Page 2 of 32 EXECUTIVE SUMMARY The chemical 1-(3-chloroally l)-3,5,7-triaza-1-azoniaadamantane chloride (CTAC) was first registered in 1964 and the Registration Eligib ility Decision (RED) was completed in 1995. There are 2 end use products, Dowicil R 75 and Dowicil R 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 regist ered for use as a materials preservative and for use in oil, pulp and paper, and textile production. CTAC is FDA approved fo r use as an indirect food additive in Adhesives and Components of Co atings, Paper and Paperboard Components and polyurethane resins. Both produc ts 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 Dowicil R 75, an Unscheduled DNA Synthesis (UDS) Study and a Dermal Reproduction/Developmental St udy in Rats. These studies were reviewed and found to be acceptable.

Because CTAC releases formaldehyde it will al so be necessary to assess formaldehyde inhalation exposures in addition to the CTAC or al, dermal and inhalation exposures from the parent compound. Based upon the use patterns, phys ical/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 e xposure 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 produ ction and textile production.

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

formaldehyde during the use of CT AC treated MWFs and paints.

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

formaldehyde during the use of treated pa ints and general purpose cleaners

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

detergents.

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

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

because the data summary tables are illegible an d 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 beca use developmental effects can vary across species.

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

been done, an oral reproductive study is need ed to assess the dietary exposures from the food packaging uses because reproduc tive effects can be route specific.

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

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

• Chronic Oral (rodent) and carci nogenicity – 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 – Leach ing 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 formalde hyde inhalation exposures during the open pouring of powders and the use of CTAC treat ed MWFs, paints, general purpose cleaners and laundry detergents.

1.0 BACKGROUND

1.1 Chemical Identity

The chemical name for CTAC is 1-(3-chloroall yl)-3,5,7-triaza-1-azoniaada mantane chloride and

it can be in the form of a ci s or trans isomer. Dowicil R 75 is a racemic mixture of the cis and

trans isomers of CTAC and Dowicil R 150 contains primarily the cis isomer of CTAC. These chemicals were previously referred to as Dowicil R 100.

Table 1 - Chemical Identity of CTAC

Chemical Name 1-(3-chloroallyl)-3,5,7-triaza-1-azo niaadamantane 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 C 9 H 16 N 4 Cl 2 Structure

trans - Form

1.2 Chemical and Physical Properties

The physical and chemical properties of CTAC that are relevant fo r 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 32Page 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 ar e 2 end use products containing CTAC as the active ingredient (ai). Th ese products include Dowicil R 75 (EPA Reg #464-403) and Dowicil R

150 (EPA Reg #464-327) both of which are register ed to the Dow Chemical Company. Both products are formulated as wate r soluble powders, and are packag ed in drums or water soluble packets.

2.2 Summary of Registered Uses

CTAC is registered for use as a preservati ve 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 flui ds, recirculated muds and underg round 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 In gredients Permitted for Use in Non-food Use Pesticide Products which was last updated on Ja nuary 27, 2009. The racemic mixture form (PC Code 817901) is a preservative in 63 end use pr oducts (EPs) and the cis form (PC Code 817902) is a preservative in 69 EPs. Most EPs are pet ca re and consumer products; most are insecticides

but some are herbicides.

2.3 Summary of Use Data

The Dow Chemical Company is the sole pr oducer of CTAC and ha s extensive product

information for Dowicil R 75 posted at www.dow.com/biocides . According to the Dowicil R 75 Preservative brochure (Dow , 2008), sales of Dowicil R 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 Dowicil R 150 is also mentioned on the Dow website, no product literature is provided, which suggests that CTAC is primarily marketed as Dowicil R

75. Dowicil R 75 contains the racemic mixture whereas Dowicil R 150 contains the cis isomer.Page 5 of 32 According to the Specialty Biocides North America Report 2004-2005 (Kline, 2004),

Dowicil R 75 is used for paints and co atings, adhesives and sealants a nd synthetic latex polymers. It is one of the top five pres ervatives used in paints and co ating 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 Dowicil R 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 Dowicil R 200. These uses are the purview of the FDA and Dowicil R 200 is not registered by the EPA.

