.html, updated 3/20/2007. 

EPA, 2008. 2007 National Monitoring Programs (UATMP and NATTS) Volume I: Main 

Content. December, 2008 (see Table 4-2) 

EPA, 2009. Response to Public Comments on the Formaldehyde Preliminary Risk Assessment. 

Antimicrobials Division, D348460 of January 6, 2009. 

EPA, 2010. Revised Occupational and Residential Exposure and Risk Assessments for the 

Active Ingredient Tetramethylol Acetylenediurea (ActicideR

 F(N)). Antimicrobials Division, 

D333887, D335192 and D342000 of January 15, 2010. 

Kline, 2004. Specialty Biocide North America 2004, Kline and Company, Inc. 

Lui et al, 2007. Predicting Personal Exposure to Airborne Carbonyls Using Residential 

Measurements and Time/Activity Data, Lui, W. et al., Atmosphere Environment, 2007: 41, 

5280-5288. Cited in: Formaldehyde in the Indoor Environment, Salthammer, T., Mentese, S. and 

Marutsky, R., Chemical Review., Online Publication January 12, 2010. 

O’ Reilly and Murphy, 1996. Occupational Contact Dermatitis in a Beautician. Contact 

Dermatitis 35: 48. 

 

Storrs et al., 1989. Prevalence and Relevance of Allergic Reactions in Patients Patch Tested in 

North America – 1984 to 1985. Journal of the American Academy of Dermatology Volume 20, 

Pages 1038-45. 

Zug et al., 2009. Patch-test Results of the North American Contact Dermatitis Group 2005-2006. 

Dermatitis 20(3), pages 149-160, May-June, 2009. 
Page 18 of 32 

This page intentionally left blank.
Appendix A – Justification for the 

Toxicology and Exposure Studies Needed fo

the Registration Review of CTAC

Page 19 of 32 
Appendix A, Table 1 - Toxicology Study Justifications 

Guideline Study Title Practical Utility of the Data 

870.3465 90-Day Inhalation 

Toxicity Study (Rat) 

1) What is the value of the study? The Agency currently does not have a repeated dose inhalation toxicity stutherefore required to extrapolate from a repeated dose oral toxicity study to 

inhalation exposure. Since the effects of a chemical can vary greatly with r

administration, the use of a route specific study will greatly increase the ac

assessment. 2) How would the data be used? The study will be used to assess risks from inhalation exposures to CTAC tpour addition of powders during materials preservation, machining with flu

and painting with paint treated with CTAC. The study will be used to detespecific endpoints that will be used to assess the inhalation exposures and iuncertainty that exists when oral studies are used to assess inhalation expos3) How could the data affect the risk assessment? The study will allow the selection of a route specific endpoint which may b

route extrapolated endpoint currently used. It is possible that the database uis associated with using route to route extrapolation can be reduced or remo

lower level of concern for the uncertainty factor. 4) What is triggering the need for this data? The potential inhalation exposures that might occur during open pour additmaterial preservation, machining with CTAC treated metal working fluids CTAC treated paints are the trigger for requiring an inhalation risk assessm

requires an inhalation toxicity study. 

Page 20 of 32 
Appendix A, Table 1 - Toxicology Study Justifications

Guideline Study Title Practical Utility of the Data 

870.4100 and 870.4200 or 870.4300* 

Chronic Oral (Rodent)  and Carcinogenicity (Rodent) 

1) What is the value of the study?These studies are needed to assess the effects of long term exposures to CTthe use of CTAC in food packaging and metal working fluids. Currently th

studies available for CTAC and thus the effects of long term exposure on h

unknown. 2) How would the data be used?The study will form the foundation for hazard characterization and toxicity for risk assessment through all exposure routes (oral, inhalation, and derma

the Agency to conclude more definitively whether or not there would be an

term exposure. This will provide a more complete hazard characterization 

the potential risks to the U.S. general population including infants and child

FQPA. 3) How could the data affect the risk assessment?The study will be used to select endpoints that will be used to assess the lonCTAC. 4) What is triggering the need for this data?

This data need is triggered by the fact that there are long term exposures to 

packaging and metal working fluid uses and there are no studies available t

these exposures. *A combined chronic toxicity/carcinogenicity study (OPPT 870.4300) can oral and carcinogenicity data requirements.