3.0 TOXICOLOGY

The toxicological database for the CTAC registra tion 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 additi onal studies include the following:

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

• An Unscheduled DNA Synthesi s (UDS) Study for Dowicil R 150 (MRID 457182-01)

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

The acute tox studies were reviewed by the Special Review and Re registration Division (EPA, 1998) and were found to be acceptable for use in supporting the re gistration of Dowicil R

75 (EPA reg. #464-403). The UDS study was revi ewed by the Antimicrobials Division (EPA, 2003) and classified as being acceptable and meeting the UDS assay guideline requirement (875.5500). The dermal reproduction/developmenta l study was reviewed by the Antimicrobials Division (EPA, 2010) and satisfies the guideline requirement for a combined repeated dose toxicity study with the repr oduction/developmental toxicity screening test (OPPTS 870.3650; OECD-422) in the rat.

3.1 Acute Toxicity

A complete database of acute t oxicity data for CTAC as Dowicil R 150 was available to the Agency at the time the RED was written and additional data for Dowicil R 75 was submitted after the RED. A summary of the fi ndings 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) Dowicil R 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) Dowicil R 75

Not a dermal sensitizer N/APage 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 Dowicil R 75 were applied to the skin of rats (6 hrs/day; 5 days/week) for 90 days. The only treatment rela ted 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

Dowicil R 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 so me of the data summar y 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

Dowicil R 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 sacr ificed due to general deterioration on the 84 th day of the study; necropsy revealed ascites with evidence of liver toxi city. The only other toxicologically significant findi ngs 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 obliter ative vasculitis and perivascul itis of hepatic blood vessels, perivascular and pericholangiol ar infiltration of mononuclear cells; and hyperplasia of the reticuloendothelial cells lining th e hepatic sinusoid. The study wa s classified as supplementary due to absence of legible summary tabl es for hematology and organ weights.

Developmental Toxicity

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

rats were administered Dowicil R 75 at doses of 0, 250 or 500 mg /kg/day. These doses were applied as a 50 percent aqueous solution to sk in 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 reproductio n/developmental dermal toxicity repeated dose screening test (MRID 472130-01) was submitt ed. During this study Cis/Trans-CTAC (Dowicil R 75) was applied to the skin of groups of 10 rats/sex/dose at dose levels of 0 (wrapped vehicle control), 0 (unwrapped, untreated co ntrol), 75, 225, or 750 mg/kg/day. Females were treated four weeks prior to br eeding, during breeding (two weeks) , gestation (three weeks), and lactation (three weeks). The adult males were do sed for 10 weeks. F1 offspring were dosed for one week after weaning. The addi tional 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 Dowicil R 75 caused excessive dermal irritation and reduced body we ight 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 de rmal 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 w eanling body weights and slightly decreased food consumption. There was slight scaling of the sk in 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 d ermal effects could not be established due to the mild severity of skin effects at 75 mg/kg/day.

The reproductive/developmental toxic ity study in the rat is classified acceptable - guideline and satisfies the guideline requirement for a co mbined repeated dose toxicity study with the reproduction/developmental toxicity screeni ng test (OPPTS 870.3650; OECD-422) in the rat.

Reproductive Toxicity

Although a dermal developmental/reproductive st udy has been done as discussed above, this study cannot be used to assess the reproductive eff ects from oral exposures because these effects could be route specific.

Mutagenicity

There were three mutagenicity studies for Dowicil R 75 reported in the RED. In the Chinese hamster ovary (CHO) cell assay (MRID#405451-01) Dowicil R 75 was mutagenic with metabolic activation and non-mutagenic withou t metabolic activation. Dowicil R 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 th e 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 Dowicil R 75 with gonadal DNA. In 2002, a UDS Study in Rat Heptocytes (MRID #457182-01) usin g Cis-CTAC (i.e. Dowicil R 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 re leased as a result of registered CTAC uses must be assessed. The characterization of formaldehyde toxicity an d the selection of endpoi nts 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 pp m for peak exposures was selected from literature studies where respiratory irrita tion was observed in workers exposed to formaldehyde. To account for the variabil ity in human sensitivity in the general population an uncertainty factor of 10 wa s added for residential exposures.Page 8 of 32 • To assess cancer risks a unit risk of 1.3 x 10 -5 per ug/m 3 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 ri sk and the results of CIIT model runs.

There were also uncertainties regarding the se lection of the non-cance r endpoint because an evaluation of formaldehyde was also being conduc ted 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 noncan cer toxicological endpoint used in this RED through the established reregistration proc ess, which includes stakeholder consultation and public comment. However, the result has not b een subjected to an interagency review or external peer review. Because of time constrai nts imposed by statutory deadline, OPP could not consider all available p eer-reviewed science (for examp le, 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 suppo rted the CTAC RED, dietary and residential exposures to CTAC were consider ed not likely due to the use pa ttern 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 formal dehyde in treated materials such as paints,

adhesives and cleaners to be minimal because an emission study on carpet adhesives indicated “formaldehyde does not presen t 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. Thes e 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 i ndirect food exposures to CTAC.

Table 4 – FDA Approved Us es 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 non acidic, 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 cont act 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 drinki ng water exposure is not expected. However, the need for a dietary drinking water exposure assessment fo r CTAC will be determined upon review of environmental fate data, which the Agency anti cipates 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 residentia l 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 environm ental fate data that are anticipated as being required.

5.0 OCCUPATIONAL AND RE SIDENTIAL EXPOSURE

Occupational Handler Exposures

CTAC is formulated as a soluble powder and is packaged in drums or in 2.5 pound water soluble packets. Occ upational handler dermal and inhalation exposures to CTAC and inhalation exposures to formaldehyde can occur when manua lly transferring the powde r from the drums to day tanks or mixing vessels during material preservation operations, oil production, paper production or textile production operations. Th ese exposures were not evaluated in the REDPage 10 of 32 and need to be assessed duri ng 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 ex posures to CTAC and inhalation exposure to formaldehyde can occur for machin ists 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 Expos ure Data for Formaldehyde

There are some exposure data for formalde hyde available from studies that the Dow Chemical Company has conducted of operations such as paint production where Dowicil R 75 was added as a preservative to day tanks. The Ag ency has several of thes e 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 Dowicil R 75 in day tank operations. During the first study, two workers were sampled and averag e daily exposure was 0.009 and 0.010 ppm and excursion exposure was 0.006 and 0.120 ppm. Du ring the second study, three workers were sampled for approximately three hours each and th e results ranged from 0.02 to 0.05 ppm. In the 2004 study, Dow collected area samples for 2 40 minutes at breathing height in areas of highest expected levels which were the make-up room and the loadi ng filter. The re sults were all

non-detect with a limit of detection of 0.04 mg/m 3 . Direct read measurements were also taken

with a Lion Formaldemeter Mark II and no form aldehyde 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 Dowicil R 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 substrat e, the testing was repeated on wallboard. The testing on wall board was done using paints form ulated in the Dow Laboratory and paints formulated by a manufacturer, both of which were treate d with 1500 ppm Dowicil R

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 Dowicil R 75 (ug/m 2 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 6.6Page 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/m 3 (EPA, 1991) to write a cancer risk assessment of occupational painter exposure to formaldehyde wh en applying a finish coat to six rooms (MRID 448957-01) and when applying a prim er and finish coat to th ree 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 appl ication concluded that the cancer risk was

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

a cancer risk of 2.6 x 10 -6 for janitors exposed to formal dehyde when mopping with cleaning solutions that contain 25 ppm Dowicil R (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 algori thm and the release rate. In particular, it was

not clear if the release rate was based on the 0 hr timepoint as describe d in the middle of the paragraph that begins with the phrase “The thre e 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 disc repancy 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 Dowicil R 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 resolv e these uncertainties.