Page 21 of 32 
Appendix A, Table 1 - Toxicology Study Justifications

Guideline Study Title Practical Utility of the Data 

870.3700 Developmental 

Toxicity Study – Non-Rodent 

1) What is the value of the study? This study is needed to verify the result of the rodent study which indicated cause developmental effects. The study in non-rodents is needed because dcan vary across species. 2) How will the data be used? The data will allow the Agency to conclude more definitively whether or nconcerns for developmental toxicity. It may also generate endpoints that ar

assessment of susceptible populations such as women of child bearing age. 3) How could the data affect the risk assessment? Currently it is assumed that there are no developmental effects and thereforfor developmental effects has been conducted. The required study may suor it may suggest that there are developmental effects that need to be assess4) What is triggering the need for this data? This study is needed to verify the result of the rodent study which indicated cause developmental effects. The study in non-rodents is needed because d

can vary across species.

Page 22 of 32 
Appendix A, Table 1 - Toxicology Study Justifications

Guideline Study Title Practical Utility of the Data 

870.3800 Reproduction and 

Fertility Effects 

1) What is the value of the study? This study is needed to verify the findings of the dermal development/reproindicated that CTAC does not cause adverse effects by the dermal route of 

study is needed because these effects can be route specific. 2) How will the data be used? The data will allow the Agency to determine is there are any concerns for rvia dietary exposure. It may also generate endpoints that are used for risk asusceptible populations such as women of child bearing age. 3) How could the data affect the risk assessment? Currently it is assumed that there are no reproductive effects from oral exporisk assessment for reproductive effects has been conducted. The required this assumption or it may suggest that there are reproductive effects that ne4) What is triggering the need for this data? This study is triggered by the fact that CTAC is registered for food packagiin dietary exposures. Although a dermal developmental/reproductive study oral reproductive study is needed to assess the dietary exposures because rebe route specific.

Page 23 of 32 
Page 24 of 32 

Appendix A, Table 1 - Toxicology Study Justifications

Guideline Study Title Practical Utility of the Data 

870.6200 90 Day Oral 

Toxicity – Rodent and Non-Rodent 

1) What is the value of the study? These studies form the core of the toxicology database for CTAC. Without insufficient information to determine if CTAC generates risks of concern fr

that result from the food packaging use and incidental oral exposures that r

use. 2) How will the data be used? These studies will be used as part of the toxicology database to assess dietaresult from the food packaging use and incidental oral exposures that result 3) How could the data affect the risk assessment? The existing studies are rated as unacceptable because some of the data sum

illegible. If legible copies of the data are obtained or if new studies are con

data, the data might indicate health effects that need to be assessed. 4) What is triggering the need for this data? These studies form the core of the toxicology database that is required to as

that result from the food packaging use and incidental oral exposures that r

use. 
Appendix A, Table 2 - Exposure Study Justifications 

Guideline Study Title Practical Utility of the Data 875.1200 875.1400 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 CTAC and inhalation exposureexpected during the open pour addition of powders during materials production and textile production. In addition, dermal and inhalatioopen pouring of powders are evident in exposure studies in the PestExposure Database (PHED). The existing Chemical Manufacturer data base and PHED for these scenarios are limited in scope for QAof replicates (i.e., number of times a worker is monitored for a specpresented 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 powders during materials preservation, oil proproduction. 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 the use of water soluble pto reduce these risks. 4) What is triggering the need for this data? The need for the exposure study is based on the potential for exposuaddition of powders during the materials preservation, oil productiolisted on label #464-403. This label indicates that the powder is avain 2.5 pound water soluble packets. If this exposure is precluded by product is always packaged in water soluble packets, then the exposneeded.