Residential Exposures

Residential inhalation and dermal exposures to CTAC and/or inhalation exposure to formaldehyde can occur during th e use of treated paints, gene ral 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 justifica tions are included in Appendix A.Page 12 of 32 6.0 AGGREGATE AND CUMULATIVE EXPOSURE

In examining aggregate exposure, EPA take s into account the available and reliable information concerning exposures to pesticide re sidues 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 aggrega tion of the dietary f ood exposure from CTAC residues in treated food packaging and the expos ure 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 determin ed when the required t oxicology studies are completed and added to the databa se for use in endpoint selection.

Section 408(b)(2)(D)(v) of FFD CA requires that, when consid ering whether to establish, modify, or revoke a tolerance, the Agency consider "available information” concerning the cumulative effects of a particular pesticide's re sidues and "other substances that have a common mechanism of toxicity.” EPA has not yet dete rmined whether CTAC has a common mechanism with other compounds; consequently, a cumulative a ssessment will not be pe rformed 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 formal dehyde air concentrations

measured at outdoor sites and inside office bu ildings and homes is in cluded in Table 6.

Table 6 – Formaldehyde Ambient Air Concentrations

Formaldehyde Air Concentrations (ppb) Location

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 (95 th percentile) EPA, 2007b

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

7.0 INCIDENTS

No CTAC specific incidents have been reporte d in the OPP Incident Data System (IDS). CTAC (as Quaternium-15) has been used as a pr eservative 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 a nd 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 a llergens, Agency cannot ru le out the possibility CATC may be related to the cosmet ic related allergic contact derm atitis. It is also not known if the contact dermatitis is due to exposure to the CT AC parent or if it is due to exposure to the formaldehyde released by the parent. In a pa tch test study (Zug et. al., 2009) of 4,454 patients who had suspected contact dermatitis, 10.3% ha d positive reactions to Quaternium 15 and 9% had positive reactions to formaldehyde. Qu aternium 15 was the among the 4 most positivePage 13 of 32 allergens with the top th ree being nickel sulfat e (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 approve d for use as an indirect food additive in adhesives and components of coatings, paper and paperboard compone nts and polyurethane

resins in contact with bul k quantities of dry foods.

It is noted that exemptions and regulati ons 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-us e 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, incl uding all antic ipated dietary exposures a nd all other exposures for

which there is reliable informati on.” 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 a ll pesticide active ingredients) "may have an

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

such endocrine effects as the Administrator ma y designate." Following recommendations of its Endocrine Disruptor Screening and Testing Ad visory 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 evalua tions 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 eff ect in humans, FFDCA authority to require the

wildlife evaluations. As the sc ience develops and resources a llow, screening of additional hormone systems may be added to the Endoc rine Disruptor Screen ing Program (EDSP).

When additional appropriate scre ening and/or testing protocol s being considered under the Agency’s EDSP have been developed, CTAC may be subjected to further screening and/or testing to better charact erize 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 additi on of CTAC powder during materials preservation, oil production, paper production and textile production.

• Occupational dermal and inhalation exposur es 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 vapor s during the use of treated paints.

• Occupational and residential dermal and inhalation exposur es to CTAC and inhalation exposure to formaldehyde during the use of cleaning solutions preserved with CTAC.

• Residential inhalation exposures to formal dehyde 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 unaccepta ble 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 an d 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 reproductiv e 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 N eed 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 packet s, 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 a ssess the formaldehyde exposures using chamber emission data and appropriate models.Page 16 of 32 11.0 REFERENCES

ATSDR, 1999. Toxicological Profile for Formalde hyde, 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 Co mputational Modeling of a Combined Rodent and Human Dataset, CIIT, Toxicological Scie nces Volume 82, pages 279-296, 2004.

De Groot et. al., 1988. The Allergens in Cosm etics, Archives of Dermatology Volume 124, Pages 1525-1529, October 1988.

Dow, 1999a. Methodology and Screening Risk Assessment for Latex Paint Formulations containing Dowicil R 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 Scre ening Risk Assessment for Vinyl Acrylic Paint/Primer Formulations containing Dowicil R 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: DOWFAX R 2A1 Product Containing Dowicil R 75 and Trace Quantities of Formaldehyde as a H ydrolysis Degradation Product (MRID 451078-01). Bryce D. Landenberger, Dow Ch emical Company, April 24, 2000.

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

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

EPA, 1995. Dowicil R CTAC Reregistration Eligibil ity 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 Registratio n Eligibility Decision Document (RED) for Dowicil, Health Effect s Division, January 27, 1995.

EPA, 1998. Memorandum from Marianne Lewis to Steve Morrill, S ubject: EPA Reg. No: 464- 403/Dowicil 75, Product Reregistra tion Branch of the Special Review and Reregistration Division. D240925 of January 27, 1998.

EPA, 2003. Memorandum from S. L. Malish to Ad am Heyward, Subject: Toxicity Review on Cis-CTAC (MRID 457182-01). Antimicrobial s Division. D285704 of January 2, 2003.

EPA, 2003. Memorandum from Siroos Mostaghimi to Adam Heyward, Subject: Review of Screening Risk Assessments for Latex Paint Fo rmulations and Cleani ng 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

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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 (Acticide R F(N)). Antimicrobials Division, D333887, D335192 and D342000 of January 15, 2010.

Kline, 2004. Specialty Biocide Nort h America 2004, Kline and Company, Inc.

Lui et al, 2007. Predicting Personal Exposur e to Airborne Carbonyl s Using Residential Measurements and Time/Activity Data, Lui, W. et al., Atmosphere Environment, 2007: 41, 5280-5288. Cited in: Formaldehyde in the Indoor Envi ronment, 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 A llergic Reactions in Patients Patch Tested in North America – 1984 to 1985. Journal of the American Academy of Dermatology Volume 20, Pages 1038-45.