Page 25 of 32 
Appendix A, Table 2 - Exposure Study Justifications 

Guideline Study Title Practical Utility of the Data 875.1200 875.1400 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 CTAC and inhalation exposureexpected during machining operations that use metal working fluids treated with CTAC. There are no studies available to assess these 2) How would the data be used? The exposure data would be used to assess dermal and inhalation exinhalation exposures to formaldehyde that result from the use of MWwith CTAC. 3) How could the data affect the risk assessment? Currently there are no data available to assess exposures resulting frin MWF 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? CTAC is labeled for use as a preservative in “Metalworking Fluids” 

Page 26 of 32 
Appendix A, Table 2 - Exposure Study Justifications 

Guideline Study Title Practical Utility of the Data 875.1200 875.1400 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 CTAC and inhalation exposureexpected during interior brush/roller application of CTAC treated p

studies available to assess these exposures. 2) How would the data be used? The exposure data would be used to assess CTAC and formaldehydfrom brush/roller application of CTAC treated paints. 3) How could the data affect the risk assessment? Current there are no data available to assess the exposure of CTAC resulting from the use of CTAC in interior paints and therefore the runknown. 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? CTAC is labeled for use as a preservative in “Paints, Coatings and I403.

Page 27 of 32 
Appendix A, Table 2 - Exposure Study Justifications 

Guideline Study Title Practical Utility of the Data 875.1100 875.1300 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 CTAC and inhalation exposureexpected during airless sprayer application of CTAC treated exteriostudies available to assess these exposures. 2) How would the data be used? The exposure data would be used to assess CTAC and formaldehydfrom airless sprayer application of CTAC treated exterior paints. 3) How could the data affect the risk assessment? Current there are no data available to assess the exposure of CTAC resulting from the use of CTAC in exterior paints and therefore the 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? CTAC is labeled for use as a preservative in “Paints, Coatings and I403. 

Page 28 of 32 
Appendix A, Table 2 - Exposure Study Justifications 

Guideline Study Title Practical Utility of the Data 875.1200 875.1400 875.1600 

Applicator Indoor Exposure (Laundry Detergent) Dermal Inhalation Data Reporting 

1) What is the value of the study? Dermal and inhalation exposures to CTAC and inhalation exposureexpected during use of laundry detergents treated with CTAC. Theavailable to assess these exposures. 2) How would the data be used? The exposure data would be used to assess CTAC and formaldehydfrom use of use of laundry detergents treated with CTAC. 3) How could the data affect the risk assessment? Current there are no data available to assess the exposure of CTAC resulting from the use of CTAC in laundry detergents and therefore are unknown. The exposure data would be used to assess these riskmitigation is needed to reduce these risks. 4) What is triggering the need for this data? CTAC is labeled for use on label #464-403 as a preservative in “Hoand Industrial Cleaning & Laundry Products”. 

Page 29 of 32 
Appendix A, Table 2 - Exposure Study Justifications 

Guideline Study Title Practical Utility of the Data 875.1200 875.1400 875.1600 

Applicator Indoor Exposure (General Purpose Cleaner) Dermal Inhalation Data Reporting 

1) What is the value of the study? Dermal and inhalation exposures to CTAC and inhalation exposureexpected during use of general purpose cleaners treated with CTAC

available to assess these exposures. 2) How would the data be used? The exposure data would be used to assess CTAC and formaldehydfrom use of use of general purpose cleaners treated with CTAC. 3) How could the data affect the risk assessment? Current there are no data available to assess the exposure of CTAC resulting from the use of CTAC in general purpose cleaners, therefouse are unknown. The exposure data would be used to assess these mitigation is needed to reduce these risks. 4) What is triggering the need for this data? CTAC is labeled for use on label #464-403 as a preservative in “Hoand Industrial Cleaning & Laundry Products”. 

Page 30 of 32 
Appendix A, Table 2 - Exposure Study Justifications 

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

Dermal and incidental oral exposures to CTAC are expected during linens made from textiles that are treated with finishing fluids that aCTAC. There are no leaching studies available to assess these exp2) How would the data be used? The leaching data would be used to assess CTAC exposures that resclothing and blankets treated with CTAC. 3) How could the data affect the risk assessment? Currently there are no leaching data available to assess the dermal aexposure of CTAC resulting from the use of CTAC in textile finishrisks from this use are unknown. 4) What is triggering the need for this data? CTAC is labeled for use on label #464-403 as a preservative in “TeSpinning Fluids”. Textile finishing fluids are used to improve surfsoftness. 

Page 31 of 32 
Page 32 of 32 

Appendix A, Table 2 - Exposure Study Justifications 

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.