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### This page intentionally left blank.Appendix A – Justification for theToxicology and Exposure Studies Needed forthe Registration Review of CTACPage 19 of 32Appendix A, Table 1 - Toxicology Study JustificationsGuidelineStudy TitlePractical Utility of the Data870.346590-Day InhalationToxicity Study(Rat)1) What is the value of the study?The Agency currently does not have a repeateddose inhalation toxicity study for CTAC and istherefore required to extrapolatefrom a repeated dose oral toxicity study to assess the risks ofinhalation exposure. Since the effects of a chemical can vary greatly withrespect to route ofadministration, the use of a route specific studywill greatly increase theaccuracy of the riskassessment.2) How would the data be used?The study will be used to assess risks from inhalation exposures to CTAC that occur during openpour addition of powders during materials preservation, machining with fluid treated with CTACand painting with paint treated with CTAC. The study will be used to determine inhalationspecific endpoints that will be used to assessthe inhalation exposures and it will eliminate theuncertainty that exists when oral studiesare used to assess inhalation exposures.3) How could the data affect the risk assessment?The study will allow the selectionof a route specific endpoint which may be different than theroute extrapolated endpointcurrently used. It ispossible that the databaseuncertainty factor thatis associated with using routeto route extrapolation can be reduced or removed, resulting in alower level of concern for the uncertainty factor.4) What is triggeringthe need for this data?The potential inhalation exposuresthat might occur during openpour addition of powder duringmaterial preservation, machining with CTAC treated metal working fluids and painting withCTAC treated paints are the trigger for requiringan inhalation risk assessment which in turnrequires an inhalation toxicity study.Page 20 of 32Appendix A, Table 1 - Toxicology Study JustificationsGuidelineStudy TitlePractical Utility of the Data870.4100and870.4200or870.4300*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 CTAC that result fromthe use of CTAC in food packaging and metalworking fluids. Currently there are no long termstudies available for CTAC and thus the effects of long term exposureon human health areunknown.2) How would the data be used?The study will form the foundation for hazard characterization and toxicity endpoints selectionfor risk assessment through all exposure routes (oral, inhalation, and dermal).The data will allowthe Agency to conclude more definitively whether or not there would beany concerns for longterm exposure. This will provide a more completehazard characterizationof CTAC in regards tothe potential risks to the U.S. general population including infants and children as required by theFQPA.3) How could the data affect the risk assessment?The study will be used to select endpoints that will be used to assess the long term exposures ofCTAC.4) What is triggeringthe need for this data?This data need is triggered by the fact that there are long term exposuresto CTAC from the foodpackaging and metal working fluid uses and there are no studies available to assess the risks fromthese exposures.*A combined chronic toxicity/carcinogenicity study (OPPT 870.4300) can fulfill both the chronicoral and carcinogenicity data requirements.Page 21 of 32Appendix A, Table 1 - Toxicology Study JustificationsGuidelineStudy TitlePractical Utility of the Data870.3700DevelopmentalToxicity Study –Non-Rodent1) What is the value of the study?This study is needed to verify the result of the rodent study which indicated that CTAC does notcause developmental effects.The study in non-rodents is neededbecause developmental effectscan vary across species.2) How will the data be used?The data will allow the Agency to conclude more definitively whether or not there are anyconcerns for developmental toxicity. It may also generate endpoints that are used for riskassessment 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 therefore no risk assessmentfor developmental effects has been conducted.The required study maysupport this assumptionor it may suggest that there are developmental effects that need to be assessed.4) What is triggeringthe need for this data?This study is needed to verify the result of the rodent study which indicated that CTAC does notcause developmental effects.The study in non-rodents is needed because developmental effectscan vary across species.Page 22 of 32Appendix A, Table 1 - Toxicology Study JustificationsGuidelineStudy TitlePractical Utility of the Data870.3800Reproduction andFertility Effects1) What is the value of the study?This study is needed to verify the findings ofthe dermal development/reproductive study whichindicated that CTAC does notcause adverse effects by the dermal route of exposure.An oralstudy is needed because these effects can be route specific.2) How will the data be used?The data will allow the Agency to determine isthere are any concerns for reproductive toxicityvia dietary exposure. It may also generate endpoints that are used for risk assessment ofsusceptible populations such aswomen 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 exposure and therefore norisk assessment for reproductive effects hasbeen conducted. The required study may supportthis assumption or it may suggest that there arereproductive effects thatneed to be assessed.4) What is triggeringthe need for this data?This study is triggered by the factthat CTAC is registered for food packaging uses that can resultin dietary exposures. Although a dermal developmental/reproductive study has been done, anoral reproductive study is needed to assess thedietary exposures because reproductive effects canbe route specific.Page 23 of 32Page 24 of 32Appendix A, Table 1 - Toxicology Study JustificationsGuidelineStudy TitlePractical Utility of the Data870.620090 Day OralToxicity – Rodentand Non-Rodent1) What is the value of the study?These studies form the core of the toxicology database for CTAC. Without this data there isinsufficient information to determine if CTAC generates risks of concernfrom dietary exposuresthat result from the food packaginguse and incidental oralexposures that result from the textileuse.2) How will the data be used?These studies will be used as part of the toxicology database to assess dietary exposures thatresult from the food packaging use and incidental oral exposures that result from the textile use.3) How could the data affect the risk assessment?The existing studies are rated as unacceptablebecause some of the data summary tables areillegible. If legible copies of the data are obtained or if new studies areconducted to obtain thisdata, the data might indicate healtheffects that need to be assessed.4) What is triggeringthe need for this data?These studies form the core of the toxicology database that is required to assess dietary exposuresthat result from the food packaginguse and incidental oralexposures that result from the textileuse.Appendix A, Table 2 - Exposure Study JustificationsGuidelineStudy TitlePractical Utility of the Data875.1200875.1400875.1600Applicator Indoor Exposure(Open Pour Powders)DermalInhalationData Reporting1) What is the value of the study?Dermal and inhalation exposures to CTAC and inhalation exposures to formaldehyde areexpected during the open pouraddition of powders during materials preservation, oilproduction and textile production.In addition, dermal andinhalation exposures fromopen pouring of powders are evident in exposure studies in the Pesticide HandlersExposure Database (PHED). The existing Chemical Manufacturer Association (CMA)data base and PHED for these scenarios are limited in scope for QA/QC and the numberof replicates (i.e., number of times a workeris monitored for a specific activity). EPApresented the need for additional handler exposure data to the January 2007 ScienceAdvisory Panel (SAP) as wellas to the April 2007 Human Studies Review Board (HSRB)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 that result from theopen pour addition of powders during materials preservation, oil production and textileproduction.3) How could the data affect the risk assessment?The exposure data would be used to assess the risks to occupational workers anddetermine if mitigation measures, such as the use of water soluble packaging, are neededto reduce these risks.4)What is triggering the need for this data?The need for the exposure study is based on the potential for exposure from the open pouraddition of powders during the materials preservation, oil production and textile useslisted on label #464-403. This label indicates that the powder is available in bulk form orin 2.5 pound water soluble packets. If this exposure is precluded by a requirement that theproduct is always packaged in water soluble packets, then the exposure data would not beneeded.Page 25 of 32Appendix A, Table 2 - Exposure Study JustificationsGuidelineStudy TitlePractical Utility of the Data875.1200875.1400875.1600Applicator Indoor Exposure(Metal Working Fluids)DermalInhalationData Reporting1) What is the value of the study?Dermal and inhalation exposures to CTAC and inhalation exposures to formaldehyde areexpected during machining operations thatuse metal working fluids (MWF) that aretreated with CTAC. There are no studiesavailable to assess these exposures.2) How would the data be used?The exposure data would be used to assess dermal and inhalation exposures to CTAC andinhalation exposures to formaldehyde that result from the use of MWFs that are treatedwith CTAC.3) How could the data affect the risk assessment?Currently there are no data available to assess exposures resulting from the use of CTACin MWF and therefore the risks from thisuse are unknown. The exposure data would beused to assess these risks and determine ifmitigation is needed to reduce exposures.4) What is triggering the need for this data?CTAC is labeled for use as a preservative in “Metalworking Fluids” on label #464-403.Page 26 of 32Appendix A, Table 2 - Exposure Study JustificationsGuidelineStudy TitlePractical Utility of the Data875.1200875.1400875.1600Applicator Indoor Exposure(Brush/Roller Painting)DermalInhalationData Reporting1) What is the value of the study?Dermal and inhalation exposures to CTAC and inhalation exposures to formaldehyde areexpected during interior brush/roller application ofCTAC treated paints. There are nostudies available to assess these exposures.2) How would the data be used?The exposure data would be used to assessCTAC and formaldehyde exposures that resultfrom 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 and formaldehyderesulting from the use of CTAC in interior paints and therefore the risks from this use areunknown. The exposure data would be usedto assess these risks and determine ifmitigation 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 Inks” on label #464-403.Page 27 of 32Appendix A, Table 2 - Exposure Study JustificationsGuidelineStudy TitlePractical Utility of the Data875.1100875.1300875.1600Applicator Outdoor Exposure(Airless Sprayer Painting)DermalInhalationData Reporting1) What is the value of the study?Dermal and inhalation exposures to CTAC and inhalation exposures to formaldehyde areexpected during airless sprayer application ofCTAC treated exterior paints. There are nostudies available to assess these exposures.2) How would the data be used?The exposure data would be used to assessCTAC and formaldehyde exposures that resultfrom airless sprayer application ofCTAC treated exterior paints.3) How could the data affect the risk assessment?Current there are no data available to assess the exposure of CTAC and formaldehyderesulting from the use of CTAC in exterior paints and therefore the risks from this use areunknown. The exposure data would be usedto assess these risks and determine ifmitigation 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 Inks” on label #464-403.Page 28 of 32Appendix A, Table 2 - Exposure Study JustificationsGuidelineStudy TitlePractical Utility of the Data875.1200875.1400875.1600Applicator Indoor Exposure(Laundry Detergent)DermalInhalationData Reporting1) What is the value of the study?Dermal and inhalation exposures to CTAC and inhalation exposures to formaldehyde areexpected during use of laundry detergents treated with CTAC. There are no studiesavailable to assess these exposures.2) How would the data be used?The exposure data would be used to assessCTAC and formaldehyde exposures that resultfrom 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 and formaldehyderesulting from the use of CTAC in laundry detergents and therefore the risks from this useare unknown. The exposure data would be usedto assess these risks and determine ifmitigation is needed to reduce these risks.4) What is triggering the need for this data?CTAC is labeled for use on label #464-403 asa preservative in “Household, Institutionaland Industrial Cleaning& Laundry Products”.Page 29 of 32Appendix A, Table 2 - Exposure Study JustificationsGuidelineStudy TitlePractical Utility of the Data875.1200875.1400875.1600Applicator Indoor Exposure(General Purpose Cleaner)DermalInhalationData Reporting1) What is the value of the study?Dermal and inhalation exposures to CTAC and inhalation exposures to formaldehyde areexpected during use of general purpose cleanerstreated with CTAC.There are no studiesavailable to assess these exposures.2) How would the data be used?The exposure data would be used to assessCTAC and formaldehyde exposures that resultfrom 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 and formaldehyderesulting from the use of CTAC in general purpose cleaners, therefore the risks from thisuse are unknown. The exposure data would be used to assess these risks and determine ifmitigation is needed to reduce these risks.4) What is triggering the need for this data?CTAC is labeled for use on label #464-403 asa preservative in “Household, Institutionaland Industrial Cleaning& Laundry Products”.Page 30 of 32Appendix A, Table 2 - Exposure Study JustificationsGuidelineStudy TitlePractical Utility of the DataN/ATextile Leaching Study1) What is the value of the study?Dermal and incidental oral exposures to CTAC are expected during use of clothing andlinens made from textiles that are treated withfinishing fluids that are preserved withCTAC. There are no leaching studiesavailable to assess these exposures.2) How would the data be used?The leaching data would be used to assess CTAC exposures that result from use of use ofclothing and blankets treated with CTAC.3) How could the data affect the risk assessment?Currently there are no leaching data availableto assess the dermal and incidental oralexposure of CTAC resulting from the use of CTACin textile finishing fluids and thus therisks from this use are unknown.4) What is triggering the need for this data?CTAC is labeled for use on label #464-403 asa preservative in “Textile Finishing andSpinning Fluids”. Textile finishing fluids are used to improve surface smoothness andsoftness.Page 31 of 32Page 32 of 32Appendix A, Table 2 - Exposure Study JustificationsGuidelineStudy TitlePractical Utility of the Data875.1700Product Use Information1) What is the value of the study?Product use information is a description of howthe product is actuallyapplied; it is not afield study. A description of how this productis used would provide for a comprehensiverealistic assessment of its potential applications.2) How would the data be used?The product use information will be used to define and characterize the exposurescenarios 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 assessment is inclusiveof the types of exposures occurring during use and that these exposures are accuratelyassessed.4)What is triggering the need for this data?The need for a risk assessment under Registration Review in turn necessitates that the riskassessor understand howthe product is used.